The Tisch Cancer Institute

New York City, NY, United States

The Tisch Cancer Institute

New York City, NY, United States
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NEW YORK, May 22, 2017 (GLOBE NEWSWIRE) -- Tyme Technologies, Inc. (OTCQB:TYMI), a clinical stage biotechnology company developing cancer therapeutics to address multiple tumor types, today announced that it will present data from its ongoing clinical trial with its investigational drug candidate SM-88 in prostate cancer at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago from June 2 – 6, 2017. Details of the Company’s poster presentation are listed below: A Phase Ib/II, Open-label, Dose Escalation Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of SM-88 in Patients with Prostate Cancer (J Clin Oncol 35, 2017 (suppl; abstr TPS2615)) Poster Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics Date and Time:  Monday June 5, 2017, 8:00 AM - 11:30 AM CT Location: Hall A, Poster Board: #97b Presenter: Dr. Giuseppe Del Priore, Chief Medical Officer of Tyme Technologies, Inc. Additionally, the following abstracts have been published online in conjunction with the Meeting and are available for review via the hyperlinks below. SMK/SM-88 Toxicity, Efficacy, and Patient Reported Outcomes in Metastatic Pancreas Cancer Author(s): Steve Hoffman, Jeanetta Stega, Giuseppe Del Priore, John Rothman; Tyme Inc, New York, NY; Morehouse School of Medicine, Atlanta, GA. J Clin Oncol 35, 2017 (suppl; abstr e14060). SM-88/SMK Non-hormonal Therapy in Recurrent or Untreated Prostate Cancer Author(s): Steve Hoffman, John Rothman, Giuseppe Del Priore, Jeanetta Stega; Tyme Inc, New York, NY; Morehouse School of Medicine, Atlanta, GA. J Clin Oncol 35, 2017 (suppl; abstr e16540). SM-88 in Non-metastatic Rising PSA-recurrent Prostate Cancer Author(s): Giuseppe Del Priore, Gerald H. Sokol, Wen-Tien Chen, Che-Kai Tsao, Steve Hoffman; Morehouse School of Medicine, Atlanta, GA; Florida Cancer Institute New Hope, Hudson, FL; Stony Brook University, Stony Brook, NY; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Tyme Inc, New York, NY. J Clin Oncol 35, 2017 (suppl; abstr e16567). Phase Ib Pharmacokinetics of Non-hormonal SM-88 in Patients with Non-metastatic Recurrent Prostate Cancer Author(s): Giuseppe Del Priore, John Rothman, Gerald H. Sokol, Karen Hoffman, Avi S. Retter, Steve Hoffman; Morehouse School of Medicine, Atlanta, GA; Tyme Inc, New York, NY; Florida Cancer Institute New Hope, Hudson, FL; Eastchester Center for Cancer Care, Bronx, NY; Montefiore Medical Center, Bronx, NY. J Clin Oncol 35, 2017 (suppl; abstr e14061). About Tyme Tyme Technologies is a clinical-stage biopharmaceutical company focused on development and commercialization of highly targeted cancer therapeutics with a broad range of oncology indications. Its lead investigational candidate, SM-88, is a novel first-in-class therapy that is designed to use cancer’s unusual metabolism to selectively break down the cellular defenses of tumors, leading to tumor cell death. Through clinical trials and expanded access programs, SM-88 has been used in over 84 individuals and shown a clinical response in thirteen cancer types. In its first-in-human trial for end-stage, metastatic cancer patients, SM-88 treatment resulted in a median overall survival of 26 months, with 32% of patients alive at the end of the three-year evaluation period without any drug-related serious adverse events. The Company is currently conducting a Phase II trial in prostate cancer in addition to ongoing collaborations with the Mayo Clinic, Mount Sinai and other institutions. For more information, visit our website: www.tymeinc.com. Forward-Looking Statements/Disclosure Notice In addition to historical information, this press release contains forward-looking statements that involve substantial risks and uncertainties. Such forward-looking statements within this press release include, without limitation, statements regarding our drug candidates (including SM-88), our drug development plans and strategies, our completed and planned clinical trials and the therapeutic design and mechanisms of our drug candidates; and readers can identify forward-looking statements by sentences or passages involving the use of terms such as “anticipates,” “believes,” “designed,” “could,” “estimates,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “projects,” “should,” “would” and similar expressions intended to identify forward-looking statements. The forward-looking statements contained in this press release are based on management’s current expectations, which are subject to uncertainty, risks and changes in circumstances that are difficult to predict and many of which are outside of Tyme’s control. These statements involve known and unknown risks, uncertainties and other factors which may cause the Company’s actual results, performance or achievements to be materially different from any historical results and future results, performances or achievements expressed or implied by the forward-looking statements. These risks and uncertainties include, but are not limited to, uncertainties inherent in research and development, including the ability to achieve clinical study start and completion dates; the possibility of unfavorable study results, including unfavorable new clinical data and additional analyses of existing data; risks associated with early, initial data, including the risk that the final Phase II data analysis, final results of additional clinical trials, or both, may be different from the preliminary data analysis and may not support further clinical development; whether and when any applications or other submissions for SM-88 may be filed with regulatory authorities; whether and when regulatory authorities may approve any applications or submissions; decisions by regulatory authorities regarding labeling and other matters that could affect commercial availability of SM-88; competitive developments; and the factors described in the section captioned “Risk Factors” of Tyme’s Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission on March 30, 2016 (available at www.sec.gov). The information contained in this press release is as of May 22, 2017 and Tyme assumes no obligation to update forward-looking statements contained in this release as a result of future events or developments.


