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tumor target treatment

Joanna Pancewicz-Wojtkiewicz
Lung cancer is the most common reason of cancer deaths and about 85% of these are non-small-cell lung cancer. Currently, lung cancer therapy is mainly based on the tumor node metastasis (TNM) disease staging and tumor histological classification. Despite therapeutic innovations, the prognosis for lung cancer patients has not significantly changed in the last years. Therefore, a proper understanding of cell signaling pathways involved in cancer pathogenesis seems to be essential for improvement in cancer therapy field...
October 21, 2016: Cancer Medicine
Michaël Duruisseaux, Anne McLeer-Florin, Martine Antoine, Sanaz Alavizadeh, Virginie Poulot, Roger Lacave, Nathalie Rabbe, Jacques Cadranel, Marie Wislez
Invasive mucinous lung adenocarcinoma (IMA) is a rare subtype of lung adenocarcinoma with no effective treatment option in advanced disease. KRAS mutations occur in 28-87% of the cases. NRG1 fusions were recently discovered in KRAS-negative IMA cases and otherwise negative for known driver oncogenes and could represent an attractive therapeutic target. Published data suggest that NRG1 fusions occur essentially in nonsmoking Asian women. From an IMA cohort of 25 French patients of known ethnicity, driver oncogenes EGFR, KRAS, BRAF, ERBB2 mutations, and ALK and ROS1 rearrangements presence were analyzed...
October 21, 2016: Cancer Medicine
Junsik Park, Minsuk Kwon, Eui-Cheol Shin
During immune responses antigen-specific T cells are regulated by several mechanisms, including through inhibitory receptors and regulatory T cells, to avoid excessive or persistent immune responses. These regulatory mechanisms, which are called 'immune checkpoints', suppress T cell responses, particularly in patients with chronic viral infections and cancer where viral antigens or tumor antigens persist for a long time and contribute to T cell exhaustion. Among these regulatory mechanisms, cytotoxic T lymphocyte associated protein-4 (CTLA-4) and programmed cell death 1 (PD-1) are the most well-known receptors and both have been targeted for drug development...
October 21, 2016: Archives of Pharmacal Research
Clement Chung
PURPOSE: Current strategies for managing neuroendocrine tumors (NETs) in adult patients are reviewed, with a focus on medication safety concerns. SUMMARY: NETs usually originate in the gastrointestinal or bronchopulmonary tract. Symptoms due to hormonal hypersecretion often occur in patients with foregut or midgut NETs or liver metastases. Surgical resection is recommended for most localized NETs, while systemic cytotoxic chemotherapy is typically used for high-grade and pancreatic tumors...
November 1, 2016: American Journal of Health-system Pharmacy: AJHP
Phei Er Saw, Jinho Park, Sangyong Jon, Omid C Farokhzad
A major problem with cancer chemotherapy begins when cells acquire resistance. Drug-resistant cancer cells typically upregulate multi-drug resistance proteins such as P-glycoprotein (P-gp). However, the lack of overexpressed surface biomarkers has limited the targeted therapy of drug-resistant cancers. Here we report a drug-delivery carrier decorated with a targeting ligand for a surface marker protein Extra-domain B(EDB) specific to drug-resistant breast cancer cells as a new therapeutic option for the aggressive cancers...
October 18, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Byung Sup Kim, Doo-Sik Kong, Ho Jun Seol, Do-Hyun Nam, Jung-Il Lee
Residual or recurrent hemangiopericytoma (HPC) has been treated with radiosurgery; however, its long-term outcome is not well known. This study is to investigate the long-term outcome of gamma knife radiosurgery (GKS) for residual or recurrent HPCs. We conducted a retrospective analysis of 18 patients who underwent gamma knife radiosurgery for residual or recurrent HPCs. Of the 18 patients, 10 patients had high-grade HPCs (27 tumors) and 8 had low-grade HPCs (13 tumors). Median overall survival (OS) after the first GKS was 134...
October 18, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Cheng-Ming Chiang
BRD4 is an epigenetic regulator and transcription cofactor whose phosphorylation by CK2 and dephosphorylation by PP2A modulates its function in chromatin targeting, factor recruitment, and cancer progression. While the bromodomains of BET family proteins, including BRD4, BRD2, BRD3 and BRDT, have been the primary targets of small compounds such as JQ1, I-BET and MS417 that show promising anticancer effects against some hematopoietic cancer and solid tumors, drug resistance upon prolonged treatment necessitates a better understanding of alternative pathways underlying not only the resistance but also persistent BET protein dependence for identifying new targets and effective combination therapy strategies...
March 2016: Drug Discovery Today. Technologies
Jeong-Eun Rah, Gwe-Ya Kim, Do Hoon Oh, Tae Hyun Kim, Jong Won Kim, Dae Yong Kim, Sung Yong Park, Dongho Shin
BACKGROUND: The purpose of this study is to evaluate the dosimetric benefits of a proton arc technique for treating tumors of the para-aortic lymph nodes (PALN). METHOD: In nine patients, a proton arc therapy (PAT) technique was compared with intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) techniques with respect to the planning target volume (PTV) and organs at risk (OAR). PTV coverage, conformity index (CI), homogeneity index (HI) and OAR doses were compared...
