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Cancer Science

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https://www.readbyqxmd.com/read/29143406/oncogenic-spiral-by-infectious-pathogens-the-cooperation-of-multiple-factors-in-cancer-development
#1
Jun-Ichirou Yasunaga, Masao Matsuoka
Chronic infection is one of the major causes of cancer, and there are several mechanisms for infection-mediated oncogenesis. Some pathogens encode gene products that behave like oncogenic factors, hijacking cellular pathways to promote the survival and proliferation of infected cells in vivo. Some of these viral oncoproteins trigger a cellular damage defense response leading to senescence; however, other viral factors hinder this suppressive effect, suggesting that cooperation of those viral factors is important for malignant transformation...
November 15, 2017: Cancer Science
https://www.readbyqxmd.com/read/29124835/clinical-characteristics-and-outcomes-of-castleman-disease-a-multicenter-study-of-185-chinese-patients
#2
Xuanye Zhang, Huilan Rao, Xiaolu Xu, Zhihua Li, Bing Liao, Hongmei Wu, Mei Li, Xiuzhen Tong, Juan Li, Qingqing Cai
Castleman disease (CD) is a rare lymphoproliferative disorder. To assess the clinical features, outcomes, and prognostic factors of this disease, we retrospectively analyzed 185 HIV-negative CD patients from four medical centers in southern China. The median age was 37 years. 121 patients (65.4%) were classified as unicentric CD (UCD) and 64 patients (34.6%) were classified as multicentric CD (MCD). The histology subtype was hyaline-vascular for 132 patients (71.4%), plasma cell for 50 patients (27%) and mixed type for 3 patients (1...
November 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/29121435/altered-intracellular-signaling-by-imatinib-increases-the-anti-cancer-effects-of-tyrosine-kinase-inhibitors-in-cml-cells
#3
Takuya Hirao, Masashi Yamaguchi, Megumi Kikuya, Hiroji Chibana, Kousei Ito, Shigeki Aoki
Tyrosine kinase inhibitors (TKIs), including imatinib (IM), improve the outcome of chronic myelogenous leukemia (CML) therapy. However, TKI treatment is long-term and can induce resistance to TKIs, which often leads to a poor clinical outcome in CML patients. Here, we examined the effect of continuous IM exposure on intracellular energy metabolism in K562 cells, a human Philadelphia chromosome-positive CML cell line, and its subsequent sensitivity to anti-cancer agents. Contrary to our expectations, we found that continuous IM exposure increased sensitivity to TKIs...
November 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/29121426/xanthohumol-inhibits-angiogenesis-by-suppressing-nuclear-factor-%C3%AE%C2%BAb-activation-in-pancreatic-cancer
#4
Kenta Saito, Yoichi Matsuo, Hiroyuki Imafuji, Tomotaka Okubo, Yuzo Maeda, Takafumi Sato, Tomoya Shamoto, Ken Tsuboi, Mamoru Morimoto, Hiroki Takahashi, Hideyuki Ishiguro, Shuji Takiguchi
Xantohumol, a prenylated chalcone from hops (Humulus lupulus L.), has been shown to inhibit proliferation in some cancers. However, little is known regarding the effects of xanthohumol in pancreatic cancer. We have previously reported that activation of the transcription factor nuclear factor-κB (NF-κB) plays a key role in angiogenesis in pancreatic cancer. In this study, we investigated whether xanthohumol inhibited angiogenesis by blocking NF-κB activation in pancreatic cancer in vitro and in vivo. We initially confirmed that xanthohumol significantly inhibited proliferation and NF-κB activation in pancreatic cancer cell lines...
November 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/29121422/investigating-the-hepatitis-b-virus-life-cycle-using-engineered-reporter-hepatitis-b-viruses
#5
Hironori Nishitsuji, Keisuke Harada, Saneyuki Ujino, Jing Zhang, Michinori Kohara, Masaya Sugiyama, Masashi Mizokami, Kunitada Shimotohno
Chronic infection with Hepatitis B virus (HBV) increases the risk of developing fibrosis, cirrhosis, or hepatocellular carcinoma. Current therapies are limited to type-I interferons and/or nucleos(t)ide analogues; however, these are only partially effective. The development of novel anti-HBV agents for new treatment strategies has been hampered by the lack of a suitable system that allows the in vitro replication of HBV. Studies of virus infection/replication at the molecular level using wild-type HBV are labor-intensive and time-consuming...
