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https://www.readbyqxmd.com/read/28724284/inter-alpha-inhibitor-h4-as-a-potential-biomarker-predicting-the-treatment-outcomes-in-patients-with-hepatocellular-carcinoma
#1
Eun-Jung Lee, Seung-Hyun Yang, Kyoung-Jin Kim, Hyejung Cha, Seo Jin Lee, Ji-Hye Kim, Junkyu Song, Kyung-Hee Chun, Jinsil Seong
Purpose: Early prediction of treatment outcomes represents an essential step towards increased treatment efficacy and survival in patients with hepatocellular carcinoma (HCC). In this study, we performed two-dimensional electrophoresis (2-DE) followed by protein profiling to identify biomarkers predictive of therapeutic outcomes in patients with HCC who received liver-directed therapy (LDTx) involving local radiotherapy (RT), and studied the underlying mechanisms of the identified proteins...
July 17, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28723928/erbb-activation-signatures-as-potential-biomarkers-for-anti-erbb3-treatment-in-hnscc
#2
Diego Alvarado, Gwenda F Ligon, Jay S Lillquist, Scott B Seibel, Gerald Wallweber, Veronique M Neumeister, David L Rimm, Gerald McMahon, Theresa M LaVallee
Head and neck squamous cell carcinoma (HNSCC) accounts for 3-5% of all tumor types and remains an unmet medical need with only two targeted therapies approved to date. ErbB3 (HER3), the kinase-impaired member of the EGFR/ErbB family, has been implicated as a disease driver in a number of solid tumors, including a subset of HNSCC. Here we show that the molecular components required for ErbB3 activation, including its ligand neuregulin-1 (NRG1), are highly prevalent in HNSCC and that HER2, but not EGFR, is the major activating ErbB3 kinase partner...
2017: PloS One
https://www.readbyqxmd.com/read/28723865/microrna-106b-5p-regulates-cisplatin-chemosensitivity-by-targeting-polycystic-kidney-disease-2-in-non-small-cell-lung-cancer
#3
Shaorong Yu, Xiaobing Qin, Tingting Chen, Leilei Zhou, Xiaoyue Xu, Jifeng Feng
Systemic therapy with cytotoxic agents remains one of the main treatment methods for non-small-cell lung cancer (NSCLC). Cisplatin is a commonly used chemotherapeutic agent, that, when combined with other drugs, is an effective treatment for NSCLC. However, effective cancer therapy is hindered by a patient's resistance to cisplatin. Unfortunately, the potential mechanism underlying such resistance remains unclear. In this study, we explored the mechanism of microRNA-106b-5p (miR-106b-5p), which is involved in the resistance to cisplatin in the A549 cell line of NSCLC...
July 18, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28723725/meningeal-melanomatosis-following-discontinuation-of-dabrafenib-implications-for-the-maintenance-of-long-term-complete-remission
#4
Victoria Grätz, Nadine Lüttmann, Ozan Haase, Ewan A Langan, André Kemmling, Detlef Zillikens, Patrick Terheyden
A subset of 10-20% of patients under continuous BRAF inhibitor monotherapy achieve long-term progression-free and overall survival. Definitive criteria for the safe cessation of BRAF inhibitor monotherapy in treatment-responsive melanoma patients are lacking. We report a patient who remained in complete remission (CR) for 5 years under dabrafenib. The treatment was withdrawn because of concerns about cardiac toxicity. Four months thereafter the patient developed neurological symptoms, including diplopia and bilateral visual loss...
July 18, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28723709/delivering-prep-to-pregnant-and-breastfeeding-women-in-sub-saharan-africa-the-implementation-science-frontier
#5
Dvora L Joseph Davey, Linda-Gail Bekker, Pamina Gorbach, Thomas Coates, Landon Myer
: HIV acquisition during pregnancy and postpartum periods remains high despite increased access to and initiation of antiretroviral therapy in sub-Saharan Africa. Moreover, maternal seroconversion during pregnancy and breastfeeding remains a source of significant paediatric HIV infection in the region. In order to curb vertical HIV transmission, HIV acquisition during pregnancy and lactation must significantly decline. Biological and behavioural factors contribute to high HIV incidence, including hormonal changes that alter genital mucosal surfaces, and frequent condomless sex with HIV-infected partners or partners of unknown serostatus...
