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981.
NET‐producing CD16high CD62Ldim neutrophils migrate to tumor sites and predict improved survival in patients with HNSCC 下载免费PDF全文
Camilla Rydberg Millrud Åsa Kågedal Susanna Kumlien Georén Ola Winqvist Rolf Uddman Ronia Razavi Eva Munck‐Wikland Lars Olaf Cardell 《International journal of cancer. Journal international du cancer》2017,140(11):2557-2567
The concept of functional neutrophil subsets is new and their clinical significance in malignancies is unknown. Our study investigated the role of CD16dim CD62Lhigh, CD16high CD62Lhigh and CD16high CD62Ldim neutrophil subsets in head and neck squamous cell carcinoma (HNSCC) patients. These neutrophil subsets may play different roles in immune‐related activity in cancer, based on their profile, activation state and migration ability within a tumor site, which may be important in predicting cancer prognoses. Tumor biopsies and blood were obtained from newly diagnosed untreated HNSCC patients and healthy controls. Neutrophil subsets and their phenotype were characterized using flow cytometry. Isolated granulocytes were assessed for anti‐tumor immune functions. Compared to controls HNSCC patients exhibited increased CD16high CD62Ldim neutrophils in blood; this subset displayed a distinct phenotypes with high expression of CD11b and CD18. This subset was prone to migrate into the tumor facilitated by tumor‐derived IL‐8. Furthermore, IL‐8 was also found to activate neutrophils and thereby promoting subset transition. Various assays demonstrated that activated CD16high CD62Ldim neutrophils inhibited migration, proliferation and induced apoptosis of FaDu cancer cells. Neutrophil elastase detected in activated CD16high CD62Ldim neutrophils and tumor biopsies suggested that CD16high CD62Ldim neutrophils impart anti‐tumoral activity via neutrophil extracellular traps. Furthermore, increased fraction of CD16high CD62Ldim neutrophils was shown to correlate with an increased survival rate. Our study demonstrates the clinical relevance of the CD16high CD62Ldim neutrophil subset, providing evidence for its increased migration capacity, its anti‐tumor activity including increased NET formation and finally its correlation with increased survival in HNSCC patients. 相似文献
982.
Metabolomics and transcriptomics profiles reveal the dysregulation of the tricarboxylic acid cycle and related mechanisms in prostate cancer 下载免费PDF全文
Hai‐Long Piao Xinjie Zhao Xin Lu Fubo Wang Wang Ma Jia Li Peiyuan Yin Tian Xia Chuanliang Xu Jane J. Yu Yinghao Sun Guowang Xu 《International journal of cancer. Journal international du cancer》2018,143(2):396-407
Genetic alterations drive metabolic reprograming to meet increased biosynthetic precursor and energy demands for cancer cell proliferation and survival in unfavorable environments. A systematic study of gene‐metabolite regulatory networks and metabolic dysregulation should reveal the molecular mechanisms underlying prostate cancer (PCa) pathogenesis. Herein, we performed gas chromatography–mass spectrometry (GC–MS)‐based metabolomics and RNA‐seq analyses in prostate tumors and matched adjacent normal tissues (ANTs) to elucidate the molecular alterations and potential underlying regulatory mechanisms in PCa. Significant accumulation of metabolic intermediates and enrichment of genes in the tricarboxylic acid (TCA) cycle were observed in tumor tissues, indicating TCA cycle hyperactivation in PCa tissues. In addition, the levels of fumarate and malate were highly correlated with the Gleason score, tumor stage and expression of genes encoding related enzymes and were significantly related to the expression of genes involved in branched chain amino acid degradation. Using an integrated omics approach, we further revealed the potential anaplerotic routes from pyruvate, glutamine catabolism and branched chain amino acid (BCAA) degradation contributing to replenishing metabolites for TCA cycle. Integrated omics techniques enable the performance of network‐based analyses to gain a comprehensive and in‐depth understanding of PCa pathophysiology and may facilitate the development of new and effective therapeutic strategies. 相似文献
983.
