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Translational Oncology

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https://www.readbyqxmd.com/read/28577439/targeted-%C3%AE-particle-radiation-therapy-of-her1-positive-disseminated-intraperitoneal-disease-an-investigation-of-the-human-anti-egfr-monoclonal-antibody-panitumumab
#1
Diane E Milenic, Kwamena E Baidoo, Young-Seung Kim, Rachel Barkley, Martin W Brechbiel
Identifying molecular targets and an appropriate targeting vehicle, i.e., monoclonal antibodies (mAb) and their various forms, for radioimmunotherapy (RIT) remains an active area of research. Panitumumab, a fully human and less immunogenic mAb that binds to the epidermal growth factor receptor (Erb1; HER1), was evaluated for targeted α-particle radiation therapy using (212)Pb, an in vivo α generator. A single dose of (212)Pb-panitumumab administered to athymic mice bearing LS-174T intraperitoneal (i.p.) tumor xenografts was found to have greater therapeutic efficacy when directly compared with (212)Pb-trastuzumab, which binds to HER2...
May 31, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28570869/the-effect-of-adding-neoadjuvant-chemotherapy-to-concurrent-chemoradiotherapy-in-patients-with-locoregionally-advanced-nasopharyngeal-carcinoma-and-undetectable-pretreatment-epstein-barr-virus-dna
#2
Ya-Nan Jin, Ji-Jin Yao, Si-Yang Wang, Wang-Jian Zhang, Fan Zhang, Guan-Qun Zhou, Zhi-Bin Cheng, Hao-Yuan Mo, Ying Sun
PURPOSE: To assess the effect of adding neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and undetectable pretreatment Epstein-Barr virus (pEBV) DNA. MATERIALS AND METHODS: We enrolled 639 NPC patients with stage II to IVB and undetectable pEBV DNA to receive CCRT with or without NACT. Radiotherapy was 2.0 to 2.27 Gy per fraction with five daily fractions per week for 6 to 7 weeks to the primary tumor and 62 to 70 Gy to the involved neck area...
May 29, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28558265/preparation-and-identification-of-her2-radioactive-ligands-and-imaging-study-of-breast-cancer-bearing-nude-mice
#3
Meng-Zhi Zhang, Yan-Xing Guan, Jin-Xiu Zhong, Xue-Zhong Chen
OBJECTIVE: A micro-molecule peptide TP1623 of (99m)Tc-human epithelial growth factor receptor 2 (HER2) was prepared and the feasibility of using it as a HER2-positive molecular imaging agent for breast cancer was evaluated. METHODS: TP1623 was chemically synthesized and labeled with (99m)Tc. The labeling ratio and stability were detected. HER2 expression levels of breast cancer cells (SKBR3 and MDA-MB-231) and cell binding activity were measured. Biodistribution of (99m)TC-TP1623 in normal mice was detected...
May 27, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28558264/positive-expression-of-programmed-death-ligand-1-in-peritumoral-liver-tissue-is-associated-with-poor-survival-after-curative-resection-of-hepatocellular-carcinoma
#4
Xiaomeng Dai, Jun Xue, Jianli Hu, Sheng-Li Yang, George G Chen, Paul B S Lai, Chao Yu, Cui Zeng, Xiefan Fang, Xiaoli Pan, Tao Zhang
BACKGROUND: Recurrence or metastasis of hepatocellular carcinoma (HCC) is mainly intrahepatic after curative resection, demonstrating that the peritumoral environment is important but often neglected. Programmed death ligand 1 (PD-L1) in intratumoral liver tissues is a poor prognosis factor whose impact is removed after curative resection. However, PD-L1 expression remains in the peritumoral liver tissues and its distribution and prognostic value are still not clear. METHODS: We assessed the expression of PD-L1 by immunohistochemistry in peritumoral liver tissues from 90 HCC patients who underwent curative hepatectomy...
May 27, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28550770/laparoscopic-versus-open-radical-nephrectomy-for-renal-cell-carcinoma-a-systematic-review-and-meta-analysis
#5
Gang Liu, Yulei Ma, Shouhua Wang, Xiancheng Han, Dianjun Gao
BACKGROUND: The aim of this study is to summarize and quantify the current evidence on the therapeutic efficacy of laparoscopic radical nephrectomy (LRN) compared with open radical nephrectomy (ORN) in patients with renal cell carcinoma (RCC) in a meta-analysis. METHODS: Data were collected by searching Pubmed, Embase, Web of Science, and ScienceDirect for reports published up to September 26, 2016. Studies that reported data on comparisons of therapeutic efficacy of LRN and ORN were included...
