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Cancer Investigation

Michael J Kelley, Gautam Jha, Debra Shoemaker, James E Herndon, Lin Gu, William T Barry, Jeffrey Crawford, Neal Ready
The Src pathway in activated in about one-third of non-small cell lung cancer (NSCLC) tumors. Dasatinib has Src-inhibitor activity. We examined the activity of dasatinib in 37 patients with advanced, previously treated NSCLC. Among the 29 patients who underwent pre-treatment biopsy for RNA biomarker analysis, 25 were treated with dasatinib 70 mg twice daily. There were no responses. Five patients discontinued treatment due to toxicity. Three patients had minor biopsy-related pneumothoraces. Given the lack of responses, no biomarkers were analyzed...
December 2, 2016: Cancer Investigation
Paola Rabasco, Rocchina Caivano, Giuseppina Dinardo, Matilde Gioioso, Antonella Lotumolo, Giancarlo Iannelli, Antonio Villonio, Giuseppe La Torre, Stefano D'Errico, Luca Macarini, Giuseppe Guglielmi, Aldo Cammarota
PURPOSE: To investigate the clinical impact of magnetic resonance imaging (MRI) in the detection of multifocal-multicentric breast cancers, already identified by mammography and ultrasound, and analyzed histologically, to evaluate its role in preoperative staging. MATERIALS AND METHODS: From January 2012 to February 2014, 188 patients, aged 28 to 74 years, newly diagnosed with breast cancer on conventional imaging (mammography and ultrasound) were enrolled. They underwent preoperative contrast-enhanced 3T MRI...
November 30, 2016: Cancer Investigation
Ghasem Azizi Tabesh, Pantea Izadi, Forouzandeh Fereidooni, Amir Nader Emami Razavi, Javad Tavakkoly Bazzaz
In breast cancer, somatic mutations of PIK3CA oncogene are common. We investigated the mutational status of exons 9 and 20 of the PIK3CA gene by polymerase chain reaction and direct sequencing in 80 breast tumors, and observed that 45% of these contained PIK3CA mutations in the mentioned exons. These mutations were found more in progesterone receptor positive and Her2- tumors, but this association did not reach a statistically significant level. Also, we observed a significant association between PIK3CA mutations and low-grade tumors...
November 30, 2016: Cancer Investigation
Stephen G Chun, Randall Hughes, Baran D Sumer, Larry L Myers, John M Truelson, Saad A Khan, Tsung-Wei Ma, Yang Xie, John S Yordy, Susan Cooley, Jean Wu, Hak Choy, Lucien A Nedzi
Nab-paclitaxel might impact efficacy of radiation for head and neck (H&N) cancer. Nab-paclitaxel, cisplatin, cetuximab, and radiation were evaluated in patients with locally advanced head and neck cancer in this phase I/II trial. Median follow-up was 24 months for 34 patients. The maximum tolerated dose of nab-paclitaxel was 20 mg/m(2) with 20 mg/m(2) cisplatin and 250 mg/m(2) cetuximab. The 2-year progression-free survival (PFS) was 60% (95% confidence interval (CI) 0.42, 0.78), local control 71% (95% CI 0...
November 28, 2016: Cancer Investigation
Tobias Fuchs, Hani Hanaya, Eckart Seilacher, Marie-Jolin Koester, Christian Keinki, Patrick Liebl, Jutta Huebner
OBJECTIVE: To learn more about cancer patients' motivation for seeking a second opinion. METHODS: Participants filled in a standardized questionnaire. RESULTS: Among 106 patients, 34% had looked for a second opinion, 81% wanted to check the accuracy of their treatment, and 49% needed to better understand the diagnosis. Low understanding of information was associated with looking for a second opinion, and 79% felt assured after a second opinion...
November 28, 2016: Cancer Investigation
Brian Y Park, Rachel N Grisham, Bjørnar den Hollander, Dharmarao Thapi, Tara Berman, Elisa de Stanchina, Qin Zhou, Gopa Iyer, Carol Aghajanian, David R Spriggs
OBJECTIVES: To investigate the tumor-suppressive properties of enzalutamide in androgen-driven ovarian cancer. METHODS: Mice were implanted subcutaneously with OVCAR-3 cells and treated with dihydrotestosterone in combination with enzalutamide or vehicle control. Tumor volumes were measured twice weekly until day 56. RESULTS: Dihydrotestosterone exposure led to a significant increase in tumor growth, while concomitant treatment with enzalutamide led to significant reductions in tumor volume compared to the androgen-exposed groups...
