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https://www.readbyqxmd.com/read/28434174/molecular-alterations-and-expression-dynamics-of-lats1-and-lats2-genes-in-non-small-cell-lung-carcinoma
#1
Showkat A Malik, Mosin S Khan, Majeed Dar, Mahboob Ul Hussain, Mohammad A Shah, Sheikh M Shafi, Syed Mudassar
Large tumor suppressor (LATS) is an important member of the Hippo pathway which can regulate organ size and cell proliferation. However, very little is known about the expression and clinical significance of LATS in lung cancer especially from this part of the world. We elucidated the frequency of LATS1 &LATS2 promoter hypermethylation (by methylation-specific PCR) and expression (by real-time PCR) in sixty nine (n = 69) Non-Small Cell Lung Cancer (NSCLC) patients and their corresponding normal lung tissue samples...
April 22, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28433679/part-i-design-synthesis-and-biological-evaluation-of-novel-pyrazole-benzimidazole-conjugates-as-checkpoint-kinase-2-chk2-inhibitors-with-studying-their-activities-alone-and-in-combination-with-genotoxic-drugs
#2
Shadia A Galal, Ahmed S Abdelsamie, Samia A Shouman, Yasmin M Attia, Hamed I Ali, Ashraf Tabll, Reem El-Shenawy, Yasmine S El Abd, Mamdouh M Ali, Abeer E Mahmoud, Abeer H Abdel-Halim, Amal A Fyiad, Adel S Girgis, Hoda I El-Diwani
Activated checkpoint kinase 2 (Chk2) is a tumor suppressor as one of the main enzymes that affect the cell cycle. 2-Biarylbenzimidazoles are potent selective class of Chk2 inhibitors; the structure-based design was applied to synthesize a new series of this class with replacing the lateral aryl group by substituted pyrazoles. Ten pyrazole-benzimidazole conjugates from the best fifty candidates according to docking programs have been subjected to chemical synthesis in this study. The activities of the conjugates 5-14 as checkpoint kinase inhibitors and as antitumor alone and in combination with genotoxic drugs were evaluated...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28433657/mir-938-promotes-colorectal-cancer-cell-proliferation-via-targeting-tumor-suppressor-phlpp2
#3
Chang-Feng Li, Yong-Chao Li, Jing-Peng Jin, Zhen-Kun Yan, Dan-Dan Li
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Although the development of therapy approaches, the outcome of CRC patients still is poor, understanding the biological mechanism of CRC progression is critical to improve the treatment strategies. miRNAs regulate CRC progression, we found miR-938 was upregulated in CRC tissues and cells, MTT assay, colony formation assay and soft agar growth assay suggested miR-938 overexpression promoted CRC cell proliferation, miR-938 knockdown inhibited CRC cell proliferation...
April 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28433629/a-novel-strategy-to-dissect-endogenous-gene-transcriptional-regulation-in-live-cells
#4
Wenqing Yang, Siliang Zhang, Yi Zhang, Xin Huang
Gene transcription is a central tenet of biology, traditionally measured by RT-PCR, microarray, or more recently, RNA sequencing. However, these measurements only provide a snapshot of the state of gene transcription and only represent an overall readout of complex transcriptional networks that regulate gene expression. In this report, we describe a novel strategy to dissect endogenous gene transcription regulation in live cells by knocking in a reporter gene, EGFP, under the control of the endogenous gene promoter, using the ARID1A gene as an example...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28433543/phenformin-inhibits-myeloid-derived-suppressor-cells-and-enhances-the-anti-tumor-activity-of-pd-1-blockade-in-melanoma
#5
Sun Hye Kim, Man Li, Sebastian Trousil, Yaqing Zhang, Marina Pasca di Magliano, Kenneth D Swanson, Bin Zheng
Biguanides, such as the diabetes therapeutics metformin and phenformin, have demonstrated antitumor activity both in vitro and in vivo. However, their potential effects on the tumor microenvironment are largely unknown. Here we report that phenformin selectively inhibits granulocytic myeloid-derived suppressor cells (G-MDSCs) in spleens of tumor bearing mice and ex vivo. Phenformin induces production of reactive oxygen species in G-MDSC, whereas the antioxidant N-acetylcysteine attenuates the inhibitory effects of phenformin...
