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Sample records for ccr national cancer

  1. [Colorectal cancer (CCR): genetic and molecular alterations].

    Science.gov (United States)

    Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra

    2014-01-01

    The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

  2. Expression and significance of CCR4 and CCR7 in triple-negative breast cancer (TNBC)%三阴性乳腺癌(TNBC)组织中CCR4和CCR7的表达及意义

    Institute of Scientific and Technical Information of China (English)

    陈祥锦; 张茂泉; 张惠灏; 朱有志; 吴坤琳; 张德杰

    2012-01-01

    目的 探讨三阴性乳腺癌(triple-negative breast cancer,TNBC)组织中CC族趋化因子受体4(cc chemokine receptor 4,CCR4)和CCR7的表达意义及其与临床病理特征和预后之间的相关性.方法 应用免疫组织化学染色SP法检测TNBC、HER-2过表达型乳腺癌、TNBC癌旁组织及乳腺良性肿瘤(3组,各38例)和管腔型乳腺癌组织(40例)中CCR4和CCR7的表达.结果 在TNBC组织中,CCR4和CCR7的表达率分别为47.4% (18/38)和50%(19/38),与非TNBC组相比,差异有统计学意义(P值分别为0.001和0.004).CCR4表达与TNBC肿瘤直径(P=0.023)、腋窝淋巴结转移(P=0.006)、肿瘤分期(P=0.016)和远处转移(P=0.028)相关.Kaplan-Meier生存分析显示CCR4表达与TNBC患者总生存率(overall survival,OS)相关(P=0.018).CCR7表达和TNBC患者的腋窝淋巴结转移相关(P=0.038),而与TNBC患者无病生存率(disease free survival,DFS)和OS无关.多因素分析显示腋窝淋巴结转移是TNBC患者DFS的独立预测因素(P=0.025),而CCR4是TNBC患者OS的独立预测因素(P=0.022).结论 TNBC中CCR4和CCR7的表达与腋窝淋巴结转移相关;CCR4可作为TNBC患者预后的独立预测指标.%Objective To investigate the relationship between the expression of both CC chemokine receptor 4 (CCR4) and CCR7 and clinical pathology as well as prognosis in triple-negative breast cancer (TNBC). Methods The expression of CCR4 and CCR7 in TNBC, Her-2 over-expression breast cancer, TNBC paracancerous tissues and mammary gland benign tumor (38 cases each for the 3 groups) , and 40 cases of lumina breast cancer were assessed by immunohistochemical technology SP method. Results The positive rate of CCR4 and CCR7 in TNBC were 47. 4% (18/38) and 50% (19/38) , respectively. The difference between the expression of CCR4 and CCR7 in TNBC and that in non-TNBC showed a statistical significance (P = 0. 001 and 0. 004, respectively). The expression of CCR4 in TNBC was correlated with tumor size (P = 0. 023) , axilla

  3. CCR5 Expression Influences the Progression of Human Breast Cancer in a p53-dependent Manner

    OpenAIRE

    2003-01-01

    Chemokines are implicated in tumor pathogenesis, although it is unclear whether they affect human cancer progression positively or negatively. We found that activation of the chemokine receptor CCR5 regulates p53 transcriptional activity in breast cancer cells through pertussis toxin–, JAK2-, and p38 mitogen–activated protein kinase–dependent mechanisms. CCR5 blockade significantly enhanced proliferation of xenografts from tumor cells bearing wild-type p53, but did not affect proliferation...

  4. Expression of chemokine receptor CCR6 and CCR7 in breast cancer and its clinical significance%趋化因子受体CCR6及CCR7在乳腺癌组织上的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    郭满盈; 罗媛烨; 陈扬; 熊春林

    2009-01-01

    目的 探讨趋化因子受体CCR6及CCR7在乳腺癌组织中的表达及其意义.方法 用免疫组织化学方法检测45例乳腺癌及10例乳腺纤维腺瘤组织中趋化因子受体CCR6及CCR7的表达,并对原位癌及发生转移的癌组织CCR6及CCR7的表达率进行比较.结果 在乳腺癌组织上检测到趋化因子受体CCR6及CCR7的表达(表达率分别为35.6%和48.9%),其中发生转移的癌组织CCR6及CCR7的表达率分别为41.7%和55.6%,未发生转移的癌组织CCR6及CCR7的表达率分别为11.1%和22.2%,乳腺纤维腺瘤组织中未发现CCR6及CCR7的表达.结论 乳腺癌组织上有趋化因子受体CCR6及CCR7的表达,其表达可能在乳腺癌的发生、发展和转移中发挥作用.%Objective To explore the expression of chemokine receptor CCR6 and CCR7 in breast cancer tissue and its clinical significance.Methods Forty-five cases of breast cancer specimens and ten cases of breast fibroadenoma specimens were analyzed by immunohistochemical staining for CCR6 and CCR7 expression. The rates of CCR6 and CCR7 expression were compared between primary and metastastic breast cancer tissue.Results The expression of CCR6 and CCR7 was detected in breast cancer (the positive rates were 35.6 % and 48.9% respectively). The CCR6 and CCR7 expression rates in primary and metastastic breast cancer tissue were 11.1%, 22.2% and 41.7%, 55.6% respectively, while CCR6 and CCR7 were not detected in breast fibroadenoma specimens.Conclusion CCR6 and CCR7 express in human breast cancer tissue, and they may play an important role in the occurrence, development and metastasis of human breast cancer.

  5. CXCR4 and CCR7: Two eligible targets in targeted cancer therapy.

    Science.gov (United States)

    Mishan, Mohammad Amir; Ahmadiankia, Naghmeh; Bahrami, Ahmad Reza

    2016-09-01

    Cancer is one of the most common cause of death in the world with high negative emotional, economic, and social impacts. Conventional therapeutic methods, including chemotherapy and radiotherapy, have not proven satisfactory and relapse is common in most cases. Recent studies have focused on targeted therapy with more precise identification and targeted attacks to the cancer cells. For this purpose, chemokine receptors are proper targets and among them, CXCR4 and CCR7, with a crucial role in cancer metastasis, are being considered as desired candidates for investigation. In this review paper, the most important experimental results are highlighted on the potential targeted therapies based on CXCR4 and CCR7 chemokine receptors.

  6. CCR5 blockage by maraviroc induces cytotoxic and apoptotic effects in colorectal cancer cells.

    Science.gov (United States)

    Pervaiz, Asim; Ansari, Shariq; Berger, Martin R; Adwan, Hassan

    2015-05-01

    Alterations in the expression of C-C chemokine receptor type 5 (CCR5 or CD195) have been correlated with disease progression in different cancers. Recently, a few investigations have reported the blockage of this receptor by an antagonist (maraviroc) and its antineoplastic effects on tumor cell growth. However, little is known about the mechanistic reasons behind these antineoplastic effects of CCR5 blockage by maraviroc. In this study, we blocked the CCR5 receptor by maraviroc in SW480 and SW620 colorectal cancer cells to study the resulting changes in biological properties and related pathways. This blockage induced significantly reduced proliferation and a profound arrest in G1 phase of the cell cycle. Concomitantly, maraviroc caused significant signs of apoptosis at morphological level. Significant modulation of multiple apoptosis-relevant genes was also noticed at mRNA levels. In addition, we found remarkable increases in cleaved caspases at protein level. These modulations led us to propose a signaling pathway for the observed apoptotic effects. In conclusion, blocking the CCR5 by maraviroc induces significant cytotoxic and apoptotic effects in colorectal cancer cells. Thus, maraviroc can be considered a model compound, which may foster the development of further CCR5 antagonists to be used for the treatment of colorectal cancer.

  7. Silencing of CCR7 inhibits the growth, invasion and migration of prostate cancer cells induced by VEGFC.

    Science.gov (United States)

    Chi, Bao-Jin; Du, Cong-Lin; Fu, Yun-Feng; Zhang, Ya-Nan; Wang, Ru Wen

    2015-01-01

    Early in prostate cancer development, tumor cells express vascular endothelial growth factor C (VEGF-C), a secreted molecule that is important in angiogenesis progression. CC-chemokine receptor 7 (CCR7), another protein involved in angiogenesis, is strongly expressed in most human cancers, where it activated promotes tumor growth as well as favoring tumor cell invasion and migration. The present study aimed to investigate the effect of down-regulating CCR7 expression on the growth of human prostate cancer cells stimulated by VEGFC. The CCR7-specific small interfering RNA (siRNA) plasmid vector was constructed and then transfected into prostate cancer cells. The expression of CCR7 mRNA and protein was detected by quantitative polymerase chain reaction and western blot analysis, respectively. Cell proliferation, apoptosis, cell cycle distribution and cell migration were assessed following knockdown of CCR7 by RNA interference (RNAi). Western blot analysis was used to identify differentially expressed angiogenesis- and cell cycle-associated proteins in cells with silenced CCR7. The expression levels of CCR7 in prostate cancer cells transfected with siRNA were decreased, leading to a significant inhibition of prostate cancer cell proliferation, migration and invasion induced by VEGFC. Western blot analysis revealed that silencing of CCR7 may inhibit vascular endothelial growth factor, matrix metalloproteinase (MMP)-2 and MMP-9 protein expression. In conclusion, the present study demonstrated that RNAi can effectively silence CCR7 gene expression and inhibit the growth of prostate cancer cells, which indicates that there is a potential of targeting CCR7 as a novel gene therapy approach for the treatment of prostate cancer.

  8. CCR7 pathway induces epithelial-mesenchymal transition through up-regulation of Snail signaling in gastric cancer.

    Science.gov (United States)

    Zhang, Jianping; Zhou, Yunzhe; Yang, Yonggang

    2015-02-01

    The chemokine receptor 7 (CCR7) and Snail signaling have been linked to various types of cancers. The associations between these signalings and the epithelial-mesenchymal transition (EMT) are not clear in gastric cancer. Here, the expression of CCR7 and Snail was detected in gastric cancer by immunohistochemistry and Western blot. Meanwhile, gastric cancer cells were subjected to CCL19, si-control, and si-Snail treatment. Cell cycle, migration, and invasion were also analyzed. The expression patterns of CCR7 and Snail were similar in either gastric cancer tissues or cells. The increased expression of CCR7 was closely associated with the increased Snail expression, which both were closely correlated with metastasis, stage and differentiation, and poor prognosis. The increased p-ERK, p-AKT, Snail, and MMP9 expression and the decreased E-cadherin were confirmed in MGC803 cells in a dose-dependent manner in response to CCL19 treatment. However, the blockade of Snail abrogated the up-regulation of MMP9 and down-regulation of E-cadherin. CCR7-induced ERK and PI3K pathway regulated Snail signaling. Besides si-Snail treatment led to MGC803 cell cycle arrest and affected the migration and invasion. In conclusion, our study suggested that CCR7 promotes Snail expression to induce the EMT, resulting in cell cycle progression, migration, and invasion in gastric cancer. CCR7-Snail pathway provided more potential regimens for cancer therapy.

  9. Clinical Case Registries (CCR)

    Data.gov (United States)

    Department of Veterans Affairs — The Clinical Case Registries (CCR) replaced the former Immunology Case Registry and the Hepatitis C Case Registry with local and national databases. The CCR:HIV and...

  10. The chemokines CCR1 and CCRL2 have a role in colorectal cancer liver metastasis.

    Science.gov (United States)

    Akram, Israa G; Georges, Rania; Hielscher, Thomas; Adwan, Hassan; Berger, Martin R

    2016-02-01

    C-C chemokine receptor type 1 (CCR1) and chemokine C-C motif receptor-like 2 (CCRL2) have not yet been sufficiently investigated for their role in colorectal cancer (CRC). Here, we investigated their expression in rat and human CRC samples, their modulation of expression in a rat liver metastasis model, as well as the effects on cellular properties resulting from their knockdown. One rat and five human colorectal cancer cell lines were used. CC531 rat colorectal cells were injected via the portal vein into rats and re-isolated from rat livers after defined periods. Following mRNA isolation, the gene expression was investigated by microarray. In addition, all cell lines were screened for mRNA expression of CCR1 and CCRL2 by reverse transcription polymerase chain reaction (RT-PCR). Cell lines with detectable expression were used for knockdown experiments; and the respective influence was determined on the cells' proliferation, scratch closure, and colony formation. Finally, specimens from the primaries of 50 patients with CRC were monitored by quantitative RT-PCR for CCR1 and CCRL2 expression levels. The microarray studies showed peak increases of CCR1 and CCRL2 in the early phase of liver colonization. Knockdown was sufficient at mRNA but only moderate at protein levels and resulted in modest but significant inhibition of proliferation (p cancer liver metastasis.

  11. Preferential recruitment of Th17 cells to cervical cancer via CCR6-CCL20 pathway.

    Science.gov (United States)

    Yu, Qing; Lou, Xiang-ming; He, Yan

    2015-01-01

    Our previous studies suggest that Th17 cells accumulate within tumor tissues and correlate with recurrence of cervical cancer patients. However, the source of the increased tumor-infiltrating Th17 cells remains poorly understood. We investigated the prevalence, phenotype and trafficking property of Th17 cells in patients with cervical cancer. Our results showed that Th17 cells highly aggregated within tumor tissues in an activated phenotype with markedly increased expression of CCR6. Correspondingly, level of CCL20 in the tumor tissues was significantly higher than that in non-tumor and normal control tissues, and strongly positively associated with Th17 cells. Further, in vitro migration assay showed CCL20 had effective chemotaxis to circulating Th17 cells. In conclusion, Th17 cells are recruited into tumor tissues preferentially through CCR6-CCL20 pathway, which can serve as a novel therapeutic target for cervical cancer.

  12. Involvement of Spinal CCR5/PKCγ Signaling Pathway in the Maintenance of Cancer-Induced Bone Pain.

    Science.gov (United States)

    Hang, Li-Hua; Li, Shu-Na; Dan, Xiang; Shu, Wei-Wei; Luo, Hong; Shao, Dong-Hua

    2017-02-01

    Cancer-induced bone pain (CIBP) is a challenging medical problem that considerably influences cancer patients' quality of life. Currently, few treatments have been developed to conquer CIBP because of a poor understanding of the potential mechanisms. Our previous work has proved that spinal RANTES (a major ligand for CCR5) was involved in the maintenance of CIBP. In this study, we attempted to investigate whether spinal CCR5 and its downstream PKCγ pathway is involved in the maintenance of CIBP. Inoculation of Walker 256 cells into the tibia could induce a marked mechanical allodynia with concomitant upregulation of spinal CCR5 and p-PKCγ expression from day 6 to day 15 after inoculation. Spinal CCR5 was prominently expressed in microglia, and mechanical allodynia was attenuated by intrathecal injection of DAPTA (a specific antagonist of CCR5) with downregulation of spinal CCR5 and p-PKCγ expression levels at day 15 in inoculated rats. Pre-intrathecal injection of RANTES could reverse the anti-allodynia effects of DAPTA. Intrathecal administration of GF109203X (an inhibitor of PKC) could alleviate mechanical allodynia as well as decrease of spinal p-PKCγ expression level, but no influence on spinal CCR5 level. Our findings suggest that CCR5/PKCγ signaling pathway in microglia may contribute to the maintenance of CIBP in rats.

  13. CCL5 activation of CCR5 regulates cell metabolism to enhance proliferation of breast cancer cells.

    Science.gov (United States)

    Gao, Darrin; Rahbar, Ramtin; Fish, Eleanor N

    2016-06-01

    In earlier studies, we showed that CCL5 enhances proliferation and survival of MCF-7 breast cancer cells in an mTOR-dependent manner and we provided evidence that, for T cells, CCL5 activation of CCR5 results in increased glycolysis and enhanced ATP production. Increases in metabolic activity of cancer cells, specifically increased glycolytic activity and increased expression of glucose transporters, are associated with tumour progression. In this report, we provide evidence that CCL5 enhances the proliferation of human breast cancer cell lines (MDA-MB-231, MCF-7) and mouse mammary tumour cells (MMTV-PyMT), mediated by CCR5 activation. Concomitant with enhanced proliferation we show that CCL5 increases cell surface expression of the glucose transporter GLUT1, and increases glucose uptake and ATP production by these cells. Blocking CCL5-inducible glucose uptake abrogates the enhanced proliferation induced by CCL5. We provide evidence that increased glucose uptake is associated with enhanced glycolysis, as measured by extracellular acidification. Moreover, CCL5 enhances the invasive capacity of these breast cancer cells. Using metabolomics, we demonstrate that the metabolic signature of CCL5-treated primary mouse mammary tumour cells reflects increased anabolic metabolism. The implications are that CCL5-CCR5 interactions in the tumour microenvironment regulate metabolic events, specifically glycolysis, to promote tumour proliferation and invasion.

  14. Evaluation of prevalence of  32 mutation in CCR5 gene in breast cancer patients in Rafsanjan city

    Directory of Open Access Journals (Sweden)

    Mohammad Kazemi Arababadi

    2009-01-01

    Full Text Available (Received 24 August, 2008; Accepted 21 May, 2009AbstractBackground and purpose: Chemokines and their receptors are expressed in different types of malignancies. CC chemokines MIP-1 (CCL3, MIP-1 (CCL4 and RANTES (CCL5 is believed to be anti-tumor and also aid to the metastasis in tumor microenvironment. CCR2 and CCR5 are special G-protein receptors for these chemokines. Due to the important role of CCR5 chemokine receptor in tumor biology, this project is designed to examine  32 mutation in CCR5 gene regards breast cancer.Materials and methods: This experimental study was performed during 2007-8 on 100 healthy adults and 36 breast cancer patients by Gap-PCR. The demographic information also was collected by questionner and t-test Chi-square was used for statistical analysis of data.Results: Our results showed that none of breast cancer patients had CCR5- 32 mutation while 3 (3% cases of controls had heterozygotic form of this mutation.Conclusion: Our results showed that there is not any CCR5- 32 mutation in patients. Therefore, it appears that this mutation don’t play any role in breast cancer.J Mazand Univ Med Sci 2009; 19(70: 49-53 (Persian

  15. Study on the function of chemokine receptor CCR7 in metastasis of stom-ach cancer%趋化因子受体CCR7在胃癌转移中的作用研究

    Institute of Scientific and Technical Information of China (English)

    王欢; 袁武锋; 蒋雷; 费鲜明

    2015-01-01

    Objective To construct stable expression system of pLVX-Pro-CCR7 and study the function of CCR7 gene in metastasis of stomach cancer. Methods PCR method was used to amplify CCR7 gene and construct pLVX-Puro-CCR7 recombinant plasmid. Lipofection was used to infect SGC7901 cell strain immediately, and puromycin was used to screen the cell strain and establish a cell strain with stable expression. Western blot method was used to test the ex-pression of CCR7 in SGC7901 cells which were stably infected. Transwell method was used to analyze the effect of overly expressed CCR7 gene on in vitro migration of stomach cancer cells of SGC7901. Living imaging was used to ob-serve the metastasis ability of stomach cancer cell strain of SGC7901 which overly expressed CCR7 in nude mice. Re-sults pLVX-Puro-CCR7 recombinant plasmid was successfully constructed and SGC791 cell strain was stably infected. The cell strain was able to correctly translate and express CCR7 protein. Metastasis ability in nude mice and in vitro migration ability of SGC7901 stomach cancer cell strain which overly expressed CCR7 gene significantly improved (P<0.05). Conclusion CCR7 may be involved in the function of promoting metastasis of stomach cancer cells.%目的:构建pLVX-Puro-CCR7稳定表达系统并研究CCR7基因在胃癌转移中的作用。方法采用PCR方法扩增CCR7基因并构建pLVX-Puro-CCR7重组质粒,通过脂质体转染法瞬时转染SGC7901细胞株,嘌呤霉素对该细胞株进行筛选并建立稳定表达细胞株。 Western blot方法检测稳定转染的SGC7901细胞中CCR7表达情况。Transwell方法分析过度表达CCR7基因对SGC7901胃癌细胞体外迁移的影响。活体成像观察过度表达CCR7的SGC7901胃癌细胞株在裸鼠体内转移能力。结果成功构建pLVX-Puro-CCR7重组质粒并稳定转染SGC7901细胞株,该细胞株能够正确翻译及表达CCR7蛋白。过度表达CCR7基因的SGC7901胃癌细胞株体外迁移能力和在裸鼠体

  16. CCL21/CCR7 prevents apoptosis via the ERK pathway in human non-small cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Ying Xu

    Full Text Available Previously, we confirmed that C-C chemokine receptor 7 (CCR7 promotes cell proliferation via the extracellular signal-regulated kinase (ERK pathway, but its role in apoptosis of non-small cell lung cancer (NSCLC cell lines remains unknown. A549 and H460 cells of NSCLC were used to examine the effect of CCL21/CCR7 on apoptosis using flow cytometry. The results showed that activation of CCR7 by its specific ligand, exogenous chemokine ligand 21 (CCL21, was associated with a significant decline in the percent of apoptosis. Western blot and real-time PCR assays indicated that activation of CCR7 significantly caused upregulation of anti-apoptotic bcl-2 and downregulation of pro-apoptotic bax and caspase-3, but not p53, at both protein and mRNA levels. CCR7 small interfering RNA significantly attenuated these effects of exogenous CCL21. Besides, PD98059, a selective inhibitor of MEK that disrupts the activation of downstream ERK, significantly abolished these effects of CCL21/CCR7. Coimmunoprecipitation further confirmed that there was an interaction between p-ERK and bcl-2, bax, or caspase-3, particularly in the presence of CCL21. These results strongly suggest that CCL21/CCR7 prevents apoptosis by upregulating the expression of bcl-2 and by downregulating the expression of bax and caspase-3 potentially via the ERK pathway in A549 and H460 cells of NSCLC.

  17. CCR5的表达在乳腺癌的诊断与转移中的临床价值%Expression and significance of chemokine receptor CCR5 for the diagnosis and metastasis of breast cancer

    Institute of Scientific and Technical Information of China (English)

    郭满盈; 陈扬; 王栋

    2012-01-01

    目的 探讨趋化因子受体CCR5在乳腺癌组织及其腋窝转移淋巴结中的表达及意义.方法 用免疫组织化学方法检测35例乳腺癌及其腋窝转移淋巴结组织、20例乳腺纤维腺瘤组织(对照组)中的CCR5.结果 乳腺癌组织CCR5阳性率为74.2%(26/35),乳腺纤维腺瘤组织中未发现CCR5的表达,两种组织阳性表达率差异显著,P<0.01.腋窝淋巴结转移灶中,CCR5阳性者21例(60.0%,21/35),原发癌灶和腋窝淋巴节转移灶CCR5同时阳性者21例.结论 CCR5在乳腺癌组织及其腋窝淋巴结中有异常表达,其可能在乳腺癌的发生、发展及转移中发挥作用.%Objective To explore the expression of chemokine receptor CCR5 in breast cancer tissue and metastatic axillary nodes, and its clinical significance. Methods CCR5 was detected by immunohistochemical staining in 35 cases of breast cancer specimens and metastatic axillary nodes and 20 cases of breast fibroadenoma specimens (normal control). Results The positive rate of CCR5 in breast cancer tissue was 74. 2%(26/35) ,higher than that in breast fibroadenoma (P<0. 05). The positive rate of CCR5 in metastatic axillary nodes was 60. 0% (21/35) ,and there were 21 cases with positive expression of CCR5 in primary cancer tissue and metastatic axillary nodes simultaneously. Conclusion CCR5 , which could be expressed abnormally in breast cancer tissues and metastatic axillary nodes,might play an important role in carcinogenesis,development and metastasis of breast cancer.

  18. CCR7 enhances TGF-β1-induced epithelial-mesenchymal transition and is associated with lymph node metastasis and poor overall survival in gastric cancer.

    Science.gov (United States)

    Ma, Huiying; Gao, Lingling; Li, Shichao; Qin, Jie; Chen, Long; Liu, Xinzhou; Xu, Pingping; Wang, Fei; Xiao, Honglei; Zhou, Shuang; Gao, Qiang; Liu, Binbin; Sun, Yihong; Liang, Chunmin

    2015-09-15

    CCR7 is a G protein-coupled chemokine receptor. In this study, we used immunohistochemistry with tissue microarrays to measure CCR7 expression in tumor specimens from 122 patients with gastric cancer. We show that CCR7 expression is associated with lymph node metastasis (P = 0.022) and overall survival (OS; P = 0.025), and is an independent factor associated with poorer overall survival (P = 0.032). The CCR7 mechanism was predicted based on bioinformatic analysis and verified in gastric cancer cell lines and primary tumor samples. The data show that CCR7 contributes to TGF-β1-induced epithelial-mesenchymal transition (EMT) and that the effects of TGF-β1 are inhibited by a CCR7 neutralizing antibody or a NF-κB inhibitor. Increased TGF-β1 expression was accompanied by nuclear localization of NF-κB-p65 and higher levels of the mesenchymal marker vimentin in human gastric cancer samples. We conclude that the CCR7 axis mediates TGF-β1-induced EMT via crosstalk with NF-κB signaling, facilitating lymph node metastasis and poorer overall survival in patients with gastric cancer. These findings suggest CCR7 is a novel prognostic indicator and a potential target for gastric cancer therapy.

  19. Expressions and Significance of CXCR4 and CCR7 Chemokine Receptor in Lung Cancer%CCR7、CXCR4在肺癌中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    王述波; 周华; 李作涛; 曹望凯; 韩其正

    2012-01-01

    目的 探讨CC族趋化因子受体7(CCR7)和CXC族趋化因子受体4(CXCR4)在肺癌组织中的表达及临床意义.方法 采用免疫组织化学检测72例肺癌组织标本和30例良性肺疾病肺组织标本中CXCR4和CCR7的表达情况,并分析其不同临床病理特征中表达的差异.结果 CCR7和CXCR4在肺癌组织中的表达阳性率均明显高于正常肺组织,差异有统计学意义(P<0.01);CCR7和CXCR4表达与肺癌患者的TNM分期,纵膈淋巴结转移密切相关(P<0.01),与年龄、性别、病例组织学类型等均无关(P>0.05),并且Spearman相关分析显示,CXCR4表达与CCR7表达呈高度正相关(r =0.623,P<0.001).结论 CXCR4和CCR7在肺癌纵膈淋巴转移中发挥重要作用.%Objective To explore the expression of the CC chemokine receptor-7 ( CCR7 ) and CXC chemokine receptor-4 (CXCR4) in lung cancer and its significance. Methods By using immunohistochemistry technique, the expression of CXCR4 and CCR7 in the cancer specimens of 72 patients with lung cancer and 30 samples of lung tissue from benign pulmonary disease were detected,and analyzed its different clinical and pathological features of expression differences. Results The express positive rate of CCR7 and CXCR4 in the observation group were significantly higher than that in the control group,the difference was statistically significant (P 0. 05). The Spearman rank correlation showed that CXCR4 expression and CCR7 expression were highly correlated(r =0.623 ,P <0.001). Conclusion The abnormal expression of CXCR4 and CCR7 play an important role in the diaphragmatic metastases of lung cancer

  20. The effect of CCL19/CCR7 on the proliferation and migration of cell in prostate cancer.

    Science.gov (United States)

    Peng, Cheng; Zhou, Keliang; An, Sensheng; Yang, Jie

    2015-01-01

    Multiple studies have shown that CC motif chemokine ligand 19 (CCL19) promotes cell proliferation in several human cancers. In this study, we investigated the clinical significance of CCL19 and its specific receptor CCR7 and its function in our large collection of prostate samples. Between August 2000 and December 2013, 108 patients with histologically confirmed prostate cancer (PCa) and 80 with benign prostate hyperplasia (BPH) were recruited into the study. Quantitative RT-PCR immunohistochemistry analyses were used to quantify CCL19 and CCR7 expression in PCa cell lines and clinical samples. The functional role of CCL19 in PCa cell lines was evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation and invasion. The positive rate of CCL19 staining was 87.04 % (94/108) in 108 cases of prostatic carcinoma and 16.25 % (13/80) in 80 cases of BPH, and high expression of CCR7 was observed in 83.33 % (90/108) of the PCa tissues versus (17.50 %; 14/80) of the BPH tissues, the difference of CCL19 and CCR7 expression between two groups was statistically significant, respectively. The results were confirmed by quantitative real-time PCR. CCL19 and CCR7 were significantly elevated in all five PCa cell lines when compared to the RWPE-1 cells. Silencing of CCL19 inhibited the proliferation of DU-145 cells which have a relatively high level of CCL19 in a time- and concentration-dependent manner, and the invasion and migration of DU-145 cells were distinctly suppressed. Our data suggest that the pathogenesis of human PCa maybe mediated by the CCL19/CCR7 axis, and CCL19 inhibition treatment may provide a promising strategy for the anti-tumor therapy of PCa.

  1. Correlation of CCR7 and VEGF-C expression with lymphatic metastasis in pancreatic cancer%CCR7和VEGF-C表达与胰腺癌淋巴结转移的关系

    Institute of Scientific and Technical Information of China (English)

    郭静会; 娄文辉; 纪元; 张顺财

    2013-01-01

    目的 探讨趋化因子受体7(CCR7)和血管内皮生长因子C(VEGF-C)在胰腺癌组织中的表达与淋巴结转移之间的关系.方法 应用实时荧光定量PCR 和免疫组化技术检测胰腺癌和正常胰腺组织中CCR7 和VEGF-C的表达情况.结果 CCR7、VEGF-C基因和蛋白在伴有淋巴结转移的胰腺癌组织中的表达显著高于不伴有淋巴结转移的胰腺癌组织;在胰腺癌组织中的表达显著高于正常胰腺组织;胰腺癌组织中CCR7 与VEGF-C 的表达具有显著的相关性.结论 CCR7和VEGF-C可以作为评估胰腺癌淋巴结转移的一个观测指标,与胰腺癌淋巴结转移明显相关.%Objective To investigate the expression of chemokine receptor 7 ( CCR7) and vascular endothelial growth factor C ( VEGF-C) in pancreatic cancer (PC) and its relationship with lymphatic metastasis . Methods The expression of CCR7 and VEGF-C was examined by fluorescence quantitative real -time PCR and immunohistochemistry. Results CCR7 , VEGF-C mRNA and protein expression levels were significantly higher in patients with cancer displaying lymph node metas -tasis. The mRNA and protein expression levels of CCR7 and VEGF-C in PC tissue were significantly higher than those in the adjacent normal tissue. There was a significant positive linear correlation between the mRNA transcription and protein expression levels of CCR7 and VEGF-C. Conclusion CCR7 and VEGF-C seem to play a pivotal role in lymph node metas -tasis of PC.

  2. Cervical cancer cell-derived interleukin-6 impairs CCR7-dependent migration of MMP-9-expressing dendritic cells.

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    Pahne-Zeppenfeld, Jennifer; Schröer, Nadine; Walch-Rückheim, Barbara; Oldak, Monika; Gorter, Arko; Hegde, Subramanya; Smola, Sigrun

    2014-05-01

    Cervical carcinogenesis is a consequence of persistent infection with high-risk human papillomaviruses (HPVs). Recent studies indicate that HPV-transformed cells actively instruct their microenvironment to promote carcinogenesis. Here, we demonstrate that cervical cancer cells activate monocytes to produce their own CCL2 for further monocyte recruitment and reprogram their function during differentiation and maturation to dendritic cells (DCs). Our data show that cervical cancer cells suppress the induction of the chemokine receptor CCR7 in phenotypically mature DCs and impair their migration toward a lymph node homing chemokine, required to initiate adaptive immune responses. We confirmed the presence of CD83(+)CCR7(low) DCs in cancer biopsies. The second factor essential for DC migration, matrix-metalloproteinase MMP-9, which also has vasculogenic and protumorigenic properties, is not suppressed but upregulated in immature as well as mature DCs. We identified interleukin-6 (IL-6) as a crucial cervical cancer cell-derived mediator and nuclear factor kappaB (NF-jB) as the central signaling pathway targeted in DCs. Anti-IL-6 antibodies reverted not only NF-jB inhibition and restored CCR7-dependent migration but also blocked MMP-9 induction. This is the first report demonstrating the dissociation of CCR7 and MMP-9 expression in phenotypically mature CD83(+) DCs by cancer cells. Our results show that cervical cancer cells actively shape the local microenvironment. They induce the accumulation of myeloid cells and skew their function from immune activation to local production of protumorigenic MMP-9. Neutralizing anti-IL-6 antibodies can counteract this functional dysbalance and should therefore be considered for adjuvant cervical cancer therapy.

  3. Expression of CCR5 and c-Met in Breast Cancer and Its Significance%乳腺癌中CCR5和c-Met的表达及意义

    Institute of Scientific and Technical Information of China (English)

    张玉文; 王丹; 刘亚

    2014-01-01

    Objective To study the signiifcance of CCR5 and c-Met expression in breast cancer.Methods The expression of CCR5 and c-Met in 45 cases of breast cancer was analyzed by using immunohistochemisty. Results CCR5 was expressed in 55.6% of cancerous breast tissue (25/45), whereas it was only expressed in 8.9% of normal breast tissue (4/45). Signiifcant difference was noted between the expression levels (P<0.01). c-Met was expressed in 51% of cancerous breast tissue (23/45), but only 6.6% (3/45) of normal tissue. The observed difference in expression level of c-Met was also statistically signiifcant (P<0.01). On the other hand, 44.4% (20/45) of breast cancer patients with lymph node metastasis showed co-expression of both c-Met and CCR5, compared to 22.2% (10/45) in the normal breast tissue. Our ifndings demonstrate signiifcant associations between the expression of c-Met, CCR5 and lymph node metastasis in breast cancer patients. Conclusion CCR5 and c-Met expression was associated with poor prognosis of breast cancer patients, which could be predict the prognosis of breast cancer.%目的:探讨乳腺癌组织中CCR5和c-Met的表达及其意义。方法采用免疫组化SP法检测45例乳腺癌中CCR5和c-Met的表达。结果乳腺癌组织CCR5阳性率55.6%(25/45),正常乳腺组织中CCR5表达率8.9%(4/45),两种组织阳性表达率差异显著(P<0.01),c-Met的阳性表达率为51%(23/45),正常乳腺组织中c-Met表达率6.6%(3/45),两种组织阳性表达率差异显著(P<0.01)。在伴有淋巴结转移的乳腺癌中c-Met和CCR5的共同阳性率44.4%(20/45),无淋巴结转移的乳腺癌中阳性表达率为22.2%(10/45)。CCR5和c-Met的表达和乳腺癌的淋巴结转移成正相关。结论CCR5和c-Met与提示乳腺癌的转移预后因素有关,可作为预测乳腺癌转移的参考指标之一。

  4. Upregulation of the Chemokine Receptor CCR7 expression by HIF-1αand HIF-2α in non-small cell lung cancer

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    Yang LI

    2008-10-01

    Full Text Available Background and objective CCR7 is closely related with the lymph node metastasis of non-small cell lung cancer. The objective of this work is to investigate the expressions of chemokine receptor CCR7, hypoxiainducible factor 1α (HIF-1α and hypoxia inducible factor 2α (HIF-2α protein in non small cell lung cancer and the relationships of their expression, and to study the mechanism of CCR7 upregulation in NSCLC. Methods T he levels of expressions of CCR7, HIF-1α and HIF-2α protein were detected in 94 specimens of human primary non small cell lung cancer by immunohistochemical S-P method. Human lung adenocarcinoma cell line A549 cells were transfected by lipofection with HIF-1α siRNA、HIF-2α siRNA, the change of CCR7 was observed by RT-PCR and immunofluorescence staining. Correlations between the expression of CCR7 and HIF-1α, HIF-2α were respectively analyzed. Results Immunohistochemistry showed that CCR7 was distributed in cytoplasm and/or membrane of tumor cells, HIF-1α, HIF-2α was distributed in nucleus and/or cytoplasm of tumor cells. The levels of expressions of CCR7, HIF-1α and HIF-2α protein were found to be 75.53% (71/94, 54.25% (51/ 94 and 70.21% (66/94 in non small celllung cancer, respectively. the levels of expression of CCR7 protein were closely related to the clinical stages (P 0.05. Furthermore, A significant correlation were found among CCR7, Hif-1α and HIF-2α (r =0.272, P <0.01 (r=0.225, P <0.05. In addition, the expression of CCR7 mRNA and protein levels were decreased in the transfected specificHIF-1α, HIF-2αsiRNA group (P <0.05. Conclusion CCR7 expression is significantly associated with non small cell lung cancer invasion and metastasis. The upregulation of CCR7 is regulated by HIF-1α and HIF-2α in non small cell lung cancer.

  5. Research on expression of CXCR4 and CCR7 in non small cell lung cancer cells%CXCR4、CCR7在非小细胞肺癌中表达的差异及意义

    Institute of Scientific and Technical Information of China (English)

    李醒; 温剑虎; 曾涛

    2008-01-01

    目的 探讨非小细胞肺癌(non small cell lung cancer,NSCLC)中CXC类趋化因子受体4(chemokine CXC motif receptor 4,CXCR4)、CC类趋化因子体7(chemokine CC motif receptor 7,CCR7)表达的差异性及其表达在局部淋巴结转移中的作用.方法 未做治疗的41例NSCLC肿瘤原发灶,以及25例移淋巴结和20例正常肺组织接SABC免疫组化法观察CXCR4、CCR7的表达.结果 NSCLC原发灶中肿瘤细胞CXCR4、CCR7阳性表达均明显高于正常肺组细胞(P<0.05);CXCR4阳性表达率高于CCR7(分别为92.68%、68.29%;P<0.05).原发灶中CCR7与TNM分期、淋巴结转移状况相关(P<0.05).淋巴结移灶中CXCR4、CCR7表达阳性率差异无统计学意义(96%、84%;P>0.05).结论 NSCLC中肿瘤细胞高表达CXCR4及CCR7可能与肿瘤细胞局部淋巴结靶性转移有关.对NSCLC而言,CCR7的作用可能更为关键.

  6. Essential roles of the interaction between cancer cell-derived chemokine, CCL4, and intra-bone CCR5-expressing fibroblasts in breast cancer bone metastasis.

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    Sasaki, Soichiro; Baba, Tomohisa; Nishimura, Tatsunori; Hayakawa, Yoshihiro; Hashimoto, Shin-Ichi; Gotoh, Noriko; Mukaida, Naofumi

    2016-08-01

    From a murine breast cancer cell line, 4T1, we established a subclone, 4T1.3, which consistently metastasizes to bone upon its injection into the mammary fat pad. 4T1.3 clone exhibited similar proliferation rate and migration capacity as the parental clone. However, the intra-bone injection of 4T1.3 clone caused larger tumors than that of the parental cells, accompanied with increases in fibroblast, but not osteoclast or osteoblast numbers. 4T1.3 clone displayed an enhanced expression of a chemokine, CCL4, but not its specific receptor, CCR5. CCL4 shRNA-transfection of 4T1.3 clone had few effects on its in vitro properties, but reduced the tumorigenicity arising from the intra-bone injection. Moreover, intra-bone injection of 4T1.3 clone caused smaller tumors in mice deficient in CCR5 or those receiving CCR5 antagonist than in wild-type mice. The reduced tumor formation was associated with attenuated accumulation of CCR5-positive fibroblasts expressing connective tissue growth factor (CTGF)/CCN2. Tumor cell-derived CCL4 could induce fibroblasts to express CTGF/CCN2, which could support 4T1.3 clone proliferation under hypoxic culture conditions. Thus, the CCL4-CCR5 axis can contribute to breast cancer metastasis to bone by mediating the interaction between cancer cells and fibroblasts in bone cavity.

  7. CCL21/CCR7 enhances the proliferation, migration, and invasion of human bladder cancer T24 cells.

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    Miao Mo

    Full Text Available To investigate the effects of CCL21/CCR7 on the proliferation, migration, and invasion of T24 cells and the possible associated mechanisms: expression of MMP-2 and MMP-9, and regulation of BCL-2 and BAX proteins.T24 cells received corresponding treatments including vehicle control, antibody (20 ng/mL CCR7 antibody and 50 ng/ml CCL21, and 50, 100, and 200 ng/ml CCL21. Proliferation was evaluated by MTT assay; cell migration and invasion were assayed using a transwell chamber. Cell apoptosis was induced by Adriamycin (ADM. The rate of cell apoptosis was examined by flow cytometry using annexin V-FITC/PI staining. Western-blot was used to analyze MMP-2 and MMP-9 and BCL-2 and BAX proteins.CCL21 promoted T24 cell proliferation in concentration-dependent manner with that 200 ng/mL induced the largest amount of proliferation. Significant differences of cell migration were found between CCL21treatment groups and the control group in both the migration and invasion studies (P < 0.001 for all. The expressions of MMP-2 and MMP-9 proteins were significantly increased after CCL21 treatment (p < 0.05 for all. Protein expression of Bcl-21 follows an ascending trend while the expression of Bax follows a descending trend as the concentration of CCL21 increases. No difference was found between the control group and antibody group for all assessments.CCL21/CCR7 promoted T24 cell proliferation and enhanced its migration and invasion via the increased expression of MMP-2 and MMP-9. CCL21/CCR7 had antiapoptotic activities on T24 cells via regulation of Bcl-2 and Bax proteins. CCL21/CCR7 may promote bladder cancer development and metastasis.

  8. Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients.

    Science.gov (United States)

    Halama, Niels; Zoernig, Inka; Berthel, Anna; Kahlert, Christoph; Klupp, Fee; Suarez-Carmona, Meggy; Suetterlin, Thomas; Brand, Karsten; Krauss, Juergen; Lasitschka, Felix; Lerchl, Tina; Luckner-Minden, Claudia; Ulrich, Alexis; Koch, Moritz; Weitz, Juergen; Schneider, Martin; Buechler, Markus W; Zitvogel, Laurence; Herrmann, Thomas; Benner, Axel; Kunz, Christina; Luecke, Stephan; Springfeld, Christoph; Grabe, Niels; Falk, Christine S; Jaeger, Dirk

    2016-04-11

    The immune response influences the clinical course of colorectal cancer (CRC). Analyzing the invasive margin of human CRC liver metastases, we identified a mechanism of immune cell exploitation by tumor cells. While two distinct subsets of myeloid cells induce an influx of T cells into the invasive margin via CXCL9/CXCL10, CCL5 is produced by these T cells and stimulates pro-tumoral effects via CCR5. CCR5 blockade in patient-derived functional in vitro organotypic culture models showed a macrophage repolarization with anti-tumoral effects. These anti-tumoral effects were then confirmed in a phase I trial with a CCR5 antagonist in patients with liver metastases of advanced refractory CRC. Mitigation of tumor-promoting inflammation within the tumor tissue and objective tumor responses in CRC were observed.

  9. Chemokine axes in breast cancer: factors of the tumor microenvironment reshape the CCR7-driven metastatic spread of luminal-A breast tumors.

    Science.gov (United States)

    Weitzenfeld, Polina; Kossover, Olga; Körner, Cindy; Meshel, Tsipi; Wiemann, Stefan; Seliktar, Dror; Legler, Daniel F; Ben-Baruch, Adit

    2016-06-01

    Chemokine axes have been shown to mediate site-specific metastasis in breast cancer, but their relevance to different subtypes has been hardly addressed. Here, with the focus on the CCR7-CCL21 axis, patient datasets demonstrated that luminal-A tumors express relatively low CCR7 levels compared with more aggressive disease subtypes. Furthermore, lymph node metastasis was not associated with high CCR7 levels in luminal-A patients. The metastatic pattern of luminal-A breast tumors may be influenced by the way luminal-A tumor cells interpret signals provided by factors of the primary tumor microenvironment. Thus, CCR7-expressing human luminal-A cells were stimulated simultaneously by factors representing 3 tumor microenvironment arms typical of luminal-A tumors, hormonal, inflammatory, and growth stimulating: estrogen + TNF-α + epidermal growth factor. Such tumor microenvironment stimulation down-regulated the migration of CCR7-expressing tumor cells toward CCL21 and inhibited the formation of directional protrusions toward CCL21 in a novel 3-dimensional hydrogel system. CCL21-induced migration of CCR7-expressing tumor cells depended on PI3K and MAPK activation; however, when CCR7-expressing cancer cells were prestimulated by tumor microenvironment factors, CCL21 could not effectively activate these signaling pathways. In vivo, pre-exposure of the tumor cells to tumor microenvironment factors has put restraints on CCL21-mediated lymph node-homing cues and shifted the metastatic pattern of CCR7-expressing cells to the aggressive phenotype of dissemination to bones. Several of the aspects were also studied in the CXCR4-CXCL12 system, demonstrating similar patient and in vitro findings. Thus, we provide novel evidence to subtype-specific regulation of the CCR7-CCL21 axis, with more general implications to chemokine-dependent patterns of metastatic spread, revealing differential regulation in the luminal-A subtype.

  10. CCR9 interactions support ovarian cancer cell survival and resistance to cisplatin-induced apoptosis in a PI3K-dependent and FAK-independent fashion

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    Johnson Erica L

    2010-06-01

    Full Text Available Abstract Background Cisplatin is more often used to treat ovarian cancer (OvCa, which provides modest survival advantage primarily due to chemo-resistance and up regulated anti-apoptotic machineries in OvCa cells. Therefore, targeting the mechanisms responsible for cisplatin resistance in OvCa cell may improve therapeutic outcomes. We have shown that ovarian cancer cells express CC chemokine receptor-9 (CCR9. Others have also shown that CCL25, the only natural ligand for CCR9, up regulates anti-apoptotic proteins in immature T lymphocytes. Hence, it is plausible that CCR9-mediated cell signals might be involved in OvCa cell survival and inhibition of cisplatin-induced apoptosis. In this study, we investigated the potential role and molecular mechanisms of CCR9-mediated inhibition of cisplatin-induced apoptosis in OvCa cells. Methods Cell proliferation, vibrant apoptosis, and TUNEL assays were performed with or without cisplatin treatment in presence or absence of CCL25 to determine the role of the CCR9-CCL25 axis in cisplatin resistance. In situ Fast Activated cell-based ELISA (FACE assays were performed to determine anti-apoptotic signaling molecules responsible for CCL25-CCR9 mediated survival. Results Our results show interactions between CCR9 and CCL25 increased anti-apoptotic signaling cascades in OvCa cells, which rescued cells from cisplatin-induced cell death. Specifically, CCL25-CCR9 interactions mediated Akt, activation as well as GSK-3β and FKHR phosphorylation in a PI3K-dependent and FAK-independent fashion. Conclusions Our results suggest the CCR9-CCL25 axis plays an important role in reducing cisplatin-induced apoptosis of OvCa cells.

  11. CCL21/CCR7 up-regulate vascular endothelial growth factor-D expression via ERK pathway in human non-small cell lung cancer cells.

    Science.gov (United States)

    Sun, Limei; Zhang, Qingfu; Li, Yang; Tang, Na; Qiu, Xueshan

    2015-01-01

    Lymphangiogenesis has received considerable attention and become a new research hotspot of tumor metastasis. Recently, C-C chemokine receptor 7 (CCR7) is known to promote metastasis of non-small cell lung cancer (NSCLC) cells into lymph nodes. In this study, we investigated the relationship between CCL21/CCR7 and the lymphangiogenic factor vascular endothelial growth factor (VEGF)-D in human lung cancer cells and its impact on patients' prognosis. We found that CCL21/CCR7 increase the expression of VEGF-D in NSCLC Cell Lines through induced ERK1/2 and Akt phosphorylation. In addition, our study found that the expression levels of CCR7 and CCL21 were correlated with VEGF-D, lymphatic vessels density (LVD), clinical stages, lymph node metastasis, and patient Survival in 90 human non-small cell lung cancer (NSCLC) specimens. Taken together, our results provide evidence that CCL21/CCR7 induce VEGF-D up-regulation and promote lymphangiogenesis via ERK/Akt pathway in lung cancer.

  12. Detection and localization of Mip-3alpha/LARC/Exodus, a macrophage proinflammatory chemokine, and its CCR6 receptor in human pancreatic cancer.

    Science.gov (United States)

    Kleeff, J; Kusama, T; Rossi, D L; Ishiwata, T; Maruyama, H; Friess, H; Büchler, M W; Zlotnik, A; Korc, M

    1999-05-17

    Macrophage Proinflammatory Human Chemokine-3alpha (Mip-3alpha/LARC/Exodus) belongs to a large family of chemotactic cytokines, which participate in directing inflammatory cell migration and in modulating angiogenesis. Mip-3alpha signals through a recently identified G-protein linked 7-transmembrane receptor, CCR6. In this study, we have characterized the expression of Mip-3alpha and CCR6 in 12 normal and 16 cancerous human pancreatic tissues and in 4 cultured pancreatic cancer cell lines, and assessed the effects of Mip-3alpha on growth and invasion of these cell lines. Pancreatic cancer tissues markedly overexpressed Mip-3alpha in comparison with normal pancreatic samples. By in situ hybridization Mip-3alpha and CCR6 mRNA moieties were present in cancer cells within the tumors. In addition, Mip-3alpha was abundant in the macrophages infiltrating the tumor mass. Mip-3alpha and its receptor CCR6 were expressed in all 4 tested pancreatic cancer cell lines. Mip-3alpha stimulated the growth of one cell line, enhanced the migration of another cell line, and was without effect in the other 2 cell lines. Together, our findings suggest that Mip-3alpha has the potential to act via autocrine and paracrine mechanisms to contribute to the pathobiology of human pancreatic cancer.

  13. Exploration on natural product anibamine side chain modification toward development of novel CCR5 antagonists and potential anti-prostate cancer agents.

    Science.gov (United States)

    Xu, Guoyan G; Zaidi, Saheem A; Zhang, Feng; Singh, Shilpa; Raborg, Thomas J; Yuan, Yunyun; Zhang, Yan

    2015-09-01

    Prostate cancer is one of the leading causes of death among males in the world. Prostate cancer cells have been shown to express upregulated chemokine receptor CCR5, a G protein-coupled receptor (GPCR) that relates to the inflammation process. Anibamine, a natural product containing a pyridine ring and two aliphatic side chains, was shown to carry a binding affinity of 1 μM at CCR5 as an antagonist with potential anti-cancer activity. However, it is not drug-like according to the Lipinski's rule of five mainly due to its two long aliphatic side chains. In our effort to improve its drug-like property, a series of anibamine derivatives were designed and synthesized by placement of aromatic side chains through an amide linkage to the pyridine ring. The newly synthesized compounds were tested for their CCR5 affinity and antagonism, and potential anti-proliferation activity against prostate cancer cell lines. Basal cytotoxicity was finally studied for compounds showing potent anti-proliferation activity. It was found that compounds with hydrophobic substitutions on the aromatic systems seemed to carry more promising CCR5 binding and prostate cancer cell proliferation inhibition activities.

  14. CCR9-CCL25 interactions promote cisplatin resistance in breast cancer cell through Akt activation in a PI3K-dependent and FAK-independent fashion

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    Lillard James W

    2011-05-01

    Full Text Available Abstract Background Chemotherapy heavily relies on apoptosis to kill breast cancer (BrCa cells. Many breast tumors respond to chemotherapy, but cells that survive this initial response gain resistance to subsequent treatments. This leads to aggressive cell variants with an enhanced ability to migrate, invade and survive at secondary sites. Metastasis and chemoresistance are responsible for most cancer-related deaths; hence, therapies designed to minimize both are greatly needed. We have recently shown that CCR9-CCL25 interactions promote BrCa cell migration and invasion, while others have shown that this axis play important role in T cell survival. In this study we have shown potential role of CCR9-CCL25 axis in breast cancer cell survival and therapeutic efficacy of cisplatin. Methods Bromodeoxyuridine (BrdU incorporation, Vybrant apoptosis and TUNEL assays were performed to ascertain the role of CCR9-CCL25 axis in cisplatin-induced apoptosis of BrCa cells. Fast Activated Cell-based ELISA (FACE assay was used to quantify In situ activation of PI3Kp85, AktSer473, GSK-3βSer9 and FKHRThr24 in breast cancer cells with or without cisplatin treatment in presence or absence of CCL25. Results CCR9-CCL25 axis provides survival advantage to BrCa cells and inhibits cisplatin-induced apoptosis in a PI3K-dependent and focal adhesion kinase (FAK-independent fashion. Furthermore, CCR9-CCL25 axis activates cell-survival signals through Akt and subsequent glycogen synthase kinase-3 beta (GSK-3β and forkhead in human rhabdomyosarcoma (FKHR inactivation. These results show that CCR9-CCL25 axis play important role in BrCa cell survival and low chemotherapeutic efficacy of cisplatin primarily through PI3K/Akt dependent fashion.

  15. CCL21/CCR7 promotes G2/M phase progression via the ERK pathway in human non-small cell lung cancer cells.

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    Ying Xu

    Full Text Available C-C chemokine receptor 7 (CCR7 contributes to the survival of certain cancer cell lines, but its role in the proliferation of human non-small cell lung cancer (NSCLC cells remains vague. Proliferation assays performed on A549 and H460 NSCLC cells using Cell Counting Kit-8 indicated that activation of CCR7 by its specific ligand, exogenous chemokine ligand 21 (CCL21, was associated with a significant linear increase in cell proliferation with duration of exposure to CCL21. The CCL21/CCR7 interaction significantly increased the fraction of cells in the G(2/M phase of the cell cycle as measured by flow cytometry. In contrast, CCL21/CCR7 had no significant influence on the G(0/G(1 and S phases. Western blot and real-time PCR indicated that CCL21/CCR7 significantly upregulated expression of cyclin A, cyclin B1, and cyclin-dependent kinase 1 (CDK1, which are related to the G(2/M phase transition. The expression of cyclin D1 and cyclin E, which are related to the G(0/G(1 and G(1/S transitions, was not altered. The CCL21/CCR7 interaction significantly enhanced phosphorylation of extracellular signal-regulated kinase (P-ERK but not Akt, as measured by Western blot. LY294002, a selective inhibitor of PI3K that prevents activation of the downstream Akt, did not weaken the effect of CCL21/CCR7 on P-ERK. Coimmunoprecipitation further confirmed that there was an interaction between P-ERK and cyclin A, cyclin B1, or CDK1, particularly in the presence of CCL21. CCR7 small interfering RNA or PD98059, a selective inhibitor of MEK that disrupts the activation of downstream ERK, significantly abolished the effects of exogenous CCL21. These results suggest that CCL21/CCR7 contributes to the time-dependent proliferation of human NSCLC cells by upregulating cyclin A, cyclin B1, and CDK1 potentially via the ERK pathway.

