300 results match your criteria mcl1 dna

CS2164 and Venetoclax Show Synergistic Antitumoral Activities in High Grade B-Cell Lymphomas With and Rearrangements.

Front Oncol 2021 10;11:618908. Epub 2021 Mar 10.

Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, China.

High-grade B-cell lymphoma with concurrent and rearrangements (HGBL-DHL) is a rare, aggressive mature B-cell malignancy with a high likelihood of treatment failure following front-line immunochemotherapies. Patients with HGBL-DHL who develop a relapsed or refractory disease have little effective therapeutic strategies and show very poor clinical outcomes, thus calling for development of novel therapies for this specific patient population. In this study, we investigated the preclinical anti-lymphoma efficacies and potential mechanism of action of a novel treatment approach, combining the BCL2 inhibitor venetoclax with CS2164, a new orally active multitarget inhibitor, in HGBL-DHL models. Read More

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Distinct genomic profile in h. pylori-associated gastric cancer.

Cancer Med 2021 Mar 9. Epub 2021 Mar 9.

Department of Oncology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Gastric cancer is one of the most common and deadly cancer types. Currently, four subtypes have been identified with unique molecular alterations: Epstein-Barr virus (EBV)-positive, microsatellite instability (MSI), chromosomal instability (CIN), and genomic stable (GS) tumors. Notably, many gastric tumors are associated with the bacterium Helicobacter pylori but the genomic landscape of this subgroup of tumors remains largely unknown. Read More

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Cytokine-like protein 1-induced survival of monocytes suggests a combined strategy targeting MCL1 and MAPK in CMML.

Blood 2021 Mar 9. Epub 2021 Mar 9.

Université Paris Saclay, Faculté de Médecine, Le Kremlin-Bicetre, France, France.

Mouse models of chronic myeloid malignancies suggest that targeting mature cells of the malignant clone disrupts feedback loops that promote disease expansion. Here, we show that, in chronic myelomonocytic leukemia (CMML), monocytes that accumulate in the peripheral blood show a decreased propensity to die by apoptosis. BH3 profiling demonstrates their addiction to MCL1 (myeloid cell leukemia-1), which can be targeted with the small molecule inhibitor S63845. Read More

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Luteolin inhibits proliferation, triggers apoptosis and modulates Akt/mTOR and MAP kinase pathways in HeLa cells.

Oncol Lett 2021 Mar 7;21(3):192. Epub 2021 Jan 7.

School of Life Sciences, Manipal Academy of Higher Education, Dubai, United Arab Emirates.

Flavonoids, a subclass of polyphenols, have been shown to be effective against several types of cancer, by decreasing proliferation and inducing apoptosis. Therefore, the aim of the present study was to assess the anti-carcinogenic potential of luteolin on HeLa human cervical cancer cells, through the use of a cell viability assay, DNA fragmentation assay, mitochondrial membrane potential assay, cell cycle analysis using Annexin/PI staining and flow cytometry, gene expression analysis and a protein profiling array. Luteolin treatment exhibited cytotoxicity towards HeLa cells in a dose- and time-dependent manner, and its anti-proliferative properties were confirmed by accumulation of luteolin-treated cells in sub-G phases. Read More

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Antileukemic efficacy of a potent artemisinin combined with sorafenib and venetoclax.

Blood Adv 2021 Feb;5(3):711-724

Center for Stem Cell Biology & Regenerative Medicine and.

Artemisinins are active against human leukemia cell lines and have low clinical toxicity in worldwide use as antimalarials. Because multiagent combination regimens are necessary to cure fully evolved leukemias, we sought to leverage our previous finding that artemisinin analogs synergize with kinase inhibitors, including sorafenib (SOR), by identifying additional synergistic antileukemic drugs with low toxicity. Screening of a targeted antineoplastic drug library revealed that B-cell lymphoma 2 (BCL2) inhibitors synergize with artemisinins, and validation assays confirmed that the selective BCL2 inhibitor, venetoclax (VEN), synergized with artemisinin analogs to inhibit growth and induce apoptotic cell death of multiple acute leukemia cell lines in vitro. Read More

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February 2021

MCL1 binds and negatively regulates the transcriptional function of tumor suppressor p73.

Cell Death Dis 2020 11 3;11(11):946. Epub 2020 Nov 3.

Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.