Novel oral transforming growth factor‐β signaling inhibitor EW‐7197 eradicates CML‐initiating cells 下载免费PDF全文
Kazuhito Naka Kaori Ishihara Yoshie Jomen Cheng Hua Jin Dong‐Hyun Kim Yoon‐Kang Gu Eun‐Sook Jeong Shaoguang Li Daniela S. Krause Dong‐Wook Kim Eunjin Bae Yoshihiro Takihara Atsushi Hirao Hiroko Oshima Masanobu Oshima Akira Ooshima Yhun Yhong Sheen Seong‐Jin Kim Dae‐Kee Kim 《Cancer science》2016,107(2):140-148
Recent strategies for treating CML patients have focused on investigating new combinations of tyrosine kinase inhibitors (TKIs) as well as identifying novel translational research agents that can eradicate CML leukemia‐initiating cells (CML‐LICs). However, little is known about the therapeutic benefits such CML‐LIC targeting therapies might bring to CML patients. In this study, we investigated the therapeutic potential of EW‐7197, an orally bioavailable transforming growth factor‐β signaling inhibitor which has recently been approved as an Investigational New Drug (NIH, USA), to suppress CML‐LICs in vivo. Compared to TKI treatment alone, administration of TKI plus EW‐7197 to CML‐affected mice significantly delayed disease relapse and prolonged survival. Notably, combined treatment with EW‐7197 plus TKI was effective in eliminating CML‐LICs even if they expressed the TKI‐resistant T315I mutant BCR‐ABL1 oncogene. Collectively, these results indicate that EW‐7197 may be a promising candidate for a new therapeutic that can greatly benefit CML patients by working in combination with TKIs to eradicate CML‐LICs. 相似文献
984.
DNA methylation changes measured in pre‐diagnostic peripheral blood samples are associated with smoking and lung cancer risk 下载免费PDF全文
Allison Hodge Manuela Bianca Assumma Chol‐Hee Jung Jessica Chung Francesca Fasanelli Florence Guida Gianluca Campanella Marc Chadeau‐Hyam Kjell Grankvist Mikael Johansson Ugo Ala Paolo Provero Ee Ming Wong Jihoon Joo Dallas R. English Nabila Kazmi Eiliv Lund Christian Faltus Rudolf Kaaks Angela Risch Myrto Barrdahl Torkjel M. Sandanger Melissa C. Southey Graham G. Giles Mattias Johansson Paolo Vineis Gianluca Severi 《International journal of cancer. Journal international du cancer》2017,140(1):50-61
DNA methylation changes are associated with cigarette smoking. We used the Illumina Infinium HumanMethylation450 array to determine whether methylation in DNA from pre‐diagnostic, peripheral blood samples is associated with lung cancer risk. We used a case‐control study nested within the EPIC‐Italy cohort and a study within the MCCS cohort as discovery sets (a total of 552 case‐control pairs). We validated the top signals in 429 case‐control pairs from another 3 studies. We identified six CpGs for which hypomethylation was associated with lung cancer risk: cg05575921 in the AHRR gene (p‐valuepooled = 4 × 10?17), cg03636183 in the F2RL3 gene (p‐valuepooled = 2 × 10 ? 13), cg21566642 and cg05951221 in 2q37.1 (p‐valuepooled = 7 × 10?16 and 1 × 10?11 respectively), cg06126421 in 6p21.33 (p‐valuepooled = 2 × 10?15) and cg23387569 in 12q14.1 (p‐valuepooled = 5 × 10?7). For cg05951221 and cg23387569 the strength of association was virtually identical in never and current smokers. For all these CpGs except for cg23387569, the methylation levels were different across smoking categories in controls (p‐valuesheterogeneity ≤ 1.8 x10 ? 7), were lowest for current smokers and increased with time since quitting for former smokers. We observed a gain in discrimination between cases and controls measured by the area under the ROC curve of at least 8% (p‐values ≥ 0.003) in former smokers by adding methylation at the 6 CpGs into risk prediction models including smoking status and number of pack‐years. Our findings provide convincing evidence that smoking and possibly other factors lead to DNA methylation changes measurable in peripheral blood that may improve prediction of lung cancer risk. 相似文献
985.
