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https://www.readbyqxmd.com/read/28350964/promoting-vaginal-distribution-of-e7-and-mcl-1-sirna-silencing-nanoparticles-for-cervical-cancer-treatment
#1
Anna Lechanteur, Tania Furst, Brigitte Evrard, Philippe Delvenne, Geraldine Piel, Pascale Hubert
There is an urgent need to develop a less aggressive and more effective treatment against cervical lesions induced by different high-risk human papillomavirus (HR-HPV). We investigated the potential of a cocktail of small interfering RNA (siRNA) directed against the oncoprotein E6 (E6), the oncoprotein E7 (E7) and/or the anti-apoptotic protein MCL-1 (MCL-1). The combination of siRNA anti-E7 and anti-MCL-1 demonstrated high efficacy on multiple HPV16 and HPV18 cell lines and no effects on healthy keratinocytes...
March 28, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28345832/metformin-inhibits-migration-and-invasion-of-cholangiocarcinoma-cells
#2
Son Xuan Trinh, Huyen Thi Bich Nguyen, Kween Saimuang, Virapong Prachayasittikul, Waraporn Chan On
Background: Metformin is an oral anti-diabetic agent that has been widely prescribed for treatment of type II diabetes. Anti-cancer properties of metformin have been revealed for numerous human malignancies including cholangiocarcinoma (CCA) with anti-proliferative effects in vitro. However, effects on CCA cell migration and invasion have not been fully investigated. The present study aimed to explore the inhibitory effects of metformin on motility, migration and invasion of the CCA cell line HuCCT1, and examine molecular mechanisms underlying metformin effects...
February 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28345453/tumor-suppressor-mir-29c-regulates-radioresistance-in-lung-cancer-cells
#3
Elena Arechaga-Ocampo, Cesar Lopez-Camarillo, Nicolas Villegas-Sepulveda, Claudia H Gonzalez-De la Rosa, Isidro X Perez-Añorve, Reynalda Roldan-Perez, Ali Flores-Perez, Omar Peña-Curiel, Oscar Angeles-Zaragoza, Rosalva Rangel Corona, Juan A Gonzalez-Barrios, Raul Bonilla-Moreno, Oscar Del Moral-Hernandez, Luis A Herrera, Alejandro Garcia-Carranca
Radiotherapy is an important treatment option for non-small cell lung carcinoma patients. Despite the appropriate use of radiotherapy, radioresistance is a biological behavior of cancer cells that limits the efficacy of this treatment. Deregulation of microRNAs contributes to the molecular mechanism underlying resistance to radiotherapy in cancer cells. Although the functional roles of microRNAs have been well described in lung cancer, their functional roles in radioresistance are largely unclear. In this study, we established a non-small cell lung carcinoma Calu-1 radioresistant cell line by continuous exposure to therapeutic doses of ionizing radiation as a model to investigate radioresistance-associated microRNAs...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28343875/discovery-and-structure-activity-relationship-studies-of-n-substituted-indole-derivatives-as-novel-mcl-1-inhibitors
#4
Shenglin Luan, Qi Ge, Yedong Chen, Mingyang Dai, Jinyu Yang, Kun Li, Dan Liu, Linxiang Zhao
Myeloid cell leukemia-1 (Mcl-1) is an important antiapoptotic protein functioning through protein-protein interactions. We discovered LSL-A6 (2-((2-carbamoyl-1-(3-(4-methoxyphenoxy)propyl)-1H-indol-6-yl)oxy)acetic acid) with a novel N-substituted indole scaffold to interfere Mcl-1 binding as a novel Mcl-1 inhibitor. Molecular modeling indicated that this compound binds with Mcl-1 by interaction with P2 and R263 hot-spots. Structure modification focused on several moieties including indole core, hydrophobic tail and acidic chain were conducted and structure-activity relationship was analyzed...
March 16, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28337703/umi-77-primes-glioma-cells-for-trail-induced-apoptosis-by-unsequestering-bim-and-bak-from-mcl-1
#5
Ji-Wei Liu, Zhi-Chuan Zhu, Kui Li, Hong-Tao Wang, Zhi-Qi Xiong, Jing Zheng
Malignant glioma is the most common and aggressive form of brain tumor with poor prognosis of survival. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent but is insufficient of inducing apoptosis in some types of gliomas. In this study, we showed that the small-molecule Mcl-1 inhibitor UMI-77 sensitized glioma cells to TRAIL treatment, as evidenced by cell viability assay, Annexin V staining and JC-1 staining. Combination of UMI-77 and TRAIL in glioma cells led to the activation of caspase-8 and Bid, cleavage of caspase-3 and poly-ADP ribose polymerase (PARP), accumulation of tBid in the mitochondria and release of cytochrome c into the cytosol...
