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Cancer Science

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https://www.readbyqxmd.com/read/30007115/exosomal-zinc-transporter-zip4-promotes-cancer-growth-and-is-a-novel-diagnostic-biomarker-for-pancreatic-cancer
#1
Haoyi Jin, Peng Liu, Yunhao Wu, Xiangli Meng, Mengwei Wu, Jiahong Han, Xiaodong Tan
Pancreatic cancer is one of the deadliest cancers with rapid disease progression, requiring further elucidation of its underlying molecular mechanisms and novel biomarkers for early detection. Exosomes are small extracellular vesicles that are released by multiple cell types acting as message carriers during intercellular communication and are promising biomarker candidates. However, the role of pancreatic cancer cell-derived exosomes in cancer progression and the application of these vesicles as novel diagnostic biomarkers are still not fully studied...
July 14, 2018: Cancer Science
https://www.readbyqxmd.com/read/30007103/a-5-day-regimen-of-azacitidine-for-lower-risk-myelodysplastic-syndromes-ra-or-rars-a-prospective-single-arm-phase-2-trial
#2
Yasuyoshi Morita, Yasuhiro Maeda, Terufumi Yamaguchi, Fumiaki Urase, Shuhei Kawata, Hitoshi Hanamoto, Kazuo Tsubaki, Jun Ishikawa, Hirohiko Shibayama, Itaru Matsumura, Mitsuhiro Matsuda
Although azacitidine is the first-line drug for higher-risk MDS patients, its efficacy for lower-risk MDS remains unestablished. So, we conducted a prospective study to examine the efficacy and safety of a 5-day regimen of azacitidine (AZA-5) for lower-risk MDS. The primary endpoint was hematological improvement (HI) after 4 courses of therapy. A total of 51 patients with lower-risk MDS by FAB classification (RA 44 patients and RARS 7 patients) were enrolled from 6 centers in Japan. The median age was 75 years (range: 51-88)...
July 14, 2018: Cancer Science
https://www.readbyqxmd.com/read/30007095/heterogeneity-of-tumor-lymphangiogenesis-progress-and-prospects
#3
Xueting Hu, Jincai Luo
Lymphangiogenesis and increased expression of lymphangiogenic growth factors are associated with high rate of lymph node (LN) metastasis and with poor prognosis in some, but not all, solid tumors. In addition to its involvement in metastasis, lymphangiogenesis has been shown to have other roles in tumor pathogenesis, such as the niche function of tumor stem cells and regulatory functions of anti-tumor immune responses. On the other hand, evidence has accumulated that tumor-induced lymphangiogenesis displays the heterogeneity in gene signature, structure, cellular origins and functional plasticity...
July 14, 2018: Cancer Science
https://www.readbyqxmd.com/read/29999574/exosome-mediated-regulation-of-tumor-immunology
#4
Naohiro Seo, Kazunari Akiyoshi, Hiroshi Shiku
Exosomes are the representative extracellular vesicles (EVs) derived from multivesicular endosomes (MVEs), and have been described as new players in communication of neighborhood and/or distant cells by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, and nucleotides including micro (mi) RNAs. Exosomes from immune cells and tumor cells act in part as a regulator in tumor immunology. CD8+ T cells that exhibit potent cytotoxic activity against tumor cells reside as an inactive naïve form in T cell zone of the secondary lymphoid organs...
July 12, 2018: Cancer Science
https://www.readbyqxmd.com/read/29999572/cost-effectiveness-of-aprepitant-in-japanese-patients-treated-with-cisplatin-containing-highly-emetogenic-chemotherapy
#5
Ikuto Tsukiyama, Shiori Hasegawa, Yoshiaki Ikeda, Masayuki Takeuchi, Sumiyo Tsukiyama, Yusuke Kurose, Masayuki Ejiri, Masaki Sakuma, Hiroko Saito, Ichiro Arakawa, Tadao Inoue, Etsuro Yamaguchi, Akihito Kubo
Chemotherapy-induced nausea and vomiting (CINV) remains a major adverse event in cancer chemotherapy. While aprepitant is effective in preventing CINV, an increment in financial burden for uniform use of aprepitant is a concern. The aim of this study is to define the cost-effectiveness of aprepitant from the perspective of the Japanese National Health Insurance system. Based on the results of a randomized phase II trial comparing an aprepitant-containing regimen versus a non-aprepitant regimen in Japanese patients who received cisplatin-containing highly emetogenic chemotherapy, a decision analytic model was developed...
