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Translational Oncology

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https://www.readbyqxmd.com/read/28806712/association-between-background-parenchymal-enhancement-and-pathologic-complete-remission-throughout-the-neoadjuvant-chemotherapy-in-breast-cancer-patients
#1
Chao You, Weijun Peng, Wenxiang Zhi, Min He, Guangyu Liu, Li Xie, Luan Jiang, Xiaoxin Hu, Xuxia Shen, Yajia Gu
PURPOSE: To retrospectively investigate the quantitative background parenchymal enhancement (BPE) of the contralateral normal breast in patients with unilateral invasive breast cancer throughout multiple monitoring points of neoadjuvant chemotherapy (NAC) and to further determine whether BPE is associated with tumor response, especially at the early stage of NAC. MATERIALS AND METHODS: A total of 90 patients with unilateral breast cancer who then received six or eight cycles of NAC before surgery were analyzed retrospectively...
August 11, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28797938/bihc-a-t-cell-engaging-bispecific-recombinant-antibody-has-potent-cytotoxic-activity-against-her2-tumor-cells
#2
Jieyu Xing, Limin Lin, Jing Li, Jiayu Liu, Changhua Zhou, Haitao Pan, Rui Shu, Bin Dong, Donglin Cao, Qing Li, Zhong Wang
Among different cancer immunotherapy approaches, bispecific antibodies (BsAbs) are of great interest due to their ability to recruit immune cells to kill tumor cells directly. Various BsAbs against Her2 tumor cells have been proposed with potent cytotoxic activities. However, most of these formats require extensive processing to obtain heterodimeric bispecific antibodies. In this study, we describe a bispecific antibody, BiHC (bispecific Her2-CD3 antibody), constructed with a single-domain anti-Her2 and a single-chain Fv (variable fragment) of anti-CD3 in an IgG-like format...
August 7, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28797937/immunohistochemical-characterization-and-sensitivity-to-human-adenovirus-serotypes-3-5-and-11p-of-new-cell-lines-derived-from-human-diffuse-grade-ii-to-iv-gliomas
#3
Minna Niittykoski, Mikael von Und Zu Fraunberg, Miika Martikainen, Tuomas Rauramaa, Arto Immonen, Susanna Koponen, Ville Leinonen, Markus Vähä-Koskela, Qiwei Zhang, Florian Kühnel, Ya-Fang Mei, Seppo Ylä-Herttuala, Juha E Jääskeläinen, Ari Hinkkanen
BACKGROUND: Oncolytic adenoviruses show promise in targeting gliomas because they do not replicate in normal brain cells. However, clinical responses occur only in a subset of patients. One explanation could be the heterogenic expression level of virus receptors. Another contributing factor could be variable activity of tumor antiviral defenses in different glioma subtypes. METHODS: We established a collection of primary low-passage cell lines from different glioma subtypes (3 glioblastomas, 3 oligoastrocytomas, and 2 oligodendrogliomas) and assessed them for receptor expression and sensitivity to human adenovirus (HAd) serotypes 3, 5, and 11p...
August 3, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28778025/comparison-of-esr1-mutations-in-tumor-tissue-and-matched-plasma-samples-from-metastatic-breast-cancer-patients
#4
Takashi Takeshita, Yutaka Yamamoto, Mutsuko Yamamoto-Ibusuki, Mai Tomiguchi, Aiko Sueta, Keiichi Murakami, Yoko Omoto, Hirotaka Iwase
BACKGROUND: ESR1 mutation in circulating cell-free DNA (cfDNA) is emerging as a noninvasive biomarker of acquired resistance to endocrine therapy, but there is a paucity of data comparing the status of ESR1 gene in cfDNA with that in its corresponding tumor tissue. The objective of this study is to validate the degree of concordance of ESR1 mutations between plasma and tumor tissue. METHODS: ESR1 ligand-binding domain mutations Y537S, Y537N, Y537C, and D538G were analyzed using droplet digital PCR in 35 patients with metastatic breast cancer (MBC) (35 tumor tissue samples and 67 plasma samples)...
July 31, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28778024/a-combination-of-radiation-and-the-hypoxia-activated-prodrug-evofosfamide-th-302-is-efficacious-against-a-human-orthotopic-pancreatic-tumor-model
#5
Carla Hajj, James Russell, Charles P Hart, Karyn A Goodman, Maeve A Lowery, Adriana Haimovitz-Friedman, Joseph O Deasy, John L Humm
This study was designed to investigate the effect of single-dose radiation therapy (RT) in combination with evofosfamide (TH-302), a hypoxia-activated prodrug, in a pre-clinical model of pancreatic cancer. AsPC1 tumors were implanted orthotopically in the pancreas of nude mice. Tumors were treated with 15 Gy of RT, using a 1 cm diameter field, and delivered as a continuous arc. Image-guidance to center the field on the tumor was based on CT imaging with intraperitoneal contrast. Evofosfamide (100 mg/kg, i.p...
