Podcasts about mda mb

BUFFALO, NY- June 17, 2024 – A new research paper was published on the cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 11, entitled, “Mitophagy and cancer: role of BNIP3/BNIP3L as energetic drivers of stemness features, ATP production, proliferation, and cell migration.” Mitophagy is a selective form of autophagy which permits the removal of dysfunctional or excess mitochondria. This occurs as an adaptative response to physiological stressors, such as hypoxia, nutrient deprivation, or DNA damage. Mitophagy is promoted by specific mitochondrial outer membrane receptors, among which are BNIP3 and BNIP3L. The role of mitophagy in cancer is being widely studied, and more specifically in the maintenance of cancer stem cell (CSC) properties, such as self-renewal. Given that CSCs are responsible for treatment failure and metastatic capacity, targeting mitophagy could be an interesting approach for CSC elimination. In this new study, researchers Marta Mauro-Lizcano, Federica Sotgia, and Michael P. Lisanti from the University of Salford describe a new model system to enrich sub-populations of cancer cells with high basal levels of mitophagy, based on the functional transcriptional activity of BNIP3 and BNIP3L. “Briefly, we employed a BNIP3(L)-promoter-eGFP-reporter system to isolate cancer cells with high BNIP3/BNIP3L transcriptional activity by flow cytometry (FACS).” The model was validated by using complementary lysosomal and mitophagy-specific probes, as well as the mitochondrially-targeted red fluorescent protein (RFP), namely mt-Keima. High BNIP3/BNIP3L transcriptional activity was accompanied by increases in i) BNIP3/BNIP3L protein levels, ii) lysosomal mass, and iii) basal mitophagy activity. Furthermore, cancer cells with increased BNIP3/BNIP3L transcriptional activity exhibited CSC features, such as greater mammosphere-forming ability and high CD44 levels. “To further explore the model, we also analysed other stemness characteristics in MCF7 and MDA-MB-231 breast cancer cell lines, directly demonstrating that BNIP3(L)-high cells were more metabolically active, proliferative, migratory, and drug-resistant, with elevated anti-oxidant capacity. Therefore, high levels of basal mitophagy appear to enhance CSC features.” DOI - https://doi.org/10.18632/aging.205939 Corresponding authors - Federica Sotgia - fsotgia@gmail.com, and Michael P. Lisanti - michaelp.lisanti@gmail.com Video short - https://www.youtube.com/watch?v=n872jCkc-q8 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205939 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging-US Aging publishes research papers in all fields of aging research, including but not limited to aging processes (from yeast to mammals), cellular senescence, age-related diseases (such as cancer and Alzheimer's disease) and their prevention and treatment, anti-aging strategies and drug development, and, importantly, the role of signal transduction pathways in aging (such as mTOR) and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Explore the incredible benefits of algae with Catharine Arnston. First, you need to know that it's not a supplement, but a true superfood. This episode focuses on two remarkable algae varieties: spirulina, a vibrant blue-green algae packed with collagen, B vitamins, and essential amino acids, and chlorella, another green gem with unique properties. Discover the differences between these algae powerhouses, when and how to incorporate them into your daily routine, and the science behind their health-boosting effects.Prepare to also dive into the intricate world of enzymes, including superoxide dismutase and ficocyanin, as we explore their role in reducing angiogenesis in cancer cells and enhancing immunity against viral infections, including a certain well-known virus we've all heard about in recent years.Our discussion doesn't stop there. Dr. Stephanie and Catharine explore the myriad applications of algae, from helping children with autism to supporting the demanding lifestyles of athletes and individuals like Dr. Stephanie, a 45-year-old woman dedicated to weight training and cardio.This episode offers a deep, scientifically rich conversation that promises to captivate your inner nerd.Bio:Catharine started ENERGYbits after her sister was diagnosed with breast cancer and advised by her oncologist that an alkaline diet would help her heal. Catharine immediately sprung into action to help her sister research alkaline foods and in the process she discovered algae. When Catharine learned that algae was the most alkaline, plant-based, nutrient-dense food in the world and had been used for fifty years in Asia to improve health and longevity, she knew she had discovered something big (and yes, her sister fully recovered - thanks for asking).As Catharine dug into the science of algae, she learned it had 64% protein, and 40 vitamins/minerals and was endorsed by the United Nations and NASA as the most nutrient-dense food in the world. She also discovered there were 100,000 studies documenting its long list of benefits and it was the world's most sustainable, eco-friendly food crop. And yet algae remained virtually unknown outside of Asia. How could this be possible? Catharine knew algae could be a game changer for our health, our children and our world if she could only convince people it wasn't weird. And so ENERGYbits was born.Links for this episode:EnergyBits.com/better and use code BETTER for 20% off anything on the websiteSpirulina in Clinical Practice: Evidence-Based Human Applications - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136577/A deep dive into Zero Hunger: the seaweed revolution - https://news.un.org/en/story/2020/11/1077212Phycocyanin: A Potential Drug for Cancer Treatment - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687155/C-Phycocyanin exerts anti-cancer effects via the MAPK signaling pathway in MDA-MB-231 cells - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785878/NAC, Spirulina, Other Nutraceuticals May Play Role On Coronavirus Treatment - https://scienceblog.com/514404/nac-spirulina-other-nutraceuticals-may-play-role-on-coronavirus-treatment/Anti-Inflammatory and Anti-Aging Evaluation of Pigment-Protein Complex Extracted from Chlorella Pyrenoidosa - https://pubmed.ncbi.nlm.nih.gov/31623220/Studies on the biosorption of heavy metals onto Chlorella vulgaris - https://www.tandfonline.com/doi/abs/10.1080/10934529409376043Chlorella vulgaris functional alcoholic beverage: Effect on propagation of cortical spreading depression and functional properties - https://pubmed.ncbi.nlm.nih.gov/34370788/Algae Protects Mitochondria Health With Superoxide Dismutase (SOD)Algae Tablets for Brain HealthBrain Health with AlgaeCancer Free with AlgaeEpisode Overview:0:04:50 Understanding Algae: Macroalgae vs. Microalgae0:09:10 Introduction to Spirulina and Chlorella0:11:35 The Power of Vegetables and Proper Supplementation0:21:06 Mechanism of Action: Phycocyanin and Cancer Cell Destruction0:30:51 Spirulina: The Ultimate Calorie-Conscious Superfood0:41:15 Collagen and its Role in Muscle Growth0:50:41 Spirulina and Chlorella for Detox and Wellness Benefits0:53:37 Spirulina and Chlorella for Improving Brain Function in Autistic Children0:57:09 Spirulina and Chlorella as Food for Athletes, Providing Focus and Energy1:00:06 Try Taking 30 EnergyBits Before Your Next WorkoutWe'd like to thank our sponsors:LEVELSLevels helps you see how food affects your health by giving you real-time feedback on your diet using a continuous glucose monitor. Right now Levels is offering you an additional two free months off of the levels annual membership when you use the link levels.link/better.

A new research paper was published in Oncotarget's Volume 14 on April 24, 2023, entitled, “Differential silencing of STAT3 isoforms leads to changes in STAT3 activation.” Signal transducer and activator of transcription 3 (STAT3) is a transcription factor involved in multiple fundamental biological processes and a key player in cancer development and progression. STAT3 is activated upon tyrosine phosphorylation and is constitutively active in various malignancies; therefore, the expression of phospho-STAT3 (pSTAT3) has been recognized as a predictor of poor survival. STAT3 encodes two alternatively-spliced STAT3 isoforms: the full-length STAT3α isoform and the truncated STAT3β isoform. These isoforms have been suggested as the reason for the occasionally observed opposing roles of STAT3 in cancer: an oncogene, on one hand, and a tumor suppressor on the other. In this new study, researchers Inbal Shamir, Ilan Tsarfaty, Gidi Paret, and Yael Nevo-Caspi from Sheba Medical Center and Tel Aviv University investigated the roles of STAT3α and STAT3β in aggressive breast cancer. They manipulated endogenous STAT3 isoform expression and measured outcomes to mimic physiological changes more accurately. “In this study we examined the roles of STAT3 isoforms using specific siRNAs that target either STAT3α or STAT3β. We used the MDA-MB-231 cell line which represents an aggressive and mortal subtype of breast cancer, in which STAT3 is overexpressed and constitutively activated [14].” The team separately silenced each isoform in the MDA-MB-231 cell line and found that they affect each other's activation, impacting cell viability, cytokine expression, and migration. Their results show that each of the isoforms affects the activation (i.e., phosphorylation) of the other isoform and leads to changes in the outcome of the cells. They conclude that both STAT3α and STAT3β play a crucial role in the function of STAT3. Distinguishing between the two isoforms and their active forms is crucial for STAT3-related cancer diagnosis and therapy. “Referring to STAT3 as a single protein can lead to wrong conclusions, as they have different functions. Current STAT3 inhibitors target both isoforms, but this approach should be revised for better patient care. We present an endogenous mechanism that can shift the balance in a favorable direction, and we suggest developing treatments that mimic this mechanism could lead to new avenues for cancer therapy.” DOI: https://doi.org/10.18632/oncotarget.28412 Correspondence to - Yael Nevo-Caspi - yael.caspi@sheba.health.gov.il Keywords - STAT3: Signal transducer and activator of transcription 3, ER: endoplasmic reticulum, TAD: transactivation domain, SH2: Src homology 2, RQ: Relative quantitative Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28412 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