NEW YORK, May 22, 2017 (GLOBE NEWSWIRE) -- Tyme Technologies, Inc. (OTCQB:TYMI), a clinical stage biotechnology company developing cancer therapeutics to address multiple tumor types, today announced that it will present data from its ongoing clinical trial with its investigational drug candidate SM-88 in prostate cancer at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago from June 2 – 6, 2017. Details of the Company’s poster presentation are listed below: A Phase Ib/II, Open-label, Dose Escalation Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of SM-88 in Patients with Prostate Cancer (J Clin Oncol 35, 2017 (suppl; abstr TPS2615)) Poster Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics Date and Time:  Monday June 5, 2017, 8:00 AM - 11:30 AM CT Location: Hall A, Poster Board: #97b Presenter: Dr. Giuseppe Del Priore, Chief Medical Officer of Tyme Technologies, Inc. Additionally, the following abstracts have been published online in conjunction with the Meeting and are available for review via the hyperlinks below. SMK/SM-88 Toxicity, Efficacy, and Patient Reported Outcomes in Metastatic Pancreas Cancer Author(s): Steve Hoffman, Jeanetta Stega, Giuseppe Del Priore, John Rothman; Tyme Inc, New York, NY; Morehouse School of Medicine, Atlanta, GA. J Clin Oncol 35, 2017 (suppl; abstr e14060). SM-88/SMK Non-hormonal Therapy in Recurrent or Untreated Prostate Cancer Author(s): Steve Hoffman, John Rothman, Giuseppe Del Priore, Jeanetta Stega; Tyme Inc, New York, NY; Morehouse School of Medicine, Atlanta, GA. J Clin Oncol 35, 2017 (suppl; abstr e16540). SM-88 in Non-metastatic Rising PSA-recurrent Prostate Cancer Author(s): Giuseppe Del Priore, Gerald H. Sokol, Wen-Tien Chen, Che-Kai Tsao, Steve Hoffman; Morehouse School of Medicine, Atlanta, GA; Florida Cancer Institute New Hope, Hudson, FL; Stony Brook University, Stony Brook, NY; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Tyme Inc, New York, NY. J Clin Oncol 35, 2017 (suppl; abstr e16567). Phase Ib Pharmacokinetics of Non-hormonal SM-88 in Patients with Non-metastatic Recurrent Prostate Cancer Author(s): Giuseppe Del Priore, John Rothman, Gerald H. Sokol, Karen Hoffman, Avi S. Retter, Steve Hoffman; Morehouse School of Medicine, Atlanta, GA; Tyme Inc, New York, NY; Florida Cancer Institute New Hope, Hudson, FL; Eastchester Center for Cancer Care, Bronx, NY; Montefiore Medical Center, Bronx, NY. J Clin Oncol 35, 2017 (suppl; abstr e14061). About Tyme Tyme Technologies is a clinical-stage biopharmaceutical company focused on development and commercialization of highly targeted cancer therapeutics with a broad range of oncology indications. Its lead investigational candidate, SM-88, is a novel first-in-class therapy that is designed to use cancer’s unusual metabolism to selectively break down the cellular defenses of tumors, leading to tumor cell death. Through clinical trials and expanded access programs, SM-88 has been used in over 84 individuals and shown a clinical response in thirteen cancer types. In its first-in-human trial for end-stage, metastatic cancer patients, SM-88 treatment resulted in a median overall survival of 26 months, with 32% of patients alive at the end of the three-year evaluation period without any drug-related serious adverse events. The Company is currently conducting a Phase II trial in prostate cancer in addition to ongoing collaborations with the Mayo Clinic, Mount Sinai and other institutions. For more information, visit our website: www.tymeinc.com. Forward-Looking Statements/Disclosure Notice In addition to historical information, this press release contains forward-looking statements that involve substantial risks and uncertainties. Such forward-looking statements within this press release include, without limitation, statements regarding our drug candidates (including SM-88), our drug development plans and strategies, our completed and planned clinical trials and the therapeutic design and mechanisms of our drug candidates; and readers can identify forward-looking statements by sentences or passages involving the use of terms such as “anticipates,” “believes,” “designed,” “could,” “estimates,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “projects,” “should,” “would” and similar expressions intended to identify forward-looking statements. The forward-looking statements contained in this press release are based on management’s current expectations, which are subject to uncertainty, risks and changes in circumstances that are difficult to predict and many of which are outside of Tyme’s control. These statements involve known and unknown risks, uncertainties and other factors which may cause the Company’s actual results, performance or achievements to be materially different from any historical results and future results, performances or achievements expressed or implied by the forward-looking statements. These risks and uncertainties include, but are not limited to, uncertainties inherent in research and development, including the ability to achieve clinical study start and completion dates; the possibility of unfavorable study results, including unfavorable new clinical data and additional analyses of existing data; risks associated with early, initial data, including the risk that the final Phase II data analysis, final results of additional clinical trials, or both, may be different from the preliminary data analysis and may not support further clinical development; whether and when any applications or other submissions for SM-88 may be filed with regulatory authorities; whether and when regulatory authorities may approve any applications or submissions; decisions by regulatory authorities regarding labeling and other matters that could affect commercial availability of SM-88; competitive developments; and the factors described in the section captioned “Risk Factors” of Tyme’s Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission on March 30, 2016 (available at www.sec.gov). The information contained in this press release is as of May 22, 2017 and Tyme assumes no obligation to update forward-looking statements contained in this release as a result of future events or developments.


NEW YORK, May 22, 2017 (GLOBE NEWSWIRE) -- Tyme Technologies, Inc. (OTCQB:TYMI), a clinical stage biotechnology company developing cancer therapeutics to address multiple tumor types, today announced that it will present data from its ongoing clinical trial with its investigational drug candidate SM-88 in prostate cancer at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago from June 2 – 6, 2017. Details of the Company’s poster presentation are listed below: A Phase Ib/II, Open-label, Dose Escalation Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of SM-88 in Patients with Prostate Cancer (J Clin Oncol 35, 2017 (suppl; abstr TPS2615)) Poster Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics Date and Time:  Monday June 5, 2017, 8:00 AM - 11:30 AM CT Location: Hall A, Poster Board: #97b Presenter: Dr. Giuseppe Del Priore, Chief Medical Officer of Tyme Technologies, Inc. Additionally, the following abstracts have been published online in conjunction with the Meeting and are available for review via the hyperlinks below. SMK/SM-88 Toxicity, Efficacy, and Patient Reported Outcomes in Metastatic Pancreas Cancer Author(s): Steve Hoffman, Jeanetta Stega, Giuseppe Del Priore, John Rothman; Tyme Inc, New York, NY; Morehouse School of Medicine, Atlanta, GA. J Clin Oncol 35, 2017 (suppl; abstr e14060). SM-88/SMK Non-hormonal Therapy in Recurrent or Untreated Prostate Cancer Author(s): Steve Hoffman, John Rothman, Giuseppe Del Priore, Jeanetta Stega; Tyme Inc, New York, NY; Morehouse School of Medicine, Atlanta, GA. J Clin Oncol 35, 2017 (suppl; abstr e16540). SM-88 in Non-metastatic Rising PSA-recurrent Prostate Cancer Author(s): Giuseppe Del Priore, Gerald H. Sokol, Wen-Tien Chen, Che-Kai Tsao, Steve Hoffman; Morehouse School of Medicine, Atlanta, GA; Florida Cancer Institute New Hope, Hudson, FL; Stony Brook University, Stony Brook, NY; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Tyme Inc, New York, NY. J Clin Oncol 35, 2017 (suppl; abstr e16567). Phase Ib Pharmacokinetics of Non-hormonal SM-88 in Patients with Non-metastatic