  16. Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in Mice

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    Mathieu Paul Rodero

    2013-06-01

    Full Text Available Expression of the CC chemokine receptor 1 (CCR1 by tumor cells has been associated with protumoral activity; however, its role in nontumoral cells during tumor development remains elusive. Here, we investigated the role of CCR1 deletion on stromal and hematopoietic cells in a liver metastasis tumor model. Metastasis development was strongly impaired in CCR1-deficient mice compared to control mice and was associated with reduced liver monocyte infiltration. To decipher the role of myeloid cells, sublethally irradiated mice were reconstituted with CCR1-deficient bone marrow (BM and showed better survival rates than the control reconstituted mice. These results point toward the involvement of CCR1 myeloid cell infiltration in the promotion of tumor burden. In addition, survival rates were extended in CCR1-deficient mice receiving either control or CCR1-deficient BM, indicating that host CCR1 expression on nonhematopoietic cells also supports tumor growth. Finally, we found defective tumor-induced neoangiogenesis (in vitro and in vivo in CCR1-deficient mice. Overall, our results indicate that CCR1 expression by both hematopoietic and nonhematopoietic cells favors tumor aggressiveness. We propose CCR1 as a potential therapeutical target for liver metastasis therapy.

  17. CCL5-403, CCR5-59029, and Delta32 polymorphisms and cancer risk: a meta-analysis based on 20,625 subjects.

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    Ying, Houqun; Wang, Jie; Gao, Xueren

    2014-06-01

    Associations between CCL5-403, CCR5-59029, and Delta32 polymorphisms and cancer risk are inconclusive. To derive a more precise estimation of the association, we performed a meta-analysis by searching PubMed, EMBASE, Google scholar, and WanFang databases. A total of 20 eligible articles with 39 studies were included. Of those studies, there were 21 studies for CCR5-Delta32 polymorphism, 9 studies for CCR5-59029 polymorphism, and 9 studies for CCL5-403 polymorphism. Combined analysis revealed no associations between these polymorphisms and cancer risk. However, subgroup analysis by ethnicity suggested that CCR5-59029 polymorphism was associated with the risk of cancer among Asian populations (A vs. G: odds ratio (OR)=1.36, 95 % confidence interval (CI) 1.13-1.65, P H=0.27; AA vs. GG: OR=2.07, 95 % CI 1.37-3.12, P H=0.17; GA+AA vs. GG: OR=1.35, 95 % CI 1.03-1.77, P H=0.92; AA vs. GA+GG: OR=1.98, 95 % CI 1.01-3.88, P H=0.08), but not among Caucasian populations. CCL5-403 polymorphism was associated with the risk of cancer among African populations (A vs. G: OR=0.68, 95 % CI 0.55-0.83, P H=0.14; AA vs. GG: OR=0.51, 95 % CI 0.33-0.77, P H=0.52; AG vs. GG: OR=0.58, 95 % CI 0.42-0.80, P H=0.14; AG+AA vs. GG: OR=0.56, 95 % CI 0.41-0.75, P H=0.13), but not among Caucasian populations and Asian populations. Overall, this meta-analysis indicated that CCR5-Delta32 was not associated with the risk of cancer. CCR5-59029 polymorphism contributed to cancer risk among Asian populations, and CCL5-403 polymorphism was associated with the decreased risk of cancer among African populations.

  18. 趋化因子受体CXCR4和CCR7在甲状腺癌中的表达及其临床病理意义%Expressions of Chemokine Receptor CXCR4 and CCR7 in Thyroid Cancer and Its Clinicopathologic Significance

    Institute of Scientific and Technical Information of China (English)

    熊斌; 王崇树

    2011-01-01

    目的 探讨趋化因子受体CXCR4和CCR7在甲状腺癌中的表达及其临床病理意义.方法 选取2006~2009年期间在我院行手术治疗的甲状腺癌患者55例和2009年在我院行手术治疗的甲状腺腺瘤患者30例,采用免疫组织化学染色SP法检测甲状腺癌及甲状腺腺瘤组织中的CXCR4和CCR7的表达.结果 CXCR4和CCR7在甲状腺癌中的表达阳性率均明显高于甲状腺腺瘤(P<0.01).CXCR4和CCR7在临床分期为Ⅲ+Ⅳ期的甲状腺癌患者中的表达阳性率均明显高于临床分期为Ⅰ+Ⅱ期者(P<0.05); CCR7在有淋巴结转移的甲状腺癌中的表达阳性率明显高于无淋巴结转移者(P<0.05),而CXCR4的表达阳性率与甲状腺癌患者有无淋巴结转移无关(P>0.05); CXCR4和CCR7在甲状腺癌组织中的表达阳性率与甲状腺癌患者的年龄和性别均无关(P>0.05).在甲状腺癌中,CXCR4阳性表达和CCR7阳性表达呈正相关(rs=0.491,P=0.000).结论 CXCR4和CCR7协同参与了甲状腺癌的进展,可作为判断甲状腺癌预后的指标;CCR7高表达提示甲状腺癌容易发生淋巴结转移.%Objective To investigate the expressions of chemokine receptor CXCR4 and CCR7 in thyroid cancer and its clinicopathologic significance. Methods Fifty-five patients with thyroid cancer were selected in the Affiliated Hospital of North Sichuan Medical College from 2006 to 2009, and 30 patients with thyroid adenoma were selected in the same hospital during 2009. The expressions of CXCR4 and CCR7 were detected in all the selected cases samples (including thyroid cancer and thyroid adenoma) by immunohistochemical SP technique. Results The positive expression rates of CXCR4 and CCR7 in the thyroid cancer were higher than those in the thyroid adenoma (P0. 05)? And which of CXCR4 and CCR7 were also independent of the age and gender of the patients with thyroid cancer (P>0. 05). The positive expressions of CCR7 and CXCR4 in all the patients with thyroid cancer was

  19. CCR7 mediates the TNF-α-induced lymphatic metastasis of gallbladder cancer through the “ERK1/2 - AP-1” and “JNK - AP-1” pathways

    OpenAIRE

    Hong, HaiJie; He, CaiLong; Zhu, Siyuan; Zhang, Yanhui; Wang, Xiaoqian; She, Feifei; Chen, Yanling

    2016-01-01

    Background CC-chemokine receptor 7 (CCR7), which plays an important role in cell directional movement, is highly expressed in various cancers and positively related to lymph node metastasis. The inflammatory cytokine tumour necrosis factor (TNF)-α promotes tumour progression and lymph node metastasis in gallbladder cancer (GBC). However, the expression of CCR7 in GBC is unclear, and its role in the TNF-α-induced lymphatic metastasis of GBC requires further research. Methods The expression of ...

  20. Expression of CCR7 and CD62L in non-small cell lung cancer and their correlation with lymph node metastasis%非小细胞肺癌中CCR7和CD62L表达及与淋巴结转移的关系

    Institute of Scientific and Technical Information of China (English)

    赵焕芬; 何春年; 陈琛; 张秀智; 徐明堂

    2012-01-01

    Objective To approach the expression of CC chemokine receptor 7 (CCR7) and L-selectin( CD62L) in non-small cell lung cancer( NSCLC) and their correlation with lymph node metastasis. Methods The expression of CCR7 and CD62L were tested by imunohistochemical method in 80 cases of NSCLC specimens and 20 cases of pericancerous normal lung specimens, the positive rates in patients with and without lymph node metastasis were analyzed. Results The positive rates of CCR7 and CD62L expression in NSCLC specimens were significantly higher than those in pericancerous normal lung specimens ( both P < 0.05 ) , further more there was correlation between the expression of CCR7 and CD62L in NSCLC ( P < 0.05). In patients with lymph node metastasis, the positive rates of CCR7 and CD62L expression were significantly higher than those in patients without lymph node metastasis ( both P < 0. 05 ). Conclusions Over-expression of CCR7 and CD62L are found in NSCLC. CCR7 and CD62L maybe participate together in the lymph node metastasis of NSCLC.%目的 探讨CC趋化因子受体7(CCR7)和L-选择素(CD62L)在非小细胞肺癌(NSCLC)组织中的表达及其与淋巴结转移的关系.方法 采用免疫组化法检测80份NSCLC癌组织和20份癌旁正常肺组织标本中CCR7和CD62L表达,比较二者在淋巴结转移者与无淋巴结转移者中的阳性表达率.结果 NSCLC癌组织中CCR7和CD62L表达阳性率均明显高于癌旁正常肺组织(P均<0.05),且CCR7表达与CD62L表达有明显相关性(P<0.05).有淋巴结转移者CCR7和CD62L表达阳性率均明显高于无淋巴结转移者(P均<0.05).结论 NSCLC癌组织中CCR7和CD62L表达均上调,二者可能共同参与了NSCLC的淋巴结转移过程.

  1. Correlation of vascular endothelial growth factor C and chemokine receptor CCR7 with lymph node metastasis in bladder cancer%血管内皮生长因子C和趋化因子受体CCR7的表达与膀胱癌淋巴结转移之间的关系

    Institute of Scientific and Technical Information of China (English)

    黄启成; 李鑫磊; 杨树才; 孔建; 马晶

    2011-01-01

    Objective To investigate the effects of vascular endothelial growth factor (VEGF)-C and CCR7 in lymph node metastasis, the expression of VEGF-C and CCR7 was observed in bladder cancer. Methods Sixty paraffinembedded specimens from patients with bladder cancer were derided into lymph node metastasis group(n=36) and nonmetastasis group(n=24). The expressions of VEGF-C and CCR7 were detected by immunohistochemical stain and Western blot. Results VEGF-C and CCR7 proteins were expressed predominantly in the cytoplasm or/and membrane of the tumor cells, the expression of VEGF-C and CCR7 in lymph node metastasis group was significantly higher than that in nonmetastnsis group (P<0.05). The expressional rate of VEGF-C and CCR7 synergically was 61.1% and 33.3% in lymph node metastasis group and in nonmetastasis group respectively. Higher accuracy to predict lymph node metastasis was found in combined examination of VEGF-C and CCR7 expression with an area 0.708 under ROC curve. Conclusion VEGF-C and CCR7 indicated synergically role in promoting tumor lymph node metastasis, combined examination of VEGF-C and CCR7 might be beneficial for diagnosis of lymph node metastasis in bladder cancer.%目的 观察血管内皮生长因子(VEGF)-C和趋化因子受体CCR7在膀胱移行细胞癌组织内的表达情况,分析VEGF-C和CCR7表达与癌淋巴结转移之间的关系.方法 取膀胱癌病例60例,其中,淋巴结转移组36例,无淋巴结转移组24例.应用免疫组化法和Western blot技术观察VEGF-C和CCR7在膀胱癌组织内的表达.结果 VEGF-C和CCR7主要表达于膀胱癌细胞胞浆或,和胞膜内,二者在淋巴结转移组的表达率明显高于无淋巴结转移组.VEGF-C和CCR7蛋白同时表达在淋巴结转移组和非淋巴结转移组中的表达率分别为61.1%和33.3%,VEGF-C和CCR7的表达具有显著的相关性,联合检测VEGF-C和CCR7诊断膀胱癌淋巴结转移具有较高的准确度,ROC曲线下面积达0.708.结论 VEGF-C和CCR7

  2. National Cancer Institute Prostate Cancer Genetics Workshop.

    Science.gov (United States)

    Catalona, William J; Bailey-Wilson, Joan E; Camp, Nicola J; Chanock, Stephen J; Cooney, Kathleen A; Easton, Douglas F; Eeles, Rosalind A; FitzGerald, Liesel M; Freedman, Matthew L; Gudmundsson, Julius; Kittles, Rick A; Margulies, Elliott H; McGuire, Barry B; Ostrander, Elaine A; Rebbeck, Timothy R; Stanford, Janet L; Thibodeau, Stephen N; Witte, John S; Isaacs, William B

    2011-05-15

    Compelling evidence supports a genetic component to prostate cancer susceptibility and aggressiveness. Recent genome-wide association studies have identified more than 30 single-nucleotide polymorphisms associated with prostate cancer susceptibility. It remains unclear, however, whether such genetic variants are associated with disease aggressiveness--one of the most important questions in prostate cancer research today. To help clarify this and substantially expand research in the genetic determinants of prostate cancer aggressiveness, the first National Cancer Institute Prostate Cancer Genetics Workshop assembled researchers to develop plans for a large new research consortium and patient cohort. The workshop reviewed the prior work in this area and addressed the practical issues in planning future studies. With new DNA sequencing technology, the potential application of sequencing information to patient care is emerging. The workshop, therefore, included state-of-the-art presentations by experts on new genotyping technologies, including sequencing and associated bioinformatics issues, which are just beginning to be applied to cancer genetics.

  3. Chemokine Ligand 5 (CCL5 and chemokine receptor (CCR5 genetic variants and prostate cancer risk among men of African Descent: a case-control study

    Directory of Open Access Journals (Sweden)

    Kidd LaCreis R

    2012-11-01

    Full Text Available Abstract Background Chemokine and chemokine receptors play an essential role in tumorigenesis. Although chemokine-associated single nucleotide polymorphisms (SNPs are associated with various cancers, their impact on prostate cancer (PCA among men of African descent is unknown. Consequently, this study evaluated 43 chemokine-associated SNPs in relation to PCA risk. We hypothesized inheritance of variant chemokine-associated alleles may lead to alterations in PCA susceptibility, presumably due to variations in antitumor immune responses. Methods Sequence variants were evaluated in germ-line DNA samples from 814 African-American and Jamaican men (279 PCA cases and 535 controls using Illumina’s Goldengate genotyping system. Results Inheritance of CCL5 rs2107538 (AA, GA+AA and rs3817655 (AA, AG, AG+AA genotypes were linked with a 34-48% reduction in PCA risk. Additionally, the recessive and dominant models for CCR5 rs1799988 and CCR7 rs3136685 were associated with a 1.52-1.73 fold increase in PCA risk. Upon stratification, only CCL5 rs3817655 and CCR7 rs3136685 remained significant for the Jamaican and U.S. subgroups, respectively. Conclusions In summary, CCL5 (rs2107538, rs3817655 and CCR5 (rs1799988 sequence variants significantly modified PCA susceptibility among men of African descent, even after adjusting for age and multiple comparisons. Our findings are only suggestive and require further evaluation and validation in relation to prostate cancer risk and ultimately disease progression, biochemical/disease recurrence and mortality in larger high-risk subgroups. Such efforts will help to identify genetic markers capable of explaining disproportionately high prostate cancer incidence, mortality, and morbidity rates among men of African descent.

  4. National Ovarian Cancer Coalition

    Science.gov (United States)

    ... List Signs & Symptoms Potential signs and symptoms of ovarian cancer: Bloating Pelvic or abdominal pain Trouble eating or ... to urinate urgently or often Other symptoms of ovarian cancer can include: Fatigue Upset stomach or heartburn Back ...

  5. National Cancer Institute News

    Science.gov (United States)

    ... life among African-American cancer survivors. Study finds premature death rates diverge in the United States by race and ethnicity January 25, 2017 Premature death rates declined among Hispanics, blacks, and Asian/Pacific ...

  6. Relationship between D2-40 and CCR7 Expression and lymph Lymph Node Metastasis in Non-small Cell Lung Cancer%非小细胞肺癌中D2-40、CCR7的表达与淋巴结转移的关系

    Institute of Scientific and Technical Information of China (English)

    杨润祥; 任宏轩; 段林灿; 罗春香; 李梅; 刘林

    2011-01-01

    Objective To explore the relationship between D2-40 and CCR7 expression and lymph node metastasis in Non-small cell lung cancer. Methods D2-40 and CCR7 expression in 104 non-small cell lung cancer patients, 10 cases of with tissues adjacent to non-small cell lung cancer, and 5 normal lung tissues is identified by MAX Vision, an immunohistochemical staining technique. The lymphatic endothelial cells are meanwhile marked by D2-40 for MLVD calculation. Results The MLVD counts are strongly increased in the non-small cell lung cancers compared with those in normal lung tissues ( 7. 81 ± 2. 22 vs. 4. 20 ± 1.07, P<0. 001 ). The MLVD counts of the 47 cases with lymph node positive also are higher than those of the 57 cases with lymph node negative (8. 39 ± 2. 35>7. 33 ± 2. 00, P<0. 001). CCR7 positive rate is 82. 7% (86/104) in the 104 cases of non-small cell lung cancers, 30% (3/10) in the 10 cases of pericancerous tissues, and 20% (1/5) in the 5 cases of normal lung tissues. The ratio of CCR7 in lymph nodes positive is more increased than that lymph nodes negative (87. 2% vs 61.4%, x2 = 87. 4, P <0. 05 ). The MLVD count of CCR7 of the positive group is(8. 51 ± 2. 03), higher than that of the CCR7 of the negative group(6. 01 ± 1.59)(P<0. 05). The expression of the MLVD marked by D)2-40 is positively correlated to the CCR7 in the non-small cell lung cancers (coefficient of correlation, r= 0. 597,P<0. 000). Conclusion In non-small cell lung cancers, the increased expression of CCR7 in the lymph node metastasis positive group is positively related to the MLVD marked by D2-40. D2-40 staining is observed only in the lymphatic endothelial cells, while the increased expression of CCR7 in cancer cells is an early event of lymph node metastases. The combination of CCR7 and D2-40 measurement is likely to predict lymphatic metastases.%目的 探讨CCR7及D2-40在非小细胞肺癌中的表达与淋巴结转移的关系.方法 采

  7. Study on the correlation between the expression levels of chemokine receptor CCR7,CXCR4 and prognosis of patients with non-small-cell lung cancer%CCR7蛋白和 CXCR4蛋白表达水平与非小细胞肺癌患者的预后及相关性研究

    Institute of Scientific and Technical Information of China (English)

    陈晓东; 任开明; 段琼玉; 宣莹; 吴荣

    2016-01-01

    Objective To observe the expression levels of chemokine receptor CCR7,CXCR4 in non-small-cell lung cancer(NSCLC)tissues,and to explore the correlation between the expression levels of CCR7,CXCR4 and prognosis of patients with non-small-cell lung cancer. Methods Seventy-two patients with NSCLC who were treated in our hospital from March 2012 to May 2013 were enrolled in the study. The expression levels of CCR7,CXCR4 were detected by immunohistochemistry(IHC)in 72 cases of NSCLC tissues and 36 cases of distal normal lung tissues of patients with NSCLC. The correlations between the expression levels of CCR7,CXCR4 and general clinical data of patients as well as between the expression levels of CCR7,CXCR4 and prognosis of patients with NSCLC were analyzed. Results There were significant differences in the expression levels of CCR7,CXCR4 between NSCLC tissues and distal normal lung tissues( P 0. 05). The prognosis of patients with high-expression of CCR7 or CXCR4 was poorer,as compared with that of patients with low-expression of CCR7 or CXCR4, moreover,the expression levels of CCR7 were positively correlated to those of CXCR4 in NSCLC. Conclusion The expression levels of CCR7,CXCR4 in NSCLC tissues are significantly higher than those in distal normal lung tissues,furthermore,the expression levels of CCR7,CXCR4 are closely correlated to clinical stagig and lymph node metastasis of NSCLC. The expression levels of CCR7 are positively related with those of CXCR4,moreover,the prognosis of patients with high-expression of CCR7 or CXCR4 is poorer,as compared with that of patients with low-expression of CCR7 or CXCR4.%目的:通过对比分析 CCR7蛋白、CXCR4蛋白在非小细胞肺癌组织中的表达水平探讨这两种趋化因子表达的相关性以及患者的预后与其相关性。方法选择2012年3月至2013年5月进行非小细胞肺癌治疗的患者72例,分别取每位患者的非小细胞肺癌组织,并且随机选择36例患者的正常组织,

  8. CCR3 is a target for age-related macular degeneration diagnosis and therapy.

    Science.gov (United States)

    Takeda, Atsunobu; Baffi, Judit Z; Kleinman, Mark E; Cho, Won Gil; Nozaki, Miho; Yamada, Kiyoshi; Kaneko, Hiroki; Albuquerque, Romulo J C; Dridi, Sami; Saito, Kuniharu; Raisler, Brian J; Budd, Steven J; Geisen, Pete; Munitz, Ariel; Ambati, Balamurali K; Green, Martha G; Ishibashi, Tatsuro; Wright, John D; Humbles, Alison A; Gerard, Craig J; Ogura, Yuichiro; Pan, Yuzhen; Smith, Justine R; Grisanti, Salvatore; Hartnett, M Elizabeth; Rothenberg, Marc E; Ambati, Jayakrishna

    2009-07-09

    Age-related macular degeneration (AMD), a leading cause of blindness worldwide, is as prevalent as cancer in industrialized nations. Most blindness in AMD results from invasion of the retina by choroidal neovascularisation (CNV). Here we show that the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in choroidal neovascular endothelial cells in humans with AMD, and that despite the expression of its ligands eotaxin-1, -2 and -3, neither eosinophils nor mast cells are present in human CNV. Genetic or pharmacological targeting of CCR3 or eotaxins inhibited injury-induced CNV in mice. CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation because it occurred in mice lacking eosinophils or mast cells, and was independent of macrophage and neutrophil recruitment. CCR3 blockade was more effective at reducing CNV than vascular endothelial growth factor A (VEGF-A) neutralization, which is in clinical use at present, and, unlike VEGF-A blockade, is not toxic to the mouse retina. In vivo imaging with CCR3-targeting quantum dots located spontaneous CNV invisible to standard fluorescein angiography in mice before retinal invasion. CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition.

  9. 宫颈癌CCR7、CXCR4和CCL21的表达与淋巴结转移的研究%Expression of CXCR4, CCL21 and CCR7 in Cervical Cancer and Their Correlation with Clinical Pathology

    Institute of Scientific and Technical Information of China (English)

    黄树峰; 蒋学锋; 盖炼炼; 朱艳宾

    2013-01-01

    目的 研究CXCR4、CCL21及CCR7在宫颈癌中的表达及其与临床病理参数的关系.方法 采用免疫组化方法检测93例宫颈癌CXCR4、CCL21及CCR7蛋白表达水平.结果 CXCR4、CCR7、CCL21在宫颈癌组织中的阳性表达率分别72.0% (67/93)、68.8% (64/93)、75.3% (70/93),主要表达于细胞膜或/和细胞浆内.CXCR4、CCR7及CCL21阳性表达与宫颈癌细胞病理分化程度和临床分期有密切关系(P<0.05或P<0.01).有淋巴结转移的CXCR4、CCR7及CCL21蛋白表达均显著高于无淋巴结转移组(P<0.01).结论 CXCR4、CCR7及CCL21可能在促进宫颈癌淋巴结转移,它们的阳性表达在宫颈癌生长、侵袭和转移过程中起重要作用.%Objective To investigate the expression of CXCR4,CCL21 and CCR7 in cervical cancer and their correlation with clinical pathology.Methods SP immunohistochemical staining was applied to detect the expression levels of CXCR4,CCL21 and CCR7 in 93 patients with cervical cancer disease.Results The positive rate of CXCR4,CCL21 and CCR7 in cervical cancers was 72.0%,68.8% and 75.3% respectively.The positive rate of CXCR4,CCL21 and CCR7 was closely related to the histological grading and clinical stage of cervical cancers(P <0.05 or P <0.01).The CXCR4,CCL21 and CCR7 protein level was significantly higher in patients with lymphatic metastasis than that in patients without lymphatic metastasis (P < 0.01).Conclusion The expression of CXCR4,CCL21 and CCR7 is correlated with lymph node metastasis,and they may play an important role in the growth in file rating development and metastasis of cervical cancers.

  10. 趋化因子受体CCR7在结直肠癌中的表达及临床意义%The expression of chemokine receptor CCR7 in colorectal cancer and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    黄河; 张才全; 赵林

    2010-01-01

    目的 检测趋化因子受体CCR7在结直肠癌中的表达状态,探讨CCR7在结直肠癌发病中的临床意义.方法 采用逆转录PCR(RT-PCR)检测CCR7mRNA表达,采用免疫组化检测CCR7蛋白表达.结果 31例结直肠癌组织中CCR7mRNA呈阳性表达,显著高于其配对的癌旁正常组织(7例阳性),38例结直肠癌组织标本检出CCR7蛋白表达,在相应配对的癌旁组织中则有9例检出.在伴发淋巴结转移的结肠癌组织中,CCR7表达比未发生转移者增强.结论 CCR7在结直肠癌中过度表达,CCR7表达可能与结直肠癌发生发展及转移存在密切关系.

  11. siRNA CCR7 inhibition of metastasis of breast cancer cells in vitro%siRNA CCR7抑制乳腺癌细胞转移的体外实验研究

    Institute of Scientific and Technical Information of China (English)

    余术宜; 吴文芳; 李建哲; 吉午阳; 陈玉祥

    2011-01-01

    目的 探讨CCR7对肿瘤转移的影响.方法 构建siRNA-CCR7载体,稳定转染表达CCR7的肿瘤细胞株MDA-MB-231,在mRNA和蛋白水平检测其对肿瘤细胞CCR7的抑制作用,再用趋化及侵袭,实验检测其对肿瘤细胞趋化、侵袭能力的影响.结果 稳定转染siRNA1、siRNA2的MDA-MB-231细胞,在mRNA、蛋白水平均能有效抑制肿瘤细胞CCR7表达,并能抑制CCL21刺激的趋化和侵袭能力.结论 siRNA-CCR7能有效抑制乳腺癌细胞MDA-MB-231的趋化和侵袭,该实验结果对进一步探讨CCR7在肿瘤转移中的作用、探讨CCR7化学抑制剂或中药成分具有重要启示作用.

  12. TGF-β1-induced EMT promotes targeted migration of breast cancer cells through the lymphatic system by the activation of CCR7/CCL21-mediated chemotaxis.

    Science.gov (United States)

    Pang, M-F; Georgoudaki, A-M; Lambut, L; Johansson, J; Tabor, V; Hagikura, K; Jin, Y; Jansson, M; Alexander, J S; Nelson, C M; Jakobsson, L; Betsholtz, C; Sund, M; Karlsson, M C I; Fuxe, J

    2016-02-11

    Tumor cells frequently disseminate through the lymphatic system during metastatic spread of breast cancer and many other types of cancer. Yet it is not clear how tumor cells make their way into the lymphatic system and how they choose between lymphatic and blood vessels for migration. Here we report that mammary tumor cells undergoing epithelial-mesenchymal transition (EMT) in response to transforming growth factor-β (TGF-β1) become activated for targeted migration through the lymphatic system, similar to dendritic cells (DCs) during inflammation. EMT cells preferentially migrated toward lymphatic vessels compared with blood vessels, both in vivo and in 3D cultures. A mechanism of this targeted migration was traced to the capacity of TGF-β1 to promote CCR7/CCL21-mediated crosstalk between tumor cells and lymphatic endothelial cells. On one hand, TGF-β1 promoted CCR7 expression in EMT cells through p38 MAP kinase-mediated activation of the JunB transcription factor. Blockade of CCR7, or treatment with a p38 MAP kinase inhibitor, reduced lymphatic dissemination of EMT cells in syngeneic mice. On the other hand, TGF-β1 promoted CCL21 expression in lymphatic endothelial cells. CCL21 acted in a paracrine fashion to mediate chemotactic migration of EMT cells toward lymphatic endothelial cells. The results identify TGF-β1-induced EMT as a mechanism, which activates tumor cells for targeted, DC-like migration through the lymphatic system. Furthermore, it suggests that p38 MAP kinase inhibition may be a useful strategy to inhibit EMT and lymphogenic spread of tumor cells.

  13. 趋化因子受体CCR7在乳腺癌淋巴结转移中的作用%Effect of chemokine receptor CCR7 in breast cancer tissue on lymph node metastasis

    Institute of Scientific and Technical Information of China (English)

    朱旬; 甄林林; 郑伟; 王汉晋; 王萱仪; 武正炎

    2006-01-01

    目的:探讨趋化因子受体CCR7在乳腺癌中的表达意义. 方法:应用RT-PCR及免疫组织化学方法检测42例乳腺癌组织和10例乳腺纤维腺瘤中CCR7的表达. 结果:在乳腺癌组织中CCR7 mRNA表达42.9%, CCR7蛋白表达35.7%,在乳腺纤维腺瘤中仅有1例CCR7 mRNA表达. 无淋巴结转移者CCR7蛋白阳性表达率为11.1%(2/18),而有淋巴结转移阳性表达率为54.2%(13/24)(P<0.01);临床TNM分期Ⅰ,Ⅱ,Ⅲ期的阳性表达率分别为0%,39.1%,60.0%(P<0.01). 结论:CCR7可能是介导淋巴结转移和组织浸润的重要机制之一.

  14. 趋化因子受体CCR7在胃癌组织和细胞株中过度表达%Overexpression of Chemokine Receptor CCR7 in Gastric Cancer Tissue and Cell Lines

    Institute of Scientific and Technical Information of China (English)

    严燕国; 吴瑞乔; 沈新明; 杨鹏平; 王益

    2010-01-01

    趋化因子受体CCR7高表达与肿瘤淋巴结转移等因素密切相关.目的:检测CCR7在胃癌组织和细胞株中的表达情况,探讨CCR7在胃癌中的作用.方法:采用实时PCR技术检测30例胃癌组织及其配对癌旁组织中的CCR7 mRNA表达,RT-PCR检测人胃癌细胞株SGC-7901和AGS中的CCR7 mRNA表达.分析胃癌组织中的CCR7mRNA表达与胃癌临床病理特征间的相关性.结果:CCR7 mRNA在胃癌组织中的表达水平显著高于其配对癌旁组织(P<0.05).人胃癌细胞株SGC-7901和AGS中均存在明显CCR7 mRNA表达.CCR7 mRNA表达与胃癌浸润深度、淋巴结转移和TNM分期相关(P<0.05).结论:CCR7在胃癌中存在过度表达,可能参与了胃癌的进展过程.

  15. COX-2、CCR7表达与乳腺癌临床病理参数的关系%Correlation between the expressions of COX-2, CCR7 and clinicopathologic parameters in breast cancer

    Institute of Scientific and Technical Information of China (English)

    余术宜; 李建哲; 吉午阳; 周志群; 庞琼; 陈玉祥

    2011-01-01

    目的 探讨环氧合酶2(cyclooxygenase 2,COX-2)、C-C家族趋化因子受体7(C-C chemokinereceptor 7,CCR7)表达与乳腺癌临床病理学参数的关系,并分析COX-2、CCR7表达的相关性.方法 用免疫组织化学检测乳腺癌组织80例、乳腺癌癌旁组织15例中COX-2、CCR7的表达,分析其表达与临床病理学参数的关系,对COX-2、CCR7的表达进行相关性分析.结果 在乳腺癌组织,COX-2、CCR7均高表达,表达率分别为42.5%和38.8%,两者表达有相关性(P<0.05).COX-2、CCR7高表达均与肿瘤的病理分化、肿瘤大小、淋巴转移、TNM分期相关(p<0.05),与组织学分型、患者年龄无关.结论 COX-2、CCR7在乳腺癌组织高表达,两者表达有相关性,且与乳腺癌临床病理学参数有关.提示临床上联合检测COX-2和CCR7对乳腺癌转移的预测可能会有所帮助.

  16. 乳腺癌组织中趋化因子受体CCR7的表达及其意义%Expression and its value of chemokine receptor CCR7 expression in breast cancer

    Institute of Scientific and Technical Information of China (English)

    杨润祥; 马飞; 李梅; 梁进; 江自然; 张灿珍

    2007-01-01

    目的:检测乳腺癌中趋化因子受体CCR7的表达及其临床意义.方法:收集65例根治性切除的乳腺癌标本,用免疫组织化学法检测CCR7的表达,分析CCR7的表达与乳腺癌患者临床病理特征之间的相关性.结果:65例标本中,42例存在CCR7的高表达(64.6%),CCR7的表达与乳腺癌患者的淋巴结转移、TNM分期和肿瘤组织中淋巴细胞的浸润程度密切相关,但与淋巴结转移的数目无关.结论:趋化因子受体CCR7与乳腺癌淋巴结转移密切相关,其在乳腺癌的临床诊治中有参考价值.

  17. Elucidating a Key Anti-HIV-1 and Cancer-Associated Axis: The Structure of CCL5 (Rantes) in Complex with CCR5

    Science.gov (United States)

    Tamamis, Phanourios; Floudas, Christodoulos A.

    2014-06-01

    CCL5 (RANTES) is an inflammatory chemokine which binds to chemokine receptor CCR5 and induces signaling. The CCL5:CCR5 associated chemotactic signaling is of critical biological importance and is a potential HIV-1 therapeutic axis. Several studies provided growing evidence for the expression of CCL5 and CCR5 in non-hematological malignancies. Therefore, the delineation of the CCL5:CCR5 complex structure can pave the way for novel CCR5-targeted drugs. We employed a computational protocol which is primarily based on free energy calculations and molecular dynamics simulations, and report, what is to our knowledge, the first computationally derived CCL5:CCR5 complex structure which is in excellent agreement with experimental findings and clarifies the functional role of CCL5 and CCR5 residues which are associated with binding and signaling. A wealth of polar and non-polar interactions contributes to the tight CCL5:CCR5 binding. The structure of an HIV-1 gp120 V3 loop in complex with CCR5 has recently been derived through a similar computational protocol. A comparison between the CCL5 : CCR5 and the HIV-1 gp120 V3 loop : CCR5 complex structures depicts that both the chemokine and the virus primarily interact with the same CCR5 residues. The present work provides insights into the blocking mechanism of HIV-1 by CCL5.

  18. Frederick National Laboratory for Cancer Research

    Data.gov (United States)

    Federal Laboratory Consortium — Among the many cancer research laboratories operated by NCI, the Frederick National Laboratory for Cancer Research(FNLCR) is unique in that it is a Federally Funded...

  19. 周围型肺癌64层螺旋CT征象、病理分型与CCR7表达相关性研究%Studies on the correlation between the 64-slice CT features, pathologic classifications and expression of CCR7 in peripheral lung cancer

    Institute of Scientific and Technical Information of China (English)

    赵胜祥; 张琴; 陈朝晖

    2013-01-01

    Objective To explore the expression relationship between 64-slice CT features and the CCR7 (CC chemokine receptor 7) in peripheral lung cancer.Methods The data of 26 cases of peripheral lung cancer confirmed by operation and pathological classifications were clected.All patients had MSCT scan before operation,and without radiotherapy or chemotherapy.The expression of CCR7 was examined by means of SP immunohistochemical technology (Max Vision TM) in the 26 patients,and compared with the 64-slice CT features of lung cancer with the CCR7 immunohistochemical test results,data was analysed by SPSS 17.0 statistical software,the rate was compared with fisher exact method test,P <0.05 and the difference was statistically significant.Results ① The expression of CCR7 in the adenocarcinoma with positive expression rate was 75.0% (15/20),and in squamous cell carcinoma the positive expression rate was 33.3% (2/6),in the peripheral lung cancer,P <0.05,the difference was statistically significant; ② The expression of CCR7 in the cancer size of ≤3.0 cm the positive expression rate was 75.0% (15/20),and in the cancer size of > 3.0 cm the positive expression rate was 33.3% (2/6),P <0.05,the difference was statistically significant; ③ It was not associated between the expression of CCR7 and CT signs of the tumor deep lobulation,spiculate protuberance,vacuole sign,pleural indentation,spiculation,mediastinal lymph node metastasis,(P >0.05).Conclusion The positive expression of peripheral lung cancer of CCR7 is related to pathologic type,not associated with the diagnostic CT features.%目的 探讨周围型肺癌CT征象与CCR7(CC chemokine receptor 7,CC类趋化因子受体7)表达的关系.方法 收集资料完整并经手术、病理证实的周围型肺癌26例.全部患者术前均行64层螺旋CT平扫及增强扫描,术前未进行放射治疗或化疗.应用免疫组织化学染色(MaxVisionTM二步法)检测26例周围型肺癌中CCR7的表达水平,并将肺癌的CT征象与CCR

  20. 78 FR 19275 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-03-29

    ... Committee: National Cancer Institute Special Emphasis Panel Tumor Immunology. Date: June 26-27, 2013. Time... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed Meeting... Training Review Branch, Division of Extramural Activities, National Cancer Institute, 6116...

  1. 趋化因子受体CCR2拮抗剂在大鼠骨癌痛治疗中的可能机制%Underlying mechanism of chemokine receptor CCR2 antagonist in the treatment of bone cancer pain

    Institute of Scientific and Technical Information of China (English)

    徐振华; 杨建平; 胡计嬅; 陈婷; 左建玲

    2014-01-01

    Aim To investigate the effect of intrathecal injection of CCR2 antagonist on pain behaviours,spinal astrocytes activation in the spinal cord in a rat model of bone cancer pain. Methods Forty female SD rats weighing 150 ~180 g were randomly divided into five groups ( n=8 each ):(Ⅰ) sham group;(Ⅱ) sham +RS102895 group;(Ⅲ) bone cancer pain group;(Ⅳ) bone cancer pain + DMSO group;(Ⅴ) bone cancer pain+RS102895 group. Rats received i. t. injections of either RS102895 (3 g·L-1 ) 10 μl or 10%DMSO 10 μl at the time of 10-12 days after the operation. Bone cancer was induced by intra-tibial inoculation of 1 × 105 Walker 256 breast cancer cell. Mechanical hind paw withdrawal threshold test was performed one day before and at 3rd,6th,9th, 10th,11th and 12th days after surgery. Immunofluorescence was used to observe the activation of the spinal astrocytes. Results Compared with group Ⅰ, the rats in bone cancer pain group appeared obvious mechanical hyperalgesia (Ⅲ、Ⅳ、Ⅴ) ,the volume,shape and mean optical den-sity ( MOD) of spinal astrocytes could be seen obvious-ly increased,groupⅡhad no obvious statistical signifi-cance (P>0. 05). Compared with group Ⅳ ,i. t. in-jections of RS102895 increased the paw mechanical withdrawal threshold, suppressed the action of astro-cytes,reduced the MOD of spinal astrocytes. Conclu-sion CCR2 might participate in the formation of bone cancer pain via activating spinal astrocytes. CCR2 will be a potential target for the treatment of bone cancer pain.%目的:观察脊髓单核细胞趋化蛋白受体CCR2在大鼠骨癌痛形成过程中的可能机制。方法大鼠左侧胫骨骨髓腔内接种Walker256乳腺癌细胞制备骨癌痛模型。观察并测量各组大鼠术前1 d,术后3、6、9、10、11、12 d的机械痛阈值。术后12 d取材,免疫组织化学法检测脊髓背角星形胶质细胞标志物( GFAP)的平均光密度值( MOD),观察脊髓小胶质细胞增殖活化情况。结果与对照组相比,鞘内给予CCR

  2. 趋化因子受体CCR7在甲状腺癌中的表达%Expression of the Chemokine Receptor CCR7 in Thyroid Cancer

    Institute of Scientific and Technical Information of China (English)

    熊斌

    2011-01-01

    目的 探讨CCR7在甲状腺癌中的表达.方法 选取2006-2009年在我院行手术治疗的甲状腺癌患者55例和2009年在我院行手术治疗的甲状腺腺瘤患者30例,采用免疫组织化学染色SP法检测甲状腺癌、甲状腺腺瘤中的CCR7的表达.结果 CCR7在甲状腺癌中的阳性表达率明显高于甲状腺腺瘤,差异有统计学意义(P<0.01).CCR7在有淋巴结转移组的甲状腺癌中的阳性表达率高于无淋巴结转移组,差异有统计学意义(P<0.05).CCR7在临床分期为Ⅲ期+Ⅳ期的甲状腺癌组的阳性表达率高于临床分期为Ⅰ期+Ⅱ期组,两组差异有统计学意义(P<0.05).CCR7的阳性表达率与甲状腺癌患者的年龄和性别无关(P>0.05),差异无统计学意义.结论 CCR7参与了甲状腺癌的进展,可作为判断甲状腺癌预后的指标;CCR7高表达提示甲状腺癌容易发生淋巴结转移;抑制它的表达可能成为甲状腺癌新的治疗靶点.

  3. CCR3 is a therapeutic and diagnostic target for neovascular age-related macular degeneration

    OpenAIRE

    2009-01-01

    Age-related macular degeneration (AMD), a leading cause of blindness worldwide, is as prevalent as cancer in industrialized nations. Most blindness in AMD results from invasion of the retina by choroidal neovascularization (CNV). We report that the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in CNV endothelial cells in humans with AMD, and that, despite the expression of its ligands eotaxin-1, -2, and -3, neither eosinophils nor mast cells are present in human CNV. ...

  4. CCR6, the sole receptor for the chemokine CCL20, promotes spontaneous intestinal tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Bisweswar Nandi

    Full Text Available Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been associated with colorectal cancer growth and metastasis, however, a causal role for CCL20 signaling through CCR6 in promoting intestinal carcinogenesis has not been demonstrated in vivo. In this study, we aimed to determine the role of CCL20-CCR6 interactions in spontaneous intestinal tumorigenesis. CCR6-deficient mice were crossed with mice heterozygous for a mutation in the adenomatous polyposis coli (APC gene (APCMIN/+ mice to generate APCMIN/+ mice with CCR6 knocked out (CCR6KO-APCMIN/+ mice. CCR6KO-APCMIN/+ mice had diminished spontaneous intestinal tumorigenesis. CCR6KO-APCMIN/+ also had normal sized spleens as compared to the enlarged spleens found in APCMIN/+ mice. Decreased macrophage infiltration into intestinal adenomas and non-tumor epithelium was observed in CCR6KO-APCMIN/+ as compared to APCMIN/+ mice. CCL20 signaling through CCR6 caused increased production of CCL20 by colorectal cancer cell lines. Furthermore, CCL20 had a direct mitogenic effect on colorectal cancer cells. Thus, interactions between CCL20 and CCR6 promote intestinal carcinogenesis. Our results suggest that the intestinal tumorigenesis driven by CCL20-CCR6 interactions may be driven by macrophage recruitment into the intestine as well as proliferation of neoplastic epithelial cells. This interaction could be targeted for the treatment or prevention of malignancy.

  5. National Cancer Moonshot Initiative platform | Office of Cancer Genomics

    Science.gov (United States)

    As part of the Vice President’s National Cancer Moonshot Initiative, the National Cancer Institute has launched an online engagement platform to enable the research community and the public to submit cancer research ideas to a Blue Ribbon Panel of scientific experts. Any member of the public is encouraged to submit his or her ideas for reducing the incidence of cancer and developing better ways to prevent, treat, and cure all types of cancer. Research ideas may be submitted in the following areas:

  6. 75 FR 16816 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-04-02

    ... Committee: National Cancer Institute Special Emphasis Panel, NCI SPORE in Skin and Prostate Cancers. Date..., Cancer Construction; 93.393, Cancer Cause and Prevention Research; 93.394, Cancer Detection and Diagnosis... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  7. Glatiramer Acetate, Dimethyl Fumarate and Monomethyl Fumarate Up-Regulate the Expression of CCR10 on the Surface of Natural Killer Cells and Enhance their Chemotaxis and Cytotoxicity. Implications for Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Azzam Maghazachi

    2016-10-01

    Full Text Available In vitro harnessing of immune cells is the most important advance in the field of cancer immunotherapy. Results shown in the current paper may be used to harness natural killer (NK cells in vitro. It is observed that drugs used to treat multiple sclerosis such as glatiramer acetate, dimethyl fumarate and monomethyl fumarate up-regulate the expression of chemokines receptor 10 (CCR10 on the surface of human IL-2-activated NK cells. This is corroborated with increased chemotaxis of these cells towards the concentration gradients of the ligands for CCR10, namely CCL27 and CCL28. It is also demonstrated that these three drugs enhance NK cell cytotoxicity against tumor target cells, an activity that is abrogated by prior incubation of the cells with anti-CCR10 antibody. Because CCL27 and CCL28 are secreted by selective tumor types such as malignant melanoma, squamous cell carcinomas and colorectal cancer, respectively, it is hypothesized that activated NK cells may be harnessed in vitro with any of these drugs before utilizing them as a therapeutic modality for cancer.

  8. New registry: National Cancer Patient Registry--Colorectal Cancer.

    Science.gov (United States)

    Wendy, L; Radzi, M

    2008-09-01

    Colorectal cancer is emerging as one of the commonest cancers in Malaysia. Data on colorectal cancer from the National Cancer Registry is very limited. Comprehensive information on all aspects of colorectal cancer, including demographic details, pathology and treatment outcome are needed as the management of colorectal cancer has evolved rapidly over the years involving several disciplines including gastroenterology, surgery, radiology, pathology and oncology. This registry will be an important source of information that can help the development of guidelines to improve colorectal cancer care relevant to this country. The database will initially recruit all colorectal cancer cases from eight hospitals. The data will be stored on a customized web-based case report form. The database has begun collecting data from 1 October 2007 and will report on its first year findings at the end of 2008.

  9. 75 FR 20370 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-04-19

    ...@mail.nih.gov . Name of Committee: National Cancer Institute Special Emphasis Panel, Breast Cancer... Construction; 93.393, Cancer Cause and Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  10. 76 FR 16431 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-03-23

    ... Committee: National Cancer Institute Special Emphasis Panel; SPORE in Lymphoma, Breast, Ovarian.... 93.392, Cancer Construction; 93.393, Cancer Cause and Prevention Research; 93.394, Cancer Detection... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  11. 75 FR 67379 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-11-02

    ... Committee: National Cancer Institute Special Emphasis Panel; SPORE in Prostate, Skin, Pancreatic and other.... 93.392, Cancer Construction; 93.393, Cancer Cause and Prevention Research; 93.394, Cancer Detection... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  12. 76 FR 9353 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-02-17

    ....nih.gov . Name of Committee: National Cancer Institute Special Emphasis Panel; Prostate Imaging..., Cancer Construction; 93.393, Cancer Cause and Prevention Research; 93.394, Cancer Detection and Diagnosis... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  13. 78 FR 8155 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-02-05

    ... Cancer Institute Special Emphasis Panel; Cancer Immunology. ] Date: March 15, 2013. Time: 8:00 a.m. to 5... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed Meetings... privacy. Name of Committee: National Cancer Institute Special Emphasis Panel; NCI Omnibus Cancer Biology...

  14. 76 FR 50487 - National Cancer Institute Notice of Closed Meetings

    Science.gov (United States)

    2011-08-15

    ... Committee: National Cancer Institute Special Emphasis Panel; NCI SPORE in Childhood ALL, Skin, Brain, Lung....395, Cancer Treatment Research; 93.396, Cancer Biology Research; 93.397, Cancer Centers Support; 93... HUMAN SERVICES National Institutes of Health National Cancer Institute Notice of Closed...

  15. National Cancer Center Singapore: the way forward.

    Science.gov (United States)

    Teo, Melissa; Soo, Khee Chee

    2016-02-01

    Cancer is the leading cause of death in Singapore, comprising almost 30% of annual deaths. The incidence and prevalence continue to rise, resulting in Singapore having the highest age-standardized rate of cancer in southeast Asia. A review of national health policies in 1992 resulted in the creation of a National Cancer Centre Singapore (NCCS) in 1999. The current NCCS, with its three pillars of clinical service, research and education, manages about 70% of all new cancer cases in the countries public healthcare system. As it outgrows its current outfit and looks to the new NCCS building in 2020, the goal must be for strategic planning to attract and retain the best minds and heart in the field of cancer if it were to continue to be successful in achieving its vision and mission. This article chronicles the NCCS's history and details the foundation of its strategic plans.

  16. 78 FR 41939 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-07-12

    ... Committee: National Cancer Institute Special Emphasis Panel; NCI Omnibus Review, Cancer Etiology/Genetics... Federal Domestic Assistance Program Nos. 93.392, Cancer Construction; 93.393, Cancer Cause and...

  17. Co-introduced functional CCR2 potentiates in vivo anti-lung cancer functionality mediated by T cells double gene-modified to express WT1-specific T-cell receptor.

    Directory of Open Access Journals (Sweden)

    Hiroaki Asai

    Full Text Available BACKGROUND AND PURPOSE: Although gene-modification of T cells to express tumor-related antigen-specific T-cell receptor (TCR or chimeric antigen receptor (CAR has clinically proved promise, there still remains room to improve the clinical efficacy of re-directed T-cell based antitumor adoptive therapy. In order to achieve more objective clinical responses using ex vivo-expanded tumor-responsive T cells, the infused T cells need to show adequate localized infiltration into the tumor. METHODOLOGY/PRINCIPAL FINDINGS: Human lung cancer cells variously express a tumor antigen, Wilms' Tumor gene product 1 (WT1, and an inflammatory chemokine, CCL2. However, CCR2, the relevant receptor for CCL2, is rarely expressed on activated T-lymphocytes. A HLA-A2402(+ human lung cancer cell line, LK79, which expresses high amounts of both CCL2 and WT1 mRNA, was employed as a target. Normal CD8(+ T cells were retrovirally gene-modified to express both CCR2 and HLA-A*2402-restricted and WT1(235-243 nonapeptide-specific TCR as an effector. Anti-tumor functionality mediated by these effector cells against LK79 cells was assessed both in vitro and in vivo. Finally the impact of CCL2 on WT1 epitope-responsive TCR signaling mediated by the effector cells was studied. Introduced CCR2 was functionally validated using gene-modified Jurkat cells and human CD3(+ T cells both in vitro and in vivo. Double gene-modified CD3(+ T cells successfully demonstrated both CCL2-tropic tumor trafficking and cytocidal reactivity against LK79 cells in vitro and in vivo. CCL2 augmented the WT1 epitope-responsive TCR signaling shown by relevant luciferase production in double gene-modified Jurkat/MA cells to express luciferase and WT1-specific TCR, and CCL2 also dose-dependently augmented WT1 epitope-responsive IFN-γ production and CD107a expression mediated by these double gene-modified CD3(+ T cells. CONCLUSION/SIGNIFICANCE: Introduction of the CCL2/CCR2 axis successfully potentiated in

  18. Positive lymph-node breast cancer patients – activation of NF-κB in tumor-associated leukocytes stimulates cytokine secretion that promotes metastasis via C-C chemokine receptor CCR7.

    Science.gov (United States)

    El-Ghonaimy, Eslam A; El-Shinawi, Mohamed; Ibrahim, Sherif A; El-Ghazaly, Hisham; Abd-El-Tawab, Reda; Nouh, Mohamed A; El-Mamlouk, Tahani; Mohamed, Mona M

    2015-01-01

    Tumor metastasis to lymph nodes is most deadly complication among breast cancer patients. Herein, we investigated the molecular mechanism by which tumor-associated leukocytes (TALs) mediate lymph node metastasis. The density of different leukocyte subtypes infiltrating the tumor microenvironment of negative and positive lymph nodes (nLNs, pLNs) in breast cancer patients was measured using immunohistochemistry. In addition, we isolated TALs from blood drained from the axillary tributaries of nLN and pLN patients during breast surgery. Secretions of TALs were subjected to cytokine profiling using a cytokine antibody array. Our results showed an increase in the number of infiltrated CD45+ cells in the carcinoma tissues of pLN patients with the major proportion being myeloid subsets compared with nLN patients. Furthermore, TALs of pLN patients show a significant fivefold increase in the secretion of interleukin (IL)-1α, interferon-γ, IL-5, IL-3 and tumor necrosis factor-β, and are characterized by enhanced constitutive NF-κB/p65 signaling compared with TALs isolated from nLN patients. Using an invasion assay, cytokines secreted by TALs of pLN patients were shown to augment the invasive phenotype of breast cancer MCF-7 and SKBR3 cells compared with nLN patients. Using flow cytometry, we found that C-C chemokine receptor 7 (CCR7) is significantly overexpressed in breast carcinoma of pLN patients compared with nLNs patients. Intriguingly, CCR7, a mechanistic clue for metastasis, is upregulated in MCF-7 cells upon stimulation with TAL-conditioned media of pLN patients. Our findings show that the molecular cues secreted by TALs alone or in combination with CCR7 may emerge as future therapeutic targets for lymph node metastasis in breast cancer patients.

  19. 77 FR 24969 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-04-26

    ... . Name of Committee: National Cancer Institute Special Emphasis Panel; SPORE in Breast, Prostate and... Construction; 93.393, Cancer Cause and Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  20. 78 FR 27408 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-05-10

    ... Methods for the Detection of Cancer Recurrence in Post-Therapy Breast Cancer Patients. Date: June 4, 2013... of Federal Domestic Assistance Program Nos. 93.392, Cancer Construction; 93.393, Cancer Cause and... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  1. 75 FR 3239 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-01-20

    ... Special Emphasis Panel, Basal-like Breast Cancer Assay. Date: March 10, 2010. Time: 8 a.m. to 7 p.m..., Cancer Cause and Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  2. 78 FR 28235 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-05-14

    ... Diagnostic Assay to Detect Basal- like Breast Cancer. Date: June 13, 2013. Time: 12:00 p.m. to 1:00 p.m..., Cancer Cause and Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  3. 76 FR 576 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-01-05

    ... Emphasis Panel; SPORE in Mesothelioma, Lung, Breast and Ovarian Cancers. Date: February 2-3, 2011. Time: 8....395, Cancer Treatment Research; 93.396, Cancer Biology Research; 93.397, Cancer Centers Support; 93... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  4. Iodine regulates G2/M progression induced by CCL21/CCR7 interaction in primary cultures of papillary thyroid cancer cells with RET/PTC expression.

