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Cancer Science

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https://www.readbyqxmd.com/read/29352488/understanding-intratumor-heterogeneity-by-combining-genome-analysis-and-mathematical-modeling
#1
REVIEW
Atsushi Niida, Satoshi Nagayama, Satoru Miyano, Koshi Mimori
Cancer is composed of multiple cell populations with different genomes. Each of the populations is called a clone (or subclone) and this phenomenon is called intratumor heterogeneity (ITH). ITH is observed in various types of cancers and presumed to be a major cause leading to therapeutic resistance. If a tumor harbors a major clone sensitive to a specific anti-cancer treatment, the tumor shrinks within a given period after the treatment. However, in most cases, a minor clone resistant to the chemotherapy exists in the tumor and predominantly regrows in spite of the intensive therapy...
January 20, 2018: Cancer Science
https://www.readbyqxmd.com/read/29345859/development-of-a-risk-prediction-model-for-lung-cancer-the-japan-public-health-center-based-prospective-study
#2
Hadrien Charvat, Shizuka Sasazuki, Taichi Shimazu, Sanjeev Budhathoki, Manami Inoue, Motoki Iwasaki, Norie Sawada, Taiki Yamaji, Shoichiro Tsugane
While the impact of tobacco consumption on the occurrence of lung cancer is well-established, risk estimation could be improved by risk prediction models that consider various smoking habits, such as quantity, duration, and time since quitting. We constructed a risk prediction model using a population of 59,161 individuals from JPHC Study Cohort II. A parametric survival model was used to assess the impact of age, gender and smoking-related factors (cumulative smoking intensity measured in pack-years, age at initiation, and time since cessation)...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29345842/pd-l1-is-a-promising-blood-marker-for-predicting-tumor-progression-and-prognosis-in-patients-with-gastric-cancer
#3
Masahiko Amatatsu, Takaaki Arigami, Yoshikazu Uenosono, Shigehiro Yanagita, Yasuto Uchikado, Yuko Kijima, Hiroshi Kurahara, Yoshiaki Kita, Shinichiro Mori, Ken Sasaki, Itaru Omoto, Kosei Maemura, Sumiya Ishigami, Shoji Natsugoe
Immune checkpoint inhibitor therapy has been clinically introduced for several malignancies, and its effectiveness has been confirmed by clinical trials. In particular, programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) are widely known as important immune checkpoint molecules associated with the mechanisms of immune escape by malignant tumor cells. On the other hand, liquid biopsy of blood specimens has the clinical benefit of providing a simple, repeatable sampling tool. Non-invasive liquid biopsy has recently been spotlighted as a promising approach to predicting tumor progression and prognosis...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29345757/whole-genome-sequencing-analysis-for-cancer-genomics-and-precision-medicine
#4
REVIEW
Hidewaki Nakagawa, Masashi Fujita
Explosive advances of next-generation sequencer (NGS) and computational analyses have been exploring somatic protein-altered mutations in most cancer types and these coding mutation data are intensively accumulated. However, there is limited information on somatic mutations in non-coding regions including introns, regulatory elements, and non-coding RNAs, structural variants and pathogen in cancer genomes remain widely unexplored. Whole genome sequencing (WGS) approaches can comprehensively explore all types of genomic alterations in cancer and help us to better understand the whole landscape of driver mutations and mutational signature in cancer genomes and elucidate functional or clinical implications of these unexplored genomic regions and mutational signature...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29345737/present-status-and-future-perspective-of-peptide-based-vaccine-therapy-for-urological-cancer
#5
REVIEW
Wataru Obara, Mitsugu Kanehira, Toyomasa Katagiri, Renpei Kato, Yoichiro Kato, Ryo Takata
The use of peptide-based vaccines as therapeutics aims to elicit immune responses through antigenic epitopes derived from tumor antigens. Peptide-based vaccines are easily synthesized and the lack of significant side effects when administered in-vivo. Peptide-based vaccine therapy against several cancers including urological cancers had made progress for several decades, but there is no approval peptide vaccine all over the world. Peptides vaccines were also shown to induce a high frequency of immune response in patients who were accompanied by clinical efficacy...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29345736/palbociclib-in-combination-with-letrozole-as-first-line-treatment-for-advanced-breast-cancer-a-japanese-phase-ii-study
#6
Norikazu Masuda, Reiki Nishimura, Masato Takahashi, Kenichi Inoue, Shinji Ohno, Hiroji Iwata, Yuko Mori, Satoshi Hashigaki, Yasuaki Muramatsu, Takashi Nagasawa, Yoshiko Umeyama, Masakazu Toi
This single-arm, open-label, phase II study in 42 Japanese postmenopausal patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer evaluated the efficacy, safety, and pharmacokinetics of first-line palbociclib (125 mg once daily, 3 weeks on/1 week off) coadministered with letrozole (2.5 mg once daily). The primary endpoint of investigator-assessed 1-year progression-free survival probability was 75.0% (90% CI, 61.3%-84.4%), far surpassing the 40% lower limit of the 90% CI supporting efficacy...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29336091/drug-resistance-in-anaplastic-lymphoma-kinase-rearranged-lung-cancer
#7
Ryohei Katayama
The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, and many kinds of ALK fusion genes have been found in a variety of carcinomas. There is almost no detectable expression of ALK in adults. However, through ALK gene rearrangement, the resultant ALK fusion protein is aberrantly overexpressed and dimerized through the oligomerization domains, such as the coiled-coil domain, in the fusion partner that induce abnormal constitutive activation of ALK tyrosine kinase. This results in dysregulated cell proliferation...