Recurrent Prostate Cancer Author(s): Giuseppe Del Priore, John Rothman, Gerald H. Sokol, Karen Hoffman, Avi S. Retter, Steve Hoffman; Morehouse School of Medicine, Atlanta, GA; Tyme Inc, New York, NY; Florida Cancer Institute New Hope, Hudson, FL; Eastchester Center for Cancer Care, Bronx, NY; Montefiore Medical Center, Bronx, NY. J Clin Oncol 35, 2017 (suppl; abstr e14061). About Tyme Tyme Technologies is a clinical-stage biopharmaceutical company focused on development and commercialization of highly targeted cancer therapeutics with a broad range of oncology indications. Its lead investigational candidate, SM-88, is a novel first-in-class therapy that is designed to use cancer’s unusual metabolism to selectively break down the cellular defenses of tumors, leading to tumor cell death. Through clinical trials and expanded access programs, SM-88 has been used in over 84 individuals and shown a clinical response in thirteen cancer types. In its first-in-human trial for end-stage, metastatic cancer patients, SM-88 treatment resulted in a median overall survival of 26 months, with 32% of patients alive at the end of the three-year evaluation period without any drug-related serious adverse events. The Company is currently conducting a Phase II trial in prostate cancer in addition to ongoing collaborations with the Mayo Clinic, Mount Sinai and other institutions. For more information, visit our website: www.tymeinc.com. Forward-Looking Statements/Disclosure Notice In addition to historical information, this press release contains forward-looking statements that involve substantial risks and uncertainties. Such forward-looking statements within this press release include, without limitation, statements regarding our drug candidates (including SM-88), our drug development plans and strategies, our completed and planned clinical trials and the therapeutic design and mechanisms of our drug candidates; and readers can identify forward-looking statements by sentences or passages involving the use of terms such as “anticipates,” “believes,” “designed,” “could,” “estimates,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “projects,” “should,” “would” and similar expressions intended to identify forward-looking statements. The forward-looking statements contained in this press release are based on management’s current expectations, which are subject to uncertainty, risks and changes in circumstances that are difficult to predict and many of which are outside of Tyme’s control. These statements involve known and unknown risks, uncertainties and other factors which may cause the Company’s actual results, performance or achievements to be materially different from any historical results and future results, performances or achievements expressed or implied by the forward-looking statements. These risks and uncertainties include, but are not limited to, uncertainties inherent in research and development, including the ability to achieve clinical study start and completion dates; the possibility of unfavorable study results, including unfavorable new clinical data and additional analyses of existing data; risks associated with early, initial data, including the risk that the final Phase II data analysis, final results of additional clinical trials, or both, may be different from the preliminary data analysis and may not support further clinical development; whether and when any applications or other submissions for SM-88 may be filed with regulatory authorities; whether and when regulatory authorities may approve any applications or submissions; decisions by regulatory authorities regarding labeling and other matters that could affect commercial availability of SM-88; competitive developments; and the factors described in the section captioned “Risk Factors” of Tyme’s Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission on March 30, 2016 (available at www.sec.gov). The information contained in this press release is as of May 22, 2017 and Tyme assumes no obligation to update forward-looking statements contained in this release as a result of future events or developments.