October 21, 2016: Radiation Oncology
Yan Zhou, Shuchen Lin, Kuo-Fu Tseng, Kun Han, Yaling Wang, Zhi-Hua Gan, Da-Liu Min, Hai-Yan Hu
BACKGROUND: Triple-negative breast cancer (TNBC) has aggressive progression with poor prognosis and ineffective treatments. Selumetinib is an allosteric, ATP-noncompetitive inhibitor of MEK1/2, which has benn known as effective antineoplastic drugs for several malignant tumors. We hypothesized that Selumetinib might be potential drug for TNBC and explore the mechanism. METHODS: After treated with Selumetinib, the viability and mobility of HCC1937 and MDA-MB-231 were detected by MTT, tunnel, wound-healing assay, transwell assay and FCM methods...
October 21, 2016: BMC Cancer
Kathrin Fielitz, Kristina Althoff, Katleen De Preter, Julie Nonnekens, Jasmin Ohli, Sandra Elges, Wolfgang Hartmann, Günter Klöppel, Thomas Knösel, Marc Schulte, Ludger Klein-Hitpass, Daniela Beisser, Henning Reis, Annette Eyking, Elke Cario, Johannes H Schulte, Alexander Schramm, Ulrich Schüller
Amplification or overexpression of MYCN is involved in development and maintenance of multiple malignancies. A subset of these tumors originates from neural precursors, including the most aggressive forms of the childhood tumors, neuroblastoma and medulloblastoma. In order to model the spectrum of MYCN-driven neoplasms in mice, we transgenically overexpressed MYCN under the control of the human GFAP-promoter that, among other targets, drives expression in neural progenitor cells. However, LSL-MYCN;hGFAP-Cre double transgenic mice did neither develop neural crest tumors nor tumors of the central nervous system, but presented with neuroendocrine tumors of the pancreas and, less frequently, the pituitary gland...
October 19, 2016: Oncotarget
Miao Liu, Ling Zhou, Baiyu Zhang, Minhong He, Xiaoying Dong, Xiaojun Lin, Chunhong Jia, Xiaochun Bai, Yifan Dai, Yongchun Su, Zhipeng Zou, Hang Zheng
Although epidemiological and preclinical studies have shown the preventative effect of n-3 polyunsaturated fatty acids (PUFAs) on colorectal cancer (CRC), the underlying molecular mechanisms are not clear. In this study, we revealed that elevation of n-3/n-6 PUFAs ratio suppress the mechanistic target of rapamycin complex 1 (mTORC1) and prevent colorectal tumorigenesis. The transgenic expression of fat-1, a desaturase that catalyzes the conversion of n-6 to n-3 PUFAs and produces n-3 PUFAs endogenously, repressed colorectal tumor cell growth and remarkably reduced tumor burden, and alleviated anemia as well as hyperlipidemia in APCMin/+ (adenomatous polyposis coli) mice, a classic CRC model that best simulates most clinical cases...
October 19, 2016: Oncotarget
Xia Wang, Qing Li, Hua Jin, Hua Zou, Wei Xia, Nan Dai, Xiao-Yan Dai, Dong Wang, Cheng-Xiong Xu, Yi Qing
Previous studies have shown that some dysregulated miRNAs are involved in radioresistance of tumor cells. Here, we identified significantly decreased miR-424 expression in radioresistant cervical cancer cells and specimens from cervical cancer patients with radioresistance compared to their radiosensitive parental cells and specimens from radiosensitive patients, respectively. Ectopic expression of miR-424 significantly increased radiation-induced DNA damage, cell apoptosis and G2/M cell cycle arrest in radioresistant cervical cancer cells...
October 18, 2016: Oncotarget
Qiyong Jiang, Yimin Liu, Shijuan Zhang, Naikun Li, Gaoling Sun
MiRNAs are emerging as important epigenetic modulators of multiple target genes, leading to abnormal cellular signaling involving cellular proliferation in cancers. Aberrant miRNA expression has been observed in human glioblastoma (GBM). The present study was to evaluate the expression and molecular mechanisms of COX-2 and miR-26b in human GBM tissues and GBM cell lines T98G, U87 and U251. In the present study, we found that expression of miR-26b was markedly downregulated in GBM cell lines and human GBM tissues, compared to matched non-tumor associated tissues...
October 17, 2016: Oncotarget
Cong Wu, Meng-Qing Gong, Bo-Ya Liu, Ren-Xi Zhuo, Si-Xue Cheng
To effectively reverse multiple drug resistance (MDR) in tumor treatments, a functional nano-sized drug delivery system with active targeting function and pH sensitivity was prepared for the co-delivery of multiple drug resistance inhibitors. Buthionine sulfoximine (BSO) to inhibit GSH synthesis and celecoxib (CXB) to down-regulate P-gp expression were co-loaded in polymer/inorganic hybrid nanoparticles to form buthionine sulfoximine/celecoxib@biotin-heparin/heparin/calcium carbonate/calcium phosphate nanoparticles (BSO/CXB@BNP)...
