Stem Cell Clinic

Micheliolide Inhibits Liver Cancer Cell Growth Via Inducing Apoptosis | CMAR – Dove Medical Press

Lili Yu,1,2,* Wancheng Chen,2,* Qingshuang Tang,2,* Kai-Yuan Ji1

1The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518033, Peoples Republic of China; 2Cancer Research Institute, Guangdong Provincial Key Laboratory of Cancer Immunotherapy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, Peoples Republic of China

*These authors contributed equally to this work

Correspondence: Kai-Yuan JiThe Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518033, Peoples Republic of ChinaTel +8675515625055871Email 369027938@qq.com

Purpose: Micheliolide (MCL) is an effector compound of the flower which has been traditionally used to treat inflammation and cancer patients in oriental medicine. MCL has killing effects on several cancer and immune cells by modulating apoptosis, cell cycle, and metabolism. However, the detail of the mechanisms of anti-cancer activity remains to be elucidated and the effect on liver cancer cells is unknown.Methods: Cell proliferation was determined by CCK8 and clone formation assay. The xenograft liver cancer model formed by injecting Huh7 cells into NUDE mice was used to evaluate the effects of MCL on liver cancer cells in vivo. We evaluated the stemness of cells with spheroid formation assay and flow cytometry assay. The apoptosis was determined by Annexin V assay. F-actin staining and ROS were performed to detect the impairment of the F-actin cytoskeleton and mitochondria.Results: Here, we first show that MCL inhibits liver cancer cells both in vivo and in vitro by triggering apoptosis which was reduced by anti-oxidant, but not cell-cycle arrest. In addition, MCL induces mitochondrial ROS and caspase-3 activation. Also, we found that the aggregation of mitochondria and the perturbation of F-actin fibers in the MCL-treated liver cancer cells coincidently occurred before the induction of apoptosis and mitochondrial ROS.Conclusion: These results suggest that F-actin perturbation is involved in impaired mitochondria and apoptosis. Therefore, MCL can be a potent therapeutic reagent for liver cancer, primarily targeting the actin cytoskeleton.

Keywords: Micheliolide, liver cancer, apoptosis, ROS, actin cytoskeleton

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Micheliolide Inhibits Liver Cancer Cell Growth Via Inducing Apoptosis | CMAR - Dove Medical Press

First Patient Dosed with Off-the-Shelf UCARTCS1 Product Candidate for Relapsed/Refractory Multiple Myeloma – Business Wire

NEW YORK--(BUSINESS WIRE)--Regulatory News:

Cellectis (Paris:ALCLS) (NASDAQ:CLLS) (Euronext Growth: ALCLS; Nasdaq: CLLS), a biopharmaceutical company focused on developing immunotherapies based on gene-edited off-the-shelf CAR T-cells (UCART), today announced the Company has dosed the first patient in its UCARTCS1 clinical trial, MELANI-01, the first allogeneic off-the-shelf CAR-T product candidate the U.S. Food and Drug Administration (FDA) has cleared to enter into clinical development for relapsed/refractory multiple myeloma (R/R MM). The UCARTCS1 clinical trial is a Phase 1 dose-escalation study to evaluate the safety, expansion, persistence and clinical activity of UCARTCS1 cells in R/R MM patients.

This first patient dosing for our MELANI-01 clinical trial is an important advancement, as our team has worked tirelessly to develop and take the CS1 target from the lab to the clinic, said Dr. Andr Choulika, Chairman and CEO, Cellectis. In taking this next clinical step, we look forward to deepening our understanding of UCARTCS1 as a potential new treatment option for relapsed/refractory multiple myeloma patients in the future.

The MELANI-01 clinical trial is currently open at MD Anderson Cancer Center in Houston, Texas, under the supervision of Dr. Krina Patel, Principal Investigator, Study Coordinating Investigator, Assistant Professor, Department of Lymphoma/Myeloma, Division of Cancer Medicine at MD Anderson Cancer Center, as well as Hackensack Meridian in New Jersey under the supervision of Dr. David Siegel, Director of the Multiple Myeloma Institute at John Theurer Cancer Center (JTCC) at Hackensack University Medical Center. Another site is planned to open at Weill Cornell Medicine in New York under the leadership of Dr. Adriana Rossi, Associate Clinical Director, Myeloma Center and Assistant Professor of Medicine, Division of Hematology and Medical Oncology.