July 21, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28738294/oral-mucosa-dose-parameters-predicting-grade-%C3%A2-3-acute-toxicity-in-locally-advanced-nasopharyngeal-carcinoma-patients-treated-with-concurrent-intensity-modulated-radiation-therapy-and-chemotherapy-an-independent-validation-study-comparing-oral-cavity-versus
#6
Kaixin Li, Ling Yang, Qiang-Ying Hu, Xiao-Zhong Chen, Ming Chen, Yuanyuan Chen
PURPOSE: To determine whether volumes based on the contours of the mucosal surface instead of the oral cavity can be used to predict grade ≥3 acute oral mucosa toxicity in patients with locally advanced nasopharyngeal carcinoma (LANPC) treated with concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy. METHODS AND MATERIALS: A standardized method for the oral cavity (oral cavity contours, OCC) and a novel method for the mucosal surface (mucosal surface contours, MSC) were developed for the oral mucosa and prospectively applied to the radiation treatment plans of 92 patients treated with concurrent IMRT and chemotherapy for LANPC...
July 21, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28735201/ultrasound-elastography-of-the-prostate-using-an-unconstrained-modulus-reconstruction-technique-a-pilot-clinical-study
#7
REVIEW
Seyed Reza Mousavi, Hassan Rivaz, Gregory J Czarnota, Abbas Samani, Ali Sadeghi-Naini
A novel full-inversion-based technique for quantitative ultrasound elastography was investigated in a pilot clinical study on five patients for non-invasive detection and localization of prostate cancer and quantification of its extent. Conventional-frequency ultrasound images and radiofrequency (RF) data (~5 MHz) were collected during mechanical stimulation of the prostate using a transrectal ultrasound probe. Pre and post-compression RF data were used to construct the strain images. The Young's modulus (YM) images were subsequently reconstructed using the derived strain images and the stress distribution estimated iteratively using finite element (FE) analysis...
July 20, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28734227/continuous-delivery-of-neutralizing-antibodies-elevate-ccl2-levels-in-mice-bearing-mcf10ca1d-breast-tumor-xenografts
#8
Min Yao, Curtis Smart, Qingting Hu, Nikki Cheng
Chemokines are small soluble molecules that play critical roles in wound healing, infection, and cancer progression. In particular, overexpression of the C-C motif chemokine ligand 2 (CCL2) in multiple cancer types correlates with poor patient prognosis. Animal studies have shown that CCL2 signals to macrophages and breast cancer cells to promote tumor growth, invasion, and metastasis, indicating that CCL2 is a promising therapeutic target. However, the effectiveness of human-specific neutralizing antibodies has not been fully evaluated...
July 19, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28734226/inhibition-of-prb-pathway-differentially-modulates-apoptosis-in-esophageal-cancer-cells
#9
Rossana C Soletti, Deborah Biasoli, Nathassya A L V Rodrigues, João M A Delou, Renata Maciel, Vera L A Chagas, Rodrigo A P Martins, Stevens K Rehen, Helena L Borges
Esophageal cancer is the sixth most common cause of cancer-related death worldwide. Current chemotherapy regimens include a combination of 5-fluorouracil (5-FU) and cisplatin, but more efficient therapy strategies are needed to increase 5-year survival. Alterations in the signaling pathway of the tumor suppressor gene Rb-1, which encodes a phosphoprotein (pRB) that negatively regulates the G1/S transition of the cell cycle, are present in 70% of all tumors, but its role in esophageal cancer is still unclear...
July 19, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28710916/systemic-immune-inflammation-index-and-circulating-t-cell-immune-index-predict-outcomes-in-high-risk-acral-melanoma-patients-treated-with-high-dose-interferon
#10
Jiayi Yu, Xiaowen Wu, Huan Yu, Siming Li, LiLi Mao, Zhihong Chi, Lu Si, Xinan Sheng, Chuanliang Cui, Jie Dai, Meng Ma, Huan Tang, Tianxiao Xu, Junya Yan, Yan Kong, Jun Guo
High-dose interferon alfa-2b (IFN-α-2b) improves the survival of patients with high-risk melanoma. We aimed to identify baseline peripheral blood biomarkers to predict the outcome of acral melanoma patients treated with IFN-α-2b. Pretreatment baseline parameters and clinical data were assessed in 226 patients with acral melanoma. Relapse-free survival (RFS) and overall survival (OS) were assessed using the Kaplan-Meier method, and multivariate Cox regression analyses were applied after adjusting for stage, lactate dehydrogenase (LDH), and ulceration...