    Science.gov (United States)

    Zhang, You-Yuan; Liu, Ze-Bing; Ye, Xuan-Guang; Ren, Wei-Min

    2016-10-01

    Treatment with high iodine concentrations can delay oncogenic activation effects, reduce cell growth and return thyroid-specific gene and protein expression levels to normal. During rearranged during transfection (RET)/papillary thyroid carcinoma (PTC) 3 activation, excess iodine can act as a protective agent in thyroid follicular cells. The chemokine receptor CCR7 serves a critical role in lymphocyte trafficking into and within lymph nodes, the preferential metastatic site for PTC. However, the potential associations between chemokine (C‑C motif) ligand 21 (CCL21)/C‑C chemokine receptor type 7 (CCR7) interaction and iodine concentrations in primary cultures of PTC with RET/PTC expression remain unclear. Proliferation assays of primary cultures of PTC cells with RET/PTC1 and RET/PTC3 expression indicated that CCR7 activation by its specific ligand, CCL21, was associated with significantly increased cell proliferation. Flow cytometry data indicated that CCL21/CCR7 interaction significantly increased the fraction of cells in the G2/M phase of the cell cycle. Western blotting indicated that CCL21/CCR7 interaction significantly upregulated cyclin A, cyclin B1 and cyclin‑dependent kinase 1 (CDK1) expression. Western blotting determined that CCL21/CCR7 interaction significantly enhanced the levels of phosphorylated extracellular signal‑regulated kinase (P‑ERK). Co-immunoprecipitation confirmed that there was interaction between P‑ERK and cyclin A, cyclin B1 or CDK1, particularly in the presence of CCL21. Sodium iodide (NaI, 10-5 M) significantly abolished the effects of exogenous CCL21. These results suggest that CCL21/CCR7 interaction contributes to G2/M progression of RET/PTC‑expressing cells via the ERK pathway in association with 10‑5 M NaI.

  5. The correlation between chemokine receptor-5, CCR5-32 and breast cancer%趋化因子受体5及其基因多态性32与乳腺癌相关性的研究

    Institute of Scientific and Technical Information of China (English)

    周长鑫; 章阳; 孟凡云; 李文磊; 关众; 范海燕

    2011-01-01

    目的 研究乳腺癌组织及腋窝淋巴结中趋化因子受体5( CCR5)的表达和基因多态性CCR5-△32的发生频率,探讨其在乳腺癌转移中的作用.方法 收集2008年8月至2009年6月聊城市人民医院乳腺甲状腺外科手术切除的组织标本35例,采用实时荧光定量RT-PCR法检测乳腺癌原发癌灶及其腋窝淋巴结、癌旁组织和乳腺纤维腺瘤组织中CCR5 mRNA相对表达量,及CCR5-△32等位基因发生频率.数据采用单因素方差分析及独立样本t检验.结果 ①乳腺癌组织CCR5 mRNA的相对表达量显著高于癌旁正常组织(P<0.01)及良性肿瘤组织(P<0.05),Ⅱ期与Ⅲ期乳腺癌组织CCR5 mRNA相对表达量差异有统计学意义(P<0.05),癌旁正常组织与纤维腺瘤组织CCR5 mRNA的相对表达量差异无统计学意义(P>0.05);②转移淋巴结组织CCR5 mRNA的相对表达量明显高于非转移淋巴结(P<0.05);③35例均未发现等位基因CCR5-△32的变异;④乳腺癌组织CCR5 mRNA的相对表达量与ER、PR等临床免疫指标无相关性,但与有无腋窝淋巴结转移及C-erbB-2表达相关.结论 CCR5在乳腺癌组织及转移淋巴结中的表达明显升高,CCR5与其配体结合促进了乳腺癌的发生发展及腋窝淋巴结的转移,可作为预测乳腺癌腋窝淋巴结转移及预后的重要分子标志物,为临床治疗提供了新靶点.%Objective To study the expression of chemokine receptor 5 (CCR5) in breast cancer and metastatic axillary nodes and the frequency of polymorphism CCR5-△32,and its effect on breast cancer metastasis.Methods Specimens were collected from Aug.2008 to Jun.2009 in Department of Breast and Thyroid Surgery,Liaocheng People's Hospital.The relative expression quantity of CCR5 mRNA was detected by real-time fluorescence quantitative PCR (RT-PCR),and polymorphism CCR5-△32 was tested by DNA electrophoresis.The data was processed by SPSS software.Results 1.The relative expression quantity of CCR5

  6. A MCP1 fusokine with CCR2-specific tumoricidal activity

    Directory of Open Access Journals (Sweden)

    Yuan Liangping

    2011-09-01

    Full Text Available Abstract Background The CCL2 chemokine is involved in promoting cancer angiogenesis, proliferation and metastasis by malignancies that express CCR2 receptor. Thus the CCL2/CCR2 axis is an attractive molecular target for anticancer drug development. Methods We have generated a novel fusion protein using GMCSF and an N-terminal truncated version of MCP1/CCL2 (6-76 [hereafter GMME1] and investigated its utility as a CCR2-specific tumoricidal agent. Results We found that distinct to full length CCL2 or its N-truncated derivative (CCL2 5-76, GMME1 bound to CCR2 on mouse lymphoma EG7, human multiple myeloma cell line U266, or murine and human medulloblastoma cell lines, and led to their death by apoptosis. We demonstrated that GMME1 specifically blocked CCR2-associated STAT3 phosphorylation and up-regulated pro-apoptotic BAX. Furthermore, GMME1 significantly inhibited EG7 tumor growth in C57BL/6 mice, and induced apoptosis of primary myeloma cells from patients. Conclusion Our data demonstrate that GMME1 is a fusokine with a potent, CCR2 receptor-mediated pro-apoptotic effect on tumor cells and could be exploited as a novel biological therapy for CCR2+ malignancies including lymphoid and central nervous system malignancies.

  7. 75 FR 16488 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-04-01

    ... the treatment of cancer. The outcome of the evaluation will provide information to internal NCI... and Diagnosis Research; 93.395, Cancer Treatment Research; 93.396, Cancer Biology Research; 93.397, Cancer Centers Support; 93.398, Cancer Research Manpower; 93.399, Cancer Control, National Institutes...

  8. 77 FR 15782 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2012-03-16

    ... the treatment of cancer. The outcome of the evaluation will provide information to internal NCI... and Diagnosis Research; 93.395, Cancer Treatment Research; 93.396, Cancer Biology Research; 93.397, Cancer Centers Support; 93.398, Cancer Research Manpower; 93.399, Cancer Control, National Institutes...

  9. National and international guidelines for rectal cancer

    DEFF Research Database (Denmark)

    Nielsen, L B J; Wille-Jørgensen, P

    2014-01-01

    AIM: Rectal cancer is a common malignancy. Differences in daily practice may influence the morbidity and mortality, and many national and international organizations have created guidelines for staging and treatment of rectal cancer. Even though consensus is reached within individual guidelines......, this might not be the case between guidelines. No formal evaluation of the contrasting guidance has been reported. METHOD: A systematic search for national and international guidelines on rectal cancer was performed. Eleven guidelines were identified for further analysis. RESULTS: There was no consensus...... excision (TME). There was no consensus concerning local treatment of T1 tumours and adjuvant therapy, and not all guidelines included metastatic disease and recurrence. There was no consensus on the protocol for follow up. The guidelines had different approaches to evidence. All referred to evidence...

  10. 75 FR 21002 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-04-22

    ... Panel, SPORE in Lymphoma and Breast Cancer. Date: June 15-16, 2010. Time: 5 p.m. to 5 p.m. Agenda: To... Domestic Assistance Program Nos. 93.392, Cancer Construction; 93.393, Cancer Cause and Prevention Research... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  11. 78 FR 14099 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-03-04

    ... Treatment for Prostate Cancer. Date: March 28, 2013. Time: 8:00 a.m. to 5:00 p.m. Agenda: To review and... Assistance Program Nos. 93.392, Cancer Construction; 93.393, Cancer Cause and Prevention Research; 93.394... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  12. 76 FR 55547 - National Childhood Cancer Awareness Month, 2011

    Science.gov (United States)

    2011-09-07

    ... Proclamation 8706--National Prostate Cancer Awareness Month, 2011 #0; #0; #0; Presidential Documents #0; #0; #0... pediatric cancer. We still know too little about the causes in young people, and cancer remains the leading... affordability. Meanwhile, the National Cancer Institute continues to conduct and fund research on the causes...

  13. 77 FR 49450 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-08-16

    ... Cancer Institute Special Emphasis Panel; NCI REVIEW of P50 and R01 applications in Lung, Skin, Ovarian... Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93.396, Cancer Biology Research; 93.397... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  14. 77 FR 26772 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2012-05-07

    ..., Cancer Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93.396, Cancer Biology... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Meeting Pursuant to... assistance, such as sign language interpretation or other reasonable accommodations, should notify...

  15. 78 FR 50068 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2013-08-16

    ..., Cancer Treatment Research; 93.396, Cancer Biology Research; 93.397, Cancer Centers Support; 93.398... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Meeting Pursuant to... sign language interpretation or other reasonable accommodations, should notify the Contact...

  16. CCR3 and choroidal neovascularization.

    Directory of Open Access Journals (Sweden)

    Yiwen Li

    Full Text Available Age-related macular degeneration (AMD is the leading cause of irreversible blindness in the elderly in industrialized countries. The "wet" AMD, characterized by the development of choroidal neovacularization (CNV, could result in rapid and severe loss of central vision. The critical role of vascular endothelial growth factor A (VEGF-A in CNV development has been established and VEGF-A neutralization has become the standard care for wet AMD. Recently, CCR3 was reported to play an important role in CNV development and that CCR3 targeting was reported to be superior to VEGF-A targeting in CNV suppression. We investigated the role of CCR3 in CNV development using the Matrigel induced CNV and found that in both rats and mice, CNV was well-developed in the control eyes as well as in eyes treated with CCR3 antagonist SB328437 or CCR3 neutralizing antibodies. No statistically significant difference in CNV areas was found between the control and SB328437 or CCR3-ab treated eyes. Immunostaining showed no specific expression of CCR3 in or near CNV. In contrast, both VEGF-A neutralizing antibodies and rapamycin significantly suppressed CNV. These results indicate that CCR3 plays no significant role in CNV development and question the therapeutic approach of CCR3 targeting to suppress CNV. On the other hand, our data support the therapeutic strategies of VEGF-A and mTOR (mammalian target of rapamycin targeting for CNV.

  17. 75 FR 56455 - National Childhood Cancer Awareness Month, 2010

    Science.gov (United States)

    2010-09-15

    ... against cancer with inspiring hope and incredible bravery. When a child is diagnosed with cancer, an... creates a treasured network of support for these courageous children. During National Childhood Cancer... symptoms, diagnosis, and treatment of childhood cancers. Tragically, the causes of cancer in children...

  18. 75 FR 60132 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-09-29

    ... the treatment of cancer. The outcome of the evaluation will provide information to internal NCI...; 93.393, Cancer Cause and Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93.395..., Cancer Research Manpower; 93.399, Cancer Control, National Institutes of Health, HHS) Dated: September...

  19. 75 FR 71712 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-11-24

    ... the treatment of cancer. The outcome of the evaluation will provide information to internal NCI...; 93.393, Cancer Cause and Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93.395..., Cancer Research Manpower; 93.399, Cancer Control, National Institutes of Health, HHS) Dated: November...

  20. 77 FR 43098 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2012-07-23

    ... the treatment of cancer. The outcome of the evaluation will provide information to internal NCI... Construction; 93.393, Cancer Cause and Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93....398, Cancer Research Manpower; 93.399, Cancer Control, National Institutes of Health, HHS) Dated:...

  1. 趋化因子受体5表达与乳腺癌临床病理特征及预后的相关性研究%Analysis of the correlation between CCR5 expression and clinicopathological features and prognosis of breast cancer

    Institute of Scientific and Technical Information of China (English)

    章阳; 孟凡云; 李文磊; 范海燕; 关众; 周长鑫

    2011-01-01

    Objective To study the expression and clinicopathological relevance of chemokine receptor 5 ( CCR5 ) in breast cancer tissues and metastatic axillary lymph nodes.Methods The paraffin specimens of 72 cases of invasive ductal carcinoma ( IDC ) along with the invoved axillary lymph nodes, 50 cases of breast fibroadenoma and 40 cases of normal mammary gland were collectod.The expression of CCR5 protein in those specimens was detected by immunohistochemical staining.Meanwhile, the expressions of C-erbB-2, P53,Ki-67, ER and PR in the specimens of IDC were also measured with immunohistochemical method.Finally,the immmohistochemical results were statistically analyzed with regard to correlations with their clinicopathological data.Results ( 1 ) The positive expression of CCR5 in IDC was 84.72% (61/72 ) , breast fibroadenoma tissue presented low positive expression of CCR5 ( 14% , 7/50 ) , and no CCR5 expression was found in normal breast tissue.(2) The expression of CCR5 in IDC had a positive correlation with lymph node metastasis ( x2 = 4.982, P = 0.026, r = 0.305 ).( 3 ) Of the 50 cases with axillary lymph node metastasis, CCR5 was simultaneously expressed both in primary cancer and its invoved axillary lymph nodes in 39 cases, which showed a high homology.(4) There was a low positive correlation between CCR5 and breast cancer oncogene C-erbB-2 ( P < 0.05 , r = 0.291 ).( 5 ) CCR5 showed no relationship with age of onset, maximum diameter of tumor, mensis status or clinical stage ( P > 0.05 ).( 6 ) CCR5 had no direct correlation with the expression of p53, Ki-67, ER, PR ( P > 0.05 ).Conclusions CCR5 plays an important role in occurrence and development as well as axillary lymph node metastasis of breast cancer.CCR5 may be one of the indirect indicators to predict axillary lymph node metastasis and prognosis of breast cancer.%目的 探讨趋化因子受体5(CCR5)在乳腺癌病灶和腋窝转移淋巴结中的表达及其与临床病理意义.方法 收集72例

  2. 广西仫佬、壮和汉三民族HIV辅助受体CCR5基因多态性研究%A comparative study on the gene-polymorphism of HIV Co-receptor CCR5 based on three nationalities,Mulao, Zhuang, and Han,in Guangxi Zhuang Autonomous Region

    Institute of Scientific and Technical Information of China (English)

    陈哲; 樊晓晖; 杨海波; 梁纲; 赖振屏

    2007-01-01

    目的 了解广西仫佬、壮和汉三民族人群中HIV辅助受体CCR5△32和CCR5-894C缺失等位基因突变频率和多态性的特点,为评估这三个民族人群对HIV的遗传易感性和艾滋病的防治提供理论依据.方法 以197例仫佬族,100例壮族和100例汉族为研究对象,应用PCR和DNA测序等方法检测CCR5△32和CCR5-894C缺失突变体.结果 未发现CCR5△32和CCR5-894C缺失突变体,均为野生型.结论 由于未发现CCR5△32和CCR5-894C缺失突变体,推测广西仫佬、壮和汉三民族人群对HIV-1病毒感染可能具有较大的遗传易感性.

  3. 广西罗城仫佬族人群HIV-1感染相关基因CCR5多态性的初步研究%A study on the Gene-Polymorphism CCR5 of HIV carriers in Mulao Nationality of Luocheng County, Guangxi Zhuang Autonomous Region

    Institute of Scientific and Technical Information of China (English)

    陈森洲; 陈哲; 樊晓晖; 杨海波; 赖振屏

    2007-01-01

    目的:了解广西仫佬人群中HIV辅助受体CCR5△32和CCR5-894C缺失等位基因突变频率和多态性的特点,为评估该民族人群对HIV的遗传易感性和艾滋病的防治提供理论依据.方法:以197例仫佬族为研究对象,应用PCR和DNA测序等方法检测CCR5△32和CCR5-894C缺失突变体.结果:未发现CCR5△32和CCR5-894C缺失突变体.结论:由于未发现CCR5△32和CCR5-894C缺失突变体,推测仫佬族人群对HIV-1病毒感染可能具有较大的遗传易感性.

  4. Improved metastasis-free survival in nonadjuvantly treated postmenopausal breast cancer patients with chemokine receptor 5 del32 frameshift mutations

    NARCIS (Netherlands)

    Span, P.N.; Pollakis, G.; Paxton, W.A.; Sweep, F.C.; Foekens, J.A.; Martens, J.W.; Sieuwerts, A.M.; Laarhoven, H.W. van

    2015-01-01

    The CC-chemokine receptor CCR5 has been associated with cancer progression and metastasis. CCR5 blockers such as Maraviroc are tested in metastatic cancer patients. A mutant allele of CCR5, CCR5-delta32 (CCR5del32), which encodes for a protein with a trans-dominant negative effect on the wildtype pr

  5. 78 FR 78982 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2013-12-27

    ... Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93.396, Cancer Biology Research; 93.397... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Meeting Pursuant to... sign language interpretation or other reasonable accommodations, should notify the Contact...

  6. 75 FR 54453 - National Prostate Cancer Awareness Month, 2010

    Science.gov (United States)

    2010-09-07

    ... the last decade, prostate cancer is still the second leading cause of cancer deaths among men in the... it. The exact causes of prostate cancer are not known, but awareness can help men make more informed... Documents#0;#0; ] Proclamation 8552 of August 31, 2010 National Prostate Cancer Awareness Month, 2010 By...

  7. 78 FR 54745 - National Prostate Cancer Awareness Month, 2013

    Science.gov (United States)

    2013-09-06

    ... Documents#0;#0; ] Proclamation 9010 of August 30, 2013 National Prostate Cancer Awareness Month, 2013 By the President of the United States of America A Proclamation Among American men, prostate cancer is both the second most commonly diagnosed cancer and the second-leading cause of cancer deaths. Although...

  8. 77 FR 55091 - National Childhood Cancer Awareness Month, 2012

    Science.gov (United States)

    2012-09-06

    ... death by disease for children under the age of 15. The causes of pediatric cancer are still largely... conditions, including cancer, nor can they drop coverage because a child is diagnosed with cancer. The law... Documents#0;#0; ] Proclamation 8851 of August 31, 2012 National Childhood Cancer Awareness Month, 2012...

  9. 78 FR 41072 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-07-09

    ... therapeutics for the treatment of cancer. The outcome of the evaluation will provide information to internal... Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93..., Cancer Control, National Institutes of Health, HHS) Dated: July 2, 2013. David Clary, Program...

  10. 78 FR 66370 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-11-05

    ... therapeutics for the treatment of cancer. The outcome of the evaluation will provide information to internal... Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93..., Cancer Control, National Institutes of Health, HHS). Dated: October 30, 2013. Melanie J. Gray,...

  11. 77 FR 12318 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2012-02-29

    ... outcome of the evaluation will provide information for consideration by an internal NCI committee that... Construction; 93.393, Cancer Cause and Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93....398, Cancer Research Manpower; 93.399, Cancer Control, National Institutes of Health, HHS)...

  12. 77 FR 70170 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2012-11-23

    ... therapeutics for the treatment of cancer. The outcome of the evaluation will provide information to internal... Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93..., Cancer Control, National Institutes of Health, HHS) Dated: November 16, 2012. Melanie J. Gray,...

  13. 77 FR 58852 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-09-24

    ... Committee: National Cancer Institute Special Emphasis Panel; R13 Review Teleconference. Date: October 24..., Panel; Immunology. Date: December 6, 2012. Time: 7:45 a.m. to 5 p.m. Agenda: To review and evaluate... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  14. 76 FR 64090 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-10-17

    ..., Resources and Training Review Branch, Division of Extramural Activities, National Cancer Institute, 6116....) Contact Person: Timothy C. Meeker, MD, PhD, Scientific Review Officer, Resources and Training Review... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  15. CRCHD Launches National Colorectal Cancer Outreach and Screening Initiative

    Science.gov (United States)

    The NCI CRCHD launches National Screen to Save Colorectal Cancer Outreach and Screening Initiative which aims to increase colorectal cancer screening rates among racially and ethnically diverse and rural communities.

  16. 77 FR 12600 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-03-01

    ...: Bethesda Marriott Suites, 6711 Democracy Boulevard, Bethesda, MD 20817. Contact Person: Ellen K Schwartz.... Place: Bethesda Marriott Suites, 6711 Democracy Boulevard, Bethesda, MD 20817. Contact Person: Savvas C...: National Cancer Institute Special Emphasis Panel; Cancer Research Infrastructure Support for HMOs....

  17. CCR2 and CCR5 genes polymorphisms in women with cervical lesions from Pernambuco, Northeast Region of Brazil: a case-control study.

    Science.gov (United States)

    Santos, Erinaldo Ubirajara Damasceno dos; Lima, Géssica Dayane Cordeiro de; Oliveira, Micheline de Lucena; Heráclio, Sandra de Andrade; Silva, Hildson Dornelas Angelo da; Crovella, Sergio; Maia, Maria de Mascena Diniz; Souza, Paulo Roberto Eleutério de

    2016-03-01

    Polymorphisms in chemokine receptors play an important role in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer (CC). Our study examined the association of CCR2-64I (rs1799864) andCCR5-Δ32 (rs333) polymorphisms with susceptibility to develop cervical lesion (CIN and CC) in a Brazilian population. The genotyping of 139 women with cervical lesions and 151 women without cervical lesions for the CCR2-64I and CCR5-Δ32 polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism. The individuals carrying heterozygous or homozygous genotypes (GA+AA) for CCR2-64I polymorphisms seem to be at lower risk for cervical lesion [odds ratio (OR) = 0.37, p = 0.0008)]. The same was observed for the A allele (OR = 0.39, p = 0.0002), while no association was detected (p > 0.05) with CCR5-Δ32 polymorphism. Regarding the human papillomavirus (HPV) type, patients carrying the CCR2-64Ipolymorphism were protected against infection by HPV type 16 (OR = 0.35, p = 0.0184). In summary, our study showed a protective effect ofCCR2-64I rs1799864 polymorphism against the development of cervical lesions (CIN and CC) and in the susceptibility of HPV 16 infection.

  18. 78 FR 15023 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-03-08

    ... applications and the discussions could disclose confidential trade secrets or commercial property such as... Review and Logistics Branch, Division of Extramural Activities, National Cancer Institute, NHH,...

  19. 76 FR 26309 - National Cancer Institute; Notice Closed Meeting

    Science.gov (United States)

    2011-05-06

    ...: Washington DC North Hilton Hotel, 620 Perry Parkway, Gaithersburg, MD 20877. Contact Person: Lalita D... Activities, National Cancer Institute, 6116 Executive Boulevard, Room 7141, Bethesda, MD 20892,...

  20. 76 FR 80375 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-12-23

    ... evaluate grant applications. Place: Hilton Washington DC/Rockville Hotel & Executive M, 1750 Rockville Pike... Review Branch, Division of Extramural Activities, National Cancer Institute, NIH, 6116...

  1. Expression of chemokine receptor CCR7 and its association with lymphatic vessel invasion in breast cancer%乳腺癌组织趋化因子受体CCR7表达及其与淋巴管浸润关系的研究

    Institute of Scientific and Technical Information of China (English)

    谢竞; 周艳; 范林军; 陈庆秋; 姜军

    2008-01-01

    目的:研究乳腺癌组织内趋化因子受体CCR7的表达及其与淋巴管浸润和淋巴结转移的关系.方法: 对102例乳腺癌组织标本分别进行CCR7和podoplanin免疫组化染色,观察CCR7的表达与临床病理参数之间的关系;并对57例淋巴管浸润标本进行CCR7和podoplanin双标免疫组化染色,观察CCR7在淋巴管内癌栓的表达情况.结果:在乳腺癌组织中CCR7阳性表达率为60.8%,CCR7的表达与患者的年龄、肿瘤大小、病理类型和雌孕激素受体(ER、PR)的表达无关,P>0.05;而与淋巴管的浸润及淋巴结的转移相关,P<0.01;双标免疫组化染色可见蓝黑色的淋巴管内CCR7阳性(红色)的癌细胞,并且CCR7在淋巴管内癌栓的表达强度为4.98±2.84,高于其周围相应的癌组织(3.84±2.51),P=0.037.结论:CCR7在介导乳腺癌细胞淋巴管浸润及淋巴结转移中可能起重要作用.

  2. The chemokine receptor CCR7 promotes mammary tumorigenesis through amplification of stem-like cells.

    Science.gov (United States)

    Boyle, S T; Ingman, W V; Poltavets, V; Faulkner, J W; Whitfield, R J; McColl, S R; Kochetkova, M

    2016-01-07

    The chemokine receptor CCR7 is widely implicated in breast cancer pathobiology. Although recent reports correlated high CCR7 levels with more advanced tumor grade and poor prognosis, limited in vivo data are available regarding its specific function in mammary gland neoplasia and the underlying mechanisms involved. To address these questions we generated a bigenic mouse model of breast cancer combined with CCR7 deletion, which revealed that CCR7 ablation results in a considerable delay in tumor onset as well as significantly reduced tumor burden. Importantly, CCR7 was found to exert its function by regulating mammary cancer stem-like cells in both murine and human tumors. In vivo experiments showed that loss of CCR7 activity either through deletion or pharmacological antagonism significantly decreased functional pools of stem-like cells in mouse primary mammary tumors, providing a mechanistic explanation for the tumor-promoting role of this chemokine receptor. These data characterize the oncogenic properties of CCR7 in mammary epithelial neoplasia and point to a new route for therapeutic intervention to target evasive cancer stem cells.

  3. Treatment of stomach cancer, a national experience.

    Science.gov (United States)

    Valen, B; Viste, A; Haugstvedt, T; Eide, G E; Søreide, O

    1988-07-01

    A total of 1165 patients with stomach cancer were entered into a prospective, observational national study. They represented 54 per cent of all stomach cancer patients reported to the Cancer Registry in Norway during the study period, and data are analysed for three hospital levels (local, county and university hospitals). The median age was 71 years (range 18-96 years). The median pretreatment delay was 113 days, and 46 per cent of patients had a performance status (Karnofsky index) of less than or equal to 80. The diagnosis was confirmed by pre-operative histology in 88 per cent of cases. In all, 88 per cent of patients underwent surgery, the resectability rate was 67 per cent and 50 per cent had a potential curative operation. Total gastrectomy was most commonly performed. Lymph node dissection was performed in 14 per cent of those undergoing a curative resection. The postoperative complication rate was 27 per cent but varied with the type of operation, being highest in proximal resection (55 per cent) and lowest after distal resection (19 per cent). A total of 7 per cent of the patients died postoperatively. Most patients had advanced disease at the time of treatment and only 6 per cent had stage I tumours. There were significant differences in patient and treatment characteristics between the three hospital levels. In conclusion, patient selection bias which will influence results does occur. A fairly aggressive attitude towards local disease was found, but the low proportion of patients undergoing lymph node dissection not only leads to questions regarding the efficacy of this treatment policy, but also casts doubt on the validity of staging of stomach cancer. Morbidity and mortality rates are still high. The consequences of the differences revealed between hospital groups are difficult to interpret. Proponents of both regionalization of treatment and small hospital care may find arguments for their case in the data.

  4. 76 FR 41273 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-07-13

    ...: Gail J Bryant, MD, Medical Officer, Resources and Training Review Branch, Division of Extramural... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  5. 新辅助化疗对乳腺癌患者外周血T淋巴细胞中CCR7表达的影响%Effect of Neoadjuvant Chemotherapy on the Expressions of CCR7 in Peripheral T Lymphocytes of Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    刘志勇

    2012-01-01

      目的检测趋化因子受体-7(CCR7)在乳腺癌患者外周血CD3+、CD8+T淋巴细胞中的表达并与健康对照组比较;探讨CCR7变化与新辅助化疗疗效的相关性.方法 采集30例健康对照组、80例乳腺癌患者新辅助化疗前、后外周血,应用流式细胞仪检测CCR7在外周血CD3+、CD8+T淋巴细胞亚群中的表达.结果 化疗前乳腺癌患者各疗效组CCR7无显著差异(P>0.05);化疗后各疗效组CCR7含量变化与临床效果一致;疗效越明显,CCR7升高越显著(P0.05);after chemotherapy, the efficacy of group CCR7 content changes and clinical effect;efficacy of the more obvious, CCR7 increased more significantly (P<0.05).  Conclusion The detection of CCR7  can better monitor breast cancer neoadjuvant chemotherapy effect and give useful evidence for prognosis and choice of chemotherapy drugs after operation.

  6. CCR4 versus CCR10 in human cutaneous TH lymphocyte trafficking.

    Science.gov (United States)

    Soler, Dulce; Humphreys, Tricia L; Spinola, Stanley M; Campbell, James J

    2003-03-01

    The chemokine receptors (CCRs) CCR4 and CCR10, and the cutaneous lymphocyte antigen (CLA), have each been proposed as critical mediators of skin-specific TH lymphocyte homing in mice and humans. CLA initiates skin homing by mediating E-selectin-dependent tethering and rolling within cutaneous venules, but the specific roles of CCR4 and CCR10 are unclear. We have generated an antihuman CCR10 monoclonal antibody (mAb; 1B5) to illuminate the individual contributions of these molecules. This mAb allows us to compare CCR10, CCR4, and CLA expression within human TH populations. The mAb 1B5 recognizes functional CCR10 expression, as chemotactic responsiveness to cutaneous T-cell-attracting chemokine (CTACK)/CCL27 (a CCR10 ligand) parallels the staining of TH subsets. We find CCR10 expressed by only a minority (approximately 30%) of blood-borne, skin-homing (CLA+/CCR4+) TH cells. However, essentially all members of the relatively small "effector" (CLA+/CCR4+/CD27-/CCR7-) skin-homing TH population express CCR10. Most skin-infiltrating lymphocytes in allergic delayed-type hypersensitivity (DTH) and bacterial chancroid skin lesions express both CCR4 and CLA, but only about 10% express CCR10. This suggests for the 2 models of TH skin homing studied here that CCR10+ TH cells have no advantage over other CLA+/CCR4+ TH cells in homing to cutaneous sites. We conclude that the skin-homing TH compartment is itself divided into distinct subpopulations, the smaller of which expresses both CCR4 and CCR10, and the larger of which expresses only CCR4. Thus, CCR10 is unlikely to be necessary for cutaneous homing of TH cells in the models studied here. CCR10 may instead play a role in the movement of specialized "effector" cutaneous TH cells to and/or within epidermal microenvironments.

  7. 75 FR 7489 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-02-19

    ... Special Emphasis Panel, Portable e-Technology Diet and Physical Activity Tools for Consumers. Date: April... Officer, Special Review and Logistics Branch, Division of Extramural Activities, National Cancer Institute... Logistics Branch, Division of Extramural Activities, National Cancer Institute, 6116 Executive Blvd.,...

  8. 76 FR 31619 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-06-01

    ..., 2011. Time: 8 a.m. to 5 p.m. Agenda: To review and evaluate grant applications. Place: Hilton Hotel... Activities, National Cancer Institute, NIH, 6116 Executive Blvd., Rm 8053, Bethesda, MD 20892, 301-496-7421... Training Review Branch, Division of Extramural Activities, National Cancer Institute, 6116...

  9. 76 FR 55551 - National Prostate Cancer Awareness Month, 2011

    Science.gov (United States)

    2011-09-07

    ... Documents#0;#0; ] Proclamation 8706 of September 1, 2011 National Prostate Cancer Awareness Month, 2011 By the President of the United States of America A Proclamation Prostate cancer is the second leading cause of cancer- related deaths among men in the United States. The weight of this illness is felt...

  10. 77 FR 55099 - National Prostate Cancer Awareness Month, 2012

    Science.gov (United States)

    2012-09-06

    ... preventing, detecting, and treating this terrible illness. While the causes of prostate cancer are still... Documents#0;#0; ] Proclamation 8855 of August 31, 2012 National Prostate Cancer Awareness Month, 2012 By the President of the United States of America A Proclamation Prostate cancer is among the most common...

  11. 78 FR 15021 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-03-08

    ... therapeutics for the treatment of cancer. The outcome of the evaluation will provide information to internal... Research; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93.396... Control, National Institutes of Health, HHS) Dated: March 4, 2013. Melanie J. Gray, Program...

  12. Correlation between CCR7 expression and lymph node metastatic potential of human tongue carcinoma.

    Science.gov (United States)

    Xia, X; Liu, K; Zhang, H; Shang, Z

    2015-01-01

    Metastasis is an important cause of cancer-related mortality. In this study, we investigated the role of CCR7 in the lymph node metastasis of tongue carcinoma. Immunohistochemistry and Western blot revealed the expression of CCR7 in tongue SCC tissues and cell lines. In addition, we examined the expression of CCL21, a ligand of CCR7, in normal and diseased lymph nodes using immunohistochemistry and/or real-time PCR. The CCR7 expression was significantly correlated with cervical lymph node metastasis, tumor staging, and histological grade (P = 0.015, 0.040, and 0.015, respectively). The multivariate analysis showed that regional lymph node metastasis, the expression of CCR7, and LVD were the independent poor prognostic factors. Knockdown of CCR7 gene resulted in a significant inhibition of migration and invasion of SCC4 cells in vitro without affecting the proliferation and apoptosis of tumor cells. Also, CCR7 knockdown obviously inhibited cervical lymph node metastasis in an animal tumor model. Our study indicated that CCR7 may play an important role in progression of tongue SCC and could be a promising target for tongue SCC therapy.

  13. Upregulation of VEGF-D Expression by Chemokine Receptor CCR7 in Non-small Cell Lung Cancer%CCR7通过上调VEGF-D表达诱导肺癌淋巴管形成促进转移

    Institute of Scientific and Technical Information of China (English)

    张轶欧; 李洋; 张清富; 邱雪杉; 王恩华

    2009-01-01

    目的 探讨CC族趋化因子受体7(CCR7)诱导肺癌组织淋巴管形成、促进转移的分子机制.方法 应用免疫组织化学染色S-P法检测90例非小细胞肺癌组织中CCR7和血管内皮生长因子D(VEGF-D)的表达及淋巴管(D2-40染色显示淋巴管)的密度,并联合运用质粒转染技术上调肺癌细胞BE1中CCR7表达,采用RT-PCR和Western blot方法观察VEGF-D的变化情况,分析VEGF-D与CCR7表达的关系.结果 CCR7主要表达于肺癌细胞胞质和(或)胞膜,VEGF-D主要表达于肺癌细胞胞质;非小细胞肺癌中CCR7、VEGF-D表达阳性率分别为70%(63/90)和60%(54/90),χ2检验显示CCR7和VEGF-D表达与非小细胞肺癌的临床病理分期(P=0.003;P=0.005)、淋巴管密度(P=0.001;P0.05);此外,CCR7和VEGF-D表达呈正相关(r=0.455,P<0.01).向BE1细胞中转染CCR7基因,CCR7表达上调后发现VEGF-D的mRNA和蛋白水平均上调(P<0.05).结论 CCR7可通过上调VEGF-D表达诱导肺癌组织淋巴管形成、促进淋巴结转移.

  14. Interfering with CCL5/CCR5 at the Tumor-Stroma Interface.

    Science.gov (United States)

    Bronte, Vincenzo; Bria, Emilio

    2016-04-11

    In this issue of Cancer Cell, Halama et al. (2016) further advance chemokine interference as a therapeutic option for cancer by demonstrating the effect of CCR5 blockade in reshaping macrophage polarization toward an anti-tumor functional state in patient-derived tumor models and liver metastases of colorectal cancer patients.

  15. The Value and Association of CCR7 Expression in NSCLC with Lymph Node Metastasis

    Directory of Open Access Journals (Sweden)

    Xing LI

    2008-04-01

    Full Text Available Background and Objective It has became a hotspot research about the target metastasis of malignant tumor in recent years. It has been proven that metastasis of malignant tumor is a nonrandom but highly-organized and selective process. The aim of this study is by analysing the expression of CC Chemokine Receptor 7 (CCR7 in pulmonary tumor tissue and metastasized lymph nodes in NSCLC, to explore the relationship between the expression of CCR7 in pulmonary tumor tissue and metastasized lymph nodes, and explore the significance. Methods SABC immunohitochemcal staining was used to investigate the expression of CCR7 by rabbit anti-human CCR7 monoclonal antibody, and the specimens were 17 cases of adenocarcinoma, 17 cases of Squamous cell Carcinoma, 12 cases of Adenosquamous Carcinoma, 4 cases of large cell carcinoma and 28 cases of metastasized lymph nodes of lung cancer. Negative control sections use 5 cases of inflammatory pseudotumor and 20 cases of normal lung tissue. Two independent pathologists observed all the specimens in the high power field (×400 of microscope by double blind method. Results 1. The expression of CCR7 in pulmonary tumor tissue was remarkably higher than normal lung tissue (P<0.005; 2. The expression of CCR7 between pulmonary tumor tissue and metastasized lymph nodes had no significant differences (P=0.177; 3. The expression of CCR7 had correlation with lymph nodes metastasis, The expression level in lymph nodes metastasis group was significantly higher than that in no lymph nodes metastasis group (P=0.016; 4. Along with the increment that clinical stage, the CCR7 expression had increases the high trend (P=0.003. Conclusion CCR7 is over-expression in carcinoma cell nests and lymph node metastasis. It demonstrates that CCR7 may be related to the development of lymph node metastasis in NSCLC.

  16. A national agenda for Latino cancer prevention and control.

    Science.gov (United States)

    Ramirez, Amelie G; Gallion, Kipling J; Suarez, Lucina; Giachello, Aida L; Marti, Jose R; Medrano, Martha A; Pérez-Stable, Eliseo J; Talavera, Gregory A; Trapido, Edward J

    2005-06-01

    Although cancer is a leading cause of morbidity and premature death among Latinos, there is limited knowledge of cancer-related issues and priorities of greatest significance to the Latino population, the largest minority group in the nation. This information is vital in helping to guide Latino cancer research, training, and awareness efforts at national, regional, and local levels. To help identify cancer issues of greatest relevance to Latinos, Redes En Accion, The National Hispanic/Latino Cancer Network, a major network among the National Cancer Institute's Special Populations Networks, conducted a survey of 624 key opinion leaders from around the country. Respondents were asked to rank the three cancer sites most important to Latinos in their region and the five issues of greatest significance for this population's cancer prevention and control. Recommendations were prioritized for three specific areas: 1) research, 2) training and/or professional education, and 3) awareness and/or public education. Among cancers, breast carcinoma was ranked number one, followed in order by cervical and lung carcinomas. The issues of greatest significance to Latinos were 1) access to cancer screening and care, 2) tobacco use, 3) patient-doctor communication, 4) nutrition, and 5) risk communication. This survey solicited information from scientists, health care professionals, leaders of government agencies, professional and community-based organizations, and other stakeholders in Latino health. The results laid the foundation for a national Redes En Accion Latino cancer agenda, thus providing a useful tool for individuals and organizations engaged in cancer prevention and control efforts among the Hispanic-Latino population.

  17. Conforming to cancer staging, prognostic indicators and national treatment guidelines.

    Science.gov (United States)

    Dykstra-Long, Gwendylen R

    2011-01-01

    Clinical cancer staging and prognostic indicators guide treatment planning, and as such the American College of Surgeons Commission on Cancer Commission on Cancer (ACoS CoC) and the American Joint Committee on Cancer (AJCC) have recognized this as quality patient care. Overton Brooks Veterans Administration (OBVAMC) developed an organizational policy and procedure, flow algorithms, treatment plan templates, and education strategies in order to conform to this quality care approach. The purpose of this article is to share this systematic approach that is able to support clinical and working cancer stage and prognostic indicators which have been recognized by national standard setting organizations as quality patient care.

  18. HIF-1α和HIF-2α上调非小细胞肺癌中CCR7的表达%Upregulation of the Chemokine Receptor CCR7 expression by HIF-1α and HIF-2α in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    李洋; 张清富; 江黎黎; 邱雪杉; 王恩华

    2008-01-01

    背景与目的 CCR7与非小细胞肺癌的淋巴结转移密切相关,但CCR7的上调机制却不是很清楚.本研究通过观察趋化因子受体CCR7和缺氧诱导因子1α(HIF-1α)、缺氧诱导因子2α(HIF-2α)在非小细胞肺癌组织中的表达及相互关系,探讨非小细胞肺癌CCR7上调机制.方法 应用免疫组织化学染色(SP法)检测94例非小细胞肺癌组织中CCR7、HIF-1α和HIF-2α的表达,并联合运用RNAi技术沉默人肺腺癌A549细胞中HIF-1α、HIF-2α表达,采用RT-PCR和免疫荧光方法观察CCR7的变化情况,分析CCR7表达与HIF-1α、HIF-2α之间的关系:结果免疫组织化学结果显示:CCR7主要表达于癌细胞质和(或)胞膜,HIF-1α、HIF-2α主要表达于癌细胞核和(或)细胞质,非小细胞肺癌中CCR7、HIF-1α和HIF-2α的表达率分别为75.53%(71/94)、54.25%(51/94)和70.21%(66194),χ2榆验显示CCR7表达与非小细胞肺癌的临床病理分期(P0.05).此外.CCR7和HIF-1α、HIF-2α表达正相关(r=0.272,P<0.01)(r=0.225,P<0.05).向A549细胞中转染HIF-1α、HIF-2α特异性siRNA.分别抑制HIF-1α、HIF-2α表达后发现CCR7的mRNA和蛋白水平均下调(P<0.05).结论 CCR7表达与非小细胞肺癌侵袭转移密切相关,CCR7在NSCLC中过表达受HIF-1α和H1F-2α调控.

  19. Expression and Clinical Significance of Chemokine Receptor CCR7 in Lung Cancer Tissues and Corresponding Metastasized Lymph Nodes%趋化因子受体CCR7在肺癌及转移淋巴结中的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    任勇; 陈寿松; 齐曼丽; 肖同浩; 陈昕薇; 梁励伟

    2008-01-01

    目的 探讨肺癌原发灶及淋巴结转移灶中趋化因子受体CCR7的表达特点及其与临床病理特征的关系. 方法对125例肺癌手术切除标本及64例淋巴结转移灶和20例癌旁正常肺组织采用免疫组化法检测CCR7表达. 结果 CCR7在57.6%(72/125)肺癌组织中呈阳性表达,20例癌旁正常组织中仅2例表达(10.0%).64例肺癌原发灶和淋巴结转移灶中CCR7高表达的阳性率分别为82.8%(53/64)和81.2%(52/64),两部位CCR7表达具有较高的同源性.CCR7的表达与肺癌患者的性别、年龄、肿瘤大小、肿瘤分化程度和组织学类型无关(P>0.05),而与肺癌患者的临床分期及有无淋巴结转移密切相关(P<0.01).结论 CCR7表达与肺癌淋巴结转移密切相关,CCR7在肺癌原发灶及转移淋巴结中的表达具有较高的同源性.CCR7的表达对指导手术方式的选择及非手术治疗选择靶点具有指导价值.

  20. [Legislation of cancer registries in Japan- an outline of the national cancer registry].

    Science.gov (United States)

    Nishino, Yoshikazu

    2015-04-01

    The national cancer registry in Japan will commence operations in January 2016 under the Cancer Registry Promotion Act, which was established in December 2013. Although data on cancer incidence and survival rates in Japan have been available for limited regions for a long time, accurate nationwide data obtained from the national cancer registry database will contribute to the planning and evaluation of cancer control in Japan. It is expected that this database will be utilized in evaluating the quality of medical care for cancer patients, in assessing the accuracy of cancer screening, and in follow-up surveys in nationwide cohort studies. Furthermore, under the Cancer Registry Promotion Act, hospitals will be permitted to obtain vital patient information from data registered in the national cancer registry database, which will promote the publication of survival rates for cancer patients and accelerate research at hospitals. The founding of the Japanese national cancer registry is a landmark development in the promotion of cancer control and cancer research in Japan and it is essential that the Japanese population benefits from the information obtained from this database.

  1. CCR7活化与人结肠癌SW620细胞的体外增殖、趋化与侵袭的关系%The relationship between CCR7 activation and proliferation,chemotaxis and invasion of human colon cancer SW620 cells in vitro

    Institute of Scientific and Technical Information of China (English)

    郭学光; 陈正堂

    2010-01-01

    目的 研究CCR7活化对结肠癌SW620细胞体外增殖、趋化与侵袭活性的影响.方法 MTT法和软琼脂细胞集落培养观察CCR7活化对细胞增殖的影响,Boyden小室法检测CCR7活化对SW620细胞趋化和侵袭活性的影响.结果 和对照组相比CCL21组细胞增殖数量、软琼脂细胞集落数和穿过Boyden小室膜的细胞数均显著增加(P<0.01).结论 CCR7活化能够促进结肠癌SW620细胞的体外增殖、趋化与侵袭,其可能参与了结肠癌淋巴结转移的过程.进一步研究CCR7在结肠癌中的作用将有助于阐明结肠癌淋巴结转移的机制.

  2. 75 FR 11896 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-03-12

    ... commercial property such as patentable material, and personal information concerning individuals associated... Officer, Special Review and Logistics Branch, Division of Extramural Activities, National Cancer Institute...: Adriana Stoica, PhD, Scientific Review Officer, Special Review & Logistics Branch, Division of...

  3. 75 FR 54161 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-09-03

    ... grant applications. Place: Doubletree Hotel Bethesda (Formerly Holiday Inn Select), 8120 Wisconsin..., Research Programs Review Branch, Division of Extramural Activities, National Cancer Institute, 6116... applications. Place: Hilton Washington/Rockville, 1750 Rockville Pike, Rockville, MD 20852. Contact...

  4. 78 FR 3901 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-01-17

    ...: Bethesda North Marriott Hotel & Conference Center, 5701 Marinelli Road, Bethesda, MD 20852. Contact Person... Extramural Activities, National Cancer Institute, NIH, ] 6116 Executive Boulevard, Room 8135, Bethesda, MD...: To review and evaluate grant applications. Place: Hilton Washington/Rockville, 1750 Rockville...

  5. 78 FR 16272 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-03-14

    ... review and evaluate grant applications. Place: Hilton Rockville, 1750 Rockville Pike, Rockville, MD 20852..., Division of Extramural Activities, National Cancer Institute, 6116 Executive Boulevard, Room 8131, Bethesda.... Agenda: To review and evaluate contract proposals. Place: Doubletree Hotel Bethesda, 8120...

  6. 78 FR 20213 - National Cancer Control Month, 2013

    Science.gov (United States)

    2013-04-04

    ... smoking, visit www.BeTobaccoFree.gov . Additional resources on what cancer is and how to prevent it are... Nation, we have measured that progress not just in the lives we have saved, but also in the moments we... efforts to prevent it. Each of us can reduce our risk of developing cancer by maintaining a healthy...

  7. 78 FR 44136 - Submission for OMB review; 30-day Comment Request: National Cancer Institute (NCI) Cancer...

    Science.gov (United States)

    2013-07-23

    ... HUMAN SERVICES National Institutes of Health Submission for OMB review; 30-day Comment Request: National Cancer Institute (NCI) Cancer Nanotechnology Platform Partnership Scientific Progress Reports SUMMARY... Institutes of Health (NIH), has submitted to the Office of Management and Budget (OMB) a request for...

  8. Completeness and validity in a national clinical thyroid cancer database

    DEFF Research Database (Denmark)

    Londero, Stefano Christian; Mathiesen, Jes Sloth; Krogdahl, Annelise

    2014-01-01

    BACKGROUND: Although a prospective national clinical thyroid cancer database (DATHYRCA) has been active in Denmark since January 1, 1996, no assessment of data quality has been performed. The purpose of the study was to evaluate completeness and data validity in the Danish national clinical thyroid...... and extended governmental databases, it is possible to establish national clinical cancer databases with a satisfactory completeness and validity. The DATHYRCA database is considered reliable in terms of describing thyroid carcinoma at a national level....... cancer database: DATHYRCA. STUDY DESIGN AND SETTING: National prospective cohort. Denmark; population 5.5 million. Completeness of case ascertainment was estimated by the independent case ascertainment method using three governmental registries as a reference. The reabstracted record method was used...

  9. Expression of CCR7, L-selectin, CD44v6 and MMP9 in colorectal cancer and their relative with lymphatic metastatic%大肠癌中CCR7、L-selectin、CD44v6和MMP9表达及其与淋巴转移的关系

    Institute of Scientific and Technical Information of China (English)

    武欣; 李坤; 张凡; 刘军超; 林媛媛; 金春亭

    2013-01-01

    目的 探讨CC趋化因子受体7(CCR7)、L-selectin、CD44v6和MMP9在大肠癌组织中的表达及其与大肠癌淋巴转移的关系.方法 采用免疫组化PV 9000两步法检测104例大肠癌组织(大肠癌组)、55例癌旁正常组织(癌旁组)和34例转移灶组织(转移组)中CCR7和L-selectin、CD44v6和MMP9的表达.结果 大肠癌组、转移组中CCR7、L-selectin、CD44v6和MMP9阳性率明显高于癌旁组(P<0.05),有淋巴结转移者明显高于无转移者(P<0.05);CCR7与L-selectin、MMP9表达呈正相关(P<0.05);CD44v6与L-selectin、MMP9表达相关;L-selectin与MMP9的表达呈正相关.结论 CCR7、L-selectin、CD44v6和MMP9在大肠癌中的表达与大肠癌的发生、淋巴转移有关,它们可能共同参与了大肠癌发生及淋巴结转移过程.%Purpose To investigate the expression of chemokine receptor 7 ( CCR7 ), adhesion molecule L-selectin, CD44v6 and MMP9 in human colorectal carcinoma, and analyze their correlation with lymph node metastasis. Methods The expression of CCR7, L-selectin, CD44v6 and MMP9 were tested by immunohistochemical method in 104 cases of colorectal carcinoma specimens ( colorectal carcinoma group ), 55 cases of normal intestinal mucosa adjacent to carcinoma ( adjacent group ) and 34 cases of metastatic tumor tissue ( metastasis group). Results The positive rate of CCR7, L-selectin, CD44v6 and MMP9 expression in the colorectal carcinoma group and metastatic tumor tissue were significantly higher than that in adjacent group and metastasis group ( P < 0. 05 ). The expression of CCR7, L-selectin, CD44v6 and MMP9 in the tissue with lymph node metastasis was significantly higher than that in the tissue without lymph node metastasis ( P <0. 05 ). There was significantly positive correlation between expression of CCR7 and L-selectin, CCR7 and MMP9, CD44v6 and L-selectin, CD44v6 and MMP9, L-selectin and MMP9 ( P < 0. 05 ). Conclusions The expression of CCR7, L-selectin, CD44v6 and MMP9 are closely

  10. 趋化因子受体CCR7在非小细胞肺癌中的表达及其与淋巴结转移的关系%A study on the relationship between chemokine receptor CCR7 expression and non-small cell lung cancer lymph node metastasis

    Institute of Scientific and Technical Information of China (English)

    孔凡华; 王鹏

    2010-01-01

    目的 探讨非小细胞肺癌中趋化因子受体CCR7的表达及其临床意义.方法 采用免疫组化和RT-PCR法检测40例非小细胞肺癌中CCR7的表达(鳞癌23例,腺癌14例,腺鳞癌3例),阴性对照标本采用20例癌旁正常肺组织.结果 免疫组化显示CCR7在25例(62.5%)非小细胞肺癌组织中表达和1例(5%)癌旁正常肺组织中表达,差异具有显著意义(P<0.01);RT-PCR显示CCR7 mRNA在29例(72.5%)非小细胞肺癌组织中表达和2例(10%)癌旁正常肺组织中表达,差异具有显著意义(P<0.01).CCR7表达与肿瘤TNM分期、淋巴结转移、分化程度、局部浸润有关,但与年龄、性别、肿瘤大小、病理类型无关.免疫组化和RT-PCR法显示CCR7表达对肺癌淋巴结转移判断的敏感性、特异性、阳性预测值及阴性预测值分别为95.9%(100%)、77.8%(61.1%)、84%(75.9%)、93.3%(100%).结论 CCR7在非小细胞肺癌中高表达,且与淋巴结转移密切相关,是肺癌淋巴结转移的独立危险因素,CCR7的表达可作为预测NSCLC患者淋巴结转移的临床候选指标之一,对指导肺癌的靶向治疗具有一定价值.

  11. NATIONAL SURVEY ON PREVALENCE OF CANCER PAIN

    Institute of Scientific and Technical Information of China (English)

    刘志民; 连智; 周伟华; 穆悦; 吕宪祥; 赵苳; 蔡志基; 曹家琪; 任正洪

    2001-01-01

    Objective. To collect nationwide basic data about cancer related pain.``Methods. Sixty cancer patients in each province were randomly selected to participate in this survey. The subjects represented all stages of cancer, tumor sites, and different demographic characteristics. Two self-designed structured questionnaires including reasons, types of pain and pain management were used by patients and physicians respectively. Subjects were asked to report whether he/she had experienced any type of cancer related pain and filled out the equivalent questionnaire. The severity of pain was assessed by using "visual analogue scale".Original data input and analysis were using EPI-INFO software package.``Results. The result showed that 61.6% (958/1555) of patients had different types of cancer related pain.Majority of pain (85.1%) were caused by advanced cancer. The major reasons (64.4%) for poor management or impedimental factors of pain care are due to patient including over-concern on opioid analgesic addiction, reluctance to report pain or refused to use opioid analgesic until at times when pain is intolerable; 26. 8% belonged to physician' s reasons including fear to cause addiction on opioid and lack of knowledge about cancer pain management; 16. 2% are due to lack of different kinds of opioid analgesic for use and 16. 1% belonged to drug regulation.``Conclusions. The results showed that majority of patients (61.6%) had different types of cancer related pain. In most of patients, cancer pain was relieved when they were treated. The major reason for under-treatment or impeded factors for effective relief of cancer pain was fear of opioid addiction by both medical professionals and patients.

