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Cancer Science

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https://www.readbyqxmd.com/read/28317223/cancer-with-low-cathepsin-d-levels-is-susceptible-to-v-atpase-inhibition
#1
Satoshi Kitazawa, Satoru Nishizawa, Hideyuki Nakagawa, Masaaki Funata, Kazuho Nishimura, Tomoyoshi Soga, Takahito Hara
Vacuolar (H(+) )-ATPases (V-ATPases) have important roles in the supply of nutrients to tumors by mediating autophagy and the endocytic uptake of extracellular fluids. Accordingly, V-ATPases are attractive therapeutic targets for cancer. However, the clinical use of V-ATPase inhibitors as anti-cancer drugs has not been realized, possibly owing to their high toxicity in humans. V-ATPase inhibition may be an appropriate strategy in highly susceptible cancers. In this study, we explored markers of V-ATPase inhibitor sensitivity...
March 19, 2017: Cancer Science
https://www.readbyqxmd.com/read/28301080/hsp90-inhibitor-auy922-can-reverse-fulvestrant-induced-feedback-reaction-in-human-breast-cancer-cells
#2
Jingchao Bai, Guanglin Zhou, Yufan Qiu, Yunhui Hu, Jingjing Liu, Jing Zhao, Sheng Zhang, Jin Zhang
Hormone therapy has become one of the main strategy for breast cancer, however, many estrogen receptor(ER) positive patients ends in tumor collapse due to initial or acquired resistance to hormone treatment, which includes Fulvestrant. Here we report that ErbB Receptors and downstream PI3K/AKT and ERK pathway have been reactivated after treatment of Fulvestrant in ER positive MCF-7 and T47D cells, which are related to Fulvestrant resistance. HSP90 is a universally expressed chaperone protein and plays a vital role in both normal and cancer cells, HSP90 inhibitor AUY922 can reverse this feedback reactivation effect of Fulvestrant by targeting multiple proteins related in ErbB Receptors, PI3K/AKT and ERK pathway, which is much better than single targeting inhibitors...
March 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28301076/clinical-development-of-anti-cd19-chimeric-antigen-receptor-t-cell-therapy-for-b-cell-non-hodgkin-lymphoma
#3
Shinichi Makita, Kiyoshi Yoshimura, Kensei Tobinai
B-cell non-Hodgkin lymphoma (B-NHL) is the most frequent hematological malignancy. Although refined chemotherapy regimens and several new therapeutics including rituximab, a chimeric anti-CD20 monoclonal antibody, have improved its prognosis in recent decades, there are still a substantial number of patients with chemorefractory B-NHL. Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is expected to be an effective adoptive cell treatment and has the potential to overcome the chemorefractoriness of B-cell leukemia and lymphoma...
March 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28295868/ciap2-promotes-gallbladder-cancer-invasion-and-lymphangiogenesis-by-activating-the-nf-%C3%AE%C2%BAb-pathway
#4
Xiaojie Jiang, Chengzong Li, Bin Lin, Haijie Hong, Lei Jiang, Siyuan Zhu, Xiaoqian Wang, Nanhong Tang, Xiujin Li, Feifei She, Chen Yanling
Several studies have produced contradictory findings about the prognostic implications for inhibitor of apoptosis proteins (IAPs) in different types of cancer. Cellular inhibitor of apoptosis 2 (cIAP2/BIRC) is one of the most extensively characterized human IAPs. To date no studies have focused on the expression level of cIAP2 in human gallbladder cancer (GBC), and the mechanism of cIAP2 in GBC invasion and lymphangiogenesis remains unclear. Therefore, in the present study, cIAP2 expression in GBC was detected using qRT-PCR and immunohistochemistry, and the relationship between cIAP2 levels in cancer tissues and the clinicopathological characteristics of patients was analysed...