January 16, 2018: Cancer Science
https://www.readbyqxmd.com/read/29325230/protocadherin8-promotes-invasion-and-metastasis-via-laminin-subunit-%C3%AE-2-in-gastric-cancer
#8
Ying Lin, Xiaoxiao Ge, Xiaofei Zhang, Zheng Wu, Kaiyi Liu, Fengjuan Lin, Congqi Dai, Weijian Guo, Jin Li
Growing evidence suggests that protocadherins (PCDHs) play crucial roles in pathogenesis and progression of cancers including gastric cancer (GC). Protocadherin8 (PCDH8) was previously reported to be involved in metastasis of GC, but functional studies yielded inconsistent results and the molecular mechanism remained unknown. This study aimed to explore the clinical relevance, function and molecular mechanism of PCDH8 in GC. Data from the GEPIA and Kaplan-Meier plotter databases showed that high expression of PCDH8 was significantly correlated with poorer prognosis in GC...
January 11, 2018: Cancer Science
https://www.readbyqxmd.com/read/29325224/hereditary-kidney-cancer-syndromes-genetic-disorders-driven-by-alterations-in-metabolism-and-epigenome-regulation
#9
Hisashi Hasumi, Masahiro Yao
Although hereditary kidney cancer syndrome accounts for around five percent of all kidney cancers, the mechanistic insight into tumor development in these rare conditions has provided the foundation for the development of molecular targeting agents currently used for sporadic kidney cancer. In the late 1980s, the comprehensive study for hereditary kidney cancer syndrome was launched in the National Cancer Institute, U.S.A. and the first kidney cancer associated gene, VHL was identified through kindred analysis of von Hippel-Lindau syndrome in 1993...
January 11, 2018: Cancer Science
https://www.readbyqxmd.com/read/29316077/cellular-stress-induces-cancer-stem-like-cells-through-expression-of-dnajb8-by-activation-of-hsf1
#10
Hiroki Kusumoto, Yoshihiko Hirohashi, Satoshi Nishizawa, Masamichi Yamashita, Kazuyo Yasuda, Aiko Murai, Akari Takaya, Takashi Mori, Terufumi Kubo, Munehide Nakatsugawa, Takayuki Kanaseki, Tomohide Tsukahara, Toru Kondo, Noriyuki Sato, Isao Hara, Toshihiko Torigoe
In a previous study, we found that DNAJB8, a heat shock protein (HSP) 40 family member is expressed in kidney cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) and that it has a role in the maintenance of kidney CSCs/CICs. Heat shock factor (HSF) 1 is a key transcription factor for responses to stress including heat shock, and it induces HSP family expression through activation by phosphorylation. In this study, we therefore examined whether heat shock (HS) induces CSCs/CICs. We treated the human kidney cancer cell line ACHN with HS, and found that HS increased side population (SP) cells...