About Multiple Myeloma (MM)Multiple myeloma is a cancer that affects a type of white blood cells called plasma cells that are specialized mature B cells, which secrete antibodies to combat infections. Multiple myeloma is characterized by the uncontrolled proliferation of neoplastic plasma cells in the bone marrow, where they overcrowd healthy blood cells. Although MM is a chronic disease and an exact cause has not yet been identified, researchers have made significant progress over the years in managing the disease through better understanding MMs pathophysiology. The progress in finding a cure needs to be continued as The American Cancer Society estimates that 32,110 new cases of MM will be diagnosed, and 12,960 deaths are expected to occur in 2019 in the U.S. alone.

About UCARTCS1UCARTCS1 is an allogeneic, off-the-shelf, gene-edited T-cell product candidate designed for the treatment of multiple myeloma. CS1 (SLAMF7) is highly expressed on MM tumor cells and is an attractive target. The limitation so far has been the presence of the CS1 target on the surface of T-cells, which has hindered the access to CAR-Ts. For example, the introduction of a CAR construct in T-cells induces cross T-cell reactivity and leads to destruction of the CS1+ T-cell population during manufacturing. Cellectis solved this issue by using TALEN gene editing to knock out the CS1 gene from T-cells before introducing the CS1 CAR construct.

About CellectisCellectis is developing the first of its kind allogeneic approach for CAR-T immunotherapies in oncology, pioneering the concept of off-the-shelf and ready-to-use gene-edited CAR T-cells to treat cancer patients. As a clinical-stage biopharmaceutical company with over 19 years of expertise in gene editing, Cellectis is developing life-changing product candidates utilizing TALEN, its proprietary gene editing technology, and PulseAgile, its pioneering electroporation system to harness the power of the immune system in order to target and eradicate cancer cells.

As part of its commitment to a cure, Cellectis remains dedicated to its goal of providing life-saving UCART product candidates to address unmet needs for multiple cancers including acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (B-ALL), multiple myeloma (MM), Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).

Cellectis headquarters are in Paris, France, with additional locations in New York, New York and Raleigh, North Carolina. Cellectis is listed on the Nasdaq Global Market (ticker: CLLS) and on Euronext Growth (ticker: ALCLS). For more information, visit http://www.cellectis.com.

Follow Cellectis on social media: @cellectis, LinkedIn and YouTube.

TALEN is a registered trademark owned by Cellectis.

DisclaimerThis press release contains forward-looking statements that are based on our managements current expectations and assumptions and on information currently available to management. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Further information on the risk factors that may affect company business and financial performance is included in Cellectis Annual Report on Form 20-F and the financial report (including the management report) for the year ended December 31, 2018 and subsequent filings Cellectis makes with the Securities Exchange Commission from time to time. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.

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First Patient Dosed with Off-the-Shelf UCARTCS1 Product Candidate for Relapsed/Refractory Multiple Myeloma - Business Wire

Cell Membrane Protein Identified as "Crucial" in Development of Liver Cancer – Technology Networks

Researchers at the Bellvitge Biomedical Research Institute (IDIBELL) have just described for the first time the crucial involvement of a cell membrane protein in the development and progression of liver cancer, according to an article published in theJournal of Hepatology. This protein, called clathrin, is known for its key role in the process of internalization of molecules from the extracellular space into the cell, called endocytosis. In this process, the cell membrane folds creating vesicles with a cladded structure. Thanks to the new results, analyzing the levels of clathrin expression in biopsies of hepatocellular carcinoma patients will help select those patients who will benefit from a much more targeted and personalized therapy.