July 18, 2017: AIDS
https://www.readbyqxmd.com/read/28723663/a-network-meta-analysis-on-the-efficacy-of-targeted-agents-in-combination-with-chemotherapy-for-treatment-of-advanced-metastatic-triple-negative-breast-cancer
#6
Long Ge, Yan Tang, Qiu-Ning Zhang, Jin-Hui Tian, Xiao-Hu Wang, Dawid Pieper, Bei Pan, Lun Li, Juan Ling, Zhi-Tong Bing, Ke-Hu Yang
OBJECTIVE: Our network meta-analysis aimed to determine the assistant efficacy of targeted therapy in combined with chemotherapy for advanced/metastatic triple-negative breast cancer (TNBC). RESULTS: A total of 15 randomized controlled trials (RCTs), involving 2,410 patients, met our inclusion criteria. Eight targeted agents involving 11 treatment arms were included. The methodological quality of included RCTs was acceptable. The results of direct comparisons showed that progression-free survival (PFS) was significantly longer with bevacizumab+chemotherapy when compared to chemotherapy alone (hazard ratio [HR] = 0...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723656/inhibitor-of-h3k27-demethylase-jmjd3-utx-gsk-j4-is-a-potential-therapeutic-option-for-castration-resistant-prostate-cancer
#7
Viacheslav M Morozov, Ying Li, Matthew M Clowers, Alexander M Ishov
Androgen receptor (AR) mediates initiation and progression of prostate cancer (PCa); AR-driven transcription is activated by binding of androgens to the ligand-binding domain (LBD) of AR. Androgen ablation therapy offers only a temporary relief of locally advanced and metastatic PCa, and the disease eventually recurs as a lethal castration-resistant PCa (CRPC) as there is no effective treatment for CRPC patients. Thus, it is critical to identify novel targeted and combinatorial regimens for clinical management of CRPC...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723643/methyltransferase-g9a-promotes-cervical-cancer-angiogenesis-and-decreases-patient-survival
#8
Ruey-Jien Chen, Chia-Tung Shun, Men-Luh Yen, Chia-Hung Chou, Ming-Chieh Lin
Research suggests that the epigenetic regulator G9a, a H3K9 histone methyltransferase, is involved in cancer invasion and metastasis. Here we show that G9a is linked to cancer angiogenesis and poor patient survival. Invasive cervical cancer has a higher G9a expression than cancer precursors or normal epithelium. Pharmacological inhibition and genetic silencing of G9a suppresses H3K9 methylation, cancer cell proliferation, angiogenesis, and cancer cell invasion/migration, but not apoptosis. Microarray and quantitative reverse transcription polymerase chain reaction analyses reveal that G9a induces a cohort of angiogenic factors that include angiogenin, interleukin-8, and C-X-C motif chemokine ligand 16...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723639/integrated-analysis-of-the-molecular-action-of-vorinostat-identifies-epi-sensitised-targets-for-combination-therapy
#9
Jodie F Hay, Katrina Lappin, Fabio Liberante, Laura M Kettyle, Kyle B Matchett, Alexander Thompson, Ken I Mills
Several histone deacetylase inhibitors including Vorinostat have received FDA approval for the treatment of haematological malignancies. However, data from these trials indicate that Vorinostat has limited efficacy as a monotherapy, prompting the need for rational design of combination therapies. A number of epi-sensitised pathways, including sonic hedgehog (SHH), were identified in AML cells by integration of global patterns of histone H3 lysine 9 (H3K9) acetylation with transcriptomic analysis following Vorinostat-treatment...