October 13, 2016: Colloids and Surfaces. B, Biointerfaces
Erik R Nelson, Shenduo Li, Margaret Kennedy, Sturgis Payne, Kelly Kilibarda, Jeffrey Groth, Michelle Bowie, Edgardo Parilla-Castellar, Gustaaf de Ridder, Paul Kelly Marcom, Matthew Lyes, Bercedis L Peterson, Michael Cook, Salvatore V Pizzo, Donald P McDonnell, Robin E Bachelder
BACKGROUND: Although most triple-negative breast cancer (TNBC) patients initially respond to chemotherapy, residual tumor cells frequently persist and drive recurrent tumor growth. Previous studies from our laboratory and others' indicate that TNBC is heterogeneous, being composed of chemo-sensitive and chemo-resistant tumor cell subpopulations. In the current work, we studied the invasive behaviors of chemo-resistant TNBC, and sought to identify markers of invasion in chemo-residual TNBC...
October 18, 2016: Oncotarget
Gianluigi Franci, Federica Sarno, Angela Nebbioso, Lucia Altucci
Epigenetic modifications are functionally involved in gene expression regulation. In particular, histone posttranslational modifications play a crucial role in functional chromatin organization. Several drugs able to inhibit or stimulate some families of proteins involved in epigenetic histone regulation have been found, a number of which are FDA-approved for the treatment of cutaneous T-cell lymphoma or are in phase I/II/III clinical trials for solid tumors. Although some protein families, such as histone deacetylases and their inhibitors, are well characterized, our understanding of histone lysine demethylases is still incomplete...
October 21, 2016: Epigenetics: Official Journal of the DNA Methylation Society
S Sengupta, G Mao, Z S Gokaslan, P Sampath
Glioblastoma (GBM) is by far the most common and the most aggressive of all the primary brain malignancies. No curative therapy exists, and median life expectancy hovers at around 1 year after diagnosis, with a minute fraction surviving beyond 5 years. The difficulty in treating GBM lies in the cancer's protected niche within the blood-brain barrier and the heterogeneity of the cancer cells, which possess varying degrees of susceptibility to various common modalities of treatment. Over time, it is the tumor heterogeneity of GBM and the ability of the cancer stem cells to evolve in response treatment that renders the cancer refractory to conventional treatment...
October 21, 2016: Cancer Gene Therapy
Yun-Wen Yang, Chun-Mei Zhang, Xian-Jie Huang, Xiao-Xin Zhang, Lin-Kai Zhang, Jia-Huang Li, Zi-Chun Hua
Fas-associated protein with death domain (FADD), a pivotal adaptor protein transmitting apoptotic signals, is indispensable for the induction of extrinsic apoptosis. However, overexpression of FADD can form large, filamentous aggregates, termed death effector filaments (DEFs) by self-association and initiate apoptosis independent of receptor cross-linking. A mutant of FADD, which is truncated of the C-terminal tail (m-FADD, 182-205 aa) named N-FADD (m-FADD, 1-181 aa), can dramatically up-regulate the strength of FADD self-association and increase apoptosis...
October 21, 2016: Scientific Reports
Sajjad Karim, Jaudah A Al-Maghrabi, Hasan M A Farsi, Ahmad J Al-Sayyad, Hans-Juergen Schulten, Abdelbaset Buhmeida, Zeenat Mirza, Alaa A Al-Boogmi, Fai T Ashgan, Manal M Shabaad, Hend F NourEldin, Khalid B M Al-Ghamdi, Adel Abuzenadah, Adeel G A Chaudhary, Mohammed H Al-Qahtani
BACKGROUND: Renal cell carcinoma (RCC) is a seventh ranked malignancy with poor prognosis. RCC is lethal at metastatic stage as it does not respond to conventional systemic treatments, and there is an urgent need to find out promising novel biomarkers for effective treatment. The goal of this study was to evaluate the biomarkers that can be potential therapeutic target and predict effective inhibitors to treat the metastatic stage of RCC. METHODS: We conducted transcriptomic profiling to identify differentially expressed genes associated with RCC...
September 30, 2016: BMC Cancer
I Nakachi, B A Helfrich, M A Spillman, E A Mickler, C J Olson, J L Rice, C D Coldren, L E Heasley, M W Geraci, R S Stearman
Src kinase is recognized as a key target for molecular cancer therapy. However, methods to efficiently select patients responsive to Src inhibitors are lacking. We explored the sensitivity of ovarian cancer cell lines to the Src kinase inhibitor saracatinib to identify predictive markers of drug sensitivity using gene microarrays. Pituitary tumor transforming gene 1 (PTTG1) was selected as a potential biomarker as mRNA levels were correlated with saracatinib resistance, as well as higher PTTG1 protein expression...
October 20, 2016: Clinical and Translational Science
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