The research team, led by Dr. Isabel Fabregat, who is a professor at the Faculty of Medicine and Health Sciences of the University of Barcelona and a researcher at the CIBER of Hepatic and Digestive Diseases, has shown that liver cells with invasive features have high levels of clathrin, a protein whose involvement in liver cancer was unknown until now. Specifically, researchers showed that high expression levels of clathrin correlate with the activation of the pro-tumorigenic pathway of a known hepatic carcinogenesis actor: TGF-. In this sense, the work provides completely new and clinically valuable knowledge when it comes to understanding the complex and controversial role of TGF- in this type of cancer.

TGF-, which belongs to a large group of proteins called cytokines, has a dual role: in normal conditions, or in early stages of carcinogenesis, it plays a tumor suppressive role, promoting cell death and reducing tumor growth. But in advanced stages of liver cancer, where this signaling pathway is highly activated, tumor cells have acquired capabilities to escape its suppressor functions and respond to TGF- by inducing cell migration and invasion, and thus contributing to tumor spreading.

Previous work by the Fabregat group had shown that for this change in cellular behavior to take place, TGF- activates the EGF receptor pathway (EGFR) in tumor cells, whose overexpression and hyperactivity has been associated with a large number of cancers. The new results have shown that clathrin is essential in the endocytosis of EGFR, a decisive step for the activation of this pathway by TGF-. In vitro experiments of this recent work have allowed the IDIBELL researchers to demonstrate that clathrin cell levels determine, via EGFR, the function of TGF-. If the expression of clathrin is eliminated, the cells die. On the contrary, high levels of clathrin promote the proinvasive and tumorigenic character of the cells. The reason for this effect must be found in the functionality of the EGFR pathway: the elimination of clathrin results in an inhibition of this signaling pathway. Researchers have also shown that TGF- is capable of inducing clathrin synthesis, ultimately encouraging a self-stimulation loop.

It is interesting to mention that the study also demonstrates that clathrin expression increases during hepatic tumorigenesis both in humans and mice, and its expression changes the response to TGF- in favor of anti-apoptotic / pro-tumorigenic signals. There is a positive correlation between the expression of TGF- and clathrin in samples of hepatocellular carcinoma patients. Patients expressing high levels of TGF- and clathrin showed a worse prognosis and reduced survival.

According to Dr. Fabregat, "determining the levels of clathrin expression in samples of hepatocellular carcinoma patients can be of great help in selecting those who can be given a therapy based on inhibitors of the TGF- pathway". All healthcare institutions surrounding IDIBELL have actively participated in this study; analyses of human tumors have been carried out by E. Ramos and T. Serrano, of Bellvitge University Hospital. On the other hand, X. Sol and A. Alay, of the Catalan Institute of Oncology, have carried out the bioinformatic treatment of the data. In addition, the Complutense University of Madrid has also made a contribution.

Reference: Caballero-Diaz et al. 2019.Clathrin switches Transforming Growth Factor- role to pro-tumorigenic in liver cancer. Journal of Hepatology. DOI: https://doi.org/10.1016/j.jhep.2019.09.012.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Cell Membrane Protein Identified as "Crucial" in Development of Liver Cancer - Technology Networks

TIMP1 Is A Potential Key Gene Associated With The Pathogenesis And Pro | OTT – Dove Medical Press

Ru Huang,1,* Kaijing Wang,2,* Lei Gao,1 Wei Gao2

1Department of Heart Failure, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Peoples Republic of China; 2Department of Colorectal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Peoples Republic of China

*These authors contributed equally to this work

Correspondence: Wei GaoDepartment of Colorectal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Peoples Republic of ChinaEmail yoursgaowei@163.comLei GaoDepartment of Heart Failure, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Peoples Republic of ChinaEmail gldlykdx@163.com