November 8, 2016: Cancer Investigation
Hamed Manoochehri Khoshinani, Saeid Afshar, Rezvan Najafi
Hypoxia is a common feature of malignant tumors. There is an interactive connection between hypoxia and chemoresistance, radioresistance, invasiveness, and angiogenesis. Therefore, tumor hypoxia has been considered as a validated target for treating cancer. This review focuses on the role of hypoxia on chemoresistance and radioresistance. In addition, we address several approaches targeting tumor hypoxia, known as hypoxia-targeted therapy.
November 8, 2016: Cancer Investigation
Christine A Garcia, Shenhong Wu
The risk of infection attributable to mTOR inhibitors has not been determined. Databases from PubMed and abstracts presented at the American Society of Clinical Oncology meetings were searched. Eligible studies included randomized controlled trials, in which everolimus or temsirolimus was compared with placebo. A total of 12 trials were included. The attributable incidences of all-grade and high-grade infections to mTOR inhibitors were 9.3% (95% confidence interval (CI): 5.8-14.6%) and 2.3% (95% CI: 1.2-4.4%) respectively...
October 28, 2016: Cancer Investigation
Wei Liu, Zhiming Dong, Jia Liang, Xin Guo, Yanli Guo, Supeng Shen, Gang Kuang, Wei Guo
Like many tumor suppressor genes, some miRNA genes harboring CpG islands undergo methylation-mediated silencing. In the study, we found significant downregulation and proximal promoter methylation of miR-203a and miR-203b in gastric cardia adenocarcinoma (GCA) tissues. The methylation status of miR-203a and miR-203b in tumor tissues was negatively correlated with their expression level. GCA patients in stage III and IV with reduced expression or hypermethylation of miR-203a demonstrated poor patient survival...
October 28, 2016: Cancer Investigation
Heidi Egloff, Aminah Jatoi
OBJECTIVE: Few studies have examined toxicity from potentially curative chemotherapy in ovarian cancer patients at risk for breast cancer susceptibility (BRCA) mutation. METHODS/RESULTS: Ninety-four of the 482 patients appeared at risk for a mutation based on family history and 23 had a confirmed mutation. Hospitalization or emergency department visits were not increased based on family history with odds ratios (95% confidence intervals) of 0.88 (0.52, 1.45) (p =...
October 28, 2016: Cancer Investigation
George A Alexiou, Paraskevi Gerogianni, Evrysthenis Vartholomatos, Athanasios P Kyritsis
Glioblastoma is the most malignant primary brain tumor with a median survival of 15 months. Temozolomide (TMZ) is the standard of care for these patients. Iron chelators have been shown to have anti-tumor activity; however, deferiprone (DFP), an orally administered iron chelator, has not been previously evaluated in gliomas. In the present study, we found that combination treatment in glioma cells with TMZ and DFP significantly reduced cell viability, produced cell cycle arrest at G2/M phase, and enhanced apoptosis...
October 21, 2016: Cancer Investigation
Yun Liang, Xin He, Xian Li, Xuzhao Zhang, Xiaohong Zhang, Lei Zhang, Xi Qiu, Xiaoying Zhao, Rongzhen Xu
Multiple myeloma (MM) remains incurable despite the development and the use of new agents. In our studies, we found that 4-chlorbenzoyl berbamine (BBMD9), a novel synthetic derivative of berbamine, inhibited the proliferation of MM cells in dose- and time-dependent manners. Flow cytometric (FCM) analysis revealed that MM cells were arrested in the G1 phase and that apoptotic cells increased in a time-dependent manner. Moreover, the BBMD9 treatment downregulated IKKα and IKKβ, inhibited p-IκBα, and blocked p65 nuclear localization...
October 21, 2016: Cancer Investigation
Qing Yang, Yingqiu Xie, Lixia Miao
Cancers induced by gene mutation, deletion, and genome instability might be related to aging. With similar pathways of aging but distinct functions, senescence at the cellular level is an irreversible arrest of cell cycle. Senescence has long been believed as a barrier to restrict tumor expansion. However, more and more evidence has been shown that senescence inducers regulate epithelial-mesenchymal transition, stem cell self-renewal, inflammatory response, crosstalk with the oncogenic bypass signaling, and conversion of oncogene to tumor suppressor...
October 18, 2016: Cancer Investigation
Damiano Caputo, Marco Caricato, Alessandro Coppola, Vincenzo La Vaccara, Michele Fiore, Roberto Coppola
In order to evaluate neutrophil-to-lymphocyte ratio (NLR) and derived neutrophil-to-lymphocyte ratio (d-NLR) in predicting response and complications in rectal cancer patients who underwent surgery after neo-adjuvant radio-chemotherapy, 87 patients were evaluated. Cutoffs before and after radio-chemotherapy were respectively 2.8 and 3.8 for NLR, and 1.4 and 2.3 for d-NLR. They were analyzed in relation to clinical and pathological outcomes. Patients with preoperative NLR and d-NLR higher than cutoffs had significantly higher rates of tumor regression grade response (TRG ≥ 4) and postoperative complications...