A new research paper was published in Oncotarget's Volume 14 on March 24, 2023, entitled, “Polyisoprenylated cysteinyl amide inhibitors deplete singly polyisoprenylated monomeric G-proteins in lung and breast cancer cell lines.” Finding effective therapies against cancers driven by mutant and/or overexpressed hyperactive G-proteins remains an area of active research. Polyisoprenylated cysteinyl amide inhibitors (PCAIs) are agents that mimic the essential posttranslational modifications of G-proteins. It is hypothesized that PCAIs work as anticancer agents by disrupting polyisoprenylation-dependent functional interactions of the G-Proteins. In their new study, researchers Nada Tawfeeq, Jassy Mary S. Lazarte, Yonghao Jin, Matthew D. Gregory, and Nazarius S. Lamango from Florida A&M University College of Pharmacy Pharmaceutical Sciences and Imam Abdulrahman bin Faisal University tested this hypothesis by determining the effect of the PCAIs on the levels of RAS and related monomeric G-proteins. “To investigate the hypothesized anticancer mechanisms of the PCAIs through disruption of G-protein function, we checked the effects of the PCAIs on the G-protein levels in lung cancer (A549 and NCI-H1299) and breast cancer (MDA-MB-231 and MDA-MB-468) cell lines.” Following 48 hours of exposure, they found significant decreases in the levels of KRAS, RHOA, RAC1, and CDC42 ranging within 20–66% after NSL-YHJ-2-27 (5 μM) treatment in all four cell lines tested, A549, NCI-H1299, MDA-MB-231, and MDA-MB-468. However, no significant difference was observed on the G-protein, RAB5A. Interestingly, 38 and 44% decreases in the levels of the farnesylated and acylated NRAS were observed in the two breast cancer cell lines, MDA-MB-231, and MDA-MB-468, respectively, while HRAS levels showed a 36% decrease only in MDA-MB-468 cells. Moreover, after PCAIs treatment, migration, and invasion of A549 cells were inhibited by 72 and 70%, respectively while the levels of vinculin and fascin dropped by 33 and 43%, respectively. Their results show that PCAIs deplete the protein levels of some significant G-proteins which are known to be involved in the migration and invasion of cells (i.e., metastasis) such as RAC1, RHOA, and CDC42. These findings implicate the potential role of PCAIs as anticancer agents through their direct interaction with monomeric G-proteins. “The initial findings presented here indicate how PCAIs can be used as potent agents in developing new anticancer therapeutics, therefore, more extensive studies need to be done to elucidate on its potency. Although we cannot conclusively explain the exact mechanism of action of PCAIs on how they affect the levels of some G-proteins yet, but we can say that these PCAIs have the ability to affect the progression of cancer.” Research paper: DOI: https://doi.org/10.18632/oncotarget.28390 Correspondence to: Nazarius S. Lamango - nazarius.lamango@famu.edu Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords: PCAIs, G-proteins, KRAS, RHOA, RAC1 About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.02.530779v1?rss=1 Authors: Issitt, T., Reilly, M., Sweeney, S. T., Brackenbury, W. J., Redeker, K. Abstract: Hypoxia in disease describes persistent low oxygen conditions, observed in a range of pathologies, including cancer. In the discovery of biomarkers in biological models, pathophysiological traits present a source of translatable metabolic products for the diagnosis of disease in humans. Part of the metabolome is represented by its volatile, gaseous fraction; the volatilome. Human volatile profiles, such as those found in breath, are able to diagnose disease, however accurate volatile biomarker discovery is required to target reliable biomarkers to develop new diagnostic tools. Using custom chambers to control oxygen levels and facilitate headspace sampling, the MDA-MB-231 breast cancer cell line was exposed to hypoxia (1% oxygen) for 24 hours. The maintenance of hypoxic conditions in the system was successfully validated over this time period. Targeting and non-targeting gas chromatography mass spectrometry approaches revealed four significantly altered volatile organic compounds when compared to control cells. Three compounds were actively consumed by cells: methyl chloride, acetone and n-Hexane. Cells under hypoxia also produced significant amounts of styrene. This work presents a novel methodology for identification of volatile metabolisms under controlled gas conditions with novel observations of volatile metabolisms by breast cancer cells. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.26.524308v1?rss=1 Authors: Chan, V., Bone, L., Anderson, K. E., Zhang, K., Orofiamma, L., Awadeh, Y., Lee, D. K. C., Fu, N. J., Chow, J. T. S., Salmena, L., Stephens, L. R., Hawkins, P. T., Antonescu, C. N., Botelho, R. J. Abstract: Receptor tyrosine kinases such as epidermal growth factor (EGF) receptor (EGFR) stimulate phosphatidylinositol 3-kinases (PI3Ks) to convert phosphaitydlinositol-4,5-bisphosophate [PtdIns(4,5)P2] into phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P3]. PtdIns(3,4,5)P3 then promotes various pathways leading to actin remodelling, changes in gene expression, and enhanced anabolic activity, cell survival and proliferation. In part, PtdIns(3,4,5)P3 achieves these functions by stimulating the kinase Akt, which phosphorylates numerous targets like Tsc2 and GSK3{beta}. Overall, unchecked upregulation of PtdIns(3,4,5)P3-Akt signalling can promote tumourgenesis and cancer progression. Interestingly, 50-70% of PtdIns and PtdInsPs have stearate and arachidonate at sn-1 and sn-2 positions of glycerol, respectively, forming a species known as 38:4-PtdIns/PtdInsPs. It is thought that LCLAT1/LYCAT and MBOAT7/LPIAT1 acyltransferases are respectively responsible for enriching PtdIns with this acyl composition. We previously showed that disruption of LCLAT1 altered the acyl profile of bis-phosphorylated PtdInsPs, lowered PtdIns(4,5)P2, and perturbed endocytosis and endocytic trafficking. However, the role of LCLAT1 in receptor tyrosine kinase and PtdIns(3,4,5)P3 signaling was not explored. Here, we show that LCLAT1 silencing in MDA-MB-231 and ARPE-19 cells abated the levels of PtdIns(3,4,5)P3 in response to EGF signalling. Importantly, LCLAT1-silenced cells were also impaired for EGF-mediated Akt activation and downstream signalling, and consequently, were depressed for cell proliferation and survival. Thus, our work provides first evidence that the LCLAT1 acyltransferase supports receptor tyrosine kinase signalling through the PtdIns(3,4,5)P3-Akt axis and may represent a novel target for therapeutic development against cancers. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.04.522609v1?rss=1 Authors: Loconte, L., Arguedas, D., Chipont, A., El, R., Guyonnet, L., Guerin, C., Piovesana, E., Vazquez-Ibar, J. L., Joliot, A., Thery, C., Martin Jaular, L. Abstract: Cell-cell communication within the complex tumor microenvironment is critical to cancer progression. Tumor-derived extracellular vesicles (TD-EVs) are key players in this process. They can interact with immune cells and modulate their activity, either suppressing or activating the immune system. Understanding the interactions between TD-EVs and immune cells is essential for understanding immune modulation by cancer cells. Fluorescent labelling of TD-EVs is a method of choice to study such interaction. This work aims to determine the impact of EV labelling methods on the detection of EV interaction and capture by the different immune cell types within human Peripheral Blood Mononuclear Cells (PBMCs), analyzed by imaging flow cytometry and multicolor spectral flow cytometry. EVs released by the triple-negative breast carcinoma cell line MDA-MB-231 were labeled either with the lipophilic dye MemGlow-488 (MG-488), with Carboxyfluorescein diacetate, succinimidyl ester (CFDA-SE), or through expression of a MyrPalm-superFolder GFP (sfGFP) that incorporates into EVs during their biogenesis using a genetically engineered cell line. Our results showed that these different labeling strategies, although analyzed with the same techniques, led to diverging results. While MG-488-labelled EVs incorporate in all cell types, CFSE-labelled EVs are restricted to a minor subset of cells and sfGFP-labelled EVs are mainly detected in CD14+ monocytes which are the main uptakers of EVs and other particles, regardless of the labeling method. Moreover, MG-488-labeled liposomes behaved similarly to MG-488 EVs, highlighting the predominant role of the labelling strategy on the visualization and analysis of TD-EVs uptake by immune cell types. Consequently, the use of different EV labeling methods has to be considered as they can provide complementary information on various types of EV-cell interaction and EV fate. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.01.514662v1?rss=1 Authors: Zhang, C., Schekman, R. Abstract: Much attention has been focused on the possibility that cytoplasmic proteins and RNA may be conveyed between cells in extracellular vesicles (EVs) and tunneling nanotube (TNT) structures. Here, we set up two quantitative delivery reporters to study cargo transfer between cells. We found that EVs are internalized by reporter cells but do not efficiently deliver functional Cas9 protein to the nucleus. In contrast, donor and acceptor cells co-cultured to permit cell contact resulted in a highly effective transfer. Among our tested donor and acceptor cell pairs, HEK293T and MDA MB-231 recorded optimal intercellular transfer. Depolymerization of F-actin greatly decreased Cas9 transfer whereas inhibitors of endocytosis or knock-down of genes implicated in this process had little effect on transfer. Imaging results suggest that intercellular transfer of cargos occurred through open-ended membrane tubular connections. In contrast, cultures consisting only of HEK293T cells form close-ended tubular connections ineffective in cargo transfer. Depletion of human endogenous fusogens, syncytins, especially syncytin-2 in MDA-MB-231 cells, significantly reduced Cas9 transfer. Full-length mouse syncytin, but not truncated mutants, rescued the effect of depletion of human syncytins on Cas9 transfer. Mouse syncytin overexpression in HEK293T cells partially facilitated Cas9 transfer among HEK293T cells. These findings suggest that syncytin may serve as the fusogen responsible for the formation of an open-ended connection between cells. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

A new research paper was published in Oncotarget's Volume 13 on October 19, 2022, entitled, “Therapeutic efficacy of the humanized JAA-F11 anti-Thomsen-Friedenreich antibody constructs H2aL2a and H3L3 in human breast and lung cancer xenograft models.” The Thomsen-Friedenreich antigen (TF-Ag-α) is found on ~85% of human carcinomas but is cryptic on normal tissue. The humanized, highly specific hJAA-F11-H2aL2a and -H3L3 antibodies target TF-Ag-α without binding to TF-Ag-beta (found on surface glycolipids of some normal cells). “The relative affinity of H3L3 is 17 times that of H2aL2a, which would seem to favor superior efficacy, however, increased affinity can result in less tumor penetration.” In a new study, researchers Diala Ghazal, Fatma Zalzala, John C. Fisk, Swetha Tati, Loukia G. Karacosta, Susan Morey, James R. Olson, Sally Quataert, Grace K. Dy, and Kate Rittenhouse-Olson from For-Robin, Inc, University at Buffalo, University of Rochester, and Roswell Park Comprehensive Cancer Center Buffalo aimed to assess the potential therapeutic efficacy of these antibodies by treating four human cancer- mouse xenograft models with H2aL2a and H3L3. The tumor xenograft models used were human non-small cell lung cancer, H520, and small cell lung cancer, HTB171 in nude mice and human triple negative breast cancer, MDA-MB-231 and HCC1806 in SCID mice. H2aL2a significantly decreased tumor growth in both breast and both lung cancer models. H2aL2a showed statistically equal or better efficacy than H3L3 and has superior production capabilities. These results suggest that H2aL2a may be superior as a naked antibody, as an antibody drug conjugate or as a radiolabeled antibody, however the higher affinity of H3L3 may lead to better efficacy in bi-specific therapies in which the binding is decreased due to the presence of only one TF-Ag-α binding site. “In conclusion, both H2aL2a and H3L3 humanized antibodies to TF-Ag-α show efficacy in in vivo xenograft models of human tumors in SCID and nude mice and thus hold promise as therapeutics for breast and lung cancer. H2aL2a significantly decreased tumor growth rate in both breast cancer and both lung cancer models tested. H2aL2a is equal to or better than H3L3 in four of the four models and H2aL2a cell lines have far superior antibody production capabilities under the conditions tested.” DOI: https://doi.org/10.18632/oncotarget.28282 Correspondence to: Kate Rittenhouse-Olson - krolson@buffalo.edu Keywords: hJAA-F11, TF-Ag, Thomsen-Friedenreich antigen, tumor immunotherapy, translational oncology About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com. Oncotarget Journal Office 6666 East Quaker Str., Suite 1A Orchard Park, NY 14127 Phone: 1-800-922-0957 (option 2)

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.23.513385v1?rss=1 Authors: Hammad, A. S., Yu, F., Horgen, F. D., Machaca, K. Abstract: Store-operated calcium entry (SOCE) contributes to several physiological and pathological conditions including transcription, secretion, immunodeficiencies, and cancer. SOCE has been shown to be important for breast cancer cell migration where knockdown of SOCE components (STIM1 or Orai1) decreases cancer metastasis. Here we show unexpectedly that STIM1 knockout (KO) metastatic MDA-MB-231 breast cancer cells migrate faster and have enhance invasion capacity compared to parental cells. In contrast, Orai1-KO cells, which have similar levels of SOCE inhibition as STIM1-KO, migrate slower than the parental cell line. This shows that the enhanced migration phenotype of STIM1-KO cells is not due to the loss of a Ca2+ entry through SOCE, rather it involves transcriptional remodeling. Interestingly, NFATC2 is significantly downregulated in STIM1-KO cells and overexpression of NFATC2 reversed the enhanced migration of STIM1-KO cells. This demonstrates that STIM1 modulates NFATC2 expression independently of its role in SOCE. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