  12. NATIONAL SURVEY ON PREVALENCE OF CANCER PAIN

    Institute of Scientific and Technical Information of China (English)

    刘志民; 连智; 周伟华; 穆悦; 吕宪祥; 赵苳; 蔡志基; 曹家琪; 任正洪

    2001-01-01

    Objective. To collect nationwide basic data about cancer related pain. Methods. Sixty cancer patients in each province were randomly selected to participate in this survey. The subjects represented all stages of cancer, tumor sites, and different demographic characteristics. Two selfdesignedstructured questionnaires including reasons, types of pain and pain management were used by patients and physicians respectively. Subjects were asked to report whether he/she had experienced any type of cancer related pain and fdled out the equivalent questionnaire. The severity of pain was assessed by using "visual analogue scale".Original data input and analysis were using EPI-INFO software package. Results. The result showed that 61.6% (958/1555) of patients had different types of cancer related pain.Majority of pain (85.1%) were caused by advanced cancer. The major reasons (64.4%) for poor management or impedimental factors of pain care are due to patient including over-concern on opioid analgesic addiction, reluc-tance to report pain or refused to use opioid analgesic until at times when pain is intolerable; 26. 8% belonged to physician' s reasons includiag fear to cause addiction on opioid and lack of knowledge about cancer pain management; 16. 2% are due to lack of different kinds of opioid analgesic for use and 16. 1% belonged to drug regulation. Conclusions. The results showed that majority of patients (61.6%) had different types of cancer related pain. In most of patients, cancer pain was relieved when they were treated. The major reason for under-treatmentor impeded factors for effective relief of cancer pain was fear of opioid addiction by both medical professionals andpatients.

  13. Essential medicines for cancer: WHO recommendations and national priorities

    Science.gov (United States)

    Robertson, Jane; Barr, Ronald; Shulman, Lawrence N; Forte, Gilles B

    2016-01-01

    Abstract Objective To examine, for essential anti-cancer medicines, the alignment of national lists of essential medicines and national reimbursable medicines lists with the World Health Organization’s (WHO’s) Model Lists. Methods National medicine lists for 135 countries with per-capita gross national incomes below 25 000 United States dollars in 2015 were compared with WHO’s 2013 and 2015 Model Lists of Essential Medicines. Correlations between numbers of anti-cancer medicines included in national lists and gross national income (GNI), government health expenditure and number of physicians per 1000 population were evaluated. Findings Of the 25 anti-cancer medicines on the 2013 Model List and the 16 added via the 2015 revision of the Model List, 0–25 (median: 17) and 0–15 (median: 3) appeared in national lists, respectively. There was considerable variability in these numbers within and between World Bank income groups. Of the 16 new medicines included in the 2015 Model List, for example, 0–10 (median: 1) and 2–15 (median: 10) were included in the national lists of low-income and high-income countries, respectively. The numbers of these new medicines included in national lists were significantly correlated (P ≤ 0.0001) with per-capita GNI (r = 0.45), per-capita annual government health expenditure (r = 0.33) and number of physicians per 1000 population (r = 0.48). Twenty-one countries (16%) included the targeted anti-cancer medicines imatinib, rituximab and trastuzumab in their national lists. Conclusion Substantial numbers of anti-cancer medicines are included in national lists of low- and middle-income countries but the availability, affordability, accessibility and administration feasibility of these medicines, at country-level, need assessment. PMID:27843163

  14. 78 FR 30933 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-05-23

    ...: Robert Bird, Ph.D., Chief, Resources and Training Review Branch, Division of Extramural Activities... Person: Timothy C. Meeker, MD, Ph.D., Scientific Review Officer, Resources and Training Review Branch... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  15. The National Lung Screening Trial (NLST) | Division of Cancer Prevention

    Science.gov (United States)

    The National Lung Screening Trial (NLST) compared two ways of detecting lung cancer: low-dose helical computed tomography (CT) and standard chest X-ray. Both chest X-rays and low-dose helical CT scans have been used to find lung cancer early, but the effects of these screening techniques on lung cancer mortality rates had not been determined. NLST enrolled 53,454 current or former heavy smokers from 33 sites and coordinating centers across the United States. | The National Lung Screening Trial (NLST) compared two ways of detecting lung cancer: participants who received low-dose helical CT scans had a 20% lower risk of dying from lung cancer than participants who received standard chest X-rays.

  16. Structure-Activity Relationships and Identification of Optmized CC-Chemokine Receptor CCR1, 5, and 8 Metal-Ion Chelators

    DEFF Research Database (Denmark)

    Chalikiopoulos, Alexander; Thiele, Stefanie; Malmgaard-Clausen, Mikkel;

    2013-01-01

    Chemokine receptors are involved in trafficking of leukocytes and represent targets for autoimmune conditions, inflammatory diseases, viral infections, and cancer. We recently published CCR1, CCR8, and CCR5 agonists and positive modulators based on a three metal-ion chelator series: 2,2'-bipyridine...... bipyridine (23). The structure-activity relationships contribute to small-molecule drug development, and the novel chelators constitute valuable tools for studies of structural mechanisms for chemokine receptor activation....

  17. CCR7和VEGF-D蛋白在乳腺癌发生发展过程中的表达及意义%Expression and Significance of CCR7 Protein and VEGF-D Protein in Progression of Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    目的 研究趋化因子受体7 (CCR7)蛋白和血管内皮生长因子D(VEGF-D)蛋白在乳腺癌癌变过程中,即正常乳腺组织、轻中度导管非典型增生组织、重度导管非典型增生+导管原位癌组织及乳腺浸润性导管癌组织中的表达及意义.方法 采用免疫组化染色法,检测正常乳腺组织(n=20)、乳腺轻中度导管非典型增生组织(n=20)、乳腺重度导管非典型增生+导管原位癌组织(n=20)及乳腺浸润性导管癌组织(n=73)中CCR7和VEGF-D蛋白的表达情况,并根据D2-40染色结果计算微淋巴管密度(LMVD).同时分析乳腺癌组织中,CCR7和VEGF-D蛋白表达与乳腺癌临床病理学特征的关系、CCR7和VEGF-D蛋白表达与LMVD值间的关系及CCR7蛋白表达与VEGF-D蛋白表达的关系.结果 ①正常乳腺组织组[CCR7蛋白:0(0/20),VEGF-D蛋白:5.0%(1/20)])、轻中度乳腺导管非典型增生组[CCR7蛋白:5.0%(1/20),VEGF-D蛋白:20.0% (4/20)])、乳腺重度导管非典型增生+导管原位癌组[CCR7蛋白:30.0% (6/20),VEGF-D蛋白:40.0%(8/20)])及乳腺癌组[CCR7蛋白:47.9% (35/73),VEGF-D蛋白:57.5% (42/73)]的CCR7蛋白(X2趋势=23.905,P<0.050)和VEGF-D蛋白(X2趋势=22.349,P<0.050)的表达阳性率逐渐增高.②正常乳腺组织组、乳腺轻中度导管非典型增生组、乳腺重度导管非典型增生+导管原位癌组及乳腺癌组的LMVD值分别为2.00±1.02、6.70±3.48、9.01±2.13及16.32±4.07,LMVD值逐渐增高,4组间两两比较差异均有统计学意义(P<0.050).③在乳腺癌患者中,CCR7蛋白和VEGF-D蛋白的表达均与临床分期、组织学分级、淋巴结转移及人类表皮生长因子2(HER-2)表达有关(P<0.050),组织学分级越高、临床分期为Ⅲ+Ⅳ期(与Ⅰ+Ⅱ期者相比)、淋巴结转移(与未发生淋巴结转移者相比)及HER-2表达阳性(与HER-2表达阴性者相比)者CCR7蛋白和VEGF-D蛋白的表达阳性率较高.在乳腺癌患者中,LMVD值和VEGF-D蛋白

  18. HIV-1 co-receptor CCR5 and CCR2 mutations among Greeks.

    Science.gov (United States)

    Papa, A; Papadimitriou, E; Adwan, G; Clewley, J P; Malissiovas, N; Ntoutsos, I; Alexiou, S; Antoniadis, A

    2000-05-01

    The frequency of CCR5 and CCR2 alleles in human immunodeficiency virus (HIV)-positive and HIV-negative populations of Northern Greece was investigated. The frequency of the CCR5Delta32 allele among the HIV-negative subjects was 0.052, while it was approximately two-fold lower among the seropositives, suggesting that the heterozygous genotype confers a partial resistance to the HIV infection. No significant difference in CCR2 allele frequency between the two groups was observed.

  19. Genetic diversity and prevalence of CCR2-CCR5 gene polymorphisms in the Omani population

    Directory of Open Access Journals (Sweden)

    Samira H. Al-Mahruqi

    2014-01-01

    Full Text Available Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Ocean. In this study, we examined the CCR2-CCR5 haplotypes in Omanis and compared the patterns of genetic diversity with those of other populations. Blood samples were collected from 115 Omani adults and genomic DNA was screened to identify the polymorphic sites in the CCR5 gene and the CCR2V64I mutation. Four minor alleles were common: CCR5-2554T and CCR5-2086G showed frequencies of 49% and 46%, respectively, whereas CCR5-2459A and CCR5-2135C both had a frequency of 36%. These alleles showed moderate levels of heterozygosity, indicating that they were under balancing selection. However, the well-known allele CCR5!32 was relatively rare. Eleven haplotypes were identified, four of which were common: HHC (46%, HHE (20%, HHA (14% and HHF*2 (12%.

  20. Genetic diversity and prevalence of CCR2-CCR5 gene polymorphisms in the Omani population.

    Science.gov (United States)

    Al-Mahruqi, Samira H; Zadjali, Fahad; Beja-Pereira, Albano; Koh, Crystal Y; Balkhair, Abdullah; Al-Jabri, Ali A

    2014-03-01

    Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Ocean. In this study, we examined the CCR2-CCR5 haplotypes in Omanis and compared the patterns of genetic diversity with those of other populations. Blood samples were collected from 115 Omani adults and genomic DNA was screened to identify the polymorphic sites in the CCR5 gene and the CCR2V64I mutation. Four minor alleles were common: CCR5-2554T and CCR5-2086G showed frequencies of 49% and 46%, respectively, whereas CCR5-2459A and CCR5-2135C both had a frequency of 36%. These alleles showed moderate levels of heterozygosity, indicating that they were under balancing selection. However, the well-known allele CCR5Δ32 was relatively rare. Eleven haplotypes were identified, four of which were common: HHC (46%), HHE (20%), HHA (14%) and HHF*2 (12%).

  1. Cancer registries in Japan: National Clinical Database and site-specific cancer registries.

    Science.gov (United States)

    Anazawa, Takayuki; Miyata, Hiroaki; Gotoh, Mitsukazu

    2015-02-01

    The cancer registry is an essential part of any rational program of evidence-based cancer control. The cancer control program is required to strategize in a systematic and impartial manner and efficiently utilize limited resources. In Japan, the National Clinical Database (NCD) was launched in 2010. It is a nationwide prospective registry linked to various types of board certification systems regarding surgery. The NCD is a nationally validated database using web-based data collection software; it is risk adjusted and outcome based to improve the quality of surgical care. The NCD generalizes site-specific cancer registries by taking advantage of their excellent organizing ability. Some site-specific cancer registries, including pancreatic, breast, and liver cancer registries have already been combined with the NCD. Cooperation between the NCD and site-specific cancer registries can establish a valuable platform to develop a cancer care plan in Japan. Furthermore, the prognosis information of cancer patients arranged using population-based and hospital-based cancer registries can help in efficient data accumulation on the NCD. International collaboration between Japan and the USA has recently started and is expected to provide global benchmarking and to allow a valuable comparison of cancer treatment practices between countries using nationwide cancer registries in the future. Clinical research and evidence-based policy recommendation based on accurate data from the nationwide database may positively impact the public.

  2. The impact of CCR5-Δ32 deletion on C-reactive protein levels and cardiovascular disease

    DEFF Research Database (Denmark)

    Dinh, Khoa M; Pedersen, Ole B; Petersen, Mikkel S;

    2015-01-01

    BACKGROUND AND PURPOSE: The C-C chemokine receptor 5-Δ32 deletion (CCR5-Δ32) has been associated with lower levels of C-reactive protein (CRP), but the effect on cardiovascular diseases is uncertain. This study addresses the impact of CCR5-Δ32 on the risk of low-grade inflammation...... and hospitalization with cardiovascular diseases in a large cohort of blood donors. METHODS: Genotyping of 15,206 healthy participants from The Danish Blood Donor Study for CCR5-Δ32 was performed and combined with CRP measurements and questionnaire data. Cardiovascular disease diagnoses were identified by ICD-10...... codes in the Danish National Patient Registry. RESULTS: CCR5-Δ32-carriers had a higher risk of hospitalization for cardiovascular diseases when compared with wild-type homozygotes (hazard ratio = 1.35, 95%-confidence interval: 1.00-1.87). CRP levels were unaffected by the CCR5-Δ32 deletion. CONCLUSION...

  3. Research progress of chemokine receptor CCR5%趋化因子受体CCR5的研究进展

    Institute of Scientific and Technical Information of China (English)

    朱长斌; 蒋子恺; 程枫; 钱关祥

    2012-01-01

    CCR5, as the member of CC receptor family, with its ligands being CCL3 (MIP-1α), CCL4 (MIP-1β) and CCL5 (RANTES), is categorized as 7 trans-membrane domain G-protein coupled receptor. CCR5 is expressed in monocytes/macrophages as well as lymphocytes inducing chemotaxis and recruitment in inflammatory response and is an important co-receptor of human immunodeficiency virus ( HIV) -1 virus, leading to the multifunction of CCR5 in progression of various kind of immunological diseases and invasion of HIV-1. Moreover, the expression of CCR5 on the surface of tumor cells and stromal cells contributes to mediating multiple biological behaviors of cancers such as proliferation and invasion. Advanced technologies also lead to the revealing of structure, function, signal transduction and roles of CCRS in the progression of related diseases.%CCR5为趋化因子CC受体家族成员,属7次跨膜G蛋白耦联受体,配体为CCL3 (MIP-1α)、CCL4( MIP-1β)、CCL5( RANTES).CCR5主要表达于单核/巨噬细胞和淋巴细胞,与其配体介导CCR5+免疫细胞的趋化、募集过程.因此,多种免疫性疾病的发生和发展过程均有CCR5参与.CCR5是人类免疫缺陷病毒Ⅰ型(HIV-1)入侵时的重要辅助受体,而在肿瘤细胞和各类肿瘤相关间质细胞的表面也可见其表达,并介导肿瘤增殖、浸润等多种生物学过程.随着相关研究技术的发展,进一步加深了对CCR5的结构、功能、信号通路及其在相关疾病中的作用的认识.

  4. Fully human antagonistic antibodies against CCR4 potently inhibit cell signaling and chemotaxis.

    Directory of Open Access Journals (Sweden)

    Urs B Hagemann

    Full Text Available CC chemokine receptor 4 (CCR4 represents a potentially important target for cancer immunotherapy due to its expression on tumor infiltrating immune cells including regulatory T cells (Tregs and on tumor cells in several cancer types and its role in metastasis.Using phage display, human antibody library, affinity maturation and a cell-based antibody selection strategy, the antibody variants against human CCR4 were generated. These antibodies effectively competed with ligand binding, were able to block ligand-induced signaling and cell migration, and demonstrated efficient killing of CCR4-positive tumor cells via ADCC and phagocytosis. In a mouse model of human T-cell lymphoma, significant survival benefit was demonstrated for animals treated with the newly selected anti-CCR4 antibodies.For the first time, successful generation of anti- G-protein coupled chemokine receptor (GPCR antibodies using human non-immune library and phage display on GPCR-expressing cells was demonstrated. The generated anti-CCR4 antibodies possess a dual mode of action (inhibition of ligand-induced signaling and antibody-directed tumor cell killing. The data demonstrate that the anti-tumor activity in vivo is mediated, at least in part, through Fc-receptor dependent effector mechanisms, such as ADCC and phagocytosis. Anti-CC chemokine receptor 4 antibodies inhibiting receptor signaling have potential as immunomodulatory antibodies for cancer.

  5. The frequency of CCR5 promoter polymorphisms and CCR5 32 mutation in Iranian populations

    Directory of Open Access Journals (Sweden)

    Mohammad Zare-Bidaki

    2015-04-01

    Full Text Available Evidence showed that chemokines serve as pro-migratory factors for immune cells. CCL3, CCL4 and CCL5, as the main CC  chemokines subfamily members, activate immune cells through binding to CC chemokine receptor 5 or CCR5. Macrophages, NK cells and T lymphocytes express CCR5 and thus, affected CCR5 expression or functions could be associated with altered immune responses. Deletion of 32 base pairs (D 32 in the exon 1 of the CCR5 gene, which is known as CCR5 D 32 mutation causes down regulation and malfunction of the molecule. Furthermore, it has been evidenced that three polymorphisms in the promoter region of CCR5 modulate its expression. Altered CCR5 expression in microbial infection and immune related diseases have been reported by several researchers but the role of CCR5 promoter polymorphisms and CCR5 D 32 mutation in Iranian patients suffering from these diseases are controversial. Due to the fact that Iranian people have different genetic backgrounds compared to other ethnics, hence, CCR5 promoter polymorphisms and CCR5 D 32 mutation association with the diseases may be different in Iranian patients. Therefore, this review addresses the most recent information regarding the prevalence as well as association of the mutation and polymorphisms in Iranian patients with microbial infection and immune related diseases as along with normal population.

  6. The frequency of CCR5 promoter polymorphisms and CCR5 Δ 32 mutation in Iranian populations.

    Science.gov (United States)

    Zare-Bidaki, Mohammad; Karimi-Googheri, Masoud; Hassanshahi, Gholamhossein; Zainodini, Nahid; Arababadi, Mohammad Kazemi

    2015-04-01

    Evidence showed that chemokines serve as pro-migratory factors for immune cells. CCL3, CCL4 and CCL5, as the main CC chemokines subfamily members, activate immune cells through binding to CC chemokine receptor 5 or CCR5. Macrophages, NK cells and T lymphocytes express CCR5 and thus, affected CCR5 expression or functions could be associated with altered immune responses. Deletion of 32 base pairs (Δ 32) in the exon 1 of the CCR5 gene, which is known as CCR5 Δ 32 mutation causes down regulation and malfunction of the molecule. Furthermore, it has been evidenced that three polymorphisms in the promoter region of CCR5 modulate its expression. Altered CCR5 expression in microbial infection and immune related diseases have been reported by several researchers but the role of CCR5 promoter polymorphisms and CCR5 Δ 32 mutation in Iranian patients suffering from these diseases are controversial. Due to the fact that Iranian people have different genetic backgrounds compared to other ethnics, hence, CCR5 promoter polymorphisms and CCR5 32 mutation association with the diseases may be different in Iranian patients. Therefore, this review addresses the most recent information regarding the prevalence as well as association of the mutation and polymorphisms in Iranian patients with microbial infection and immune related diseases as along with normal population.

  7. Frequency of CCR5Δ32 allele in healthy Bosniak population.

    Directory of Open Access Journals (Sweden)

    Grażyna Adler

    2014-08-01

    Full Text Available Recent evidence has demonstrated the role of CCR5Δ32 in a variety of human diseases: from infectious and inflammatory diseases to cancer. Several studies have confirmed that genetic variants in chemokine receptor CCR5 gene are correlated with susceptibility and resistance to HIV infection. A 32-nucleotide deletion within the CCR5 reading frame is associated with decreased susceptibility to HIV acquisition and a slower progression to AIDS. Mean frequency of CCR5Δ32 allele in Europe is approximately 10%. The highest allele frequency is observed among Nordic populations (about 12% and lower in the regions of Southeast Mediterranean (about 5%. Although the frequency of CCR5Δ32 was determined in numerous European populations, there is a lack of studies on this variant in the Bosnia and Hercegovina population. Therefore, the aim of our study was to assess the frequency of CCR5Δ32 allele in the cohort of Bosniaks and compare the results with European reports. CCR5Δ32 was detected by sequence-specific PCR in a sample of 100 healthy subjects from Bosnia and Herzegovina (DNA collected 2011-2013.  Mean age of the cohort being 58.8 (±10.7 years, with 82% of women. We identified 17 heterozygotes and one mutant homozygote in study group, with mean ∆32 allele frequency of 9.5%. CCR5∆32 allele frequency among Bosniaks is comparable to that found in Caucasian populations and follows the pattern of the north-southern gradient observed for Europe. Further studies on larger cohorts with adequate female-to-male ratio are necessary. 

  8. CCR2, CCR5, and CXCL12 variation and HIV/AIDS in Papua New Guinea.

    Science.gov (United States)

    Mehlotra, Rajeev K; Hall, Noemi B; Bruse, Shannon E; John, Bangan; Blood Zikursh, Melinda J; Stein, Catherine M; Siba, Peter M; Zimmerman, Peter A

    2015-12-01

    Polymorphisms in chemokine receptors, serving as HIV co-receptors, and their ligands are among the well-known host genetic factors associated with susceptibility to HIV infection and/or disease progression. Papua New Guinea (PNG) has one of the highest adult HIV prevalences in the Asia-Pacific region. However, information regarding the distribution of polymorphisms in chemokine receptor (CCR5, CCR2) and chemokine (CXCL12) genes in PNG is very limited. In this study, we genotyped a total of nine CCR2-CCR5 polymorphisms, including CCR2 190G >A, CCR5 -2459G >A and Δ32, and CXCL12 801G >A in PNG (n=258), North America (n=184), and five countries in West Africa (n=178). Using this data, we determined previously characterized CCR5 haplotypes. In addition, based on the previously reported associations of CCR2 190, CCR5 -2459, CCR5 open reading frame, and CXCL12 801 genotypes with HIV acquisition and/or disease progression, we calculated composite full risk scores, considering both protective as well as susceptibility effects of the CXCL12 801 AA genotype. We observed a very high frequency of the CCR5 -2459A allele (0.98) in the PNG population, which together with the absence of Δ32 resulted in a very high frequency of the HHE haplotype (0.92). These frequencies were significantly higher than in any other population (all P-valuesCCR5 variation in the PNG population, and suggest that the collective variation in CCR2, CCR5, and CXCL12 may increase the risk of HIV/AIDS in a large majority of Papua New Guineans.

  9. New Hires at the National Cancer Institute at Frederick | Poster

    Science.gov (United States)

    Fifty-one people joined the facility in November and December 2013. The National Cancer Institute welcomes… Emily Boward Emad Darvishi Shuo Gu Sanath Kumar Janaka Robert Kortum Yasmin Lachir Jinbian Liu Yang Liu Eric Ramirez Salazar Brett Shelley Li Xia Jaeho Yoon

  10. 75 FR 10295 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-03-05

    ... review and evaluate grant applications. Place: Hilton Washington, DC/Rockville Hotel, 1750 Rockville Pike.... Place: Legacy Hotel and Meeting Center, 1775 Rockville Pike, Rockville, MD 20852. Contact Person: Gerald... Extramural Activities, National Cancer Institute, 6116 Executive Blvd., Room 8101, Bethesda, MD...

  11. 76 FR 42718 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-07-19

    .... Time: 8 a.m. to 2 p.m. Agenda: To review and evaluate grant applications. Place: Hilton Washington/DC Rockville, Hotel and Executive Meeting Center, 1750 Rockville Pike, Rockville, MD 20582. Contact Person... Activities, National Cancer Institute, NIH, 6116 Executive Boulevard, Room 8113, Bethesda, MD 20892,...

  12. 77 FR 14026 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-03-08

    ... 5 p.m. Agenda: To review and evaluate contract proposals. Place: Hilton Washington DC/Rockville Hotel & Executive Meeting Center, 1750 Rockville Pike, Rockville, MD 20852. Contact Person: Zhiqiang Zou... Activities, National Cancer Institute, NIH, 6116 Executive Blvd., Room 8050A, MSC 8329, Bethesda, MD...

  13. 76 FR 5597 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-02-01

    ... applications. Place: Hilton Washington DC/Rockville Hotel, 1750 Rockville Pike, Rockville, MD 20852. Contact...D, Scientific Review Officer, Special Review and Logistics Branch, Division of Extramural Activities..., Division of Extramural Activities, National Cancer Institute, NIH, 6116 Executive Boulevard, Room...

  14. 76 FR 81952 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-12-29

    ... 24-25, 2012. Time: 8 a.m. to 7 p.m. Agenda: To review and evaluate grant applications. Place: Hilton...., Scientific Review Officer, Research Programs Review Branch, Division of Extramual Activities, National Cancer... evaluate grant applications. Place: Bethesda North Marriott Hotel & Conference Center, 5701 Marinelli...

  15. 77 FR 4052 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-01-26

    ...: To review and evaluate grant applications. Place: Hilton Washington DC/Rockville Hotel & Executive....m. Agenda: To review and evaluate grant applications. Place: Hilton Washington DC/Rockville, 1750... Programs Review Branch, Division of Extramural Activities, National Cancer Institute, NIH, 6116...

  16. 75 FR 3242 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-01-20

    .... Place: Washington DC North Hilton Hotel, 620 Perry Parkway, Gaithersburg, MD 20877. Contact Person... Activities, National Cancer Institute, 6116 Executive Boulevard, Room 7147, Bethesda, MD 20892-8329, 301-496.... Time: 7:45 a.m. to 6 p.m. Agenda: To review and evaluate grant applications. Place: Hilton...

  17. 75 FR 57473 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-09-21

    ....m. to 6 p.m. Agenda: To review and evaluate grant applications. Place: Hilton Alexandria Old Town..., Resources and Training Review Branch, Division of Extramural Activities, National Cancer Institute, NIH... evaluate contract proposals. Place: Bethesda North Marriott Hotel & Conference Center, 5701 Marinelli...

  18. 78 FR 38355 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-06-26

    ...: Hilton Washington DC/Rockville Hotel, 1750 Rockville Pike, Rockville, MD 20852. Contact Person: Peter J... Activities, National Cancer Institute, NIH, 9606 Medical Center Drive, 7W514, MSC 9750, Bethesda, MD 20892... evaluate grant applications. Place: Doubletree Hotel Bethesda, 8120 Wisconsin Avenue, Bethesda, MD...

  19. 75 FR 7489 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-02-19

    ... applications. Place: Legacy Hotel and Meeting Center, 1775 Rockville Pike, Rockville, MD 20852. Contact Person... Extramural Activities, National Cancer Institute, 6116 Executive Boulevard, Room 7141, Bethesda, MD 20892.... Place: Hilton Washington/Rockville, 1750 Rockville Pike, Rockville, MD 20852. Contact Person:...

  20. From Bombs to Breast Cancer Imaging: Los Alamos National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Martineau, Rebecca M [Los Alamos National Laboratory

    2012-07-26

    . Currently, there is fierce debate surrounding the age at which breast cancer screening should begin, and once begun, how often it should occur. The American Cancer Society recommends yearly mammograms starting at age 40. On the other hand, the U.S. Preventive Services Task Force recommends against routine so early. Rather, the Task Force recommends biennial mammography screening for women aged 50 to 74 years. The ten-year discrepancy in the onset of screening results from recent data suggesting that the frequent use of X-ray radiation during screenings could potentially increase the likelihood of developing cancer. This danger is increased by the low sensitivity and accuracy of mammograms, which sometimes require multiple screenings to yield results. Furthermore, mammograms are often not only inaccurate, but average appalling misdiagnoses rates: about 80% false positives and 15% false negatives. These misdiagnoses lead to unwarranted biopsies at an estimated health care cost of $2 billion per year, while at the same time, resulting in excessive cases of undetected cancer. As such, the National Cancer Institute recommends more studies on the advantages of types and frequency of screenings, as well as alternative screening options. The UST technology developed at LANL could be an alternative option to greatly improve the specificity and sensitivity of breast cancer screening without using ionizing radiation. LANL is developing high-resolution ultrasound tomography algorithms and a clinical ultrasound tomography scanner to conduct patient studies at the UNM Hospital. During UST scanning, the patient lies face-down while her breast, immersed in a tank of warm water, is scanned by phased-transducer arrays. UST uses recorded ultrasound signals to reconstruct a high-resolution three-dimensional image of the breast, showing the spatial distribution of mechanical properties within the breast. Breast cancers are detected by higher values of mechanical properties compared to

  1. Expression of CCR7 and its correlation with epithelial-mesenchymal transition in breast carcinoma%乳腺癌组织 CCR7的表达及其与上皮间质转化的关系

    Institute of Scientific and Technical Information of China (English)

    徐蕴; 张肇林; 窦珊珊; 崔利德

    2015-01-01

    Objective To investigate the association between the expression of CCR7 and clinical parameters in human breast carcinoma and analyze the relationship between CCR 7 and the epithelial‐mesenchymal transition (EMT) .Methods CCR7 ,Slug and N‐cadherin were examined by immunohistochemistry in 56 cases of breast car‐cinoma tissues .The correlation between clinical parameters and CCR7 expression were retrospectively analyzed . Results 1)The expressions of CCR7 in lymph node metastasis group were significantly higher than those in the group that without lymph node metastasis (χ2 = 5 .061 ,P < 0 .05) .2)The expression of CCR7 in human breast cancer increased with the increase of the pathological stage of the patients .3)High expressions of CCR7 ,Slug and N‐cadherin were found in human breast carcinoma and the positive rate was 60 .71% ,66 .07% and 76 .78 % re‐spectively .4)The CCR7 expression was significantly associated to Slug and N‐cadherin( P < 0 .001) .Conclusion CCR7 was closely related to EMT indicators (Slug and N‐cadherin) in human breast carcinoma .CCR7 may play a role in the genesis of EMT in human breast carcinoma and be expected to become the biomarker of cancer metasta ‐sis .%目的:研究趋化因子受体‐7(chemokine receptor 7,CCR7)在乳腺癌组织中的表达及临床意义,并探讨 CCR7与上皮间质转化(epithelial mesenchymal transformation ,EM T )的关系。方法采用免疫组织化学检测 CCR7、EM T 相关标志物转录因子 Slug 和 N‐cadherin 的表达,分析 CCR7与患者病理特征的关系。结果1) CCR7在淋巴结转移组的表达明显高于无淋巴结转移组(χ2=5.061,P<0.05);2)CCR7在人乳腺癌组织的表达随患者病理分期的增加(Ⅰ→Ⅳ)而增加;3)CCR7、Slug 和 N‐cadherin 在人乳腺癌组织中均呈高表达,阳性率分别为60.71%(34/56)、66.07%(37/56)、76.78%(43/56);4)CCR7与 Slug

  2. CCL21/CCR7 axis activating chemotaxis accompanied with epithelial-mesenchymal transition in human breast carcinoma.

    Science.gov (United States)

    Li, Fei; Zou, Zhigeng; Suo, Ning; Zhang, Zongpu; Wan, Fangzhu; Zhong, Guangxin; Qu, Yan; Ntaka, Kwanele Siphelele; Tian, Hua

    2014-09-01

    Secondary lymphoid tissue chemokine (SLC/CCL21) and its receptor CCR7 have been implicated in lymph node metastasis, whereas the mechanism of which remains unclear. Epithelial-mesenchymal transition (EMT) plays an important role in invasion and migration of cancer cells. We presumed that CCL21/CCR7 axis activates EMT process to induce cancer cell invasion and metastasis. Firstly, the expressions of CCR7 and EMT markers were examined by immunohistochemical staining in the primary breast carcinoma tissues from 60 patients who underwent radical mastectomy. Then, we investigated whether CCL21/CCR7 induces EMT process during mediating cancer cell invasion or migration in vitro. By immunohistolochemistry, high expressions of CCR7, Slug and N-cadherin were seen in 60, 65, and 76.67 % of tumors, respectively, and significantly associated with lymph node metastases as well as clinical pathological stage. Furthermore, the CCR7 expression was significantly correlated to Slug and N-cadherin. In vitro, stimulating breast cancer cell lines 1428, MCF-7 and MDA-MB-231 with CCL21, the invasion and migration of tumor cells were promoted, and simultaneously, EMT phenotype of tumor cells was enhanced, including down-regulation of E-cadherin, up-regulation of Slug, Vimentin and N-cadherin at both protein and mRNA levels. Inversely, knockdown of CCR7 by shRNA suppressed tumor cell invasion, migration and EMT phenotype induced by CCL21. These results indicated that CCL21/CCR7 axis could activate EMT process during chemotaxis of breast carcinoma cells.

  3. 78 FR 36788 - Proposed Collection; 60-Day Comment Request; Awareness and Beliefs About Cancer Survey, National...

    Science.gov (United States)

    2013-06-19

    ... Beliefs About Cancer Survey, National Cancer Institute (NCI) Summary: In compliance with the requirement... this publication. Proposed Collection: Awareness and Beliefs about Cancer Survey, 0925-NEW, National... objective of the study is gather data about American adults' awareness and beliefs about cancer....

  4. Cancer complementary and alternative medicine research at the US National Cancer Institute.

    Science.gov (United States)

    Jia, Libin

    2012-05-01

    The United States National Cancer Institute (NCI) supports complementary and alternative medicine (CAM) research which includes different methods and practices (such as nutrition therapies) and other medical systems (such as Chinese medicine). In recent years, NCI has spent around $120 million each year on various CAM-related research projects on cancer prevention, treatment, symptom/side effect management and epidemiology. The categories of CAM research involved include nutritional therapeutics, pharmacological and biological treatments, mind-body interventions, manipulative and body based methods, alternative medical systems, exercise therapies, spiritual therapies and energy therapies on a range of types of cancer. The NCI Office of Cancer Complementary and Alternative Medicine (OCCAM) supports various intramural and extramural cancer CAM research projects. Examples of these cancer CAM projects are presented and discussed. In addition, OCCAM also supports international research projects.

  5. Differential ligand-signaling network of CCL19/CCL21-CCR7 system.

    Science.gov (United States)

    Raju, Rajesh; Gadakh, Sachin; Gopal, Priyanka; George, Bijesh; Advani, Jayshree; Soman, Sowmya; Prasad, T S K; Girijadevi, Reshmi

    2015-01-01

    Chemokine (C-C motif) receptor 7 (CCR7), a class A subtype G-Protein Coupled Receptor (GPCR), is involved in the migration, activation and survival of multiple cell types including dendritic cells, T cells, eosinophils, B cells, endothelial cells and different cancer cells. Together, CCR7 signaling system has been implicated in diverse biological processes such as lymph node homeostasis, T cell activation, immune tolerance, inflammatory response and cancer metastasis. CCL19 and CCL21, the two well-characterized CCR7 ligands, have been established to be differential in their signaling through CCR7 in multiple cell types. Although the differential ligand signaling through single receptor have been suggested for many receptors including GPCRs, there exists no resource or platform to analyse them globally. Here, first of its kind, we present the cell-type-specific differential signaling network of CCL19/CCL21-CCR7 system for effective visualization and differential analysis of chemokine/GPCR signaling. Database URL: http:// www. netpath. org/ pathways? path_ id= NetPath_ 46.

  6. Chemokine receptor CCR5 in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Kristiansen, Thomas Birk; Wittenhagen, P

    2007-01-01

    OBJECTIVE: To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta). METHODS: The CCR5 Delta32 allele and a CCR5 promoter polymorphism associated with cell surface expression of CCR5 were...

  7. The burden of prostate cancer in Asian nations

    Directory of Open Access Journals (Sweden)

    Jennifer Cullen

    2012-01-01

    Full Text Available Introduction: In this review, the International Agency for Research on Cancer′s cancer epidemiology databases were used to examine prostate cancer (PCa age-standardized incidence rates (ASIR in selected Asian nations, including Cancer Incidence in Five Continents (CI5 and GLOBOCAN databases, in an effort to determine whether ASIRs are rising in regions of the world with historically low risk of PCa development. Materials and Methods: Asian nations with adequate data quality were considered for this review. PCa ASIR estimates from CI5 and GLOBOCAN 2008 public use databases were examined in the four eligible countries: China, Japan, Korea and Singapore. Time trends in PCa ASIRs were examined using CI5 Volumes I-IX. Results: While PCa ASIRs remain much lower in the Asian nations examined than in North America, there is a clear trend of increasing PCa ASIRs in the four countries examined. Conclusion: Efforts to systematically collect cancer incidence data in Asian nations must be expanded. Current CI5 data indicate a rise in PCa ASIR in several populous Asian countries. If these rates continue to rise, it is uncertain whether there will be sufficient resources in place, in terms of trained personnel and infrastructure for medical treatment and continuum of care, to handle the increase in PCa patient volume. The recommendation by some experts to initiate PSA screening in Asian nations could compound a resource shortfall. Obtaining accurate estimates of PCa incidence in these countries is critically important for preparing for a potential shift in the public health burden posed by this disease.

  8. Comparing local TV news with national TV news in cancer coverage: an exploratory content analysis.

    Science.gov (United States)

    Lee, Chul-Joo; Long, Marilee; Slater, Michael D; Song, Wen

    2014-12-01

    The authors compared local TV news with national TV news in terms of cancer coverage using a nationally representative sample of local nightly TV and national network TV (i.e., ABC, CBS, NBC, and CNN) cancer news stories that aired during 2002 and 2003. Compared with national TV news, local TV cancer stories were (a) much shorter in length, (b) less likely to report on cancer prevention (i.e., preventive behaviors and screening tests), and (c) less likely to reference national organizations (i.e., National Cancer Institute, American Cancer Society, National Institutes of Health, Centers for Disease Control and Prevention, Food and Drug Administration) that have made clear recommendations about ways to prevent cancer. The implications of these findings for health communication research and cancer education were discussed.

  9. Cancer screening status in Korea, 2011: results from the Korean National Cancer Screening Survey.

    Science.gov (United States)

    Park, Boyoung; Choi, Kui Son; Lee, Yoon Young; Jun, Jae Kwan; Seo, Hong Gwan

    2012-01-01

    This study was conducted to determine the use of screening for stomach, liver, colorectal, breast, and cervical cancers, which are included in the Korean National Cancer Screening Programme. In 2011 the National Cancer Centre in Korea conducted a nationwide, population-based, cross-sectional interview survey using multi-stage random sampling. Participants included 4,100 cancer-free men 40 years and over of age and women over 30 years of age. The lifetime screening rates for stomach, liver, colorectal, breast, and cervical cancers were 76.2%, 54.3%, 56.1%, 79.0%, and, 74.8%, respectively. The rates of recommended screening for stomach, liver, colorectal, breast, and cervical cancers were 64.6%, 22.9%, 35.3%, 60.4%, and 62.4%, respectively. More than 70% of all screening was attributed to organised cancer screening programmes. The main reason given for non attendance was 'no symptoms'. A greater effort is needed to increase screening rates, especially for liver and colorectal cancers.

  10. CCR3, CCR5, CCR8 and CXCR3 expression in memory T helper cells from allergic rhinitis patients, asymptomatically sensitized and healthy individuals

    DEFF Research Database (Denmark)

    Holse, Mille; Assing, Kristian; Poulsen, Lars K.

    2006-01-01

    Chemokine receptors have been suggested to be preferentially expressed on CD4+ T cells with CCR3 and CCR8 linked to the T helper (Th) 2 subset and CCR5 and CXCR3 to the Th1 subset, however this remains controversial.......Chemokine receptors have been suggested to be preferentially expressed on CD4+ T cells with CCR3 and CCR8 linked to the T helper (Th) 2 subset and CCR5 and CXCR3 to the Th1 subset, however this remains controversial....

  11. Lack of Correlation Between the CCR5-Δ32 Mutation and Acute Myeloid Leukemia in Iranian Patients.

    Science.gov (United States)

    Khorramdelazad, Hossein; Mortazavi, Yousef; Momeni, Mohammad; Arababadi, Mohammad Kazemi; Khandany, Behjat Kalantary; Moogooei, Mozhgan; Hassanshahi, Gholamhossein

    2015-03-01

    Chemokines and their receptors are crucially important in the pathogenesis of acute myeloblastic leukemia (AML). The CC chemokine receptor 5 (CCR5) is a specific chemokine receptor for CC chemokine ligand 3 (CCL3), CCL4 and CCL5 which all play key roles in identifying cancer properties and localization of leukemia cells. It has been demonstrated that the known mutation in CCR5 gene (CCR5-Δ32) leads to mal-expression of the receptor and affect its function. The aim of this study was to determine the rate of CCR5-Δ32 mutation within Iranian AML patients. In this study, blood samples were obtained from 60 AML patients and 300 healthy controls. The CCR5-Δ32 mutation was evaluated using Gap-PCR technique. Our results showed that CCR5-Δ32 mutation was not found in the patients, while three out of the controls had hetrozygotic form of this mutation. The rest of studied samples had the wild form of the gene. According to these findings, it can probably be concluded that the CCR5-Δ32 is not associated with susceptibility to AML in Iranian patients.

  12. Genetic diversity and prevalence of CCR2-CCR5 gene polymorphisms in the Omani population

    OpenAIRE

    2014-01-01

    Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Oc...

  13. Genetic diversity and prevalence of CCR2-CCR5 gene polymorphisms in the Omani population

    OpenAIRE

    2013-01-01

    Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Oc...

  14. Cancer incidence by marital status: U. S. Third National Cancer Survey

    Energy Technology Data Exchange (ETDEWEB)

    Ernster, V.L. (Univ. of California, San Francisco); Sacks, S.T.; Selvin, S.; Petrakis, N.L.

    1979-09-01

    Site-specific cancer incidence rats were computed by sex, age, and marital status for whites and blacks separately for ages 35-64 years with the use of population-based incidence data from the Third National Cancer Survey (1969-71) and with demographic data from the 1970 U.S. Census. Although rates were presented for all cancer sites combined and for 44 specific sites or rubrics, discussion focused on the 17 most common cancers. Within age, race, and sex groups, patterns of cancer incidence by marital status were compared by means of standardized incidence ratios, and the consistency of marital status patterns across age groups was assessed statistically. Among the most notable findings were: excess cancer rates across most sites and age groups in single black males, consistently high rates for cancer of the lung and bronchus in divorced white males and in single black females, low rates for the hormone-dependent reproductive tumors (prostate gland, breast, uterine corpus, and ovary) in separated white males and females, and high rates for cervical cancer among separated white women. Marital status patterns, where found, frequently differed between whites and blacks and between males and females.

  15. Enrollment and Racial Disparities in National Cancer Institute Cancer Treatment Clinical Trials in North Carolina

    Science.gov (United States)

    Zullig, Leah L.; Fortune-Britt, Alice G.; Rao, Shangbang; Tyree, Seth D.; Godley, Paul A.; Carpenter, William R.

    2015-01-01

    Background Clinical trials provide access to innovative, quality cancer treatment. Simultaneously, broad access helps ensure trial inclusion of heterogeneous patient populations, which improves generalizability of findings and development of interventions that are effective for diverse populations. We provide updated data describing enrollment into cancer treatment trials in North Carolina. Methods For 1996 to 2009, person-level data regarding cancer clinical trial enrollment and cancer incidence were obtained from the North Carolina Central Cancer Registry and the National Cancer Institute (NCI). Enrollment rates were estimated as the ratio of trial enrollment to cancer incidence for race, gender, and year for each county, Area Health Education Center (AHEC) region, and the state overall. Enrollment rates for common cancers are presented. Results From 1996 to 2009, North Carolina NCI treatment trial enrollment rate was 2.4% and 2.2% for whites and minorities, respectively. From 2007 to 2009, rates were 3.8% for white females, 3.5% for minority females, 1.3% for white men, and 1.0% for minority men, with greater enrollment among more urban populations (2.4%) than the most rural populations (1.5%). Limitations This study is limited to NCI-sponsored treatment trials in North Carolina. Policies governing collection of original data necessitate a delay in data availability. Conclusions Effort is needed to ensure trial access and enrollment among all North Carolina populations. Specifically, we identified racial and gender disparities, particularly for certain cancers (e.g., breast). Programs in North Carolina and across the nation can use the methods we employ to assess their success in broadening clinical trials enrollment for diverse populations. PMID:26763244

  16. Relationship between mTOR, CCR7 and the invasion and metastasis of breast carcinoma%mTOR和CCR7与乳腺癌侵袭转移的关系

    Institute of Scientific and Technical Information of China (English)

    刘清华; 李媛媛; 徐滨; 王竹青; 刘雨清

    2013-01-01

    目的:探讨乳腺浸润性导管癌组织中哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)与趋化因子受体7(chemokine receptor 7,CCR7)蛋白的表达,以及二者与乳腺癌侵袭、转移之间的关系.方法:采用免疫组织化学方法检测65例乳腺浸润性导管癌及32例正常乳腺组织中mTOR和CCR7的表达情况,并分析二者之间的相关性及其与各临床病理特征之间的关系.结果:mTOR和CCR7蛋白在乳腺浸润性导管癌中的阳性表达率(mTOR为68%,CCR7为74%)高于癌旁正常乳腺组织中的阳性表达率(mTOR为25%,CCR7为28%),差异有统计学意义(P<0.01).mTOR与CCR7的表达呈正相关(r=0.485,P<0.05).mTOR和CCR7的高表达均与淋巴结转移、临床恶性肿瘤分期有关(均P<0.05),而与年龄、雌激素受体、孕激素受体无关(均P>0.05).结论:mTOR和CCR7的异常高表达可能与乳腺癌的侵袭、转移有关,且检测二者的表达可作为判断乳腺癌转移的预测指标.%Objective:To detect the expression of mammalian target of rapamycin (mTOR) and chemokine receptor chemokine receptor 7 (CCRV) protein in breast infiltrating duct carcinoma, and to analyze the correlation between mTOR, CCR7 protein and the invasion and metastasis of breast cancer. Methods:Immunohistochemistry was used to detect the mTOR and CCR7 protein expression level in 65 patients with breast infiltrating duct carcinoma and 32 cases of normal breast tissue. At the same time, the relationship between the expression of mTOR, CCR7 and the clinicopathologic characteristics was analyzed. Results:The positive expression rates of the mTOR and CCR7 protein in the breast infiltrating duct carcinoma tissue (mTOR:68%, CCR7:74%) was significantly higher than those in the cancer adjacent tissue (mTOR:25%, CCR:7 28%)(P0.05). Conclusion:The abnormal expression of mTOR and CCR7 may be related with the occurrence, development, invasion and metastasis of the breast cancer, and the

  17. High-level production, solubilization and purification of synthetic human GPCR chemokine receptors CCR5, CCR3, CXCR4 and CX3CR1.

    Science.gov (United States)

    Ren, Hui; Yu, Daoyong; Ge, Baosheng; Cook, Brian; Xu, Zhinan; Zhang, Shuguang

    2009-01-01

    Chemokine receptors belong to a class of integral membrane G-protein coupled receptors (GPCRs) and are responsible for transmitting signals from the extracellular environment. However, the structural changes in the receptor, connecting ligand binding to G-protein activation, remain elusive for most GPCRs due to the difficulty to produce them for structural and functional studies. We here report high-level production in E.coli of 4 human GPCRs, namely chemokine receptors (hCRs) CCR5, CCR3, CXCR4 and CX3CR1 that are directly involved in HIV-1 infection, asthma and cancer metastasis. The synthetic genes of CCR5, CCR3, CXCR4 and CX3CR1 were synthesized using a two-step assembly/amplification PCR method and inserted into two different kinds of expression systems. After systematic screening of growth conditions and host strains, TB medium was selected for expression of pEXP-hCRs. The low copy number pBAD-DEST49 plasmid, with a moderately strong promoter tightly regulated by L-arabinose, proved helpful for reducing toxicity of expressed membrane proteins. The synthetic Trx-hCR fusion genes in the pBAD-DEST49 vector were expressed at high levels in the Top10 strain. After a systematic screen of 96 detergents, the zwitterionic detergents of the Fos-choline series (FC9-FC16) emerged as the most effective for isolation of the hCRs. The FC14 was selected both for solubilization from bacterial lysates and for stabilization of the Trx-hCRs during purification. Thus, the FC-14 solubilized Trx-hCRs could be purified using size exclusion chromatography as monomers and dimers with the correct apparent MW and their alpha-helical content determined by circular dichroism. The identity of two of the expressed hCRs (CCR3 and CCR5) was confirmed using immunoblots using specific monoclonal antibodies. After optimization of expression systems and detergent-mediated purification procedures, we achieved large-scale, high-level production of 4 human GPCR chemokine receptor in a two

  18. High-level production, solubilization and purification of synthetic human GPCR chemokine receptors CCR5, CCR3, CXCR4 and CX3CR1.

    Directory of Open Access Journals (Sweden)

    Hui Ren

    Full Text Available Chemokine receptors belong to a class of integral membrane G-protein coupled receptors (GPCRs and are responsible for transmitting signals from the extracellular environment. However, the structural changes in the receptor, connecting ligand binding to G-protein activation, remain elusive for most GPCRs due to the difficulty to produce them for structural and functional studies. We here report high-level production in E.coli of 4 human GPCRs, namely chemokine receptors (hCRs CCR5, CCR3, CXCR4 and CX3CR1 that are directly involved in HIV-1 infection, asthma and cancer metastasis. The synthetic genes of CCR5, CCR3, CXCR4 and CX3CR1 were synthesized using a two-step assembly/amplification PCR method and inserted into two different kinds of expression systems. After systematic screening of growth conditions and host strains, TB medium was selected for expression of pEXP-hCRs. The low copy number pBAD-DEST49 plasmid, with a moderately strong promoter tightly regulated by L-arabinose, proved helpful for reducing toxicity of expressed membrane proteins. The synthetic Trx-hCR fusion genes in the pBAD-DEST49 vector were expressed at high levels in the Top10 strain. After a systematic screen of 96 detergents, the zwitterionic detergents of the Fos-choline series (FC9-FC16 emerged as the most effective for isolation of the hCRs. The FC14 was selected both for solubilization from bacterial lysates and for stabilization of the Trx-hCRs during purification. Thus, the FC-14 solubilized Trx-hCRs could be purified using size exclusion chromatography as monomers and dimers with the correct apparent MW and their alpha-helical content determined by circular dichroism. The identity of two of the expressed hCRs (CCR3 and CCR5 was confirmed using immunoblots using specific monoclonal antibodies. After optimization of expression systems and detergent-mediated purification procedures, we achieved large-scale, high-level production of 4 human GPCR chemokine receptor in a

  19. 3 CFR 8354 - Proclamation 8354 of April 1, 2009. National Cancer Control Month, 2009

    Science.gov (United States)

    2010-01-01

    ... reduce the risk of cancer. Physical inactivity and obesity may cause a substantial proportion of colon... 3 The President 1 2010-01-01 2010-01-01 false Proclamation 8354 of April 1, 2009. National Cancer... 1, 2009 Proc. 8354 National Cancer Control Month, 2009By the President of the United States...

  20. Cancer screening in Korea, 2012: results from the Korean National Cancer Screening Survey.

    Science.gov (United States)

    Suh, Mina; Choi, Kui Son; Lee, Yoon Young; Park, Boyoung; Jun, Jae Kwan

    2013-01-01

    We investigated the cancer screening rates for five types of cancer (stomach, liver, colorectal, breast, and cervix uteri) using data from the Korean National Cancer Screening Survey (KNCSS), which is a nationwide, annual cross-sectional survey. The eligible study population included cancer-free men 40 years of age and older and women 30 years of age and older. The lifetime screening rate and screening rate with recommendation were calculated. The lifetime screening rates for gastric, liver, colorectal, breast, and cervical cancers were 77.9%, 69.9%, 65.8%, 82.9%, and 77.1%, respectively. The screening rates with recommendation were 70.9%, 21.5%, 44.7%, 70.9%, and 67.9%, respectively. The most common reason for all types of cancer was "no symptoms, " followed by "lack of time" and "fear of the examination procedure. " Efforts to facilitate participation in liver and colorectal cancer screening among Korean men and women are needed.

  1. Dietary Screener Questionnaire in the National Health Interview Survey Cancer Control Supplement 2010: Overview

    Science.gov (United States)

    The National Health Interview Survey (NHIS) Cancer Control Supplement (CCS) is administered every five years and focuses on knowledge, attitudes, and practices in cancer-related health behaviors, screening, and risk assessment.

  2. Prognostic Factors and Recurrence in Breast Cancer: Experience at the National Cancer Institute of Mexico

    OpenAIRE

    Stankov, A.; J. E. Bargallo-Rocha; A. Ñamendys-Silva Silvio; Ramirez, M. T.; Stankova-Ninova, K.; Meneses-Garcia, A.

    2012-01-01

    The purpose of this study was to analyze the prognostic and predictive factors that relate to locoregional or distant recurrences in breast cancer patients who have been treated at the National Cancer Institute of Mexico. Multivariate, time-dependent Cox regression analyses indicate that the pN status (positive versus negative lymph node; P = 0.003; HR (hazard ratio), 3.47; CI (confidence interval), 1.52–7.91) and the pathological complete response of the patient to neoadjuvant chemotherapy (...

  3. Effect of CCR7, CXCR4 and VEGF-C on the lymph node metastasis of human pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Guo, Jinghui; Lou, Wenhui; Ji, Yuan; Zhang, Shuncai

    2013-05-01

    The aim of the present study was to investigate the association between the expression of chemokine receptors CCR7 and CXCR4 and vascular endothelial growth factor (VEGF)-C and the lymph node metastasis of pancreatic ductal adenocarcinoma (PDAC). The mRNA transcription levels of CCR7, CXCR4 and VEGF-C were measured in 24 specimens by real-time reverse transcription (RT)-PCR, while the protein expression levels were measured in 65 specimens by immuohistochemistry. Professional software for pathological image manipulation (Image Pro Plus 6.0) was used to quantitate the results of the immunohistochemical staining. The mRNA and protein expression levels of CCR7, CXCR4 and VEGF-C were all significantly higher in the cancer samples compared with those in the adjacent normal tissue. The CCR7 and VEGF-C mRNA and protein expression levels were significantly higher in the patients with cancer types exhibiting lymph node metastasis and an advanced International Union Against Cancer (UICC) stage (PCCR7 expression (PCCR7 and VEGF-C (P0.05), however the strong positive expression of CCR7 and VEGF-C was significantly associated with the lymph node metastasis of PDAC.