October 14, 2016: Cancer Investigation
Yu Ma, Yan Lu, Bingjian Lu
Reliable biomarkers for the detection of early ovarian carcinoma are currently unavailable. MicroRNA and long non-coding RNA may be important in cancer initiation and progression by regulating gene expression through post-transcriptional mechanisms. MicroRNAs, such as miR-26a and miR-132, have been investigated as novel biomarkers for diagnosis, prognosis, monitoring of therapeutic response, and therapeutic targets in ovarian carcinomas. Some long non-coding RNAs, such as H19 and UCA1, may be involved in the pathogenesis of ovarian carcinomas...
October 20, 2016: Cancer Investigation
Shu-Xiang Cui, Xin-Feng Yu, Xian-Jun Qu
Des-γ-carboxyprothrombin (DCP), an abnormal prothrombin produced in human hepatocellular carcinoma (HCC), plays crucial roles in the progression of HCC. DCP binding to cellular mesenchymal-epithelial transition factor (c-Met) is an initial event and consequently stimulates HCC through the increase of c-Met-Janus kinase 1- signal transducers and activators of transcription pathways. DCP stimulates HCC invasion through activation of matrix metalloproteinase via upregulation of extracellular signal-regulated kinase-mitogen-activated protein kinase (MAPK) pathway...
October 20, 2016: Cancer Investigation
Bagher Eftekhari-Sis, Sajede Karaminejad, Farrokh Karimi
A method was developed for the detection of 185delAG mutation in BRCA1 gene, which is responsible for 85% and 63% lifetime risks of hereditary breast and ovarian cancer in women, respectively. The protocol is based on the quenching and recovering fluorescence emission of fluorescein-based dye (FAM)-labeled DNA in the presence of graphene oxide (GO), followed by addition of cDNA or mDNA. In addition, ligase reaction between a DNA probe attached to GO and a DNA possessing FAM on 5' terminal in the presence of cDNA or mDNA was applied...
October 20, 2016: Cancer Investigation
Wei Li, Shuanlin Miao, Manyuan Miao, Renshuan Li, Xiaopeng Cao, Kun Zhang, Genzuan Huang, Bin Fu
Previous studies have established that hedgehog (Hh) signaling mediates tumor-stroma interaction and promotes hepatocellular carcinoma progression. Here, we demonstrated that activation of Hh signaling in hepatic stellate cell (HSC) line LX-2 by Huh-7-derived sonic Hh led to increased secretion of angiogenic factors and promoted angiogenesis in vitro. The activated LX-2 also enhanced vascular mimicry of hepatoma cells. Furthermore, co-injection of Huh-7 and LX-2 significantly accelerated tumor growth with enhanced angiogenesis compared with Huh-7 alone, which could be partly abrogated by Hh signaling inhibitor...
October 20, 2016: Cancer Investigation
Gaetano Leto, Lorena Incorvaia, Carla Flandina, Chiara Ancona, Fabio Fulfaro, Marilena Crescimanno, Maria Vittoria Sepporta, Giuseppe Badalamenti
This study was directed to assess the clinical impact of the circulating cathepsin L, cystatin C, activin A, and follistatin in breast cancer patients. The serum concentrations of these molecules were determined by immunoenzymatic assays, and their association with some clinico-pathological parameters of breast cancer progression was evaluated. Our results identified cystatin C and activin A as predictive markers for the presence of breast cancer and bone metastasis, respectively. Therefore, these proteins may have a clinical role as circulating biomarkers in the diagnosis and therapeutic monitoring of breast cancer patients...
October 20, 2016: Cancer Investigation
Nadine G D Schirmbeck, Ulrich J M Mey, Attilio Olivieri, Yon-Dschun Ko, Ulrich Kaiser, Dimitri Flieger, Mathias Witzens-Harig, Ingo G H Schmidt-Wolf
This analysis reports on 72 patients with relapsed or refractory non-Hodgkin lymphoma who were treated with R-DHAP salvage chemotherapy regimen followed by high-dose chemotherapy and stem cell transplantation. The overall remission rate was 58.3%. Median time of follow-up was 28.7 months. Median progression-free survival was 29 months, estimated median overall survival was 37 months. Within a matched pair analysis these results were compared to a group that received DHAP salvage therapy without rituximab showing similar overall response rates and better estimated five-year overall survival of 59...
September 13, 2016: Cancer Investigation
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