FGF‐1/‐3/FGFR4 signaling in cancer‐associated fibroblasts promotes tumor progression in colon cancer through Erk and MMP‐7 下载免费PDF全文
Yu‐Pan Bai Kun Shang Huan Chen Fei Ding Zhen Wang Chen Liang Ye Xu Meng‐Hong Sun Ying‐Yi LI 《Cancer science》2015,106(10):1278-1287
Cancer‐associated fibroblasts (CAFs), as the activated fibroblasts in the tumor stroma, are important modifiers of tumour progression. In the present study, we observed that azoxymethane and dextran sodium sulfate treatments induced increasingly severe colorectal mucosal inflammation and the intratumoural accumulation of CAFs. Fibroblast growth factor (FGF)‐1 and FGF‐3 were detected in infiltrating cells, and FGFR4, the specific receptor for FGF‐1 and FGF‐3, was detected in colon cancer tissues. The phosphorylation of FGFR4 enhanced the production of metalloproteinase (MMP)‐7 and mitogen‐activated protein kinase kinase (Mek)/extracellular signal‐regulated kinase (Erk), which was accompanied by excessive vessel generation and cell proliferation. Moreover, we separated CAFs, pericarcinoma fibroblasts (PFs), and normal fibroblasts (NFs) from human colon tissue specimens to characterize the function of CAFs. We observed that CAFs secrete more FGF‐1/‐3 than NFs and PFs and promote cancer cell growth and angiogenesis through the activation of FGFR4, which is followed by the activation of Mek/Erk and the modulation of MMP‐7 expression. The administration of FGF‐1/‐3‐neutralizing antibodies or the treatment of cells with FGFR4 siRNA or the FGFR4 inhibitor PD173074 markedly suppressed colon cancer cell proliferation and neovascularization. These observations suggest a crucial role for CAFs and FGF signaling in the initiation and progression of colorectal cancer. The inhibition of the FGF signaling pathway may be a useful strategy for the treatment of colon cancer. 相似文献
986.
Implementation of the Edmonton Symptom Assessment System for Symptom Distress Screening at a Community Cancer Center: A Pilot Program 下载免费PDF全文
987.
Does a Higher Cutoff Value of Lymph Node Retrieval Substantially Improve Survival in Patients With Advanced Gastric Cancer?—Time to Embrace a New Digit 下载免费PDF全文
988.
CD10 down expression in follicular lymphoma correlates with gastrointestinal lesion involving the stomach and large intestine 下载免费PDF全文
Nobuhiko Ohnishi Katsuyoshi Takata Tomoko Miyata‐Takata Yasuharu Sato Akira Tari Yuka Gion Mai Noujima‐Harada Kohei Taniguchi Tetsuya Tabata Keina Nagakita Shizuma Omote Hiroyuki Takahata Masaya Iwamuro Hiroyuki Okada Yoshinobu Maeda Hiroyuki Yanai Tadashi Yoshino 《Cancer science》2016,107(11):1687-1695
Follicular lymphoma (FL) shows co‐expression of B‐cell lymphoma 2 (BCL2) and CD10, whereas downexpression of CD10 is occasionally experienced in gastrointestinal (GI) FL with unknown significance. Gastrointestinal FL is a rare variant of FL, and its similarity with mucosa‐associated lymphoid tissue lymphoma was reported. We investigated the clinicopathological and genetic features of CD10 downexpressed (CD10down) GI‐FL. The diagnosis of CD10down FL was carried out with a combination of pathological and molecular analyses. The incidence of CD10down GI‐FL was shown in 35/172 (20.3%) cases, which was more frequent than nodal FL (3.5%, P < 0.001). The difference was additionally significant between GI‐FL and nodal FL when the analysis was confined to primary GI‐FL (55.2% vs 3.5%, P < 0.001). Compared to CD10+ GI‐FL, CD10down GI‐FL significantly involved the stomach or large intestine (P = 0.015), and additionally showed the downexpression of BCL6 (P < 0.001). The follicular dendritic cell meshwork often showed a duodenal pattern in the CD10down group (P = 0.12). Furthermore, a lymphoepithelial lesion was observed in 5/12 (40%) gastric FL cases, which indicated caution in the differentiation of mucosa‐associated lymphoid tissue lymphoma. Molecular analyses were undertaken in seven cases of CD10down GI‐FL, and an identical clone was found between CD10down follicles and CD10+BCL2+ neoplastic follicles. In the diagnosis of cases with CD10down BCL2+ follicles, careful examination with molecular studies should be carried out. 相似文献
989.