March 23, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28337656/what-factors-are-associated-with-femoral-component-internal-rotation-in-tka-using-the-gap-balancing-technique
#6
Seung-Yup Lee, Hong-Chul Lim, Ki-Mo Jang, Ji-Hoon Bae
BACKGROUND: When using the gap-balancing technique for TKA, excessive medial release and varus proximal tibial resection can be associated with internal rotation of the femoral component. Previous studies have evaluated the causes of femoral component rotational alignment with a separate factor analysis using unadjusted statistical methods, which might result in treatment effects being attributed to confounding variables. QUESTIONS/PURPOSES: (1) What pre- and intraoperative factors are associated with internal rotation of the femoral component in TKA using the gap balancing technique? (2) To what degree does femoral component rotation as defined by the navigation system differ from rotation as measured by postoperative CT? METHODS: Three hundred seventy-seven knees that underwent computer-assisted primary TKA attributable to degenerative osteoarthritis with varus or mild valgus alignment in which medial soft tissue release was performed, and those with preoperative radiographs including preoperative CT between October 2007 and June 2014 were included in the study...
March 23, 2017: Clinical Orthopaedics and related Research
https://www.readbyqxmd.com/read/28337384/topoisomerase-i-top1-a-major-target-of-fl118-for-its-antitumor-efficacy-or-mainly-involved-in-its-side-effects-of-hematopoietic-toxicity
#7
EDITORIAL
Fengzhi Li, Xiang Ling, Danni L Harris, Jianqun Liao, Yuping Wang, David Westover, Guohui Jiang, Bo Xu, Patrick M Boland, Chunyang Jin
FL118 is a novel camptothecin (CPT) analogue that possesses exceptional antitumor efficacy in human tumor animal models. To date, two CPT analogues, irinotecan and topotecan, have been approved by the FDA for cancer treatment. FL118 exhibits superior antitumor activity over irinotecan and topotecan, and effectively overcomes the irinotecan- or topotecan-resistant human tumors in animal models. Accordingly, FL118 selectively inhibits the expression of multiple cancer-associated proteins (survivin, Mcl-1, XIAP, cIAP2, MdmX)...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28333959/fnc-efficiently-inhibits-mantle-cell-lymphoma-growth
#8
Yan Zhang, Rong Zhang, Xixi Ding, Bangan Peng, Ning Wang, Fang Ma, Youmei Peng, Qingduan Wang, Junbiao Chang
FNC, 2'-deoxy-2'-β-fluoro-4'-azidocytidine, is a novel cytidine analogue, that has shown strong antiproliferative activity in human lymphoma, lung adenocarcinoma and acute myeloid leukemia. In this study, we investigated the effects of FNC on mantle cell lymphoma (MCL) and the underlying mechanisms. In in vitro experiments, cell viability was detected by the CCK8 assay, and cell cycle progression and apoptosis were assessed by flow cytometry, and the expression of relative apoptosis proteins were detected by Western Blot...
2017: PloS One
https://www.readbyqxmd.com/read/28331804/infected-ascites-distinguishing-secondary-peritonitis-from-spontaneous-bacterial-peritonitis-in-a-cirrhotic-patient-with-classic-symptoms
#9
Marvin Louis Roy Lu, Akanksha Agarwal, Josh Sloan, Aaron Kosmin
INTRODUCTION: Spontaneous bacterial peritonitis can be differentiated from secondary bacterial peritonitis by the absence of a surgically treatable intra-abdominal source of infection. However, oftentimes this is unapparent and other clinical clues need to be sought after to make the right diagnosis. CASE: A 64-year-old woman was admitted because of three days of worsening diffuse abdominal pain and distention. She was morbidly obese and had a history of non-alcoholic steatohepatitis (NASH) cirrhosis...