NEW YORK, May 22, 2017 (GLOBE NEWSWIRE) -- Tyme Technologies, Inc. (OTCQB:TYMI), a clinical stage biotechnology company developing cancer therapeutics to address multiple tumor types, today announced that it will present data from its ongoing clinical trial with its investigational drug candidate SM-88 in prostate cancer at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago from June 2 – 6, 2017. Details of the Company’s poster presentation are listed below: A Phase Ib/II, Open-label, Dose Escalation Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of SM-88 in Patients with Prostate Cancer (J Clin Oncol 35, 2017 (suppl; abstr TPS2615)) Poster Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics Date and Time:  Monday June 5, 2017, 8:00 AM - 11:30 AM CT Location: Hall A, Poster Board: #97b Presenter: Dr. Giuseppe Del Priore, Chief Medical Officer of Tyme Technologies, Inc. Additionally, the following abstracts have been published online in conjunction with the Meeting and are available for review via the hyperlinks below. SMK/SM-88 Toxicity, Efficacy, and Patient Reported Outcomes in Metastatic Pancreas Cancer Author(s): Steve Hoffman, Jeanetta Stega, Giuseppe Del Priore, John Rothman; Tyme Inc, New York, NY; Morehouse School of Medicine, Atlanta, GA. J Clin Oncol 35, 2017 (suppl; abstr e14060). SM-88/SMK Non-hormonal Therapy in Recurrent or Untreated Prostate Cancer Author(s): Steve Hoffman, John Rothman, Giuseppe Del Priore, Jeanetta Stega; Tyme Inc, New York, NY; Morehouse School of Medicine, Atlanta, GA. J Clin Oncol 35, 2017 (suppl; abstr e16540). SM-88 in Non-metastatic Rising PSA-recurrent Prostate Cancer Author(s): Giuseppe Del Priore, Gerald H. Sokol, Wen-Tien Chen, Che-Kai Tsao, Steve Hoffman; Morehouse School of Medicine, Atlanta, GA; Florida Cancer Institute New Hope, Hudson, FL; Stony Brook University, Stony Brook, NY; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Tyme Inc, New York, NY. J Clin Oncol 35, 2017 (suppl; abstr e16567). Phase Ib Pharmacokinetics of Non-hormonal SM-88 in Patients with Non-metastatic Recurrent Prostate Cancer Author(s): Giuseppe Del Priore, John Rothman, Gerald H. Sokol, Karen Hoffman, Avi S. Retter, Steve Hoffman; Morehouse School of Medicine, Atlanta, GA; Tyme Inc, New York, NY; Florida Cancer Institute New Hope, Hudson, FL; Eastchester Center for Cancer Care, Bronx, NY; Montefiore Medical Center, Bronx, NY. J Clin Oncol 35, 2017 (suppl; abstr e14061). About Tyme Tyme Technologies is a clinical-stage biopharmaceutical company focused on development and commercialization of highly targeted cancer therapeutics with a broad range of oncology indications. Its lead investigational candidate, SM-88, is a novel first-in-class therapy that is designed to use cancer’s unusual metabolism to selectively break down the cellular defenses of tumors, leading to tumor cell death. Through clinical trials and expanded access programs, SM-88 has been used in over 84 individuals and shown a clinical response in thirteen cancer types. In its first-in-human trial for end-stage, metastatic cancer patients, SM-88 treatment resulted in a median overall survival of 26 months, with 32% of patients alive at the end of the three-year evaluation period without any drug-related serious adverse events. The Company is currently conducting a Phase II trial in prostate cancer in addition to ongoing collaborations with the Mayo Clinic, Mount Sinai and other institutions. For more information, visit our website: www.tymeinc.com. Forward-Looking Statements/Disclosure Notice In addition to historical information, this press release contains forward-looking statements that involve substantial risks and uncertainties. Such forward-looking statements within this press release include, without limitation, statements regarding our drug candidates (including SM-88), our drug development plans and strategies, our completed and planned clinical trials and the therapeutic design and mechanisms of our drug candidates; and readers can identify forward-looking statements by sentences or passages involving the use of terms such as “anticipates,” “believes,” “designed,” “could,” “estimates,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “projects,” “should,” “would” and similar expressions intended to identify forward-looking statements. The forward-looking statements contained in this press release are based on management’s current expectations, which are subject to uncertainty, risks and changes in circumstances that are difficult to predict and many of which are outside of Tyme’s control. These statements involve known and unknown risks, uncertainties and other factors which may cause the Company’s actual results, performance or achievements to be materially different from any historical results and future results, performances or achievements expressed or implied by the forward-looking statements. These risks and uncertainties include, but are not limited to, uncertainties inherent in research and development, including the ability to achieve clinical study start and completion dates; the possibility of unfavorable study results, including unfavorable new clinical data and additional analyses of existing data; risks associated with early, initial data, including the risk that the final Phase II data analysis, final results of additional clinical trials, or both, may be different from the preliminary data analysis and may not support further clinical development; whether and when any applications or other submissions for SM-88 may be filed with regulatory authorities; whether and when regulatory authorities may approve any applications or submissions; decisions by regulatory authorities regarding labeling and other matters that could affect commercial availability of SM-88; competitive developments; and the factors described in the section captioned “Risk Factors” of Tyme’s Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission on March 30, 2016 (available at www.sec.gov). The information contained in this press release is as of May 22, 2017 and Tyme assumes no obligation to update forward-looking statements contained in this release as a result of future events or developments.