MCL1, an anti-apoptotic protein that controls chemosensitivity and cell fate through its regulation of intrinsic apoptosis, has been identified as a high-impact target in anti-cancer therapeutic development. With MCL1-specific inhibitors currently in clinical trials, it is imperative that we understand the roles that MCL1 plays in cells, especially when targeting the Bcl-2 homology 3 (BH3) pocket, the central region of MCL1 that mediates apoptotic regulation. Here, we establish that MCL1 has a direct role in controlling p73 transcriptional activity, which modulates target genes associated with DNA damage response, apoptosis, and cell cycle progression. Read More

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November 2020

miRNA Modulation and Antitumor Activity by the Extra-Virgin Olive Oil Polyphenol Oleacein in Human Melanoma Cells.

Front Pharmacol 2020 23;11:574317. Epub 2020 Sep 23.

Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Pisa, Pisa, Italy.

Extra-virgin olive oil (EVOO) polyphenols contribute to Mediterranean diet health-promoting properties. One of the most abundant secoiridoid present in EVOO, Oleacein (OA), demonstrated anticancer activity against several tumors. Nevertheless, its role against melanoma has not still investigated. Read More

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September 2020

Downregulation of CDC20 Increases Radiosensitivity through Mcl-1/p-Chk1-Mediated DNA Damage and Apoptosis in Tumor Cells.

Int J Mol Sci 2020 Sep 12;21(18). Epub 2020 Sep 12.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences; Anhui Province Key Laboratory of Environmental Toxicology and Pollution Control Technology, Hefei 230031, China.

Radiotherapy is an important modality for the local control of human cancers, but the radioresistance induced by aberrant apoptotic signaling is a hallmark of cancers. Restoring the aberrant apoptotic pathways is an emerging strategy for cancer radiotherapy. In this study, we determined that targeting cell division cycle 20 (CDC20) radiosensitized colorectal cancer (CRC) cells through mitochondrial-dependent apoptotic signaling. Read More

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September 2020

DNA Methylation Profiling Reveals Prognostically Significant Groups in Pediatric Adrenocortical Tumors: A Report From the International Pediatric Adrenocortical Tumor Registry.

JCO Precis Oncol 2019 18;3. Epub 2019 Nov 18.

St Jude Children's Research Hospital, Memphis, TN.

Purpose: Pediatric adrenocortical carcinomas (ACCs) are aggressive; the overall survival of patients with ACCs is 40%-50%. Appropriate staging and histologic classification are crucial because children with incomplete resections, metastases, or relapsed disease have a dismal prognosis. The clinical course of pediatric adrenocortical tumors (ACTs) is difficult to predict using the current classification schemas, which rely on subjective microscopic and gross macroscopic variables. Read More

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November 2019

MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.

Nat Commun 2020 09 10;11(1):4527. Epub 2020 Sep 10.

Department of Medicine III, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany.

Evasion of programmed cell death represents a critical form of oncogene addiction in cancer cells. Understanding the molecular mechanisms underpinning cancer cell survival despite the oncogenic stress could provide a molecular basis for potential therapeutic interventions. Here we explore the role of pro-survival genes in cancer cell integrity during clonal evolution in non-small cell lung cancer (NSCLC). Read More

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September 2020

Pervasive chromosomal instability and karyotype order in tumour evolution.

Nature 2020 11 2;587(7832):126-132. Epub 2020 Sep 2.

Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.

Chromosomal instability in cancer consists of dynamic changes to the number and structure of chromosomes. The resulting diversity in somatic copy number alterations (SCNAs) may provide the variation necessary for tumour evolution. Here we use multi-sample phasing and SCNA analysis of 1,421 samples from 394 tumours across 22 tumour types to show that continuous chromosomal instability results in pervasive SCNA heterogeneity. Read More

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November 2020

Gene expression profile identifies distinct molecular subtypes and potential therapeutic genes in Merkel cell carcinoma.

Transl Oncol 2020 Nov 6;13(11):100816. Epub 2020 Aug 6.

Department of Preventive Medicine, Institute of Biomedical Informatics, Cell Signal Transduction Laboratory, Bioinformatics Center, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China. Electronic address:

Merkel cell carcinoma (MCC) is a rare primary cutaneous neoplasm of neuroendocrine carcinoma of the skin. About 80% of the MCC occurs due to Merkel cell polyomavirus (MCPyV) and 20% of the tumors usually occur due to severe UV exposure which is a more aggressive type of MCC. It tends to have an increased incidence rate among elderly and immunosuppressed individuals. Read More

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November 2020

Genetic alterations and their association with clinicopathologic characteristics in advanced breast carcinomas: focusing on clinically actionable genetic alterations.

