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Cancer Biology & Therapy

Bhanvi Mishra, Sufang Zhang, Hong Zhao, Zbigniew Darzynkiewicz, Ernest Y C Lee, Marietta Y W T Lee, Zhongtao Zhang
Chromosomal duplication is targeted by various chemotherapeutic agents for the treatment of cancer. However, there is no specific inhibitor of DNA polymerases that is viable for cancer management. Through structure-based in silico screening of the ZINC database, we identified a specific inhibitor of DNA polymerase δ. The discovered inhibitor, Zelpolib, is projected to bind to the active site of Pol δ when it is actively engaged in DNA replication through interactions with DNA template and primer. Zelpolib shows robust inhibition of Pol δ activity in reconstituted DNA replication assays...
November 14, 2018: Cancer Biology & Therapy
Chunfang Wang, Ke Su, Yanyan Zhang, Weiwei Zhang, Qian Zhao, Danxia Chu, Ruixia Guo
BACKGROUND: Obesity is a risk factor for endometrial cancer (EC). However, it is not known how insulin receptor isoform A (IR-A) and insulin-like growth factor 1 receptor (IGF-1R), cognate receptors for insulin and IGFs, respectively, regulate malignant behaviors of EC. In this study, we examined the biological effects of IR-A/IGF-1R, explored the downstream signaling cascades, and assessed the therapeutic potential of targeting IR-A/IGF-1R in vivo. METHODS: The expression levels of IR-A and IGF-1R were examined by qRT-PCR and Western blotting...
November 14, 2018: Cancer Biology & Therapy
Nina Anika Richarz, Luis Puig, Noelia Pérez, Jose Cuadra-Urteaga, Elena Elez, Maria Teresa Fernández-Figueras
Neutrophilic panniculitis is an infrequent but characteristic adverse event under therapy with BRAF inhibitors (BRAFi). Since the approval of vemurafenib for treatment of metastatic melanoma in 2011, only two cases of neutrophilic panniculitis in malignancies other than melanoma have been published. Histiocytoid infiltrates of immature neutrophils resembling histiocytes or myelocytes have been reported in Sweet's syndrome and rarely in other neutrophilic dermatoses. We describe a novel variant of neutrophilic panniculitis with histiocytoid myeloid cells in an early lesion from a patient treated with vemurafenib in combination with an anti-EGFR (epidermal growth factor receptor) agent for metastatic colon carcinoma, three weeks after initiation of therapy...
November 14, 2018: Cancer Biology & Therapy
Yanjun Xu, Yun Fan
Evidence suggests that activation of the MET signaling pathway might be associated with EGFR-TKI resistance. EGFR TKI-resistant lung cancers often remain sensitive to inhibition of the EGFR pathway; thus, c-MET inhibitors are likely to be effective when combined with continued EGFR-TKI treatment. Here, we described a 56-year-old male who became refractory after first-line gefitinib therapy and was confirmed to have c-MET overexpression without a T790M mutation, c-MET amplification or MET exon 14 alterations...
November 13, 2018: Cancer Biology & Therapy
Serena Montagnaro, Sara Damiano, Roberto Ciarcia, Maria Valeria Puzio, Gianmarco Ferrara, Valentina Iovane, Iris Maria Forte, Antonio Giordano, Ugo Pagnini
Caprine Herpesvirus type 1 (CpHV-1) is a species-specific herpes virus able to induce apoptosis in several biological systems. In the present study we aimed to investigate the ability of CpHV-1 to reduce cells viability, to replicate and to cause cell death also in human cancer cell lines. We tested the CpHV-1 effects on HEL-299, Vero, MDA-MB-468, HeLa, U2OS, PC3, A549 and K562 neoplastic cell lines and on MDBK cells. Firstly, we evaluated the effect of CpHV-1 infection on cell viability by MTT assay and our data showed that CpHV-1 can induce a marked cytopathic effect (CPE) in most of cell lines tested, except for HEL-299, Vero and K562 cells...