January 8, 2018: Cancer Science
https://www.readbyqxmd.com/read/29316075/monitoring-tki-therapeutic-responses-with-the-panel-of-metabolic-biomarkers-in-the-chronic-myeloid-leukemia-patients
#11
Bingyu Yang, Chang Wang, Yiyu Xie, Liangjing Xu, Xiaojin Wu, Depei Wu
To investigate the potential biomarkers associated with Chronic Myeloid Leukemia (CML), reveal the metabolite changes related to the continuous phases of tyrosine kinase inhibitors (TKI) and find the potential biomarkers associated with treatment effects. 52 patients with CML and matched 26 healthy people were enrolled as discovery set. Another 194 randomly selected CML patients treated with TKI were chosen as external validation set. Plasma samples from the patients and controls were profiled by using gas chromatography-mass spectrometry (GC-MS) based metabonomic approach...
January 8, 2018: Cancer Science
https://www.readbyqxmd.com/read/29288563/cdc37-facilitates-cell-survival-of-colorectal-carcinoma-via-activating-the-cdk4-signaling-pathway
#12
Jianjun Zhu, Fang Yan, Jia Tao, Xiaohua Zhu, Jiayou Liu, Shishan Deng, Xiaoming Zhang
Cdc37 is an important partner for HSP90, assisting in molecular chaperone activities, particularly with regard to the regulation of protein kinases. Given its influence on cell growth pathways, Cdc37 has been discussed as a potential intermediate in carcinogenesis. However, to date, the potential functional roles and molecular mechanisms by which Cdc37 regulated cell survival remained unclear in colorectal carcinoma. Here, we investigated the expression of Cdc37 and its clinical significance in colorectal carcinoma, and systematically explored the role of Cdc37 in colorectal carcinoma cell survival both in vitro and in vivo and the underlying mechanism...
December 30, 2017: Cancer Science
https://www.readbyqxmd.com/read/29288560/dietary-acrylamide-intake-and-risk-of-breast-cancer-the-japan-public-health-center-based-prospective-study
#13
Ayaka Kotemori, Junko Ishihara, Ling Zha, Rong Liu, Norie Sawada, Motoki Iwasaki, Tomotaka Sobue, Shoichiro Tsugane
Acrylamide forms during cooking and is classified as a probable carcinogen in humans, mandating the need for epidemiological studies of dietary acrylamide and cancers. However, the risk of dietary acrylamide exposure to breast cancer in Japanese women has not been assessed. We investigated the association between dietary acrylamide intake and risk of breast cancer in the Japan Public Health Center-based Prospective Study. The present study included 48,910 women aged 45-74 years who responded to a 5-year follow-up survey questionnaire...
December 30, 2017: Cancer Science
https://www.readbyqxmd.com/read/29288540/expansion-of-human-%C3%AE-%C3%AE-t-cells-for-adoptive-immunotherapy-using-a-bisphosphonate-prodrug
#14
Yoshimasa Tanaka, Kaoru Murata-Hirai, Masashi Iwasaki, Kenji Matsumoto, Kosuke Hayashi, Asuka Kumagai, Mohanad H Nada, Hong Wang, Hirohito Kobayashi, Hiroshi Kamitakahara, Haruki Okamura, Tomoharu Sugie, Nagahiro Minato, Masakazu Toi, Craig T Morita
Cancer immunotherapy with human γδ T cells expressing Vγ2Vδ2 T cell receptor (also termed Vγ9Vδ2) has shown promise because of their ability to recognize and kill most types of tumors in an MHC-unrestricted fashion that is independent of the number of tumor mutations. In clinical trials, adoptive transfer of Vγ2Vδ2 T cells has been shown to be safe and does not require preconditioning. In this report, we describe a method for preparing highly enriched human Vγ2Vδ2 T cells using the bisphosphonate prodrug, tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino)ethylidene-1,1-bisphosphonate (PTA)...
December 30, 2017: Cancer Science
https://www.readbyqxmd.com/read/29288523/ccl5-promotes-migration-of-prostate-cancer-cells-in-the-prostate-cancer-bone-metastasis-microenvironment
#15
Satoko Urata, Kouji Izumi, Kaoru Hiratsuka, Aerken Maolake, Ariunbold Natsagdorj, Kazuyoshi Shigehara, Hiroaki Iwamoto, Suguru Kadomoto, Tomoyuki Makino, Renato Naito, Yoshifumi Kadono, Wen-Jye Lin, Guzailinuer Wufuer, Kazutaka Narimoto, Atsushi Mizokami
Chemokines and their receptors have key roles in cancer progression. This study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co-cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration-dependent promoter of LNCaP cell migration...