News Article | May 4, 2017
Site: www.eurekalert.org

(New York, NY - May 4, 2017) -- Immunotherapy, which has achieved remarkable results in late-stage lung cancer patients, can also hold great hope for newly diagnosed patients, cutting the deadly disease off before it has the chance to take hold and offering a potential cure, according to a new Mount Sinai study published today in Cell. Researchers at The Tisch Cancer Institute at Mount Sinai discovered that some of the same immune cells that allow immunotherapy to turn around some late-stage lung cancers are also present just as the disease takes hold. Before now, little was known about the immune response in early lung cancer, said Miriam Merad, MD, PhD, Professor of Oncological Sciences and of Medicine (Hematology and Medical Oncology) at The Tisch Cancer Institute at Mount Sinai. Dr. Merad and a multidisciplinary team of thoracic surgeons, pathologists, and scientists devised a comprehensive study that began when patients went into surgery to have cancerous lesions removed. The patients' lung tumor samples, samples of surrounding healthy lung tissue, and blood samples were immediately analyzed on a cellular level to map out the immune system components present. The team of researchers crafted a barcoding method that attaches cells in each sample to a different metal isotope, allowing the samples to be pooled for a simultaneous analysis of cells from all three tissue types. The scientists combined this barcoding approach with high-dimensional profiling to map the complete immune landscape to search for tumor-driven changes that would be vulnerable to targeted immunotherapy. The analysis of the samples showed that stage I lung cancer lesions already harbor immune system components that likely compromise anti-tumor T cells' ability to fend off cancer. These single-cell analyses offered unprecedented detail of tumor-driven immune changes, providing a powerful tool for the future design of immunotherapies such as checkpoint inhibitors, particularly those that target the PD-1 and PD-L1 proteins that shield cancer from the immune system; these checkpoint inhibitors have shown great promise in later-stage cancers. "Immunotherapy has mostly been used in advanced or metastatic lung cancer, but its benefit in early-stage tumors remains unknown," Dr. Merad said. "The standard treatment for early lung cancer is normally surgical removal of the lesions--sometimes with chemotherapy and radiation. Our study reveals that early lung lesions are heavily infiltrated with many different immune cells, suggesting that immunotherapy could also work on very early lesions and potentially lead to a cure by heading cancer off at the pass before it really takes root in the lungs." This new research also identified a multitude of additional immunotherapy targets to increase the number of patients that would significantly benefit from immunotherapy, which at the moment remains fairly small. This research is being used to develop immunotherapy trials with early lung cancer patients. "About 50 percent of patients with small lung cancer lesions relapse," Merad said. "And when lung cancer is advanced, chemotherapy does not have a great success rate, so knowing how to attack the cancer at an early stage could have huge impacts on the number of patients relapsing and their overall survival. Our research further corroborates the belief that immunotherapy agents are most efficient at early stages of cancer, particularly in patients who have never been treated with chemotherapy." Raja M. Flores, MD, Chair of the Department of Thoracic Surgery at Mount Sinai Health System, and his team contributed significantly to the study by identifying patients and providing their tissue samples. Mount Sinai's Human Immune Monitoring Center (HIMC) also played an integral role, by providing a platform to analyze patient samples using quality control assays and cutting-edge technology. Through the HIMC, Dr. Merad plans to build a portal to share the results of this study and of other HIMC research to collaborate with colleagues at other cancer centers in the hopes of promoting further cancer and immunology research. This study was funded by Foundation pour la Recherche Medicale DEA20150633125 and NIH grants R01, R01 CA173861, U19AI128949, U24 AI 118644, U19 AI 117873-01. The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is on the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www. or find Mount Sinai on Facebook, Twitter and YouTube.


Renault T.T.,Mount Sinai School of Medicine | Renault T.T.,The Tisch Cancer Institute | Renault T.T.,The Metabolism Institute | Floros K.V.,Mount Sinai School of Medicine | And 4 more authors.
Methods | Year: 2013

The mitochondrial pathway of apoptosis proceeds when the outer mitochondrial membrane (OMM) is compromised by the pro-apoptotic BCL-2 family members, BAK and BAX. Once activated, BAK and BAX form proteolipid pores in the OMM leading to mitochondrial outer membrane permeabilization (MOMP), and the release of inner membrane space proteins, such as cytochrome c, which promotes caspase activation. The use of isolated mitochondria has been instrumental to understanding the key interactions necessary to engage BAK and BAX activation, MOMP, and apoptosis. Furthermore, it is possible to biochemically define the relationships between BCL-2 family function and mitochondrial physiology using isolated systems. Our laboratory uses freshly isolated mitochondria from numerous sources to better understand BCL-2 family function and requirements for BAK and BAX activation. Here, we will discuss commonly used in vitro techniques to perform MOMP and cytochrome c release assays; and provide several key methodologies to implicate BAK and BAX activity in these processes. © 2013 Elsevier Inc.


