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Cancer Science

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https://www.readbyqxmd.com/read/28544544/insulin-like-growth-factor-1-signaling-is-responsible-for-cathepsin-g-induced-aggregation-of-breast-cancer-mcf-7-cells
#1
Riyo Morimoto-Kamata, Satoru Yui
Cathepsin G (CG), a neutrophil serine protease, induces cell migration and multicellular aggregation of human breast cancer MCF-7 cells in a process that is dependent on E-cadherin and CG enzymatic activity. While these tumor cell aggregates can cause tumor emboli that could represent intravascular growth and extravasation into the surrounding tissues, resulting in metastasis, the molecular mechanism underlying this process remains poorly characterized. In this study, we aimed to identify the signaling pathway that is triggered during CG-mediated stimulation of cell aggregation...
May 24, 2017: Cancer Science
https://www.readbyqxmd.com/read/28544233/bcl6-overexpression-alters-gene-expression-profile-in-a-myeloma-cell-line-and-is-associated-with-decreased-dna-damage-response
#2
Kenichi Tahara, Makiko Takizawa, Arito Yamane, Yohei Osaki, Takuma Ishizaki, Takeki Mitsui, Akihiko Yokohama, Takayuki Saitoh, Norifumi Tsukamoto, Morio Matsumoto, Hirokazu Murakami, Yoshihisa Nojima, Hiroshi Handa
BCL6 attenuates DNA damage response (DDR) through gene repression and facilitates tolerance to genomic instability during immunoglobulin affinity maturation in germinal center (GC) B cells. Although BCL6 expression is repressed through normal differentiation of GC B cells into plasma cells, a recent study showed the ectopic expression of BCL6 in primary multiple myeloma (MM) cells. However, the functional roles of BCL6 in MM cells are largely unknown. Here, we report that overexpression of BCL6 in a MM cell line, KMS12PE, induced transcriptional repression of ataxia telangiectasia mutated (ATM), a DDR signaling kinase, which was associated with a reduction in γH2AX formation after DNA damage...
May 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28514062/locoregional-therapy-with-%C3%AE-emitting-trastuzumab-against-peritoneal-metastasis-of-her2-positive-gastric-cancer-in-mice
#3
Huizi Keiko Li, Yukie Morokoshi, Kotaro Nagatsu, Tadashi Kamada, Sumitaka Hasegawa
Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found however that locoregionally administered trastuzumab armed with a radionuclide astatine-211 ((211) At)-emitting α-particle ((211) At-trastuzumab) is effective against HER2-positive PMGC in a xenograft mouse model. We first observed that (211) At-trastuzumab can specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2-positive human metastatic GC cells, both in vitro and in subcutaneous tumors...
May 17, 2017: Cancer Science
https://www.readbyqxmd.com/read/28502111/asap3-upregulation-contributes-to-colorectal-carcinogenesis-and-indicates-poor-survival-outcome
#4
Haiying Tian, Jin Qian, Luoyan Ai, Yueyuan Li, Wenyu Su, Xian-Ming Kong, Jie Xu, Jing-Yuan Fang
The function and clinical implication of ArfGAP With SH3 Domain, Ankyrin Repeat And PH Domain 3 (ASAP3) in colorectal cancer (CRC) remains undefined. In the present study, we showed that the expression level of ASAP3 was dramatically increased in CRC and its upregulation was associated with American Joint Committee on Cancer (AJCC) stage (P<0.001) and poor prognosis (P=0.0022). The combination of AJCC stage and ASAP3 expression improved the prediction of survival in CRC patients. Suppression of ASAP3 inhibited cell proliferation by inducing G1-phase arrest without influencing apoptosis...
May 14, 2017: Cancer Science
https://www.readbyqxmd.com/read/28502078/dyrk2-is-a-suppressor-and-potential-prognostic-marker-for-liver-metastasis-of-colorectal-cancer
#5
Daisuke Ito, Satomi Yogosawa, Rei Mimoto, Shinichi Hirooka, Takashi Horiuchi, Ken Eto, Katsuhiko Yanaga, Kiyotsugu Yoshida
Colorectal cancer is a common cancer and a leading cause of cancer-related death worldwide. The liver is a dominant metastatic site for patients with colorectal cancer. Molecular mechanisms that allow colorectal cancer cells to form liver metastases are largely unknown. Activation of epithelial-mesenchymal-transition (EMT) is the key step for metastasis of cancer cells. We have recently demonstrated in breast cancer and ovarian serous adenocarcinoma that dual-specificity tyrosine-regulated kinase 2 (DYRK2) controls EMT...