July 12, 2018: Cancer Science
https://www.readbyqxmd.com/read/29993160/a-double-negative-feedback-interaction-between-dnmt3a-and-mir-145-in-the-warburg-effect-of-ovarian-cancer-cells
#6
Songlin Zhang, Meili Pei, Zhen Li, Han Li, Yanli Liu, Jie Li
Ovarian cancer is the most lethal gynecologic malignancy because of its poor prognosis. The Warburg effect is one of the key mechanisms mediating cancer progression. Molecules targeting the Warburg effect are therefore of significant therapeutic value for the treatment of cancers. Many microRNAs (miRs) are dysregulated in cancers, and aberrant miR expression patterns have been suggested to correlate with the Warburg effect in cancer cells. In our study, We found that miR-145 negatively correlated with DNMT3A expression at cellular/histological levels...
July 11, 2018: Cancer Science
https://www.readbyqxmd.com/read/29989289/unveiling-epigenetic-regulation-in-cancer-aging-and-rejuvenation-with-in-vivo-reprogramming-technology
#7
Yuko Sogabe, Hiroshi Seno, Takuya Yamamoto, Yasuhiro Yamada
Reprogramming technology has enabled the fate conversion of terminally differentiated somatic cells into pluripotent stem cells or into another differentiated state. A dynamic reorganization of epigenetic regulation takes place during cellular reprogramming. Given that reprogramming does not require changes in the underlying genome, the technology can be used to actively modify epigenetic regulation. Although reprogramming has been investigated mostly at the cellular level in vitro, studies have demonstrated that somatic cells are reprogrammable in multicellular organisms in vivo...
July 10, 2018: Cancer Science
https://www.readbyqxmd.com/read/29989268/analysis-of-cabazitaxel-resistant-mechanism-in-human-castration-resistant-prostate-cancer
#8
Hiroshi Hongo, Takeo Kosaka, Mototsugu Oya
Cabazitaxel (CBZ) is approved for docetaxel-resistant castration-resistant prostate cancer (CRPC). However, efficacy of CBZ for CRPC is limited and there are no effective treatments for CBZ-resistant CRPC. In order to investigate the CBZ-resistant mechanism, the establishment of a CBZ-resistant cell line is urgently needed. We established CBZ-resistant CRPC cell lines, DU145CR and PC3CR, by incubating DU145 and PC3 cells with gradually increasing concentrations of CBZ for about 2 years. We analyzed the gene expression profiles and cell cycle changes using microarray and flow cytometry...
July 10, 2018: Cancer Science
https://www.readbyqxmd.com/read/29987920/aberrant-methylation-and-silencing-of-the-spint2-gene-in-high-grade-gliomas
#9
Tsuyoshi Fukushima, Makiko Kawaguchi, Koji Yamamoto, Fumiki Yamashita, Aya Izumi, Takashi Kaieda, Yuka Takezaki, Hiroshi Itoh, Hideo Takeshima, Hiroaki Kataoka
Hepatocyte growth factor activator inhibitor type 2 (HAI-2), encoded by the SPINT2 gene, is a membrane-anchored protein that inhibits proteases involved in the activation of hepatocyte growth factor (HGF), a ligand of MET receptor. Epigenetic silencing of the SPINT2 gene has been reported in a human glioblastoma cell line (U87) and glioblastoma-derived cancer stem cells. However, the incidence of SPINT2 methylation in tumor tissues obtained from glioma patients is unknown. In this study, we analyzed the methylation status of the SPINT2 gene of eight human glioblastoma cell lines and surgically resected glioma tissues of different grades (II, III and IV) by bisulfite sequence analysis and methylation-specific PCR (MSP)...