  4. Study on CCR5 analogs and affinity peptides.

    Science.gov (United States)

    Wu, Yingping; Deng, Riqiang; Wu, Wenyan

    2012-03-01

    The G protein-coupled receptor of human chemokine receptor 5 (CCR5) is a key target in the human immunodeficiency virus (HIV) infection process due to its major involvement in binding to the HIV type 1 (HIV-1) envelope glycoprotein gp120 and facilitating virus entry into the cells. The identification of naturally occurring CCR5 mutations (especially CCR5 delta-32) has allowed us to address the CCR5 molecule as a promising target to prevent or resist HIV infection in vivo. To obtain high-affinity peptides that can be used to block CCR5, CCR5 analogs with high conformational similarity are required. In this study, two recombinant proteins named CCR5 N-Linker-E2 and CCR5 mN-E1-E2 containing the fragments of the CCR5 N-terminal, the first extracellular loop or the second extracellular loop are cloned from a full-length human CCR5 cDNA. The recombinant human CCR5 analogs with self-cleavage activity of the intein Mxe or Ssp in the vector pTwinI were then produced with a high-yield expression and purification system in Escherichia coli. Experiments of extracellular epitope-activity identification (such as immunoprecipitation and indirective/competitive enzyme-linked immunosorbent assay) confirmed the close similarity between the epitope activity of the CCR5 analogs and that of the natural CCR5, suggesting the applicability of the recombinant CCR5 analogs as antagonists of the chemokine ligands. Subsequent screening of high-affinity peptides from the phage random-peptides library acquired nine polypeptides, which could be used as CCR5 peptide antagonists. The CCR5 analogs and affinity peptides elucidated in this paper provide us with a basis for further study of the mechanism of inhibition of HIV-1 infection.

  5. The essential roles of CCR7 in epithelial-to-mesenchymal transition induced by hypoxia in epithelial ovarian carcinomas.

    Science.gov (United States)

    Cheng, Shaomei; Han, Lin; Guo, Jingyan; Yang, Qing; Zhou, Jianfang; Yang, Xiangshan

    2014-12-01

    The chemokine receptor CCR7 and its ligands CCL19/21 mediate the tumor mobility, invasion, and metastasis (Wu et al. Curr Pharm Des. 15:742-57, 2009). Hypoxia induced epithelial-to-mesenchymal transition (EMT) to facilitate the tumor biology. Here, we addressed the roles of CCR7 in epithelial ovarian carcinoma tissues and hypoxia-induced serous papillary cystic adenocarcinoma (SKOV-3) EMT. The expression level of CCR7 protein was analyzed by immunohistochemistry in 30 specimens of epithelial ovarian carcinomas. Western blot was used to investigate the expression of hypoxia-induced CCR7, HIF-1α, and EMT markers (N-cadherin, Snail, MMP-9). In addition, wound healing and Transwell assay were introduced to observe the capacity of migration and invasiveness. Our data showed CCR7 expression was observed in 22 cases of tissues and closely associated with lymph node metastasis and FIGO stage (III + IV). At 6, 12, 24, and 36 h following hypoxia, CCR7 and HIF-1α proteins were both obviously upregulated in a time-dependent method, compared with normal oxygen. In vitro, SKOV-3 expressed N-cadherin, Snail, and MMP-9 once either CCL21 stimulation or hypoxia induction, while hypoxia accompanied with CCL21 induction exhibited strongest upregulation of N-cadherin, Snail, and MMP-9 proteins. Besides, wound healing and Transwell assay further identified that hypoxia with CCL21 stimulation can remarkably promote cell migration and invasiveness. Taken together, CCR7 can constitutively express in epithelial ovarian carcinomas and be induced rapidly in response to hypoxia, which indeed participates in EMT development and prompts the cell migration and invasion. Thus, this study suggested that the epithelial ovarian cancer invasion and metastasis can be inhibited by antagonizing CCR7.

  6. Oral cancer: the association between nation-based alcohol-drinking profiles and oral cancer mortality.

    Science.gov (United States)

    Petti, Stefano; Scully, Crispian

    2005-09-01

    The unclear association between different nation-based alcohol-drinking profiles and oral cancer mortality was investigated using, as observational units, 20 countries from Europe, Northern America, Far Eastern Asia, with cross-nationally comparable data. Stepwise multiple regression analyses were run with male age-standardised, mortality rate (ASMR) as explanatory variable and annual adult alcohol consumption, adult smoking prevalence, life expectancy, as explanatory. Large between-country differences in ASMR (range, 0.88-6.87 per 100,000) were found, but the mean value was similar to the global estimate (3.31 vs. 3.09 per 100,000). Differences in alcohol consumption (2.06-21.03 annual litres per capita) and in distribution between beverages were reported. Wine was the most prevalent alcoholic beverage in 45% of cases. Significant increases in ASMR for every litre of pure ethanol (0.15 per 100,000; 95 CI, 0.01-0.29) and spirits (0.26 per 100,000; 95 CI, 0.03-0.49), non-significant effects for beer and wine were estimated. The impact of alcohol on oral cancer deaths would be higher than expected and the drinking profile could affect cancer mortality, probably because of the different drinking pattern of spirit drinkers, usually consuming huge alcohol quantities on single occasions, and the different concentrations of ethanol and cancer-preventing compounds such as polyphenols, in the various beverages.

  7. Postpartum remodeling, lactation, and breast cancer risk: summary of a National Cancer Institute-sponsored workshop.

    Science.gov (United States)

    Faupel-Badger, Jessica M; Arcaro, Kathleen F; Balkam, Jane J; Eliassen, A Heather; Hassiotou, Foteini; Lebrilla, Carlito B; Michels, Karin B; Palmer, Julie R; Schedin, Pepper; Stuebe, Alison M; Watson, Christine J; Sherman, Mark E

    2013-02-06

    The pregnancy-lactation cycle (PLC) is a period in which the breast is transformed from a less-developed, nonfunctional organ into a mature, milk-producing gland that has evolved to meet the nutritional, developmental, and immune protection needs of the newborn. Cessation of lactation initiates a process whereby the breast reverts to a resting state until the next pregnancy. Changes during this period permanently alter the morphology and molecular characteristics of the breast (molecular histology) and produce important, yet poorly understood, effects on breast cancer risk. To provide a state-of-the-science summary of this topic, the National Cancer Institute invited a multidisciplinary group of experts to participate in a workshop in Rockville, Maryland, on March 2, 2012. Topics discussed included: 1) the epidemiology of the PLC in relation to breast cancer risk, 2) breast milk as a biospecimen for molecular epidemiological and translational research, and 3) use of animal models to gain mechanistic insights into the effects of the PLC on breast carcinogenesis. This report summarizes conclusions of the workshop, proposes avenues for future research on the PLC and its relationship with breast cancer risk, and identifies opportunities to translate this knowledge to improve breast cancer outcomes.

  8. Consensus report of the national cancer institute clinical trials planning meeting on pancreas cancer treatment.

    Science.gov (United States)

    Philip, Philip A; Mooney, Margaret; Jaffe, Deborah; Eckhardt, Gail; Moore, Malcolm; Meropol, Neal; Emens, Leisha; O'Reilly, Eileen; Korc, Murray; Ellis, Lee; Benedetti, Jacqueline; Rothenberg, Mace; Willett, Christopher; Tempero, Margaret; Lowy, Andrew; Abbruzzese, James; Simeone, Diane; Hingorani, Sunil; Berlin, Jordan; Tepper, Joel

    2009-11-20

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality, despite significant improvements in diagnostic imaging and operative mortality rates. The 5-year survival rate remains less than 5% because of microscopic or gross metastatic disease at time of diagnosis. The Clinical Trials Planning Meeting in pancreatic cancer was convened by the National Cancer Institute's Gastrointestinal Cancer Steering Committee to discuss the integration of basic and clinical knowledge in the design of clinical trials in PDAC. Major emphasis was placed on the enhancement of research to identify and validate the relevant targets and molecular pathways in PDAC, cancer stem cells, and the microenvironment. Emphasis was also placed on developing rational combinations of targeted agents and the development of predictive biomarkers to assist selection of patient subsets. The development of preclinical tumor models that are better predictive of human PDAC must be supported with wider availability to the research community. Phase III clinical trials should be implemented only if there is a meaningful clinical signal of efficacy and safety in the phase II setting. The emphasis must therefore be on performing well-designed phase II studies with uniform sets of basic entry and evaluation criteria with survival as a primary endpoint. Patients with either metastatic or locally advanced PDAC must be studied separately.

  9. A polymorphism in CCR1/CCR3 is associated with narcolepsy.

    Science.gov (United States)

    Toyoda, Hiromi; Miyagawa, Taku; Koike, Asako; Kanbayashi, Takashi; Imanishi, Aya; Sagawa, Yohei; Kotorii, Nozomu; Kotorii, Tatayu; Hashizume, Yuji; Ogi, Kimihiro; Hiejima, Hiroshi; Kamei, Yuichi; Hida, Akiko; Miyamoto, Masayuki; Imai, Makoto; Fujimura, Yota; Tamura, Yoshiyuki; Ikegami, Azusa; Wada, Yamato; Moriya, Shunpei; Furuya, Hirokazu; Takeuchi, Masaki; Kirino, Yohei; Meguro, Akira; Remmers, Elaine F; Kawamura, Yoshiya; Otowa, Takeshi; Miyashita, Akinori; Kashiwase, Koichi; Khor, Seik-Soon; Yamasaki, Maria; Kuwano, Ryozo; Sasaki, Tsukasa; Ishigooka, Jun; Kuroda, Kenji; Kume, Kazuhiko; Chiba, Shigeru; Yamada, Naoto; Okawa, Masako; Hirata, Koichi; Mizuki, Nobuhisa; Uchimura, Naohisa; Shimizu, Tetsuo; Inoue, Yuichi; Honda, Yutaka; Mishima, Kazuo; Honda, Makoto; Tokunaga, Katsushi

    2015-10-01

    Etiology of narcolepsy-cataplexy involves multiple genetic and environmental factors. While the human leukocyte antigen (HLA)-DRB1*15:01-DQB1*06:02 haplotype is strongly associated with narcolepsy, it is not sufficient for disease development. To identify additional, non-HLA susceptibility genes, we conducted a genome-wide association study (GWAS) using Japanese samples. An initial sample set comprising 409 cases and 1562 controls was used for the GWAS of 525,196 single nucleotide polymorphisms (SNPs) located outside the HLA region. An independent sample set comprising 240 cases and 869 controls was then genotyped at 37 SNPs identified in the GWAS. We found that narcolepsy was associated with a SNP in the promoter region of chemokine (C-C motif) receptor 1 (CCR1) (rs3181077, P=1.6×10(-5), odds ratio [OR]=1.86). This rs3181077 association was replicated with the independent sample set (P=0.032, OR=1.36). We measured mRNA levels of candidate genes in peripheral blood samples of 38 cases and 37 controls. CCR1 and CCR3 mRNA levels were significantly lower in patients than in healthy controls, and CCR1 mRNA levels were associated with rs3181077 genotypes. In vitro chemotaxis assays were also performed to measure monocyte migration. We observed that monocytes from carriers of the rs3181077 risk allele had lower migration indices with a CCR1 ligand. CCR1 and CCR3 are newly discovered susceptibility genes for narcolepsy. These results highlight the potential role of CCR genes in narcolepsy and support the hypothesis that patients with narcolepsy have impaired immune function.

  10. Cancer in human immunodeficiency virus-infected children : A case series from the Children's Cancer Group and the National Cancer Institute

    NARCIS (Netherlands)

    Granovsky, MO; Mueller, BU; Nicholson, HS; Rosenberg, PS; Rabkin, CS

    1998-01-01

    Purpose: To describe the spectrum of malignancies in human immunodeficiency virus (HIV)-infected children and the clinical outcome of patients with these tumors. Methods: We retrospectively surveyed the Children's Cancer Group (CCG) and the National Cancer institute (NCI) for cases of cancer that oc

  11. Annual Report to the Nation on the Status of Cancer, 1975–2010

    Science.gov (United States)

    The Annual Report to the Nation on the Status of Cancer, covering the period 1975–2010, showed death rates for lung cancer, which accounts for more than one in four cancer deaths, dropping at a faster pace than in previous years.

  12. Effect of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in colorectal liver metastases

    Institute of Scientific and Technical Information of China (English)

    Claudia Rubie; Vilma Oliveira Frick; Pirus Ghadjar; Mathias Wagner; Christoph Justinger; Stefan Graeber; Jens Sperling; Otto Kollmar; Martin K Schilling

    2011-01-01

    AIM: To evaluate the influence of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in liver metastases of stage Ⅳ colorectal cancer (CRC) patients. METHODS: Using Real Time-PCR, enzyme-linked immunosorbent assay, Western Blots and immunohistochemistry, we have analyzed the expression of CCL20, CCR6 and proliferation marker Ki-67 in colorectal liver metastasis (CRLM) specimens from stage Ⅳ CRC patients who received preoperative FOLFOX chemotherapy (n = 53) and in patients who did not receive FOLFOX chemotherapy prior to liver surgery (n = 29). RESULTS: Of the 53 patients who received FOLFOX, time to liver surgery was ≤ 1 mo in 14 patients, ≤ 1 year in 22 patients and > 1 year in 17 patients, respectively. In addition, we investigated the proliferation rate of CRC cells in liver metastases in the different patient groups. Both CCL20 and CCR6 mRNA and protein expression levels were significantly increased in patients who received preoperative FOLFOX chemotherapy ≤ 12 mo before liver surgery (P < 0.001) in comparison to patients who did not undergo FOLFOX treatment. Further, proliferation of CRLM cells as measured by Ki-67 was increased in patients who underwent FOLFOX treatment. CCL20 and CCR6 expression levels were significantly increased in CRLM patients who had undergone preoperative FOLFOX chemotherapy. CONCLUSION: This chemokine/receptor up-regulation could lead to increased proliferation/migration through an autocrine mechanism which might be used by surviving metastatic cells to escape cell death caused by FOLFOX.

  13. The national database of hospital-based cancer registries: a nationwide infrastructure to support evidence-based cancer care and cancer control policy in Japan.

    Science.gov (United States)

    Higashi, Takahiro; Nakamura, Fumiaki; Shibata, Akiko; Emori, Yoshiko; Nishimoto, Hiroshi

    2014-01-01

    Monitoring the current status of cancer care is essential for effective cancer control and high-quality cancer care. To address the information needs of patients and physicians in Japan, hospital-based cancer registries are operated in 397 hospitals designated as cancer care hospitals by the national government. These hospitals collect information on all cancer cases encountered in each hospital according to precisely defined coding rules. The Center for Cancer Control and Information Services at the National Cancer Center supports the management of the hospital-based cancer registry by providing training for tumor registrars and by developing and maintaining the standard software and continuing communication, which includes mailing lists, a customizable web site and site visits. Data from the cancer care hospitals are submitted annually to the Center, compiled, and distributed as the National Cancer Statistics Report. The report reveals the national profiles of patient characteristics, route to discovery, stage distribution, and first-course treatments of the five major cancers in Japan. A system designed to follow up on patient survival will soon be established. Findings from the analyses will reveal characteristics of designated cancer care hospitals nationwide and will show how characteristics of patients with cancer in Japan differ from those of patients with cancer in other countries. The database will provide an infrastructure for future clinical and health services research and will support quality measurement and improvement of cancer care. Researchers and policy-makers in Japan are encouraged to take advantage of this powerful tool to enhance cancer control and their clinical practice.

  14. Between prevention and therapy: Gio Batta Gori and the National Cancer Institute's Diet, Nutrition and Cancer Programme, 1974-1978.

    Science.gov (United States)

    Cantor, David

    2012-10-01

    This paper explores the origins of the Diet, Nutrition and Cancer Programme (DNCP) of the National Cancer Institute (NCI) and its fate under its first director, Gio Batta Gori. The DNCP is used to explore the emergence of federal support for research on diet, nutrition and cancer following the 1971 Cancer Act, the complex relations between cancer prevention and therapeutics in the NCI during the 1970s, the broader politics around diet, nutrition and cancer during that decade, and their relations to Senator George McGovern's select committee on Nutrition and Human Needs. It also provides a window onto the debates and struggles over whether NCI research should be funded by contracts or grants, the nature of the patronage system within the federal cancer research agency, how a director, Gio Gori, lost patronage within that system and how a tightening of the budget for cancer research in the mid-to-late 1970s affected the DNCP.

  15. Harold Fred Dorn and the First National Cancer Survey (1937-1939): the founding of modern cancer epidemiology.

    Science.gov (United States)

    Lilienfeld, David E

    2008-12-01

    The development of modern epidemiology, particularly cancer epidemiology, is often seen as a post-World War II phenomenon. However, the First National Cancer Survey, conducted from 1937 to 1939 as part of the newly formed National Cancer Institute's initial activities, provided the first data on the occurrence of cancer in the United States. This project was directed by a young sociologist, Harold Fred Dorn. Through Dorn, many of the methodological innovations in sociology, such as the use of surveys and observational study designs, were incorporated into modern epidemiology. I examine Dorn's training and early career in the context of the First National Cancer Survey as a means of investigating the beginnings of modern epidemiology.

  16. 75 FR 62297 - National Breast Cancer Awareness Month, 2010

    Science.gov (United States)

    2010-10-08

    ... breast cancer is an important part of its prevention. Risk factors for breast cancer include family and personal history, radiation therapy to the chest for previous cancers, obesity, and certain genetic changes... commitment to supporting breast cancer research, and to educating all Americans about its risk...

  17. A study of the effect of CCL21/CCR7 axis on VEGF-C expression in human lung adenocarcinoma A549 cells%CCL21/CCR7轴对人肺癌A549细胞VEGF-C表达影响的研究

    Institute of Scientific and Technical Information of China (English)

    郭学光; 陈正堂; 刘长庭

    2011-01-01

    目的 研究二级淋巴组织趋化因子/CC趋化因子受体7(CCL21/CCR7)轴对肺癌A549细胞血管内皮细胞生长因子-C(VEGF-C)表达的影响.方法 实时定量PCR及Western Blot法检测CCL21作用前后A549细胞及A549-CCR7细胞VEGF-C mRNA及蛋白的表达.结果 CCL21作用下无论是在mRNA水平还是蛋白水平A549-CCR7细胞VEGF-C的表达均较A549细胞高.结论 CCL21与其受体CCR7结合能够促进A549细胞VEGF-C的表达,CCL21/CCR7轴可能参与了肺癌淋巴结转移的过程.进一步研究CCL21/CCR7轴和VEGF-C 的关系可能有助于阐明肺癌淋巴结转移的机制.%Objective To investigate the effects of CCL21/CCR7 axis on VEGF - C expression of human lung adenocarcinoma A549 cells and A549 - CCR7 cells. Methods VEGF - C expression was detected using Real - Time RT - PCR and Western Blot in A549 cells and A549 -CCR7 cells before and after incuhation with CCL21 . Results Under the influence of CCL21 , the VEGF - C expression of the A549 - CCR7 cells ,in mRNA and protein levels, was significantly increased compared to that of A549 cells ( P <0. 01 ). Conclusion These data suggest that the bind of CCL21 to its receptor CCR7 leads to the increase of the VE(-JF - C expression of A549 cells, and CCL21/CCR7 axis may play a role in lymph node metastasis of lung cancer. To further study the relationship between CCL21/CCR7 axis and VEGF - C may help to elucidate the mechanism of lymph node metastasis in human lung cancer.

  18. Adverse effect of the CCR5 promoter -2459A allele on HIV-1 disease progression

    DEFF Research Database (Denmark)

    Knudsen, T B; Kristiansen, T B; Katzenstein, T L;

    2001-01-01

    HIV positive individuals heterozygous for a 32 basepair deletion in the CCR5 encoding gene (CCR5 Delta32) have a reduced number of CCR5 receptors on the cell surface and a slower progression towards AIDS and death. Other human polymorphisms, such as the CCR2 64I and the CCR5 promoter -2459 A...

  19. CCR7在非小细胞肺癌中的表达及其与淋巴结转移的关系%CCR7 expression and its role in lymph node metastasis in NSCLC

    Institute of Scientific and Technical Information of China (English)

    郭学光; 陈正堂

    2007-01-01

    目的 检测CCR7在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达,并分析其与肺癌临床病理参数间的关系,探讨CCR7在NSCLC淋巴结转移中的作用.方法 选用65例NSCLC临床切除组织石蜡标本,以免疫组化SP法检测CCR7蛋白的表达.结果 65例肺癌组织中,CCR7阳性表达37例,阳性率为56.9%(37/65),且其表达与淋巴结转移存在非常显著相关性(P<0.01).结论 CCR7在NSCLC组织中高表达,且其表达与NSCLC淋巴结转移密切相关.

  20. CCR1 and CCR5 expression on inflammatory cells is related to cigarette smoking and chronic obstructive pulmonary disease severity

    Institute of Scientific and Technical Information of China (English)

    WANG Fei; HE Bei

    2012-01-01

    Background Chronic obstructive pulmonary disease (COPD) is a progressive disease associated with a cellular inflammatory response mostly concerned with cigarette smoking.Chemokine receptors CCR1/5 play an important role in the inflammatory cells recruitment in the lung of COPD patients.The aim of this study was to determine the impact of cigarette smoking on the expression of CCR1/5 on inflammatory cells in induced sputum,and the relationship between the receptors expression and COPD severity.Methods Differential cells in induced sputum were counted and the optical densities of CCR1 and CCR5 on inflammatory cells in induced sputum from COPD patients (n=29),healthy smokers (n=11),and nonsmokers (n=6) were measured using immunocytochemistry.Concentrations of CCL3,the ligand of CCR1/5,in supernatant of induced sputum were detected by enzyme-linked immunosorbent assay.Results The expressions of CCR1 and CCR5 on inflammatory cells in healthy smokers were significantly higher than those in nonsmokers,and the expression of CCR1 in patients with COPD was significantly increased when compared with nonsmokers but not healthy smokers.The expressions of CCR1 and CCR5 on inflammatory cells in severe and very severe COPD patients were higher compared with mild and moderate COPD patients.CCL3 level was positively correlated with the total cell counts in induced sputum and smoking history,and negatively correlated with percentage of predicted FEV1.Conclusions Cigarette smoking could increase the expression of CCR1 on the inflammatory cells.Both CCR1 and CCR5 expressions on the inflammatory cells in induced sputum could be associated with COPD severity.

  1. Elucidation of binding sites of dual antagonists in the human chemokine receptors CCR2 and CCR5.

    Science.gov (United States)

    Hall, Spencer E; Mao, Allen; Nicolaidou, Vicky; Finelli, Mattea; Wise, Emma L; Nedjai, Belinda; Kanjanapangka, Julie; Harirchian, Paymann; Chen, Deborah; Selchau, Victor; Ribeiro, Sofia; Schyler, Sabine; Pease, James E; Horuk, Richard; Vaidehi, Nagarajan

    2009-06-01

    Design of dual antagonists for the chemokine receptors CCR2 and CCR5 will be greatly facilitated by knowledge of the structural differences of their binding sites. Thus, we computationally predicted the binding site of the dual CCR2/CCR5 antagonist N-dimethyl-N-[4-[[[2-(4-methylphenyl)-6,7-dihydro-5H-benzohepten-8-yl] carbonyl]amino]benzyl]tetrahydro-2H-pyran-4-aminium (TAK-779), and a CCR2-specific antagonist N-(carbamoylmethyl)-3-trifluoromethyl benzamido-parachlorobenzyl 3-aminopyrrolidine (Teijin compound 1) in an ensemble of predicted structures of human CCR2 and CCR5. Based on our predictions of the protein-ligand interactions, we examined the activity of the antagonists for cells expressing thirteen mutants of CCR2 and five mutants of CCR5. The results show that residues Trp98(2.60) and Thr292(7.40) contribute significantly to the efficacy of both TAK-779 and Teijin compound 1, whereas His121(3.33) and Ile263(6.55) contribute significantly only to the antagonistic effect of Teijin compound 1 at CCR2. Mutation of residues Trp86(2.60) and Tyr108(3.32) adversely affected the efficacy of TAK-779 in antagonizing CCR5-mediated chemotaxis. Y49A(1.39) and E291A(7.39) mutants of CCR2 showed a complete loss of CCL2 binding and chemotaxis, despite robust cell surface expression, suggesting that these residues are critical in maintaining the correct receptor architecture. Modeling studies support the hypothesis that the residues Tyr49(1.39), Trp98(2.60), Tyr120(3.32), and Glu291(7.39) of CCR2 form a tight network of aromatic cluster and polar contacts between transmembrane helices 1, 2, 3, and 7.

  2. Mapping HPV Vaccination and Cervical Cancer Screening Practice in the Pacific Region-Strengthening National and Regional Cervical Cancer Prevention

    DEFF Research Database (Denmark)

    Obel, J; McKenzie, J; Buenconsejo-Lum, L E

    2015-01-01

    OBJECTIVE: To provide background information for strengthening cervical cancer prevention in the Pacific by mapping current human papillomavirus (HPV) vaccination and cervical cancer screening practices, as well as intent and barriers to the introduction and maintenance of national HPV vaccination...... guidelines and policies for HPV vaccination. CONCLUSION: Current practices to prevent cervical cancer in the Pacific Region do not match the high burden of disease from cervical cancer. A regional approach, including reducing vaccine prices by bulk purchase of vaccine, technical support for implementation...

  3. Proton treatment facility at National Cancer Center Hospital East

    Energy Technology Data Exchange (ETDEWEB)

    Nishio, Teiji [National Cancer Center, Kashiwa, Chiba (Japan). Hospital East

    2002-06-01

    In 1997, the proton- treatment facility that has the therapeutic Azimuthally Varying Field (AVF) cyclotron accelerator (C235) is constructed at National Cancer Center Hospital East. The facility has 3-irradiation ports (rooms) that are 2-rotationg gantry ports and 1-horizontal fixed port. The C235 can accelerate proton to 235 MeV with the beam intensity of 300 nA. The external diameter is a very compact with about 4 m. The radio frequency is 106 MHz, the accelerating voltage is about 60 kV, and the harmonic number is 4. A beam stability of the C235 has an important relation with the uniformity of an irradiation field and is a very difficulty. The measured result indicated that the incident beam position against the 2.5-% dose uniformity must be into the 0.5- and 6.6-mm{phi} circles with the double-scattering and wobbler methods, respectively. The proton beam therapy began at the end of November 1998. It has been curing 97 patients by the present. Also, the proton therapy system at our hospital got an approval as medical equipment from the Japanese government in April 2001. And the proton therapy at our hospital was approved as a high advanced medical technology from the Japanese government in July 2001. The treatment expenses are 2883,000 yen uniformly. (author)

  4. Role of CCR5 and CCR5δ32 in the pathogenesis of liver diseases%趋化因子受体CCR5和CCR5δ32在肝脏疾病中的作用

    Institute of Scientific and Technical Information of China (English)

    马海龙; 郑明华; 陈永平

    2007-01-01

    趋化因子受体CCR5是一种G-蛋白耦联受体,分布在T细胞和单核细胞表面,CCR5δ32是CCR5的一种变异型.研究发现,CCR5介导的信号通路参与了炎症反应、自身免疫性疾病和移植物抗宿主病等多种疾病的发病机制和转归过程.在肝脏疾病中,CCR5至少与病毒性肝炎、肝硬化、移植物抗宿主病等的发病过程有关.此文就CCR5与肝脏疾病的关系进行综述.

  5. 78 FR 61805 - National Breast Cancer Awareness Month, 2013

    Science.gov (United States)

    2013-10-04

    ... every individual and every family struggling with breast cancer; and we pause to remember those we have... cancer, I encourage women to speak with their doctors about recommended mammograms and clinical...

  6. A clinicoepidemiological study of esophageal cancer patients at the National Cancer Institute, Cairo University, Egypt

    Institute of Scientific and Technical Information of China (English)

    Soumaya Ezzat; Hisham El Hossieny; Mohamed Abd Alla; Azza Nasr; Nagwan Anter; Ahmed Adel

    2016-01-01

    Objective The purposes of this study were to (1) assess the clinicoepidemiological characteristics of esopha-geal cancer patients, (2) analyze the prognostic factors determining treatment failure and survival, and (3) evaluate the results of various treatment modalities for locoregional and disseminated disease and their ef ect on disease-free survival and overal survival (OS). Methods Clinicoepidemiological retrospective data from 81 esophageal cancer patients treated at the Na-tional Cancer Institute of Cairo between 2007 and 2011 were evaluated. Results The study showed that patients with esophageal cancer commonly present with local y advanced disease (87.7% had T-stage 3 and 12.3% had T-stage 4). There was a significant correlation between surgery and survival; patients who received radical surgery and postoperative radiation had a better median survival than patients who received radical radiotherapy (20 months vs. 16 months, respectively; P = 0.04). There was also a significant statistical correlation between radical concomitant chemoradiotherapy (NCRT) and pal iative treatment. Patients who received radical NCRT had a better median survival than patients who received pal-liative radiotherapy (16 months vs. 10 months, respectively; P = 0.001). The median fol ow-up period for al patients was 7 months. The median OS of the whole group was 12 months. The OS after 1 and 2 years was 57.8% and 15%, respectively. Conclusion High-dose NCRT is an acceptable alternative for patients unfit for surgery or with inoperable disease. High-dose radiation is more ef ective than low-dose radiation in terms of local control, time to relapse, and OS. Further study using a larger series of patients and introducing new treatment protocols is necessary for a final evaluation.

  7. Marsdenia tenacissima extract suppresses A549 cell migration through regulation of CCR5-CCL5 axis, Rho C, and phosphorylated FAK.

    Science.gov (United States)

    Lin, Sen-Sen; Li, Fang-Fang; Sun, Li; Fan, Wei; Gu, Ming; Zhang, Lu-Yong; Qin, Song; Yuan, Sheng-Tao

    2016-03-01

    Marsdenia tenacissima, a traditional Chinese medicine, is long been used to treat various diseases including asthma, cancer, trachitis, tonsillitis, pharyngitis, cystitis, and pneumonia. Although Marsdenia tenacissima has been demonstrated to have strong anti-tumor effects against primary tumors, its effect on cancer metastasis remains to be defined, and the molecular mechanism underlying the anti-metastatic effect is unknown. In the present study, we investigated the effects of XAP (an extract of Marsdenia tenacissima) on A549 lung cancer cell migration and explored the role of CCR5-CCL5 axis in the anti-metastatic effects of XAP. Our resutls showed that XAP inhibited A549 lung cancer cell migration and invasion in a dose-dependent manner. The protein levels of CCR5, but not CCR9 and CXCR4, were decreased by XAP. The secretion of CCL5, the ligand of CCR5, was reduced by XAP. XAP down-regulated Rho C expression and FAK phosphorylation. In conclusion, XAP inhibited A549 cell migration and invasion through down-regulation of CCR5-CCL5 axis, Rho C, and FAK.

  8. 75 FR 42453 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2010-07-21

    .... Time: 8 a.m. to 5 p.m. Agenda: The Future of Cancer Research: Accelerating Scientific Innovation. Place... language interpretation or other reasonable accommodations, should notify the Contact Person listed below... Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer Treatment Research;...

  9. Genetic and Epigenetic Regulation of CCR5 Transcription

    OpenAIRE

    2012-01-01

    The chemokine receptor CCR5 regulates trafficking of immune cells of the lymphoid and the myeloid lineage (such as monocytes, macrophages and immature dendritic cells) and microglia. Because of this, there is an increasing recognition of the important role of CCR5 in the pathology of (neuro-) inflammatory diseases such as atherosclerosis and multiple sclerosis. Expression of CCR5 is under the control of a complexly organized promoter region upstream of the gene. The transcription factor cAMP-...

  10. Modeling the allosteric modulation of CCR5 function by Maraviroc.

    Science.gov (United States)

    Lagane, Bernard; Garcia-Perez, Javier; Kellenberger, Esther

    2013-01-01

    Maraviroc is a non-peptidic, low molecular weight CC chemokine receptor 5 (CCR5) ligand that has recently been marketed for the treatment of HIV infected individuals. This review discusses recent molecular modeling studies of CCR5 by homology to CXC chemokine receptor 4, their contribution to the understanding of the allosteric mode of action of the inhibitor and their potential for the development of future drugs with improved efficiency and preservation of CCR5 biological functions.

  11. Prostate Cancer in South Africa: Pathology Based National Cancer Registry Data (1986–2006 and Mortality Rates (1997–2009

    Directory of Open Access Journals (Sweden)

    Chantal Babb

    2014-01-01

    Full Text Available Prostate cancer is one of the most common male cancers globally; however little is known about prostate cancer in Africa. Incidence data for prostate cancer in South Africa (SA from the pathology based National Cancer Registry (1986–2006 and data on mortality (1997–2009 from Statistics SA were analysed. World standard population denominators were used to calculate age specific incidence and mortality rates (ASIR and ASMR using the direct method. Prostate cancer was the most common male cancer in all SA population groups (excluding basal cell carcinoma. There are large disparities in the ASIR between black, white, coloured, and Asian/Indian populations: 19, 65, 46, and 19 per 100 000, respectively, and ASMR was 11, 7, 52, and 6 per 100 000, respectively. Prostate cancer was the second leading cause of cancer death, accounting for around 13% of male deaths from a cancer. The average age at diagnosis was 68 years and 74 years at death. For SA the ASIR increased from 16.8 in 1986 to 30.8 in 2006, while the ASMR increased from 12.3 in 1997 to 16.7 in 2009. There has been a steady increase of incidence and mortality from prostate cancer in SA.

  12. Prostate cancer in South Africa: pathology based national cancer registry data (1986-2006) and mortality rates (1997-2009).

    Science.gov (United States)

    Babb, Chantal; Urban, Margaret; Kielkowski, Danuta; Kellett, Patricia

    2014-01-01

    Prostate cancer is one of the most common male cancers globally; however little is known about prostate cancer in Africa. Incidence data for prostate cancer in South Africa (SA) from the pathology based National Cancer Registry (1986-2006) and data on mortality (1997-2009) from Statistics SA were analysed. World standard population denominators were used to calculate age specific incidence and mortality rates (ASIR and ASMR) using the direct method. Prostate cancer was the most common male cancer in all SA population groups (excluding basal cell carcinoma). There are large disparities in the ASIR between black, white, coloured, and Asian/Indian populations: 19, 65, 46, and 19 per 100 000, respectively, and ASMR was 11, 7, 52, and 6 per 100 000, respectively. Prostate cancer was the second leading cause of cancer death, accounting for around 13% of male deaths from a cancer. The average age at diagnosis was 68 years and 74 years at death. For SA the ASIR increased from 16.8 in 1986 to 30.8 in 2006, while the ASMR increased from 12.3 in 1997 to 16.7 in 2009. There has been a steady increase of incidence and mortality from prostate cancer in SA.

  13. Prostate Cancer in South Africa: Pathology Based National Cancer Registry Data (1986–2006) and Mortality Rates (1997–2009)

    Science.gov (United States)

    Babb, Chantal; Urban, Margaret; Kielkowski, Danuta; Kellett, Patricia

    2014-01-01

    Prostate cancer is one of the most common male cancers globally; however little is known about prostate cancer in Africa. Incidence data for prostate cancer in South Africa (SA) from the pathology based National Cancer Registry (1986–2006) and data on mortality (1997–2009) from Statistics SA were analysed. World standard population denominators were used to calculate age specific incidence and mortality rates (ASIR and ASMR) using the direct method. Prostate cancer was the most common male cancer in all SA population groups (excluding basal cell carcinoma). There are large disparities in the ASIR between black, white, coloured, and Asian/Indian populations: 19, 65, 46, and 19 per 100 000, respectively, and ASMR was 11, 7, 52, and 6 per 100 000, respectively. Prostate cancer was the second leading cause of cancer death, accounting for around 13% of male deaths from a cancer. The average age at diagnosis was 68 years and 74 years at death. For SA the ASIR increased from 16.8 in 1986 to 30.8 in 2006, while the ASMR increased from 12.3 in 1997 to 16.7 in 2009. There has been a steady increase of incidence and mortality from prostate cancer in SA. PMID:24955252

  14. Temporal expression and cellular origin of CC chemokine receptors CCR1, CCR2 and CCR5 in the central nervous system: insight into mechanisms of MOG-induced EAE

    Directory of Open Access Journals (Sweden)

    Ericsson-Dahlstrand Anders

    2007-05-01

    Full Text Available Abstract Background The CC chemokine receptors CCR1, CCR2 and CCR5 are critical for the recruitment of mononuclear phagocytes to the central nervous system (CNS in multiple sclerosis (MS and other neuroinflammatory diseases. Mononuclear phagocytes are effector cells capable of phagocytosing myelin and damaging axons. In this study, we characterize the regional, temporal and cellular expression of CCR1, CCR2 and CCR5 mRNA in the spinal cord of rats with myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE. While resembling human MS, this animal model allows unique access to CNS-tissue from various time-points of relapsing neuroinflammation and from various lesional stages: early active, late active, and inactive completely demyelinated lesions. Methods The expression of CCR1, CCR2 and CCR5 mRNA was studied with in situ hybridization using radio labelled cRNA probes in combination with immunohistochemical staining for phenotypic cell markers. Spinal cord sections from healthy rats and rats with MOG-EAE (acute phase, remission phase, relapse phase were analysed. In defined lesion stages, the number of cells expressing CCR1, CCR2 and CCR5 mRNA was determined. Data were statistically analysed by the nonparametric Mann-Whitney U test. Results In MOG-EAE rats, extensive up-regulation of CCR1 and CCR5 mRNA, and moderate up-regulation of CCR2 mRNA, was found in the spinal cord during episodes of active inflammation and demyelination. Double staining with phenotypic cell markers identified the chemokine receptor mRNA-expressing cells as macrophages/microglia. Expression of all three receptors was substantially reduced during clinical remission, coinciding with diminished inflammation and demyelination in the spinal cord. Healthy control rats did not show any detectable expression of CCR1, CCR2 or CCR5 mRNA in the spinal cord. Conclusion Our results demonstrate that the acute and chronic-relapsing phases of MOG

  15. High level expression, purification and characterization of recombinant CCR5 as a vaccine candidate against HIV.

    Science.gov (United States)

    Wu, Kongtian; Xue, Xiaochang; Li, Meng; Qin, Xin; Zhang, Cun; Li, Weina; Hao, Qiang; Wang, Zenglu; Liu, Qian; Zhang, Wei; Zhang, Yingqi

    2013-06-01

    Cysteine-cysteine chemokine receptor type 5 (CCR5) is an important co-receptor for human immunodeficiency virus (HIV) infection and CCR5 neutralizing agents have proven efficient in patients suffering from HIV infection. Here, we expressed and purified various CCR5 vaccines named rCCR5, PADRE-rCCR5, GST-C1 and GST-C2 composed of different epitopes of CCR5. Results showed that vaccines containing multiple epitopes (rCCR5 and PADRE-rCCR5) induced stronger immune responses than single-epitope ones (GST-C1 and GST-C2). In addition, the elicited antibodies can specifically bind CCR5(+) U937 but not CCR5(-) Wish cells. These results demonstrate that the CCR5 vaccines are useful for further research, especially for the in vitro preclinical evaluation of their potential as biological CCR5 neutralizing agents.

  16. Chemokine receptor CCR5 polymorphisms and Chagas' disease cardiomyopathy.

    Science.gov (United States)

    Calzada, J E; Nieto, A; Beraún, Y; Martín, J

    2001-09-01

    In this study we investigated the possible role of two CCR5 gene polymorphisms, CCR5Delta32 deletion and CCR5 59029 A-->G promoter point mutation, in determining the susceptibility to Trypanosoma cruzi infection as well as in the development of chagasic heart disease. These CCR5 polymorphisms were assessed in 85 seropositive (asymptomatic, n=53; cardiomyopathic, n=32) and 87 seronegative individuals. The extremely low frequency (0.009) of the CCR5Delta32 allele in our population did not allow us to analyse its possible influence on T. cruzi infection. We found no differences in the distribution of CCR5 59029 promoter genotype or phenotype frequencies between total chagasic patients and controls. However, we observed that the CCR5 59029-A/G genotype was significantly increased in asymptomatic with respect to cardiomyopathic patients (P=0.02; OR=0.33, 95% CI 0.10-0.94). In addition, the presence of the CCR5 59029-G allele was also increased in asymptomatics when compared with cardiomyopathics (P=0.02; OR=0.35, 95% CI 0.12-0.96). Our data suggest that the CCR5 59029 promoter polymorphism may be involved in a differential susceptibility to chagasic cardiomyopathy.

  17. Extracellular Disulfide Bridges Serve Different Purposes in Two Homologous Chemokine Receptors, CCR1 and CCR5

    DEFF Research Database (Denmark)

    Rummel, Pia Cwarzko; Thiele, Stefanie; Hansen, Laerke Smidt

    2013-01-01

    In addition to the 7TM receptor-conserved disulfide bridge between transmembrane helix (TM) 3 and extracellular loop (ECL) 2, chemokine receptors contain a disulfide bridge between the N-terminus and what previously was believed to be ECL-3. Recent crystal- and NMR-structures of CXCR4 and CXCR1...... where dispensable for small-molecule activation. This indicates that CCR5 activity is independent of extracellular regions, whereas in CCR1, preserved folding of ECL2 is necessary for activation. These results indicate that conserved structural features in a receptor subgroup, does not necessarily...

  18. Expression of the Chemokine Receptors CCR4, CCR5, and CXCR3 by Human Tissue-Infiltrating Lymphocytes

    OpenAIRE

    2002-01-01

    Differential expression of adhesion molecules and chemokine receptors has been useful for identification of peripheral blood memory lymphocyte subsets with distinct tissue and microenvironmental tropisms. Expression of CCR4 by circulating memory CD4+ lymphocytes is associated with cutaneous and other systemic populations while expression of CCR9 is associated with a small intestine-homing subset. CCR5 and CXCR3 are also expressed by discrete memory CD4+ populations in blood, as well as by tis...

  19. Annual Report to the Nation on the Status of Cancer, 1975-2010: Questions and Answers

    Science.gov (United States)

    ... Home News & Events Press Releases 2013 Press Releases Annual Report to the Nation on the Status of Cancer, ... Other Information 27. Why is this the second Annual Report published in 2013? The first Annual Report published ...

  20. Improving population-based cervical cancer screening in general practice : effects of a national strategy

    NARCIS (Netherlands)

    Hermens, R P; Hak, E; Hulscher, M E; Mulder, J; Tacken, M A; Braspenning, J C; Grol, R P

    1999-01-01

    OBJECTIVE: To assess the effects of a Dutch national prevention programme, aimed at general practitioners (GPs), on the adherence to organizational guidelines for effective cervical cancer screening in general practice. To identify the characteristics of general practices determining success. DESIGN

  1. Psycho-oncological support for breast cancer patients: A brief overview of breast cancer services certification schemes and national health policies in Europe.

    Science.gov (United States)

    Neamţiu, L; Deandrea, S; Pylkkänen, L; Freeman, C; López Alcalde, J; Bramesfeld, A; Saz-Parkinson, Z; Ulutürk, A; Lerda, D

    2016-10-01

    Psycho-oncology addresses the psychological, social, behavioural, and ethical aspects of cancer. Identification and proper management of the patients' psychosocial needs, as well as the needs of their caregivers and family are essential for a person-centred concept of breast cancer care. The aim of this overview is to describe how psychosocial support in breast cancer is incorporated in cancer-related policy documents, such as national cancer plans and breast cancer care certification schemes.

  2. Progress in breast cancer: overview.

    Science.gov (United States)

    Arteaga, Carlos L

    2013-12-01

    This edition of CCR Focus titled Research in Breast Cancer: Frontiers in Genomics, Biology, and Clinical Investigation reviews six topics that cover areas of translational research of high impact in breast cancer. These topics represent areas of breast cancer research where significant progress has occurred but also where very important challenges remain. The papers in this CCR Focus section are contributed by experts in the respective areas of investigation. Herein, key aspects of these contributions and the research directions they propose are reviewed.

  3. A Comparative Docking Study of Anibamine as the First Natural Product CCR5 Antagonist in CCR5 Homology Models

    OpenAIRE

    2009-01-01

    Anibamine, a novel pyridine quaternary alkaloid recently isolated from Aniba sp., has been found to effectively bind to the chemokine receptor CCR5 with an IC50 at 1 μM in competition with 125I-gp120, an HIV viral envelope protein binding to CCR5 with high affinity. Since CCR5, a G-protein-coupled receptor, is an essential co-receptor for the human immunodeficiency virus type I (HIV-1) entry to host cells, a CCR5 antagonist that inhibits the cellular entry of HIV-1 provides a new therapy choi...

  4. From cancer screening to treatment: service delivery and referral in the National Breast and Cervical Cancer Early Detection Program.

    Science.gov (United States)

    Miller, Jacqueline W; Hanson, Vivien; Johnson, Gale D; Royalty, Janet E; Richardson, Lisa C

    2014-08-15

    The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides breast and cervical cancer screening and diagnostic services to low-income and underserved women through a network of providers and health care organizations. Although the program serves women 40-64 years old for breast cancer screening and 21-64 years old for cervical cancer screening, the priority populations are women 50-64 years old for breast cancer and women who have never or rarely been screened for cervical cancer. From 1991 through 2011, the NBCCEDP provided screening and diagnostic services to more than 4.3 million women, diagnosing 54,276 breast cancers, 2554 cervical cancers, and 123,563 precancerous cervical lesions. A critical component of providing screening services is to ensure that all women with abnormal screening results receive appropriate and timely diagnostic evaluations. Case management is provided to assist women with overcoming barriers that would delay or prevent follow-up care. Women diagnosed with cancer receive treatment through the states' Breast and Cervical Cancer Treatment Programs (a special waiver for Medicaid) if they are eligible. The NBCCEDP has performance measures that serve as benchmarks to monitor the completeness and timeliness of care. More than 90% of the women receive complete diagnostic care and initiate treatment less than 30 days from the time of their diagnosis. Provision of effective screening and diagnostic services depends on effective program management, networks of providers throughout the community, and the use of evidence-based knowledge, procedures, and technologies.

  5. Chemoirradiation for glioblastoma multiforme: the national cancer institute experience.

    Directory of Open Access Journals (Sweden)

    Jennifer Ho

    Full Text Available PURPOSE: Standard treatment for glioblastoma (GBM is surgery followed by radiation (RT and temozolomide (TMZ. While there is variability in survival based on several established prognostic factors, the prognostic utility of other factors such as tumor size and location are not well established. EXPERIMENTAL DESIGN: The charts of ninety two patients with GBM treated with RT at the National Cancer Institute (NCI between 1998 and 2012 were retrospectively reviewed. Most patients received RT with concurrent and adjuvant TMZ. Topographic locations were classified using preoperative imaging. Gross tumor volumes were contoured using treatment planning systems utilizing both pre-operative and post-operative MR imaging. RESULTS: At a median follow-up of 18.7 months, the median overall survival (OS and progression-free survival (PFS for all patients was 17.9 and 7.6 months. Patients with the smallest tumors had a median OS of 52.3 months compared to 16.3 months among patients with the largest tumors, P = 0.006. The patients who received bevacizumab after recurrence had a median OS of 23.3 months, compared to 16.3 months in patients who did not receive it, P = 0.0284. The median PFS and OS in patients with periventricular tumors was 5.7 and 17.5 months, versus 8.9 and 23.3 months in patients with non-periventricular tumors, P = 0.005. CONCLUSIONS: Survival in our cohort was comparable to the outcome of the defining EORTC-NCIC trial establishing the use of RT+TMZ. This study also identifies several potential prognostic factors that may be useful in stratifying patients.

  6. 77 FR 55095 - National Ovarian Cancer Awareness Month, 2012

    Science.gov (United States)

    2012-09-06

    ... their lives to ovarian cancer. They are mothers and daughters, sisters and grandmothers, community... treatments. Through the Centers for Disease Control's Inside Knowledge campaign, we are working to...

  7. Attenuation of rodent neuropathic pain by an orally active peptide, RAP-103, which potently blocks CCR2- and CCR5-mediated monocyte chemotaxis and inflammation.

    Science.gov (United States)

    Padi, Satyanarayana S V; Shi, Xiang Q; Zhao, Yuan Q; Ruff, Michael R; Baichoo, Noel; Pert, Candace B; Zhang, Ji

    2012-01-01

    Chemokine signaling is important in neuropathic pain, with microglial cells expressing CCR2 playing a well-established key role. DAPTA, a HIV gp120-derived CCR5 entry inhibitor, has been shown to inhibit CCR5-mediated monocyte migration and to attenuate neuroinflammation. We report here that as a stabilized analog of DAPTA, the short peptide RAP-103 exhibits potent antagonism for both CCR2 (half maximal inhibitory concentration [IC50] 4.2 pM) and CCR5 (IC50 0.18 pM) in monocyte chemotaxis. Oral administration of RAP-103 (0.05-1 mg/kg) for 7 days fully prevents mechanical allodynia and inhibits the development of thermal hyperalgesia after partial ligation of the sciatic nerve in rats. Administered from days 8 to 12, RAP-103 (0.2-1 mg/kg) reverses already established hypersensitivity. RAP-103 relieves behavioral hypersensitivity, probably through either or both CCR2 and CCR5 blockade, because by using genetically deficient animals, we demonstrated that in addition to CCR2, CCR5 is also required for the development of neuropathic pain. Moreover, RAP-103 is able to reduce spinal microglial activation and monocyte infiltration, and to inhibit inflammatory responses evoked by peripheral nerve injury that cause chronic pain. Our findings suggest that targeting CCR2/CCR5 should provide greater efficacy than targeting CCR2 or CCR5 alone, and that dual CCR2/CCR5 antagonist RAP-103 has the potential for broad clinical use in neuropathic pain treatment.

  8. Crk-like adapter protein regulates CCL19/CCR7-mediated epithelial-to-mesenchymal transition via ERK signaling pathway in epithelial ovarian carcinomas.

    Science.gov (United States)

    Cheng, Shaomei; Guo, Jingyan; Yang, Qing; Yang, Xiangshan

    2015-03-01

    Recent studies have suggested that Crk-like adapter protein (CrkL) and epithelial-to-mesenchymal transition (EMT) induced by CCL19/CCR7 play an important role in ovarian epithelial carcinogenesis. However, the regulatory mechanisms of CrkL on the CCL19/CCR7 signaling pathways in epithelial ovarian carcinomas (EOC) are not well characterized. Here, CCR7 and CrkL proteins were tested in 30 EOC tissues and cell lines. In vitro, the roles of CrkL in CCL19-stimulated SKOV-3 cell invasion and migration were investigated. In this work, CCR7 and CrkL over-expressed in EOC tissues and cell lines and correlated with FIGO stage and lymph node metastasis. Moreover, CCR7 and CrkL serve as an independent prognostic factor. In SKOV-3 cells, CrkL knockdown markedly suppressed the CCL19-stimulated expression of p-ERK and EMT biomarkers (N-cadherin, Snail and MMP9), compared with control. In contrast, p-AKT expression level did not change. On the other hand, functional analysis revealed CrkL knockdown could significantly decrease SKOV-3 cell invasion number of transwell invasion assay, and wound closure area of wound healing assay, compared to control. In conclusion, CrkL regulates CCL19/CCR7-induced EMT via ERK signaling pathway in EOC patients, which further suggested CrkL could be suggested as an efficient target in ovarian cancer treatment.

  9. 78 FR 59362 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-09-26

    ... Boulevard, Gaithersburg, MD 20878. Contact Person: Caron A. Lyman, Ph.D., Chief, Research Programs Review... B: Exploratory Grants. Date: November 18, 2013. Time: 7:30 a.m. to 5:00 p.m. Agenda: To review and... Research; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer Treatment Research;...

  10. 78 FR 4422 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-01-22

    ... Prevention and Etiology. Date: February 27, 2013. Time: 10:00 a.m. to 2:00 p.m. Agenda: To review and... Federal Domestic Assistance Program Nos. 93.392, Cancer Construction; 93.393, Cancer Cause and...

  11. A Simplified Technique for Evaluating Human "CCR5" Genetic Polymorphism

    Science.gov (United States)

    Falteisek, Lukáš; Cerný, Jan; Janštová, Vanda

    2013-01-01

    To involve students in thinking about the problem of AIDS (which is important in the view of nondecreasing infection rates), we established a practical lab using a simplified adaptation of Thomas's (2004) method to determine the polymorphism of HIV co-receptor CCR5 from students' own epithelial cells. CCR5 is a receptor involved in…

  12. A Simplified Technique for Evaluating Human "CCR5" Genetic Polymorphism

    Science.gov (United States)

    Falteisek, Lukáš; Cerný, Jan; Janštová, Vanda

    2013-01-01

    To involve students in thinking about the problem of AIDS (which is important in the view of nondecreasing infection rates), we established a practical lab using a simplified adaptation of Thomas's (2004) method to determine the polymorphism of HIV co-receptor CCR5 from students' own epithelial cells. CCR5 is a receptor involved in inflammatory…

  13. Phenotypic expressions of CCR5-Delta 32/Delta 32 homozygosity

    NARCIS (Netherlands)

    Nguyen, GT; Carrington, M; Beeler, JA; Dean, M; Aledort, LM; Blatt, PM; Cohen, AR; DiMichele, D; Eyster, ME; Kessler, CM; Konkle, B; Leissinger, C; Luban, N; O'Brien, SJ; Goedert, JJ; O'Brien, TR

    1999-01-01

    Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Delta 32/Delta 32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia wh

  14. Chemokine receptor CCR5 in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Kristiansen, T B; Wittenhagen, P

    2007-01-01

    To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta).......To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta)....

  15. Allosteric and orthosteric sites in CC chemokine receptor (CCR5), a chimeric receptor approach

    DEFF Research Database (Denmark)

    Thiele, Stefanie; Steen, Anne; Jensen, Pia C;

    2011-01-01

    molecules often act more deeply in an allosteric mode. However, opposed to the well described molecular interaction of allosteric modulators in class C 7-transmembrane helix (7TM) receptors, the interaction in class A, to which the chemokine receptors belong, is more sparsely described. Using the CCR5...... chemokine receptor as a model system, we studied the molecular interaction and conformational interchange required for proper action of various orthosteric chemokines and allosteric small molecules, including the well known CCR5 antagonists TAK-779, SCH-C, and aplaviroc, and four novel CCR5 ago......-allosteric molecules. A chimera was successfully constructed between CCR5 and the closely related CCR2 by transferring all extracellular regions of CCR2 to CCR5, i.e. a Trojan horse that resembles CCR2 extracellularly but signals through a CCR5 transmembrane unit. The chimera bound CCR2 (CCL2 and CCL7), but not CCR5...

  16. 78 FR 19496 - Submission for OMB Review; 30-day Comment Request; The National Cancer Institute (NCI...