March 15, 2017: Cancer Science
https://www.readbyqxmd.com/read/28294486/pd-l1-expression-at-tumor-invasive-front-is-associated-with-emt-and-poor-prognosis-in-esophageal-squamous-cell-carcinoma
#5
Satoshi Tsutsumi, Hiroshi Saeki, Yuichiro Nakashima, Shuhei Ito, Eiji Oki, Masaru Morita, Yoshinao Oda, Shinji Okano, Yoshihiko Maehara
Programmed death-ligand 1 (PD-L1) plays a crucial role in the host immune system in cancer progression. The gene promoter region of PD-L1 also contains a binding site for ZEB1, a transcription factor related to epithelial-mesenchymal transition (EMT). The purpose of this study was to clarify the relationship between PD-L1 and EMT and its clinical importance in esophageal squamous cell carcinoma (ESCC). PD-L1 and ZEB1 expression at the tumor invasive front was examined by immunohistochemistry in resected specimens from 90 patients with ESCC who underwent surgery without preoperative therapy, and their expression and clinicopathological factors were compared...
March 14, 2017: Cancer Science
https://www.readbyqxmd.com/read/28294470/exome-sequencing-deciphers-a-germline-met-mutation-in-familial-epidermal-growth-factor-receptor-mutant-lung-cancer
#6
Naoki Tode, Toshiaki Kikuchi, Tomohiro Sakakibara, Taizou Hirano, Akira Inoue, Shinya Ohkouchi, Tsutomu Tamada, Tatsuma Okazaki, Akira Koarai, Hisatoshi Sugiura, Tetsuya Niihori, Yoko Aoki, Keiko Nakayama, Kunio Matsumoto, Yoichi Matsubara, Masayuki Yamamoto, Akira Watanabe, Toshihiro Nukiwa, Masakazu Ichinose
Lung cancer accompanied by somatic activating mutations in the epidermal growth factor receptor (EGFR) gene, which is associated with a significant clinical response to the targeted therapy, is frequently found in never-smoking Asian women with adenocarcinoma. Although this implies genetic factors underlying the carcinogenesis, the etiology remains unclear. To gain insight into the pathogenic mechanisms, we sequenced the exomes in the peripheral-blood DNA from six siblings, four affected and two unaffected siblings, of a kindred with familial EGFR-mutant lung adenocarcinoma...
March 13, 2017: Cancer Science
https://www.readbyqxmd.com/read/28295876/a-vicious-partnership-between-akt-and-phlda3-to-facilitate-neuroendocrine-tumors
#7
Masahiro Takikawa, Rieko Ohki
Neuroendocrine tumors (NETs) are rare cancers that generally have a poor prognosis. Accurate diagnosis and proper treatment of these tumors requires a better understanding of the molecular mechanisms underlying the development of NETs. It has been shown that the mTOR inhibitor everolimus can improve the progression-free survival of pancreatic NET (PanNET) patients, suggesting that inhibition of the PI3K-Akt-mTOR pathway may suppress the progression of PanNETs. PHLDA3 is a novel tumor suppressor protein that inhibits Akt activation by competition for binding to PIP3 ...
March 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28281325/b-raf-mutations-are-associated-with-increased-iron-regulatory-protein-2-expression-in-colorectal-tumourigenesis
#8
Richard D Horniblow, Matthew Bedford, Robert Hollingworth, Sarah Evans, Emily Sutton, Neeraj Lal, Andrew Beggs, Tariq H Iqbal, Chris Tselepis
A role for iron in carcinogenesis is supported by evidence that iron metabolism proteins are modulated in cancer progression. To date however, the expression of IRP2 (Iron Regulatory Protein-2), which is known to regulate several iron metabolism proteins, has not been assessed in colorectal cancer. Expression of IRP2 was assessed by qRT-PCR and immunohistochemistry in human colorectal cancer tissue. By interrogating The Cancer Genome Atlas (TCGA) database, expression of IRP2 and transferrin receptor-1 (TfR1) was assessed relative to common mutations that are known to occur in cancer...