Purpose: Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide. As a high-risk factor for CRC, ulcerative colitis (UC) has been demonstrated to lead to epithelial dysplasia, DNA damage, and eventually cancer. There are approximately 18% of patients with UC may develop CRC.Patients and methods: The gene expression profiles were retrieved from the Gene Expression Omnibus. The Database for Annotation, Visualization and Integrated Discovery was employed to conduct gene annotations. Protein-protein interaction network was constructed by the Search Tool for the Retrieval of Interacting Genes, and further analysed by the Molecular Complex Detection. The correlation between TIMP1 and prognosis was evaluated by the Gene Expression Proling Interactive Analysis. To predict the potential functions of TIMP1, the GeneMANIA, Coremine, and FunRich were employed. After transfection with small interfering RNA targeting TIMP1, cell proliferation, migration, and apoptosis were determined by CCK-8, scratch wound, and Annexin V-FITC/PI assays, respectively.Results: TIMP1, consistently overexpressed in the initiation and progression of UC-associated CRC (ucaCRC), was identified to be a potential biomarker for the prognosis of patients with CRC. Experimental results showed knockdown of TIMP1 could increase the migration, while did not affect the proliferation and apoptosis of RKO cells. The role of TIMP1 in the malignant transformation of ucaCRC was confirmed by using the protein/gene interactions and biological process annotation and validated by analysing the transcription factors targeting TIMP1.Conclusion: TIMP1 is consistently upregulated in the pathological process of ucaCRC and can be a potential biomarker for the worse prognosis of CRC.

Keywords: colitis ulcerative, colorectal neoplasms, high-throughput screening assays, prognosis

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Aileron Therapeutics Announces Positive Nonclinical Myelopreservation Results for ALRN-6924 at the 2019 AACR-NCI-EORTC Conference – GlobeNewswire

Nonclinical research results show that ALRN-6924 prevented the toxic side effects of chemotherapy in normal cells and enhanced the anti-cancer activity of chemotherapy

ALRN-6924 could enable a precision-medicine strategy to prevent the toxic side effects of chemotherapy in patients with p53-mutated cancer, representing approximately 50% of all patients with cancer

WATERTOWN, Mass., Oct. 29, 2019 (GLOBE NEWSWIRE) -- Aileron Therapeutics (NASDAQ:ALRN), the clinical-stage leader in the field of stabilized, cell-permeating peptides, presented new data at the 2019 AACR-NCI-EORTC Conference from nonclinical studies in which ALRN-6924, a dual inhibitor of MDM2 and MDMX, prevented chemotherapy-related toxicities in cellular studies and mouse models of cancer without limiting and even enhancing anti-cancer efficacy.

Chemotherapy is widely used to treat and often cure millions of cancer patients each year, but chemotherapy is toxic and commonly causes severe or life-threatening side effects, said Dr. Manuel Aivado, President and CEO of Aileron Therapeutics. Based on the findings of our nonclinical studies and mechanism of ALRN-6924, we believe that patients with p53-mutant cancers who are treated with chemotherapy may suffer fewer and less severe chemotherapy-related side effects if ALRN-6924 is administered prior to chemotherapy.

Our nonclinical results show that ALRN-6924 significantly reduces the toxic effects of chemotherapy in normal, healthy bone marrow cells and gastrointestinal tissues, stated Allen Annis, Ailerons SVP of Research. The results of these in vivo studies are impressive and suggest that ALRN-6924 activates the p53 gene to temporarily induce cell cycle arrest and prevent the toxic effects of chemotherapy in normal cells. Importantly, about half of all cancer patients have a mutation in the p53-gene. Our findings suggest that prophylactic use of ALRN-6924 can protect p53-wildtype normal cells while allowing chemotherapy to be effective against p53 mutant cancer cells. With this mechanism, we believe ALRN-6924 may enable a precision-medicine strategy to prevent chemotherapy-related toxicities in patients with p53-mutated cancer.