July 10, 2018: Cancer Science
https://www.readbyqxmd.com/read/29987902/identification-of-entpd8-and-cytidine-in-pancreatic-cancer-by-metabolomics-and-transcriptomics-conjoint-analysis
#10
Yong An, Huihua Cai, Yong Yang, Yue Zhang, Shengyong Liu, Xinquan Wu, Yunfei Duan, Donglin Sun, Xuemin Chen
To identify metabolic pathways that were perturbed in pancreatic cancer (PC), we investigated gene-metabolite networks by integration of metabolomics and transcriptomics. In this study, we performed metabolomics study of 43 paired human PC samples, aiming to identify key metabolic alterations in PC. And we performed in vitro experiments to validate that the key metabolite cytidine and its related gene ENTPD8 played an important role in PC cell proliferation indeed. We screened out 13 metabolites differentially expressed in pancreatic cancer tissue (PCT) by LC-MS analysis on 34 metabolites, and the PLS-DA results revealed that 9 metabolites among them were remarkably altered in PCT compared to adjacent noncancerous tissue (ANT) (variable importance in projection (VIP)>1, P<0...
July 10, 2018: Cancer Science
https://www.readbyqxmd.com/read/29981256/a-novel-chemical-compound-sincro-with-dual-function-in-the-sting-type-i-interferon-and-tumor-cell-death-pathways
#11
Yoshitaka Kimura, Hideo Negishi, Atsushi Matsuda, Nobuyasu Endo, Sho Hangai, Asuka Inoue, Junko Nishio, Tadatsugu Taniguchi, Hideyuki Yanai
Recent years have seen a number of regulatory approvals for immune oncology or immunotherapies based on their ability to enhance anti-tumor immune responses. Nevertheless, the majority of the patients remain refractory to these treatments; hence, new therapies that augment current immunotherapies are required. Innate immune receptors that recognize nucleic acid are potent activators of subsequent T cell responses and, as a result, can evoke potent anti-tumor immune responses. Here, we present a novel compound N-{3-[(1,4'-bipiperidin)-1'-yl]propyl}-6-[4-(4-methylpiperazin-1-yl)phenyl]picolinamide (SINCRO; STING-mediated interferon-inducing and cytotoxic reagent, original) as an anti-cancer drug that activates the cytosolic DNA-sensing STING (stimulator of interferon genes) signaling pathway leading to the induction of type I interferon (IFN) genes...
July 7, 2018: Cancer Science
https://www.readbyqxmd.com/read/29981251/branched-rolling-circle-amplification-method-for-measuring-serum-circulating-microrna-levels-for-early-breast-cancer-detection
#12
Tingting Fan, Yu Mao, Qinsheng Sun, Feng Liu, Jin-Shun Lin, Yajie Liu, Junwei Cui, Yuyang Jiang
Serum circulating microRNAs (c-miRNAs) are serving as useful biomarkers for cancer diagnosis. Here, we describe the development of a one-step branched rolling circle amplification (BRCA) method to measure serum c-miRNAs levels for early diagnosis of breast cancer. Four c-miRNAs, c-miRNA16 (c-miR-16), c-miRNA21 (c-miR-21), c-miRNA155 (c-miR-155), and c-miRNA195 (c-miR-195) were isolated from the serum of 49 breast cancer patients (stages I-IV) and 19 healthy controls, and analyzed using one-step BRCA. The serum levels of c-miR16, c-miR21, c-miR155, and c-miR195 were higher (P < 0...
July 7, 2018: Cancer Science
https://www.readbyqxmd.com/read/29981249/updated-long-term-outcomes-after-carbon-ion-radiotherapy-for-primary-renal-cell-carcinoma
#13
Goro Kasuya, Hiroshi Tsuji, Takuma Nomiya, Hirokazu Makishima, Yasuo Haruyama, Gen Kobashi, Daniel K Ebner, Kazuhiko Hayashi, Tokuhiko Omatsu, Riwa Kishimoto, Shigeo Yasuda, Tatsuo Igarashi, Mototsugu Oya, Koichiro Akakura, Hiroyoshi Suzuki, Tomohiko Ichikawa, Jun Shimazaki, Tadashi Kamada
The long-term oncologic outcomes for primary renal cell carcinoma (RCC) treated with carbon-ion radiotherapy (CIRT) are poorly understood. Patients with primary RCC were treated with 12/16-fraction CIRT at our institution outside of clinical trials. The outcome data were pooled and retrospectively analyzed for toxicity, local control, and disease-free, cancer-specific, and overall survival. From 1997 to 2014, 19 RCC patients (11 with T1aN0M0, 4 with T1bN0M0, and 4 with inoperable advanced stage [T4N0M0, T3aN1M0, and T1aN0M1]) were treated with CIRT and followed up for a median of 6...