July 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723634/synergistic-interaction-between-galectin-3-and-carcinoembryonic-antigen-promotes-colorectal-cancer-metastasis
#10
Keng-Liang Wu, Eng-Yen Huang, Wen-Ling Yeh, Chang-Chun Hsiao, Chung-Mou Kuo
In this study, we investigated the role of galectin-3 and carcinoembryonic antigen (CEA) in metastasis and survival of colorectal cancer (CRC) patients. CEA interacted with galectin-3 at the cell surface and cytoplasm of Caco2 and DLD1 CRC cells. Knocking down galectin-3 did not affect CEA expression in CRC cells. However, there was a dose-dependent increase in CRC cell migration upon addition of small amounts of exogenous CEA (≤1ng/ml). Galectin-3 knockdown blocked induction of CRC cell migration by CEA, suggesting interaction between galectin-3 and CEA was necessary for CRC cell migration...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723625/2-acetylamino-3-4-2-acetylamino-2-carboxyethylsulfanylcarbonylamino-phenyl-carbamoylsulfanyl-propionic-acid-a-glutathione-reductase-inhibitor-induces-g2-m-cell-cycle-arrest-through-generation-of-thiol-oxidative-stress-in-human-esophageal-cancer-cells
#11
Xia Li, Zhiming Jiang, Jianguo Feng, Xiaoying Zhang, Junzhou Wu, Wei Chen
Esophageal squamous cell carcinoma (ESCC) is a highly malignant cancer with poor response to both of chemotherapy and radiotherapy. 2-Acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylcarbonylamino) phenyl carbamoylsulfanyl] propionic acid (2-AAPA), an irreversible inhibitor of glutathione reductase (GR), is able to induce intracellular oxidative stress, and has shown anticancer activity in many cancer cell lines. In this study, we investigated the effects of 2-AAPA on the cell proliferation, cell cycle and apoptosis and aimed to explore its mechanism of action in human esophageal cancer TE-13 cells...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723624/lncrna-ancr-down-regulation-promotes-tgf-%C3%AE-induced-emt-and-metastasis-in-breast-cancer
#12
Zhongwei Li, Meichen Dong, Dongmei Fan, Pingfu Hou, Hongyuan Li, Lingxia Liu, Cong Lin, Jiwei Liu, Liangping Su, Lan Wu, Xiaoxue Li, Baiqu Huang, Jun Lu, Yu Zhang
Epithelial to mesenchymal transition (EMT) is a progression of cellular plasticity critical for development, differentiation, cancer cells migration and tumor metastasis. As a well-studied factor, TGF-β participates in EMT and involves in physiological and pathological functions of tumor progression. Accumulating evidence indicates that long noncoding RNAs(lncRNAs) play crucial roles in EMT and tumor metastasis. Here, we find that lncRNA ANCR participates in TGF-β1-induced EMT. By our ChIP and Real-time PCR assays, we reveal that TGF-β1 down-regulates ANCR expression by increasing HDAC3 enrichment at ANCR promoter region, which decreases both H3 and H4 acetylation of ANCR promoter...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723547/the-p2x7-receptor-in-infection-and-inflammation
#13
REVIEW
Francesco Di Virgilio, Diego Dal Ben, Alba Clara Sarti, Anna Lisa Giuliani, Simonetta Falzoni
Adenosine triphosphate (ATP) accumulates at sites of tissue injury and inflammation. Effects of extracellular ATP are mediated by plasma membrane receptors named P2 receptors (P2Rs). The P2R most involved in inflammation and immunity is the P2X7 receptor (P2X7R), expressed by virtually all cells of innate and adaptive immunity. P2X7R mediates NLRP3 inflammasome activation, cytokine and chemokine release, T lymphocyte survival and differentiation, transcription factor activation, and cell death. Ten human P2RX7 gene splice variants and several SNPs that produce complex haplotypes are known...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723515/understanding-mechanisms-of-resistance-in-metastatic-castration-resistant-prostate-cancer-the-role-of-the-androgen-receptor
#14
REVIEW
Derya Tilki, Edward M Schaeffer, Christopher P Evans
CONTEXT: After initiation of androgen deprivation therapy (ADT), most patients progress to castration-resistant prostate cancer (CRPC) within 2 or 3 yr. In the USA, approximately 67000 men are estimated to have metastatic CRPC. OBJECTIVE: To provide an overview of different mechanisms driving resistance to therapy in metastatic CRPC, with a focus on androgen receptor (AR)-dependent pathways. EVIDENCE ACQUISITION: A Medline search via PubMed was performed using the keywords metastatic castration resistant prostate cancer (mCRPC), castration-resistant, CRPC, prostate cancer, androgen resistance, hormone-refractory, hormone-independent, androgen receptor, and androgen receptor axis...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723508/targeting-adaptive-pathways-in-metastatic-treatment-resistant-prostate-cancer-update-on-the-stand-up-2-cancer-prostate-cancer-foundation-supported-west-coast-prostate-cancer-dream-team
#15
Rahul Aggarwal, Tomasz M Beer, Martin Gleave, Joshua M Stuart, Matthew Rettig, Christopher P Evans, Jack Youngren, Joshi J Alumkal, Jiaoti Huang, George Thomas, Owen Witte, Eric J Small
The Stand Up 2 Cancer/Prostate Cancer Foundation-funded West Coast Dream Team project is a prospective multi-institutional study focused on acquiring metastatic castration-resistant prostate cancer (mCRPC) biopsy tissue at the time of resistance to abiraterone or enzalutamide. It is the first large-scale study designed to analyze mCRPC tissue specifically in this patient population. Study accrual is on target, with 261 out of a planned 300 metastatic tumor biopsies performed by August 2016. Paired biopsies have been completed in 42 patients, with paired genomic data before and after therapy obtained in 26 cases...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723497/pharmacogenomic-markers-of-targeted-therapy-toxicity-in-patients-with-metastatic-renal-cell-carcinoma
#16
Guillermo de Velasco, Kathryn P Gray, Lana Hamieh, Yuksel Urun, Hallie A Carol, Andre P Fay, Sabina Signoretti, David J Kwiatkowski, David F McDermott, Matthew Freedman, Mark M Pomerantz, Toni K Choueiri
BACKGROUND: Targeted therapy (TT) in metastatic renal cell carcinoma (mRCC) may be associated with a high rate of toxicity that undermines treatment efficacy and patient quality of life. Polymorphisms in genes involved in the pharmacokinetic pathways of TTs may predict toxicity. OBJECTIVE: To investigate whether selected single-nucleotide polymorphisms (SNPs) in three core genes involved in the metabolism and transport of sunitinib and the mTOR inhibitors everolimus and temsirolimus are associated with adverse events (AEs)...