The results presented at the conference show that low doses of ALRN-6924 trigger reversible cell cycle arrest in human bone marrow cells ex vivo and in mouse bone marrow cells in vivo to limit toxicity caused by topotecan, a chemotherapy used in small-cell lung cancer (SCLC) and other cancer indications. The results also show that gastrointestinal toxicity caused by topotecan is also reduced as a result of pretreatment with ALRN-6924, which we believe could potentially translate to the clinic as an improvement in gastrointestinal side effects of chemotherapy. In three p53-mutant tumor models, the anti-cancer activity of topotecan is not diminished, and in fact the results show that the anti-cancer activity is improved by administering ALRN-6924 prior to topotecan, a result that we believe may be due to stimulation of the immune system, which has previously been shown for ALRN-6924 and other p53-activating agents.

Improving the tolerability of chemotherapy with ALRN-6924 has the potential to reduce dose delays and dose reductions. Such improved chemotherapy delivery and the potential stimulation of the immune system are two independent mechanisms that may enhance the anti-tumor effects of chemotherapy, stated Dr. Vojislav Vukovic, Chief Medical Officer of Aileron. While our first myelopreservation trial for ALRN-6924 is in SCLC patients treated with topotecan, we plan to develop ALRN-6924 as a tumor type-agnostic and chemotherapy-agnostic drug.

Millions of cancer patients worldwide receive chemotherapy each year. Published literature indicates that p53 mutations are found in about 50% of those cancer patients.

ALRN-6924 is currently being evaluated in the dose-optimization phase 1b portion of a Phase 1b/2 myelopreservation trial designed to identify a recommended phase 2 dose for ALRN-6924 and to evaluate the safety and efficacy of ALRN-6924 in preventing or limiting toxicities caused by treatment with topotecan in SCLC patients. Based on Ailerons nonclinical data, and contingent on results from the ongoing dose-optimization phase 1b, the Company plans to expand its clinical program in myelopreservation to include an additional Phase 1b cohort in non-small cell lung cancer patients treated with docetaxel, and a randomized expansion cohort of the Phase 1b SCLC trial to treat patients with alternating cycles of chemotherapy with and without ALRN-6924 (the on/off cohort) where each patient will serve as his/her own control. The Company expects to present key findings from the ongoing dose-optimization Phase 1b SCLC portion of the Phase 1b/2 myelopreservation trial in the second quarter of 2020.

Poster Presentation Details:Conference: 2019 AACR-NCI-EORTC Conference on Molecular Targets and Cancer TherapeuticsPoster Title: The Investigational Peptide Drug ALRN-6924, a Dual Inhibitor of MDMX and MDM2, is an Effective Myelopreservation Agent.

The Aileron poster can be accessed via the following link:http://share.aileronrx.com/posters/Aileron_AACR-NCI-EORTC_2019_Carvajal_Final.pdf

About ALRN-6924ALRN-6924 is a first-in-class dual MDM2/MDMX inhibitor that is currently being evaluated as an anti-cancer agent in a Phase 2a clinical trial in combination with Pfizers palbociclib (Ibrance) for the treatment of MDM2-amplified advanced solid tumors, and in a Phase 1b/2 clinical trial to evaluate ALRN-6924 as a myelopreservative agent to protect against chemotherapy-related toxicities.

About AileronAileron is a clinical-stage biopharmaceutical company advancing a proprietary platform of cell-permeating alpha-helical peptides. The stabilized helical structure of our peptides allows the design of cell-permeating therapeutic agents with large molecular surfaces for optimal target binding properties, resulting in drug candidates like ALRN-6924. Our current focus is to improve the standard of care for patients with cancer by developing safe and effective therapies and cancer supportive care treatments that leverage our proprietary peptide platform. For more information, visit http://www.aileronrx.com, and for more information about our clinical trials please visit http://www.clinicaltrials.gov.

Forward-Looking StatementsStatements in this press release about Aileron's future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements about the Companys strategy and clinical development plans. The words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, should, target, would and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether Ailerons cash resources will be sufficient to fund its continuing operations for the periods and/or trials anticipated, including the additional myelopreservation trials planned; whether results obtained in preclinical and nonclinical studies and clinical trials will be indicative of results obtained in future clinical trials; whether Ailerons product candidates will advance through the clinical trial process on a timely basis, or at all; whether the results of such trials will warrant submission for approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether Aileron's product candidates will receive approval from regulatory agencies on a timely basis or at all; whether, if product candidates obtain approval, they will be successfully distributed and marketed; and other factors discussed in the "Risk Factors" section of Aileron's quarterly report on Form 10-Q for the period ended June 30, 2019, filed on August 6, 2019, and risks described in other filings that Aileron may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Aileron specifically disclaims any obligation to update any forward-looking statement, whether because of new information, future events or otherwise.