November 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/29121415/efficacy-and-safety-of-trametinib-in-japanese-patients-with-advanced-biliary-tract-cancers-refractory-to-gemcitabine
#6
Masafumi Ikeda, Tatsuya Ioka, Akira Fukutomi, Chigusa Morizane, Akiyoshi Kasuga, Hideaki Takahashi, Akiko Todaka, Takuji Okusaka, Caretha L Creasy, Shelby Gorman, Daniel J Felitsky, Mikiro Kobayashi, Fanghong Zhang, Junji Furuse
Gemcitabine-based therapy remains the mainstay of treatment for patients with biliary tract cancers (BTCs) with no second-line treatment(s) established yet. Aberrant activation of MAPK pathway in patients with BTC indicates its importance in BTC. Trametinib is a potent, highly selective, allosteric non-competitive inhibitor of MEK1/MEK2. In this Phase IIa open-label, single-arm study, we investigated efficacy and safety of trametinib in Japanese patients with advanced BTC refractory to gemcitabine-based therapy...
November 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/29114963/potential-utility-of-a-longitudinal-relative-dose-intensity-of-molecularly-targeted-agents-in-phase-1-dose-finding-trials
#7
Akihiro Hirakawa, Kan Yonemori, Fumie Kinoshita, Yumiko Kobayashi, Hitomi S Ohkuma, Asuka Kawachi, Kenji Tamura, Yasuhiro Fujiwara, Larry Rubinstein, Pamela Jo Harris, Naoko Takebe
Phase 1 trials of molecularly targeted agents (MTA) often do not use toxicity data beyond the first cycle of treatment to determine a recommended phase 2 dose (RP2D). We investigated the potential utility of longitudinal relative dose intensity (RDI) that may be a better new way of determining a more accurate RP2D as a lower dose that is presumably more tolerable over the long term without compromising efficacy. All consecutive patients who initially were treated using a single MTA at the conventional RP2D or at one level lower dose (OLLD) of that RP2D in nine phase 1 trials sponsored by the National Cancer Institute were included...
November 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/29110374/towards-understanding-the-mechanisms-of-actions-of-ceacam6-in-cancer-progression
#8
REVIEW
Balsam Rizeq, Zain Zakaria, Allal Ouhtit
Human carcinoembryonic antigen (CEA) is the prototypic member of highly related cell surface glycoproteins that includes Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) and others. CEACAM6 (formerly NCA) that belongs to the immunoglobulin superfamily, is a cell adhesion proteins of the CEA family. It is normally expressed on the epithelial surfaces and the surface of myeloid (CD66c). CEACAM6 is a multi-functional glycoprotein that mediates homotypic binding with other CEA family members and heterotypic binding with integrin receptors...
November 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/29095550/downregulation-of-cd24-suppresses-bone-metastasis-of-lung-cancer
#9
Hinako Okabe, Katsuhiko Aoki, Satomi Yogosawa, Mitsuru Saito, Keishi Marumo, Kiyotsugu Yoshida
Suppression of bone metastasis can improve patient quality of life. Current drugs for bone metastasis have been shown to prolong progression-free survival but not overall survival; therefore, other potential therapeutic targets for bone metastasis should be investigated. Cell-surface antigens, such as CD24, have been recently shown to be involved in the metastasis of various cancers. However, whether CD24 plays a role in bone metastasis of lung cancer remains unknown. To observe metastasis of lung cancer cells by imaging technology, we introduced a near-infrared fluorescent protein, iRFP720, into a bone-seeking subclone established from lung cancer cells, HARA-B4 cells...
November 2, 2017: Cancer Science
https://www.readbyqxmd.com/read/29095547/rac-gtpase-activating-protein-1-promotes-the-oncogenic-progression-of-epithelial-ovarian-cancer
#10
Chuanjiang Wang, Wenxia Wang, Yujuan Liu, Min Yong, Yamei Yang, Honggui Zhou
Rac GTPase activating protein 1 (RacGAP1) can regulate cytokinesis and cell differentiation. The oncogenic role of RacGAP1 has been partially studied in gastric cancer, colorectal cancer, and breast cancer. In this study, we endeavor to evaluate its expression and functions in epithelial ovarian cancer (EOC). We retrospectively collected the clinicopathological information of 117 patients who underwent curative surgery for EOC. The expression of RacGAP1 protein in primary tumor tissues was evaluated by immunohistochemistry, which was significantly associated with tumor pathological grade, tumor stage, and lymph node metastasis...
November 2, 2017: Cancer Science
https://www.readbyqxmd.com/read/29090850/immune-suppressive-effects-of-il-6-on-t-cell-mediated-anti-tumor-immunity
#11
REVIEW
Hirotake Tsukamoto, Koji Fujieda, Satoru Senju, Tokunori Ikeda, Hiroyuki Oshiumi, Yasuharu Nishimura
Accompanied by the growing clinical applications of immunotherapy in treatment for cancer patients, the development of novel therapeutic approaches to reverse the immune-suppressive environment in cancer patients is eagerly anticipated, because the success of cancer immunotherapy is currently limited by immune-suppressive effects in tumor-bearing hosts. Interleukin (IL)-6, a pleotropic pro-inflammatory cytokine, participates in tumor cell-autonomous processes that are required for their survival and growth, and is therefore known as a poor prognostic factor in cancer patients...