VIDEOS : WES2022 | Yuval Noah Harari and Vanessa Nakate in conversation (3:19) Why Colleges Are Becoming Cults [Full Series] | Dr. Lyell Asher (15:00 to 43:42 Gary Null Speaking Out at the NYS Assembly Hearing  (25:00)   Astragulus found to inhibit breast cancer cell proliferation Fujian University of Traditional Medicine (China), September 8, 2022 Huang qi (Astragalus) is one of the fundamental herbs in traditional Chinese medicine, with earliest records of its use dating back over 2,000 years ago. Now, a study in BMC Complementary and Alternative Medicine has found that astragulus is also able to prevent the spread of breast cancer cells in the body. In the study, researchers from the Fujian University of Traditional Chinese Medicine in China looked at how astragulus extract can affect breast cancer cells and the process behind this biological effect. They also looked at the primary isoflavones in the extract, as well as its anti-proliferative activity on three breast cancer lines: MCF-7 (ER+), SK-BR-3 (HER2+) and MDA-MB-231 (triple-negative). They did this by exposing these breast cancer cells to the extract for 48 hours. In addition, they examined the effect of astragulus extract on phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways, a primary intracellular signaling pathway that contributes to cell proliferation, growth, migration, metabolism, and apoptosis. The results of the study showed that the treatment of astragulus exhibited anti-proliferative activity on breast cancer cells. Furthermore, the therapy promoted the death of breast cancer cells. These suggested that it's ability to inhibit breast cancer cell growth was linked to its ability to inhibit PI3K/Akt/mTOR activity. Moreover, the researchers found that the Huang qi extract contains four types of isoflavones, such as campanulin, ononin, calycosin, and formononetin, which contributed to the inhibitory effect of Huang qi extract on breast cancer cells proliferation. Vitamin D supplementation could help critically ill patients University Hospital Würzburg (Germany) September 12 2022. Findings from a review and meta-analysis reported in Critical Care suggest that providing critically ill patients with vitamin D supplements may improve some clinical outcomes, including survival. “Upon ICU admission, the majority of patients have significantly reduced 25-hydroxyvitamin D levels, which remain significantly reduced over the entire ICU length of stay,” Johannes Menger and colleagues wrote. “In these patients, significantly reduced vitamin D (25-hydroxyvitamin D) serum levels are frequent and independently associated with higher incidence and severity of sepsis.” Sixteen randomized, controlled trials that evaluated vitamin D supplementation's association with mortality were identified. Vitamin D supplementation was associated with a 22% lower risk of overall mortality in comparison with a placebo or standard care. Among studies that reported 28-day mortality, vitamin D supplementation was associated with a trend toward lower a lower risk. Receiving vitamin D by injection or intravenously had the strongest effect. Patients who received vitamin D spent an average of 3.13 days less in the ICU and 5 fewer days on a ventilator than those who received a placebo. “The results of this systematic review and meta-analysis suggest that vitamin D supplementation may be associated with reduced overall mortality in critically ill patients,” they concluded. Natural compound could reduce breast cancer risk in some women Luteolin may inhibit growth of human breast cancer cells in postmenopausal women taking hormone replacement therapy University of Missouri-Columbia, September 9, 2022 More than 100 women die from breast cancer every day in the United States. The odds increase in postmenopausal women who have taken a combined estrogen and progestin hormone replacement therapy; these women also have an increased risk of developing progestin-accelerated breast tumors. Now, University of Missouri researchers have found that luteolin, a natural compound found in herbs such as thyme and parsley as well as vegetables such as celery and broccoli, could reduce the cancer risk for women who have taken hormone replacement therapy. “Most older women normally have benign lesions in breast tissue,” Hyder said. “These lesions typically don't form tumors until they receive the ‘trigger'– in this case, progestin–that attracts blood vessels to cells essentially feeding the lesions causing them to expand.” His newest study shows that when the supplement luteolin is administered to human breast cancer cells in the lab, benefits can be observed including the reduction of those vessels “feeding” the cancer cells causing cancer cell death. Hyder's lab has found that as human breast cancer cells develop, they tend to take on stem cell-like properties, which can make them harder to kill. Here, luteolin was used to monitor stem cell-like characteristics of breast cancer cells and his team saw a vast reduction in this phenomenon, further proving that the natural compound exerts its anti-tumor effects in a variety of ways. “We feel that luteolin can be effective when injected directly into the bloodstream, so IV supplements may still be a possibility,” Hyder said. “But, until the supplement is tested for safety and commercialized, which we hope will happen after further testing and clinical trials, women should continue consuming a healthy diet with fresh fruits and vegetables.” CBD shows health benefits in estrogen-deficient mice that model postmenopause Rutgers University, September 14, 2022 A Rutgers study points to cannabidiol (CBD), a major component of hemp and medical marijuana used to treat conditions such as chronic pain, inflammation, migraines, epilepsy, autoimmune diseases, depression, and anxiety, as a possible treatment for postmenopausal women whose ovaries no longer make estrogen. In a study published in Frontiers in Pharmacology, scientists reported that when estrogen-deficient mice were fed CBD, a non-intoxicating compound extracted from hemp, they showed marked improvement in several areas. Their bloodstreams more readily disposed of glucose, and they burned more energy. In addition, their bone density improved, they had less inflammation in gut and bone tissues and they possessed higher levels of beneficial gut bacteria. “This preclinical study is the first to suggest the therapeutic potential of CBD for alleviating symptoms of estrogen deficiency,” said Diana Roopchand, an assistant professor in the Department of Food Science of the Rutgers School of Environmental and Biological Sciences (SEBS) and senior author on the study. “There is much anecdotal evidence of CBD's health benefits for menopausal and postmenopausal women, but our study is the first to investigate some of the claims in an established preclinical model of postmenopause.” Over 18 weeks, researchers fed the estrogen-deficient mice a steady diet of either tiny, CBD-laced peanut butter balls or peanut butter balls without CBD. The untreated estrogen-deficient mice developed symptoms that resembled those of postmenopausal human females, such as metabolic dysfunction, evidence of inflammation, lower bone density, and lower levels of beneficial gut bacteria. However, in mice that ingested CBD, these conditions were significantly improved. Mediterranean diet and depression among older individuals Harokopio University (Greece), September 9, 2022 According to news originating from Athens, Greece,research stated, “In Europe, depression is one of the most frequent mental disorders across all age groups, but particularly in people aged 65 years and over, and higher depressive symptoms have been reported among individuals with chronic diseases (e.g., diabetes and heart disease).” Research from Harokopio University stated, “To evaluate the role of adherence to the Mediterranean diet (MedDiet) in depression in a sample of older people living in the Mediterranean basin. Standard procedures were used to determine socio-demographic, lifestyle, and clinical characteristics of the participants, as well as their dietary habits, and depressive symptoms were evaluated using the Geriatric Depression Scale (GDS). Participants classified as having mild or severe depression were less educated and physically active, and more diabetic, and they reported less adherence to the MedDiet. Adherence to the MedDiet was associated with the absence of depression [(OR, 95% CI): 0.65, 0.50 – 0.85]. In addition, daily tea drinking was also related to the absence of depression [(OR, 95% CI): 0.51, 0.40 – 0.65].” According to the news editors, the research concluded: “Greater adherence to the MedDiet and daily tea drinking seem to have a beneficial effect on depressive symptoms in older adults.” High cholesterol leads to long-term liver scarring and immune cell dysfunction in lab study University of Southern California, September 15, 2022 There's a long-established link between a high-fat, high-sugar diet and fatty liver disease, which can lead to life-threatening conditions such as cirrhosis and liver cancer. Now, new research from the Keck School of Medicine of USC adds some detail and dimension to this picture. The lab study, published in Frontiers in Immunology, is the first-ever to focus on how different amounts of cholesterol as part of a diet high in fat and sugar affect fatty liver disease progression. Modeling the disease in mice, the investigators demonstrated that high cholesterol intake can make fatty liver disease worse—driving inflammation and scarring—and that, importantly, scar tissuecan persist even after switching to a diet low in cholesterol. The findings also indicated that a high-cholesterol diet can create long-lasting dysfunction in a specific population of immune cells previously shown to play a role in fatty liver disease. “We saw that you may have a high-fat and high-sugar diet, but when you add high cholesterol to that, it will accelerate the process that causes inflammation in your liver,” said corresponding author Ana Maretti-Mira, Ph.D., an assistant research professor of medicine at USC. “People focus on high cholesterol as a risk for heart disease, but we showed that your liver may also be affected, causing inflammation, scarring and, potentially, cirrhosis.” High cholesterol makes fatty liver disease worse The researchers fed mice a high-fat, high-sugar diet shown to cause a form of advanced fatty liver disease similar to human illness. The mice were split into three groups that received different amounts of cholesterol in their food for 20 weeks—midlife for the animals. The low-cholesterol group received one-quarter the cholesterol compared to medium; the high-cholesterol group received 25 times more than the low-cholesterol group. After 20 weeks, the livers of mice from all three groups showed accumulation of fat, a benign feature of fatty liver disease, but the high-cholesterol group had more advanced disease, with increased inflammation and scar tissue. For the following 10 weeks, mice from all three groups received low cholesterol as part of a diet that remained high in fat and sugar. At the end of that time, that change in diet had reversed inflammation in the original high-cholesterol mice, but had not reduced scar tissue. This finding shows that damage caused by high cholesterol can be hard to undo. The high-fat, high-sugar diet given to mice in the study has unfortunate similarities to the typical Western diet in humans. “Our daily diet has lots of carbohydrates, such as sugary drinks, bread, rice and pasta,” Maretti-Mira said. “Then there's high fat, since everybody likes deep fried foods. At the same time, we don't have the same active life we used to, so we end up eating much more than our body needs.”