April 19, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28432813/targeting-on-poly-adp-ribose-polymerase-activity-with-dna-damaging-hybrid-lactam-steroid-alkylators-in-wild-type-and-brca1-mutated-ovarian-cancer-cells
#6
Dimitrios T Trafalis, Aikaterini Polonifi, Panayiotis Dalezis, Nikolaos Nikoleousakos, Sotirios Katsamakas, Vassiliki Sarli
Conjugated lactam-steroid alkylators (LSA), have been shown to exhibit superior activity at controlling cancer models and overlap drug resistance to conventional chemotherapy. Hybrid LSAs combine two active compounds in a single molecule and incorporate modified steroids bearing lactam moiety in one or more steroid rings functioning as vectors for cytotoxic agents. We first describe a novel class of LSAs that generate excellent anticancer activity against UWB1.289 and UWB1.289+BRCA1 human ovarian cancer cell lines...
April 22, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28432273/mir-509-3-5p-inhibits-the-invasion-and-lymphatic-metastasis-by-targeting-podxl-and-serves-as-a-novel-prognostic-indicator-for-gastric-cancer
#7
Jing Zhang, Zhonglin Zhu, Jinxin Sheng, Zhilong Yu, Bin Yao, Kejian Huang, Lisheng Zhou, Zhengjun Qiu, Chen Huang
BACKGROUND: Our study aimed to investigate the clinicopathological feature and prognostic role of miR-509-3-5P in gastric cancer, to determine the invasive and metastatic role of miR-509-3-5P in vitro and in vivo and to explore the molecular mechanism between miR-509-3-5P and PODXL. RESULTS: Strikingly lower miR-509-3-5P expression was detected in gastric cancer tissues with advanced tumor stage, poor differentiation and advanced pT stage, and was regarded as an independent prognostic role for poor prognosis...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28432122/dual-regulation-of-stat1-and-stat3-by-the-tumor-suppressor-protein-pml-contributes-to-ifn%C3%AE-mediated-inhibition-of-angiogenesis
#8
Kuo-Sheng Hsu, Xuan Zhao, Xiwen Cheng, Dongyin Guan, Ganapati H Mahabeleshwar, Yu Liu, Ernest Borden, Mukesh K Jain, Hung-Ying Kao
IFNs are effective in inhibiting angiogenesis in preclinical models and in treating several angio-proliferative disorders. However, the detailed mechanisms of IFNα-mediated anti-angiogenesis are not completely understood. Stat1/2/3 and PML are IFNα downstream effectors and are pivotal regulators of angiogenesis. Here, we investigated PML's role in the regulation of Stat1/2/3 activity. In Pml knockout (KO) mice, ablation of Pml largely reduces IFNα angiostatic ability in Matrixgel plug assays. This suggested an essential role for PML in IFNα's anti-angiogenic function...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28431527/evaluation-of-the-correlation-of-vasculogenic-mimicry-aldh1-kai1-and-microvessel-density-in-the-prediction-of-metastasis-and-prognosis-in-colorectal-carcinoma
#9
Bo Zhu, Lei Zhou, Lan Yu, Shiwu Wu, Wenqing Song, Xiaomeng Gong, Danna Wang
BACKGROUND: Metastasis and recurrence are the most common reasons for treatment failure of colorectal carcinoma (CRC). Vasculogenic mimicry (VM, blood supply formation often seen in highly aggressive tumors), Aldehyde dehydrogenase 1 (ALDH1, a biomarker of cancer stem cells), KAI1 (a suppressor gene of tumor metastasis) are all valuable factors for metastasis and prognosis in diverse human cancers. However, the correlation of VM, ALDH1, KAI1 and microvessel density (MVD) in CRC is unclear...
April 21, 2017: BMC Surgery
https://www.readbyqxmd.com/read/28431342/discovery-of-tetrahydrocarbazoles-as-dual-perk-and-prb-inhibitors
#10
Mahesh R Kulkarni, Madhav S Mane, Usha Ghosh, Rajiv Sharma, Nitin P Lad, Ankita Srivastava, Asha Kulkarni-Almeida, Prashant S Kharkar, Vijay M Khedkar, Shivaji S Pandit
The extracellular signal-regulated kinase (ERK) is one of the most important molecular targets for cancer that controls diverse cellular processes such as proliferation, survival, differentiation and motility. Similarly, the Rb (retinoblastoma protein) is a tumor suppressor protein and its function is to prevent excessive cell growth by inhibiting cell cycle progression. When the cell is ready to divide, pRb is phosphorylated, becomes inactive and allows cell cycle progression. Herein, we discovered a new series of tetrahydrocarbazoles as dual inhibitors of pERK and pRb phosphorylation...