March 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/28267244/a-multicenter-phase-ii-study-of-nivolumab-in-japanese-patients-with-relapsed-or-refractory-classical-hodgkin-lymphoma
#9
Dai Maruyama, Kiyohiko Hatake, Tomohiro Kinoshita, Noriko Fukuhara, Ilseung Choi, Masafumi Taniwaki, Kiyoshi Ando, Yasuhito Terui, Yusuke Higuchi, Yasushi Onishi, Yasunobu Abe, Tsutomu Kobayashi, Yukari Shirasugi, Kensei Tobinai
Overexpression of programmed death-1 (PD-1) ligands contributes to an immunosuppressive microenvironment. Nivolumab is a PD-1-blocking antibody that inhibits the PD-1 pathway and showed good efficacy in several types of malignancy. This phase II study examined the efficacy and safety of nivolumab in 17 Japanese patients with refractory/relapsed classical Hodgkin lymphoma previously treated with brentuximab vedotin. Sixteen patients were included in efficacy analyses and 17 in safety analyses. The primary endpoint was the centrally assessed objective response rate (ORR)...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28267243/overall-survival-of-1st-line-axitinib-in-metastatic-renal-cell-carcinoma-japanese-subgroup-analysis-from-phase-ii-study
#10
Mototsugu Oya, Yoshihiko Tomita, Satoshi Fukasawa, Nobuo Shinohara, Tomonori Habuchi, Brian I Rini, Yosuke Fujii, Yoichi Kamei, Yoshiko Umeyama, Angel H Bair, Hirotsugu Uemura
Subgroup analyses of a randomized global phase II study of axitinib showed objective response rate of 66% and median progression-free survival of 27.6 months in treatment-naïve Japanese patients with metastatic renal cell carcinoma (RCC). This analysis evaluated overall survival (OS) and updated safety in 44 Japanese patients and compared with 169 non-Japanese patients. In addition, baseline characteristics for predictive factors that may influence OS in first-line metastatic RCC were explored using a Cox proportional hazard model in all patients...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28267240/integrated-functions-of-membrane-type-1-matrix-metalloproteinase-in-regulating-cancer-malignancy-beyond-a-proteinase
#11
REVIEW
Takeharu Sakamoto, Motoharu Seiki
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is expressed in different types of invasive and proliferative cells, including cancer cells and stromal cells. MT1-MMP cleaves extracellular matrix proteins, membrane proteins, and other pericellular proteins, thereby changing the cellular microenvironment and regulating signal activation. Critical roles of protease activity in cancer cell proliferation, invasion, and metastasis have been demonstrated by many groups. MT1-MMP also has a non-protease activity in that it inhibits the oxygen-dependent suppression of hypoxia-inducible factors (HIFs) via Munc18-1-interacting protein 3 (Mint3) and thereby enhances the expression of HIF target genes...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28267224/prognostic-value-of-programmed-death-ligand-1-expression-in-patients-with-stage-iii-colorectal-cancer
#12
Shigehiro Koganemaru, Naoko Inoshita, Yuji Miura, Yu Miyama, Yudai Fukui, Yukinori Ozaki, Kenji Tomizawa, Yutaka Hanaoka, Shigeo Toda, Koichi Suyama, Yuko Tanabe, Jin Moriyama, Takeshi Fujii, Shuichiro Matoba, Hiroya Kuroyanagi, Toshimi Takano
The Programmed death-1/ Programmed death-ligand 1 (PD-L1) pathway is a negative feedback pathway that suppresses the activity of T cells. Previous studies reported that high PD-L1 expression on tumor cells (TCs) was associated with poor survival in patients with colorectal cancer; however, the prognostic evaluation of these studies was limited because they included patients at various disease stages. The purpose of this study was to evaluate the relationship between PD-L1 status in the immune microenvironment and the clinicopathological features of stage III colorectal cancer...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28266780/recent-advances-in-genetic-modification-of-adenovirus-vectors-for-cancer-treatment