November 8, 2018: Cancer Biology & Therapy
Hua Sheng, Xiangyang Li, Yi Xu
Lung cancer is one of the most common cancers in the world, which accounts for about 27% of all cancer deaths. However, the mechanisms underlying the pathogenesis of lung cancer cells remain largely elusive. In this study, we examined the role of the Forkhead box protein P1 (FOXP1) in lung cancer development. Our Oncomine analysis shows that FOXP1 is downregulated in lung adenocarcinoma compared with normal lung tissue. Knockdown of FOXP1 promotes the growth and invasion of PC9 and A549 cells by regulating genes of chemokine signaling molecules, including CCR1, ADCY5, GNG7, VAV3, and PLCB1...
November 8, 2018: Cancer Biology & Therapy
Haifang Wang, Wenxiang Chen, Peng Yang, Jun Zhou, Kaiyuan Wang, Qingchun Tao
BACKGROUND: Gastric cancer (GC) is a serious threat for public health worldwide. Long non-coding RNA (lncRNA) linc00152 has been well reported to be an oncogene and a potential biomarker in multiple cancers including GC. However, the molecular mechanisms of linc00152 in GC development need to be further investigated. METHODS: RT-qPCR assay was employed to detect the levels of linc00152, microRNA-193b-3p (miR-193b-3p) and ETS1 mRNA. ETS1 protein level was measured by western blot assay...
November 7, 2018: Cancer Biology & Therapy
Jingfei Teng, Xing Ai, Zhuomin Jia, Kai Wang, Yawei Guan, Yanjie Guo
Accumulative reports have documented the critical functions of long non-coding RNAs (lncRNAs) in the progression of malignant tumors, including bladder cancer (BCa). LncRNA ARAP1-AS1 was chosen to be the object of this study due to it was significantly upregulated in the BCa samples of TCGA database. qRT-PCR further validated the dysregulation of ARAP1-AS1 in 88 pairs of BCa tissues and six BCa cells. Kaplan Meier analysis was utilized to analyze the prognostic value of ARAP1-AS1 for patients with BCa. To evaluate the oncogenic property of ARAP1-AS1 in bladder cancer, loss-of-function assays were conducted in two BCa cells in which ARAP1-AS1 was expressed highest...
November 7, 2018: Cancer Biology & Therapy
Dong Cui, Yongfu Zhao, Jingchao Xu
C-X-C motif chemokine ligand 5 (CXCL5) is initially identified to recruit neutrophils by interacting with its receptor, C-X-C motif chemokine receptor 2 (CXCR2). Our prior work demonstrated that the expression levels of CXCL5 and CXCR2 were higher in the papillary thyroid carcinoma (PTC) tumors than that in the non-tumors. This study was performed to further investigate how this axis regulates the growth of PTC cells. B-CPAP cells (BRAFV600E ) and TPC-1 cells (RET/PTC rearrangement) expressing CXCR-2 were used as in vitro cell models...
November 7, 2018: Cancer Biology & Therapy
Zhe Liu, Hong Li, Sumeng Fan, Hui Lin, Wenwei Lian
Long non-coding RNAs (lncRNAs) are a group of biomarkers which can regulate the biological processes of various human cancers. LncRNA HNF1A-AS1 has been reported in human cancers for its oncogenic role. This study focused on the biological function and molecular mechanism of HNF1A-AS1 in oral squamous cell carcinoma (OSCC). The high expression of HNF1A-AS1 was examined in OSCC tissues and cell lines. Kaplan Meier method revealed that high expression of HNF1A-AS1 predicted poor prognosis for patients with OSCC...