Hum Pathol 2020 08 21;102:94-103. Epub 2020 May 21.

Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA. Electronic address:

Breast carcinomas (BCs) are genetically heterogeneous and associated with numerous mutations which can be used to predict outcomes and initiate targeted therapies. We investigated clinicopathologic characteristics associated with gene mutations detected using the FoundationOne CDx assay in a cohort of 223 clinically advanced BCs (66 locally recurrent and 157 metastatic) from our institution. One hundred fifty unique mutations were identified (total 1008) in the cohort, with the most prevalent (>10%) including TP53 (53. Read More

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The role of MITF and Mcl-1 proteins in the antiproliferative and proapoptotic effect of ciprofloxacin in amelanotic melanoma cells: In silico and in vitro study.

Toxicol In Vitro 2020 Aug 8;66:104884. Epub 2020 May 8.

Medical University of Silesia, Faculty of Pharmaceutical Sciences in Sosnowiec, Department of Pharmaceutical Chemistry, Jagiellońska 4, 41-200 Sosnowiec, Poland.

Mcl-1 is a potent antiapoptotic protein which is amplified in many human cancer, while microphthalmia associated transcription factor (MITF) promotes cell proliferation and has pro-survival role. The study was designed to examine whether the interaction between ciprofloxacin, one of the fluoroquinolones derivative, and MITF/Mcl-1 proteins affects C32 melanoma cells viability, proliferation and induces apoptosis. Preliminary molecular docking studies, Western blot analysis and fluorescence image cytometry were applied to demonstrate the signaling pathway underlying antiproliferative and proapoptotic effect of the drug. Read More

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Identification of Lenalidomide Sensitivity and Resistance Mechanisms in Non-Del(5q) Myelodysplastic Syndromes.

Int J Mol Sci 2020 May 8;21(9). Epub 2020 May 8.

Division of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.

Whereas lenalidomide is an effective therapy for del(5q) MDS patients, a minority of non-del(5q) MDS patients achieve hematologic improvement with lenalidomide. We used computational biology modeling and digital drug simulation to examine genomic data from 56 non-del(5q) MDS patients treated with lenalidomide, and then matched treatment response with molecular pathways. The computer inferred genomic abnormalities associating with lenalidomide treatment response in non-del(5q) MDS to include trisomy 8, del(20q), or loss of function mutations. Read More

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A broad-based approach to differentiate CIN from its mimics: The utility of in situ hybridization and immunohistochemistry.

Gerard Nuovo

Ann Diagn Pathol 2020 Jun 13;46:151515. Epub 2020 Apr 13.

The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States of America; Discovery Life Sciences, Powell, OH, United States of America. Electronic address:

The hematoxylin and eosin slides of 100 consecutive cases diagnosed as CIN 1-2 were combined with 25 CIN 1 and 25 negative for CIN as documented by in situ HPV testing. The 150 cases were then reviewed blinded and scored as "CIN" or "negative for CIN". Each of the 50 controls was correctly scored. Read More

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MCL1 Is Required for Maintenance of Intestinal Homeostasis and Prevention of Carcinogenesis in Mice.

Gastroenterology 2020 07 14;159(1):183-199. Epub 2020 Mar 14.

Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland; Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland. Electronic address:

Background & Aims: Intestinal epithelial homeostasis depends on a tightly regulated balance between intestinal epithelial cell (IEC) death and proliferation. While the disruption of several IEC death regulating factors result in intestinal inflammation, the loss of the anti-apoptotic BCL2 family members BCL2 and BCL2L1 has no effect on intestinal homeostasis in mice. We investigated the functions of the antiapoptotic protein MCL1, another member of the BCL2 family, in intestinal homeostasis in mice. Read More

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The X-linked trichothiodystrophy-causing gene RNF113A links the spliceosome to cell survival upon DNA damage.

Nat Commun 2020 03 9;11(1):1270. Epub 2020 Mar 9.

Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liege, CHU, Sart-Tilman, Liège, Belgium.