March 2, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28430874/developmental-sall2-transcription-factor-a-new-player-in-cancer
#11
Viviana E Hermosilla, Matias I Hepp, David Escobar, Carlos Farlas, Elizabeth N Riffo, Ariel F Castro, Roxana Pincheira
SALL2, also known as Spalt-like transcription factor 2, is a member of the SALL family of transcription factors involved in development and conserved through evolution. Since its identification in 1996, findings indicate that SALL2 plays a role in neurogenesis, neuronal differentiation and eye development. Consistently, SALL2 deficiency associates with neural tube defects and coloboma, a congenital eye disease. Relevant to cancer, clinical studies indicate that SALL2 is deregulated in various cancers, and is a specific biomarker for Synovial Sarcoma...
April 18, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28430625/mir-766-induces-p53-accumulation-and-g2-m-arrest-by-directly-targeting-mdm4
#12
Qingqing Wang, Luke A Selth, David F Callen
p53, a transcription factor that participates in multiple cellular functions, is considered the most important tumor suppressor. Previous evidence suggests that post-transcriptional deregulation of p53 by microRNAs contributes to tumorigenesis, tumor progression and therapeutic resistance. In the present study, we found that the microRNA miR-766 was aberrantly expressed in breast cancer, and that over-expression of miR-766 caused accumulation of wild-type p53 protein in multiple cancer cell lines. Supporting its role in the p53 signalling pathway, miR-766 decreased cell proliferation and colony formation in several cancer cell lines, and cell cycle analyses revealed that miR-766 causes G2 arrest...
February 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430604/signal-transducing-adaptor-protein-2-promotes-generation-of-functional-long-term-memory-cd8-t-cells-by-preventing-terminal-effector-differentiation
#13
Daisuke Muraoka, Naohiro Seo, Tae Hayashi, Chisaki Hyuga-Amaike, Kana Okamori, Isao Tawara, Naozumi Harada, Hiroshi Shiku
Long-surviving memory CD8+ T cells generated by stimulation with appropriate tumor-associated antigens are the most aggressive and persistent tumoricidal effectors. In this event of memory CD8+ T cell development, the signal transducer and activator of transcription (STAT) proteins function as the crucial intracellular signaling molecules, but the regulatory mechanism of STATs in CD8+ T cells is not fully understood. In this study, we report for the first time, by using murine vaccination models, that signal-transducing adaptor protein-2 (STAP2) maintains the cytotoxicity of long-lived memory CD8+ T cells by controlling a STAT3/suppressor of cytokine signaling 3 (SOCS3) cascade...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430585/foxd3-regulates-anaplastic-thyroid-cancer-progression
#14
Huabin Yin, Tong Meng, Lei Zhou, Feixing Zhao, Xiufang Li, Yundong Li, Mengjun Hu, Haiyan Chen, Dianwen Song
Anaplastic thyroid cancer (ATC) is an aggressive malignancy with poor prognosis. It was reported that Forkhead box D3 (FOXD3) transcription factor is associated with several cancers. We investigated its antitumorigenic role of ATC in this study. The ATC cell lines SW1736 and K18 exhibited lower FOXD3 expression than the Nthy-ori-3-1 normal thyroid cell line. FOXD3 downregulation in ATC cell lines promoted invasiveness and epithelial-to-mesenchymal transition (EMT) and decreased cellular apoptosis. FOXD3 silencing also enhanced p-ERK levels in the ATC cell lines, suggesting it negatively regulated MAPK/ERK signaling...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430582/lncrna-chrf-induced-mir-489-loss-promotes-metastasis-of-colorectal-cancer-via-twist1-emt-signaling-pathway
#15
Youmao Tao, Tao Han, Tao Zhang, Chong Ma, Caixia Sun
microRNA-489 (miR-489) is a novel cancer-related miRNAs and functions as a tumor suppressor in human cancers. While, the clinical significance of miR-489 and its role in colorectal cancer (CRC) remain rarely known. Here, we found that the levels of miR-489 in CRC tissues were significantly lower than those in matched tumor-adjacent tissues. Furthermore, decreased levels of miR-489 also observed in CRC cell lines compared to HIEC cells. Clinicopathological analysis revealed that miR-489 underexpression was positively correlated with advanced pT stage, pN stage and AJCC stage...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430184/the-ubiquitin-ligase-lin41-trim71-targets-p53-to-antagonize-cell-death-and-differentiation-pathways-during-stem-cell-differentiation
#16
Duong Thi Thuy Nguyen, Daniel Richter, Geert Michel, Sibylle Mitschka, Waldemar Kolanus, Elisa Cuevas, F Gregory Wulczyn
Rapidity and specificity are characteristic features of proteolysis mediated by the ubiquitin-proteasome system. Therefore, the UPS is ideally suited for the remodeling of the embryonic stem cell proteome during the transition from pluripotent to differentiated states and its inverse, the generation of inducible pluripotent stem cells. The Trim-NHL family member LIN41 is among the first E3 ubiquitin ligases to be linked to stem cell pluripotency and reprogramming. Initially discovered in C. elegans as a downstream target of the let-7 miRNA, LIN41 is now recognized as a critical regulator of stem cell fates as well as the timing of neurogenesis...