July 12, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28710915/potent-therapeutic-activity-against-peritoneal-dissemination-and-malignant-ascites-by-the-novel-anti-folate-receptor-alpha-antibody-khk2805
#11
Munetoshi Ando, Keiko Nagata, Kaito Nihira, Yui Suzuki, Yutaka Kanda, Maiko Adachi, Tsuguo Kubota, Naoya Kameyama, Mariko Nakano, Hiroshi Ando, Kazuya Yamano, Toshihiko Ishii, Ryuichiro Nakai, Kazuyasu Nakamura
Many ovarian cancer patients often show peritoneal metastasis with malignant ascites. However, unmet medical needs remain regarding controlling these symptoms after tumors become resistant to chemotherapies. We developed KHK2805, a novel anti-folate receptor α (FOLR1) humanized antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). The primary aim of the present study was to evaluate whether the anti-tumor activity of KHK2805 was sufficient for therapeutic application against peritoneal dissemination and malignant ascites of platinum-resistant ovarian cancer in preclinical models...
July 11, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28704710/dissecting-the-biological-heterogeneity-within-hormone-receptor-positive-her2-negative-breast-cancer-by-gene-expression-markers-identifies-indolent-tumors-within-late-stage-disease
#12
Jyothi S Prabhu, Aruna Korlimarla, C E Anupama, Annie Alexander, Rohini Raghavan, Roma Kaul, Krisha Desai, Savitha Rajarajan, Suraj Manjunath, Marjorrie Correa, R Raman, Anjali Kalamdani, Msn Prasad, Shekar Patil, K S Gopinath, B S Srinath, T S Sridhar
Hormone receptor positive (HR+) breast cancers are a heterogeneous class with differential prognosis. Although more than half of Indian women present with advanced disease, many such patients do well. We have attempted identification of biologically indolent tumors within HR+HER2- tumors based on gene expression using histological grade as a guide to tumor aggression. 144 HR+HER2- tumors were divided into subclasses based on scores derived by using transcript levels of multiple genes representing survival, proliferation, and apoptotic pathways and compared to classification by Ki-67 labeling index (LI)...
August 2017: Translational Oncology
https://www.readbyqxmd.com/read/28692881/detection-of-kras-exon-2-mutations-in-circulating-tumor-cells-isolated-by-the-iset-system-from-patients-with-ras-wild-type-metastatic-colorectal-cancer
#13
Alexios Matikas, Alexandra Voutsina, Eleni Lagoudaki, Dora Hatzidaki, Maria Trypaki, Giannis Stoupis, Maria Tzardi, Dimitrios Mavroudis, Vasilios Georgoulias
INTRODUCTION: The presence of KRAS mutations in patients with metastatic colorectal cancer (mCRC) predicts poor response to agents targeting the EGFR. Even in patients with RAS wild type (WT) tumors, resistance eventually develops due to multiple mechanisms, including the expansion of previously undetected KRAS mutated clones. In this feasibility study, we aimed to detect KRAS exon 2 mutations in serial samples of circulating tumor cells (CTCs) of RAS WT patients with mCRC captured by the Isolation by Size of Epithelial Tumor cells (ISET) system...
August 2017: Translational Oncology
https://www.readbyqxmd.com/read/28683435/validation-and-comparison-of-the-therapeutic-efficacy-of-boron-neutron-capture-therapy-mediated-by-boron-rich-liposomes-in-multiple-murine-tumor-models
#14
Charles A Maitz, Aslam A Khan, Peter J Kueffer, John D Brockman, Jonathan Dixson, Satish S Jalisatgi, David W Nigg, Thomas A Everett, M Frederick Hawthorne
Boron neutron capture therapy (BNCT) was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. Mice were implanted with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the lipid bilayer and encapsulated Na3[1-(2`-B10H9)-2-NH3B10H8] within the liposomal core...
August 2017: Translational Oncology
https://www.readbyqxmd.com/read/28672196/contrast-enhanced-ct-density-predicts-response-to-sunitinib-therapy-in-metastatic-renal-cell-carcinoma-patients
#15
Simon Matoori, Yeeliang Thian, Dow-Mu Koh, Aslam Sohaib, James Larkin, Lisa Pickering, Andreas Gutzeit
The first-line therapy in metastatic renal cell carcinoma (mRCC), sunitinib, exhibits an objective response rate of approximately 30%. Therapeutic alternatives such as other tyrosine kinase inhibitors, VEGF inhibitors, or mTOR inhibitors emphasize the clinical need to predict the patient's response to sunitinib therapy before treatment initiation. In this study, we evaluated the prognostic value of pretreatment portal venous phase contrast-enhanced computed tomography (CECT) mean tumor density on overall survival (OS), progression-free survival (PFS), and tumor growth in 63 sunitinib-treated mRCC patients...