Strawberries may fend off Alzheimer's Rush University Medical Center, July 28, 2022   Could strawberries as a snack or in your cereal, salads or smoothie help protect your brain from Alzheimer's? Maybe so, according to a new study from researchers at RUSH. RUSH researchers found that a bioactive compound found in strawberries called pelargonidin may be associated with fewer neurofibrillary tau tangles in the brain. Tau tangles are one of the hallmarks of Alzheimer's disease, which is caused by abnormal changes with tau proteins that accumulate in the brain. The study was published in the Journal of Alzheimer's Disease. "We suspect the anti-inflammatory properties of pelargonidin may decrease overall neuroinflammation, which may reduce cytokine production," said Dr. Julie Schneider, author of the study. Schneider is associate professor and neuropathologist in the Rush Alzheimer's Disease Center at Rush University Medical Center in Chicago. Among berries, strawberries are the most abundant source of pelargonidin.     Florida Seaweed may Hold Promise as Protector Against Cancer  University of Florida College of Pharmacy, July 24, 2022   Among all cancers, new cases of prostate cancer are the most prevalent in the United States. While there are numerous tips for preventing and even reversing prostate cancer, one new study suggests a seaweed found off the coast of Florida could hold the key to preventing this and other forms of cancer. The news potentially brings the U.S. closer to Asian countries in prostate cancer prevalence—countries that incidentally have high rates of seaweed consumption. Researchers with the University of Florida screened several different seaweeds, searching for one with the most cancer-protective promise. They found it in a common green algae known as sea lettuce. “We now have scientific evidence that this seaweed raises the body's antioxidant defense system and therefore might potentially prevent a number of diseases, including cancer,” said Hendrik Luesch, Ph.D., lead research and associate professor of medicinal chemistry in the UF College of Pharmacy. “This mechanism appears to be most relevant to prostate cancer.” “Antioxidant-rich fruits and vegetables protect the body against these free radicals, mostly through a scavenging process of elimination. Rather than simply removing the damaging free radicals through this direct reaction, compounds in sea lettuce worked through an indirect mechanism, Luesch found. This process increases the levels of a suite of antioxidant enzymes and boosts antioxidants in cells, producing longer-lasting protection. Regulated by stretches of DNA called antioxidant response elements, the enzymes prevent oxidative damage and inflammation.” Luesch compares the possibilities of sea lettuce compounds to the proven benefits of sulforaphane in broccoli, an enzyme that works through similar methods to prevent damage from oxidative stress and cancer.   Fast food diet before pregnancy can impact breast milk and baby's health, say scientists University of Cambridge, July 27, 2022 A diet high in sugar and fat such as burgers, fries and fizzy drinks can negatively affect a new mother's breast milk and baby's health even before the child is conceived. The new study using lab mice has found that even relatively short-term consumption of a fast food diet impacts women's health, reducing their ability to produce nutritional breast milk after giving birth. This can affect the newborn's well-being, as well as increasing the risk of both mother and child developing potentially fatal conditions such as heart disease, stroke and diabetes in later life. Even mothers who appear to be a healthy weight can be suffering from hidden issues such as a fatty liver—which may be seen in people who are overweight or obese—from eating a diet heavy in processed foods, which tend to be high in fat and sugar. This can lead to advanced scarring (cirrhosis) and liver failure. In this new study, a group of mice was fed a diet of processed high fat pellet with sweetened condensed milk for just three weeks before pregnancy, during the three-week pregnancy itself, and following birth. This diet was designed to mimic the nutritional content of a fast food burger, fries and sugary soft drink. The aim was to determine the impacts on fertility, fetus growth and neonatal outcomes.  The researchers discovered that even a short-term high fat, high sugar diet impacted on the survival of the mice pups in the early period after birth, with an increased loss during the time the mother was feeding her offspring. Milk proteins are hugely important for newborn development but the quality was found to be poor in mouse mothers eating the high fat, high sugar diet. "They ended up with fatty livers, which is really dangerous for the mum, and there was altered formation of the placenta. The weight of the fetus itself wasn't affected. They seemed lighter, but it wasn't significant. But what was also apparent was that the nutrition to the fetus was changed in pregnancy. Then when we looked at how the mum may be supporting the baby after pregnancy, we found that her mammary gland development and her milk protein composition was altered, and that may have been the explanation for the greater health problems of the newborn pups."   Meditation And Yoga Change Your DNA To Reverse Effects Of Stress, Study Shows Coventry University (UK), July 25, 2022 Many people participate in practices such as meditation and yoga because they help us relax. At least those are the immediate effects we feel. But much more is happening on a molecular level, reveal researchers out of Coventry University in England. Published in the journal Frontiers in Immunology, this new research examined 18 studies on mind-body interventions (MBIs). These include practices such as mindfulness meditation and yoga. Comprehensively, these studies encompassed 846 participants over 11 years. The new analysis reveals that MBIs result in molecular changes in the human body. Furthermore, researchers claim that these changes are beneficial to our mental and physical health. To elaborate, consider the effect that stress has on the body. When we are under stress, the body increases the production of proteins that cause cell inflammation. This is the natural effect of the body's fight-or-flight response. It is widely believed that inflammation in the body leads to numerous illnesses, including cancer. Moreover, scientists also deduct that a persistent inflammation is more likely to cause psychiatric problems. Unfortunately, many people suffer from persistent stress, therefore they suffer from pro-inflammatory gene expression. According to this new analysis out of Coventry, people that practice MBIs such as meditation and yoga can reverse pro-inflammatory gene expression. This results in a reduced risk of inflammation-related diseases and mental conditions.   EGCG in Green Tea inhibits the growth of breast cancer cells Chonbuk National University School of Medicine (S Korea), July 21, 2022 According to news reporting originating in Chonbuk, South Korea, research stated, "Epigallocatechin gallate (EGCG), a major constituent of green tea, has potential as a treatment for a variety of diseases, including cancer. EGCG induces apoptosis and inhibits tumorigenesis through multiple signaling pathways in breast cancer cells. b-catenin signaling modulators could be useful in the prevention and therapy of breast cancer." Research from the Chonbuk National University School of Medicine states, "However, the precise anticancer effect of EGCG through the b-catenin signaling pathway in breast cancer is unclear. The present study investigated the association between b-catenin expression and clinicopathological factors of breast cancer patients, and the effect of EGCG on b-catenin expression in breast cancer cells. b-catenin expression was analyzed according to the clinicopathological factors of 74 patients with breast cancer. Western blot analysis revealed that b-catenin was expressed at higher levels in breast cancer tissue than in normal tissue. b-catenin expression was associated with lymph node metastasis, tumor-node-metastasis stage and estrogen receptor status. EGCG dsignificantly downregulated the expression of b-catenin, phosphorylated Akt and cyclin D1.  The present results suggest that EGCG inhibits the growth of MDA-MB-231 cells through the inactivation of the b-catenin signaling pathway."   According to the news reporters, the research concluded: "Based on these promising results, EGCG may be a potential treatment for triple negative breast cancer patients."     Turmeric eye drops could treat glaucoma University College London, July 264, 2022 A derivative of turmeric could be used in eye drops to treat the early stages of glaucoma, finds a new study led by UCL and Imperial College London researchers. In the new Scientific Reports paper, the researchers report a new method to deliver curcumin, extracted from the yellow spice turmeric, directly to the back of the eye using eye drops, overcoming the challenge of curcumin's poor solubility. The research team found the eye drops can reduce the loss of retinal cells in rats, which is known to be an early sign of glaucoma. "Curcumin is an exciting compound that has shown promise at detecting and treating the neurodegeneration implicated in numerous eye and brain conditions from glaucoma to Alzheimer's disease, so being able to administer it easily in eye drops may end up helping millions of people," said the study's lead author, Professor Francesca Cordeiro. Curcumin has previously been shown to protect retinal ganglion cells when administered orally. For the current study, the researchers were seeking to find a more reliable method to deliver curcumin. Oral administration is difficult because curcumin has poor solubility, so it does not easily dissolve and get absorbed into the bloodstream, and would require people to take large amounts of tablets (up to 24 a day) that may cause gastrointestinal side effects. The team developed a novel nanocarrier, wherein the curcumin is contained within a surfactant combined with a stabiliser, both of which are known to be safe for human use and are already in existing eye products. The nanocarrier can be used in eye drops to deliver much higher loads of curcumin than other products in development, increasing the drug's solubility by a factor of almost 400,000, and localises the curcumin in the eyes instead of throughout the body. After twice-daily use of eye drops in the rats for three weeks, retinal ganglion cell loss was significantly reduced compared to matched controls, and the treatment was found to be well-tolerated with no signs of eye irritation or inflammation.