May 14, 2017: Cancer Science
https://www.readbyqxmd.com/read/28498637/%C3%AE-2-ar-activation-induces-chemoresistance-by-modulating-p53-acetylation-through-upregulating-sirt1-in-cervical-cancer-cells
#6
Hongyu Chen, Wei Zhang, Xiang Cheng, Liang Guo, Shuai Xie, Yuanfang Ma, Ning Guo, Ming Shi
It has been suggested that β2-adrenergic receptor (β2-AR)-mediated signaling induced by catecholamines regulates the degradation of p53. However, the underlying molecular mechanisms were not known. In the present study, we demonstrated that catecholamines upregulated the expression of silent information regulator 1 (Sirt1) through activating β2-AR-mediated signaling pathway, since selective β2-AR antagonist ICI 118, 551 and non-selective β-blocker proprenolol effectively repressed isoproterenol (ISO)-induced Sirt1 expression...
May 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28498618/phase-i-clinical-trial-of-cell-division-associated-1-cdca1-peptide-vaccination-for-castration-resistant-prostate-cancer
#7
Wataru Obara, Fuminori Sato, Kazuyoshi Takeda, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata, Hiromitsu Mimata, Tamotsu Sugai, Yusuke Nakamura, Tomoaki Fujioka
We screened cell division associated 1 (CDCA1) as an oncogene that is overexpressed on several cancers, including prostate cancer. We also identified a highly immunogenic HLA-A*2402-restricted epitope peptide corresponding to part of the CDCA1 protein. We conducted a phase I clinical trial for patients with castration resistant prostate cancer (CRPC) using a CDCA1 peptide vaccination. Twelve patients having HLA-A*2402 with CRPC after failure of docetaxel chemotherapy were enrolled. They received subcutaneous administration of the CDCA1 peptide as an emulsion with Montanide ISA51VG once a week in a dose-escalation manner (doses of 1...
May 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28498550/hbx-protein-mediated-atoh1-downregulation-suppresses-arid2-expression-and-promotes-hepatocellular-carcinoma
#8
Qingzhu Gao, Kai Wang, Ke Chen, Li Liang, Yaqiu Zheng, Yunzhi Zhang, Jin Xiang, Ni Tang
Hepatitis B virus X protein plays a crucial role in the pathogenesis of hepatocellular carcinoma. We previously showed that the tumor suppressor ARID2 inhibits hepatoma cell cycle progression and tumor growth. Here, we evaluated whether hepatitis B virus X protein was involved in the modulation of ARID2 expression and hepatocarcinogenesis associated with hepatitis B virus infection. ARID2 expression was downregulated in HBV-replicative hepatoma cells, HBV transgenic mice, and HBV-related clinical HCC tissues...
May 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28498513/saha-sensitizes-neuroblastoma-to-paclitaxel-by-inhibiting-trp14-mediated-autophagy
#9
Zijun Zhen, Kaibin Yang, Litong Ye, Zhiyao You, Rirong Chen, Ying Liu, Youjian He
Paclitaxel is not as effective for neuroblastoma as most of the front-line chemotherapeutics due to drug resistance. This study explored the regulatory mechanism of paclitaxel-associated autophagy and potential solutions to paclitaxel resistance in neuroblastoma. The formation of autophagic vesicles was detected by scanning transmission electron microscopy and flow cytometry. The autophagy-associated proteins were assessed by western blot. Autophagy was induced and the autophagy-associated proteins LC3-I, LC3-II, Beclin 1, and thioredoxin-related protein 14 (TRP14), were found to be up-regulated in neuroblastoma cells that were exposed to paclitaxel...
May 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28498503/p62-sqstm1-as-an-oncotarget-mediates-cisplatin-resistance-through-activating-rip1-nf-%C3%AE%C2%BAb-pathway-in-human-ovarian-cancer-cells
#10
Xiao-Yu Yan, Yu Zhang, Juan-Juan Zhang, Li-Chao Zhang, Ya-Nan Liu, Yao Wu, Ya-Nan Xue, Sheng-Yao Lu, Jing Su, Lian-Kun Sun
Platinum-based therapeutic strategies have been widely used in ovarian cancer treatment. However, drug resistance has greatly limited therapeutic efficacy. Recently, tolerance to cisplatin has been attributed to other factors unrelated to DNA. p62 (also known as SQSTM1) functions as a multifunctional hub participating in tumorigenesis and may be a therapeutic target. Our previous study showed that p62 was overexpressed in drug-resistant ovarian epithelial carcinoma and its inhibition increased the sensitivity to cisplatin...