#13
REVIEW
Yuki Yamamoto, Masaki Nagasato, Teruhiko Yoshida, Kazunori Aoki
Adenoviruses are widely used to deliver genes to a variety of cell types and have been employed in a number of clinical trials for gene therapy and oncolytic virotherapy. However, several issues must be addressed for the clinical use of adenovirus vectors. Selective delivery of a therapeutic gene by adenovirus vectors to target cancer is precluded by the widespread distribution of the primary cellular receptors. The systemic administration of adenoviruses results in hepatic tropism independent of the primary receptors...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28266765/phase-1-study-of-ocv-c02-a-peptide-vaccine-consisting-of-two-peptide-epitopes-for-refractory-metastatic-colorectal-cancer
#14
Hiroya Taniguchi, Satoru Iwasa, Kentaro Yamazaki, Takayuki Yoshino, Chika Kiryu, Yoshiharu Naka, Ei Leen Liew, Yuh Sakata
OCV-C02 is a peptide vaccine consisting of two peptide epitopes derived from ring finger protein 43 (RNF43) and translocase of outer mitochondrial membrane 34 (TOMM34). This Phase 1 study assessed the safety, preliminary efficacy and immunological responses following OCV-C02 administration in patients with advanced or relapsed colorectal cancer who were intolerant or refractory to standard chemotherapy. The primary endpoint was any occurrence of dose limiting toxicity (DLT) during Cycle 1. The secondary endpoints were treatment-emergent adverse events, efficacy and immunological responses...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28266163/quality-evaluation-of-investigator-initiated-trials-using-post-approval-cancer-drugs-in-japan
#15
Shunsuke Kondo, Hiroko Hosoi, Jun Hashimoto
Investigator-initiated trials (IITs) are important aspects of medical research and have contributed substantially to modern oncology. IITs using post-approval drugs have been conducted by domestic institutions in Japan. Data from this study were obtained by all IITs registered clinical trials for five cancers (lung, colorectal cancer, gastric cancer, liver cancer, and breast cancer) using drugs approved from 1999 to 2009 in Japan. The Kaplan-Meier method, analysis of variance (ANOVA), and Kruskal-Wallis test were used to estimate time to enrolment completion (TTEC) and time to enrolment per patient (TTEP)...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28266140/cytokine-biomarkers-to-predict-antitumor-responses-to-nivolumab-suggested-in-a-phase-ii-study-for-advanced-melanoma
#16
Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Hajime Iizuka, Jiro Uehara, Fujio Otsuka, Yasuhiro Fujisawa, Tatsuya Takenouchi, Taiki Isei, Keiji Iwatsuki, Hiroshi Uchi, Hironobu Ihn, Hironobu Minami, Hideaki Tahara
Promising anti-tumor activities of nivolumab, a fully humanized IgG4 inhibitor antibody against the programmed death-1 protein, were suggested in previous phase 1 studies. The present phase 2, single-arm study (JAPIC-CTI #111681) evaluated the anti-tumor activities of nivolumab and explored its predictive correlates in advanced melanoma patients at 11 sites in Japan. Intravenous nivolumab 2 mg/kg was given repeatedly at 3-week intervals to 35 of 37 patients enrolled from December 2011 to May 2012 until they experienced unacceptable toxicity, disease progression, or complete response...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28266091/efficacy-and-safety-of-nivolumab-in-japanese-patients-with-advanced-or-recurrent-squamous-non-small-cell-lung-cancer
#17
Toyoaki Hida, Makoto Nishio, Naoyuki Nogami, Yuichiro Ohe, Hiroshi Nokihara, Hiroshi Sakai, Miyako Satouchi, Kazuhiko Nakagawa, Mitsuhiro Takenoyama, Hiroshi Isobe, Shiro Fujita, Hiroshi Tanaka, Koichi Minato, Toshiaki Takahashi, Makoto Maemondo, Koji Takeda, Hideo Saka, Koichi Goto, Shinji Atagi, Tomonori Hirashima, Naoki Sumiyoshi, Tomohide Tamura