November 1, 2017: Cancer Science
https://www.readbyqxmd.com/read/29080383/clinical-significance-of-tryptophan-catabolism-in-hodgkin-lymphoma
#12
Ayako Masaki, Takashi Ishida, Yasuhiro Maeda, Asahi Ito, Susumu Suzuki, Tomoko Narita, Shiori Kinoshita, Hisashi Takino, Takashi Yoshida, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Hiroshi Inagaki, Ryuzo Ueda, Ilseung Choi, Youko Suehiro, Shinsuke Iida
Indoleamine 2,3-dioxygenase 1 (IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway. The purpose of the present study was to determine the clinical significance of Trp catabolism in newly-diagnosed Hodgkin Lymphoma (HL) patients. We quantified serum Trp and Kyn in 52 HL patients, and analyzed their associations with different clinical parameters including serum soluble CD30 (sCD30) concentration. IDO expression was evaluated in the patients' affected lymph nodes. The enrolled patients comprised 22 males and 30 females (age range 15-81, median 45 years), with a 5-year overall survival (OS) of 88...
October 28, 2017: Cancer Science
https://www.readbyqxmd.com/read/29077243/dual-inhibition-of-the-mtorc1-and-mtorc2-signaling-pathways-is-a-promising-therapeutic-target-for-adult-t-cell-leukemia
#13
Takahito Kawata, Kohei Tada, Masayuki Kobayashi, Takashi Sakamoto, Yoko Takiuchi, Fumie Iwai, Maki Sakurada, Masakatsu Hishizawa, Kotaro Shirakawa, Keisuke Shindo, Hironori Sato, Akifumi Takaori-Kondo
ATL has a poor prognosis due to severe immunosuppression and rapid tumor progression with resistance to conventional chemotherapy. Recent integrated-genome analysis has revealed mutations in many genes involved in the T-cell signaling pathway, suggesting that the aberration of this pathway is an important factor in ATL pathogenesis and ATL-cell proliferation. We screened a siRNA library to examine signaling-pathway functionality and found that the PI3K/Akt/mTOR pathway is critical to ATL-cell proliferation...
October 27, 2017: Cancer Science
https://www.readbyqxmd.com/read/29059496/increased-th17-cell-differentiation-mediated-by-exosome-mediated-mir-451-re-distribution-in-gastric-cancer-infiltrated-t-cells
#14
Feng Liu, Zhouyan Bu, Feng Zhao, Daping Xiao
miR-451 is a cell metabolism related miRNA which can mediate cell energy consuming models by several targets. Since miR-451 can promote mTOR activity, and the increased mTOR activity was related to increased differentiation of Th17 cells, we sought to investigate whether miR-451 can re-distributed from cancer cells to infiltrated T cells and enhance the distribution of Th17 cells through mTOR. Real-time PCR was used for detecting the expression of miR-451 in gastric cancer, tumor infiltrated T cell and exosome, the distribution of Th17 was evaluated by both flow cytometry and immunohistochemistry...
October 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/29059492/a-phase-1-study-of-single-agent-ribociclib-in-japanese-patients-with-advanced%C3%A2-solid%C3%A2-tumors
#15
Toshihiko Doi, Becker Hewes, Tomoyuki Kakizume, Takeshi Tajima, Norifumi Ishikawa, Yasuhide Yamada
The cyclin D-CDK4/6-INK4-Rb pathway is frequently dysregulated in cancers. Ribociclib, an orally available, selective CDK4/6 inhibitor, demonstrated preliminary clinical activity in a phase 1 study in the United States and Europe for patients with solid tumors and lymphomas. The present study aimed to determine the single-agent maximum tolerated dose (MTD) and recommended dose for expansion (RDE) in Japanese patients with advanced solid tumors. Ribociclib safety, tolerability, pharmacokinetic profile, and preliminary antitumor activity were also assessed...