April 21, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28429357/inhibition-of-pulmonary-carcinoma-proliferation-or-metastasis-of-mir-218-via-down-regulating-cdcp1-expression
#17
X-J Zeng, Y-H Wu, M Luo, P-G Cong, H Yu
OBJECTIVE: Pulmonary carcinoma is one common malignant tumor with a high risk of recurrence and metastasis. Non-small cell lung cancer (NSCLC) is the most common subtype. As one tumor biomarker, microRNA (miR) has tissue sensitivity and can facilitate oncogene or inhibit tumor suppressor gene. MiR-218 has abnormal expression and can work as one molecular marker for tumors. However, its expression and function mechanism in lung cancer cells have not been fully illustrated. MATERIALS AND METHODS: In vitro cultured pulmonary adenoma A549 cells and normal bronchial epithelial cell line 16HBE were tested for miR-218 expression...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28428276/micellar-delivery-of-mir-34a-modulator-rubone-and-paclitaxel-in-resistant-prostate-cancer
#18
Di Wen, Yang Peng, Feng Lin, Rakesh K Singh, Ram I Mahato
Treatment of prostate cancer with paclitaxel (PTX) often fails due to development of chemoresistance caused by downregulation of the tumor suppressor gene miR-34a. In this study, we demonstrate that co-delivery of PTX and 2'-hydroxy-2,4,4',5,6'-pentamethoxychalcone (termed rubone) drives upregulation of miR-34a and chemosensitizes PTX-resistant prostate cancer cells, killing both cancer stem-like cells (CSCs) and bulk tumor cells. Rubone upregulated miR-34a and reversed its downstream target genes in DU145-TXR and PC3-TXR cells...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427434/adenovirus-mediated-cd40l-gene-transfer-increases-teffector-tregulatory-cell-ratio-and-upregulates-death-receptors-in-metastatic-melanoma-patients
#19
A Schiza, J Wenthe, S Mangsbo, E Eriksson, Anders Nilsson, T H Tötterman, A Loskog, G Ullenhag
BACKGROUND AND AIMS: Malignant melanoma is an aggressive tumor sensitive for immunotherapy such as checkpoint blockade antibodies. Still, most patients with late stage disease do not respond, and the side effects can be severe. Stimulation of the CD40 pathway to initiate anti-tumor immunity is a promising alternative. Herein, we demonstrate immune profiling data from melanoma patients treated with an adenovirus-based CD40 ligand gene therapy (AdCD40L). METHODS: Peripheral blood mononuclear cells and plasma were collected from malignant melanoma patients (n = 15) enrolled in a phase I/IIa study investigating intratumoral delivery of AdCD40L with or without low dose cyclophosphamide...
April 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28427224/ponatinib-promotes-a-g1-cell-cycle-arrest-of-merlin-nf2-deficient-human-schwann-cells
#20
Alejandra M Petrilli, Jeanine Garcia, Marga Bott, Stephani Klingeman Plati, Christine T Dinh, Olena R Bracho, Denise Yan, Bing Zou, Rahul Mittal, Fred F Telischi, Xue-Zhong Liu, Long-Sheng Chang, D Bradley Welling, Alicja J Copik, Cristina Fernández-Valle
Neurofibromatosis type 2 (NF2) is a genetic syndrome that predisposes individuals to multiple benign tumors of the central and peripheral nervous systems, including vestibular schwannomas. Currently, there are no FDA approved drug therapies for NF2. Loss of function of merlin encoded by the NF2 tumor suppressor gene leads to activation of multiple mitogenic signaling cascades, including platelet-derived growth factor receptor (PDGFR) and SRC in Schwann cells. The goal of this study was to determine whether ponatinib, an FDA-approved ABL/SRC inhibitor, reduced proliferation and/or survival of merlin-deficient human Schwann cells (HSC)...
March 6, 2017: Oncotarget
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