Hoeffel G.,Agency for Science, Technology and Research Singapore | Chen J.,Agency for Science, Technology and Research Singapore | Lavin Y.,The Tisch Cancer Institute | Lavin Y.,Mount Sinai School of Medicine | And 20 more authors.
Immunity | Year: 2015

Although classified as hematopoietic cells, tissue-resident macrophages (MFs) arise from embryonic precursors that seed the tissues prior to birth togenerate a self-renewing population, which is maintained independently of adult hematopoiesis. Here we reveal the identity of these embryonic precursors using an in utero MF-depletion strategy and fate-mapping of yolk sac (YS) and fetal liver (FL) hematopoiesis. We show that YS MFs are the main precursors of microglia, while most other MFs derive from fetal monocytes (MOs). Both YS MFs and fetal MOs arise from erythro-myeloid progenitors (EMPs) generated in the YS. In the YS, EMPs gave rise to MFs without monocytic intermediates, while EMP seeding the FL upon the establishment of blood circulation acquired c-Myb expression and gave rise to fetal MOs that then seeded embryonic tissues and differentiated into MFs. Thus, adult tissue-resident MFs established from hematopoietic stem cell-independent embryonic precursors arise from two distinct developmental programs. © 2015 Elsevier Inc.


News Article | December 14, 2016
Site: www.eurekalert.org

(New York, NY - December 12, 2016) -- Even before tumors develop, breast cancer cells with a few defined molecular alterations can spread to organs, remain quiet for long periods of time, and then awaken to form aggressive, deadly breast cancer metastasis, says a team of investigators led by researchers at Icahn School of Medicine at Mount Sinai and the University of Regensburg in Germany. They say their finding, published in two papers in the journal Nature, and conducted in animal models and tested in human samples, now solves the mystery of how breast cancer metastasis forms without a primary tumor in this new model of early dissemination and metastasis. Furthermore, a clinical primary tumor may never develop, investigators say. The University of Regensburg team had discovered that cancer cells could spread not only from a highly mutated, overtly evolved and pathologically-defined invasive tumors, but also from early stage cancers commonly considered incapable of spreading cells. However, how these early cancer lesions could spawn cells with traits of malignant tumors was unknown. In two papers published in the journal Nature, and conducted in animal models and tested in human samples, the two teams now have identified the first mechanisms that allow cells to spread early in cancer progression and contribute to metastasis. In the study from Mount Sinai, two changes in mammary cancer cells -- a switched-on oncogene and a turned-off tumor suppressor-- motivated cells to travel from breast tissue to the lungs and other parts of the body. There, the cells stayed quiet until a growth switch was activated and metastases developed in lungs. "This research provides insight into the mechanisms of early cancer spread and may shed light into unexplained phenomena -- among them, why as many as 5 percent of cancer patients worldwide have cancer metastases but no original tumor, and most importantly, why it is so difficult to treat cancer that has spread," says the study's senior investigators, Julio A. Aguirre-Ghiso, PhD, Professor of Medicine, Hematology and Medical Oncology, Maria Soledad Sosa, PhD, Assistant Professor of Pharmacological Sciences, and graduate student Kathryn Harper of The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. "Biologically, this new model of early metastasis challenges everything we thought we knew about how cancer spreads and forms metastasis. It feels like we are going to have to adjust our ideas about the subject of metastasis," he says. "Our hope is that these findings will reshape the way we think about how metastasis should be treated." An important finding from the Mount Sinai team is that most early spread cells remain dormant and most chemotherapy and targeted therapies are aimed at those cells that are proliferative. So early spread cancer cells would escape these conventional therapies even if it kills a primary tumor, Dr. Aguirre-Ghiso says. The work also poses new questions on how early spread cancer cells support metastasis development. Do they do it on their own, do they set the soil for later arriving cells from tumors not caught early, or do they cooperate with later arriving cells? This study reveals a new biological mechanism of early dissemination that must be explored to fully understand how to target the seeds of metastasis. The companion paper headed by Dr. Christoph Klein at the University of Regensburg in Germany, published in the same issue of Nature and co-authored by Dr. Aguirre-Ghiso and members of his team provides additional key mechanistic clues on how early spread is controlled and proof in human cancer cells and tumors of the preclinical findings in this study. Researchers