May 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28474864/the-impact-of-met-inhibition-on-small-cell-lung-cancer-cells-exhibiting-aberrant-activation-of-the-hgf-met-pathway
#11
Hirokazu Taniguchi, Tadaaki Yamada, Shinji Takeuchi, Sachiko Arai, Koji Fukuda, Shuichi Sakamoto, Manabu Kawada, Hiroyuki Yamaguchi, Hiroshi Mukae, Seiji Yano
Small-cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers, and is characterized as being extremely aggressive, often displaying rapid tumor growth and multiple organ metastases. In addition, the clinical outcome of SCLC patients is poor due to early relapse and acquired resistance to standard chemotherapy treatments. Hence, novel therapeutic strategies for the treatment of SCLC are urgently required. Accordingly, several molecular targeted therapies were evaluated in SCLC; however, they failed to improve the clinical outcome...
May 5, 2017: Cancer Science
https://www.readbyqxmd.com/read/28474808/ttf-1-regulated-mir-532-5p-targets-kras-and-mkl2-oncogenes-and-induces-apoptosis-in-lung-adenocarcinoma-cells
#12
Sebastian Griesing, Taisuke Kajino, Mei Chee Tai, Zhuoran Liu, Masahiro Nakatochi, Yukako Shimada, Motoshi Suzuki, Takashi Takahashi
Thyroid transcription factor-1 (TTF-1), also known as NKX2-1, plays a role as a lineage-survival oncogene in lung adenocarcinoma that possesses double-edged sword characteristics. Although evidence from previous studies has steadily accumulated regarding the roles of TTF-1 in transcriptional regulation of protein-coding genes, little is known about its regulatory relationship with miRNAs. Here, we utilized an integrative approach designed to extract maximal information from expression profiles of both patient tumors in vivo and TTF-1-inducible cell lines in vitro, which identified miR-532-5p as a novel transcriptional target of TTF-1...
May 5, 2017: Cancer Science
https://www.readbyqxmd.com/read/28474805/cldn8-an-androgen-regulated-gene-promotes-prostate-cancer-cell-proliferation-and-migration
#13
Daisaku Ashikari, Kenichi Takayama, Daisuke Obinata, Satoru Takahashi, Satoshi Inoue
The proliferation of prostate cancer cells is controlled by androgen receptor (AR) signaling pathway. However, the function of AR target genes has not been fully elucidated. In the previous studies, we have identified global AR binding sites (ARBSs) and AR target genes in prostate cancer cells. Here, we focused on Claudin 8 (CLDN8), a protein constituting tight junction in cell membrane. We found one ARBS in the promoter region and two functional androgen-responsive elements (AREs) in the sequence. Reporter assay demonstrated transcriptional activation of the CLDN8 promoter by androgen is dependent on these AREs...
May 5, 2017: Cancer Science
https://www.readbyqxmd.com/read/28474802/rapid-and-sensitive-detection-of-ugt1a1-polymorphisms-associated-with-irinotecan-toxicity-by-a-novel-dna-microarray
#14
Ryouichi Tsunedomi, Shoichi Hazama, Naoko Okayama, Masaaki Oka, Hiroaki Nagano
Recent developments in the field of human genomics have greatly enhanced the potential for precision and personalized medicine. We have developed a novel DNA microarray, using a 3-mm square chip coated with diamond-like carbon to enhance the signal-to-background ratio, for use as an in vitro diagnostic tool in precision medicine. To verify the genotyping effectiveness of this newly developed DNA microarray we examined UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms in DNA extracted from patients with metastatic colorectal cancer...
May 5, 2017: Cancer Science
https://www.readbyqxmd.com/read/28474791/multi-institutional-retrospective-study-of-mucoepidermoid-carcinoma-treated-with-carbon-ion-radiotherapy
#15
Katsuyuki Shirai, Masashi Koto, Yusuke Demizu, Hiroaki Suefuji, Tatsuya Ohno, Hiroshi Tsuji, Tomoaki Okimoto, Yoshiyuki Shioyama, Jun-Ichi Saitoh, Kenji Nemoto, Takashi Nakano, Tadashi Kamada
To evaluate the clinical outcomes of patients with mucoepidermoid carcinomas in the head and neck treated with carbon-ion radiotherapy. Data from 26 patients who underwent carbon-ion radiotherapy in four facilities were analyzed in this multi-institutional retrospective study: the Japan Carbon-ion Radiation Oncology Study Group (J-CROS). The median follow-up time was 34 months. One patient experienced local recurrence, and the 3-year local control rate was 95%. One patient developed lymph node recurrence and five developed distant metastases...
May 5, 2017: Cancer Science
https://www.readbyqxmd.com/read/28474758/atp-p2y2-%C3%AE-catenin-axis-promotes-cell-invasion-in-breast-cancer-cells
#16
Jiang-Lan Zhang, Ying Liu, Hui Yang, Hong-Quan Zhang, Xin-Xia Tian, Wei-Gang Fang
Extracellular ATP, secreted by living cancer cells or released by necrotic tumor cells, plays an important role in tumor invasion and metastasis. Our previous study demonstrated that ATP treatment in vitro could promote invasion in human prostate cancer cells via P2Y2, a preferred receptor for ATP, by enhancing EMT process. However, the pro-invasion mechanisms of ATP and P2Y2 are still poorly studied in breast cancer. In this study, we found that P2Y2 was highly expressed in breast cancer cells and associated with human breast cancer metastasis...