    Science.gov (United States)

    2013-04-01

    ... HUMAN SERVICES National Institutes of Health Submission for OMB Review; 30-day Comment Request; The National Cancer Institute (NCI) SmokefreeTXT Program Evaluation SUMMARY: Under the provisions of Section... submitted ] to the Office of Management and Budget (OMB) a request to review and approve the...

  17. Trends in Cancer Screening Rates among Korean Men and Women: Results from the Korean National Cancer Screening Survey (KNCSS), 2004-2010

    OpenAIRE

    Lee, Eun-Ha; Lee, Hoo-Yeon; Choi, Kui Son; Jun, Jae Kwan; Park, Eun-Cheol; Lee, Jin Soo

    2011-01-01

    Purpose The Korean National Cancer Screening Survey (KNCSS) is a continuous nationwide survey implemented by the National Cancer Center in Korea since 2004. The purpose of the present study was to report trends in cancer screening rates for the five major cancers (stomach, liver, colorectal, breast, and cervix uteri) in Korean men and women. Materials and Methods The study used KNCSS data collected between 2004 and 2010. The survey was conducted on Korean men aged 40-74 years and Korean women...

  18. Coincident expression of the chemokine receptors CCR6 and CCR7 by pathologic Langerhans cells in Langerhans cell histiocytosis.

    Science.gov (United States)

    Fleming, Mark D; Pinkus, Jack L; Fournier, Marcia V; Alexander, Sarah W; Tam, Carmen; Loda, Massimo; Sallan, Stephen E; Nichols, Kim E; Carpentieri, David F; Pinkus, Geraldine S; Rollins, Barrett J

    2003-04-01

    It has been suggested that a switch in chemokine receptor expression underlies Langerhans cell migration from skin to lymphoid tissue. Activated cells are thought to down-regulate CCR6, whose ligand macrophage inflammatory protein-3 alpha (MIP-3 alpha)/CCL20 is expressed in skin, and up-regulate CCR7, whose ligands are in lymphoid tissues. In Langerhans cell histiocytosis (LCH), pathologic Langerhans cells (LCs) accumulate in several tissues, including skin, bone, and lymphoid organs. We have examined 24 LCH cases and find that pathologic LCs expressed CCR6 and CCR7 coincidentally in all cases. Furthermore, MIP-3 alpha/CCL20 is expressed by keratinocytes in involved skin and by macrophages and osteoblasts in involved bone. Expression of CCR6 by pathologic LCs may contribute to their accumulation in nonlymphoid organs such as skin and bone, whereas CCR7 expression may direct them to lymphoid tissue. Histiocytes in Rosai-Dorfman disease and hemophagocytic syndrome also coexpressed CCR6 and CCR7, suggesting that this may be a general attribute of abnormal histiocytes.

  19. Exchange of extracellular domains of CCR1 and CCR5 reveals confined functions in CCL5-mediated cell recruitment.

    Science.gov (United States)

    Kramp, Birgit K; Megens, Remco T A; Sarabi, Alisina; Winkler, Sabine; Projahn, Delia; Weber, Christian; Koenen, Rory R; von Hundelshausen, Philipp

    2013-10-01

    The chemokine CCL5 recruits monocytes into inflamed tissues by triggering primarily CCR1-mediated arrest on endothelial cells, whereas subsequent spreading is dominated by CCR5. The CCL5-induced arrest can be enhanced by heteromer formation with CXCL4. To identify mechanisms for receptor-specific functions, we employed CCL5 mutants and transfectants expressing receptor chimeras carrying transposed extracellular regions. Mutation of the basic 50s cluster of CCL5, a coordinative site for CCL5 surface presentation, reduced CCR5- but not CCR1-mediated arrest and transmigration. Impaired arrest was restored by exchanging the CCR5-N-terminus for that of CCR1, which supported arrest even without the 50s cluster, whereas mutation of the basic 40s cluster essential for proteoglycan binding of CCL5 could not be rescued. The enhancement of CCL5-induced arrest by CXCL4 was mediated by CCR1 requiring its third extracellular loop. The domain exchanges did not affect formation and co-localisation of receptor dimers, indicating a sensing role of the third extracellular loop for hetero-oligomers in an arrest microenvironment. Our data identify confined targetable regions of CCR1 specialised to facilitate CCL5-induced arrest and enhanced responsiveness to the CXCL4-CCL5 heteromer.

  20. Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3

    Directory of Open Access Journals (Sweden)

    Lund Eiliv

    2009-07-01

    Full Text Available Abstract Background Gonadotropin releasing hormone (GNRH1 triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3. Methods We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs were genotyped and used to identify haplotype-tagging SNPs (htSNPS in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II, European Prospective Investigation on Cancer and Nutrition (EPIC, Multiethnic Cohort (MEC, Nurses' Health Study (NHS, and Women's Health Study (WHS. Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone were also measured in 4713 study subjects. Results Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Conclusion Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.

  1. 76 FR 55209 - National Ovarian Cancer Awareness Month, 2011

    Science.gov (United States)

    2011-09-07

    ... cancer deaths among women in the United States. This month, we remember the mothers, sisters, and... professionals working to end this disease. The Centers for Disease Control and Prevention and the Department...

  2. Role of the chemokine receptors CCR1, CCR2 and CCR4 in the pathogenesis of experimental dengue infection in mice.

    Directory of Open Access Journals (Sweden)

    Rodrigo Guabiraba

    Full Text Available Dengue virus (DENV, a mosquito-borne flavivirus, is a public health problem in many tropical countries. Recent clinical data have shown an association between levels of different chemokines in plasma and severity of dengue. We evaluated the role of CC chemokine receptors CCR1, CCR2 and CCR4 in an experimental model of DENV-2 infection in mice. Infection of mice induced evident clinical disease and tissue damage, including thrombocytopenia, hemoconcentration, lymphopenia, increased levels of transaminases and pro-inflammatory cytokines, and lethality in WT mice. Importantly, infected WT mice presented increased levels of chemokines CCL2/JE, CCL3/MIP-1α and CCL5/RANTES in spleen and liver. CCR1⁻/⁻ mice had a mild phenotype with disease presentation and lethality similar to those of WT mice. In CCR2⁻/⁻ mice, lethality, liver damage, levels of IL-6 and IFN-γ, and leukocyte activation were attenuated. However, thrombocytopenia, hemoconcentration and systemic TNF-α levels were similar to infected WT mice. Infection enhanced levels of CCL17/TARC, a CCR4 ligand. In CCR4⁻/⁻ mice, lethality, tissue injury and systemic inflammation were markedly decreased. Despite differences in disease presentation in CCR-deficient mice, there was no significant difference in viral load. In conclusion, activation of chemokine receptors has discrete roles in the pathogenesis of dengue infection. These studies suggest that the chemokine storm that follows severe primary dengue infection associates mostly to development of disease rather than protection.

  3. The National Cancer Institute's Physical Sciences - Oncology Network

    Science.gov (United States)

    Espey, Michael Graham

    In 2009, the NCI launched the Physical Sciences - Oncology Centers (PS-OC) initiative with 12 Centers (U54) funded through 2014. The current phase of the Program includes U54 funded Centers with the added feature of soliciting new Physical Science - Oncology Projects (PS-OP) U01 grant applications through 2017; see NCI PAR-15-021. The PS-OPs, individually and along with other PS-OPs and the Physical Sciences-Oncology Centers (PS-OCs), comprise the Physical Sciences-Oncology Network (PS-ON). The foundation of the Physical Sciences-Oncology initiative is a high-risk, high-reward program that promotes a `physical sciences perspective' of cancer and fosters the convergence of physical science and cancer research by forming transdisciplinary teams of physical scientists (e.g., physicists, mathematicians, chemists, engineers, computer scientists) and cancer researchers (e.g., cancer biologists, oncologists, pathologists) who work closely together to advance our understanding of cancer. The collaborative PS-ON structure catalyzes transformative science through increased exchange of people, ideas, and approaches. PS-ON resources are leveraged to fund Trans-Network pilot projects to enable synergy and cross-testing of experimental and/or theoretical concepts. This session will include a brief PS-ON overview followed by a strategic discussion with the APS community to exchange perspectives on the progression of trans-disciplinary physical sciences in cancer research.

  4. Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates

    NARCIS (Netherlands)

    B.K. Edwards (Brenda); E. Ward (Elizabeth); B.A. Kohler (Betsy); C. Eheman (Christie); A. Zauber (Ann); R.N. Anderson (Robert); A. Jemal (Ahmedin); M.J. Schymura (Maria); I. Lansdorp-Vogelaar (Iris); L.C. Seeff (Laura); M. van Ballegooijen (Marjolein); S.L. Goede (Luuk); L.A.G. Ries (Lynn)

    2010-01-01

    textabstractBACKGROUND. The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information regarding cancer occurrence and

  5. 78 FR 57400 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2013-09-18

    ...: Biomedical Cloud Technology; Electronic Health Records; Advocate and Organizational Engagement; and Proposed Organizational Change: Division of Extramural Activities. Place: National Institutes of Health, Building 31,...

  6. Adoption of Hypofractionated Whole-Breast Irradiation for Early-Stage Breast Cancer: A National Cancer Data Base Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Elyn H. [Yale School of Medicine, Yale School of Medicine, New Haven, Connecticut (United States); Mougalian, Sarah S. [Yale School of Medicine, Yale School of Medicine, New Haven, Connecticut (United States); Department of Medical Oncology, Yale School of Medicine, New Haven, Connecticut (United States); Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale, New Haven, Connecticut (United States); Soulos, Pamela R. [Yale School of Medicine, Yale School of Medicine, New Haven, Connecticut (United States); Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale, New Haven, Connecticut (United States); Rutter, Charles E.; Evans, Suzanne B. [Yale School of Medicine, Yale School of Medicine, New Haven, Connecticut (United States); Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale, New Haven, Connecticut (United States); Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Haffty, Bruce G. [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, New Jersey (United States); Gross, Cary P. [Yale School of Medicine, Yale School of Medicine, New Haven, Connecticut (United States); Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, New Jersey (United States); Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut (United States); Yu, James B., E-mail: james.b.yu@yale.edu [Yale School of Medicine, Yale School of Medicine, New Haven, Connecticut (United States); Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale, New Haven, Connecticut (United States); Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States)

    2014-12-01

    Purpose: To evaluate the relationship of patient, hospital, and cancer characteristics with the adoption of hypofractionation in a national sample of patients diagnosed with early-stage breast cancer. Methods and Materials: We performed a retrospective study of breast cancer patients in the National Cancer Data Base from 2004-2011 who were treated with radiation therapy and met eligibility criteria for hypofractionation. We used logistic regression to identify factors associated with receipt of hypofractionation (vs conventional fractionation). Results: We identified 13,271 women (11.7%) and 99,996 women (88.3%) with early-stage breast cancer who were treated with hypofractionation and conventional fractionation, respectively. The use of hypofractionation increased significantly, with 5.4% of patients receiving it in 2004 compared with 22.8% in 2011 (P<.001 for trend). Patients living ≥50 miles from the cancer reporting facility had increased odds of receiving hypofractionation (odds ratio 1.57 [95% confidence interval 1.44-1.72], P<.001). Adoption of hypofractionation was associated with treatment at an academic center (P<.001) and living in an area with high median income (P<.001). Hypofractionation was less likely to be used in patients with high-risk disease, such as increased tumor size (P<.001) or poorly differentiated histologic grade (P<.001). Conclusions: The use of hypofractionation is rising and is associated with increased travel distance and treatment at an academic center. Further adoption of hypofractionation may be tempered by both clinical and nonclinical concerns.

  7. CCR5 Deletion Protects Against Inflammation-Associated Mortality in Dialysis Patients

    NARCIS (Netherlands)

    Muntinghe, Friso L. H.; Verduijn, Marion; Zuurman, Mike W.; Grootendorst, Diana C.; Carrero, Juan Jesus; Qureshi, Abdul Rashid; Luttropp, Karin; Nordfors, Louise; Lindholm, Bengt; Brandenburg, Vincent; Schalling, Martin; Stenvinkel, Peter; Boeschoten, Elisabeth W.; Krediet, Raymond T.; Navis, Gerjan; Dekker, Friedo W.

    2009-01-01

    The CC-chemokine receptor 5 (CCR5) is a receptor for various proinflammatory chemokines, and a deletion variant of the CCR5 gene (CCR5 Delta 32) leads to deficiency of the receptor. We hypothesized that CCR5 Delta 32 modulates inflammation-driven mortality in patients with ESRD. We studied the inter

  8. The CCR5 receptor acts as an alloantigen in CCR5Δ32 homozygous individuals: Identification of chemokineand HIV-1-blocking human antibodies

    OpenAIRE

    1998-01-01

    The chemokine receptor CCR5 is the major coreceptor for infection by macrophage-tropic R5 HIV-1. A 32-bp deletion in the gene coding for CCR5 (CCR5Δ32) occurs with a frequency of 10% in the Caucasian population and results in a receptor protein that is truncated and not expressed at the cell surface. CCR5Δ32 homozygous individuals are apparently normal but resistant to infection with R5 HIV-1. In two individuals homozygous for CCR5Δ32, who had been repeatedly exposed to CCR5-expressing blood ...

  9. The Calculus Concept Readiness (CCR) Instrument: Assessing Student Readiness for Calculus

    CERN Document Server

    Carlson, Marilyn; West, Richard

    2010-01-01

    The Calculus Concept Readiness (CCR) instrument is based on the broad body of mathematics education research that has revealed major understandings, representational abilities, and reasoning abilities students need to construct in precalculus level courses to be successful in calculus. The CCR is a 25-item multiple-choice instrument, and the CCR taxonomy articulates what the CCR assesses. The methodology used to develop and validate the CCR is described and illustrated. Results from administering the CCR as a readiness examination in calculus are provided along with data to guide others in using the CCR as a readiness examination for beginning calculus.

  10. Editing CCR5: a novel approach to HIV gene therapy.

    Science.gov (United States)

    Cornu, Tatjana I; Mussolino, Claudio; Bloom, Kristie; Cathomen, Toni

    2015-01-01

    Acquired immunodeficiency syndrome (AIDS) is a life-threatening disorder caused by infection of individuals with the human immunodeficiency virus (HIV). Entry of HIV-1 into target cells depends on the presence of two surface proteins on the cell membrane: CD4, which serves as the main receptor, and either CCR5 or CXCR4 as a co-receptor. A limited number of people harbor a genomic 32-bp deletion in the CCR5 gene (CCR5∆32), leading to expression of a truncated gene product that provides resistance to HIV-1 infection in individuals homozygous for this mutation. Moreover, allogeneic hematopoietic stem cell (HSC) transplantation with CCR5∆32 donor cells seems to confer HIV-1 resistance to the recipient as well. However, since Δ32 donors are scarce and allogeneic HSC transplantation is not exempt from risks, the development of gene editing tools to knockout CCR5 in the genome of autologous cells is highly warranted. Targeted gene editing can be accomplished with designer nucleases, which essentially are engineered restriction enzymes that can be designed to cleave DNA at specific sites. During repair of these breaks, the cellular repair pathway often introduces small mutations at the break site, which makes it possible to disrupt the ability of the targeted locus to express a functional protein, in this case CCR5. Here, we review the current promise and limitations of CCR5 gene editing with engineered nucleases, including factors affecting the efficiency of gene disruption and potential off-target effects.

  11. Oral cavity and lip cancer: United Kingdom National Multidisciplinary Guidelines.

    Science.gov (United States)

    Kerawala, C; Roques, T; Jeannon, J-P; Bisase, B

    2016-05-01

    This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It provides recommendations on the assessment and management of patients with cancer of the oral cavity and the lip. Recommendations • Surgery remains the mainstay of management for oral cavity tumours. (R) • Tumour resection should be performed with a clinical clearance of 1 cm vital structures permitting. (R) • Elective neck treatment should be offered for all oral cavity tumours. (R) • Adjuvant radiochemotherapy in the presence of advanced neck disease or positive margins improves control rates. (R) • Early stage lip cancer can be treated equally well by surgery or radiation therapy. (R).

  12. Efficient Use of a Crude Drug/Herb Library Reveals Ephedra Herb As a Specific Antagonist for TH2-Specific Chemokine Receptors CCR3, CCR4, and CCR8.

    Science.gov (United States)

    Matsuo, Kazuhiko; Koizumi, Keiichi; Fujita, Mitsugu; Morikawa, Toshio; Jo, Michiko; Shibahara, Naotoshi; Saiki, Ikuo; Yoshie, Osamu; Nakayama, Takashi

    2016-01-01

    Chemokine receptors CCR3 and CCR4 are preferentially expressed by TH2 cells, mast cells, and/or eosinophils, all of which are involved in the pathogenesis of allergic diseases. Therefore, CCR3 and CCR4 have long been highlighted as potent therapeutic targets for allergic diseases. Japanese traditional herbal medicine Kampo consists of multiple crude drugs/herbs, which further consist of numerous chemical substances. Recent studies have demonstrated that such chemical substances appear to promising sources in the development of novel therapeutic agents. Based on these findings, we hypothesize that Kampo-related crude drugs/herbs would contain chemical substances that inhibit the cell migration mediated by CCR3 and/or CCR4. To test this hypothesis, we screened 80 crude drugs/herbs to identify candidate substances using chemotaxis assay. Among those tested, Ephedra Herb inhibited the chemotaxis mediated by both CCR3 and CCR4, Cornus Fruit inhibited that mediated by CCR3, and Rhubarb inhibited that mediated by CCR4. Furthermore, Ephedra Herb specifically inhibited the chemotaxis mediated by not only CCR3 and CCR4 but CCR8, all of which are selectively expressed by TH2 cells. This result led us to speculate that ephedrine, a major component of Ephedra Herb, would play a central role in the inhibitory effects on the chemotaxis mediated by CCR3, CCR4, and CCR8. However, ephedrine exhibited little effects on the chemotaxis. Therefore, we fractionated Ephedra Herb into four subfractions and examined the inhibitory effects of each subfraction. As the results, ethyl acetate-insoluble fraction exhibited the inhibitory effects on chemotaxis and calcium mobilization mediated by CCR3 and CCR4 most significantly. In contrast, chloroform-soluble fraction exhibited a weak inhibitory effect on the chemotaxis mediated by CCR8. Furthermore, maoto, one of the Kampo formulations containing Ephedra Herb, exhibited the inhibitory effects on the chemotaxis mediated by CCR3, CCR4, and CCR8

  13. Clinical use of CCR5 inhibitors in HIV and beyond

    Directory of Open Access Journals (Sweden)

    Gilliam Bruce

    2010-01-01

    Full Text Available Abstract Since the discovery of CCR5 as a coreceptor for HIV entry, there has been interest in blockade of the receptor for treatment and prevention of HIV infection. Although several CCR5 antagonists have been evaluated in clinical trials, only maraviroc has been approved for clinical use in the treatment of HIV-infected patients. The efficacy, safety and resistance profile of CCR5 antagonists with a focus on maraviroc are reviewed here along with their usage in special and emerging clinical situations. Despite being approved for use since 2007, the optimal use of maraviroc has yet to be well-defined in HIV and potentially in other diseases. Maraviroc and other CCR5 antagonists have the potential for use in a variety of other clinical situations such as the prevention of HIV transmission, intensification of HIV treatment and prevention of rejection in organ transplantation. The use of CCR5 antagonists may be potentiated by other agents such as rapamycin which downregulate CCR5 receptors thus decreasing CCR5 density. There may even be a role for their use in combination with other entry inhibitors. However, clinical use of CCR5 antagonists may have negative consequences in diseases such as West Nile and Tick-borne encephalitis virus infections. In summary, CCR5 antagonists have great therapeutic potential in the treatment and prevention of HIV as well as future use in novel situations such as organ transplantation. Their optimal use either alone or in combination with other agents will be defined by further investigation.

  14. Associations of cancer site and type with occupation and industry from the Third National Cancer Survey Interview.

    Science.gov (United States)

    Williams, R R; Stegens, N L; Goldsmith, J R

    1977-10-01

    From the Third National Cancer Survey (TNCS) Interview Study of 7,518 incident cases, lifetime histories of occupations and industries were studied for associations with specific cancer sites and types while controlling for age, sex, race, education, use of cigarettes or alcohol, and geographic location. Lung cancer patients were found more often than expected among several categories including trucking, air transportation, wholesaling, painting, building construction, building maintenance, and manufacturing (furniture, transportation equipment, and food products). Controlling for cigarette smoking did not change these associations. Leukemia and multiple myeloma were associated with sales personnel of both sexes, whereas lymphomas and Hodgkin's disease were excessive among women working in the medical industry. Other associations included rectal cancer with several retail industries; prostate cancer with ministers, farmers, plumbers, and coal miners; malignant melanoma with school teachers; and invasive cervical cancer with women working in hotels and restaurants. Breast cancer patients were more common among women who were teachers or other professionals and who worked in business and finance (even after controlling for education). Many other findings are presented in detailed tables. Results are reported mainly as a research resource for use by other investigators doing work in this field. Suggestions are given for future studies.

  15. CCR5 inhibitors: Emerging promising HIV therapeutic strategy

    Directory of Open Access Journals (Sweden)

    Surya Rao Padmasri

    2009-01-01

    Full Text Available Though potent anti-HIV therapy has spectacularly reduced the morbidity and mortality of human immunodeficiency virus (HIV-1 infection in the advanced countries, it continues to be associated with substantial toxicity, drug-drug interactions, difficulties in adherence, and abnormal cost. As a result, better effective, safe antiretroviral drugs and treatment strategies keep on to be pursued. In this process, CCR5 (chemokine receptor 5 inhibitors are a new class of antiretroviral drug used in the treatment of HIV. They are designed to prevent HIV infection of CD4 T-cells by blocking the CCR5. When the CCR5 receptor is unavailable, ′R5-tropic′ HIV (the variant of the virus that is common in earlier HIV infection cannot engage with a CD4 T-cell to infect the cell. In August 2007, the FDA approved the first chemokine (C-C motif CCR5 inhibitor, maraviroc, for treatment-experienced patients infected with R5-using virus. Studies from different cohort in regions, affected by clad B HIV-1, demonstrate that 81-88% of HIV-1 variants in treatment naïve patients are CCR5 tropic and that virtually all the remaining variants are dual/mixed tropic i.e., are able to utilize both CCR5 and CXCR4 coreceptors. In treatment experienced patients, 49−78% of the variants are purely CCR5 tropic, 22−48% are dual/mixed tropic, and 2-5% exclusively utilize CXCR4. A 32 bp deletion in the CCR5 gene, which results in a frame shift and truncation of the normal CCR5 protein, was identified in a few persons who had remained uninfected after exposure to CCR5 tropic HIV-1 virus. This allele is common in white of European origin, with prevalence near to 10%, but is absent among East Asian, American Indian, Tamil Indian, and African ethnic groups. HIV-infected individuals, who are heterozygous for CCR5 delta 32, have slower rates of disease progression. The currently available data supports the continuation of the development of CCR5 antagonists in different settings related

  16. Cohort Profile: the National Prostate Cancer Register of Sweden and Prostate Cancer data Base Sweden 2.0.

    Science.gov (United States)

    Van Hemelrijck, Mieke; Wigertz, Annette; Sandin, Fredrik; Garmo, Hans; Hellström, Karin; Fransson, Per; Widmark, Anders; Lambe, Mats; Adolfsson, Jan; Varenhorst, Eberhard; Johansson, Jan-Erik; Stattin, Pär

    2013-08-01

    In 1987, the first Regional Prostate Cancer Register was set up in the South-East health-care region of Sweden. Other health-care regions joined and since 1998 virtually all prostate cancer (PCa) cases are registered in the National Prostate Cancer Register (NPCR) of Sweden to provide data for quality assurance, bench marking and clinical research. NPCR includes data on tumour stage, Gleason score, serum level of prostate-specific antigen (PSA) and primary treatment. In 2008, the NPCR was linked to a number of other population-based registers by use of the personal identity number. This database named Prostate Cancer data Base Sweden (PCBaSe) has now been extended with more cases, longer follow-up and a selection of two control series of men free of PCa at the time of sampling, as well as information on brothers of men diagnosed with PCa, resulting in PCBaSe 2.0. This extension allows for studies with case-control, cohort or longitudinal case-only design on aetiological factors, pharmaceutical prescriptions and assessment of long-term outcomes. The NPCR covers >96% of all incident PCa cases registered by the Swedish Cancer Register, which has an underreporting of <3.7%. The NPCR is used to assess trends in incidence, treatment and outcome of men with PCa. Since the national registers linked to PCBaSe are complete, studies from PCBaSe 2.0 are truly population based.

  17. Expression of the Chemokine Receptors CCR4, CCR5, and CXCR3 by Human Tissue-Infiltrating Lymphocytes

    Science.gov (United States)

    Kunkel, Eric J.; Boisvert, Judie; Murphy, Kristine; Vierra, Mark A.; Genovese, Mark C.; Wardlaw, Andrew J.; Greenberg, Harry B.; Hodge, Martin R.; Wu, Lijun; Butcher, Eugene C.; Campbell, James J.

    2002-01-01

    Differential expression of adhesion molecules and chemokine receptors has been useful for identification of peripheral blood memory lymphocyte subsets with distinct tissue and microenvironmental tropisms. Expression of CCR4 by circulating memory CD4+ lymphocytes is associated with cutaneous and other systemic populations while expression of CCR9 is associated with a small intestine-homing subset. CCR5 and CXCR3 are also expressed by discrete memory CD4+ populations in blood, as well as by tissue-infiltrating lymphocytes from a number of sites. To characterize the similarities and differences among tissue-infiltrating lymphocytes, and to shed light on the specialization of lymphocyte subsets that mediate inflammation and immune surveillance in particular tissues, we have examined the expression of CCR4, CXCR3, and CCR5 on CD4+ lymphocytes directly isolated from a wide variety of normal and inflamed tissues. Extra-lymphoid tissues contained only memory lymphocytes, many of which were activated (CD69+). As predicted by classical studies, skin lymphocytes were enriched in CLA expression whereas intestinal lymphocytes were enriched in α4β7 expression. CCR4 was expressed at high levels by skin-infiltrating lymphocytes, at lower levels by lung and synovial fluid lymphocytes, but never by intestinal lymphocytes. Only the high CCR4 levels characteristic of skin lymphocytes were associated with robust chemotactic and adhesive responses to TARC, consistent with a selective role for CCR4 in skin lymphocyte homing. In contrast, CXCR3 and CCR5 were present on the majority of lymphocytes from each non-lymphoid tissue examined, suggesting that these receptors are unlikely to determine tissue specificity, but rather, may play a wider role in tissue inflammation. PMID:11786428

  18. The majority of surgical departments adhere to national Danish guidelines for surveillance after colorectal cancer surgery

    DEFF Research Database (Denmark)

    Lykke, Jakob; Roikjær, Ole; Jess, Per

    2013-01-01

    In 2003 the use of post-operative surveillance (POS) after surgery for colorectal cancer (CRC) in Denmark was studied. Diversity in the choice and frequency of surveillance modalities was found. Subsequently, the Danish Colorectal Cancer Group (DCCG) has published guidelines for POS. In the same...... period, the number of departments performing CRC surgery has been reduced by 50% nationally. The aim of the present study was to describe the POS after CRC in Denmark following a reduction in the number of departments performing operations for CRC and the DCCG's publication of national recommendations...

  19. National Cancer Information Service in Italy: an information points network as a new model for providing information for cancer patients.

    Science.gov (United States)

    Truccolo, Ivana; Bufalino, Rosaria; Annunziata, Maria Antonietta; Caruso, Anita; Costantini, Anna; Cognetti, Gaetana; Florita, Antonio; Pero, Dina; Pugliese, Patrizia; Tancredi, Roberta; De Lorenzo, Francesco

    2011-01-01

    The international literature data report that good information and communication are fundamental components of a therapeutic process. They contribute to improve the patient-health care professional relationship, to facilitate doctor-patient relationships, therapeutic compliance and adherence, and to the informed consent in innovative clinical trials. We report the results of a multicentric national initiative that developed a 17-information-structure network: 16 Information Points located in the major state-funded certified cancer centers and general hospitals across Italy and a national Help-line at the nonprofit organization AIMaC (the Italian oncologic patients, families and friends association), and updated the already existing services with the aim to create the National Cancer Information Service (SION). The project is the result of a series of pilot and research projects funded by the Italian Ministry of Health. The Information Service model proposed is based on some fundamental elements: 1) human interaction with experienced operators, adequately trained in communication and information, complemented with 2) virtual interaction (Help line, Internet, blog, forum and social network); 3) informative material adequate for both scientific accuracy and communicative style; 4) adequate locations for appropriate positioning and privacy (adequate visibility); 5) appropriate advertising. First results coming from these initiatives contributed to introduce issues related to "Communication and Information to patients" as a "Public Health Instrument" to the National Cancer Plan approved by the Ministry of Health for the years 2010-2012.

  20. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques

    OpenAIRE

    2007-01-01

    Monocytes participate critically in atherosclerosis. There are 2 major subsets expressing different chemokine receptor patterns: CCR2+CX3CR1+Ly-6Chi and CCR2–CX3CR1++Ly-6Clo monocytes. Both C-C motif chemokine receptor 2 (CCR2) and C-X3-C motif chemokine receptor 1 (CX3CR1) are linked to progression of atherosclerotic plaques. Here, we analyzed mouse monocyte subsets in apoE-deficient mice and traced their differentiation and chemokine receptor usage as they accumulated within atherosclerotic...

  1. Binding of fusion protein FLSC IgG1 to CCR5 is enhanced by CCR5 antagonist Maraviroc.

    Science.gov (United States)

    Latinovic, Olga; Schneider, Kate; Szmacinski, Henryk; Lakowicz, Joseph R; Heredia, Alonso; Redfield, Robert R

    2014-12-01

    The CCR5 chemokine receptor is crucial for human immunodeficiency virus type 1 (HIV-1) infection, acting as the principal coreceptor for HIV-1 entry and transmission and is thus an attractive target for antiviral therapy. Studies have suggested that CCR5 surface density and its conformational changes subsequent to virion engagement are rate limiting for entry, and consequently, infection. Not all CCR5 antibodies inhibit HIV-1 infection, suggesting a need for more potent reagents. Here we evaluated full length single chain (FLSC) IgG1, a novel IgG-CD4-gp120(BAL) fusion protein with several characteristics that make it an attractive candidate for treatment of HIV-1 infections, including bivalency and a potentially increased serum half-life over FLSC, the parental molecule. FLSC IgG1 binds two domains on CCR5, the N-terminus and the second extracellular loop, lowering the levels of available CCR5 viral attachment sites. Furthermore, FLSC IgG1 synergizes with Maraviroc (MVC), the only licensed CCR5 antagonist. In this study, we used both microscopy and functional assays to address the mechanistic aspects of the interactions of FLSC IgG1 and MVC in the context of CCR5 conformational changes and viral infection. We used a novel stochastic optical reconstruction microscopy (STORM), based on high resolution localization of photoswitchable dyes to visualize direct contacts between FLSC IgG1 and CCR5. We compared viral entry inhibition by FLSC IgG1 with that of other CCR5 blockers and showed FLSC IgG1 to be the most potent. We also showed that lower CCR5 surface densities in HIV-1 infected primary cells result in lower FLSC IgG1 EC50 values. In addition, CCR5 binding by FLSC IgG1, but not CCR5 Ab 2D7, was significantly increased when cells were treated with MVC, suggesting MVC allosterically increases exposure of the FLSC IgG1 binding site. These data have implications for future antiviral therapy development.

  2. Burden of cancer in Malawi; common types, incidence and trends: National population-based cancer registry

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    Msyamboza Kelias

    2012-03-01

    Full Text Available Abstract Background Cancer is a leading cause of morbidity and mortality worldwide with a majority of cases and deaths occurring in developing countries. While cancer of the lung, breast, colorectum, stomach and prostate are the most common types of cancer globally, in east and southern Africa these are less common and comprehensive data to inform policies are lacking. Methods Nationwide cancer registry was conducted between September and October 2010 in Malawi. New cancer cases registered from 2007 to 2010 were identified from hospital and clinic registers of 81 out of 84 health facilities providing cancer diagnosis, treatment or palliative care services. Demographic and cancer data were extracted from registers and case notes using a standard form. Results A total of 18,946 new cases of cancer were registered in Malawi from 2007-2010. Of these 55.9% were females, 7.2% were children aged less than 15 years, 76.5% were adults aged 15-59 years and 16.4% were elderly aged 60 years or more. Only 17.9% of the cases had histologically verified diagnosis, 33.2% were diagnosed clinically and 49.6% based on clinical and some investigations. Amongst females, cancer of the cervix was the commonest accounting for 45.4% of all cases followed by Kaposi sarcoma (21.1%, cancer of the oesophagus (8.2%, breast (4.6% and non-Hodgkin lymphoma (4.1%. In males, Kaposi sarcoma was the most frequent (50.7% then cancer of oesophagus (16.9%, non-Hodgkin lymphoma (7.8, prostate (4.0% and urinary bladder (3.7%. Age-standardised incidence rate per 100,000 population for all types of cancer in males increased from 31 in 1999-2002 to 56 in 2007-2010. In females it increased from 29 to 69. Kaposi sarcoma and cancer of the oesophagus, cervical cancer and Kaposi sarcoma were the main causes for the increased incidence in males and females respectively. It was estimated that, annually at least 8,151 new cases of cancer (all types occur in Malawi. Conclusions This study provided

  3. Preventing cervical cancer : overviews of the National Breast and Cervical Cancer Early Detection Program and 2 US immunization programs.

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    Khan, Kris; Curtis, C Robinette; Ekwueme, Donatus U; Stokley, Shannon; Walker, Chastity; Roland, Katherine; Benard, Vicki; Saraiya, Mona

    2008-11-15

    Three federal programs with the potential to reduce cervical cancer incidence, morbidity, and mortality, especially among underserved populations, are administered by the Centers for Disease Control and Prevention (CDC): the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), the Vaccines for Children (VFC) Program, and the Section 317 immunization grant program. The NBCCEDP provides breast and cervical cancer screening and diagnostic services to uninsured and underinsured women. The VFC program and the Section 317 immunization grant program provide vaccines, including human papillomavirus (HPV) vaccine, to targeted populations at no cost for these vaccines. This article describes the programs, their histories, populations served, services offered, and roles in preventing cervical cancer through HPV vaccination and cervical cancer screening. Potential long-term reduction in healthcare costs resulting from HPV vaccination is also discussed. As an example of an initiative to vaccinate uninsured women aged 19-26 years through a cancer services program, a state-based effort that was recently launched in New York, is highlighted.

  4. The National Program of Cancer Registries: Explaining State Variations in Average Cost per Case Reported

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    Hannah K. Weir, PhD

    2005-07-01

    Full Text Available Introduction The Centers for Disease Control and Prevention’s National Program of Cancer Registries is a federally funded surveillance program that provides support and assistance to state and territorial health departments for the operation of cancer registries. The objective of this study was to identify factors associated with the Centers for Disease Control and Prevention’s costs to report cancer cases during the first 5 years of the National Program of Cancer Registries. Methods Information on expenditures and number of cases reported through the National Program of Cancer Registries was used to estimate the average cost per case reported for each state program. Additional information was obtained from other sources, and regression analyses were used to assess the contribution of each factor. Results Average costs of the National Program of Cancer Registries differed substantially among programs and were inversely associated with the number of cases reported (P < .001. The geographic area of the state was positively associated with the cost (P = .01, as was the regional cost of living (P = .08, whereas the program type (i.e., enhancement or planning was inversely associated with cost (P = .08. Conclusion The apparent existence of economies of scale suggests that contiguous state programs might benefit from sharing infrastructure and other fixed costs, such as database management resources, depending on the geographic area and population size served. Sharing database management resources might also promote uniform data collection and quality control practices, reduce the information-sharing burden among states, and allow more resources to be used for other cancer prevention and control activities.

  5. Management of thyroid cancer: United Kingdom National Multidisciplinary Guidelines.

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    Mitchell, A L; Gandhi, A; Scott-Coombes, D; Perros, P

    2016-05-01

    This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. This paper provides recommendations on the management of thyroid cancer in adults and is based on the 2014 British Thyroid Association guidelines. Recommendations • Ultrasound scanning (USS) of the nodule or goitre is a crucial investigation in guiding the need for fine needle aspiration cytology (FNAC). (R) • FNAC should be considered for all nodules with suspicious ultrasound features (U3-U5). If a nodule is smaller than 10 mm in diameter, USS guided FNAC is not recommended unless clinically suspicious lymph nodes on USS are also present. (R) • Cytological analysis and categorisation should be reported according to the current British Thyroid Association Guidance. (R) • Ultrasound scanning assessment of cervical nodes should be done in FNAC-proven cancer. (R) • Magnetic resonance imaging (MRI) or computed tomography (CT) should be done in suspected cases of retrosternal extension, fixed tumours (local invasion with or without vocal cord paralysis) or when haemoptysis is reported. When CT with contrast is used pre-operatively, there should be a two-month delay between the use of iodinated contrast media and subsequent radioactive iodine (I131) therapy. (R) • Fluoro-deoxy-glucose positron emission tomography imaging is not recommended for routine evaluation. (G) • In patients with thyroid cancer, assessment of extrathyroidal extension and lymph node disease in the central and lateral neck compartments should be undertaken pre-operatively by USS and cross-sectional imaging (CT or MRI) if indicated. (R) • For patients with Thy 3f or Thy 4 FNAC a diagnostic hemithyroidectomy is recommended. (R) • Total thyroidectomy is recommended for patients with tumours greater than 4 cm in diameter or tumours of any size in association with any of the following characteristics: multifocal disease, bilateral disease, extrathyroidal

  6. Short Communication: HIV-1 Variants That Use Mouse CCR5 Reveal Critical Interactions of gp120's V3 Crown with CCR5 Extracellular Loop 1.

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    Platt, Emily J; Durnin, James P; Kabat, David

    2015-10-01

    The CCR5 coreceptor amino terminus and extracellular (ECL) loops 1 and 2 have been implicated in HIV-1 infections, with species differences in these regions inhibiting zoonoses. Interactions of gp120 with CD4 and CCR5 reduce constraints on metastable envelope subunit gp41, enabling gp41 conformational changes needed for infection. We previously selected HIV-1JRCSF variants that efficiently use CCR5(Δ18) with a deleted amino terminus or CCR5(HHMH) with ECL2 from an NIH/Swiss mouse. Unexpectedly, the adaptive gp120 mutations were nearly identical, suggesting that they function by weakening gp120's grip on gp41 and/or by increasing interactions with ECL1. To analyze this and further wean HIV-1 from human CCR5, we selected variants using CCR5(HMMH) with murine ECL1 and 2 sequences. HIV-1JRCSF mutations adaptive for CCR5(Δ18) and CCR5(HHMH) were generally maladaptive for CCR5(HMMH), whereas the converse was true for CCR5(HMMH) adaptations. The HIV-1JRCSF variant adapted to CCR5(HMMH) also weakly used intact NIH/Swiss mouse CCR5. Our results strongly suggest that HIV-1JRCSF makes functionally critical contacts with human ECL1 and that adaptation to murine ECL1 requires multiple mutations in the crown of gp120's V3 loop.

  7. Multiple CCR5 Conformations on the Cell Surface Are Used Differentially by Human Immunodeficiency Viruses Resistant or Sensitive to CCR5 Inhibitors

    NARCIS (Netherlands)

    R. Berro; P.J. Klasse; D. Lascano; A. Flegler; K.A. Nagashima; R.W. Sanders; T.P. Sakmar; T.J. Hope; J.P. Moore

    2011-01-01

    Resistance to small-molecule CCR5 inhibitors arises when HIV-1 variants acquire the ability to use inhibitor-bound CCR5 while still recognizing free CCR5. Two isolates, CC101.19 and D1/85.16, became resistant via four substitutions in the gp120 V3 region and three in the gp41 fusion peptide (FP), re

  8. AHNS Series - Do you know your guidelines? Principles of treatment for nasopharyngeal cancer: A review of the National Comprehensive Cancer Network guidelines.

    Science.gov (United States)

    Gooi, Zhen; Richmon, Jeremy; Agrawal, Nishant; Blair, Elizabeth; Portugal, Louis; Vokes, Everett; Seiwert, Tanguy; de Souza, Jonas; Saloura, Vassiliki; Haraf, Daniel; Goldenberg, David; Chan, Jason

    2017-02-01

    This article is a continuation of the "Do You Know Your Guidelines" series, an initiative of the American Head and Neck Society's Education Committee to increase awareness of current best practices pertaining to head and neck cancer. The National Comprehensive Cancer Network guidelines for the management of nasopharyngeal cancer are reviewed here in a systematic fashion. These guidelines outline the workup, treatment and surveillance of patients with nasopharyngeal cancer. © 2016 Wiley Periodicals, Inc. Head Neck 39: 201-205, 2017.

  9. CC chemokine receptor-like 1 functions as a tumour suppressor by impairing CCR7-related chemotaxis in hepatocellular carcinoma.

    Science.gov (United States)

    Shi, Jie-Yi; Yang, Liu-Xiao; Wang, Zhi-Chao; Wang, Ling-Yan; Zhou, Jian; Wang, Xiao-Ying; Shi, Guo-Ming; Ding, Zhen-Bin; Ke, Ai-Wu; Dai, Zhi; Qiu, Shuang-Jian; Tang, Qi-Qun; Gao, Qiang; Fan, Jia

    2015-03-01

    Atypical chemokine receptors (ACRs) have been discovered to participate in the regulation of tumour behaviour. Here we report a tumour-suppressive role of a novel ACR member, CC chemokine receptor like 1 (CCRL1), in human hepatocellular carcinoma (HCC). Both mRNA and protein expressions of CCRL1 correlated with the malignant phenotype of HCC cells and were significantly down-regulated in tumour tissue compared with paired normal liver tissue. In both the initial and validation cohorts (n = 240 and n = 384, respectively), CCRL1 deficiency was associated with advanced tumour stage and was an independent index for worse survival and increased recurrence. Furthermore, knock-down or forced expression of CCRL1 revealed that CCRL1 suppressed the proliferation and invasion of HCC cells in vitro and reduced tumour growth and lung metastasis in vivo, with depressed levels of CCL19 and CCL21. By sequestrating CCL19 and CCL21, CCRL1 reduced their binding to CCR7 and consequently mitigated the detrimental impact of CCR7, including Akt-GSK3β pathway activation and nuclear accumulation of β-catenin in tumour cells. Clinically, the prognostic value of the CCR7 expression in HCC depended on the expression level of CCRL1, suggesting that CCRL1 may serve as an upstream switch for the CCR7 signalling cascade. Together, our findings suggest that CCRL1 impairs chemotactic events associated with CCR7 in the progression and metastasis of HCC. Our results also show a potential interplay between typical and atypical chemokine receptors in human cancer. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  10. CCR2 and coronary artery disease: a woscops substudy

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    Gray Ian C

    2010-02-01

    Full Text Available Abstract Background Several lines of evidence support a role for CCL2 (monocyte chemotactic protein-1 and its receptor CCR2 in the development of atherosclerosis. The aim of the present study was to determine the association of the CCR2 Val64Ile polymorphism with the development of coronary artery disease in the WOSCOPS study sample set. Findings A total of 443 cases and 1003 controls from the West of Scotland Coronary Prevention Study (WOSCOPS were genotyped for the Val64Ile polymorphism in the CCR2 gene. Genotype frequencies were compared between cases and controls. The CCR2 Val64Ile polymorphism was found not to be associated with coronary events in this study population (odds ratio 1.15, 95% CI 0.82-1.61, p = 0.41. Conclusions This case-control study does not support an association of the CCR2 Val64Ile polymorphism with coronary artery disease in the WOSCOPS sample set and does not confirm a possible protective role for CCR2 Val64Ile in the development of coronary artery disease.

  11. [Targeted modification of CCR5 gene in rabbits by TALEN].

    Science.gov (United States)

    Tang, Chengcheng; Zhang, Quanjun; Li, Xiaoping; Fan, Nana; Yang, Yi; Quan, Longquan; Lai, Liangxue

    2014-04-01

    The lack of suitable animal model for HIV-1 infection has become a bottleneck for the development of AIDS vaccines and drugs. Wild-type rabbits can be infected by HIV-1 persistently and HIV-1 can be efficiently replicated resulting in syncytia in rabbit cell line co-expressing human CD4 and CCR5.Therefore, a rabbit highly expressing human CD4 and CCR5 may be an ideal animal model for AIDS disease study. In the present report, by using the efficient gene targeting technology, transcription activator-like effector nuclease (TALEN), we explored the feasibility of generating a HIV-1 model by knocking in human CD4 and CCR5 into rabbit genome. First we constructed two TALEN vectors targeting rabbit CCR5 gene and a vector with homologous arms. TALEN mRNAs and donor DNA were then co-injected into fertilized oocytes. After 3?5 days, 24 embryos were collected and used to conduct mutation analysis with PCR and sequencing. All the 24 embryos were detected with CCR5 knockouts and 5 were human CD4 and CCR5 knockins. Our results laid a foundation for establishing a new animal model for the study of AIDS.

  12. The case for selection at CCR5-Delta32.

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    Pardis C Sabeti

    2005-11-01

    Full Text Available The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32 allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 arose within the past 1,000 y and rose to its present high frequency (5%-14% in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5, they imply that the pattern of genetic variation seen at CCR5-Delta32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome.

  13. The case for selection at CCR5-Delta32.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32 allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 arose within the past 1,000 y and rose to its present high frequency (5%-14% in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5, they imply that the pattern of genetic variation seen atCCR5-Delta32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome.

  14. 78 FR 76311 - Submission for OMB Review; 30-Day Comment Request: Outcomes Evaluation of the National Cancer...

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    2013-12-17

    ... HUMAN SERVICES National Institutes of Health Submission for OMB Review; 30-Day Comment Request: Outcomes Evaluation of the National Cancer Institute (NCI) Cancer Prevention Fellowship Program (CPFP) SUMMARY: Under... Institutes of Health (NIH), has submitted to the Office of Management and Budget (OMB) a request to...

  15. Expression of CCR7 in squamous cell carcinoma of the esophagus after esophagectomy: correlation with lymph node metastasis and prognosis%趋化因子受体CCR7表达与胸中段食管癌淋巴结转移及预后的关系

    Institute of Scientific and Technical Information of China (English)

    宋亮; 王洲; 刘相燕; 陈钢; 刘凡英

    2011-01-01

    目的 探讨趋化因子受体CCR7表达与胸中段食管鳞癌淋巴结转移及预后的相关性.方法 回顾2003年6月至2005年6月手术治疗184例胸中段食管癌病例临床资料.采用免疫组化进行趋化因子受体CCR7检测,Kaplan-meier法进行生存分析、用Cox回归分析判定独立预后因素.结果 CCR7表达率Ⅱ期和Ⅲ期病例分别为70.3%和85.5%(x2=5.0,P=0.02);T2和T3病例分别为64.9%和80.9%(x2=5.4,P=0.01);有、无淋巴结转移病例分别为86.4%和65.0%(x2=10.8,P=0.00)两组差异均有统计学意义.有、无CCR7表达病例的5年生存率为26.3%和66.0%,差异有统计学意义(x2=23.7,P=0.00);其中T2病例分别为35.1%和70.0%(P=0.01);T3病例分别为22.4%和60.9%(P=0.00);pN0分别为28.8%和66.7%(p=0.00);pN1分别为14.3%和63.6%(P=0.00),两组差异亦均有统计学意义.Cox回归分析结果显示,T分类、N分类和CCR7表达是预后独立的危险因素.结论 食管鳞癌不同的T、N分类中CCR7表达存在差别;CCR7表达者5年生存率降低;肿瘤的T分类、淋巴结转移和CCR7表达是独立的不利预后因素.%Objective To investigate the expression of chemokine receptor CCR7 and its correlation with lymph node metastasis and prognosis in esophageal cancer after esophagectomy. Methods One hundred and eighty-four patients with middle third squamous cell carcinoma of the esophagus were enrolled in this study. All patients underwent operation in Provincial Hospital Affiliated to Shandong University between June, 2003 and June, 2005. The expression of CCR7 was detected by immunohistochemistry. All statistic analyses were performed with SPSS 13.0 statistical software. According to the clinico-patho-logic factors, the difference of CCR7 expression was compared by x2 test. Kaplan-meier method was performed to calculate the survival rate, Cox regression multivariate analysis was performed to determine independent prognostic factors. Results The expression rate of CCR7 in stage

  16. Selected National Cancer Institute Breast Cancer Research Topics | NIH MedlinePlus the Magazine

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    ... associated with risk of recurrence in women with early-stage breast cancer can be used to identify the most appropriate ... novel agents, technologies, and markers for better diagnosis, prognosis, screening, prevention, and treatment of breast cancer. Summer 2014 Issue: Volume 9 Number 2 Page ...

  17. CCR7-mediated migration in the thymus controls γδ T-cell development.

    Science.gov (United States)

    Reinhardt, Annika; Ravens, Sarina; Fleige, Henrike; Haas, Jan D; Oberdörfer, Linda; Łyszkiewicz, Marcin; Förster, Reinhold; Prinz, Immo

    2014-05-01

    αβ T-cell development and selection proceed while thymocytes successively migrate through distinct regions of the thymus. For γδ T cells, the interplay of intrathymic migration and cell differentiation is less well understood. Here, we crossed C-C chemokine receptor (CCR)7-deficient (Ccr7(-/-) ) and CCR9-deficient mice (Ccr9(-/-) ) to mice with a TcrdH2BeGFP reporter background to investigate the impact of thymic localization on γδ T-cell development. γδ T-cell frequencies and numbers were decreased in CCR7-deficient and increased in CCR9-deficient mice. Transfer of CCR7- or CCR9-deficient BM into irradiated C57BL/6 WT recipients reproduced these phenotypes, pointing toward cell-intrinsic migration defects. Monitoring recent thymic emigrants by intrathymic labeling allowed us to identify decreased thymic γδ T-cell output in CCR7-deficient mice. In vitro, CCR7-deficient precursors showed normal γδ T-cell development. Immunohistology revealed that CCR7 and CCR9 expression was important for γδ T-cell localization within thymic medulla or cortex, respectively. However, γδ T-cell motility was unaltered in CCR7- or CCR9-deficient thymi. Together, our results suggest that proper intrathymic localization is important for normal γδ T-cell development.

  18. Mexico’s National Cancer Control Plan: From Development to Implementation

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    The National Cancer Institute and the Center for Global Health have had a long-standing and successful partnership with INCan, and at their request are identifying new or enhanced ways to provide technical support by way of resources, training, and collaborative programs to facilitate the implementation of the NCCP.

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    ... (OMB) for review and approval. Written comments and/or suggestions from the public and affected... comments in writing, request more information on the proposed project, or to obtain a copy of the data... developed (and is managed) by the ] National Cancer Institute (NCI) Tobacco Control Research Branch...

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    ... projects to be submitted to the Office of Management and Budget (OMB) for review and approval. Written... comments in writing, or request more information on the proposed project, contact: Dorothy Farrell, Center for Strategic Scientific Initiatives, Office of Cancer Nanotechnology Research, National...

  1. Cancer

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    ... cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer Symptoms Symptoms of cancer ... tumor Obesity Pancreatic cancer Prostate cancer Stomach cancer Testicular cancer Throat or larynx cancer Thyroid cancer Patient Instructions ...

  2. Structural insights from binding poses of CCR2 and CCR5 with clinically important antagonists: a combined in silico study.

    Directory of Open Access Journals (Sweden)

    Gugan Kothandan

    Full Text Available Chemokine receptors are G protein-coupled receptors that contain seven transmembrane domains. In particular, CCR2 and CCR5 and their ligands have been implicated in the pathophysiology of a number of diseases, including rheumatoid arthritis and multiple sclerosis. Based on their roles in disease, they have been attractive targets for the pharmaceutical industry, and furthermore, targeting both CCR2 and CCR5 can be a useful strategy. Owing to the importance of these receptors, information regarding the binding site is of prime importance. Structural studies have been hampered due to the lack of X-ray crystal structures, and templates with close homologs for comparative modeling. Most of the previous models were based on the bovine rhodopsin and β2-adrenergic receptor. In this study, based on a closer homolog with higher resolution (CXCR4, PDB code: 3ODU 2.5 Å, we constructed three-dimensional models. The main aim of this study was to provide relevant information on binding sites of these receptors. Molecular dynamics simulation was done to refine the homology models and PROCHECK results indicated that the models were reasonable. Here, binding poses were checked with some established inhibitors of high pharmaceutical importance against the modeled receptors. Analysis of interaction modes gave an integrated interpretation with detailed structural information. The binding poses confirmed that the acidic residues Glu291 (CCR2 and Glu283 (CCR5 are important, and we also found some additional residues. Comparisons of binding sites of CCR2/CCR5 were done sequentially and also by docking a potent dual antagonist. Our results can be a starting point for further structure-based drug design.

  3. Plasmodium yoelii 17XL infection up-regulates RANTES, CCR1, CCR3 and CCR5 expression, and induces ultrastructural changes in the cerebellum

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    Singh Shailesh

    2005-12-01

    Full Text Available Abstract Background Malaria afflicts 300–500 million people causing over 1 million deaths globally per year. The immunopathogenesis of malaria is mediated partly by co mplex cellular and immunomodulator interactions involving co-regulators such as cytokines and adhesion molecules. However, the role of chemokines and their receptors in malaria immunopathology remains unclear. RANTES (Regulated on Activation Normal T-Cell Expressed and Secreted is a chemokine involved in the generation of inflammatory infiltrates. Recent studies indicate that the degradation of cell-cell junctions, blood-brain barrier dysfunction, recruitment of leukocytes and Plasmodium-infected erythrocytes into and occlusion of microvessels relevant to malaria pathogenesis are associated with RANTES expression. Additionally, activated lymphocytes, platelets and endothelial cells release large quantities of RANTES, thus suggesting a unique role for RANTES in the generation and maintenance of the malaria-induced inflammatory response. The hypothesis of this study is that RANTES and its corresponding receptors (CCR1, CCR3 and CCR5 modulate malaria immunopathogenesis. A murine malaria model was utilized to evaluate the role of this chemokine and its receptors in malaria. Methods The alterations in immunomodulator gene expression in brains of Plasmodium yoelii 17XL-infected mice was analysed using cDNA microarray screening, followed by a temporal comparison of mRNA and protein expression of RANTES and its corresponding receptors by qRT-PCR and Western blot analysis, respectively. Plasma RANTES levels was determined by ELISA and ultrastructural studies of brain sections from infected and uninfected mice was conducted. Results RANTES (p Conclusion The upregulation of RANTES, CCR1, CCR3, and CCR5 mRNA, and RANTES protein mediate inflammation and cellular degradation in the cerebellum during P. yoelii 17XL malaria.