August 2017: Translational Oncology
https://www.readbyqxmd.com/read/28672195/combination-treatment-with-the-gsk-3-inhibitor-9-ing-41-and-ccnu-cures-orthotopic-chemoresistant-glioblastoma-in-patient-derived-xenograft-models
#16
Andrey Ugolkov, Wenan Qiang, Gennadiy Bondarenko, Daniel Procissi, Irina Gaisina, C David James, James Chandler, Alan Kozikowski, Hendra Gunosewoyo, Thomas O'Halloran, Jeffrey Raizer, Andrew P Mazar
Resistance to chemotherapy remains a major challenge in the treatment of human glioblastoma (GBM). Glycogen synthase kinase-3β (GSK-3β), a positive regulator of NF-κB-mediated survival and chemoresistance of cancer cells, has been identified as a potential therapeutic target in human GBM. Our objective was to determine the antitumor effect of GSK-3 inhibitor 9-ING-41 in combination with chemotherapy in patient-derived xenograft (PDX) models of human GBM. We utilized chemoresistant PDX models of GBM, GBM6 and GBM12, to study the effect of 9-ING-41 used alone and in combination with chemotherapy on tumor progression and survival...
August 2017: Translational Oncology
https://www.readbyqxmd.com/read/28672194/systematic-analysis-of-the-expression-of-the-mitochondrial-atp-synthase-complex-v-subunits-in-clear-cell-renal-cell-carcinoma
#17
Maria Brüggemann, Arabella Gromes, Mirjam Poss, Doris Schmidt, Niklas Klümper, Yuri Tolkach, Dimo Dietrich, Glen Kristiansen, Stefan C Müller, Jörg Ellinger
Mitochondrial dysfunction is common in cancer and the mitochondrial electron transport chain is often affected in carcinogenesis. To date, little is known about the expression of the ATP synthase subunits in clear cell renal cell carcinoma (ccRCC). The NextBio database was used to determine an expression profile of the ATP synthase subunits based on published microarray studies. We observed down-regulation of 23 out of 29 subunits of the ATP synthase. Differential expression was validated exemplarily for 12 genes (ATP5A1, ATP5B, ATPAF1, ATP5C1, ATP5D, ATP5O, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5I, ATP5S; screening cohort ccRCC n=18 and normal renal tissue n=10) using real-time PCR...
August 2017: Translational Oncology
https://www.readbyqxmd.com/read/28668763/vascular-mimicry-a-novel-neovascularization-mechanism-driving-anti-angiogenic-therapy-aat-resistance-in-glioblastoma
#18
REVIEW
Kartik Angara, Thaiz F Borin, Ali S Arbab
Glioblastoma (GBM) is a hypervascular neoplasia of the central nervous system with an extremely high rate of mortality. Owing to its hypervascularity, anti-angiogenic therapies (AAT) have been used as an adjuvant to the traditional surgical resection, chemotherapy, and radiation. The benefits of AAT have been transient and the tumors were shown to relapse faster and demonstrated particularly high rates of AAT therapy resistance. Alternative neovascularization mechanisms were shown to be at work in these resilient tumors to counter the AAT therapy insult...
August 2017: Translational Oncology
https://www.readbyqxmd.com/read/28668762/mangafodipir-a-selective-cytoprotectant-with-special-reference-to-oxaliplatin-and-its-association-to-chemotherapy-induced-peripheral-neuropathy-cipn
#19
REVIEW
Jan Olof G Karlsson, Rolf Gg Andersson, Per Jynge
Oxaliplatin, in combination with 5-fluorouracil plus folinate (or capecitabine), has increased survival substantially in stage III colorectal cancer and prolonged life in stage IV patients, but its use is compromised because of severe toxicity. Chemotherapy-induced peripheral neuropathy (CIPN) is the most problematic dose-limiting toxicity of oxaliplatin. Oncologists included for years calcium and magnesium infusion as part of clinical practice for preventing CIPN. Results from a phase III prospective study published in 2014, however, overturned this practice...
August 2017: Translational Oncology
https://www.readbyqxmd.com/read/28668761/selinexor-overcomes-hypoxia-induced-drug-resistance-in-multiple-myeloma
#20
Barbara Muz, Feda Azab, Pilar de la Puente, Yosef Landesman, Abdel Kareem Azab
Increased levels of the nuclear export protein, exportin 1 (XPO1), were demonstrated in multiple myeloma (MM) patients. Targeting XPO1 with selinexor (the selective inhibitor of nuclear export; SINE compound KPT-330) demonstrates broad antitumor activity also in patient cells resistant to bortezomib; hence, it is a promising target in MM patients. Hypoxia is known to mediate tumor progression and drug resistance (including bortezomib resistance) in MM cells. In this study, we tested the effects of selinexor alone or in combination with bortezomib in normoxia and hypoxia on MM cell survival and apoptosis in vitro and in vivo...
August 2017: Translational Oncology
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