July 7, 2018: Cancer Science
https://www.readbyqxmd.com/read/29981246/high-expression-of-cd44v9-and-xct-in-chemoresistant-hepatocellular-carcinoma-potential-targets-by-sulfasalazine
#14
Fumitaka Wada, Hironori Koga, Jun Akiba, Takashi Niizeki, Hideki Iwamoto, Yu Ikezono, Toru Nakamura, Mitsuhiko Abe, Atsutaka Masuda, Takahiko Sakaue, Toshimitsu Tanaka, Tatsuyuki Kakuma, Hirohisa Yano, Takuji Torimura
CD44v9 is expressed in cancer stem cells (CSCs) and stabilizes the glutamate-cystine transporter xCT on the cytoplasmic membrane, thereby decreasing intracellular levels of reactive oxygen species (ROS). This mechanism confers ROS-resistance to CSCs and CD44v9-expressing cancer cells. The aims of this study were to assess 1) expression status of CD44v9 and xCT in hepatocellular carcinoma (HCC) tissues, including those derived from patients treated with hepatic arterial infusion chemoembolization (HAIC) therapy with cisplatin (CDDP) and 2) whether combination of CDDP with sulfasalazine (SASP), an inhibitor of xCT, was more effective on the tumor cells than CDDP alone via inducing ROS-mediated apoptosis...
July 7, 2018: Cancer Science
https://www.readbyqxmd.com/read/29972716/clinical-activity-of-asp8273-in-asian-patients-with-non-small-cell-lung-cancer-with-egfr-activating-and-t790m-mutations
#15
Haruyasu Murakami, Hiroshi Nokihara, Hidetoshi Hayashi, Takashi Seto, Keunchil Park, Koichi Azuma, Chun-Ming Tsai, James Chih-Hsin Yang, Makoto Nishio, Sang-We Kim, Katsuyuki Kiura, Akira Inoue, Koji Takeda, Jin-Hyoung Kang, Tomoki Nakagawa, Kentaro Takeda, Rio Akazawa, Yuichiro Kaneko, Masashi Shimazaki, Satoshi Morita, Masahiro Fukuoka, Kazuhiko Nakagawa
Epidermal growth factor receptor (EGFR)-activating mutations confer sensitivity to tyrosine kinase inhibitor (TKI) treatment for non-small cell lung cancer (NSCLC). ASP8273 is a highly specific, irreversible, once-daily, oral, EGFR TKI that inhibits both activating and resistance mutations. This ASP8273 dose-escalation/dose-expansion study (NCT02192697) was conducted in two phases. In phase 1, Japanese patients (aged ≥20 years) with NSCLC previously treated with ≥1 EGFR TKI received escalating ASP8273 doses (25-600mg) to assess safety/tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) by Bayesian Continual Reassessment Method...
July 4, 2018: Cancer Science
https://www.readbyqxmd.com/read/29968393/regulation-of-anti-tumor-mir-144-5p-targets-oncogenes-direct-regulation-of-syndecan-3-and-its-clinical-significance
#16
Yasutaka Yamada, Takayuki Arai, Satoko Kojima, Sho Sugawara, Mayuko Kato, Atsushi Okato, Kazuto Yamazaki, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki
In the human genome, miR-451a, miR-144-5p (passenger strand) and miR-144-3p (guide strand) reside in clustered miRNA sequences located within the 17q11.2 region. Low expression of these miRNAs is significantly associated with poor prognosis of patients with renal cell carcinoma (RCC) (miR-451a: p = 0.00305; miR-144-5p: p = 0.00128; miR-144-3p: p = 9.45 x 10-5 ). We previously demonstrated that miR-451a acted as an anti-tumor miRNA in RCC cells (Cancer Sci, 109: 1239-1253, 2018). Involvement of the passenger strand of the miR-144 duplex in the pathogenesis of RCC is not well understood...