Prolonged cell survival occurs through the expression of specific protein isoforms generated by alternate splicing of mRNA precursors in cancer cells. How alternate splicing regulates tumor development and resistance to targeted therapies in cancer remain poorly understood. Here we show that RNF113A, whose loss-of-function causes the X-linked trichothiodystrophy, is overexpressed in lung cancer and protects from Cisplatin-dependent cell death. Read More

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Gossypol inhibits cullin neddylation by targeting SAG-CUL5 and RBX1-CUL1 complexes.

Neoplasia 2020 04;22(4):179-191

Cancer Institute of the 2nd Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

Cullin-RING E3 ligase (CRL) is the largest family of E3 ubiquitin ligase, responsible for ubiquitylation of ∼20% of cellular proteins. CRL plays an important role in many biological processes, particularly in cancers due to abnormal activation. CRL activation requires neddylation, an enzymatic cascade transferring small ubiquitin-like protein NEDD8 to a conserved lysine residue on cullin proteins. Read More

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MARCH5 requires MTCH2 to coordinate proteasomal turnover of the MCL1:NOXA complex.

Cell Death Differ 2020 08 24;27(8):2484-2499. Epub 2020 Feb 24.

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.

MCL1, a BCL2 relative, is critical for the survival of many cells. Its turnover is often tightly controlled through both ubiquitin-dependent and -independent mechanisms of proteasomal degradation. Several cell stress signals, including DNA damage and cell cycle arrest, are known to elicit distinct E3 ligases to ubiquitinate and degrade MCL1. Read More

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miR-125b lowers sensitivity to apoptosis following mitotic arrest: Implications for breast cancer therapy.

J Cell Physiol 2020 10 13;235(10):6335-6344. Epub 2020 Feb 13.

Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 R. Weigla Street, 53-114, Wroclaw, Poland.

The process of apoptosis begins when the balance between proapoptotic and antiapoptotic stimuli is disturbed, leading to oligomerization of apoptosis effectors and disruption of the outer mitochondrial membrane. BCL-2 family proteins are the major regulators of mitochondrial pathway of apoptosis. In turn, microRNA-125b (miR-125b) is a member of microRNAs, which are short single-stranded noncoding RNAs that negatively regulate gene expression at the posttranscriptional level. Read More

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October 2020

Genetic screens in isogenic mammalian cell lines without single cell cloning.

Nat Commun 2020 02 6;11(1):752. Epub 2020 Feb 6.

Genetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA, 02142, USA.

Isogenic pairs of cell lines, which differ by a single genetic modification, are powerful tools for understanding gene function. Generating such pairs of mammalian cells, however, is labor-intensive, time-consuming, and, in some cell types, essentially impossible. Here, we present an approach to create isogenic pairs of cells that avoids single cell cloning, and screen these pairs with genome-wide CRISPR-Cas9 libraries to generate genetic interaction maps. Read More

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February 2020

Genome-wide DNA methylation analysis of Metarhizium anisopliae during tick mimicked infection condition.

BMC Genomics 2019 Nov 11;20(1):836. Epub 2019 Nov 11.

Centro de Biotecnologia, UFRGS, Porto Alegre, RS, Brazil.

Background: The Metarhizium genus harbors important entomopathogenic fungi. These species have been widely explored as biological control agents, and strategies to improve the fungal virulence are under investigation. Thus, the interaction between Metarhizium species and susceptible hosts have been explored employing different methods in order to characterize putative virulence determinants. Read More

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November 2019

p53 mitotic centrosome localization preserves centrosome integrity and works as sensor for the mitotic surveillance pathway.

Cell Death Dis 2019 11 7;10(11):850. Epub 2019 Nov 7.

Unit of Cellular Networks and Molecular Therapeutic Targets, IRCCS-Regina Elena National Cancer Institute, Rome, Italy.

Centrosomal p53 has been described for three decades but its role is still unclear. We previously reported that, in proliferating human cells, p53 transiently moves to centrosomes at each mitosis. Such p53 mitotic centrosome localization (p53-MCL) occurs independently from DNA damage but requires ATM-mediated p53Ser15 phosphorylation (p53Ser15) on discrete cytoplasmic p53 foci that, through MT dynamics, move to centrosomes during the mitotic spindle formation. Read More

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November 2019

Bile acid-induced "Minority MOMP" promotes esophageal carcinogenesis while maintaining apoptotic resistance via Mcl-1.