2017: IDCases
https://www.readbyqxmd.com/read/28331288/development-of-venetoclax-for-therapy-of-lymphoid-malignancies
#10
REVIEW
Huayuan Zhu, Alexandru Almasan
B-cell lymphoma-2 (BCL-2) family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax (Venclexta™, formerly ABT-199, GDC-0199) is a highly selective BCL-2 inhibitor, which mimics its BCL-2 homology 3-domain to induce apoptosis. It was approved for treatment of previously treated chronic lymphocytic leukemia (CLL) patients with 17p deletion early in 2016. It has also been in clinical trials for other B-cell lymphoid malignancies. Unlike the other recently approved targeted agents idelalisib and ibrutinib, so far there has been no relapse reported in some patients...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28316081/the-antidiabetic-drug-metformin-decreases-mitochondrial-respiration-and-tricarboxylic-acid-cycle-activity-in-cultured-primary-rat-astrocytes
#11
Michaela C Hohnholt, Eva-Maria Blumrich, Helle S Waagepetersen, Ralf Dringen
Metformin is an antidiabetic drug that is used daily by millions of patients worldwide. Metformin is able to cross the blood-brain barrier and has recently been shown to increase glucose consumption and lactate release in cultured astrocytes. However, potential effects of metformin on mitochondrial tricarboxylic acid (TCA) cycle metabolism in astrocytes are unknown. We investigated this by mapping (13) C labeling in TCA cycle intermediates and corresponding amino acids after incubation of primary rat astrocytes with [U-(13) C]glucose...
March 19, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28315432/splicing-factors-of-sr-and-hnrnp-families-as-regulators-of-apoptosis-in-cancer
#12
Hanna Kędzierska, Agnieszka Piekiełko-Witkowska
SR and hnRNP proteins were initially discovered as regulators of alternative splicing: the process of controlled removal of introns and selective joining of exons through which multiple transcripts and, subsequently, proteins can be expressed from a single gene. Alternative splicing affects genes involved in all crucial cellular processes, including apoptosis. During cancerogenesis impaired apoptotic control facilitates survival of cells bearing molecular aberrations, contributing to their unrestricted proliferation and chemoresistance...
March 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28302065/lamivudine-dolutegravir-dual-therapy-in-hiv-infected-virologically-suppressed-patients
#13
Franco Maggiolo, Roberto Gulminetti, Layla Pagnucco, Margherita Digaetano, Simone Benatti, Daniela Valenti, Annapaola Callegaro, Diego Ripamonti, Cristina Mussini
BACKGROUND: Little is known about the applicability of dual treatments based on integrase inhibitors. We explored the combination of lamivudine + dolutegravir as an option when switching from standard cART in virologically suppressed patients. METHODS: In this prospective cohort we enrolled patients previously switched to 3TC + DTG who were 18 years or older, with no previous resistance mutations to the used drugs, having a HIV-RNA <50 copies/ml for 6 months or longer, negative for HBsAg and on a stable (>6 months) cART...
March 16, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28301598/regulation-of-anti-apoptotic-bcl-2-family-protein-mcl-1-by-s6-kinase-2
#14
Alakananda Basu, Savitha Sridharan
The anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1) plays an important role in breast cancer cell survival and chemoresistance. We have previously shown that knockdown of the 40S ribosomal protein S6 kinase-2 (S6K2), which acts downstream of the mechanistic target of rapamycin complex 1 (mTORC1), enhanced breast cancer cell death by apoptotic stimuli. The increase in cell death by S6K2 depletion was partly due to inactivation of Akt. In the present study, we investigated if S6K2 regulates Mcl-1, which acts downstream of Akt...
2017: PloS One
https://www.readbyqxmd.com/read/28301380/nitroxoline-shows-antimyeloma-activity-by-targeting-the-trim25-p53-axle
#15
Hongwu Mao, Yanyun Du, Zubin Zhang, Biyin Cao, Jun Zhao, Haibin Zhou, Xinliang Mao
The aim of this study was to identify the most potent quinoline-based anti-infectives for the treatment of multiple myeloma (MM) and to understand the molecular mechanisms. A small-scale screen against a panel of marketed quinoline-based drugs was performed in MM cell lines. Cell apoptosis was examined by flow cytometry. Anti-MM activity was also evaluated in nude mice. Western blotting was performed to investigate mechanisms. Nitroxoline (NXQ) was the most effective in suppressing MM cell proliferation. NXQ induced more than 40% MM cell apoptosis within 24 h and potentiated anti-MM activities of current major drugs including doxorubicin and lenalidomide...