Limited treatment options are available for stage IIIB/IV non-small cell lung cancer (NSCLC). Nivolumab, a programmed cell death-1 immune checkpoint inhibitor antibody, has been shown to be effective for the treatment of NSCLC. This study investigated the effectiveness and safety of nivolumab in Japanese patients with advanced or recurrent squamous NSCLC that progressed after platinum-containing chemotherapy. In this multicenter phase II study, patients were treated with nivolumab (3mg/kg, intravenously) every 2 weeks until progressive disease or unacceptable toxicity was seen...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28256076/meat-consumption-and-colorectal-cancer-risk-in-japan-the-takayama-study
#18
Keiko Wada, Shino Oba, Michiko Tsuji, Takashi Tamura, Kie Konishi, Yuko Goto, Fumi Mizuta, Sachi Koda, Akihiro Hori, Shinobu Tanabashi, Shogen Matsushita, Naoki Tokimitsu, Chisato Nagata
Compared with the abundant data from Western countries, evidence regarding meat consumption and colorectal cancer is limited in the Japanese population. We evaluated colorectal cancer risk in relation to meat consumption in a population-based prospective cohort study in Japan. Participants were 13,957 men and 16,374 women aged ≥35 years in September 1992. Meat intake, assessed with a validated food frequency questionnaire, was controlled for the total energy intake. The incidence of colorectal cancer was confirmed through regional population-based cancer registries and histological identification from colonoscopy in two main hospitals in the study area...
March 3, 2017: Cancer Science
https://www.readbyqxmd.com/read/28256066/a-randomized-phase-ii-study-of-nab-paclitaxel-as-first-line-chemotherapy-in-patients-with-her2-negative-metastatic-breast-cancer
#19
Kenji Tamura, Kenichi Inoue, Norikazu Masuda, Shintaro Takao, Masahiro Kashiwaba, Yutaka Tokuda, Hiroji Iwata, Naohito Yamamoto, Kenjiro Aogi, Toshiaki Saeki, Takahiro Nakayama, Nobuaki Sato, Tatsuya Toyama, Takanori Ishida, Hitoshi Arioka, Mitsue Saito, Shinji Ohno, Hideko Yamauchi, Kimito Yamada, Junichiro Watanabe, Hiroshi Ishiguro, Yasuhiro Fujiwara
Weekly administration of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has been shown to be a safe and effective treatment for metastatic breast cancer (MBC) in clinical studies. We conducted a multicenter, randomized, open-label phase II study to compare the efficacy and safety of weekly nab-paclitaxel and docetaxel in Japanese patients with human epidermal growth factor receptor 2-negative MBC. The primary endpoint was progression-free survival (PFS). Patients were randomized to receive nab-paclitaxel (150 mg/m(2) nab-paclitaxel once per week for 3 of 4 weeks; n = 100) or docetaxel (75 mg/m(2) docetaxel every 3 weeks; n = 100)...
March 3, 2017: Cancer Science
https://www.readbyqxmd.com/read/28256061/intraoperative-peritoneal-lavage-cytology-offers-prognostic-significance-for-gastric-cancer-patients-with-curative-resection
#20
Eiji Higaki, Shinya Yanagi, Naoto Gotohda, Takahiro Kinoshita, Takeshi Kuwata, Masato Nagino, Atsushi Ochiai, Satoshi Fujii
Outcomes of patients with gastric cancer who exhibit positive peritoneal lavage cytology findings (CY(+) ) vary by diagnostic methods because of quantitative and qualitative cancer cell diversity. This study sought to establish practical diagnostic criteria for performing curative resections, based on peritoneal lavage cytology findings in gastric cancer patients. We enrolled 1028 patients with gastric cancer who underwent R0/1 (n=911) or R2 (n=117) resections and analyzed relationships between cancer cell findings in peritoneal lavage fluid and clinicopathological factors in the R0/1 group...
March 3, 2017: Cancer Science
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