May 24, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28550769/mk-8776-a-novel-chk1-inhibitor-exhibits-an-improved-radiosensitizing-effect-compared-to-ucn-01-by-exacerbating-radiation-induced-aberrant-mitosis
#6
Motofumi Suzuki, Tohru Yamamori, Tomoki Bo, Yuri Sakai, Osamu Inanami
Checkpoint kinase 1 (Chk1) is an evolutionarily conserved serine/threonine kinase that plays an important role in G2/M checkpoint signaling. Here, we evaluate the radiosensitizing effects of a novel selective Chk1 inhibitor MK-8776, comparing its efficacy with a first-generation Chk1 inhibitor UCN-01, and attempt to elucidate the mechanism of radiosensitization. In a clonogenic survival assay, MK-8776 demonstrated a more pronounced radiosensitizing effect than UCN-01, with lower cytotoxicity. Importantly, radiosensitization by MK-8776 can be achieved at doses as low as 2...
May 24, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28521182/should-nonsmokers-be-excluded-from-early-lung-cancer-screening-with-low-dose-spiral-computed-tomography-community-based-practice-in-shanghai
#7
Xiaoyang Luo, Shanbo Zheng, Quan Liu, Shengping Wang, Yuan Li, Lei Shen, Guodong Li, Wentao Li, Yanping Zhao, Huilin Xu, Jing Wang, Xiaohua Liu, Yunjian Pan, Hong Hu, Yihua Sun, Haiyan Yang, Su Xu, Haiquan Chen
OBJECTIVE: We investigated the efficacy of early lung cancer screening with low-dose spiral computed tomography(LDCT) in both smokers and nonsmokers based on the current situation of community health service, with integration of superior resources of medical institutions at all levels in Shanghai. METHODS: From August 2013 to August 2014, we screened 11,332 (male 7144; female 4188) high-risk individuals in selected communities of Minhang, Shanghai City, for early diagnosis of lung cancer with LDCT combined with multidisciplinary comprehensive treatment pattern including minimally invasive surgery, exploring the medical service network covering prevention, diagnosis, treatment, rehabilitation, and follow-up...
May 15, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28505517/a-modified-adenovirus-vector-mediated-antibody-screening-method-identifies-epha2-as-a-cancer-target
#8
Toshihiro Tanaka, Hiromi Yamada, Masahide Kuroki, Shohta Kodama, Kazuo Tamura, Yasushi Takamatsu
BACKGROUND: We constructed a genetically modified adenovirus vector incorporating an IgG Fc-binding motif from staphylococcal protein A, Z33 (Adv-FZ33). Adv-FZ33 allows an antibody to redirect the vector to a target molecule on the cell surface. We attempted to search for target antigen candidates and antibodies that allowed highly selective gene transduction into malignant tumors. METHODS: Hybridoma libraries producing monoclonal antibodies (mAbs) were screened that increased transduction efficiency in cancer cell lines after cross-linking with Adv-FZ33...
May 12, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28501555/antitumor-effect-of-azd4547-in-a-fibroblast-growth-factor-receptor-2-amplified-gastric-cancer-patient-derived-cell-model
#9
Jiryeon Jang, Hee Kyung Kim, Heejin Bang, Seung Tae Kim, Sun Young Kim, Se Hoon Park, Ho Yeong Lim, Won Ki Kang, Jeeyun Lee, Kyoung-Mee Kim
BACKGROUND: FGFR2 amplification is associated with aggressive gastric cancer (GC), and targeted drugs have been developed for treatment of GC. We evaluated the antitumor activity of an FGFR inhibitor in FGFR2-amplified GC patients with peritoneal carcinomatosis. METHODS: Two GC patients with FGFR2 amplification confirmed by fluorescence in situ hybridization showed peritoneal seeding and malignant ascites. We used the patient-derived xenograft model; patient-derived cells (PDCs) from malignant ascites were used to assess FGFR2 expression and its downstream pathway using immunofluorescence analysis and immunoblot assay in vitro...
May 10, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28456115/magnetic-resonance-imaging-mri-of-intratumoral-voxel-heterogeneity-as-a-potential-response-biomarker-assessment-in-a-her2-esophageal-adenocarcinoma-xenograft-following-trastuzumab-and-or-cisplatin-therapy
#10
Connie Yip, Amanda Weeks, Karen Shaw, Musib Siddique, Fuju Chang, David B Landau, Gary Jr Cook, Vicky Goh
We evaluated magnetic resonance imaging (MRI) voxel heterogeneity following trastuzumab and/or cisplatin in a HER2+ esophageal xenograft (OE19) as a potential response biomarker. OE19 xenografts treated with saline (controls), monotherapy, or combined cisplatin and trastuzumab underwent 9.4-T MRI. Tumor MRI parametric maps of T1 relaxation time (pre/post contrast), T2 relaxation time, T2* relaxation rate (R2*), and apparent diffusion coefficient obtained before (TIME0), after 24hours (TIME1), and after 2weeks of treatment (TIME2) were analyzed...