Biomarkers are any measurement in the body that can indicate disease, infection, or effects of the environment. These indicators are commonly used to reveal disease, but they can also be used to support ​​personalized cancer therapy. “In recent years, there has been an increased focus on personalized cancer therapy. One important aspect is the identification of key biomarkers that support a given treatment plan.” Multiple biomarkers have been identified in breast cancers as helpful tools to guide targeted therapies, including the expression of HER2 and estrogen and progesterone receptors. In triple-negative breast cancer (TNBC), a number of distinct biomarkers have given rise to new targeted therapies, such as EGFR antibodies, AKT inhibitors, and PARP inhibitors. In a well-read paper from Immunomedics, Inc. (recently acquired by Gilead Sciences, Inc.), researchers analyzed sacituzumab govitecan (SG; Trodelvy™) in TNBC. The team authored a research paper that was published by Oncotarget in 2020, and entitled, “Predictive biomarkers for sacituzumab govitecan efficacy in Trop-2-expressing triple-negative breast cancer.” To date, this paper has scored an Altmetric Attention score of 48. “Here we examined the potential role of biomarkers in predicting the efficacy of SG.” Sacituzumab govitecan is an antibody-drug conjugate that targets human trophoblast cell-surface antigen-2 (Trop-2)ーwhich is a glycoprotein that is commonly overexpressed in many solid tumor types. “Trop-2 is a 46 KDa transmembrane glycoprotein that is overexpressed on many solid tumor types and is correlated with an overall poor prognosis in patients, making it an attractive target for therapy [7, 9].” The researchers examined a highly invasive and aggressive TNBC cell line (MDA-MB-231), which is not responsive to SG, and compared their findings to TNBC cell lines that are responsive to SG. Their goal was to determine how Trop-2 expression and the homologous recombination repair (HRR) pathway (through Rad51 expression) play roles in protecting the MDA-MB-231 cell line from SG mediated DNA damage. Trop-2 expression in transfected MDA-MB-231 and tumor xenografts were assessed, in vitro and in vivo Rad51 expression and DNA damagewere assessed via western blot, and statistical analysis was carried out for data from in vivo therapy studies. “Trop-2 expression levels as a positive, primary biomarker and HRR proficiency as a secondary, negative biomarker were assessed in vitro and in vivo.” Full blog: https://www.impactjournals.com/journals/blog/oncotarget/biomarker-predicts-treatment-efficacy-in-triple-negative-breast-cancer/ Press release - https://www.oncotarget.com/news/pr/predictive-biomarkers-in-trop-2-expressing-triple-negative-breast-cancer/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27766 DOI - https://doi.org/10.18632/oncotarget.27766 Full text - https://www.oncotarget.com/article/27766/text/ Correspondence to - Thomas M. Cardillo - tcardillo@immunomedics.com Keywords - sacituzumab govitecan, Trop-2, biomarker, RAD51, triple-negative breast cancer About Oncotarget Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Greater adherence to Mediterranean diet associated with better cognitive performance in older individuals University of South Australia, July 13, 2021 According to news originating from Adelaide, Australia, by NewsRx correspondents, research stated, “Adherence to a Mediterranean diet is associated with higher cognitive function and reduced risk of dementia in Mediterranean populations. However, few studies have investigated the association between Mediterranean diet adherence and cognition in populations outside of the Mediterranean basin.” Our news journalists obtained a quote from the research from the University of South Australia, “Furthermore, it is currently unknown whether the association between Mediterranean diet adherence and cognitive function differs between middle-aged and older individuals. Cross-sectional (n = 894) and longitudinal (n = 530) multivariable analyses were undertaken using data from community-dwelling adults from the Maine-Syracuse Longitudinal Study (MSLS). Mediterranean diet adherence was measured by applying a literature-based Mediterranean diet score to food frequency questionnaire data. Cognitive function was assessed with a battery of tests and composites scores were computed for global cognitive function, Visual-Spatial Organisation and Memory, verbal memory, working memory, scanning and tracking and abstract reasoning. No cross-sectional associations between Mediterranean diet adherence and cognitive function were detected. Over a period of five years, higher adherence to a Mediterranean diet was associated with improvements in Global Cognitive Function, Visual-Spatial Organisation and Memory and scanning and tracking in participants >= 70 years.” According to the news editors, the research concluded: “No significant longitudinal associations were observed for participants Conclusion: Our findings suggest that higher adherence to a Mediterranean diet is associated with better cognitive performance, and therefore less cognitive decline, in older but not middle-aged individuals.” This research has been peer-reviewed.     Coffee and veggies may protect against COVID-19 Northwestern University, July 20, 2021 Sip a venti dark roast and eat a salad. A new Northwestern Medicine study shows coffee consumption and eating lots of vegetables may offer some protection against COVID-19. The authors believe this is the first study using population data to examine the role of specific dietary intake in prevention of COVID-19. "A person's nutrition impacts immunity," said senior author Marilyn Cornelis, associate professor of preventive medicine at Northwestern University Feinberg School of Medicine. "And the immune system plays a key role in an individual's susceptibility and response to infectious diseases, including COVID-19." Being breastfed may also offer protection as well as eating less processed meats, the study found. "Besides following guidelines currently in place to slow the spread of the virus, we provide support for other relatively simple ways in which individuals can reduce their risk and that is through diet and nutrition," Cornelis said.  The paper on nutrition and COVID-19 protection was published recently in the journal Nutrients. One or more cups of coffee per day was associated with about a 10% decrease in risk of COVID-19 compared to less than one cup per day. Consumption of at least 0.67 servings per day of vegetables (cooked or raw, excluding potatoes) was associated with a lower risk of COVID-19 infection. Processed meat consumption of as little as 0.43 servings per day was associated with a higher risk of COVID-19. Having been breastfed as a baby reduced the risk 10% compared to not having been breastfed.  While the study shows diet appears to modestly reduce disease risk, the Centers for Disease Control and Prevention recommends vaccines as the most effective way to prevent COVID-19 disease, especially severe illness and death. COVID-19 vaccines also reduce the risk of people spreading the virus that causes COVID-19. Thus far, most COVID-19 research has focused on individual factors assessed after a positive COVID-19 test. Individuals with suppressed immune systems such as the elderly and those with existing comorbidities including cardiovascular diseases, hypertension, diabetes and obesity, are more likely to experience severe outcomes of COVID-19.  But other than weight management, less attention has focused on other modifiable risk factors preceding COVID-19 infection, said Cornelis, who studies how diet and nutrition contribute to chronic disease.  Dr. Thanh-Huyen Vu, the study's first author and a research associate professor of medicine at Northwestern, is now leading analyses to determine whether these protective diet behaviors are specific to COVID or respiratory infections more broadly.  Exact mechanisms linking these diet factors to COVID are unknown.  "Coffee is a major source of caffeine, but there are also dozens of other compounds that may potentially underlie the protective associations we observed," Cornelius said. "Associations with processed meat, but not red meat, point to non-meat factors." Using data from the UK Biobank, researchers examined the associations between dietary behaviors measured in 2006-2010 and COVID-19 infections in March to December 2020, before vaccines were available. They focused on 1) diet factors for which data were available and previously implicated in immunity based on human and animal studies; 2) self-reported intakes of coffee, tea, vegetables, fruit, fatty fish, processed meat and red meat. An early-life exposure to breastmilk also was analyzed.  Among the 37,988 participants tested for COVID-19 and included in the study, 17% tested positive.  The observational nature of the UK Biobank research limits the extent to which mechanisms of protection can be tested, Cornelis said. However, much of her nutrition research uses genetics, and with all UK Biobank participants currently genotyped, she hopes to use this information to gain better insight into how diet and nutrition offer protection from the disease.   Biologic age reversed with lifestyle improvement plus supplements Institute for Functional Medicine (Seattle), July 14 2021.  The April 15, 2021 issue of Aging published the results of an eight-week randomized trial which resulted in a reduction in biologic age among men who participated in lifestyle changes and consumed nutritional supplements. "The combined intervention program was designed to target a specific biological mechanism called DNA methylation, and in particular the DNA methylation patterns that have been identified as highly predictive of biological age,” explained lead author Kara Fitzgerald, ND. “We suspect that this focus was the reason for its remarkable impact.”  The trial included 38 men between the ages of 50 and 72 years. Eighteen participants consumed a plant-based, low carbohydrate diet that included limited nutrient-dense animal proteins. The diet was supplemented with a vegetable and fruit powder and the probiotic Lactobacillus plantarum 299v. The group was advised to participate in a minimum of 30 minutes of exercise daily and to perform breathing exercises twice per day for stress reduction.  According to the Horvath DNAmAge clock, which evaluates DNA methylation patterns as a marker of biologic age, men who participated in the lifestyle program had scores that averaged 1.96 younger at the end of the program in comparison with the beginning, while control participants scored 1.27 years older. Additionally, triglycerides were reduced in the lifestyle program group. “To our knowledge, this is the first randomized controlled study to suggest that specific diet and lifestyle interventions may reverse Horvath DNAmAge epigenetic aging in healthy adult males,” the authors announced.  “These early results appear to be consistent with, and greatly extend, the very few existing studies that have so far examined the potential for biological age reversal,” Dr Fitzgerald commented. “And it is unique in its use of a safe, non-pharmaceutical dietary and lifestyle program, control group, and the extent of the age reduction."       Research suggests L-carnitine could aid burn recovery Anhui Medical University (China), July 12, 2021 According to news reporting from First Affiliated Hospital of Anhui Medical University research stated, “Impaired hepatic fatty acid metabolism and persistent mitochondrial dysfunction are phenomena commonly associated with liver failure. Decreased serum levels of L-carnitine, a amino acid derivative involved in fatty-acid and energy metabolism, have been reported in severe burn patients.” Our news editors obtained a quote from the research from First Affiliated Hospital of Anhui Medical University: “The current study aimed to evaluate the effects of L-carnitine supplementation on mitochondrial damage and other hepatocyte injuries following severe burns and the related mechanisms. Serum carnitine and other indicators of hepatocytic injury, including AST, ALT, LDH, TG, and OCT, were analyzed in severe burn patients and healthy controls. A burn model was established on the back skin of rats; thereafter, carnitine was administered, and serum levels of the above indicators were evaluated along with Oil Red O and TUNEL staining, transmission electron microscopy, and assessment of mitochondrial membrane potential and carnitine palmitoyltransferase 1 (CPT1) activity and expression levels in the liver. HepG2 cells pretreated with the CPT1 inhibitor etomoxir were treated with or without carnitine for 24 h. Next, the above indicators were examined, and apoptotic cells were analyzed via flow cytometry. High-throughput sequencing of rat liver tissues identified several differentially expressed genes (Fabp4, Acacb, Acsm5, and Pnpla3) were confirmed using RT-qPCR. Substantially decreased serum levels of carnitine and increased levels of AST, ALT, LDH, and OCT were detected in severe burn patients and the burn model rats. Accumulation of TG, evident mitochondrial shrinkage, altered mitochondrial membrane potential, decreased ketogenesis, and reduced CPT1 activity were detected in the liver tissue of the burned rats. Carnitine administration recovered CPT1 activity and improved all indicators related to cellular and fatty acid metabolism and mitochondrial injury. Inhibition of CPT1 activity with etomoxir induced hepatocyte injuries similar to those in burn patients and burned rats; carnitine supplementation restored CPT1 activity and ameliorated these injuries. The expression levels of the differentially expressed genes Fabp4, Acacb, Acsm5, and Pnpla3 in the liver tissue from burned rats and etomoxir-treated hepatocytes were also restored by treatment with exogenous carnitine.” According to the news editors, the research concluded: “Exogenous carnitine exerts protective effects against severe burn-induced cellular, fatty-acid metabolism, and mitochondrial dysfunction of hepatocytes by restoring CPT1 activity.”     Red blood cell ‘traffic' contributes to changes in brain oxygenation   Penn State University, July 19, 2021 Adequate blood flow supplies the brain with oxygen and nutrients, but the oxygenation tends to fluctuate in a distinct, consistent manner. The root of this varied activity, though, is poorly understood. Now, Penn State researchers have identified one cause of the fluctuations: inherent randomness in the flow rate of red blood cells through tiny blood vessels called capillaries. According to the researchers, this randomness could have potential implications for understanding the biological build-up mechanisms underlying neurodegenerative diseases, such as Alzheimer's disease. They published their findings in PLOS Biology today. “These oxygenation fluctuations also occur in other tissues, like muscle,” said Patrick Drew, Huck Distinguished Associate Professor of Engineering Science and Mechanics, Neurosurgery and Biomedical Engineering. “The question we had was: Are these fluctuations caused by neural activity or something else?” The fluctuations resemble 1/f-like noise, a statistical pattern showing large fluctuations made up of many small fluctuations and naturally occurring in a variety of phenomena, from stock-market prices to river heights. The researchers investigated the fluctuations in mice due to their brains' similarities to those of humans, according to Drew, who also serves as associate director of the Penn State Neuroscience Institute. First, the researchers monitored the blood flow, oxygenation and electrical signals produced by brain activity—the first time the latter two had been tracked simultaneously, according to Drew—in awake mice. They collected the data as mice moved on a spherical treadmill for up to 40 minutes at a time. Next, to investigate the relationship between brain activity and oxygenation fluctuations, the researchers used pharmacological compounds to temporarily and reversibly silence neural signals in the mice's brains. Despite the silencing, the fluctuations continued, showing little correlation between neural activity and oxygenation. The passage of red blood cells, however, told a different story. Using two-photon laser scanning microscopy, an imaging technique used to visualize cells deep inside living tissue, the researchers could visualize the passage of individual red blood cells through capillaries. “It's like traffic,” Drew said. “Sometimes there are a lot of cars going by, and the traffic gets plugged up, and sometimes there aren't. And red blood cells go either way when they approach a junction, so this random flow can lead to bottlenecks and stalls in the vessel.” Importing experimental data into a statistical model allowed the researchers to run further simulations and make inferences based on massive amounts of data produced by the model. The researchers discovered that these random red blood cell stoppages contributed to the fluctuations in oxygenation, further supporting a relationship between the flow of red blood cells through capillaries and the tiny changes in oxygenation that formed larger trends. Better understanding the regulation of blood flow and subsequent transport of oxygen can help researchers improve medical technology and explore causes of diseases such as Alzheimer's, according to Drew. While the researchers identified the link between red blood cell transport and oxygenation, further research is needed to investigate additional contributors to oxygenation fluctuations that could play a role in neurodegenerative diseases. Kyle Gheres, a graduate student in the intercollege Graduate Program in Molecular Cellular and Integrative Biosciences, also contributed to this paper. Qingguang Zhang, assistant research professor of engineering science and mechanics, served as first author on the paper. This work was supported by the National Institutes of Health.     EGCG in Green Tea inhibits the growth of breast cancer cells Chonbuk National University School of Medicine (S Korea), July 21, 2021   Findings on Breast Cancer Reported by Researchers at Chonbuk National University School of Medicine(Epigallocatechin gallate inhibits the growth of MDA-MB-231 breast cancer cells via inactivation of the b-catenin signaling pathway) According to news reporting originating in Chonbuk, South Korea, research stated, "Epigallocatechin gallate (EGCG), a major constituent of green tea, has potential as a treatment for a variety of diseases, including cancer. EGCG induces apoptosis and inhibits tumorigenesis through multiple signaling pathways in breast cancer cells. b-catenin signaling modulators could be useful in the prevention and therapy of breast cancer." The news reporters obtained a quote from the research from the Chonbuk National University School of Medicine, "However, the precise anticancer effect of EGCG through the b-catenin signaling pathway in breast cancer is unclear. The present study investigated the association between b-catenin expression and clinicopathological factors of breast cancer patients, and the effect of EGCG on b-catenin expression in breast cancer cells. b-catenin expression was analyzed according to the clinicopathological factors of 74 patients with breast cancer. All patients were females diagnosed with invasive ductal carcinoma. Western blot analysis revealed that b-catenin was expressed at higher levels in breast cancer tissue than in normal tissue. b-catenin expression was associated with lymph node metastasis (p=0.04), tumor-node-metastasis stage (p=0.03) and estrogen receptor status (p