December 15, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723488/case-discussion-systemic-therapy-for-metastatic-renal-cell-carcinoma
#17
Manuel C Maia, Paulo Bergerot, Sumanta K Pal
First-line systemic therapy for patients with metastatic renal cell carcinoma should largely entail the use of targeted agents. Depending on the clinical factors, VEGF- or mTOR-directed agents may be appropriate.
December 15, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723416/unravelling-the-pharmacologic-opportunities-and-future-directions-for-targeted-therapies-in-gastro-intestinal-cancers-part-2-neuroendocrine-tumours-hepatocellular-carcinoma-and-gastro-intestinal-stromal-tumours
#18
REVIEW
Cindy Neuzillet, Louis de Mestier, Benoît Rousseau, Olivier Mir, Mohamed Hebbar, Hemant M Kocher, Philippe Ruszniewski, Christophe Tournigand
Until the 1990s, cytotoxic chemotherapy has been the cornerstone of medical therapy for gastrointestinal (GI) cancers. Better understanding of the cancer cell molecular biology has led to the therapeutic revolution of targeted therapies, i.e. monoclonal antibodies or small molecule inhibitors directed against proteins that are specifically overexpressed or mutated in cancer cells. These agents, being more specific to cancer cells, were expected to be less toxic than conventional cytotoxic agents. However, their effects have sometimes been disappointing, due to intrinsic or acquired resistance mechanisms, or to an activity restricted to some tumour settings, illustrating the importance of patient selection and early identification of predictive biomarkers of response to these therapies...
July 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28723377/external-validation-of-the-mskcc-and-imdc-risk-models-in-patients-treated-with-targeted-therapy-as-a-first-line-and-subsequent-second-line-treatment-a-japanese-multi-institutional-study
#19
Nobuyuki Tanaka, Ryuichi Mizuno, Keiichi Ito, Suguru Shirotake, Yota Yasumizu, Ayako Masunaga, Yujiro Ito, Yasumasa Miyazaki, Masayuki Hagiwara, Kent Kanao, Shuji Mikami, Ken Nakagawa, Tetsuo Momma, Takeshi Masuda, Tomohiko Asano, Masafumi Oyama, Mototsugu Oya
BACKGROUND: Two risk models, the Memorial Sloan Kettering Cancer Center (MSKCC) model and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model, have been studied in metastatic renal cell carcinoma (mRCC) treated with targeted therapy. OBJECTIVE: To validate externally the predictive accuracies of the MSKCC and IMDC models for prognosis in mRCC patients treated with first-line and subsequent second-line targeted therapy. DESIGN, SETTING, AND PARTICIPANTS: A total of 311 patients were assessed retrospectively...
August 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723234/flexible-small-molecular-anti-estrogens-with-n-n-dialkylated-2-5-diethoxy-4-morpholinoaniline-scaffold-targets-multiple-estrogen-receptor-conformations
#20
Bethany K Asare, Emmanuel Yawson, Rajendram V Rajnarayanan
Estrogen mediates various cellular processes including cell proliferation, differentiation, growth and mammary gland function. Estrogen Receptors (ERs) are expressed in 70% of breast cancers. Consequently, estrogen mediated ER signaling plays a critical role in breast cancer diagnosis, prognosis, and treatment. Estrogen Receptors are ligand-triggered transcription factors. However, in the absence of a cognate estrogenic ligand, ERs can be activated by a variety of other extracellular signals. Tamoxifen, an anti-estrogen that selectively targets ER, induces substantial regression of breast tumors and an increase in disease-free survival...
July 19, 2017: Cell Cycle
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