  4. 多发性骨髓瘤骨髓单个核细胞CCR1和CCR5的表达及临床意义%The expression and clinic significance of CCR1 and CCR5 in patients with multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    王晓桃; 林文远; 陈蓓莉; 刘冯; 吴洪; 刘健; 莫东华

    2009-01-01

    目的:探讨趋化因子受体CCR1和CCR5在多发性骨髓瘤(MM)患者骨髓单个核细胞(BMMNC)中的表达及临床意义.方法:半定量RT-PCR检测28例MM患者BMMNC中的CCR1和CCR5 mRNA水平.结果:46.4%患者同时表达CCR1、CCR5,17.86%患者仅表达CCR1,7.1%患者仅表达CCR5;骨质破坏>2级患者的CCR1、CCR5相对灰度值明显高于骨质破坏≤2级的患者(P<0.05);高度危险组中的CCR1、CCR5 相对灰度值明显高于中、低度危险组(P<0.05),而中、低度危险组中的CCR1、CCR5相对灰度值无显著性差异(P>0.05).结论:大部分MM 患者均表达CCR1和CCR5受体,监测CCR1、CCR5两种受体在MM中BMMNC的表达可以作为评价患者骨质破坏及预后的指标.

  5. The strength of the chemotactic response to a CCR5 binding chemokine is determined by the level of cell surface CCR5 density.

    Science.gov (United States)

    Desmetz, Caroline; Lin, Yea-Lih; Mettling, Clément; Portalès, Pierre; Rabesandratana, Herisoa; Clot, Jacques; Corbeau, Pierre

    2006-12-01

    We have shown that the intensity of expression of the C-C chemokine receptor CCR5 at the single CD4(+) cell level strongly determines the efficiency of its function as a coreceptor for human immunodeficiency virus type 1. By analogy, we examined if the number of CCR5 molecules at the cell surface might determine its chemotactic response to CCR5 ligands. To test this hypothesis, we measured by flow cytometry the migration of primary human T cells towards the CCR5-binding chemokine CCL5 in vitro. First, we observed a dose-dependent blockage of this migration exerted by an anti-CCR5 monoclonal antibody. Second, we sorted peripheral blood mononuclear cells into five subpopulations expressing various cell surface CCR5 densities, and observed a correlation between the intensity of migration towards CCL5 and the level of CCR5 expression on these subpopulations. Third, we transduced CCR5(+) peripheral blood mononuclear cells with the CCR5 gene, and observed that the CCR5 over-expression induced an over-migration towards CCL5. Finally, we observed in healthy donors a correlation between the chemotactic response of peripheral blood CD8(+) T cell to CCL5 and their level of surface CCR5 expression. T-cell surface CCR5 density, which is constant over time for a given individual, but varies drastically among individuals, might therefore be an important personal determinant of T-cell migration in many biological situations where CCR5-binding chemokines play a role, such as graft rejection, T helper 1-mediated auto-immune diseases, and infectious diseases involving CCR5. Moreover, our data highlight the therapeutic potential of CCR5 antagonists in these situations.

  6. CCR5 knockout suppresses experimental autoimmune encephalomyelitis in C57BL/6 mice

    OpenAIRE

    2016-01-01

    Multiple sclerosis (MS) is an inflammatory disease in which myelin in the spinal cord is damaged. C-C chemokine receptor type 5 (CCR5) is implicated in immune cell migration and cytokine release in central nervous system (CNS). We investigated whether CCR5 plays a role in MS progression using a murine model, experimental autoimmune encephalomyelitis (EAE), in CCR5 deficient (CCR5−/−) mice. CCR5−/− and CCR5+/+ (wild-type) mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG3...

  7. CCR5稳定表达的CHO细胞的构建%Construction of CHO Cells Stably Expressing CCR5

    Institute of Scientific and Technical Information of China (English)

    王芳宇; 潘忠诚

    2006-01-01

    在人体内,CCR5与许多免疫疾病有关,CCR5有望成为众多药物的作用靶点.将ccr5基因与真核表达载体pBBS242构建成重组质粒pBBS242-ccr5,转染CHO细胞,并经潮霉素B筛选.流式细胞仪检测结果表明CCR5在CHO细胞得到了稳定表达.

  8. Asbestos-related occupational cancers compensated under the Spanish National Insurance System, 1978–2011

    Science.gov (United States)

    García-Gómez, Montserrat; Menéndez-Navarro, Alfredo; López, Rosario Castañeda

    2015-01-01

    Background: In 1978, asbestos-related occupational cancers were added to the Spanish list of occupational diseases. However, there are no full accounts of compensated cases since their inclusion. Objective: To analyze the cases of asbestos-related cancer recognized as occupational in Spain between 1978 and 2011. Methods: Cases were obtained from the Spanish Employment Ministry. Specific incidence rates by year, economic activity, and occupation were obtained. We compared mortality rates of mesothelioma and bronchus and lung cancer mortality in Spain and the European Union. Results: Between 1978 and 2011, 164 asbestos-related occupational cancers were recognized in Spain, with a mean annual rate of 0·08 per 105 employees (0·13 in males, 0·002 in females). Under-recognition rates were an estimated 93·6% (males) and 99·7% (females) for pleural mesothelioma and 98·8% (males) and 100% (females) for bronchus and lung cancer. In Europe for the year 2000, asbestos-related occupational cancer rates ranged from 0·04 per 105 employees in Spain to 7·32 per 105 employees in Norway. Conclusions: These findings provide evidence of gross under-recognition of asbestos-related occupational cancers in Spain. Future work should investigate cases treated in the National Healthcare System to better establish the impact of asbestos on health in Spain. PMID:25335827

  9. Non-melanoma skin cancer: United Kingdom National Multidisciplinary Guidelines.

    Science.gov (United States)

    Newlands, C; Currie, R; Memon, A; Whitaker, S; Woolford, T

    2016-05-01

    This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. This paper provides consensus recommendations on the management of cutaneous basal cell carcinoma and squamous cell carcinoma in the head and neck region on the basis of current evidence. Recommendations • Royal College of Pathologists minimum datasets for NMSC should be adhered to in order to improve patient care and help work-force planning in pathology departments. (G) • Tumour depth is of critical importance in identifying high-risk cutaneous squamous cell carcinoma (cSCC), and should be reported in all cases. (R) • Appropriate imaging to determine the extent of primary NMSC is indicated when peri-neural involvement or bony invasion is suspected. (R) • In the clinically N0 neck, radiological imaging is not beneficial, and a policy of watchful waiting and patient education can be adopted. (R) • Patients with high-risk NMSC should be treated by members of a skin cancer multidisciplinary team (MDT) in secondary care. (G) • Non-infiltrative basal cell carcinoma (BCC) Radiotherapy (RT) is an effective therapy for primary BCC and cSCC. (R) • Re-excision should be carried out for incompletely excised high-risk BCC or where there is deep margin involvement. (R) • Incompletely excised high-risk cSCC should be re-excised. (R) • Further surgery should involve confirmed marginal clearance before reconstruction. (R) • P+ N0 disease: Resection should include involved parotid tissue, combined with levels I-III neck dissection, to include the external jugular node. (R) • P+ N+ disease: Resection should include level V if that level is clinically or radiologically involved. (R) • Adjuvant RT should include level V if not dissected. (R) • P0 N+ disease: Anterior neck disease should be managed with levels I-IV neck dissection to include the external jugular node. (R) • P0 N+ posterior echelon nodal disease (i

  10. Assessment of required resources for implementation of national breast cancer screening program in Serbia

    Directory of Open Access Journals (Sweden)

    Majstorović Nemanja

    2014-01-01

    Full Text Available Introduction. High values of standardized mortality and morbidity rates of standardized cancer mortality in Serbia, especially colorectal, cervical and breast cancer led to creation of national programs for their early detection and engagement of the international support for their implementation. Objective. Assessment of required resources (time, personnel, financial to implement the National program for screening of breast cancer in the Republic of Serbia. Methods. Three possible scenarios have been prepared (optimistic, realistic and pessimistic based on the expected coverage by screening of women aged 45 to 69 years, and time, personnel and financial feasibility estimates were made for a two-year screening cycle. Results. Time aspect of feasibility even under conditions of “relaxation” of the assumption on the number of working days during the year did not question feasibility of any of the scenarios. Personnel feasibility is only possible in the pessimistic scenario, while the financial feasibility only makes sense in optimistic scenario as the least unfavorable solution due to economies of scale. Conclusion. Establishment of the initial base of skilled radiologists and radiology technicians and the system for their continuous medical education as well as allocation of specific MoH budget line for screening program expenditures, along with donated mammographs and good organization and coordination, may provide unobstructed implementation of the National program for early detection of breast cancer in the Republic of Serbia.

  11. CCR5 deficiency accelerates lipopolysaccharide-induced astrogliosis, amyloid-beta deposit and impaired memory function.

    Science.gov (United States)

    Hwang, Chul Ju; Park, Mi Hee; Hwang, Jae Yeon; Kim, Ju Hwan; Yun, Na Young; Oh, Sang Yeon; Song, Ju Kyung; Seo, Hyun Ok; Kim, Yun-Bae; Hwang, Dae Yeon; Oh, Ki-Wan; Han, Sang-Bae; Hong, Jin Tae

    2016-03-15

    Chemokine receptors are implicated in inflammation and immune responses. Neuro-inflammation is associated with activation of astrocyte and amyloid-beta (Aβ) generations that lead to pathogenesis of Alzheimer disease (AD). Previous our study showed that deficiency of CC chemokine receptor 5 (CCR5) results in activation of astrocytes and Aβ deposit, and thus memory dysfunction through increase of CC chemokine receptor 2 (CCR2) expression. CCR5 knockout mice were used as an animal model with memory dysfunction. For the purpose LPS was injected i.p. daily (0.25 mg/kg/day). The memory dysfunctions were much higher in LPS-injected CCR5 knockout mice compared to CCR5 wild type mice as well as non-injected CCR5 knockout mice. Associated with severe memory dysfuction in LPS injected CCR5 knockout mice, LPS injection significant increase expression of inflammatory proteins, astrocyte activation, expressions of β-secretase as well as Aβ deposition in the brain of CCR5 knockout mice as compared with that of CCR5 wild type mice. In CCR5 knockout mice, CCR2 expressions were high and co-localized with GFAP which was significantly elevated by LPS. Expression of monocyte chemoattractant protein-1 (MCP-1) which ligands of CCR2 also increased by LPS injection, and increment of MCP-1 expression is much higher in CCR5 knockout mice. BV-2 cells treated with CCR5 antagonist, D-ala-peptide T-amide (DAPTA) and cultured astrocytes isolated from CCR5 knockout mice treated with LPS (1 μg/ml) and CCR2 antagonist, decreased the NF-ĸB activation and Aβ level. These findings suggest that the deficiency of CCR5 enhances response of LPS, which accelerates to neuro-inflammation and memory impairment.

  12. In vitro immunological effects of blocking CCR5 on T cells.

    Science.gov (United States)

    Yuan, Jing; Ren, Han-Yun; Shi, Yong-Jin; Liu, Wei

    2015-04-01

    Blockade of CC chemokine receptor 5 (CCR5) by maraviroc may induce immunological changes independent of its antiviral effects and may have immunoregulation properties. This study was designed to determine the effects of blocking CCR5 on human activated T cells in vitro and investigate the potential immunological mechanisms. Human CD3+ T cells were purified from peripheral blood mononuclear cells and then activated by cytokines. We tested the surface expressions and relative messenger RNA (mRNA) levels of CCR2, CCR5, CCR6, CCR7, and CXCR3, chemotaxis toward their cognate ligands, internalization of chemokine receptors, and production of cytokines. In conclusion, blocking CCR5 by maraviroc not only can block CCR5 and CCR2 internalization processes induced by CCL5 and CCL2, but also inhibit T cell chemotactic activities toward their cognate ligands, respectively. Moreover, blocking CCR5 with maraviroc at high doses tends to decrease the production of TNF-α and IFN-γ. In addition, there might be a form of cross talk between CCR5 and CCR2, and this may offer a novel immunological effect for blockade of CCR5.

  13. CCR5 knockout suppresses experimental autoimmune encephalomyelitis in C57BL/6 mice.

    Science.gov (United States)

    Gu, Sun Mi; Park, Mi Hee; Yun, Hyung Mun; Han, Sang Bae; Oh, Ki Wan; Son, Dong Ju; Yun, Jae Suk; Hong, Jin Tae

    2016-03-29

    Multiple sclerosis (MS) is an inflammatory disease in which myelin in the spinal cord is damaged. C-C chemokine receptor type 5 (CCR5) is implicated in immune cell migration and cytokine release in central nervous system (CNS). We investigated whether CCR5 plays a role in MS progression using a murine model, experimental autoimmune encephalomyelitis (EAE), in CCR5 deficient (CCR5-/-) mice. CCR5-/- and CCR5+/+ (wild-type) mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) followed by pertussis toxin, after which EAE paralysis was scored for 28 days. We found that clinical scoring and EAE neuropathology were lower in CCR5-/- mice than CCR5+/+ mice. Immune cells (CD3+, CD4+, CD8+, B cell, NK cell and macrophages) infiltration and astrocytes/microglial activation were attenuated in CCR5-/- mice. Moreover, levels of IL-1β, TNF-α, IFN-γ and MCP-1 cytokine levels were decreased in CCR5-/- mice spinal cord. Myelin basic protein (MBP) and CNPase were increased while NG2 and O4 were decreased in CCR5-/- mice, indicating that demyelination was suppressed by CCR5 gene deletion. These findings suggest that CCR5 is likely participating in demyelination in the spinal cord the MS development, and that it could serve as an effective therapeutic target for the treatment of MS.

  14. Transoral resection of pharyngeal cancer: summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting, November 6-7, 2011, Arlington, Virginia.

    Science.gov (United States)

    Adelstein, David J; Ridge, John A; Brizel, David M; Holsinger, F Christopher; Haughey, Bruce H; O'Sullivan, Brian; Genden, Eric M; Beitler, Jonathan J; Weinstein, Gregory S; Quon, Harry; Chepeha, Douglas B; Ferris, Robert L; Weber, Randal S; Movsas, Benjamin; Waldron, John; Lowe, Val; Ramsey, Scott; Manola, Judith; Yueh, Bevan; Carey, Thomas E; Bekelman, Justin E; Konski, Andre A; Moore, Eric; Forastiere, Arlene; Schuller, David E; Lynn, Jean; Ullmann, Claudio Dansky

    2012-12-01

    Recent advances now permit resection of many pharyngeal tumors through the open mouth, an approach that can greatly reduce the morbidity of surgical exposure. These transoral techniques are being rapidly adopted by the surgical community and hold considerable promise. On November 6-7, 2011, the National Cancer Institute sponsored a Clinical Trials Planning Meeting to address how to further investigate the use of transoral surgery, both in the good prognosis human papillomavirus (HPV)-initiated oropharyngeal cancers, and in those with HPV-unrelated disease. The proceedings of this meeting are summarized.

  15. CCR5 Expression Levels Influence NFAT Translocation, IL-2 Production, and Subsequent Signaling Events during T Lymphocyte Activation1

    OpenAIRE

    2009-01-01

    Ligands of CCR5, the major coreceptor of HIV-1, costimulate T lymphocyte activation. However, the full impact of CCR5 expression on T cell responses remains unknown. Here, we show that compared with CCR5+/+, T cells from CCR5−/− mice secrete lower amounts of IL-2, and a similar phenotype is observed in humans who lack CCR5 expression (CCR5-Δ32/Δ32 homozygotes) as well as after Ab-mediated blockade of CCR5 in human T cells genetically intact for CCR5 expression. Conversely, overexpression of C...

  16. Pattern and Distribution of Colorectal Cancer in Tanzania: A Retrospective Chart Audit at Two National Hospitals

    Directory of Open Access Journals (Sweden)

    Leonard K. Katalambula

    2016-01-01

    Full Text Available Background. Colorectal cancer (CRC is a growing public health concern with increasing rates in countries with previously known low incidence. This study determined pattern and distribution of CRC in Tanzania and identified hot spots in case distribution. Methods. A retrospective chart audit reviewed hospital registers and patient files from two national institutions. Descriptive statistics, Chi square (χ2 tests, and regression analyses were employed and augmented by data visualization to display risk variable differences. Results. CRC cases increased sixfold in the last decade in Tanzania. There was a 1.5% decrease in incidences levels of rectal cancer and 2% increase for colon cancer every year from 2005 to 2015. Nearly half of patients listed Dar es Salaam as their primary residence. CRC was equally distributed between males (50.06% and females (49.94%, although gender likelihood of diagnosis type (i.e., rectal or colon was significantly different (P=0.027. More than 60% of patients were between 40 and 69 years. Conclusions. Age (P=0.0183 and time (P=0.004 but not gender (P=0.0864 were significantly associated with rectal cancer in a retrospective study in Tanzania. Gender (P=0.0405, age (P=0.0015, and time (P=0.0075 were all significantly associated with colon cancer in this study. This retrospective study found that colon cancer is more prevalent among males at a relatively younger age than rectal cancer. Further, our study showed that although more patients were diagnosed with rectal cancer, the trend has shown that colon cancer is increasing at a faster rate.

  17. Cancer Information Seeking Among Adult New Zealanders: a National Cross-Sectional Study.

    Science.gov (United States)

    Richards, Rosalina; McNoe, Bronwen; Iosua, Ella; Reeder, Anthony; Egan, Richard; Marsh, Louise; Robertson, Lindsay; Maclennan, Brett; Dawson, Anna; Quigg, Robin; Petersen, Anne-Cathrine

    2016-11-16

    Organisations seeking to establish themselves as leading cancer information sources for the public need to understand patterns and motivators for information seeking. This study describes cancer information seeking among New Zealanders through a national cross-sectional survey conducted in 2014/15 with a population-based sample of adults (18 years and over). Participants were asked if they had sought information about cancer during the past 12 months, the type of information they sought, what prompted them to look for information and ways of getting information they found helpful. Telephone interviews were completed by 1064 participants (588 females, 476 males, 64% response rate). Of these, 33.8% of females and 23.3% of males (total, 29.2%) had searched for information about cancer over the past year. A search was most frequently prompted by a cancer diagnosis of a family member or friend (43.3%), a desire to educate themselves (17.5%), experience of potential symptoms or a positive screening test (9.4%), family history of cancer (8.9%) or the respondent's own cancer diagnosis (7.7%). Across the cancer control spectrum, the information sought was most commonly about treatment and survival (20.2%), symptoms/early detection (17.2%) or risk factors (14.2%), although many were general or non-specific queries (50.0%). The internet was most commonly identified as a helpful source of information (71.7%), followed by health professionals (35.8%), and reading material (e.g. books, pamphlets) (14.7%).This study provides a snapshot of cancer information seeking in New Zealand, providing valuable knowledge to help shape resource delivery to better meet the diverse needs of information seekers and address potential unmet needs, where information seeking is less prevalent.

  18. Frontiers in cancer epidemiology: a challenge to the research community from the Epidemiology and Genomics Research Program at the National Cancer Institute.

    Science.gov (United States)

    Khoury, Muin J; Freedman, Andrew N; Gillanders, Elizabeth M; Harvey, Chinonye E; Kaefer, Christie; Reid, Britt C; Rogers, Scott; Schully, Sheri D; Seminara, Daniela; Verma, Mukesh

    2012-07-01

    The Epidemiology and Genomics Research Program (EGRP) at the National Cancer Institute (NCI) is developing scientific priorities for cancer epidemiology research in the next decade. We would like to engage the research community and other stakeholders in a planning effort that will include a workshop in December 2012 to help shape new foci for cancer epidemiology research. To facilitate the process of defining the future of cancer epidemiology, we invite the research community to join in an ongoing web-based conversation at http://blog-epi.grants.cancer.gov/ to develop priorities and the next generation of high-impact studies.

  19. CCR9 Antagonists in the Treatment of Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Pirow Bekker

    2015-01-01

    Full Text Available While it has long been established that the chemokine receptor CCR9 and its ligand CCL25 are essential for the movement of leukocytes into the small intestine and the development of small-intestinal inflammation, the role of this chemokine-receptor pair in colonic inflammation is not clear. Toward this end, we compared colonic CCL25 protein levels in healthy individuals to those in patients with ulcerative colitis. In addition, we determined the effect of CCR9 pharmacological inhibition in the mdr1a−/− mouse model of ulcerative colitis. Colon samples from patients with ulcerative colitis had significantly higher levels of CCL25 protein compared to healthy controls, a finding mirrored in the mdr1a−/− mice. In the mdr1a−/− mice, CCR9 antagonists significantly decreased the extent of wasting and colonic remodeling and reduced the levels of inflammatory cytokines in the colon. These findings indicate that the CCR9:CCL25 pair plays a causative role in ulcerative colitis and suggest that CCR9 antagonists will provide a therapeutic benefit in patients with colonic inflammation.

  20. CCR5与艾滋病的防治

    Institute of Scientific and Technical Information of China (English)

    陈琳玲; 张佳; 高汉林; 廖端芳; 李凯

    2005-01-01

    人类获得性免疫缺乏症——艾滋病主要由于HIV-1病毒感染,在体内快速繁殖并导致宿主白细胞的大量破坏所致。在HIV进入白细胞过程中,结构正常的CCR5蛋白质起到促进HIV入胞的通道蛋白的功能。临床观察表明,CCR5的不同基因型个体对HIV的易感性有明显差异,在CCR5的几种基因变异型中,CCR5-△32的杂合子HIV携带者从病毒携带状态转变为艾滋病患者的时间较正常CCR5野生型人群长,

  1. Assessment of the psychological distress difficulties in patients with cancer using the national comprehensive cancer network rapid screening measure

    Institute of Scientific and Technical Information of China (English)

    Hamid Saeedi Saedi; Mona Koochak Pour; Emad Sabahi; Soodabeh Shahidsales

    2012-01-01

    Objective: Clinical guidelines like National Comprehensive Cancer Network Disease recommend routine psychological distress screening as a common problem among patients with cancer. The purpose of this study was to assess the prevalence of clinically significant emotional distress related to demographic and clinical association by standard distress thermometer (DT) within the patients lived in different regions of Gilan state, Iran. Methods: Participants (n = 256) completed the DT, rapid screening measure for distress and identified the presence or absence of 34 problems using the standardized checklist. Results: More than 59 percent of participants had more than 4 cut-off score for distress. The scores varied significantly in case of reported emotional source of distress, physical, physiological and total number of concerns (P < 0.001).DT scores more than four were more likely to report 22 of 32 problems on the problem list. In case of the practical and family problems, the main problems were related to child care and dealing with children, respectively. Moreover worrisome and nervousness were considered the prominent emotional problems in the list. Conclusion: Our result promise that distress thermometer measurement tool compare favorably with longer measures used to screening of distress in cancerous patients. Accompaniment of a psychologist expert in lethal or chronic disease consultation with the therapeutic team and training the rest of members of the team might be able to decrease the emotional distress problems of the cancerous patients.

  2. Specificity for a CCR5 Inhibitor Is Conferred by a Single Amino Acid Residue: ROLE OF ILE198.

    Science.gov (United States)

    Lau, Gloria; Labrecque, Jean; Metz, Markus; Vaz, Roy; Fricker, Simon P

    2015-04-24

    The chemokine receptors CCR5 and CCR2b share 89% amino acid homology. CCR5 is a co-receptor for HIV and CCR5 antagonists have been investigated as inhibitors of HIV infection. We describe the use of two CCR5 antagonists, Schering-C (SCH-C), which is specific for CCR5, and TAK-779, a dual inhibitor of CCR5 and CCR2b, to probe the CCR5 inhibitor binding site using CCR5/CCR2b chimeric receptors. Compound inhibition in the different chimeras was assessed by inhibition of chemokine-induced calcium flux. SCH-C inhibited RANTES (regulated on activation, normal T cell expressed and secreted) (CCL5)-mediated calcium flux on CCR5 with an IC50 of 22.8 nM but was inactive against monocyte chemoattractant protein-1 (CCL2)-mediated calcium flux on CCR2b. However, SCH-C inhibited CCL2-induced calcium flux against a CCR5/CCR2b chimera consisting of transmembrane domains IV-VI of CCR5 with an IC50 of 55 nM. A sequence comparison of CCR5 and CCR2b identified a divergent amino acid sequence located at the junction of transmembrane domain V and second extracellular loop. Transfer of the CCR5 sequence KNFQTLKIV into CCR2b conferred SCH-C inhibition (IC50 of 122 nM) into the predominantly CCR2b chimera. Furthermore, a single substitution, R206I, conferred partial but significant inhibition (IC50 of 1023 nM) by SCH-C. These results show that a limited amino acid sequence is responsible for SCH-C specificity to CCR5, and we propose a model showing the interaction with CCR5 Ile(198).

  3. 77 FR 57566 - Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review...

    Science.gov (United States)

    2012-09-18

    ... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review and Request for Public Comment on Potential Approaches to Electronic Delivery of the CCR;...

  4. CCR7和EGFR在非小细胞肺癌中的表达及其与淋巴结转移的关系%Expression of CCR7 And EGFR and their roles in lymph node metastasis in NSCLC

    Institute of Scientific and Technical Information of China (English)

    赵国昌; 白玉; 陈志军; 王永连; 王忠民

    2010-01-01

    目的 检洲CCR7和EGFR在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达,并分析其与肺癌临床病理特征间的关系,探讨CCR7和EGFR在NSCLC淋巴结转移中的作用.方法 选用55例NSCLC临床切除组织石蜡标本,以免疫组化SP法检测CCR7和EGFR的表达.结果 55例肺癌组织中,CCR7阳性表迭37例,阳性率为67.2%(37/55),EGFR阳性表达40例,阳性率为72.7%(40/55),二者的表达与淋巴结转移存在非常显著相关性.结论 CCR7和EGFK在NSCLC组织中高表达,且其表达与NSCLC淋巴结转移密切相关.

  5. 2014 Korean Liver Cancer Study Group-National Cancer Center Korea practice guideline for the management of hepatocellular carcinoma.

    Science.gov (United States)

    2015-01-01

    The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.

  6. Trends in Cancer Screening Rates among Korean Men and Women: Results of the Korean National Cancer Screening Survey, 2004-2013

    OpenAIRE

    Suh, Mina; Choi, Kui Son; Park, Boyoung; Lee, Yoon Young; Jun, Jae Kwan; Lee, Duk-Hyoung; Kim, Yeol

    2015-01-01

    Purpose The Korean National Cancer Screening Survey (KNCSS), a nationwide cross-sectional survey, has been conducted annually since 2004. The current study was conducted to report on the trends in screening rates among Korean men and women, and to evaluate policies regarding cancer screening programs implemented to reduce the burden of cancer. Materials and Methods The current study used KNCSS data. The eligible study population included men aged 40-74 years and women aged 30-74 years with no...

  7. HIV-1 exploits CCR5 conformational heterogeneity to escape inhibition by chemokines.

    Science.gov (United States)

    Colin, Philippe; Bénureau, Yann; Staropoli, Isabelle; Wang, Yongjin; Gonzalez, Nuria; Alcami, Jose; Hartley, Oliver; Brelot, Anne; Arenzana-Seisdedos, Fernando; Lagane, Bernard

    2013-06-04

    CC chemokine receptor 5 (CCR5) is a receptor for chemokines and the coreceptor for R5 HIV-1 entry into CD4(+) T lymphocytes. Chemokines exert anti-HIV-1 activity in vitro, both by displacing the viral envelope glycoprotein gp120 from binding to CCR5 and by promoting CCR5 endocytosis, suggesting that they play a protective role in HIV infection. However, we showed here that different CCR5 conformations at the cell surface are differentially engaged by chemokines and gp120, making chemokines weaker inhibitors of HIV infection than would be expected from their binding affinity constants for CCR5. These distinct CCR5 conformations rely on CCR5 coupling to nucleotide-free G proteins ((NF)G proteins). Whereas native CCR5 chemokines bind with subnanomolar affinity to (NF)G protein-coupled CCR5, gp120/HIV-1 does not discriminate between (NF)G protein-coupled and uncoupled CCR5. Interestingly, the antiviral activity of chemokines is G protein independent, suggesting that "low-chemokine affinity" (NF)G protein-uncoupled conformations of CCR5 represent a portal for viral entry. Furthermore, chemokines are weak inducers of CCR5 endocytosis, as is revealed by EC50 values for chemokine-mediated endocytosis reflecting their low-affinity constant value for (NF)G protein-uncoupled CCR5. Abolishing CCR5 interaction with (NF)G proteins eliminates high-affinity binding of CCR5 chemokines but preserves receptor endocytosis, indicating that chemokines preferentially endocytose low-affinity receptors. Finally, we evidenced that chemokine analogs achieve highly potent HIV-1 inhibition due to high-affinity interactions with internalizing and/or gp120-binding receptors. These data are consistent with HIV-1 evading chemokine inhibition by exploiting CCR5 conformational heterogeneity, shed light into the inhibitory mechanisms of anti-HIV-1 chemokine analogs, and provide insights for the development of unique anti-HIV molecules.

  8. CCR5 deficiency increased susceptibility to lipopolysaccharide-induced acute renal injury.

    Science.gov (United States)

    Lee, Dong Hun; Park, Mi Hee; Hwang, Chul Ju; Hwang, Jae Yeon; Yoon, Hae Suk; Yoon, Do Young; Hong, Jin Tae

    2016-05-01

    C-C chemokine receptor 5 (CCR5) regulates leukocyte chemotaxis and activation, and its deficiency exacerbates development of nephritis. Therefore, we investigated the role of CCR5 during lipopolysaccharide (LPS)-induced acute kidney injury. CCR5-deficient (CCR5-/-) and wild-type (CCR5+/+) mice, both aged about 10 months, had acute renal injury induced by intraperitoneal injection of LPS (10 mg/kg). Compared with CCR5+/+ mice, CCR5-/- mice showed increased mortality and renal injury, including elevated creatinine and blood urea nitrogen levels, following LPS challenge. Compared to CCR5+/+ mice, CCR5-/- mice also exhibited greater increases in the serum concentrations of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β following LPS challenge. Furthermore, infiltration of macrophages and neutrophils, expression of intracellular adhesion molecule (ICAM)-1, and the number of apoptotic cells were more greatly increased by LPS treatment in CCR5-/- mice than in CCR5+/+ mice. The concentrations of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β were also significantly increased in the kidney of CCR5-/- mice after LPS challenge. Moreover, primary kidney cells from CCR5-/- mice showed greater increases in TNF-α production and p38 MAP kinase activation following treatment with LPS compared with that observed in the cells from CCR5+/+ mice. LPS-induced TNF-α production and apoptosis in the primary kidney cells from CCR5-/- mice were inhibited by treatment with p38 MAP kinase inhibitor. These results suggest that CCR5 deficiency increased the production of TNF-α following LPS treatment through increased activation of the p38 pathway in the kidney, resulting in renal apoptosis and leukocyte infiltration and led to exacerbation of LPS-induced acute kidney injury.

  9. 受激活调节正常T细胞表达和分泌因子(RANTES)受体CCR1和CCR5在人附睾中的表达%Expression of Regulated upon Activation Normal T Cell Expressed and Secreted (RANTES) Receptors CCR1 and CCR5 in Human Epididymis

    Institute of Scientific and Technical Information of China (English)

    马斌芳; 孙质健; 赵洁; 魏金花; 程胖; 冯潇; 李臻

    2013-01-01

    目的:探讨受激活调节正常T细胞表达和分泌因子(RANTES)受体CCR1、CCR5在成人附睾中的表达和定位.方法:采用RT-PCR检测CCR1和CCR5 mRNA在成人附睾中的表达,免疫组织化学法观察CCR1和CCR5在人附睾中的细胞定位,免疫荧光双标染色分别检测RANTES与CCR1及CCR5的共定位情况.结果:在人附睾组织中获得了RANTES受体CCR1、CCR5的cDNA片段,免疫组织化学显示CCR1表达于输出小管的纤毛细胞,附睾管的顶细胞和基细胞;CCR5表达于附睾输出小管的纤毛细胞以及全部附睾管上皮细胞.免疫荧光双标显示RANTES分别与CCR1和CCR5的阳性信号在输出小管的纤毛细胞、附睾管的顶细胞和基细胞共存.结论:CCR1和CCR5在附睾上皮有表达,且与RANTES共定位,推测RANTES可能通过其受体在附睾中起作用,从而为精子成熟和储存提供适宜的微环境.

  10. Immunotherapy of head and neck cancer: Emerging clinical trials from a National Cancer Institute Head and Neck Cancer Steering Committee Planning Meeting.

    Science.gov (United States)

    Bauman, Julie E; Cohen, Ezra; Ferris, Robert L; Adelstein, David J; Brizel, David M; Ridge, John A; O'Sullivan, Brian; Burtness, Barbara A; Butterfield, Lisa H; Carson, William E; Disis, Mary L; Fox, Bernard A; Gajewski, Thomas F; Gillison, Maura L; Hodge, James W; Le, Quynh-Thu; Raben, David; Strome, Scott E; Lynn, Jean; Malik, Shakun

    2016-12-01

    Recent advances have permitted successful therapeutic targeting of the immune system in head and neck squamous cell carcinoma (HNSCC). These new immunotherapeutic targets and agents are being rapidly adopted by the oncologic community and hold considerable promise. The National Cancer Institute sponsored a Clinical Trials Planning Meeting to address the issue of how to further investigate the use of immunotherapy in patients with HNSCC. The goals of the meeting were to consider phase 2 or 3 trial designs primarily in 3 different patient populations: those with previously untreated, human papillomavirus-initiated oropharyngeal cancers; those with previously untreated, human papillomavirus-negative HNSCC; and those with recurrent/metastatic HNSCC. In addition, a separate committee was formed to develop integrative biomarkers for the clinical trials. The meeting started with an overview of key immune components and principles related to HNSCC, including immunosurveillance and immune escape. Four clinical trial concepts were developed at the meeting integrating different immunotherapies with existing standards of care. These designs were presented for implementation by the head and neck committees of the National Cancer Institute-funded National Clinical Trials Network. This article summarizes the proceedings of this Clinical Trials Planning Meeting, the purpose of which was to facilitate the rigorous development and design of randomized phase 2 and 3 immunotherapeutic trials in patients with HNSCC. Although reviews usually are published immediately after the meeting is held, this report is unique because there are now tangible clinical trial designs that have been funded and put into practice and the studies are being activated to accrual. Cancer 2016. © 2016 American Cancer Society.

  11. Vaginal Radical Trachelectomy for early stage cervical cancer. Results of the Danish National Single Center Strategy

    DEFF Research Database (Denmark)

    Hauerberg, L; Høgdall, C; Loft, A

    2015-01-01

    OBJECTIVE: To present and evaluate an unselected national single center strategy with fertility preserving trachelectomy in cervical cancer. In 2003 nationwide single-center referral of women for trachelectomies was agreed upon between all Danish departments performing cervical cancer surgery...... with the purpose of increasing volume, to increase surgical safety and facilitate follow-up. METHODS: Prospective data were recorded in the Danish Gynecological Cancer Database of all Vaginal Radical Trachelectomies (VRT) performed in Denmark between 2002 and 2013. Oncologic, fertility and obstetrical outcomes...... of 120 unselected consecutive VRTs were assessed. To obtain complete follow-up about fertility treatment, pregnancy and obstetric outcome the women filled out an electronic questionnaire. Median follow-up: 55.7 months. RESULTS: 85.8% of the patients had stage IB1 disease, 68.3% squamous cell carcinomas...

  12. Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting.

    Science.gov (United States)

    Thomas, Melanie B; Jaffe, Deborah; Choti, Michael M; Belghiti, Jacques; Curley, Steven; Fong, Yuman; Gores, Gregory; Kerlan, Robert; Merle, Phillipe; O'Neil, Bert; Poon, Ronnie; Schwartz, Lawrence; Tepper, Joel; Yao, Francis; Haller, Daniel; Mooney, Margaret; Venook, Alan

    2010-09-01

    Hepatocelluar carcinoma (HCC) is the most common primary malignancy of the liver in adults and the third most common cause of cancer death worldwide. The incidence of HCC in the United States is rising steadily because of the prevalence of hepatitis C viral infection and other causes of hepatic cirrhosis. The majority of patients have underlying hepatic dysfunction, which complicates patient management and the search for safe and effective therapies. The Clinical Trials Planning Meeting (CTPM) in HCC was convened by the National Cancer Institute's Gastrointestinal Cancer Steering Committee to identify the key knowledge gaps in HCC and define clinical research priorities. The CTPM structured its review according to current evidence-based treatment modalities in HCC and prioritized the recommendations on the basis of the patient populations representing the greatest unmet medical need.

  13. Use of G-protein-coupled and -uncoupled CCR5 receptors by CCR5 inhibitor-resistant and -sensitive human immunodeficiency virus type 1 variants.

    Science.gov (United States)

    Berro, Reem; Yasmeen, Anila; Abrol, Ravinder; Trzaskowski, Bartosz; Abi-Habib, Sarya; Grunbeck, Amy; Lascano, Danny; Goddard, William A; Klasse, Per Johan; Sakmar, Thomas P; Moore, John P

    2013-06-01

    Small-molecule CCR5 inhibitors such as vicriviroc (VVC) and maraviroc (MVC) are allosteric modulators that impair HIV-1 entry by stabilizing a CCR5 conformation that the virus recognizes inefficiently. Viruses resistant to these compounds are able to bind the inhibitor-CCR5 complex while also interacting with the free coreceptor. CCR5 also interacts intracellularly with G proteins, as part of its signal transduction functions, and this process alters its conformation. Here we investigated whether the action of VVC against inhibitor-sensitive and -resistant viruses is affected by whether or not CCR5 is coupled to G proteins such as Gαi. Treating CD4(+) T cells with pertussis toxin to uncouple the Gαi subunit from CCR5 increased the potency of VVC against the sensitive viruses and revealed that VVC-resistant viruses use the inhibitor-bound form of Gαi-coupled CCR5 more efficiently than they use uncoupled CCR5. Supportive evidence was obtained by expressing a signaling-deficient CCR5 mutant with an impaired ability to bind to G proteins, as well as two constitutively active mutants that activate G proteins in the absence of external stimuli. The implication of these various studies is that the association of intracellular domains of CCR5 with the signaling machinery affects the conformation of the external and transmembrane domains and how they interact with small-molecule inhibitors of HIV-1 entry.

  14. Relationship between expression of chemokine receptors CCR3,CCR5 and CXCR3 on CD4+ T cells and spontaneous abortion in mice

    Institute of Scientific and Technical Information of China (English)

    JIANG Pei-juan; LIN Qi-de; BAO Shi-min; ZHAO Ai-min; ZHANG Yu; XIAO Shi-jin

    2009-01-01

    Background Previous studies have shown that local immune cells in the feto-maternal interface are recruited from peripheral blood, and that chemokines and their receptors play an initial and key role in this recruitment process. In this study, we aimed to determine whether spontaneous abortion is associated with the expression of chemokine receptors CCR3, CCR5, and CXCR3 on CD4+ T cells.Methods Peripheral blood, spleen, and thymus were collected from the spontaneous abortion mouse model CBA/J×DBN2 (SA group, n=14), the normal pregnant mouse model CBA/J×BALB/c (NP group, n=13), and normal non-pregnant CBA/J mice (NNP group, n=11). The number of chemokine receptors CCR3, CCR5, and CXCR3 expressed on CD4+ T cells was measured by double-label flow cytometry (FCM) method.Results In peripheral blood, the SA group had significantly lower CCR3 expression (P 0.05). In spleen, the SA group expressed significantly lower CCR3 expression (P 0.05). In thymus, the SA group had significantly lower CCR3 expression (P 0.05). Compared with the NNP group, the SA group had higher CCR3 expression (P 0.05) between the two groups.Conclusion The abnormal expression of CCR3, CCR5 and CXCR3 on CD4+ T cells may play an important role in the pathogenesis of spontaneous abortion.

  15. CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Madsen, Hans O; Jensen, Claus V

    2000-01-01

    Chemokines and matrix metalloproteinases (MMPs) appear to be crucial in leukocyte recruitment to the central nervous system in multiple sclerosis (MS). CCR5 delta32, a truncated allele of the CC chemokine receptor CCR5 gene encoding a non-functional receptor, did not confer protection from MS. CCR5...

  16. CCR7 facilitates the pro-inflammatory function of dendritic cells in experimental leishmaniasis.

    Science.gov (United States)

    Kling, J C; Darby, J; Körner, H

    2014-04-01

    Cutaneous leishmaniasis, caused by the parasite Leishmania major, results in lesions at the site of infection, which are self-healing in resistant hosts. However, in the absence of the chemokine receptor CCR7, mice are unable to heal the lesion and develop chronic disease. These B6.CCR7(-/-) mice display an increased number of Th2 cells and immunosuppressive cytokine levels, as well as more regulatory T cells. As CCR7 is expressed on activated dendritic cells (DCs), and these cells require CCR7 to migrate to the draining lymph node, we expected decreased migration of DCs into the lymph node in the absence of CCR7 during cutaneous leishmaniasis. Consequently, in an attempt to initiate a self-healing response, we adoptively transferred CCR7(+) (B6.WT) DCs into the site of infection of B6.CCR7(-/-) mice. Surprisingly, instead of healing the lesion, B6.CCR7(-/-) mice inoculated with B6.WT DCs developed augmented lesions and showed increased immunosuppression compared to control B6.CCR7(-/-) mice transferred with B6.CCR7(-/-) DCs or B6.WT mice with B6.WT DCs. Finally, B6.WT mice injected with B6.CCR7(-/-) DCs also presented delayed healing of the lesion. These results indicate that CCR7 must be expressed on DCs, as well as peripheral cells, to allow an efficient immune response to L. major.

  17. Genetic Association of the CCR5 Region With Lipid Levels in At-Risk Cardiovascular Patients

    NARCIS (Netherlands)

    C.L. Hyde; A. MacInnes; F.A. Sanders; J.F. Thompson; R.A. Mazzarella; O. Faergeman; D.F. van Wijk; L. Wood; M. Lira; S.A. Paciga

    2010-01-01

    Background-There is mounting evidence to suggest that chemokine receptor 5 (CCR5) plays an important role in the development and progression of atherosclerosis. A naturally occurring variant of the CCR5 gene CCR532, exists at allele frequencies of typically 10% in European populations and results in

  18. CCR5 Delta 32 genotype is associated with outcome in type 2 diabetes mellitus

    NARCIS (Netherlands)

    Muntinghe, Friso L. H.; Gross, Sascha; Bakker, Stephan J. L.; Landman, Gijs W. D.; van der Harst, Pim; Bilo, Henk J. G.; Navis, Gerjan; Zuurman, Mike W.

    2009-01-01

    Aims: To test whether the genetic variant CCR5 Delta 32 in the CC-chemokine receptor 5, which is known to lead to CCR5 deficiency, is associated with mortality in type 2 diabetes patients. Methods: We examined the effect of presence or absence of the CCR5 Delta 32 on overall and cardiovascular morta

  19. Epidemiology of cancer in end-stage renal disease dialysis patients: a national cohort study in Taiwan

    Science.gov (United States)

    Chien, Chih-Chiang; Han, Ming-Ming; Chiu, Yu-Hsien; Wang, Jhi-Joung; Chu, Chin-Chen; Hung, Chien-Ya; Sun, Yih-Min; Yeh, Nai-Cheng; Ho, Chung-Han; Lin, Chih-Ching; Kao, Hao-Yun; Weng, Shih-Feng

    2017-01-01

    The incidence and mortality of site-specific cancers in patients with end-stage renal disease (ESRD) on maintenance dialysis have been rarely studied for Asian populations. We tapped Taiwan`s National Health Insurance Research Database to identify and recruit patients starting maintenance dialysis between 1999 and 2004. They were followed from initiation of dialysis until death, discontinuation of dialysis, or the end of 2008. We calculated the survival rate and mortality risk of dialysis patients with cancer. Of 40,833 dialysis patients, 2352 (5.8%) had been newly diagnosed with cancer. Being older, being male, and having chronic liver disease were factors associated with a higher risk for new cancer in ESRD dialysis patients. In men, liver cancer (20.63%) was the most frequent, followed by cancers of the bladder (16.88%) and kidney (11.61%). In women, bladder cancer (25.57%) was the most frequent, followed by cancers of the kidney (16.31%) and breast (11.20%). The 5-year survival rates for kidney and bladder cancer were higher than for other cancers; the survival rates for lung, stomach, and liver cancer were lower. In conclusion, the distribution of site-specific cancer was different between men and women in patients with ESRD on dialysis. More attention should be paid to teaching dialysis patients how to avoid the well-known cancer risks and carcinogens and individualized regular cancer screenings. PMID:28123593

  20. CCR7上调MMP-9表达促进非小细胞肺癌转移%Chemokine Receptor 7 Induces Metastasis of NSCLC via Upregulating MMP-9 Expression

    Institute of Scientific and Technical Information of China (English)

    李洋; 刘巍; 方莉; 南娟; 张占雀; 周清华

    2010-01-01

    背景与目的 趋化因子激素受体(CC chemokine receptor 7,CCR7)与非小细胞肺癌(non-small celllung cancer,NSCLC)的淋巴结转移密切相关,但CCR7促进其淋巴结转移的机制尚不明了.本研究通过观察CCR7和MMP.9在NSCLC组织中的表达和相互关系.探讨CCR7促进NSCLC淋巴结转移的机制.方法 应用免疫组织化学染色(SP法)检测90例NSCLC组织中CCR7、MMP-9的表达;将BEI细胞经趋化因子CCLl9处理24 hA,应用RT-PCR和Western blot方法检测MMP-9 mRNA和蛋白表达水平.结果 免疫组织化学结果显示:CCR7主要表达于癌细胞胞质和(或)胞膜,MMP-9主要表达于癌细胞胞质,NSCLC中CCR7、MMP.9阳性表达率分别为70%(63/90)和65.5%(59/90),X2检验显示CCR7和MMP-9表达与NSCLC的临床病理分期(P=0.003,P=0.001)和淋巴结转移(P=0.0042 P=0.003)密切相关,而与年龄、组织学类型、分化程度无关(P>0.05).此外,CCR7和MMP-9表达正相关(r=0.342,P=0.001).CCL21处理组BEI细胞后MMP-9 mRNA和蛋白水平均上调(P<0.05).结论 CCR7和MMP-9表达与NSCLC侵袭转移密切相关,CCL19/CCR7通过上调NSCLC中MMP-9表达促进其转移.

  1. Eurocan plus report: feasibility study for coordination of national cancer research activities.

    Science.gov (United States)

    2008-01-01

    The EUROCAN+PLUS Project, called for by the European Parliament, was launched in October 2005 as a feasibility study for coordination of national cancer research activities in Europe. Over the course of the next two years, the Project process organized over 60 large meetings and countless smaller meetings that gathered in total over a thousand people, the largest Europe-wide consultation ever conducted in the field of cancer research.Despite a strong tradition in biomedical science in Europe, fragmentation and lack of sustainability remain formidable challenges for implementing innovative cancer research and cancer care improvement. There is an enormous duplication of research effort in the Member States, which wastes time, wastes money and severely limits the total intellectual concentration on the wide cancer problem. There is a striking lack of communication between some of the biggest actors on the European scene, and there are palpable tensions between funders and those researchers seeking funds.It is essential to include the patients' voice in the establishment of priority areas in cancer research at the present time. The necessity to have dialogue between funders and scientists to establish the best mechanisms to meet the needs of the entire community is evident. A top priority should be the development of translational research (in its widest form), leading to the development of effective and innovative cancer treatments and preventive strategies. Translational research ranges from bench-to-bedside innovative cancer therapies and extends to include bringing about changes in population behaviours when a risk factor is established.The EUROCAN+PLUS Project recommends the creation of a small, permanent and independent European Cancer Initiative (ECI). This should be a model structure and was widely supported at both General Assemblies of the project. The ECI should assume responsibility for stimulating innovative cancer research and facilitating processes

  2. Combined Effect of CCR5-Δ32 Heterozygosity and the CCR5 Promoter Polymorphism −2459 A/G on CCR5 Expression and Resistance to Human Immunodeficiency Virus Type 1 Transmission

    OpenAIRE

    2005-01-01

    Exposed seronegative individuals (ES) with persistent high-risk sexual behavior may be less susceptible to human immunodeficiency virus type 1 (HIV-1) infection because they carry the chemokine receptor (CR) gene alleles CCR5 open reading frame (ORF) Δ32, CCR5 promoter −2459G, or CCR2 ORF 64I (CCR2-64I), all of which have been found to diminish HIV-1 infectivity and/or disease progression. To investigate this, we determined the haplotypes for these three genetic loci in 93 ES and 247 low-risk...

  3. Combined 3D-QSAR modeling and molecular docking study on azacycles CCR5 antagonists

    Science.gov (United States)

    Ji, Yongjun; Shu, Mao; Lin, Yong; Wang, Yuanqiang; Wang, Rui; Hu, Yong; Lin, Zhihua

    2013-08-01

    The beta chemokine receptor 5 (CCR5) is an attractive target for pharmaceutical industry in the HIV-1, inflammation and cancer therapeutic areas. In this study, we have developed quantitative structure activity relationship (QSAR) models for a series of 41 azacycles CCR5 antagonists using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and Topomer CoMFA methods. The cross-validated coefficient q2 values of 3D-QASR (CoMFA, CoMSIA, and Topomer CoMFA) methods were 0.630, 0.758, and 0.852, respectively, the non-cross-validated R2 values were 0.979, 0.978, and 0.990, respectively. Docking studies were also employed to determine the most probable binding mode. 3D contour maps and docking results suggested that bulky groups and electron-withdrawing groups on the core part would decrease antiviral activity. Furthermore, docking results indicated that H-bonds and π bonds were favorable for antiviral activities. Finally, a set of novel derivatives with predicted activities were designed.

  4. Differences in Cancer Information Seeking Behavior, Preferences, and Awareness Between Cancer Survivors and Healthy Controls: A National, Population-Based Survey

    Science.gov (United States)

    Roach, Abbey R.; Lykins, Emily L.B.; Gochett, Celestine G.; Brechting, Emily H.; Graue, Lili O.; Andrykowski, Michael A.

    2012-01-01

    Background No research has examined how cancer diagnosis and treatment might alter information source preferences or opinions. Methods Data from 719 cancer survivors (CS group) and 2012 matched healthy controls (NCC group) regarding cancer-related information seeking behavior, preferences, and awareness from the population-based 2003 Health Information National Trends Survey (HINTS) was examined. Results The CS group reported greater consumption of cancer-related information but the CS and NCC groups did not differ in information source use or preferences. The CS group was more confident of their ability to get cancer information, reported more trust in health care professionals and television as cancer information sources, but evaluated their recent cancer information seeking experiences more negatively than the NCC group. Awareness of cancer information resources was surprisingly low in both the CS and NCC groups. Conclusions Cancer diagnosis and treatment subtly alters cancer information seeking preferences and experience. However awareness and use of cancer information resources was relatively low regardless of personal history of cancer. PMID:19259869

  5. 趋化因子受体CXCR4及CCR5真核表达载体的构建及其在卵巢癌细胞中的表达%Construction and expression of vectors carrying chemokine receptors CXCR4/CCR5 in SKOV3 cells

    Institute of Scientific and Technical Information of China (English)

    谢婷婷; 魏莉; 宋辉; 于月成

    2010-01-01

    目的:构建人CXCR4及CCR5真核表达重组质粒,转染人卵巢癌细胞SKOV3,建立稳定转染细胞系并观察其表达效果.方法:从人外周血单个核细胞中提取RNA,采用反转录PCR技术扩增CXCR4及CCR5的基因编码序列,将序列克隆至真核表达载体pEGFP,经酶切和测序鉴定后,应用脂质体转染技术将质粒cancer.pEGFP-CXCR4和pEGFP-CCR5分别导入不表达CXCR4及CCR5蛋白的SKOV3细胞,经G418抗性筛选得到阳性细胞克隆并扩大培养成系.分别采用免疫荧光染色和流式细胞术方法(FCM)检测稳定转染细胞株CXCR4和CCR5的表达.结果:构建了真核表达载体pEG-FP-CXCR4和pEGFP-CCR5;得到了抗G418阳性细胞克隆;免疫荧光染色和FCM检测结果显示,转染质粒的SKOV3细胞表达CXCR4和CCR5.结论:成功建立稳定表达趋化因子受体CXCR4和CCR5的卵巢癌细胞株,为CXCR4和CCR5在卵巢癌中的研究工作提供依据及平台.

  6. Gender Differences in Elders’ Participation in the National Can-cer Screening Program: Evidence from the Korean National Health and Nutrition Examination Survey 2010–12

    Directory of Open Access Journals (Sweden)

    Yang-Hyun KIM

    2015-10-01

    Full Text Available Background: Cancer-screening programs are effective in reducing cancer prevalence and mortality; however, cancer remains the leading cause of death in elderly people in Korea. The aim of this study was to identify the factors associated with elders’ participation in the National Cancer Screening Program (NCSP and differences in screening rates by gender.Methods: Original data from the Korea National Health and Nutrition and Examination Survey were analyzed by logistic regression analysis. The sample consisted of 5,505 elderly individuals over age 60. Selected demographic variables, cancer screening participation, physical and psychological health status, and lifestyle were examined.Results: The NCSP participation rates decreased in both men and women as age increased. Private medical insurance (OR 95% CI: 1.04–1.78, one or more chronic disease (OR 95% CI: 1.07–1.71, and current smoker (OR 95% CI: 0.52–0.94 had the strongest associations with cancer screening participation among men after multivariate adjustment. In contrast, cancer screening participation among women was significantly associated only with living place (OR 95% CI: 1.06–2.203 after multivariate adjustment.Conclusions: Effective health promoting interventions for elders require individualized programs that address gender-related factors associated with elders’ participation in cancer screening programs.