Investors:Aileron TherapeuticsRick Wanstall, VP Finance & Operations617-995-0900rwanstall@aileronrx.com

Hans C. VitzthumLifeSci Advisors, LLC.617-430-7578hans@lifesciadvisors.com

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Aileron Therapeutics Announces Positive Nonclinical Myelopreservation Results for ALRN-6924 at the 2019 AACR-NCI-EORTC Conference - GlobeNewswire

An alternative to dry ice could revolutionise cell and tissue transportation worldwide – Mirage News

Scientists from the University of Nottingham have discovered an easy, cost-effective and safe method of sending cells and small living samples worldwide, which could revolutionize conventional practice.

Cultured cells are currently transported using dry ice the solid form of carbon dioxide which keeps them frozen at -80oC. However, dry ice shipping is expensive, voluminous and hazardous, so much so that many couriers refuse to handle it. Also, if it evaporates before a shipment reaches its destination, cellular recovery is jeopardised, as the cells get crushed and the cryoprotectant needed for their storage at low temperatures, is toxic to cells at ambient temperatures.

Dry ice is also damaging to the environment, with 5kg (the quantity typically used in a consignment of frozen cells) turning into 23,000 litres of CO2 gas on evaporation.

An alternative, devised by experts in the School of Life Sciences at the University, uses a gel-based substance for transportation, which will eliminate these problems.

The Transporter is based on a gel of low-melting temperature agarose the main constituent of many sea-weeds in which cells are suspended and kept at room temperature. Using this method, excellent cell recovery can be achieved for over seven days in transit, and in some cases two or three times longer.

Sending cells in small volumes of Transporter (100 microlitres) in microfuge tubes at 5106 cells/ml at ambient temperature is recommended by the research team for the best results. The new method has been successfully used on three occasions when cells were taken in hand-luggage from the UK to Hong Kong (five days in transit). The method has also been independently trialled by seven cell biologists using both mailing and courier routes.

Whilst dry ice has long provided a way of transporting cells across the globe, the cost and hazards have always been a major problem. We have developed a gel alternative, which is superior in many ways and will be of immediate benefit to all biomedical researchers because of its simplicity and cost-effectiveness. On medical grounds, it may now be possible to send, for example, stem cells quickly from one hospital to another over long distances. Its wider application is being investigated in veterinary medicine, microbiology and other biological fields.

The findings are published in the Journal of Cell Science.

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An alternative to dry ice could revolutionise cell and tissue transportation worldwide - Mirage News

CARsgen Announces Investigational CAR-T Therapy CT053 Granted RMAT Designation by the U.S. FDA for R/R Multiple Myeloma – Yahoo Finance

SHANGHAI, Oct.28, 2019 /PRNewswire/ -- CARsgen Therapeutics Co. Ltd., a clinical-stage biopharmaceutical company today announced that the United States Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to its investigational CT053 CAR-T cell therapy. CT053 is a fully human anti-BCMA (B Cell Maturation Antigen) autologous chimeric antigen receptor (CAR) T Celltherapy for the treatment of relapsed and/or refractory multiple myeloma (rrMM).

RMAT designation was based on clinical data from an ongoing CT053 phase 1 study in heavily pre-treated multiple myeloma patients in China. Updated data from CT053 will be presented at the 61th annual meeting of the American Society of Hematology in Orlando on December 9.