April 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28300289/dehydrocostus-lactone-suppresses-proliferation-of-human-chronic-myeloid-leukemia-cells-through-bcr-abl-jak-stat-signaling-pathways
#16
Hong Cai, Xiaosong Qin, Chunhui Yang
This study evaluates the anticancer effects of dehydrocostus lactone, a plant-derived sesquiterpene lactone, on human chronic myeloid leukemia cells. Dehydrocostus lactone significantly inhibits cell proliferation by inducing cells to undergo cell cycle arrest, apoptosis and differentiation. Dehydrocostus lactone suppresses the expression of cyclin B1, cyclin A, cyclin E, cyclin-dependent kinase 2 (CDK2), and cyclin-dependent kinase 1 (CDK2) and increases p21 expression, resulting in S-G2/M phase arrest in K562 cells...
March 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28298521/the-interaction-of-pneumocystis-with-the-c-type-lectin-receptor-mincle-exerts-a-significant-role-in-host-defense-against-infection
#17
Theodore J Kottom, Deanne M Hebrink, Paige E Jenson, Vijayalakshmi Nandakumar, Marcel Wüthrich, Huafeng Wang, Bruce Klein, Sho Yamasaki, Bernd Lepenies, Andrew H Limper
Pneumocystis pneumonia (PCP) remains a major cause of morbidity and mortality within immunocompromised patients. In this study, we examined the potential role of macrophage-inducible C-type lectin (Mincle) for host defense against Pneumocystis Binding assays implementing soluble Mincle carbohydrate recognition domain fusion proteins demonstrated binding to intact Pneumocystis carinii as well as to organism homogenates, and they purified major surface glycoprotein/glycoprotein A derived from the organism. Additional experiments showed that rats with PCP expressed increased Mincle mRNA levels...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28296749/gastrointestinal-involvement-by-mantle-cell-lymphoma-observed-by-endoscopy-a-case-report
#18
De-Ming Li, Yue-Ping Jiang
INTRODUCTION: Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin B-cell lymphoma, accounting for 6% of all non-Hodgkin lymphoma. The typical appearance of intestinal MCL is multiple lymphomatous polyposis, whereas presentation as protruding lesions is uncommon. We herein report the case of a 64-year-old male patient who was admitted to our hospital with epigastric pains. On endoscopy, submucosal neoplasma were identified in the gastric antrum, the duodenal bulb, and the rectum. On endoscopic ultrasonography (EUS) (OLYMPUS EUS EU-ME2, Miniprobe sonography), the lesions were homogeneously hypoechoic and originated from the submucous layer or muscularis mucosa...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28295729/targeting-of-b-cell-receptor-signalling-in-b-cell-malignancies
#19
M Jerkeman, M Hallek, M Dreyling, C Thieblemont, E Kimby, L Staudt
Pharmacological agents that inhibit enzymes of the B-cell receptor (BCR) pathway are of increasing importance in the treatment of B-cell malignancies. These include inhibitors of Bruton tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), splenic tyrosine kinase and protein kinase Cβ. Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia; and idelalisib, a PI3Kδ inhibitor, for the treatment of CLL and follicular lymphoma...
March 14, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28295185/dual-targeting-of-mcl1-and-noxa-as-effective-strategy-for-treatment-of-mantle-cell-lymphoma
#20
Elisabeth Höring, Arnau Montraveta, Simon Heine, Markus Kleih, Lea Schaaf, Matthias C Vöhringer, Anna Esteve-Arenys, Gael Roué, Dolors Colomer, Elias Campo, German Ott, Walter E Aulitzky, Heiko van der Kuip
Imbalances in the composition of BCL2 family proteins contribute to tumourigenesis and therapy resistance of mantle cell lymphoma (MCL), making these proteins attractive therapy targets. We studied the efficiency of dual targeting the NOXA/MCL1 axis by combining fatty acid synthase inhibitors (NOXA stabilization) with the CDK inhibitor Dinaciclib (MCL1 reduction). This combination synergistically induced apoptosis in cell lines and primary MCL cells and led to almost complete inhibition of tumour progression in a mouse model...
March 14, 2017: British Journal of Haematology
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