May 5, 2017: Cancer Science
https://www.readbyqxmd.com/read/28474753/pathological-features-of-triple-negative-breast-cancers-that-showed-progressive-disease-during-neoadjuvant-chemotherapy
#17
Yuko Tanabe, Hitoshi Tsuda, Masayuki Yoshida, Mayu Yunokawa, Kan Yonemori, Chikako Shimizu, Seiichiro Yamamoto, Takayuki Kinoshita, Yasuhiro Fujiwara, Tamura Kenji
Clinical progressive disease (cPD) occurs during neoadjuvant chemotherapy (NAC) in 3-5% of triple-negative breast cancer (TNBC) patients. We aimed to identify the histopathological and immunohistochemical parameters that are correlated with the TNBC that showed cPD. We identified 22 TNBCs that showed cPD during NAC (cPD group) and 80 TNBCs that did not receive NAC (control group). Using surgically resected tumor specimens, we performed histopathologic examinations and immunohistochemical analysis of 11 molecules that appeared relevant to epithelial-mesenchymal transition (EMT), and basal-like, molecular apocrine and other features...
May 5, 2017: Cancer Science
https://www.readbyqxmd.com/read/28445002/glucose-metabolism-targeting-therapy-and-withaferin-a-are-effective-for-egfr-tki-induced-drug-tolerant-persisters
#18
Kei Kunimasa, Tatsuya Nagano, Yohei Shimono, Ryota Dokuni, Tatsunori Kiriu, Shuntaro Tokunaga, Daisuke Tamura, Masatsugu Yamamoto, Motoko Tachihara, Kazuyuki Kobayashi, Miyako Satouchi, Yoshihiro Nishimura
In pathway-targeted cancer drug therapies, the relatively rapid emergence of drug-tolerant persisters (DTPs) substantially limits the overall therapeutic benefit. However, little is known about the roles of DTPs in drug resistance. In this study, we investigated the features of EGFR-TKI induced DTPs and explored a new treatment strategy to overcome the emergence of these DTPs. We used two EGFR mutated lung adenocarcinoma cell lines, PC9 and II-18. They were treated with 2 μM gefitinib for 6, 12, or 24 days or 6 month...
April 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28444967/co-delivery-of-microrna-21-antisense-oligonucleotides-and-gemcitabine-using-nanomedicine-for-pancreatic-cancer-therapy
#19
Yaqing Li, Yinting Chen, Jiajia Li, Zuoquan Zhang, Chumei Huang, Guoda Lian, Kege Yang, Shaojie Chen, Ying Lin, Lingyun Wang, Kaihong Huang, Linjuan Zeng
Tumor metastasis occurs naturally in pancreatic cancer, and the efficacy of chemotherapy is usually poor. Precision medicine, combining down-regulation of target genes with chemotherapy drugs, is expected to improve the therapeutic effects. Therefore, we developed a combined therapy of microRNA-21 antisense oligonucleotides (ASO-miR-21) and Gemcitabine (Gem) using a targeted co-delivery nanoparticle (NP) carrier and investigated the synergistic inhibitory effects on pancreatic cancer cells metastasis and growth...
April 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28440963/clinical-sequencing-using-a-next-generation-sequencing-based-multiplex-gene-assay-in-patients-with-advanced-solid-tumors
#20
Tadayuki Kou, Masashi Kanai, Yoshihiro Yamamoto, Mayumi Kamada, Masahiko Nakatsui, Tomohiro Sakuma, Hiroaki Mochizuki, Akinori Hiroshima, Aiko Sugiyama, Eijiro Nakamura, Hidehiko Miyake, Sachiko Minamiguchi, Kyoichi Takaori, Shigemi Matsumoto, Hironori Haga, Hiroshi Seno, Shinji Kosugi, Yasushi Okuno, Manabu Muto
Advances in next-generation sequencing (NGS) technologies have enabled physicians to test for genomic alterations in multiple cancer-related genes at once in daily clinical practice. In April 2015, we introduced clinical sequencing using an NGS-based multiplex gene assay (OncoPrime) certified by the Clinical Laboratory Improvement Amendment. This assay covers the entire coding regions of 215 genes and the rearrangement of 17 frequently rearranged genes with clinical relevance in human cancers. The principal indications for the assay were cancers of unknown primary site, rare tumors, and any solid tumors that were refractory to standard chemotherapy...
April 25, 2017: Cancer Science
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