June 2017: Translational Oncology
https://www.readbyqxmd.com/read/28456114/gene-expression-signature-differentiates-histology-but-not-progression-status-of-early-stage-nsclc
#11
Radoslaw Charkiewicz, Jacek Niklinski, Jürgen Claesen, Anetta Sulewska, Miroslaw Kozlowski, Anna Michalska-Falkowska, Joanna Reszec, Marcin Moniuszko, Wojciech Naumnik, Wieslawa Niklinska
Advances in molecular analyses based on high-throughput technologies can contribute to a more accurate classification of non-small cell lung cancer (NSCLC), as well as a better prediction of both the disease course and the efficacy of targeted therapies. Here we set out to analyze whether global gene expression profiling performed in a group of early-stage NSCLC patients can contribute to classifying tumor subtypes and predicting the disease prognosis. Gene expression profiling was performed with the use of the microarray technology in a training set of 108 NSCLC samples...
June 2017: Translational Oncology
https://www.readbyqxmd.com/read/28448960/utility-of-genomic-analysis-in-differentiating-synchronous-and-metachronous-lung-adenocarcinomas-from-primary-adenocarcinomas-with-intrapulmonary-metastasis
#12
Jad Saab, Hamid Zia, Susan Mathew, Michael Kluk, Navneet Narula, Helen Fernandes
Distinguishing synchronous and metachronous primary lung adenocarcinomas from adenocarcinomas with intrapulmonary metastasis is essential for optimal patient management. In this study, multiple lung adenocarcinomas occurring in the same patient were evaluated using comprehensive histopathologic evaluation supplemented with molecular analysis. The cohort included 18 patients with a total of 52 lung adenocarcinomas. Eleven patients had a new diagnosis of multiple adenocarcinomas in the same lobe (n=5) or different lobe (n=6)...
June 2017: Translational Oncology
https://www.readbyqxmd.com/read/28448959/detection-of-circulating-tumor-cells-and-circulating-tumor-microemboli-in-gastric-cancer
#13
Xiumei Zheng, Li Fan, Pengfei Zhou, Hong Ma, Shaoyi Huang, Dandan Yu, Lei Zhao, Shengli Yang, Jun Liu, Ai Huang, Congli Cai, Xiaomeng Dai, Tao Zhang
PURPOSE: Gastric cancer studies indicated a potential correlation between circulating tumor cells (CTCs) in peripheral blood and tumor relapse/metastasis. The prevalence and significance of circulating tumor microemboli (CTM) in gastric cancer remain unknown. We investigated the prevalence and prognostic value of CTCs and CTM for progression-free survival (PFS) and overall survival (OS) in gastric cancer patients. METHODS: Eighty-one gastric cancer patients consented to provide 5ml of peripheral blood before systematic therapy...
June 2017: Translational Oncology
https://www.readbyqxmd.com/read/28448958/evaluation-of-f8-tnf-%C3%AE-in-models-of-early-and-progressive-metastatic-osteosarcoma
#14
Bernhard Robl, Sander Martijn Botter, Aleksandar Boro, Daniela Meier, Dario Neri, Bruno Fuchs
The targeted delivery of tumor necrosis factor-α (TNF-α) with antibodies specific to splice isoforms of fibronectin [e.g., F8-TNF, specific to the extra-domain A (EDA) domain of fibronectin] has already shown efficacy against experimental sarcomas but has not yet been investigated in orthotopic sarcomas. Here, we investigated F8-TNF in a syngeneic K7 M2-derived orthotopic model of osteosarcoma as a treatment against pulmonary metastases, the most frequent cause of osteosarcoma-related death. Immunofluorescence on human osteosarcoma tissue confirmed the presence of EDA in primary tumors (PTs) as well as metastases...
June 2017: Translational Oncology
https://www.readbyqxmd.com/read/28445844/upregulation-of-mir-142-3p-improves-drug-sensitivity-of-acute-myelogenous-leukemia-through-reducing-p-glycoprotein-and-repressing-autophagy-by-targeting-hmgb1
#15
Yuan Zhang, Yufeng Liu, Xueju Xu
miR-142-3p was reported to be downregulated in acute myelogenous leukemia (AML) and acted as a novel diagnostic marker. However, the regulatory effect of miR-142-3p on drug resistance of AML cells and its underlying mechanism have not been elucidated. Here, we found that miR-142-3p was significantly downregulated and high mobility group box 1 (HMGB1) was dramatically upregulated in AML samples and cells, as well as drug-resistant AML cells. P-gp level and autophagy were markedly enhanced in HL-60/ADR and HL-60/ATRA cells...
