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Anti-cancer Drugs

Alireza Kazemi, Mohammadreza Sadri, Mohammad Houshmand, Narjes Yazdi, Mahin Nikougoftar Zarif, Ali Anjam-Najmedini, Rezvan Tavakoli, Mohammad Ojaghi, Mansoureh Ajami, Monireh Ajami, Amir Atashi
Although recent studies have reported different aspects of autophagy, from pro-survival to pro-death roles of this process in malignant cells, the underlying mechanisms by which autophagy inhibitors contribute toward the induction of programmed cell death in cancerous cells are still unclear. In the present study, we have attempted to explore some of the molecular features of pharmacological inhibition of autophagy in TF-1 cells (an acute erythroid leukemia model). Our findings indicated that ara-C induces autophagy (with alteration of LC3B, p62, and Beclin-1) in the cells; however, targeting autophagy by 3-methyladenine and chloroquine significantly increased caspase-dependent apoptosis and the sub-G1 compartment in ara-C-treated cells...
July 9, 2018: Anti-cancer Drugs
Jian Chu, Zhan Shi, Yutao Jiao, Zhitao Han, Qifeng Dou, Jianqing Ye, Xingang Cui
Testicular cancer (TC) is the most common malignancy in men. Although the 5-year survival rate of TC patients exceeds 95%, the prognosis of patients with platinum-resistant tumors remains poor because of limited therapeutic options. Overcoming chemoresistance is the key to improving survival in poor-prognosis patients. However, the mechanism remains poorly understood. B-cell lymphoma 2 ovarian killer (BOK) is a proapoptotic protein and functions as a tumor suppressor in malignancy tumors. In this study, we found that BOK was frequently downregulated in TC tissues compared with paratumor tissues...
July 5, 2018: Anti-cancer Drugs
Weiming Li, Weili Xue, Xinhua Wang, Xiaorui Fu, Zhenchang Sun, Zhaoming Li, Yu Chang, Xudong Zhang, Zhiyuan Zhou, Changying Chen, Mingzhi Zhang
Mantle cell lymphoma (MCL) is a rare but deadly subtype of non-Hodgkin's lymphomas because of it can progress rapidly and has a poor prognosis. MicroRNA-199a (miR-199a) is a potential diagnostic marker and therapeutic target for MCL patients. However, the function and molecular mechanisms of miRNA-199a in MCL cells are still unclear. In this study, we first analyzed the levels of miR-199a and C-C chemokine receptor 7 (CCR7) in the tumor tissues and tumor-adjacent tissues, and found that the level of miRNA-199a was lower, whereas the level of CCR7 was higher in tumor tissues...
July 3, 2018: Anti-cancer Drugs
Magdalena Philipp, Nina Frischhut, Antonia Tschachler, Fabian Steinkohl, Georg Weinlich, Matthias Schmuth, Van Anh Nguyen
In this case report, we describe a patient with an inoperable mucosal melanoma of the sinonasal cavity who achieved an ongoing complete response to combined immunotherapy with ipilimumab and nivolumab after initial pseudoprogression. Despite massive enlargement of the tumor 9 weeks after treatment initiation, we decided to continue with checkpoint inhibitor immunotherapy because of lacking potent therapeutic alternatives and the possibility of pseudoprogression. In the computed tomography scan 3 months later, the tumor was no longer detectable...
June 26, 2018: Anti-cancer Drugs
Ni Zhen, Lei Jin, Ji Ma, Jiabei Zhu, Song Gu, Jing Wang, Qiuhui Pan, Xiaorong Ni, Min Xu
The ginsenoside Rg1, the primary pharmacologically active ingredient of the traditional Chinese herb ginseng, is widely used in the clinical treatment of diseases of the immune and nervous systems. Recent studies have shown that it also has an antitumor effect. In this study, we explored the effects of Rg1 on hepatoblastoma (HB) and its underlying mechanisms. We demonstrated that Rg1 significantly inhibited HB cell growth both in vivo and in vitro. Mechanistic studies revealed that Rg1 impaired homologous recombination and triggered double-strand breaks in HB cells by directly targeting CtBP-interacting protein (CtIP), a key double-strand break repair factor, which is highly expressed in HB tissues...
June 26, 2018: Anti-cancer Drugs
Shi Qiu, Linghui Deng, Yige Bao, Kun Jin, Xiang Tu, Jiakun Li, Xinyang Liao, Zhenhua Liu, Lu Yang, Qiang Wei
Acquired docetaxel (Doc) resistance in hormone-refractory prostate cancer (HRPC) remains an ongoing clinical challenge, resulting in failed chemotherapy and tumor recurrence. However, the mechanism of Doc-resistance development in prostate cancer cells is still unclear. Here, we observed a subpopulation of prostate cancer cells, in both Doc-resistant cell lines and the tumors of patients with HRPC, which show stem cell markers and greater tumorigenic potential. Those stem-like prostate cancer cells show high expression of ABCB1, which encodes multidrug resistance-related protein P-glycoprotein, leading to the Doc-resistance in prostate cancer...