October 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/29058817/dasatinib-cessation-after-deep-molecular-response-exceeding-2-years-and-nk-cell-transition-during-dasatinib-consolidation
#16
Takashi Kumagai, Chiaki Nakaseko, Kaichi Nishiwaki, Chikashi Yoshida, Kazuteru Ohashi, Naoki Takezako, Hina Takano, Yasuji Kouzai, Tadashi Murase, Kosei Matsue, Satoshi Morita, Junichi Sakamoto, Hisashi Wakita, Hisashi Sakamaki, Koiti Inokuchi
Tyrosine kinase inhibitors (TKIs) improve the prognosis of patients with chronic myelogenous leukemia (CML) by inducing substantial deep molecular responses (DMRs); some patients could successfully discontinue TKI therapy after maintaining DMR for ≥1 year. In this cessation study, we investigated the optimal conditions for dasatinib discontinuation in patients who maintained DMR for ≥2 years. This study included 54 patients with CML who were enrolled in D-STOP multicenter prospective trial, had achieved DMR, and had discontinued dasatinib after 2-year consolidation...
October 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/29055056/everolimus-in-advanced-progressive-well-differentiated-non-functional-neuroendocrine-tumors-radiant-4-lung-subgroup-analysis
#17
Nicola Fazio, Roberto Buzzoni, Gianfranco Delle Fave, Margot E Tesselaar, Edward Wolin, Eric Van Cutsem, Paolo Tomassetti, Jonathan Strosberg, Maurizio Voi, Lida Bubuteishvili-Pacaud, Antonia Ridolfi, Fabian Herbst, Jiri Tomasek, Simron Singh, Marianne Pavel, Matthew H Kulke, Juan W Valle, James C Yao
In the phase III RADIANT-4 study, everolimus improved median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated (grade 1 or grade 2), non-functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.67; P < .00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT-4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care...
October 21, 2017: Cancer Science
https://www.readbyqxmd.com/read/29047188/the-predictive-value-of-brca1-2-mrna-expression-for-response-to-neoadjuvant-chemotherapy-in-brca-negative-breast-cancers
#18
Ye Xu, Tao Ouyang, Jinfeng Li, Tianfeng Wang, Zhaoqing Fan, Tie Fan, Benyao Lin, Yuntao Xie
It is well known that BRCA1 and BRCA2 play a central role in DNA repair, but the relationship between BRCA1 and BRCA2 mRNA expression and response to neoadjuvant chemotherapy in sporadic breast cancer patients has not been well established. Here, we investigate the association between BRCA1 or BRCA2 mRNA expression levels and pathological response in 674 BRCA1/2 mutation-negative breast cancer patients who received neoadjuvant chemotherapy. BRCA1and BRCA2 mRNA expression were assessed using quantitative real-time polymerase chain reaction in core biopsy breast cancer tissue obtained prior to the initiation of neoadjuvant chemotherapy...
October 19, 2017: Cancer Science
https://www.readbyqxmd.com/read/29034589/involvement-of-local-renin-angiotensin-system-in-immunosuppression-of-tumor-microenvironment
#19
Kenta Nakamura, Tomonori Yaguchi, Gaku Ohmura, Asuka Kobayashi, Naoshi Kawamura, Takashi Iwata, Yukiko Kiniwa, Ryuhei Okuyama, Yutaka Kawakami
To improve the current cancer immunotherapies, strategies to modulate various immunosuppressive cells including myeloid derived suppressor cells (MDSCs) which were shown to be negative factors in the immune-checkpoint blockade therapy, need to be developed. In this study, we have evaluated the role of local renin-angiotensin system (RAS) in the tumor immune-microenvironment using murine models bearing tumor cell lines in which RAS was not involved in their proliferation and angiogenetic ability. Administration of angiotensin II receptor blockers (ARBs) to C57BL/6 mice bearing murine colon cancer cell line MC38 resulted in significant enhancement of tumor antigen gp70 specific T cells...
October 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/29034543/pd-l1-expression-is-mainly-regulated-by-ifn-%C3%AE-associated-with-jak-stat-pathway-in-gastric-cancer
#20
Kousaku Mimura, Jun Liang Teh, Hirokazu Okayama, Kensuke Shiraishi, Ley-Fang Kua, Vivien Koh, Duane T Smoot, Hassan Ashktorab, Takahiro Oike, Yoshiyuki Suzuki, Zul Fazreen, Bernadette R Asuncion, Asim Shabbir, Wei-Peng Yong, Jimmy So, Richie Soong, Koji Kono
Despite multidisciplinary treatment for patients with advanced gastric cancer, their prognosis still remains poor. Therefore, the development of novel therapeutic strategies is urgently needed, and immunotherapy utilizing anti-programmed death 1/-programmed death ligand-1 mAb is an attractive approach. However, as there is limited information on how programmed death ligand-1 is upregulated on tumor cells within the tumor microenvironment, we examined the mechanism of programmed death ligand-1 regulation with a particular focus on interferon gamma in in-vitro setting and in clinical samples...
October 16, 2017: Cancer Science
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