November 7, 2018: Cancer Biology & Therapy
Teresa Gamucci, Laura Pizzuti, Clara Natoli, Lucia Mentuccia, Isabella Sperduti, Maddalena Barba, Domenico Sergi, Laura Iezzi, Marcello Maugeri-Saccà, Angela Vaccaro, Emanuela Magnolfi, Alain Gelibter, Giacomo Barchiesi, Valentina Magri, Loretta D'Onofrio, Alessandra Cassano, Ernesto Rossi, Andrea Botticelli, Luca Moscetti, Claudia Omarini, Maria Agnese Fabbri, Angelo Fedele Scinto, Domenico Corsi, Luisa Carbognin, Marco Mazzotta, Emilio Bria, Jennifer Foglietta, Riccardo Samaritani, Carlo Garufi, Luciano Mariani, Sandro Barni, Rosanna Mirabelli, Roberta Sarmiento, Vincenzo Graziano, Daniele Santini, Paolo Marchetti, Giuseppe Tonini, Luigi Di Lauro, Giuseppe Sanguineti, Giancarlo Paoletti, Silverio Tomao, Ruggero De Maria, Enzo Veltri, Ida Paris, Francesco Giotta, Agnese Latorre, Antonio Giordano, Gennaro Ciliberto, Patrizia Vici
We carried out a retrospective observational study of 264 HER2-positive advanced breast cancer (ABC) patients to explore the efficacy of first-line treatment with pertuzumab/trastuzumab/taxane in real-world setting. Survival data were analyzed by Kaplan Meier curves and log rank test. Median follow-up, length of pertuzumab/trastuzumab/taxane treatment and of pertuzumab, trastuzumab maintenance were 21, 4 and 15 months, respectively. The response rate was 77.3%, and the clinical benefit rate 93.6%. Median progression-free survival (mPFS) was 21 months, and median overall survival (mOS) was not reached...
November 7, 2018: Cancer Biology & Therapy
Kara McNair, Caroline M Forrest, Maria C J Vincenten, L Gail Darlington, Trevor W Stone
Expression of the tumour suppressor Deleted in Colorectal Cancer (DCC) and the related protein neogenin is reduced by the mammalian serine protease chymotrypsin or the bacterial serine protease subtilisin, with increased cell migration. The present work examines whether these actions are associated with changes in the expression of cadherins, β-catenin and vimentin, established markers of the Epithelial-Mesenchymal Transition (EMT) which has been linked with cell migration and tumour metastasis. The results confirm the depletion of DCC and neogenin and show that chymotrypsin and subtilisin also reduce expression of β-catenin in acutely prepared tissue sections but not in human mammary adenocarcinoma MCF-7 or MDA-MB-231 cells cultured in normal media, or primary normal human breast cells...
November 7, 2018: Cancer Biology & Therapy
Jing Jing Li, Shi Yan, Yaqi Pan, Zhen Liu, Ying Liu, Qiuju Deng, Qin Tan, Emma R Woodward, Nan Wu
Targeting FGFRs is one of the most promising therapeutic strategies in squamous non-small cell lung cancer (SQCC). However, different FGFR genomic aberrations can be associated with distinct biological characteristics that result in different clinical outcomes or therapeutic consequences. Currently, the full spectrum of FGFR gene aberrations and their clinical significance in SQCC have not been comprehensively studied. Here, we used Next-generation sequencing to investigate the presence of FGFR gene mutations in 143 tumors from patients with stage I, II or III SQCC and who had not been treated with chemotherapy or radiotherapy prior to surgery...
November 7, 2018: Cancer Biology & Therapy
Yi Ma, Xin Zhang, Yi-Zhi Wang, Hao Tian, Shun Xu
Lung cancer is one of the most common cancers and the leading cause of cancer-related death worldwide. Despite encouraging results achieved with targeted therapy in recent years, the early diagnosis and treatment of lung cancer remains a major problem. Circular RNA (circRNA), a type of RNA with covalently closed continuous loop structures, has structural stability and certain tissue specificity. Recent studies have found that circRNAs have an important role in tumor development and are expected to be revealed as new targets for tumor prediction and treatment...
November 7, 2018: Cancer Biology & Therapy
Shenpeng Ying, Honggang Ke, Yan Ding, Yanmei Liu, Xiaowan Tang, Dongyong Yang, Min Li, Junjun Liu, Bing Yu, Jianxing Xiang, Xinru Mao, Han Han-Zhang, Wei Hu, Lili Chen
BACKGROUND: Leptomeningeal metastases (LM), associated with poor prognosis, are frequent complications of advanced non-small cell lung cancer (NSCLC) patients, especially in patients with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the mutational landscape of LM has not been comprehensively investigated in large cohorts and the underlining biology of LM remains elusive. Some studies have explored the potential of cerebrospinal fluid (CSF) in reflecting the molecular profile of LM but with limited number of patients enrolled...