June 2017: Translational Oncology
https://www.readbyqxmd.com/read/28433800/chromosomal-alterations-and-gene-expression-changes-associated-with-the-progression-of-leukoplakia-to-advanced-gingivobuccal-cancer
#16
Priyanka G Bhosale, Simona Cristea, Srikant Ambatipudi, Rajiv S Desai, Rajiv Kumar, Asawari Patil, Shubhada Kane, Anita M Borges, Alejandro A Schäffer, Niko Beerenwinkel, Manoj B Mahimkar
We present an integrative genome-wide analysis that can be used to predict the risk of progression from leukoplakia to oral squamous cell carcinoma (OSCC) arising in the gingivobuccal complex (GBC). We find that the genomic and transcriptomic profiles of leukoplakia resemble those observed in later stages of OSCC and that several changes are associated with this progression, including amplification of 8q24.3, deletion of 8p23.2, and dysregulation of DERL3, EIF5A2, ECT2, HOXC9, HOXC13, MAL, MFAP5 and NELL2. Comparing copy number profiles of primary tumors with and without lymph-node metastasis, we identify alterations associated with metastasis, including amplifications of 3p26...
June 2017: Translational Oncology
https://www.readbyqxmd.com/read/28433799/affinity-proteomics-exploration-of-melanoma-identifies-proteins-in-serum-with-associations-to-t-stage-and-recurrence
#17
Sanna Byström, Claudia Fredolini, Per-Henrik Edqvist, Etienne-Nicholas Nyaiesh, Kimi Drobin, Mathias Uhlén, Michael Bergqvist, Fredrik Pontén, Jochen M Schwenk
BACKGROUND: Blood-based proteomic profiling may aid and expand our understanding of diseases and their different phenotypes. The aim of the presented study was to profile serum samples from patients with malignant melanoma using affinity proteomic assays to describe proteins in the blood stream that are associated to stage or recurrence of melanoma. MATERIAL AND METHODS: Multiplexed protein analysis was conducted using antibody suspension bead arrays. A total of 232 antibodies against 132 proteins were selected from (i) a screening with 4595 antibodies and 32 serum samples from melanoma patients and controls, (ii) antibodies used for immunohistochemistry, (iii) protein targets previously related with melanoma...
June 2017: Translational Oncology
https://www.readbyqxmd.com/read/28432899/serum-micrornas-related-with-chemoradiotherapy-resistance-in-advanced-stage-cervical-squamous-cell-carcinoma
#18
Ying Han, Mei Liu, Ziyi Wang, Manni Huang, Ningzhi Xu, Lingying Wu
OBJECTIVE: To investigate the serum microRNAs as biomarkers in predicting chemoradiotherapy resistance in advanced-stage cervical squamous cell carcinoma (ACSCC) patients. METHODS: Serum samples were collected from International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IIIB cervical squamous cell carcinoma patients treated with platinum based Concomitant Chemoradiotherapy (CCRT) in our hospital during September 2013 to November 2015. Twenty well-matched samples (10 resistant and 10 sensitive) were chosen to screen the miRNA expression profile using serum samples pooled with microarrays...
June 2017: Translational Oncology
https://www.readbyqxmd.com/read/28431392/characterization-of-aurora-a-and-its-impact-on-the-effect-of-cisplatin-based-chemotherapy-in-patients-with-non-small-cell-lung-cancer
#19
Peng Kuang, Zuhua Chen, JiaYuan Wang, Zhentao Liu, Jingyuan Wang, Jing Gao, Lin Shen
BACKGROUND AND OBJECTIVE: Aurora A, as a member of serine/threonine kinase family and a common characteristic of epithelial cancers, plays a critical role in cell mitosis. However, the clinical significance of Aurora A in non-small cell lung cancer (NSCLC) remains undetermined. METHODS: The expression of Aurora A in NSCLC and paired normal adjacent lung tissues was determined by immunohistochemistry, Western blot, and reverse transcriptase polymerase chain reaction...
June 2017: Translational Oncology
https://www.readbyqxmd.com/read/28342996/induction-of-neuroendocrine-differentiation-in-prostate-cancer-cells-by-dovitinib-tki-258-and-its-therapeutic-implications
#20
Shalini S Yadav, Jinyi Li, Jennifer A Stockert, Bryan Herzog, James O'Connor, Luis Garzon-Manco, Ramon Parsons, Ashutosh K Tewari, Kamlesh K Yadav
Prostate cancer (PCa) remains the second-leading cause of cancer-related deaths in American men with an estimated mortality of more than 26,000 in 2016 alone. Aggressive and metastatic tumors are treated with androgen deprivation therapies (ADT); however, the tumors acquire resistance and develop into lethal castration resistant prostate cancer (CRPC). With the advent of better therapeutics, the incidences of a more aggressive neuroendocrine prostate cancer (NEPC) variant continue to emerge. Although de novo occurrences of NEPC are rare, more than 25% of the therapy-resistant patients on highly potent new-generation anti-androgen therapies end up with NEPC...
June 2017: Translational Oncology
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