Oncogene 2020 01 30;39(4):877-890. Epub 2019 Sep 30.

Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.

Barrett's esophagus (BE) is associated with reflux and is implicated the development of esophageal adenocarcinoma (EAC). Apoptosis induces cell death through mitochondrial outer membrane permeabilization (MOMP), which is considered an irreversible step in apoptosis. Activation of MOMP to levels that fail to reach the apoptotic threshold may paradoxically promote cancer-a phenomenon called "Minority MOMP. Read More

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January 2020

Immunization against poly--acetylglucosamine reduces neutrophil activation and GVHD while sparing microbial diversity.

Proc Natl Acad Sci U S A 2019 10 16;116(41):20700-20706. Epub 2019 Sep 16.

Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Faculty of Medicine, 79106 Freiburg, Germany;

Microbial invasion into the intestinal mucosa after allogeneic hematopoietic cell transplantation (allo-HCT) triggers neutrophil activation and requires antibiotic interventions to prevent sepsis. However, antibiotics lead to a loss of microbiota diversity, which is connected to a higher incidence of acute graft-versus-host disease (aGVHD). Antimicrobial therapies that eliminate invading bacteria and reduce neutrophil-mediated damage without reducing the diversity of the microbiota are therefore highly desirable. Read More

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October 2019

Association of Leukemia Target Genes , and in Vitamin C Pathways.

Cancer Genomics Proteomics 2019 Sep-Oct;16(5):333-344

Department of Orthopedic Surgery and BME-Campbell Clinic, University of Tennessee Health Science Center, Memphis, TN, U.S.A.

Background: Vitamin C has been used in combination with several target genes in the treatment of leukemia. Tet methylcytosine dioxygenase (Tet2), B-cell lymphoma 2 (Bcl2), and solute carrier family 23 member 2 (Slc23a2) are the major target genes in the treatment of leukemia and are relevant to vitamin C.

Materials And Methods: Using whole-genome expression profiles from mouse livers, the expression quantitative trait locus (eQTL), correlation matrix, and gene network graph were constructed with probes from each of these three genes and with their relative genes. Read More

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January 2020

Mcl-1 Inhibitor Induces Cells Death in BRAF-Mutant Amelanotic Melanoma Trough GSH Depletion, DNA Damage and Cell Cycle Changes.

Pathol Oncol Res 2020 Jul 20;26(3):1465-1474. Epub 2019 Aug 20.

School of Pharmacy with the Division of Laboratory Medicine, Department of Pharmaceutical Chemistry, Medical University of Silesia, Jagiellońska 4, 41-200, Sosnowiec, Poland.

Mcl-1 is a potent antiapoptotic protein and amplifies frequently in many human cancer. Currently, it is considered that the extensively expressed of Mcl-1 protein in melanoma cells is associated with rapid tumor progression, poor prognosis and low chemosensitivity. Therefore, the antiapoptotic protein Mcl-1 could be considered as a potential target for malignant melanoma treatment. Read More

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Bcl2-Expressing Quiescent Type B Neural Stem Cells in the Ventricular-Subventricular Zone Are Resistant to Concurrent Temozolomide/X-Irradiation.

Stem Cells 2019 12 17;37(12):1629-1639. Epub 2019 Oct 17.

Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

The ventricular-subventricular zone (V-SVZ) of the mammalian brain is a site of adult neurogenesis. Within the V-SVZ reside type B neural stem cells (NSCs) and type A neuroblasts. The V-SVZ is also a primary site for very aggressive glioblastoma (GBM). Read More

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December 2019

MIM1 induces COLO829 melanoma cell death through mitochondrial membrane breakdown, GSH depletion, and DNA damage.

Fundam Clin Pharmacol 2020 Feb 5;34(1):20-31. Epub 2019 Sep 5.

Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Jagiellońska, 441-200, Sosnowiec, Poland.

Malignant melanoma is a high aggressive malignancy in humans and causes 60-80% of deaths from skin cancer. Defect in an intrinsic pathway of apoptosis via overexpression of Mcl-1 is responsible for malignant melanoma development and progression, and also for resistance to chemotherapeutic agents. MIM1 is a specific low molecular Mcl-1 protein inhibitor that is able to induce Mcl-1-dependent cancer cells death. Read More

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February 2020