Copy number variations in DCC/18q and ERBB2/17q are associated with disease‐free survival in microsatellite stable colon cancer 下载免费PDF全文
David Sefrioui Thomas Vermeulin France Blanchard Caroline Chapusot Ludivine Beaussire Laura Armengol‐Debeir Richard Sesboué Alice Gangloff Mohamed Hebbar Marie‐Christine Copin Estelle Houivet Lilian Schwarz Florian Clatot Jean‐Jacques Tuech Jacques Bénichou Laurent Martin Anne‐Marie Bouvier Jean‐Christophe Sabourin Nasrin Sarafan‐Vasseur Thierry Frébourg Côme Lepage Pierre Michel Frédéric Di Fiore 《International journal of cancer. Journal international du cancer》2017,140(7):1653-1661
We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in Stage II–III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end‐point was the impact of the CNVs on the 4‐year disease‐free survival (DFS). The recurrence rate at 4 years was 20.9%, corresponding to 14% Stage II patients versus 31% Stage III patients (p < 0.0001). The 4‐year DFS was significantly decreased in patients with a loss at DCC/18q (p = 0.012) and a gain at ERBB2/17q (p = 0.041). The multivariate analysis demonstrated that Stage III, a loss at DCC/18q and a gain at ERBB2/17q were independent factors associated with DFS. A combination of DCC/18q and ERBB2/17q was also associated with relapse, with the hazard ratio increasing from 1 to 2.4 (95% confidence interval (CI), 1.5–4.1) and 3.1 (95% CI, 1.2–8.4) in the presence of 0, 1 or 2 alterations, respectively (p = 0.0013). CNVs in DCC/18q and ERBB2/17q are significantly associated with DFS in Stage II–III MSS colon cancer. 相似文献
990.
Ted A. Skolarus MD MPH Andrew M.D. Wolf MD Nicole L. Erb BA Durado D. Brooks MD MPH Brian M. Rivers PhD MPH Willie Underwood III MD MPH MSci Andrew L. Salner MD Michael J. Zelefsky MD Jeanny B. Aragon‐Ching MD Susan F. Slovin MD PhD Daniela A. Wittmann PhD MSW CST Michael A. Hoyt PhD Victoria J. Sinibaldi CRNP Gerald Chodak MD Mandi L. Pratt‐Chapman MA Rebecca L. Cowens‐Alvarado MPH 《CA: a cancer journal for clinicians》2014,64(4):225-249
Answer questions and earn CME/CNE Prostate cancer survivors approach 2.8 million in number and represent 1 in 5 of all cancer survivors in the United States. While guidelines exist for timely treatment and surveillance for recurrent disease, there is limited availability of guidelines that facilitate the provision of posttreatment clinical follow‐up care to address the myriad of long‐term and late effects that survivors may face. Based on recommendations set forth by a National Cancer Survivorship Resource Center expert panel, the American Cancer Society developed clinical follow‐up care guidelines to facilitate the provision of posttreatment care by primary care clinicians. These guidelines were developed using a combined approach of evidence synthesis and expert consensus. Existing guidelines for health promotion, surveillance, and screening for second primary cancers were referenced when available. To promote comprehensive follow‐up care and optimal health and quality of life for the posttreatment survivor, the guidelines address health promotion, surveillance for prostate cancer recurrence, screening for second primary cancers, long‐term and late effects assessment and management, psychosocial issues, and care coordination among the oncology team, primary care clinicians, and nononcology specialists. A key challenge to the development of these guidelines was the limited availability of published evidence for management of prostate cancer survivors after treatment. Much of the evidence relies on studies with small sample sizes and retrospective analyses of facility‐specific and population databases. CA Cancer J Clin 2014;64:225–249. © 2014 American Cancer Society . 相似文献