July 3, 2018: Cancer Science
https://www.readbyqxmd.com/read/29959821/rsv-ameliorates-llc-bearing-mice-development-decreases-g-mdscs-accumulation-and-impairs-its-suppressive-ability
#17
Yilin Zhao, Qi Shao, Haitao Zhu, Haiyuan Xu, Wei Long, Bin Yu, Lining Zhou, Huaxi Xu, Yan Wu, Zhaoliang Su
Myeloid-derived suppressor cells (MDSCs) are heterogeneous population of immature myeloid cells which consist of two subsets: granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (M-MDSCs). MDSCs expand in tumor-bearing hosts and contribute to immunotherapeutic resistance by remarkably blocking effector T-cell activation via different mechanisms. Resveratrol (RSV) is a polyphenol and it has been widely used for its various health benefits. However, the underlying mechanism of its anti-tumor properties remains unclear...
June 30, 2018: Cancer Science
https://www.readbyqxmd.com/read/29959809/phase-2-study-of-ceritinib-in-alectinib-pretreated-patients-with-alk-rearranged-metastatic-nsclc-in-japan-ascend-9
#18
Toyoaki Hida, Takashi Seto, Hidehito Horinouchi, Makoto Maemondo, Masayuki Takeda, Katsuyuki Hotta, Fumihiko Hirai, Young Hak Kim, Shingo Matsumoto, Masayuki Ito, Koichi Ayukawa, Kota Tokushige, Masataka Yonemura, Testuya Mitsudomi, Makoto Nishio
Clinical experience of ceritinib in patients who progressed on alectinib is limited. In this prospective phase 2 study, we evaluated the activity of ceritinib in alectinib-pretreated patients with anaplastic lymphoma kinase (ALK)-rearranged metastatic (stage IIIB/IV) non-small cell lung cancer (NSCLC) in Japan. All patients needed to have ≥ 1 measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST, 1.1), and a World Health Organization Performance Status (WHO PS) of 0-1. Prior crizotinib and/or up to 1 chemotherapy regimen was allowed...
June 30, 2018: Cancer Science
https://www.readbyqxmd.com/read/29957865/r-high-chop-chaser-leed-with-autologous-stem-cell-transplantation-in-newly-diagnosed-mantle-cell-lymphoma-jcog0406
#19
Michinori Ogura, Kazuhito Yamamoto, Yasuo Morishima, Masashi Wakabayashi, Kensei Tobinai, Kiyoshi Ando, Naokuni Uike, Mitsutoshi Kurosawa, Hiroshi Gomyo, Masafumi Taniwaki, Kisato Nosaka, Norifumi Tsukamoto, Tatsu Shimoyama, Noriko Fukuhara, Yoshihiro Yakushijin, Kazunori Ohnishi, Kana Miyazaki, Kenichi Sawada, Nobuyuki Takayama, Ichiro Hanamura, Hirokazu Nagai, Hirofumi Kobayashi, Kensuke Usuki, Naoki Kobayashi, Kazuma Ohyashiki, Takahiko Utsumi, Kyoya Kumagai, Dai Maruyama, Ken Ohmachi, Yoshihiro Matsuno, Shigeo Nakamura, Tomomitsu Hotta, Kunihiro Tsukasaki
Although induction immunochemotherapy including high-dose cytarabine and rituximab followed by high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) is recommended for younger patients (≤65 years old) with untreated mantle cell lymphoma (MCL), no standard induction and HDC regimen has been established. We conducted a phase II study of induction immunochemotherapy of R-High-CHOP/CHASER followed by HDC of LEED with ASCT in younger patients with untreated advanced MCL. Eligibility criteria included untreated MCL, stage II bulky to IV, and age 20-65 years...
June 29, 2018: Cancer Science
https://www.readbyqxmd.com/read/29957833/inhibition-of-stim1-mediated-soce-as-a-novel-strategy-for-the-treatment-of-acquired-imatinib-resistant-gist
#20
Ziyi Yang, Lijia Pan, Shilei Liu, Fengnan Li, Wenjie Lv, Yijun Shu, Ping Dong
Imatinib has revolutionized the treatment of gastrointestinal stromal tumors (GIST); however, primary and secondary resistance to imatinib is still a major cause of treatment failure. Multiple mechanisms are involved in this progression. In the present study, we reported a novel mechanism for the acquired resistance to imatinib, which was induced by enhanced Ca2+ influx via stromal-interacting molecule 1 (STIM1)-mediated store-operated Ca2+ entry (SOCE). We found that the STIM1 expression level was related to the acquired resistance to imatinib in our studied cohort...
June 29, 2018: Cancer Science
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