"RMAT eligibility is an important regulatory milestone for CARsgen in the continued development and commercialization of CT053 anti-BCMA CAR T cell therapy," said Zonghai Li, M.D., Ph.D., the chief executive officer of CARsgen. "The RMAT designation indicates that CT053 has demonstrated potential to address unmet medical needs for patients with rrMM. The designation is a remarkable achievement towards expediting the product development and review of our planned biologics license application (BLA) and will be invaluable to bringing this cutting-edge advance to patients as quickly as possible. RMAT as well as the PRIority MEdicines (PRIME) eligibility received from the European Medicines Agency (EMA)empower us to collaborate closely with the U.S. FDA and EMA to rapidly advance the CT053 development program toward global regulatory approvals." The CT053 anti-BCMA CAR-T program has also received Investigational New Drug (IND) clearance and Orphan Drug designation from the U.S. FDA and authorization of its Clinical Trial Application (CTA) from Health Canada.

Established under the 21st Century Cures Act, RMAT designation is a dedicated program designed to expedite the drug development and review processes for promising regenerative medicines and advanced therapies, including CAR T cell therapies. The designation includes all the benefits of the FDA's Fast Track and Breakthrough Therapy designations, providing the benefits of intensive FDA guidance on efficient drug development, including the ability for early interactions with FDA senior management to discuss surrogate or intermediate endpoints, potential ways to support accelerated approval and satisfy post-approval requirements, potential priority review of the BLA and other opportunities to expedite development and review. Between December 13, 2016 and September 30, 2019, the FDA received and assessed a total of 115 requests for eligibility. Of these, only 44 have been granted RMAT designation.

About CARsgen Therapeutics, Inc.CARsgen Therapeutics is a clinical-stage immune-oncology company committed to the development and commercialization of CAR-T therapeutics for unmet medical need. The company has collaborated with top hospitals in China to launch several other First-in-Human studies such as anti-GPC3 CAR-T cell therapy for hepatocellular carcinoma and squamous lung cancer, anti-EGFR/EGFRvIII CAR-T cell therapy for glioblastoma multiforme and anti-Claudin18.2 CAR-T cell therapy for gastric and pancreatic cancer.

For more information, please visit:www.carsgen.com

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CARsgen Announces Investigational CAR-T Therapy CT053 Granted RMAT Designation by the U.S. FDA for R/R Multiple Myeloma - Yahoo Finance

Coexistence Of A Huge Venous Thromboembolism And Bleeding Tendency In | OTT – Dove Medical Press

Haiyan Liu,1,* Ye Yang,2,* Jie Jiang,1 Xinfeng Wang,1 Chenlu Zhang,1 Yijing Jiang,1 Lemin Hong,1 Hongming Huang1

1Department of Hematology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, Peoples Republic of China; 2School of Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, Peoples Republic of China

*These authors contributed equally to this work

Correspondence: Hongming HuangDepartment of Hematology, The Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Peoples Republic of ChinaEmail hhmmmc@163.com

Abstract: Chimeric antigen receptor (CAR)-modified T cell therapy is increasingly administered for hematological malignancies. Cytokine release syndrome (CRS) is a common and severe complication of CAR-T therapy. In the present case, a 62-year-old male patient was diagnosed with relapsed and refractory multiple myeloma (RRMM). Treated with CART-CD19/BCMA therapy, his symptoms remitted, during which occasional but severe CRS associated with coagulation disorder still appeared, as evidenced by the coexistence of a huge thrombosis and bleeding tendency. Through the First Generation Sequencing, we extracted genomic DNA from the patients peripheral blood to analyze the distribution of polymorphism at the 572C/G site of the promoter of IL-6 gene. The results showed that the genotype of 572C/G promoter polymorphism was CC, indicating that high level of IL-6 and 572C/G polymorphism might be associated with the risk of thrombotic disorders. We concluded that immediate diagnosis and appropriate treatment of coagulopathy could reduce CRS-related mortality.

Keywords: chimeric antigen receptor-T therapy, cytokine release syndrome, multiple myeloma, coagulation disorder, thrombosis

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Coexistence Of A Huge Venous Thromboembolism And Bleeding Tendency In | OTT - Dove Medical Press