from both teams arrived at their findings independently and then collaborated on the project. Researchers from both teams studied very early stages of breast cancer including DCIS (ductal carcinoma in situ), a noninvasive breast lesion, since 2-3 percent of women who have been treated for DCIS die of metastasis without ever developing a primary tumor. "The best explanation for this phenomenon is that early metastasis occurs before or as DCIS develops. A key finding from this second paper is that in the mouse models, 80% of metastasis originated from the early spread cells and not from the large tumors. In fact, the Klein group identified a mechanism by which spread is more efficient in early lesions than in large tumors. In both studies, investigators found that early cancer cell spread is an extension of the normal process of creating a branching tree of breast milk ducts in females. Two major pathways are activated in this ancient process -- p38, a tumor suppressor, and HER2, an oncogene. Switching off p38 and turning on HER2 activates a module of the EMT (epithelial to mesenchymal transition) signaling pathway. EMT promotes movement of cells during embryogenesis and tissue development. The Klein paper also shows that progesterone receptor signaling, which controls branching of the mammary tree, is important for this early spread by regulating cues involved in EMT and growth programs, a mechanism that was hinted in his earlier studies. As a mammary tree develops, p38, HER2, and EMT are alternatively turned on and off. This, in cooperation with progesterone signaling, allows mammary cells to move through the mammary gland, hollow out a tubular, branching network of milk ducts that flow to the nipple. "Tweaking these pathways are a normal way of forming hollow branching tubes," Dr. Aguirre-Ghiso says. But in their experiments, they found that if HER2 is over-activated (not switched off) or mutated, and p38 is permanently turned off, EMT was continually activated, allowing cells to move out of the mammary gland and into the animal's body through the blood. "We were able to use organoids in three-dimensional cultures, and high resolution imaging directly in the live animal models to actually see these cells enter the blood stream from the mammary tree and travel to the lung, the bone marrow, and other places," he says. "We hadn't thought about oncogenes and tumor suppressors in this way before. This is a new function for these pathways." John S. Condeelis, PhD, co-Director of the Gruss Lipper Biophotonics Center and its Integrated Imaging Program at Einstein, where the high resolution intravital imaging was performed, noted that "We were surprised to learn that cancer cells from DCIS-like lesions could show such robust dissemination using similar machinery found in tumor cells from invasive carcinoma. This is a new insight with implications beyond our expectations." Also David Entenberg MSc, Director of Technological Development and Intravital Imaging who led the imaging efforts within the same Center said, "A few years ago, it would not have been possible to image these disseminating cells inside a living animal with this level of detail. We're pleased that Einstein's imaging technology could, through this collaboration, contribute to the definitive proof of early dissemination." And while both studies focus on the mechanisms of early dissemination in breast cancer, similar processes could control early dissemination and metastasis in other human cancers, including melanoma and pancreatic cancer. In fact, pancreatic cancer early dissemination has also been linked to an EMT process, Dr. Aguirre-Ghiso says. Among the critical avenues they are investigating, Mount Sinai researchers are looking for the growth switch that pushes early spread of dormant cancer cells to form metastases. "While our findings add a whole new level of complexity to the understanding of cancer, they also add energy to our efforts to finally solve the big issue in cancer -- stop the metastasis that kills patients," Dr. Aguirre-Ghiso says. Study contributors include lead co-authors Kathryn L. Harper, PhD, Maria Soledad Sosa, PhD, Julie F. Cheung, BSc, Rita Nobre MSc, Alvaro Avivar-Valderas, PhD, Chandandaneep Nagi, MD, and Eduardo F. Farias, PhD, from Icahn School of Medicine at Mount Sinai; Christoph Klein, MD and Hedayatollah Hosseini, PhD from the University of Regensburg, Germany; Nomeda Girnius, PhD and Roger J. Davis, PhD from Howard Hughes Medical Institute at the University of Massachusetts Medical School; and David Entenberg, MSc and John Condeelis, PhD from Albert Einstein College of Medicine in New York. The study was supported by grants SWCRF, CA109182, CA196521, CA163131, CA100324, F31CA183185, BC132674, BC112380, NIH 1S10RR024745 Microscopy CoRE at ISMMS, the Integrated Imaging Program at Einstein, HHMI, DFG KL 1233/10-1 and the ERC (322602). For a video on this release: https:/ The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. 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