June 25, 2018: Anti-cancer Drugs
Ying Wang, Qiuyun Liu, Haojie Chen, Jun You, Bin Peng, Fanfan Cao, Xue Zhang, Qing Chen, Georges Uzan, Limin Xu, Denghai Zhang
The development of resistance to therapy continues to be a serious clinical problem in lung cancer management. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is one of the most common chemotherapy drugs to treat non-small-cell lung cancer. However, almost all treatments fail after ∼1 year of treatment because of drug tolerance, probably occurring from the threonine 790 mutation (T790M) of the EGFR, resulting in overactivation of the EGFR. Celastrol is a natural compound that exhibits antiproliferative activity...
June 20, 2018: Anti-cancer Drugs
Liang Liu, Jianjiao Ni, Junhua Zhang, Xinhong He
A previous study has proven that cycle inhibiting factors (Cifs) inhibit Cullin E3 ubiquitin ligases, resulting in cell cycle arrest. More importantly, Cifs are also involved in cancer progression by deamidating Nedd8. Here we aimed to explore a novel insight into the treatment implications of Cifs in colon cancers by Tet-on system. The anticancer activity of Cif by doxycycline induction was investigated in the colon cell lines based upon Tet-On system. The expression of Cif in the colon cancer cells was determined by western blot...
June 19, 2018: Anti-cancer Drugs
Mingjiu Chen, Zhenkun Xia, Chen Chen, Wen Hu, Yunchang Yuan
To investigate effect of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on epithelial-to-mesenchymal transition (EMT) of esophageal cancer (EC) and role of enhancer of zeste homolog 2 (Ezh2)-Notch1 signaling pathway in the process. The expression of MALAT1 was determined in four EC cell lines by real-time PCR. TE-1 and EC109 cells were transfected with sh-MALAT1 to inhibit expression of MALAT1 or transfected with pcDNA3.1-Ezh2 to overexpress Ezh2. Invasion and migration assays were conducted to analyze cell metastasis, and expressions of Ezh2-Notch1 signaling-related proteins as well as EMT related proteins were determined using both real-time PCR and western blot...
June 18, 2018: Anti-cancer Drugs
Veronica Mollica, Vincenzo Di Nunno, Beniamino Corcioni, Michelangelo Fiorentino, Elisabetta Nobili, Riccardo Schiavina, Rita Golfieri, Eugenio Brunocilla, Andrea Ardizzoni, Francesco Massari
Nivolumab is an effective and tolerable treatment for metastatic renal cell carcinoma, showing longer median overall survival than everolimus and achieving a good percentage of objective response, stable disease, and prolonged responses. However, very few cases have been reported in the literature of a complete response to nivolumab in the metastatic pretreated setting. Here, we report a case of complete response to nivolumab in II line following sunitinib in a metastatic clear cell renal cell carcinoma with favorable risk according to the IMDC criteria...
June 18, 2018: Anti-cancer Drugs
Yi Tang, GaoMing Xiao, YueJun Chen, Yu Deng
Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) functions as a crucial regulator of metastasis in lung cancer. The aim of this study is to unravel the underlying mechanisms of lncRNA MALAT1 in non-small-cell lung cancer (NSCLC). A cohort of 36 NSCLC tumor tissues and adjacent normal tissues was collected postoperatively from patients with NSCLC. qRT-PCR was performed to detect the expression of MALAT1 in both NSCLC tissues and cell lines. Cell migration and invasion were monitored by wound healing assay and transwell invasion assay...
June 18, 2018: Anti-cancer Drugs
Yan Xu, Junwen Yang, Fujun Li, Guanghui Lian, Miao Ouyang
Ulcerative colitis (UC), with high morbidity has become one of the fastest-growing severe illnesses in the world. Although MiR-29a is highly expressed in the tissues of UC patients, the mechanism of miR-29a involved in the specific pathogenesis of UC is not known. In this study, a GFP-light chain 3 (LC3) immunofluorescence assay was used to observe the formation of the autophagic spot; qRT-PCR and western blotting analyses were carried out to detect the expression of autophagy-related proteins, including BECN1, Autophagy-related gene (ATG)5, ATG16L, and transcription factor EB...
June 18, 2018: Anti-cancer Drugs
Bei Zhang, Zhenghui Deng, Baishuang Zeng, Shilong Yang, Xin Chen, Xueqing Xu, Jiguo Wu
Voltage-gated sodium channel activity enhances the motility and oncogene expression of metastasic cancer cells that express a neonatal alternatively spliced form of the NaV1.5 isoform. We reported previously that FS50, a salivary protein from Xenopsylla cheopis, showed inhibitory activity against the NaV1.5 channel when assayed in HEK 293T cells and antiarrhythmia effects on rats and monkeys after induction of arrhythmia by BaCl2. This study aims to identify the effect of FS50 on voltage-gated sodium channel activity and the motility of MDA-MB-231 human breast cancer cells in vitro...