December 30, 2017: Cancer Science
https://www.readbyqxmd.com/read/29288516/il-6-stat3-promotes-prostate-cancer-resistance-to-androgen-deprivation-therapy-via-regulating-pttg1-expression
#16
Shengquan Huang, Qian Liu, Qianjin Liao, Qingjian Wu, Bishao Sun, Zhenxing Yang, Xiaoyan Hu, Mingjia Tan, Longkun Li
Prostate cancer can progress from androgen dependence to androgen deprivation resistance with some unknown mechanisms. The current study aims to explore the possible role of pituitary tumor transforming gene1 (PTTG1) in castration-resistant prostate cancer (CRPC). Initially, we found that PTTG1 expression was significantly increased in androgen-independent prostate cancer cell lines PC3, DU145 and CRPC specimens compared with that in androgen-dependent prostate cancer cell line LNCaP and initial prostate cancer specimens...
December 30, 2017: Cancer Science
https://www.readbyqxmd.com/read/29288515/a-third-generation-oncolytic-herpes-simplex-virus-inhibits-the-growth-of-liver-tumors-in-mice
#17
Richi Nakatake, Masaki Kaibori, Yusuke Nakamura, Yoshito Tanaka, Hideyuki Matushima, Tadayoshi Okumura, Takashi Murakami, Yasushi Ino, Tomoki Todo, Masanori Kon
Multimodality therapies are used to manage patients with hepatocellular carcinoma (HCC), although advanced HCC is incurable. Oncolytic virus therapy is probably the next major breakthrough in cancer treatment. The third-generation oncolytic herpes simplex virus type 1 (HSV-1) T-01 kills tumor cells without damaging the surrounding normal tissues. Here we investigated the antitumor effects of T-01 on HCC and the host's immune response to HCC cells. The cytopathic activities of T-01 were tested in 14 human and one murine hepatoma cell lines in vitro...
December 30, 2017: Cancer Science
https://www.readbyqxmd.com/read/29288513/immunopharmacogenomics-towards-personalized-cancer-immunotherapy-targeting-neoantigens
#18
REVIEW
Kazuma Kiyotani, Hiu Ting Chan, Yusuke Nakamura
Utilizing the host immune system to eradicate cancer cells has been the most investigated subject in the cancer research field in recent years. However, most of the studies have focused on highly variable responses from immunotherapies such as immune checkpoint inhibitors, where the majority of patients experienced no or minimum clinical benefits. Advances in genomic sequencing technologies have improved our understanding of immunopharmacogenomics and allowed us to identify novel cancer-specific immune targets...
December 30, 2017: Cancer Science
https://www.readbyqxmd.com/read/29288512/pretreatment-of-probiotic-bifico-ameliorates-colitis-associated-cancer-in-mice-transcriptome-and-gut-flora-profiling
#19
Huan Song, Weiyi Wang, Bo Shen, Hao Jia, Zhaoyuan Hou, Ping Chen, Yunwei Sun
Individuals with inflammatory bowel disease (IBD) are at a high risk for developing colitis-associated cancer (CAC). Strategies to block the process from IBD to CAC should be considered. In the experiment, we aim to explore the chemopreventive efficacy of the probiotic cocktail Bifico and its potential mechanism in azoxymethane (AOM) and dextran sodium sulphate (DSS) induced colitis-associated cancer in mice. Oral pretreatment of Bifico was adopted to evaluate its protective effect. The colorectums of thirty-five C57BL/6 mice were collected and examined for degree of inflammation and tumorigenesis...
December 30, 2017: Cancer Science
https://www.readbyqxmd.com/read/29285854/c-c-chemokine-receptor-type-1-mediates-osteopontin-promoted-metastasis-in-hepatocellular-carcinoma
#20
Ying Zhu, Xiao-Mei Gao, Jing Yang, Da Xu, Yu Zhang, Ming Lu, Ze Zhang, Yuan-Yuan Sheng, Jian-Hua Li, Xin-Xin Yu, Yan Zheng, Qiong-Zhu Dong, Lun-Xiu Qin
In hepatocellular carcinoma (HCC) microenvironment, chemokine receptors have a critical role in tumorigenesis and metastasis. Our previous studies have found that osteopontin (OPN) is a promoter for HCC metastasis. However, the role of chemokine receptors in OPN-induced HCC metastasis still remains unclear. In this study, we demonstrate that OPN is dramatically elevated in HCC tissues with metastasis and high expression of OPN correlates with poorer overall survival and higher recurrence rate. OPN upregulates chemokine receptor expression, migration, invasion, and pulmonary metastasis in HCC...
December 29, 2017: Cancer Science
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