Oncotarget published "TRAIL receptor agonists convert the response of breast cancer cells to ONC201 from anti-proliferative to apoptotic" which reported normal fibroblasts do not undergo apoptosis following rhTRAIL plus ONC201. In vivo, MDA-MB-361 tumor growth rate is significantly reduced following treatment with a combination of ONC201 and rhTRAIL as compared to control tumors. Natural killer cells which use TRAIL to kill DR5-expressing cancer cells, exhibit greater cytotoxicity against ONC201-treated breast cancer cells compared to controls. rhTRAIL also converts the response of cells from other tumor types to ONC201 from anti-proliferative to apoptotic. A monoclonal DR5-agonistic antibody converts the response of non-TNBC cells to ONC201 from anti-proliferative to apoptotic. These Oncotarget findings describe a novel therapeutic strategy that potently converts the response of a cancer cell to ONC201 from anti-proliferative to apoptotic. Dr. Wafik S. El-Deiry Founding Editorial Board Member of Oncotarget said, "Breast cancer is the most commonly diagnosed cancer and is the number three cause of cancer-related death in United States women." The potential of TRAIL to kill cancerous cells while leaving normal cells unharmed led to the development and clinical testing of TRAIL-based therapies such as recombinant human TRAIL and death receptor agonistic antibodies. ONC201 potently induced cell death through the extrinsic pathway in cancer cells from a variety of tumor types. The compound is unique in that it is a dual activator of the TRAIL pathway, able not only to upregulate pro-death ligand TRAIL, but also its receptor DR5. Early studies of the mechanism of action of ONC201 showed that the compound inhibited pro-survival kinases Akt and ERK, leading to the dephosphorylation and activation of transcription factor FOXO3a. Previous work has shown that ONC201 is a potent dual inducer of the TRAIL pathway at the level of both the ligand and the receptor, and that breast cancers show decreased sensitivity to TRAIL . The authors hypothesized that profiling the effects of the compound on the TRAIL pathway in breast cancer and identifying blocks in signal transduction would allow us to identify therapeutic strategies with the potential to induce apoptosis and that could potentially translate to tumor regressions in patients who do not respond to treatment with ONC201 alone. The El-Deiry Research Team concluded in their Oncotarget Research Output that this team's previous data showed that in breast cancer, the anti-proliferative effects of ONC201 are more common than the apoptotic effects. While the apoptotic effects of ONC201 led to in vivo efficacy of the compound, the anti-proliferative effects did not. In the present study, they investigated mechanisms as well as strategies to convert the response of breast cancer cells to ONC201 from anti-proliferative to pro-apoptotic. TRAIL receptor agonists such as rhTRAIL or a DR5-agonistic antibody convert the response of these cells to ONC201 from anti-proliferative to apoptotic. These findings may have clinical relevance as ONC201 is currently being tested in patients with breast cancer, and the authors believe that this newly identified combinatorial strategy has the potential to induce tumor regressions in patients with limited response to ONC201 monotherapy. DOI - https://doi.org/10.18632/oncotarget.27773 Full text - https://www.oncotarget.com/article/27773/text/ Correspondence to - Wafik S. El-Deiry - wafik@brown.edu Keywords - ONC201, TRAIL, breast cancer, death receptors, apoptosis

Oncotarget published this trending research paper on October 20, 2020, entitled, "TRAIL receptor agonists convert the response of breast cancer cells to ONC201 from anti-proliferative to apoptotic" by researchers from Temple University, Philadelphia, PA; Fox Chase Cancer Center, Philadelphia, PA; Brown University, Providence, RI; Brown University and the Lifespan Health System, Providence, RI. Abstract: ONC201 was initially identified as an inducer of cell death through the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway. The compound is currently being tested in patients with hematological malignancies and solid tumors, including those of the breast. We investigated strategies to convert the response of breast cancers to ONC201 from anti-proliferative to apoptotic. ONC201 treatment upregulates TRAIL and primes TRAIL-resistant non-triple negative breast cancer (TNBC) cells to undergo cell death through the extrinsic pathway. Remarkably, the addition of exogenous recombinant human TRAIL (rhTRAIL) converts the response of TRAIL-resistant non-TNBC cells to ONC201 from anti-proliferative to apoptotic in a death receptor 5 (DR5)-dependent manner in vitro. Importantly, normal fibroblasts do not undergo apoptosis following rhTRAIL plus ONC201. In vivo, MDA-MB-361 tumor growth rate is significantly reduced following treatment with a combination of ONC201 and rhTRAIL as compared to control tumors. Natural killer (NK) cells which use TRAIL to kill DR5-expressing cancer cells, exhibit greater cytotoxicity against ONC201-treated breast cancer cells compared to controls. rhTRAIL also converts the response of cells from other tumor types to ONC201 from anti-proliferative to apoptotic. A monoclonal DR5-agonistic antibody converts the response of non-TNBC cells to ONC201 from anti-proliferative to apoptotic. Our findings describe a novel therapeutic strategy that potently converts the response of a cancer cell to ONC201 from anti-proliferative to apoptotic. This approach may be clinically relevant and has potential to induce tumor regression of patient tumors with relative resistance to ONC201 monotherapy. Press release - https://www.oncotarget.com/news/pr/breast-cancer-cells-to-onc201-from-anti-proliferative-to-apoptotic/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27773 DOI - https://doi.org/10.18632/oncotarget.27773 Full text - https://www.oncotarget.com/article/27773/text/ Correspondence to - Wafik S. El-Deiry - wafik@brown.edu Keywords - ONC201, TRAIL, breast cancer, death receptors, apoptosis About Oncotarget Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

醫學研究發現大蒜中的大蒜素可以抑制某些癌細胞，並且促進這些癌細胞的凋亡，例如乳癌和胃癌。有沒有人體試驗證實在人體也有這種功效呢？ 參考文獻： Bhaumika I, Pal k, Debnath U. Natural product inspired allicin analogs as novel anti-cancer agents. Bioorg Chem. 2019 May;86:259-272. Abstract A series of novel analogs of Allicin (S-allyl prop-2-ene-1-sulfinothioate) present in garlic has been synthesized in high yield. Synthesized 23 compounds were evaluated against different breast cancer cells (MDA-MB-468 and MCF-7) and non-cancer cells (WI38). Four compounds (3f, 3h, 3m and 3u) showed significant cytotoxicity against cancer cells whereas nontoxic to the normal cells. Based on the LD50 values and selectivity index (SI), compound 3h (S-p-methoxybenzyl (p-methoxyphenyl)methanesulfinothioate) was considered as most promising anticancer agent amongst the above three compounds. Further bio-chemical studies confirmed that compound 3h promotes ROS generation, changes in mitochondrial permeability transition and induced caspase mediated DNA damage and apoptosis. Gastric cancer remains high prevalence and fatality rates in China even though its morbidity has been decreased drastically. Allicin, which is from an assistance food-garlic (Allium Sativum L), was found to be effective in gastric cancer treatment. It is a defensive substance with a board biological properties: inhibition of bacteria, fungus, virus, controlled hypertension, diabetes, and chemoprevention of several cancers, etc. Experiments have shown that allicin can be chemopreventive to gastric cancer by inhibiting the growth of cancer cells, arresting cell cycle at G2/M phase, endoplasmic reticulum (ER) stress, and mitochondria-mediated apoptosis, which includes the caspase-dependent/-independent pathways and death receptor pathway. Those mechanisms probably involve in modulating enzymatic activity, restraining DNA formation, scavenging free radicals, and affecting cell proliferation and even tumor growth. Therefore, this review is focus on the mechanism of allicin in gastric cancer. 各位朋友，若您有醫美、減肥、健康相關問題，請直接到「景升診所」官網任一頁面留言，或用下列方法與我們聯絡： 直接撥打24小時專線 +886-931919066 Line id=“Gscline" WeChat id=“Gscline" 哈囉，大家好: 我們有幾個不同的頻道： Grand Health 大健康 （健康加財富、知足就是福）https://goo.gl/6EGLMd Grand Beauty 大醫美 （好好愛自己、就從現在起）https://goo.gl/g1E1rq Grand Touring 大旅遊 （大叔向前跑、永遠沒煩惱）https://goo.gl/7HN4bk 歡迎大家欣賞，喜歡就請按個讚，想獲取最新訊息就按「訂閱」吧！ 我們會提供更多更新的知識和訊息給大家。 感謝以下單位的幫助： ✪景升診所 https://www.genesis-clinic.org https://www.gscline.com ✪愛瘦美官網 https://www.isome.com.tw ✪邱醫師醫話園 https://www.okclinic.gscline.com ✪隆乳 https://www.gscline.com/ifatgraft/breast-adsc-htm ✪減肥 https://www.gscline.com/islimcenter-htm/fat-htm ✪自體脂肪隆乳 https://www.gscline.com/ifatgraft/breast-adsc-htm ✪瘦臉 https://www.gscline.com/ilipolysis-htm/fll-face-htm ✪瘦手臂 https://www.gscline.com/ilipolysis-htm/fll-arm-htm ✪瘦小腹 https://www.gscline.com/ilipolysis-htm/fll-abdomen-htm ✪瘦腿 https://www.gscline.com/ilipolysis-htm/fll-leg-htm ✪瘦大腿 https://www.gscline.com/ilipolysis-htm/fll-thigh-htm ✪抽脂 https://www.gscline.com/liposuction-new-technique/fat_liposuction-htm ✪男性女乳 https://www.gscline.com/ihair-htm/fll-gynecomastia-htm ✪狐臭 https://www.gscline.com/ihair-htm/laserhyperhidrosis-htm

Light Em UP! Targeted Combination Therapy Kills Cancer Cells in Less than 2 Hours Show Guests: Matthew Gdovin & Tom Roberts, CEO According the National Cancer Society, a staggering 606,000 people died of cancer in the U.S in 2019. When a cancer tumor grows in the body, it creates an acidic environment on the outside of its cells. This acidic environment causes blood vessels to grow and attach to the tumor in an attempt to remove the acid. In something of a biological trick, the tumor then commandeers the blood vessels and uses them as a source of nutrients to help it grow. The current standard of care to treat cancer is to cut (surgery), poison (chemotherapy), or ablate (radiation therapy). Unfortunately, these treatments can cause debilitating unwanted side-effects. Vitanova Biomedical (VNB) is developing an alternative therapy, Light-Activated Acidosis (LAIA), which uses a focused beam of light to activate a targeted drug injected into the tumor. Once activated, this drug causes the cancer cell to become very acid on the inside triggering rapid apoptosis (cell death). LAIA therapy has proven capable of killing up to 95 percent of cancer cells within two hours across five different cancer cell types including breast cancers including the very aggressive triple negative breast cancer (MDA-MB-231), two types of prostate cancers (LNCaP and 22RV1), and a pancreatic cancer (BxPC3). sparing near-by healthy tissue, and potentially causes no debilitating unwanted side effects. Tom Roberts, the company’s CEO, resports that VNB has entered a global strategic partnership with LiteCure Medical Lasers, and was awarded a competitive National Science Foundation SBIR Program Phase I grant to further develop LAIA therapy. Together, these partnerships should help to advance VNB’s LAIA therapy from laboratory bench to an FDA submission….and ultimately provide an effective alternative cancer treatment for multiple cancer types.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.12.248179v1?rss=1 Authors: Szulczewski, J. M., Inman, D. R., Proestaki, M., Notbohm, J., Burkel, B. M., Ponik, S. M. Abstract: Mechanosensory cues from the extracellular matrix underpin numerous cellular behaviors including tumor cell migration yet are influenced by the local structure and organization of the matrix in unknown ways. To investigate mechanical cues with respect to local collagen organization, we used a combination of intravital imaging of the mammary tumor microenvironment and 3D collagen gel systems with both migratory MDA-MB-231 cells and acellular pNIPAAm beads. We identified that fiber organization directs a bias in cell response along the axis of alignment. Using innovative methodology, we determined that local collagen alignment resulted in a 30-fold difference in directional cell-scale stiffness and also dramatically altered the rate at which cell-induced fiber displacements decayed over distance. Our results reveal differential mechanical properties across orthogonal directions in aligned matrices that provide sizeable cues to the cell and have important implications for cellular mechanosensing and cell-cell communication within the tissue microenvironment. Copy rights belong to original authors. Visit the link for more info