November 5, 2018: Cancer Biology & Therapy
Mingbao Zhang, Yue Li, Hongbo Wang, Weihua Yu, Sen Lin, Jianqiang Guo
We aimed at the effects of long non-coding RNA (lncRNA) SNHG5 on proliferation, metastasis and migration of colorectal cancer (CRC) cells. We also investigated regulatory relationships among miR-132-3p, SNHG5 and CREB5 and their roles in CRC. 25 pairs of samples containing CRC tissues and matched para-tumor tissues were obtained to examine SNHG5, miR-132-3p and CREB5 expression by qRT-PCR or Western blot. The targeted relationship between miR-132-3p and SNHG5 or CREB5 was confirmed by dual luciferase report assay as well as RNA pull down assay...
November 5, 2018: Cancer Biology & Therapy
Ahsan Wahab, Juan Jose Gonzalez, Vishal Devarkonda, Tryphene Saint-Phard, Trevor Singh, Orimisan Samuel Adekolujo
A 65-year-old Caucasian female presented with abdominal symptoms and obstructive jaundice. She reported a significant pancreatic cancer history in her family. Her CT of the abdomen and pelvis showed 3.9 × 3.5 cm centrally necrotic mass within the pancreatic head, occluding the superior mesenteric and splenic veins; peripancreatic lymph nodes were enlarged, and there were many hepatic lesions. She underwent biopsy of the hepatic lesions showing metastatic tumor cells, arranged in the form of nests, with enlarged and hyperchromatic irregular nuclei with some nucleoli and moderate eosinophilic cytoplasm...
November 2, 2018: Cancer Biology & Therapy
Chen Xi, Zhang Wencheng, Qian Dong, Guan Yong, Yan Cihui, Wang Yuwen, Zhang Hualei, Er Puchun, Pang Qingsong, Wang Ping
The PD-1/PD-L1 axis is characterized as an important checkpoint of immune activation, particularly through negatively regulating T cell function. Although accumulated evidence has demonstrated the patients with some types of tumor benefit from blockade of PD-1/PD-L1 signaling pathway, the possible synergistic effect of combination of radiotherapy and anti-PD-1/PD-L1 antibody still need to be explored. Here, we report a case of patient who was diagnosed with metastatic mediastinal leiomyosarcoma and treated by combination of local radiotherapy and anti-PD-1 antibody nivolumab...
November 2, 2018: Cancer Biology & Therapy
Taryn L Cranford, Kandy T Velázquez, Reilly T Enos, Alexander T Sougiannis, Jackie E Bader, Meredith S Carson, Rebecca R Bellone, Ioulia Chatzistamou, Mitzi Nagarkatti, E Angela Murphy
Clinical studies provide strong evidence that obesity and associated adipose tissue (AT) inflammation are risk factors for breast cancer (BrCA); however, mechanistic knowledge of the interaction of obesity, BrCA, and menopausal status has proven to be not only lacking, but contradictory. Obesity-induced inflammation and elevated biosynthesis of estrogens, through aromatase-mediated metabolism of precursors, have been linked with hormone receptor positive (HP) postmenopausal BrCA but not previously associated with premenopausal BrCA risk...
November 2, 2018: Cancer Biology & Therapy
Laurence Booth, Jane L Roberts, Sarah Spiegel, Andrew Poklepovic, Paul Dent
Overall, NSCLC has a poor 5-year survival and new therapeutic approaches are urgently needed. ERBB-addicted NSCLC that have become resistant to ERBB inhibitors are often refractory to additional therapeutic interventions. The sphingosine-1-phosphate receptor modulator fingolimod (FTY720), approved for the treatment of multiple sclerosis, synergized with the NSCLC therapeutic pemetrexed to kill NSCLC and ovarian cancer cells. This occurred in lung cancer cells expressing mutated K-RAS, mutated ERBB1, or in NSCLC cells resistant to afatinib (an ERBB1/2/4 inhibitor)...
November 2, 2018: Cancer Biology & Therapy
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