June 16, 2018: Anti-cancer Drugs
Zhen-Tao Song, Leshuai W Zhang, Li-Qiang Fan, Jing-Wen Kong, Jun-Hua Mao, Jian Zhao, Fu-Jun Wang
Cyclosporin A (CsA) is a calcium antagonist and can enhance the efficacy of some protein drugs, but its mechanism remains unknown. In this study, MAP30, a ribosome-inactivating protein reported to have apoptotic effects on cancer cells, was fused with S3, an epidermal growth factor receptor (EGFR)-targeting peptide. In addition, CsA was used to investigate whether it can further promote the apoptotic effects of S3 fused MAP30 (MAP30-S3). Our result showed that the internalization of FITC-labeled MAP30-S3 was increased significantly by S3 in HeLa cells...
June 14, 2018: Anti-cancer Drugs
Barbacki Ariane, Peter G Maliha, Marie Hudson, David Small
Immune checkpoint inhibitors have revolutionized cancer therapy. Given their mechanism of action, immune-related adverse events have been associated with their use. We present the first documented case of pembrolizumab-induced grade IV neutropenia. A 73-year-old women known for myositis, Crohn's disease, and hypothyroidism and diagnosed with PD-L1 positive stage IV pulmonary adenocarcinoma is treated with Pembrolizumab. She develops grade IV neutropenia 2 weeks after her second infusion. She is therefore hospitalized and treated initially with corticosteroids, granulocyte colony-stimulating factor, and intravenous immunoglobulins...
June 8, 2018: Anti-cancer Drugs
Cynthia Bernier, Ahmed Soliman, Michel Gravel, Matthew Dankner, Paul Savage, Kevin Petrecca, Morag Park, Peter M Siegel, Gordon C Shore, Anne Roulston
Triple-negative breast cancer (TNBC) is typically aggressive, difficult to treat, and commonly metastasizes to the visceral organs and soft tissues, including the lungs and the brain. Taxanes represent the most effective and widely used therapeutic class in metastatic TNBC but possess limiting adverse effects that often result in a delay, reduction, or cessation of their use. DZ-2384 is a candidate microtubule-targeting agent with a distinct mechanism of action and strong activity in several preclinical cancer models, with reduced toxicities...
June 6, 2018: Anti-cancer Drugs
Qing Li, Li Zhang, Li Ma, Xue Bai, Xin Li, Mingfeng Zhao, Tao Sui
STAT5 is an important transcription factor that is constitutively activated in various types of malignancies, including chronic myelogenous leukemia (CML). Whether the antitumor effects of resveratrol (RES) are linked to its capability to inhibit STAT5 activation in CML cells was investigated. We found that RES inhibited STAT5 activation in K562 and KU812 cell lines; RES also reduced the STAT5 concentration in the nucleus of K562 and KU812 cells. Protein tyrosine phosphatase (PTP) inhibitor, sodium pervanadate, reversed the RES-induced downregulation of STAT5, suggesting the involvement of a PTP...
June 6, 2018: Anti-cancer Drugs
Sufana Shikdar, David Totton, Thomas Turco, Michael Rachshtut
Bendamustine, an alkylating agent with cytotoxic properties, has been increasingly employed in the treatment of chronic lymphocytic leukemia (CLL) either as a single agent or combination with rituximab. Although rarely reported, they can potentially cause hypersensitivity reactions with serious consequences. The objective of the case report was to offer a safe and effective bendamustine desensitization protocol to patients with a hypersensitivity reaction to this drug. We report a case of a patient with a CLL who developed a type IV hypersensitivity reaction to bendamustine and who was successfully treated by drug desensitization...
June 5, 2018: Anti-cancer Drugs
Andrey V Ugolkov, Gennadiy I Bondarenko, Oleksii Dubrovskyi, Ana P Berbegall, Samuel Navarro, Rosa Noguera, Thomas V O'Halloran, Mary J Hendrix, Francis J Giles, Andrew P Mazar
Advanced stage neuroblastoma is a very aggressive pediatric cancer with limited treatment options and a high mortality rate. Glycogen synthase kinase-3β (GSK-3β) is a potential therapeutic target in neuroblastoma. Using immunohistochemical staining, we observed positive GSK-3β expression in 67% of human neuroblastomas (34 of 51 cases). Chemically distinct GSK-3 inhibitors (AR-A014418, TDZD-8, and 9-ING-41) suppressed the growth of neuroblastoma cells, whereas 9-ING-41, a clinically relevant small-molecule GSK-3β inhibitor with broad-spectrum preclinical antitumor activity, being the most potent...
May 25, 2018: Anti-cancer Drugs
Vincenzo Di Nunno, Veronica Mollica, Beniamino Corcioni, Michelangelo Fiorentino, Elisabetta Nobili, Riccardo Schiavina, Rita Golfieri, Eugenio Brunocilla, Andrea Ardizzoni, Francesco Massari
In very few years, several treatments have significantly improved the prognosis of patients with metastatic renal cell carcinoma (RCC). Despite this, the clinical outcomes of specific subgroups of patients including those with central nervous metastases still remain poor. In this population, a very infrequent and poorly described site of metastases is the pituitary gland. Because of the important endocrinal function and the anatomic site of this specific organ, clinical management of this complication requires several additional precautions compared with other central nervous metastases...
May 25, 2018: Anti-cancer Drugs
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