Volume 11, Issue 22 of Oncotarget reported that the goal of this study was to explore the involvement of mi RNAs in beneficial effects exerted by physical activity in breast cancer prevention. The levels of extracellular mi RNAs were evaluated in blood plasma before and after structured exercise by means of microarray analysis of 1,900 mi RNAs identifying mostly modulated mi RNAs. The different expressions of two mi RNAs involved in breast cancer progression, i. e. up-regulation of mi R-206 and down-regulation of anti-miR-30c, were the most striking effects induced by exercise. The biological effects of these mi RNAs were investigated in MCF-7 human breast cancer cells. The evaluation of these mi RNAs in the blood can be used as non-invasive biomarkers for breast cancer prevention. Dr. Alessandra Pulliero from the Department of Health Sciences at The University of Genoa said, "The relevance of structured exercise for public health has been addressed by the World Health Organization, and its lack is estimated to be the main risk factor for 21–25% of breast and colon cancer cases, 27% of diabetes cases, and 30% of ischemic heart disease cases." Breast cancer survivors engaging in structured exercise increase the drainage of lymph from their upper limbs, thereby decreasing the side effects of mastectomy, significantly lowering their risk of cancer relapse and improving their immune functions. Structured exercise improves insulin resistance, reduces hyperinsulinaemia and reduces the risk for diabetes, which could explain the link between increased structured exercise and reduced risk for these cancers. Recent findings indicate that women with a history of breast cancer who engage in more than 9 metabolic equivalent h/week of structured exercise after a breast cancer diagnosis had a significantly lower risk of death or breast cancer recurrence than women who were physically inactive. Incubation of MCF-7 estrogen-responsive breast cancer cells and MDA-MB-231 triple-negative breast cancer cells treated with post-exercise serum, from both healthy volunteers and operated cancer patients resulted in a reduction of breast cancer cell viability in comparison with breast cancer cells incubated with pre-exercise sera. Accordingly, the authors analyzed circulating mi RNAs expression profiles before and after structured exercise and evaluated their potential anti-cancer properties in breast cancer cells. The Pulliero Research Team concluded in their Oncotarget Research Article, "this study provides evidence that miRNA modulation is a specific molecular mechanism through which structured exercise exerts preventive effects against cancer. The possibility of using these two miRNAs for breast cancer prevention is of interest. MicroRNA as delivered by lipid nanoparticles has been already been effective in mice in preventing NNK induced lung cancer [46]. However, insofar no similar experiments exist as far as concern breast cancer prevention. Moreover, the evaluation of miR-206 and anti-miR-30c levels in the blood of breast cancer patients could be useful as non-invasive biomarkers in guiding future strategies for cancer prevention." DOI - https://doi.org/10.18632/oncotarget.27609 Full text - https://www.oncotarget.com/article/27609/text/ Correspondence to - Alessandra Pulliero - alessandra.pulliero@unige.it About Oncotarget Oncotarget is a weekly, peer-reviewed, open-access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls

The SLAS2020 Student Poster Competition Award winners were chosen out of more than 300 poster abstract submissions and were judged on various content and design themes. The SLAS Student Poster Award recognizes the innovative research by students, graduate students, post-doctoral associates and junior faculty (less than four years in first academic appointment) who are chosen to present a poster during the SLAS International Conference and Exhibition. This year's winners are:Choon Leng So, School of Pharmacy, The University of QueenslandA High-Throughput Assessment of Calcium Signaling in MDA-MB-231 Breast Cancer Cells Expressing the Genetically Encoded Calcium Indicator GCaMP6m and Cultured in Different Matrix StiffnessShingo Honda, The University of TokyoAn Air-Sealed Multi-Dimensional (MD) Digital Assay for Detection of Inhibitor-Resistant Influenza VirusSunil Singh, University of AkronA High-Throughput Organotypic Breast Tumor Model Elucidates Dynamic Remodeling of Tumor MicroenvironmentRegistration is now open for the 2022 AI Data Pipelines for Life Sciences Symposium in Seattle, WA, September 26-27.This two-day symposium will allow participants to explore how AI data pipelines are integrated into the life sciences. Attendees will learn about MLOPS, applications, techniques, and architectures of data and their uses in the life sciences. The SLAS 2022 Bio Entrepreneurship Symposium will allow emerging bio entrepreneurs, start-up companies, academics and those considering bio-entrepreneurship to explore the start-up ecosystem. Register by visiting: https://www.slas.org/events-calendar/slas-2022-bio-entrepreneurship-symposium/attend/register/

Pomegranates are as close to a miracle food as Mother Nature gets. Pomegranates protect your heart, safeguard your estrogens, “sensitize” insulin receptors better than many diabetic drugs without nasty side effects, slow down aging, and fight cancer.   Pomegranates fight against lots of bad stuff. Anti-inflammatory Anti-oxidant Anti-bad cholesterol Anti-heart disease Anti-kidney disease Anti-cognitive disease Anti-diabetic Anti-obesity Anti-carcinogenic   Pomegranates support a lot of good actions: Pro-nitric oxide availability and levels Pro-kidney health Pro-blood vessel health Pro-heart health Pro-bone health Pro-immune supportive Pro-mitochondrial support Pro-brain protection   In this show you will learn exactly how pomegranates protect heart health: Makes APOCIII genetic glitches work better. Lowers bad cholesterol Lowers Oxidized Cholesterol Makes cholesterol less dangerous and less sticky. Boosts enzymes that keep blood fats healthier. Reduces size of plaque (atherosclerotic lesions). Lower blood pressure Reduce Blood clotting Increases nitric oxide Treats angina You’ll discover that allparts of pomegranates contain healthy plant compounds. The reddish kernel(referred to as a pomegranate “aril”), and The whitish seed corein the middle of the kernel where the distinct oiland fiber Pomegranate juicecontains all of these components, though it contains more available sugars then chewing the arils whole. Hard to conceive that pomegranates contain a one-of-a-kind omega fatty acid, omega-5 fatty acid. No other plant on earth contains this special compound. You will hear what omega-5 fatty acid does for the human body, including liver, brain, breast and prostate tissue. It is rather stunning to realize that numerous scientific articles conclude that pomegranates are type-2 diabetics best friend. Why?  Because Punicicacid, the main ingredient of pomegranateomega-5 seed oil, is a “peroxisome proliferator-activated receptor gamma” agonist. This means it signals insulin receptors. Yet, unlike synthetic insulin signalers, such as the diabetic family of drugs called thiazolidinedione’s, pomegranate oil has no nasty side effects. Pomegranates also fight insulin resistance.. You will hear a discussion on pomegranates as an “Adaptogenic Food Estrogen” and how consuming pomegranates regularly effects sex steroid hormones, such as estrogen. Pomegranates also fight cancer. The compounds in the arils fight tumors cells as well as inhibit cancer stem cells. It's cancer stem cells that cause most of cancer recurrences. Pomegranateseed oil blocks most (90% inhibition) of proliferation of ER+ laboratory breast cancer cells (called MCF-7cells, first harvested from a nun and then cultured continually in experimental cancer labs all over the world). Pomegranates cause 54% of cancer cell death in ER- breast cancer cells (MDA-MB-435). Pomegranates are strikingly kidney protective and reduce both renal and heart complications in kidney patients down the road. After this show you will know exactly what a pomegranate aril is, where to get it and how often to consume it. And you will realize the few pomegranate contraindications. This show is jammed packed with “food as medicine” facts! Also, don’t miss Berkson Blog on pomegranates coming soon, too, at drlindseyberkson.com

Full text - http://bit.ly/2mlYU6k "ERβ inhibits cyclin dependent kinases 1 and 7 in triple negative breast cancer" Abstract - Triple negative breast cancer (TNBC), which comprises approximately 15% of all primary breast cancer diagnoses, lacks estrogen receptor alpha, progesterone receptor and human epidermal growth factor receptor 2 expression. However, we, and others, have demonstrated that approximately 30% of TNBCs express estrogen receptor beta (ERβ), a nuclear hormone receptor and potential drug target. Treatment of ERβ expressing MDA-MB-231 cells with estrogen or the ERβ selective agonist, LY500307, was shown to result in suppression of cell proliferation. This inhibitory effect was due to blockade of cell cycle progression. In vivo, estrogen treatment significantly repressed the growth of ERβ expressing MDA-MB-231 cell line xenografts. Gene expression studies and ingenuity pathway analysis identified a network of ERβ down-regulated genes involved in cell cycle progression including CDK1, cyclin B and cyclin H. siRNA mediated knockdown or drug inhibition of CDK1 and CDK7 in TNBC cells resulted in substantial decreases in proliferation regardless of ERβ expression. These data suggest that the tumor suppressive effects of ERβ in TNBC result from inhibition of cell cycle progression, effects that are in part mediated by suppression of CDK1/7. Furthermore, these data indicate that blockade of CDK1/7 activity in TNBC may be of therapeutic benefit, an area of study that has yet to be explored. Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N www.Oncotarget.com

Targeting the cytoskeleton (CSK) of cancer cells offers a valuable strategy in cancer therapy. Whereas drugs which address microtubule CSK such as vinca alkaloids or taxanes are well established in the clinic, compounds binding to the actin CSK are still far away from their therapeutical application. One reason might be the lacking knowledge on their mode of cytotoxicity and moreover their tumor specific mechanism of action. We used the myxobacterial compound Chondramide as a tool to first elucidate the mechanisms of cytotoxicity by actin targeting in different breast cancer cells, namely MCF7 and MDA-MB-231. Chondramide inhibits actin filament assembly and dynamics shown by a fluorescence-based analysis (FRAP) in whole cells and leads to apoptosis characterized by phosphatidylserine exposure, release of cytochrome C from mitochondria and finally activation of caspases (-9 and -3). Detailed analysis revealed, that Chondramide induces apoptosis by enhancing the occurrence of mitochondrial permeability transition (MPT). Known MPT-modulators were found to be affected by Chondramide: Hexokinase II (HkII) bound to the voltage dependent anion channel (VDAC) translocated from the outer mitochondrial membrane to the cytosol and the proapoptotic protein Bad was recruited to the mitochondria. Importantly, PKCε, a prosurvival serine/threonine kinase possessing an actin-binding site and known to regulate the HkII/VDAC interaction as well as Bad phosphoylation was identified as the link between actin CSK and apoptosis induction. PKCε which was found overexpressed in breast cancer cells accumulated in actin bundles induced by Chondramide and lost its activity. The second goal of our work was to inform on a potential tumor specific action of actin binding agents such as Chondramide. As the nontumor breast epithelial cell line MCF-10A in fact shows resistance to Chondramide induced apoptosis and notably express very low level of PKCε we claim that trapping PKCε via Chondramide induced actin hyperpolymerization displays tumor cell specificity. Our work provides a link between targeting the ubiquitously occurring actin CSK and selective inhibition of pro-tumorigenic PKCε, thus setting the stage for actin-stabilizing agents as innovative cancer drugs. This is moreover supported by the in vivo efficacy of Chondramide triggered by abrogation of PKCε signaling shown in a xenograft breast cancer model. For the actin targeting compound Doliculide we could show that Doliculide impairs the dynamics of the actin CSK similar to Chondramide. Moreover, it reduces the proliferation rate and migration of cancer cells and also leads to the induction of apoptosis, thus Doliculide is also an interesting lead structure for further preclinical investigations.

Fighting metastasis is a major challenge in cancer therapy and novel therapeutic targets and drugs are highly appreciated. Resistance of invasive cells to anoikis, a particular type of apoptosis induced by loss of cell-extracellular matrix (ECM) contact, is a major prerequisite for their metastatic spread. Inducing anoikis in metastatic cancer cells is therefore a promising therapeutic approach. The vacuolar H+-ATPase (V-ATPase), a proton pump located at the membrane of acidic organelles, has recently come to focus as an anti-metastatic cancer target. As V-ATPase inhibitors have shown to prevent invasion of tumor cells and are able to induce apoptosis we proposed that V-ATPase inhibition induces anoikis related pathways in invasive cancer cells. In this study the V-ATPase inhibitor archazolid A was used to investigate the mechanism of anoikis induction in various metastatic cancer cells (T24, MDA-MB-231, 4T1, 5637). Therefore, cells were forced to stay in a detached status to mimic loss of cell-ECM engagement following treatment with archazolid. Indeed, anoikis induction by archazolid was characterized by decreased expression of the caspase-8 inhibitor c-FLIP and caspase-8 activation, thus triggering the extrinsic apoptotic pathway. Interestingly, active integrin β1, which is known to play a major role in anoikis induction and resistance, is reduced on the cell surface of archazolid treated cells. Furthermore, a diminished phosphorylation of the integrin downstream target focal adhesion kinase could be demonstrated. The intrinsic apoptotic pathway was initiated by the pro-apoptotic protein BIM, increasing early after treatment. BIM activates cytochrome C release from the mitochondria consequently leading to cell death and is described as one major inducer of anoikis in non-malignant and anoikis sensitive cancer cells. Of note, we observed that archazolid also induces mechanisms opposing anoikis such as proteasomal degradation of BIM mediated by the pro-survival kinases ERK, c-Src and especially Akt at later time points. Moreover, induction of reactive oxygen species (ROS) influences BIM removal as well, as moderate levels of ROS have second messenger properties amplifying cell survival signals. Thus, to antagonize these anoikis escape strategies a combination of archazolid with proteasome or ROS inhibitors amplified cancer cell death synergistically. Most importantly, intravenous injection of archazolid treated 4T1-Luc2 mouse breast cancer cells in BALB/cByJRj mice resulted in reduced lung metastases in vivo. To summarize this work we propose archazolid as a very potent drug in inducing anoikis pathways in metastatic cancer cells even though having learned that detachment together with treatment triggers multiple resistance mechanisms opposing cell death. Hence, V-ATPase inhibition is not only an interesting option to reduce cancer metastasis but also to better understand anoikis resistance and to find choices to fight against it.

Micro-patterned surfaces are frequently used in high-throughput single-cell studies, as they allow one to image isolated cells in defined geometries. Commonly, cells are seeded in excess onto the entire chip, and non-adherent cells are removed from the unpatterned sectors by rinsing. Here, we report on the phenomenon of cellular self-organization, which allows for autonomous positioning of cells on micro-patterned surfaces over time. We prepared substrates with a regular lattice of protein-coated adhesion sites surrounded by PLL-g-PEG passivated areas, and studied the time course of cell ordering. After seeding, cells randomly migrate over the passivated surface until they find and permanently attach to adhesion sites. Efficient cellular self-organization was observed for three commonly used cell lines (HuH7, A549, and MDA-MB-436), with occupancy levels typically reaching 40-60% after 3-5 h. The time required for sorting was found to increase with increasing distance between adhesion sites, and is well described by the time-to-capture in a random-search model. Our approach thus paves the way for automated filling of cell arrays, enabling high-throughput single-cell analysis of cell samples without losses.

Introduction: The HIV protease inhibitor nelfinavir is currently under investigation as a new anti-cancer drug. Several studies have shown that nelfinavir induces cell cycle arrest, endoplasmic reticulum stress, autophagy, and apoptosis in cancer cells. In the present article, the effect of nelfinavir on human breast cancer cells is examined and potential combination treatments are investigated. Methods: The effects of nelfinavir and tamoxifen on the human breast cancer cell lines MCF7, T47 D, MDA-MB-453, and MDA-MB-435 were tested by analysing their influence on cell viability (via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay), apoptosis (annexin binding, poly(ADP-ribose) polymerase cleavage), autophagy (autophagy marker light chain 3B expression), endoplasmic reticulum stress (binding protein and activating transcription factor 3 expression), and the occurrence of oxidative stress (intracellular glutathione level). Results: Nelfinavir induced apoptosis in all four breast cancer cell lines tested, although the extent of autophagy and endoplasmic reticulum stress varied among the cell lines. The concentration of nelfinavir needed for an efficient induction of apoptosis in breast cancer cells could be reduced from 15 mu g/ml to 6 mu g/ml when combined with tamoxifen. At a concentration of 6 mu g/ml, tamoxifen substantially enhanced the endoplasmic reticulum stress reaction in those cell lines that responded to nelfinavir with binding protein (BiP) upregulation (MCF7, T47D), and enhanced autophagy in cell lines that responded to nelfinavir treatment with autophagy marker light chain 3B upregulation (MDA-MB-453). Although tamoxifen has been described to be able to induce oxidative stress at concentrations similar to those applied in this study (6 mu g/ml), we observed that nelfinavir but not tamoxifen reduced the intracellular glutathione level of breast cancer cells within hours of application by up to 32%, suggesting the induction of oxidative stress was an early event and an additional cause of the apoptosis induced by nelfinavir. Conclusions: The results demonstrate that nelfinavir may be an effective drug against breast cancer and could be combined with tamoxifen to enhance its efficacy against breast cancer cells. Moreover, the cytotoxic effect of a tamoxifen and nelfinavir combination was independent of the oestrogen receptor status of the analysed breast cancer cells, suggesting a potential benefit of a combination of these two drugs even in patients with no hormone-responsive tumours. We therefore recommend that clinical studies on nelfinavir with breast cancer patients should include this drug combination to analyse the therapeutic efficacy as well as the safety and tolerability of this potential treatment option.

Background: Curcumin induces apoptosis in many cancer cells and it reduces xenograft growth and the formation of lung metastases in nude mice. Moreover, the plant derived polyphenol has been reported to be able to overcome drug resistance to classical chemotherapy. These features render the drug a promising candidate for tumor therapy especially for cancers known for their high rates concerning therapy resistance like melanoma. Results: We show here that the melanoma cell line M14 is resistant to Curcumin induced apoptosis, which correlates with the absence of any effect on NF kappa B signaling. We show that CXCL1 a chemokine that is down regulated in breast cancer cells by Curcumin in an NF kappa B dependant manner is expressed at variable levels in human melanomas. Yet in M14 cells, CXCL1 expression did not change upon Curcumin treatment. Following the hypothesis that Curcumin is rapidly removed from the resistant cells, we analyzed expression of known multi drug resistance genes and cellular transporters in M14 melanoma cells and in the Curcumin sensitive breast cancer cell line MDA-MB-231. ATP-binding cassette transporter ABCA1, a gene involved in the cellular lipid removal pathway is over-expressed in resistant M14 melanoma as compared to the sensitive MDA-MB-231 breast cancer cells. Gene silencing of ABCA1 by siRNA sensitizes M14 cells to the apoptotic effect of Curcumin most likely as a result of reduced basal levels of active NF kappa B. Moreover, ABCA1 silencing alone also induces apoptosis and reduces p65 expression. Conclusion: Resistance to Curcumin thus follows classical pathways and ABCA1 expression should be considered as response marker.

Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel.

Maligne Tumorzellen besitzen die Fähigkeit, sich vom Primärtumor zu lösen und Metastasen zu bilden. Ein Verlust oder Mutationen im Kalzium-abhängigen, homophilen Zell-Adhäsionsmolekül E-Cadherin korrelieren häufig mit der Metastasierung epithelialer Tumore. Vorarbeiten haben gezeigt, dass in humanen E-Cadherin negativen MDA-MB-435S Zellen die Transfektion von bestimmten mutierten E-Cadherin Genen zu einer reduzierten Adhäsion, erhöhten Motilität und veränderten Zellmorphologie führt. Basierend auf diesen Vorarbeiten war das Ziel dieser Arbeit zu untersuchen, welchen Einfluß mutierte E-Cadherine und der Zellkontakt auf das Genexpressionsprofil haben. Das Genexpressionsprofil wurde mittels eines im Rahmen dieser Arbeit etablierten 1259 Sonden (~899 Gene) umfassenden cDNA Mikroarrays bestimmt. Es konnten 88 Prozent der mittels des cDNA Mikroarrays gefundenen Genexpressionsunterschiede durch die Validierung mit Northern Blot Analyse und 94 Prozent durch quantitative realtime RT PCR im Bezug auf die Richtung der Genexpressionsveränderung bestätigt werden. Mit Hilfe des cDNA Mikroarrays wurde der Einfluß von E-Cadherin auf den WNT-Signalweg untersucht. Die in dieser Arbeit durchgeführten Gen- und Proteinexpressionsuntersuchungen zeigten, dass der E-Cadherin Status die Expression der im WNT-Signalweg involvierten Gene DKK1, SFRP1, SFRP3, CTNNAL1 und FZD7 so beeinflusst, dass die beta-Catenin Menge in der Zelle stabil gehalten wird. Diese Ergebnisse wurden bereits in Laboratory Investigation (Laux et al., 2004) publiziert. Die Zelllinien, die aufgrund von E-Cadherin Mutationen den Zell-zu-Zellkontakt verloren haben, zeigten eine differentielle Expression von Genen, die in der Angiogenese, Proliferation, Matrix Degradierung und Motilität involviert sind. Viele dieser Gene spielen in der Metastasierung als auch in der Wundheilung eine wichtige Rolle. Die Zelllinie mit WT E-Cadherin Status hat einen engen Zell-zu-Zellkontakt und zeigte eine erhöhte Expression von E-Cadherin Repressoren im Vergleich zu den E-Cadherin negativen oder mutierten Zelllinien. Bei einer hohen Zelldichte konnte ebenfalls eine erhöhte Genexpression der E-Cadherin Repressoren detektiert werden. Die Zelllinien erkennen sensitiv den Zell-zu-Zellkontakt Status und regulieren daraufhin autokrin den E-Cadherin Status über eine veränderte Expression der E-Cadherin Repressoren. Eine Regulation des E-Cadherin Status war bei den hier verwendeten Zelllinien aber aufgrund eines artfremden beta-Aktin Promotors vor den E-Cadherin Konstrukten nicht möglich. Um festzustellen, inwieweit der Zell-zu-Zellkontakt für die E-Cadherin abhängige differentielle Expressionen verantwortlich ist, wurde dessen Einfluß auf das Genexpressionsprofil mittels Zelldichteversuche untersucht. Bei einer geringen Zelldichte, bei der die Zellen wenig Kontakt zueinander haben, korrelieren die Genexpressionsver-änderungen mit denen der Zelllinien, die aufgrund von E-Cadherin Mutationen keinen Zell-zu-Zellkontakt haben. Die vorliegende Arbeit hat zur Identifikation von Genen, welche eine wichtige Rolle in der durch mutiertes E-Cadherin vermittelten Invasion spielen (z.B. MMP1, MMP3, VEGFC, SPARC, ITGA3, CYR61, TIMP3, PRKCD, MXI1, PRLR, PLAUR und LASP1), beigetragen. Ebenso konnte gezeigt werden, dass der Zellkontakt maßgeblich an der differentiellen Expression deren Gene beteiligt ist. Weiterführende Studien können nun die gefundenen Kandidatengene bezüglich Diagnose und Therapie von malignen Tumoren mit E-Cadherin Mutationen genauer charakterisieren. Die Inhibition einiger dieser Proteine stellt einen viel versprechenden Therapieansatz zur Behandlung dieser Tumoren dar.