  7. Can the National Health Service Cancer Plan timeline be applied to colorectal hepatic metastases?

    LENUS (Irish Health Repository)

    Jones, Claire

    2012-02-01

    INTRODUCTION: The National Health Service (NHS) Cancer Plan guidelines recommend a maximum 2-week wait from referral to first appointment, and 2 months from referral to treatment for primary cancers. However, there are currently no guidelines available for metastatic disease. In the UK, nearly half of all colorectal cancer patients develop hepatic metastases. Timely, surgical resection offers the potential for cure. The aim of this study was to audit current practice for colorectal liver metastases in a regional hepatobiliary unit, and compare this to the NHS Cancer Plan standards for primary disease. PATIENTS AND METHODS: A retrospective review of the unit\\'s database was performed for all hepatic metastases referrals from January 2006 to December 2008. The dates of referral, first appointment, investigations and initiation of treatment, along with patient\\'s age and sex, were recorded on Microsoft Excel and analysed. Time was expressed as mean +\\/- SD in days. RESULTS: A total of 102 patients with hepatic metastases were identified. Five were excluded due to incomplete data. The average time from referral to first appointment was 10.6 +\\/- 9.4 days and the average time from referral to treatment was 38.5 +\\/- 28.6 days. Seventy-five (72.7%) had surgical intervention, of whom 37 also had chemotherapy. CONCLUSIONS: The data compare favourably to the NHS Cancer Plan guidelines for primary malignancy, demonstrating that a regional hepatobiliary unit is capable of delivering a service for colorectal liver metastases that adheres to the NHS Cancer Plan. Therefore, the NHS Cancer Plan can be applied to this cohort.

  8. Prevalence of CCR5-Δ32 and CCR2-V64I polymorphisms in a mixed population from northeastern Brazil.

    Science.gov (United States)

    Ferreira-Fernandes, H; Santos, A C C; Motta, F J N; Canalle, R; Yoshioka, F K N; Burbano, R R; Rey, J A; da Silva, B B; Pinto, G R

    2015-10-02

    Chemokines are low-molecular weight proteins that play a key role in inflammatory processes. Genomic variations in chemokine receptors are associated with the susceptibility to various diseases. Polymorphisms in chemokine receptor type 5 (CCR5)-Δ32 and CCR2-V64I are related to human immunodeficiency virus infection resistance, which has led to genetic association studies for several other diseases. Given the heterogeneous distribution of these polymorphisms in different global populations and within Brazilian populations, we analyzed the prevalence of CCR5-Δ32 and CCR2-V64I polymorphisms in a mixed population from northeastern Brazil. The study included 223 individuals from the general population of the city of Parnaíba, Piauí, who had a mean age of 73 years. Of these individuals, 37.2% were men and 62.8% were women. Polymorphisms were analyzed using DNA extracted from peripheral blood leukocytes by using polymerase chain reaction alone (CCR5-Δ32) or accompanied by restriction endonuclease digestion (CCR2-V64I). In both cases, the genotypes were determined using 8% polyacrylamide gel electrophoresis and silver nitrate staining. The population conformed to Hardy-Weinberg equilibrium for both the loci studied. No individuals were homozygous for allele-Δ32, which was present in 1.8% of the population, whereas allele-64I was present in 13.9% of the participants studied; 74.9% were homozygous for the wild-type allele, while 22.4 and 2.7% were heterozygous and homozygous for the mutant allele, respectively. Additional studies are needed to investigate the relationship between these polymorphisms and disease etiopathogenesis in reference populations.

  9. The Regina Elena National Cancer Institute process of accreditation according to the standards of the Organisation of European Cancer Institutes.

    Science.gov (United States)

    Canitano, Stefano; Di Turi, Annunziata; Caolo, Giuseppina; Pignatelli, Adriana C; Papa, Elena; Branca, Marta; Cerimele, Marina; De Maria, Ruggero

    2015-01-01

    The accreditation process is, on the one hand, a tool used to homogenize procedures, rendering comparable and standardized processes of care, and on the other, a methodology employed to develop a culture of quality improvement. Although not yet proven by evidence-based studies that health outcomes improve as a result of an accreditation to excellence, it is undeniable that better control of healthcare processes results in better quality and safety of diagnostic and therapeutic pathways. The Regina Elena National Cancer Institute underwent the accreditation process in accordance with the standards criteria set by the Organisation of European Cancer Institutes (OECI), and it has recently completed the process, acquiring its designation as a Comprehensive Cancer Center (CCC). This was an invaluable opportunity for the Regina Elena Institute to create a more cohesive environment, to widely establish a culture of quality, to implement an institutional information system, and to accelerate the process of patient involvement in strategic decisions. The steps of the process allowed us to evaluate the performance and the organization of the institute and put amendments in place designed to be adopted through 26 improvement actions. These actions regarded several aspects of the institute, including quality culture, information communication technology system, care, clinical trials unit, disease management team, nursing, and patient empowerment and involvement. Each area has a timeline. We chose to present the following 3 improvement actions: clinical trial center, computerized ambulatory medical record, and centrality of patient and humanization of clinical pathway.

  10. National Cancer Data Base Analysis of Radiation Therapy Consolidation Modality for Cervical Cancer: The Impact of New Technological Advancements

    Energy Technology Data Exchange (ETDEWEB)

    Gill, Beant S. [Department of Radiation Oncology, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Lin, Jeff F. [Department of Gynecologic Oncology, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Krivak, Thomas C. [Department of Gynecologic Oncology, Western Pennsylvania Hospital, Pittsburgh, Pennsylvania (United States); Sukumvanich, Paniti; Laskey, Robin A.; Ross, Malcolm S.; Lesnock, Jamie L. [Department of Gynecologic Oncology, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Beriwal, Sushil, E-mail: beriwals@upmc.edu [Department of Radiation Oncology, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States)

    2014-12-01

    Purpose: To utilize the National Cancer Data Base to evaluate trends in brachytherapy and alternative radiation therapy utilization in the treatment of cervical cancer, to identify associations with outcomes between the various radiation therapy modalities. Methods and Materials: Patients with International Federation of Gynecology and Obstetrics stage IIB-IVA cervical cancer in the National Cancer Data Base who received treatment from January 2004 to December 2011 were analyzed. Overall survival was estimated by the Kaplan-Meier method. Univariate and multivariable analyses were performed to identify factors associated with type of boost radiation modality used and its impact on survival. Results: A total of 7654 patients had information regarding boost modality. A predominant proportion of patients were Caucasian (76.2%), had stage IIIB (48.9%) disease with squamous (82.0%) histology, were treated at academic/research centers (47.7%) in the South (34.8%), and lived 0 to 5 miles (27.9%) from the treating facility. A majority received brachytherapy (90.3%). From 2004 to 2011, brachytherapy use decreased from 96.7% to 86.1%, whereas intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) use increased from 3.3% to 13.9% in the same period (P<.01). Factors associated with decreased brachytherapy utilization included older age, stage IVA disease, smaller tumor size, later year of diagnosis, lower-volume treatment centers, and facility type. After controlling for significant factors from survival analyses, IMRT or SBRT boost resulted in inferior overall survival (hazard ratio, 1.86; 95% confidence interval, 1.35-2.55; P<.01) as compared with brachytherapy. In fact, the survival detriment associated with IMRT or SBRT boost was stronger than that associated with excluding chemotherapy (hazard ratio, 1.61′ 95% confidence interval, 1.27-2.04′ P<.01). Conclusions: Consolidation brachytherapy is a critical treatment component for

  11. Who tended to continue smoking after cancer diagnosis: the national health and nutrition examination survey 1999–2008

    Directory of Open Access Journals (Sweden)

    Tseng Tung-Sung

    2012-09-01

    Full Text Available Abstract Background It has been estimated that there are approximately 12 million cancer survivors in the United States. Continued smoking after a cancer diagnosis is linked to adverse effects among cancer survivors on overall survival, treatment effectiveness, and quality of life. Little is known about who is more likely to quit smoking after his/her cancer diagnosis. The objective of this study is to evaluate factors associated with smoking cessation in cancer survivors, which to date has not been well studied. Method The National Health and Nutrition Examination Survey (NHANES 1999–2008 surveys were used in this study. A total of 2,374 cancer survivors aged 20 and over with valid smoking status in the NHANES 99–08 survey were included in this study. Among them, 566 cancer survivors who regularly smoked at the time of their cancer diagnosis were included in the analyses. Results Around 50.6% of cancer survivors smoked regularly prior to their cancer diagnosis and only 36.1% of them quit smoking after their cancer diagnosis. Racial disparity was observed in smoking cessation among cancer survivors. Hispanics (OR = 0.23, 95% CI = 0.10-0.57 were less likely to quit smoking than Whites after their cancer diagnosis. Conclusion Two-thirds of cancer survivors continued smoking after cancer diagnosis. Our study observed that the high risk group of continued smokers among cancer survivors is made up of those who are female, younger, Hispanic, with longer smoking history, underweight or with normal weight and without smoking-related cancer. These findings suggest that smoking cessation for cancer survivors should target on the high risk subgroups.

  12. Creating a “culture of research” in a community hospital: Strategies and tools from the National Cancer Institute Community Cancer Centers Program

    Science.gov (United States)

    St. Germain, Diane; Nacpil, Lianne M; Zaren, Howard A; Swanson, Sandra M; Minnick, Christopher; Carrigan, Angela; Denicoff, Andrea M; Igo, Kathleen E; Acoba, Jared D; Gonzalez, Maria M; McCaskill-Stevens, Worta

    2015-01-01

    Background The value of community-based cancer research has long been recognized. In addition to the National Cancer Institute’s Community Clinical and Minority-Based Oncology Programs established in 1983, and 1991 respectively, the National Cancer Institute established the National Cancer Institute Community Cancer Centers Program in 2007 with an aim of enhancing access to high-quality cancer care and clinical research in the community setting where most cancer patients receive their treatment. This article discusses strategies utilized by the National Cancer Institute Community Cancer Centers Program to build research capacity and create a more entrenched culture of research at the community hospitals participating in the program over a 7-year period. Methods To facilitate development of a research culture at the community hospitals, the National Cancer Institute Community Cancer Centers Program required leadership or chief executive officer engagement; utilized a collaborative learning structure where best practices, successes, and challenges could be shared; promoted site-to-site mentoring to foster faster learning within and between sites; required research program assessments that spanned clinical trial portfolio, accrual barriers, and outreach; increased identification and use of metrics; and, finally, encouraged research team engagement across hospital departments (navigation, multidisciplinary care, pathology, and disparities) to replace the traditionally siloed approach to clinical trials. Limitations The health-care environment is rapidly changing while complexity in research increases. Successful research efforts are impacted by numerous factors (e.g. institutional review board reviews, physician interest, and trial availability). The National Cancer Institute Community Cancer Centers Program sites, as program participants, had access to the required resources and support to develop and implement the strategies described. Metrics are an important

  13. Clinical–Pathologic Stage Discrepancy in Bladder Cancer Patients Treated With Radical Cystectomy: Results From the National Cancer Data Base

    Energy Technology Data Exchange (ETDEWEB)

    Gray, Phillip J. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Lin, Chun Chieh; Jemal, Ahmedin [Surveillance and Health Services Research Program, American Cancer Society, Atlanta, Georgia (United States); Shipley, William U. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Fedewa, Stacey A. [Surveillance and Health Services Research Program, American Cancer Society, Atlanta, Georgia (United States); Kibel, Adam S. [Division of Urology, Brigham and Women' s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Rosenberg, Jonathan E. [Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kamat, Ashish M. [Division of Surgery, Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Virgo, Katherine S. [Department of Health Policy and Management, Emory University, Atlanta, Georgia (United States); Blute, Michael L. [Department of Urology, Massachusetts General Hospital, Boston, Massachusetts (United States); Zietman, Anthony L. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Efstathiou, Jason A., E-mail: jefstathiou@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2014-04-01

    Purpose: To examine the accuracy of clinical staging and its effects on outcome in bladder cancer (BC) patients treated with radical cystectomy (RC), using a large national database. Methods and Materials: A total of 16,953 patients with BC without distant metastases treated with RC from 1998 to 2009 were analyzed. Factors associated with clinical–pathologic stage discrepancy were assessed by multivariate generalized estimating equation models. Survival analysis was conducted for patients treated between 1998 and 2004 (n=7270) using the Kaplan-Meier method and Cox proportional hazards models. Results: At RC 41.9% of patients were upstaged, whereas 5.9% were downstaged. Upstaging was more common in females, the elderly, and in patients who underwent a more extensive lymphadenectomy. Downstaging was less common in patients treated at community centers, in the elderly, and in Hispanics. Receipt of preoperative chemotherapy was highly associated with downstaging. Five-year overall survival rates for patients with clinical stages 0, I, II, III, and IV were 67.2%, 62.9%, 50.4%, 36.9%, and 27.2%, respectively, whereas those for the same pathologic stages were 70.8%, 75.8%, 63.7%, 41.5%, and 24.7%, respectively. On multivariate analysis, upstaging was associated with increased 5-year mortality (hazard ratio [HR] 1.80, P<.001), but downstaging was not associated with survival (HR 0.88, P=.160). In contrast, more extensive lymphadenectomy was associated with decreased 5-year mortality (HR 0.76 for ≥10 lymph nodes examined, P<.001), as was treatment at an National Cancer Institute–designated cancer center (HR 0.90, P=.042). Conclusions: Clinical–pathologic stage discrepancy in BC patients is remarkably common across the United States. These findings should be considered when selecting patients for preoperative or nonoperative management strategies and when comparing the outcomes of bladder sparing approaches to RC.

  14. CCL5/CCR5 axis induces vascular endothelial growth factor-mediated tumor angiogenesis in human osteosarcoma microenvironment.

    Science.gov (United States)

    Wang, Shih-Wei; Liu, Shih-Chia; Sun, Hui-Lung; Huang, Te-Yang; Chan, Chia-Han; Yang, Chen-Yu; Yeh, Hung-I; Huang, Yuan-Li; Chou, Wen-Yi; Lin, Yu-Min; Tang, Chih-Hsin

    2015-01-01

    Chemokines modulate angiogenesis and metastasis that dictate cancer development in tumor microenvironment. Osteosarcoma is the most frequent bone tumor and is characterized by a high metastatic potential. Chemokine CCL5 (previously called RANTES) has been reported to facilitate tumor progression and metastasis. However, the crosstalk between chemokine CCL5 and vascular endothelial growth factor (VEGF) as well as tumor angiogenesis in human osteosarcoma microenvironment has not been well explored. In this study, we found that CCL5 increased VEGF expression and production in human osteosarcoma cells. The conditioned medium (CM) from CCL5-treated osteosarcoma cells significantly induced tube formation and migration of human endothelial progenitor cells. Pretreatment of cells with CCR5 antibody or transfection with CCR5 specific siRNA blocked CCL5-induced VEGF expression and angiogenesis. CCL5/CCR5 axis demonstrably activated protein kinase Cδ (PKCδ), c-Src and hypoxia-inducible factor-1 alpha (HIF-1α) signaling cascades to induce VEGF-dependent angiogenesis. Furthermore, knockdown of CCL5 suppressed VEGF expression and attenuated osteosarcoma CM-induced angiogenesis in vitro and in vivo. CCL5 knockdown dramatically abolished tumor growth and angiogenesis in the osteosarcoma xenograft animal model. Importantly, we demonstrated that the expression of CCL5 and VEGF were correlated with tumor stage according the immunohistochemistry analysis of human osteosarcoma tissues. Taken together, our findings provide evidence that CCL5/CCR5 axis promotes VEGF-dependent tumor angiogenesis in human osteosarcoma microenvironment through PKCδ/c-Src/HIF-1α signaling pathway. CCL5 may represent a potential therapeutic target against human osteosarcoma.

  15. Melanoma cell lysate induces CCR7 expression and in vivo migration to draining lymph nodes of therapeutic human dendritic cells.

    Science.gov (United States)

    González, Fermín E; Ortiz, Carolina; Reyes, Montserrat; Dutzan, Nicolás; Patel, Vyomesh; Pereda, Cristián; Gleisner, Maria A; López, Mercedes N; Gutkind, J Silvio; Salazar-Onfray, Flavio

    2014-07-01

    We have previously reported a novel method for the production of tumour-antigen-presenting cells (referred to as TAPCells) that are currently being used in cancer therapy, using an allogeneic melanoma-derived cell lysate (referred to as TRIMEL) as an antigen provider and activation factor. It was recently demonstrated that TAPCell-based immunotherapy induces T-cell-mediated immune responses resulting in improved long-term survival of stage IV melanoma patients. Clinically, dendritic cell (DC) migration from injected sites to lymph nodes is an important requirement for an effective anti-tumour immunization. This mobilization of DCs is mainly driven by the C-C chemokine receptor type 7 (CCR7), which is up-regulated on mature DCs. Using flow cytometry and immunohistochemistry, we investigated if TRIMEL was capable of inducing the expression of the CCR7 on TAPCells and enhancing their migration in vitro, as well as their in vivo relocation to lymph nodes in an ectopic xenograft animal model. Our results confirmed that TRIMEL induces a phenotypic maturation and increases the expression of surface CCR7 on melanoma patient-derived DCs, and also on the monocytic/macrophage cell line THP-1. Moreover, in vitro assays showed that TRIMEL-stimulated DCs and THP-1 cells were capable of migrating specifically in the presence of the CCR7 ligand CCL19. Finally, we demonstrated that TAPCells could migrate in vivo from the injection site into the draining lymph nodes. This work contributes to an increased understanding of the biology of DCs produced ex vivo allowing the design of new strategies for effective DC-based vaccines for treating aggressive melanomas.

  16. The National Cancer Institute's PREVENT Cancer Preclinical Drug Development Program: overview, current projects, animal models, agent development strategies, and molecular targets.

    Science.gov (United States)

    Shoemaker, Robert H; Suen, Chen S; Holmes, Cathy A; Fay, Judith R; Steele, Vernon E

    2016-02-01

    The PREVENT Cancer Preclinical Drug Development Program (PREVENT) is a National Cancer Institute, Division of Cancer Prevention (NCI, DCP)-supported program whose primary goal is to bring new cancer preventive interventions (small molecules and vaccines) and biomarkers through preclinical development towards clinical trials by creating partnerships between the public sector (eg, academia, industry) and DCP. PREVENT has a formalized structure for moving interventions forward in the prevention pipeline using a stage-gate process with go/no go decision points along the critical path for development. This review describes the structure of the program, its focus areas, and provides examples of projects currently in the pipeline.

  17. Trends in Cancer Screening Rates among Korean Men and Women: Results from the Korean National Cancer Screening Survey (KNCSS), 2004-2011

    OpenAIRE

    Park, Boyoung; Choi, Kui Son; Lee, Yoon Young; Jun, Jae Kwan; Seo, Hong Gwan

    2012-01-01

    Purpose The Korean National Cancer Screening Survey (KNCSS) is a nationwide survey conducted annually, since 2004. This study was conducted in order to report on trends in rates of cancer screening for five major cancers-stomach, liver, colorectal, breast, and cervix uteri in Korea. Materials and Methods Data collected by the KNCSS between 2004 and 2011 were used in this study. The eligible study population included cancer-free men who were 40 years old and over, and women who were 30 years o...

  18. Head and neck cancer in India: Need to formulate uniform national treatment guideline?

    Directory of Open Access Journals (Sweden)

    N P Trivedi

    2012-01-01

    Full Text Available Background: In a large and diverse country like India, there is a wide variation in the availability of infrastructure and expertise to treat head-neck cancer patients. Lack of consistent adherence to evidence-based management is the biggest problem. Aims: There is an unmet need to evaluate the existing treatment practices to form the basis for development of effective and uniform treatment policies. Settings and Designs: Prospective case series. Materials and Methods: A group of previously treated, potentially curable patients presenting to our institution (from April 2009 to March 2011 were evaluated for appropriateness of initial treatment based on National Comprehensive Cancer Network or Tata Memorial Hospital guidelines. Data regarding treatment center, protocol and accuracy of delivered treatment and their eventual outcome were analyzed. Statistical Analysis: Descriptive. Results: Amongst 450 newly registered patients, 77(17% were previously treated with curative intent and 69(89% of them were inappropriately treated. Seventeen (25% patients were treated in clinics while 12(17% in cancer centers and 34(50% in corporate hospitals. Fourteen (20% patients received chemotherapy, 22(32% received radiotherapy and 14(20% underwent surgery while 19(28% patients received multimodality treatment. Disease stage changed to more advanced stage in 40(58% patients and curative intent treatment could be offered only to 33(48% patients. Amongst 56 patients available for outcome review, 18(32% patients were alive disease-free, 20(36% had died and 18(32% were alive with disease. Conclusion: Large numbers of potentially curable patients are inappropriately treated and their outcome is significantly affected. Many initiatives have been taken in the existing National Cancer Control Program but formulation of a uniform national treatment guideline should be prioritized.

  19. Discovery and mapping of an intracellular antagonist binding site at the chemokine receptor CCR2

    DEFF Research Database (Denmark)

    Zweemer, Annelien J M; Bunnik, Julia; Veenhuizen, Margo;

    2014-01-01

    be divided into two groups with most likely two topographically distinct binding sites. The aim of the current study was to identify the binding site of one such group of ligands, exemplified by three allosteric antagonists, CCR2-RA-[R], JNJ-27141491, and SD-24. We first used a chimeric CCR2/CCR5 receptor......The chemokine receptor CCR2 is a G protein-coupled receptor that is involved in many diseases characterized by chronic inflammation, and therefore a large variety of CCR2 small molecule antagonists has been developed. On the basis of their chemical structures these antagonists can roughly...

  20. Die Bedeutung der Chemokinrezeptoren CCR7 und CXCR4 sowie des CCR7-Liganden CCL21 für die Ausbreitung des duktalen Adenokarzinoms des Pankreas

    OpenAIRE

    Frank, Sunna

    2010-01-01

    In dieser Arbeit wurde ein Kollektiv von duktalen Adenokarzinomen des Pankreas hinsichtlich einer Expression der Chemokinrezeptoren CCR7 und CXCR4 sowie des CCR7-Liganden CCL21 untersucht. Es konnte ein Zusammenhang zwischen der lymphatischen Ausbreitung des Karzinoms und der CCR7-Expression sowie ein Zusammenhang zwischen der CXCR4-Expression und hohen klinischen Tumorstadien dargestellt werden. Weiterhin wird die Expression CCL21 in intra- und peritumoralen Lymphgefäßen sowie in entzündeten...

  1. CCR5 Delta 32 Genotype Leads to a Th2 Type Directed Immune Response in ESRD Patients

    NARCIS (Netherlands)

    Muntinghe, Friso L. H.; Abdulahad, Wayel H.; Huitema, Minke G.; Damman, Jeffrey; Seelen, Marc A.; Lems, Simon P. M.; Hepkema, Bouke G.; Navis, Gerjan; Westra, Johanna

    2012-01-01

    Background: In patients with end stage renal disease (ESRD) we observed protection from inflammation-associated mortality in CCR5 Delta 32 carriers, leading to CCR5 deficiency, suggesting impact of CCR5 Delta 32 on inflammatory processes. Animal studies have shown that CCR5 deficiency is associated

  2. Gene-environment interactions in cancer epidemiology: a National Cancer Institute Think Tank report.

    Science.gov (United States)

    Hutter, Carolyn M; Mechanic, Leah E; Chatterjee, Nilanjan; Kraft, Peter; Gillanders, Elizabeth M

    2013-11-01

    Cancer risk is determined by a complex interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified hundreds of common (minor allele frequency [MAF] > 0.05) and less common (0.01 Think Tank" on January 10-11, 2012. The objective of the Think Tank was to facilitate discussions on (1) the state of the science, (2) the goals of G × E interaction studies in cancer epidemiology, and (3) opportunities for developing novel study designs and analysis tools. This report summarizes the Think Tank discussion, with a focus on contemporary approaches to the analysis of G × E interactions. Selecting the appropriate methods requires first identifying the relevant scientific question and rationale, with an important distinction made between analyses aiming to characterize the joint effects of putative or established genetic and environmental factors and analyses aiming to discover novel risk factors or novel interaction effects. Other discussion items include measurement error, statistical power, significance, and replication. Additional designs, exposure assessments, and analytical approaches need to be considered as we move from the current small number of success stories to a fuller understanding of the interplay of genetic and environmental factors.

  3. CCR5Δ32 59537-G/A Promoter Polymorphism Is Associated with Low Translational Efficiency and the Loss of CCR5Δ32 Protective Effects▿

    OpenAIRE

    2007-01-01

    We have recently demonstrated that the CCR5Δ32 protein interacts with CCR5 and CXCR4 and down-modulates their cell surface expression. We have also reported the absence of detectable expression of the truncated CCR5Δ32 protein in four out of six human immunodeficiency virus-infected (HIV+) CCR5−/− individuals. To explain the defect in protein expression in these samples, we cloned and sequenced the promoter regions of the six HIV+ individuals. We have identified several polymorphisms in the C...

  4. Identification of a binding element for the cytoplasmic regulator FROUNT in the membrane-proximal C-terminal region of chemokine receptors CCR2 and CCR5.

    Science.gov (United States)

    Toda, Etsuko; Terashima, Yuya; Esaki, Kaori; Yoshinaga, Sosuke; Sugihara, Minoru; Kofuku, Yutaka; Shimada, Ichio; Suwa, Makiko; Kanegasaki, Shiro; Terasawa, Hiroaki; Matsushima, Kouji

    2014-01-15

    Chemokine receptors mediate the migration of leucocytes during inflammation. The cytoplasmic protein FROUNT binds to chemokine receptors CCR2 [chemokine (C-C motif) receptor 2] and CCR5, and amplifies chemotactic signals in leucocytes. Although the interaction between FROUNT and chemokine receptors is important for accurate chemotaxis, the interaction mechanism has not been elucidated. In the present study we identified a 16-amino-acid sequence responsible for high-affinity binding of FROUNT at the membrane-proximal C-terminal intracellular region of CCR2 (CCR2 Pro-C) by yeast two-hybrid analysis. Synthesized peptides corresponding to the CCR2 Pro-C sequence directly interacted with FROUNT in vitro. CCR2 Pro-C was predicted to form an amphipathic helix structure. Residues on the hydrophobic side are completely conserved among FROUNT-binding receptors, suggesting that the hydrophobic side is the responsible element for FROUNT binding. The L316T mutation to the hydrophobic side of the predicted helix decreased the affinity for FROUNT. Co-immunoprecipitation assays revealed that the CCR2 L316T mutation diminished the interaction between FROUNT and full-length CCR2 in cells. Furthermore, this mutation impaired the ability of the receptor to mediate chemotaxis. These findings provide the first description of the functional binding element in helix 8 of CCR2 for the cytosolic regulator FROUNT that mediates chemotactic signalling.

  5. The Ccr4-Not Complex: Architecture and Structural Insights.

    Science.gov (United States)

    Collart, Martine A; Panasenko, Olesya O

    2017-01-01

    The Ccr4-Not complex is an essential multi-subunit protein complex that plays a fundamental role in eukaryotic mRNA metabolism and has a multitude of different roles that impact eukaryotic gene expression . It has a conserved core of three Not proteins, the Ccr4 protein, and two Ccr4 associated factors, Caf1 and Caf40. A fourth Not protein, Not4, is conserved, but is only a stable subunit of the complex in yeast. Certain subunits have been duplicated during evolution, with functional divergence, such as Not3 in yeast, and Ccr4 or Caf1 in human. However the complex includes only one homolog for each protein. In addition, species-specific subunits are part of the complex, such as Caf130 in yeast or Not10 and Not11 in human. Two conserved catalytic functions are associated with the complex, deadenylation and ubiquitination . The complex adopts an L-shaped structure, in which different modules are bound to a large Not1 scaffold protein. In this chapter we will summarize our current knowledge of the architecture of the complex and of the structure of its constituents.

  6. The role and modulation of CCR6+ Th17 cell populations in rheumatoid arthritis.

    Science.gov (United States)

    Paulissen, Sandra M J; van Hamburg, Jan Piet; Dankers, Wendy; Lubberts, Erik

    2015-07-01

    The IL-17A producing T-helper-17 (Th17) cell population plays a major role in rheumatoid arthritis (RA) pathogenesis and has gained wide interest as treatment target. IL-17A expressing Th cells are characterized by the expression of the chemokine receptor CCR6 and the transcription factor RORC. In RA, CCR6+ Th cells were identified in peripheral blood, synovial fluid and inflamed synovial tissue. CCR6+ Th cells might drive the progression of an early inflammation towards a persistent arthritis. The CCR6+ Th cell population is heterogeneous and several subpopulations can be distinguished, including Th17, Th22, Th17.1 (also called non-classic Th1 cells), and unclassified or intermediate populations. Interestingly, some of these populations produce low levels of IL-17A but are still very pathogenic. Furthermore, the CCR6+ Th cells phenotype is unstable and plasticity exists between CCR6+ Th cells and T-regulatory (Treg) cells and within the CCR6+ Th cell subpopulations. In this review, characteristics of the different CCR6+ Th cell populations, their plasticity, and their potential impact on rheumatoid arthritis are discussed. Moreover, current approaches to target CCR6+ Th cells and future directions of research to find specific CCR6+ Th cell targets in the treatment of patients with RA and other CCR6+ Th cell mediated autoimmune diseases are highlighted.

  7. Naive Treg-like CCR7(+) mononuclear cells indicate unfavorable prognosis in hepatocellular carcinoma.

    Science.gov (United States)

    Shi, Jie-Yi; Duan, Meng; Sun, Qi-Man; Yang, Liuxiao; Wang, Zhi-Chao; Mynbaev, Ospan A; He, Yi-Feng; Wang, Ling-Yan; Zhou, Jian; Tang, Qi-Qun; Cao, Ya; Fan, Jia; Wang, Xiao-Ying; Gao, Qiang

    2016-07-01

    Chemokine receptor-like 1 (CCRL1) has the potential in creating a low level of CCL19 and CCL21 to hinder CCR7(+) cell tracking to tumor tissue. Previously, we found a tumor suppressive role of CCRL1 by impairing CCR7-related chemotaxis of tumor cells in human hepatocellular carcinoma (HCC). Here, we reported a contribution of CCR7(+) mononuclear cells in the tumor microenvironment to the progression of disease. Immunohistochemistry was used to investigate the distribution and clinical significance of CCR7(+) cells in a cohort of 240 HCC patients. Furthermore, the phenotype, composition, and functional status of CCR7(+) cells were determined by flow cytometry, immunofluorescence, and in vitro co-culture assays. We found that CCR7(+) mononuclear cells were dispersed around tumor tissue and negatively related to tumoral expression of CCRL1 (P CCR7(+) mononuclear cells positively correlated with the absence of tumor capsule, vascular invasion, and poor differentiation (P CCR7(+) mononuclear cells was significantly associated with worse survival and increased recurrence. We found that CCR7(+) mononuclear cells featured a naive Treg-like phenotype (CD45RA(+)CD25(+)FOXP3(+)) and possessed tumor-promoting potential by producing TGF-β1. Moreover, CCR7(+) cells were also composed of several immunocytes, a third of which were CD8(+) T cells. CCR7(+) Treg-like cells facilitate tumor growth and indicate unfavorable prognosis in HCC patients, but fortunately, their tracking to tumor tissue is under the control of CCRL1.

  8. Highly specific blockade of CCR5 inhibits leukocyte trafficking and reduces mucosal inflammation in murine colitis.

    Science.gov (United States)

    Mencarelli, Andrea; Cipriani, Sabrina; Francisci, Daniela; Santucci, Luca; Baldelli, Franco; Distrutti, Eleonora; Fiorucci, Stefano

    2016-08-05

    Targeted disruption of leukocyte trafficking to the gut represents a promising approach for the treatment of inflammatory bowel diseases (IBDs). CCR5, the shared receptor for MIP1α and β and RANTES, is expressed by multiple leukocytes. Here, we aimed to determine the role of CCR5 in mediating leukocyte trafficking in models of colitis, and evaluate the therapeutic potential of maraviroc, an orally active CCR5 antagonist used in the treatment of CCR5-tropic HIV. Acute and chronic colitis were induced by administration of DSS or TNBS to wild-type and CCR5(-/-) mice or adoptive transfer of splenic naïve CD4(+) T-cells from wild type or CCR5(-/-) mice into RAG-1(-/-). CCR5 gene ablation reduced the mucosal recruitment and activation of CCR5-bearing CD4(+) and CD11b(+) leukocytes, resulting in profound attenuation of signs and symptoms of inflammation in the TNBS and transfer models of colitis. In the DSS/TNBS colitis and in the transfer model, maraviroc attenuated development of intestinal inflammation by selectively reducing the recruitment of CCR5 bearing leukocytes. In summary, CCR5 regulates recruitment of blood leukocytes into the colon indicating that targeting CCR5 may offer therapeutic options in IBDs.

  9. Decreased HIV type 1 transcription in CCR5-Δ32 heterozygotes during suppressive antiretroviral therapy.

    Science.gov (United States)

    Wang, Charlene; Abdel-Mohsen, Mohamed; Strain, Matthew C; Lada, Steven M; Yukl, Steven; Cockerham, Leslie R; Pilcher, Christopher D; Hecht, Frederick M; Sinclair, Elizabeth; Liegler, Teri; Richman, Douglas D; Deeks, Steven G; Pillai, Satish K

    2014-12-01

    Individuals who are heterozygous for the CCR5-Δ32 mutation provide a natural model to examine the effects of reduced CCR5 expression on human immunodeficiency virus (HIV) persistence. We evaluated the HIV reservoir in 18 CCR5-Δ32 heterozygotes and 54 CCR5 wild-type individuals during suppressive antiretroviral therapy. Cell-associated HIV RNA levels (P=.035), RNA to DNA transcriptional ratios (P=.013), and frequency of detectable HIV 2-long terminal repeat circular DNA (P=.013) were significantly lower in CD4+ T cells from CCR5-Δ32 heterozygotes. Cell-associated HIV RNA was significantly correlated with CCR5 surface expression on CD4+ T cells (r2=0.136; P=.002). Our findings suggest that curative strategies should further explore manipulation of CCR5.

  10. Speech and swallow rehabilitation in head and neck cancer: United Kingdom National Multidisciplinary Guidelines.

    Science.gov (United States)

    Clarke, P; Radford, K; Coffey, M; Stewart, M

    2016-05-01

    This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. The disease itself and the treatment can have far reaching effects on speech and swallow function, which are consistently prioritised by survivors as an area of concern. This paper provides recommendations on the assessments and interventions for speech and swallow rehabilitation in this patient group. Recommendations • All multidisciplinary teams should have rehabilitation patient pathways covering all stages of the patient's journey including multidisciplinary and pre-treatment clinics. (G) • Clinicians treating head and neck cancer patients should consult the National Cancer Rehabilitation Pathway for head and neck cancers. (G) • All head and neck cancer patients should have a pre-treatment assessment of speech and swallowing. (G) • A programme of prophylactic exercises and the teaching of swallowing manoeuvres can reduce impairments, maintain function and enable a speedier recovery. (R) • Continued speech and language therapist input is important in maintaining voice and safe and effective swallow function following head and neck cancer treatment. (R) • Disease recurrence must be ruled out in the management of stricture and/or stenosis. (R) • Continuous radial expansion balloons offer a safe, effective dilation method with advantages over gum elastic bougies. (R) • Site, length and completeness of strictures as well as whether they are in the presence of the larynx or not, need to be assessed when establishing the likelihood of surgically improved outcome. (G) • Primary surgical voice restoration should be offered to all patients undergoing laryngectomy. (R) • Attention to surgical detail and long-term speech and language therapist input is required to optimise speech and swallowing after laryngectomy. (G) • Patients should commence wearing heat and moisture exchange devices as soon as possible after

  11. The HIV-1 Gp120/CXCR4 axis promotes CCR7 ligand-dependent CD4 T cell migration: CCR7 homo- and CCR7/CXCR4 hetero-oligomer formation as a possible mechanism for up-regulation of functional CCR7.

    Science.gov (United States)

    Hayasaka, Haruko; Kobayashi, Daichi; Yoshimura, Hiromi; Nakayama, Emi E; Shioda, Tatsuo; Miyasaka, Masayuki

    2015-01-01

    During human immunodeficiency virus (HIV) infection, enhanced migration of infected cells to lymph nodes leads to efficient propagation of HIV-1. The selective chemokine receptors, including CXCR4 and CCR7, may play a role in this process, yet the viral factors regulating chemokine-dependent T cell migration remain relatively unclear. The functional cooperation between the CXCR4 ligand chemokine CXCL12 and the CCR7 ligand chemokines CCL19 and CCL21 enhances CCR7-dependent T cell motility in vitro as well as cell trafficking into the lymph nodes in vivo. In this study, we report that a recombinant form of a viral CXCR4 ligand, X4-tropic HIV-1 gp120, enhanced the CD4 T cell response to CCR7 ligands in a manner dependent on CXCR4 and CD4, and that this effect was recapitulated by HIV-1 virions. HIV-1 gp120 significantly enhanced CCR7-dependent CD4 T cell migration from the footpad of mice to the draining lymph nodes in in vivo transfer experiments. We also demonstrated that CXCR4 expression is required for stable CCR7 expression on the CD4 T cell surface, whereas CXCR4 signaling facilitated CCR7 ligand binding to the cell surface and increased the level of CCR7 homo- as well as CXCR4/CCR7 hetero-oligomers without affecting CCR7 expression levels. Our findings indicate that HIV-evoked CXCR4 signaling promotes CCR7-dependent CD4 T cell migration by up-regulating CCR7 function, which is likely to be induced by increased formation of CCR7 homo- and CXCR4/CCR7 hetero-oligomers on the surface of CD4 T cells.

  12. Retinal Inhibition of CCR3 Induces Retinal Cell Death in a Murine Model of Choroidal Neovascularization.

    Directory of Open Access Journals (Sweden)

    Haibo Wang

    Full Text Available Inhibition of chemokine C-C motif receptor 3 (CCR3 signaling has been considered as treatment for neovascular age-related macular degeneration (AMD. However, CCR3 is expressed in neural retina from aged human donor eyes. Therefore, broad CCR3 inhibition may be harmful to the retina. We assessed the effects of CCR3 inhibition on retina and choroidal endothelial cells (CECs that develop into choroidal neovascularization (CNV. In adult murine eyes, CCR3 colocalized with glutamine-synthetase labeled Műller cells. In a murine laser-induced CNV model, CCR3 immunolocalized not only to lectin-stained cells in CNV lesions but also to the retina. Compared to non-lasered controls, CCR3 mRNA was significantly increased in laser-treated retina. An intravitreal injection of a CCR3 inhibitor (CCR3i significantly reduced CNV compared to DMSO or PBS controls. Both CCR3i and a neutralizing antibody to CCR3 increased TUNEL+ retinal cells overlying CNV, compared to controls. There was no difference in cleaved caspase-3 in laser-induced CNV lesions or in overlying retina between CCR3i- or control-treated eyes. Following CCR3i, apoptotic inducible factor (AIF was significantly increased and anti-apoptotic factor BCL2 decreased in the retina; there were no differences in retinal vascular endothelial growth factor (VEGF. In cultured human Műller cells exposed to eotaxin (CCL11 and VEGF, CCR3i significantly increased TUNEL+ cells and AIF but decreased BCL2 and brain derived neurotrophic factor, without affecting caspase-3 activity or VEGF. CCR3i significantly decreased AIF in RPE/choroids and immunostaining of phosphorylated VEGF receptor 2 (p-VEGFR2 in CNV with a trend toward reduced VEGF. In cultured CECs treated with CCL11 and/or VEGF, CCR3i decreased p-VEGFR2 and increased BCL2 without increasing TUNEL+ cells and AIF. These findings suggest that inhibition of retinal CCR3 causes retinal cell death and that targeted inhibition of CCR3 in CECs may be a safer if CCR3

  13. Cancer risks from soil emissions of volatile organic compounds at the Lawrence Livermore National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Dibley, V. R., LLNL

    1998-02-01

    The emission isolation flux chamber (EIFC) methodology was applied to Superfund investigations at the Lawrence Livermore National Laboratory Site 300 to determine if on-site workers were exposed to VOCs volatilizing from the subsurface and what, if any, health risks could be attributed to the inhalation of the VOCs volatilizing from the subsurface. During July and August of 1996, twenty, eighteen, and twenty six VOC soil vapor flux samples were collected in the Building 830, 832, and 854 areas, respectively using EIFCS. The VOC concentrations in the vapor samples were used to calculate soil flux rates which were used as input into an air dispersion model to calculate ambient air exposure-point concentrations. The exposure-point concentrations were compared to EPA Region IX Preliminary Remediation Goals (PRGs). Buildings 830 and 832 exposure-point concentrations were less then the PRGs therefore no cancer risks were calculated. The cancer risks for Building 854 ranged from 1.6 x 10{sup -7} to 2.1 x 10{sup -6}. The resultant inhalation cancer risks were all within the acceptable range, implying that on-site workers were not exposed to VOC vapors volatilizing from the subsurface soil that could have significant cancer risks. Therefore remediation in these areas would not be necessary.

  14. CCR2+ and CCR5+ CD8+ T cells increase during viral infection and migrate to sites of infection

    DEFF Research Database (Denmark)

    Nansen, A; Marker, O; Bartholdy, C;

    2000-01-01

    Chemokines and their receptors play a critical role in the selective recruitment of various leukocyte subsets. In this study, we correlated the expression of multiple chemokine and CC chemokine receptor (CCR) genes during the course of intracerebral (i.c.) infection with lymphocytic...

  15. Epigenetic mechanisms, T-cell activation, and CCR5 genetics interact to regulate T-cell expression of CCR5, the major HIV-1 coreceptor.

    Science.gov (United States)

    Gornalusse, German G; Mummidi, Srinivas; Gaitan, Alvaro A; Jimenez, Fabio; Ramsuran, Veron; Picton, Anabela; Rogers, Kristen; Manoharan, Muthu Saravanan; Avadhanam, Nymisha; Murthy, Krishna K; Martinez, Hernan; Molano Murillo, Angela; Chykarenko, Zoya A; Hutt, Richard; Daskalakis, Demetre; Shostakovich-Koretskaya, Ludmila; Abdool Karim, Salim; Martin, Jeffrey N; Deeks, Steven G; Hecht, Frederick; Sinclair, Elizabeth; Clark, Robert A; Okulicz, Jason; Valentine, Fred T; Martinson, Neil; Tiemessen, Caroline Tanya; Ndung'u, Thumbi; Hunt, Peter W; He, Weijing; Ahuja, Sunil K

    2015-08-25

    T-cell expression levels of CC chemokine receptor 5 (CCR5) are a critical determinant of HIV/AIDS susceptibility, and manifest wide variations (i) between T-cell subsets and among individuals and (ii) in T-cell activation-induced increases in expression levels. We demonstrate that a unifying mechanism for this variation is differences in constitutive and T-cell activation-induced DNA methylation status of CCR5 cis-regulatory regions (cis-regions). Commencing at an evolutionarily conserved CpG (CpG -41), CCR5 cis-regions manifest lower vs. higher methylation in T cells with higher vs. lower CCR5 levels (memory vs. naïve T cells) and in memory T cells with higher vs. lower CCR5 levels. HIV-related and in vitro induced T-cell activation is associated with demethylation of these cis-regions. CCR5 haplotypes associated with increased vs. decreased gene/surface expression levels and HIV/AIDS susceptibility magnify vs. dampen T-cell activation-associated demethylation. Methylation status of CCR5 intron 2 explains a larger proportion of the variation in CCR5 levels than genotype or T-cell activation. The ancestral, protective CCR5-HHA haplotype bears a polymorphism at CpG -41 that is (i) specific to southern Africa, (ii) abrogates binding of the transcription factor CREB1 to this cis-region, and (iii) exhibits a trend for overrepresentation in persons with reduced susceptibility to HIV and disease progression. Genotypes lacking the CCR5-Δ32 mutation but with hypermethylated cis-regions have CCR5 levels similar to genotypes heterozygous for CCR5-Δ32. In HIV-infected individuals, CCR5 cis-regions remain demethylated, despite restoration of CD4+ counts (≥800 cells per mm(3)) with antiretroviral therapy. Thus, methylation content of CCR5 cis-regions is a central epigenetic determinant of T-cell CCR5 levels, and possibly HIV-related outcomes.

  16. A role for CCR5(+)CD4 T cells in cutaneous psoriasis and for CD103(+) CCR4(+) CD8 Teff cells in the associated systemic inflammation.

    Science.gov (United States)

    Sgambelluri, Francesco; Diani, Marco; Altomare, Andrea; Frigerio, Elena; Drago, Lorenzo; Granucci, Francesca; Banfi, Giuseppe; Altomare, Gianfranco; Reali, Eva

    2016-06-01

    Recent results have identified critical components of the T cell response involved in the initiation and amplification phases of psoriasis. However the link between T cell responses arising in the skin and the systemic inflammation associated with severe psoriasis is largely unknown. We hypothesized that specific subsets of memory T cells recirculating from the skin could play a role. We therefore dissected the circulating memory T cell compartment in patients by analyzing the TCM, TEM and Teff phenotype, the pattern of CCR4 and CCR5 chemokine receptor expression and the expression of the tissue homing molecule CD103. For each subset we calculated the correlation with the Psoriasis Area and Severity Index (PASI) and with the extent of systemic inflammation measured as serum level of the prototypic short pentraxin, C reactive protein (CRP). Validation was performed by comparison with gene expression data in psoriatic plaques. We found that circulating CD103(+)CCR4(+)CCR5(+) and CCR4(+)CCR6(-) CD8(+) Teff cells, were highly correlated with CRP levels as well as with the validated index PASI, reflecting a link between skin involvement and systemic inflammation in patients with severe psoriasis. In addition we observed a contraction of circulating CCR5(+) T cells in psoriasis patients, with a highly significant inverse correlation between CCR5(+)CD4 T cells and the PASI score. Increased expression of CCR5 and CCL5 genes in psoriatic skin lesions was consistent with an accumulation of CCR5(+) cells in psoriatic plaques indicating a role for CCR5/CCL5 axis in disease pathogenesis.

  17. Preliminary Analysis of Difficulty of Importing Pattern-Based Concepts into the National Cancer Institute Thesaurus.

    Science.gov (United States)

    He, Zhe; Geller, James

    2016-01-01

    Maintenance of biomedical ontologies is difficult. We have developed a pattern-based method for dealing with the problem of identifying missing concepts in the National Cancer Institute thesaurus (NCIt). Specifically, we are mining patterns connecting NCIt concepts with concepts in other ontologies to identify candidate missing concepts. However, the final decision about a concept insertion is always up to a human ontology curator. In this paper, we are estimating the difficulty of this task for a domain expert by counting possible choices for a pattern-based insertion. We conclude that even with support of our mining algorithm, the insertion task is challenging.

  18. Symptoms and problems in a nationally representative sample of advanced cancer patients

    DEFF Research Database (Denmark)

    Johnsen, A T; Groenvold, M; Pedersen, Lise

    2009-01-01

    stage 3 or 4 from 54 hospital departments (n = 1630) received the EORTC QLQ-C30 questionnaire. Mean scores were calculated according to the scoring manual and in addition a 'symptom/problem' and a 'severe symptom/problem' was defined and calculated. Multiple logistic regression was used to identify...... or not were associated with several symptoms and problems. This is probably the first nationally representative study of its kind. It shows that advanced cancer patients in Denmark have symptoms and problems that deserve attention and that some patient groups are especially at risk....

  19. Sunitinib treatment in patients with advanced renal cell cancer: the Brazilian National Cancer Institute (INCA experience

    Directory of Open Access Journals (Sweden)

    Rafael Corrêa Coelho

    Full Text Available ABSTRACT Purpose: The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC treated by the Brazilian Unified Health System (SUS at a single reference institution. Material and Methods: Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. Results: Fifty-eight patients were eligible. Most patients were male 41 (71%, with a median age of 58 years. Nephrectomy was performed in 41 (71% patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2% patients. In 50 patients (86%, sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%, hypothyroidism (43%, mucositis (33% and diarrhea (29%. Grade 3 and 4 adverse effects were infrequent: fatigue (12%, hypertension (12%, thrombocytopenia (7%, neutropenia (5% and hand-foot syndrome (5%. Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. Conclusion: Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS.

  20. Sunitinib treatment in patients with advanced renal cell cancer: the Brazilian National Cancer Institute (INCA) experience

    Science.gov (United States)

    Coelho, Rafael Corrêa; Reinert, Tomás; Campos, Franz; Peixoto, Fábio Affonso; de Andrade, Carlos Augusto; Castro, Thalita; Herchenhorn, Daniel

    2016-01-01

    ABSTRACT Purpose: The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC) treated by the Brazilian Unified Health System (SUS) at a single reference institution. Material and Methods: Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. Results: Fifty-eight patients were eligible. Most patients were male 41 (71%), with a median age of 58 years. Nephrectomy was performed in 41 (71%) patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2%) patients. In 50 patients (86%), sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%), hypothyroidism (43%), mucositis (33%) and diarrhea (29%). Grade 3 and 4 adverse effects were infrequent: fatigue (12%), hypertension (12%), thrombocytopenia (7%), neutropenia (5%) and hand-foot syndrome (5%). Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. Conclusion: Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS. PMID:27564279

  1. Glatiramer Acetate, Dimethyl Fumarate, and Monomethyl Fumarate Upregulate the Expression of CCR10 on the Surface of Natural Killer Cells and Enhance Their Chemotaxis and Cytotoxicity

    Science.gov (United States)

    Maghazachi, Azzam A.; Sand, Kristin L.; Al-Jaderi, Zaidoon

    2016-01-01

    In vitro harnessing of immune cells is the most important advance in the field of cancer immunotherapy. Results shown in the current paper may be used to harness natural killer (NK) cells in vitro. It is observed that drugs used to treat multiple sclerosis such as glatiramer acetate, dimethyl fumarate, and monomethyl fumarate upregulate the expression of chemokines receptor 10 (CCR10) on the surface of human IL-2-activated NK cells. This is corroborated with increased chemotaxis of these cells toward the concentration gradients of the ligands for CCR10, namely CCL27 and CCL28. It is also demonstrated that these three drugs enhance NK cell cytotoxicity against tumor target cells, an activity that is abrogated by prior incubation of the cells with anti-CCR10 antibody. Because CCL27 and CCL28 are secreted by selective tumor types such as malignant melanoma, squamous cell carcinomas, and colorectal cancer, respectively, it is hypothesized that activated NK cells may be harnessed in vitro with any of these drugs before utilizing them as a therapeutic modality for cancer.

  2. Expression of chemokine recepter CCR4 and CCR5 on peripheral blood CD4+T cells in systemic lupus erythematosus patients%趋化因子受体CCR4、CCR5在系统性红斑狼疮患者外周血CD4+T淋巴细胞上的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    程慧玲; 刘建伟; 马万山; 迟伟玲

    2008-01-01

    目的 探讨系统性红斑狼疮(SLE)患者趋化因子受体CCR4和CCR5在外周血淋巴细胞表面的表达及其意义.方法 流式细胞仪计数法对113例SLE患者和50例健康体检者外周血淋巴细胞表面CCR4和CCR5的表达情况进行检测,分析及评价SLE患者外周血淋巴细胞中CCR4+和CCR5+T淋巴细胞的百分数.结果 非狼疮性肾炎(nLN)SLE组外周血CCR4+CD4+T%明显高于健康对照组(P<0.01);狼疮性肾炎SLE组外周血CCR4+CD4+T%明显高于健康对照组(P<0.001);LN SLE组外周血CCR4+CD4+T%明显高于nLN SLE组(P<0.01);nLN SLE组外周血CCR5+CD4+T%高于健康对照组(P<0.05);LN SLE组外周血CCR5+CD4+T%明显高于健康对照组(P<0.001);LN SLE组外周血CCR5+CD4+T%明显高于nLN SLE组(P<0.01).SLE活动组血清CCR4+CD4+T%与CCR5+CD4+T%较非活动组和对照组明显升高(P<0.01);活动性狼疮性肾炎(LN)与活动性无肾损伤组及对照组比较,其差异具有显著统计学意义(P<0.01).nLN SLE组外周血CCR4+CD4+T%与CCR5+CD4+T%有相关性(r=0.619,P<0.05);LN SLE组外周血CCR4+CD4+T%与CCR5+CD4+T%有明显相关性(r=0.68,P<0.01);血清CCR4+CD4+T%水平随着SLE疾病活动水平明显升高,与总的系统性红斑狼疮疾病活动性指数(SLEDAI)评分密切相关(r=0.6382,P<0.001);与SLEDAI肾评分亦密切相关(r=0.6980,P<0.001);而CCR5+CD4+T%与疾病活动度不相关(r=0.16,P>0.05).结论 以上结果表明CCR4和CCR5在T细胞趋化至病变部位的过程中可能发挥重要作用,CCR4+CD4+T%与CCR5+CD4+T%可能在肾损伤中起着十分重要的作用,血清CCR4+CD4+T%、CCR5+CD4+T%与SLE疾病活动密切相关,可作为SLE疾病活动,尤其是监测狼疮性肾损伤的重要指标.

  3. Data quality at the Bulgarian National Cancer Registry: An overview of comparability, completeness, validity and timeliness.

    Science.gov (United States)

    Dimitrova, Nadya; Parkin, Donald Maxwell

    2015-06-01

    Reporting of neoplasms in Bulgaria has been compulsory since a directive from the Ministry of Health in 1951. The quality of cancer registry data has been estimated rather infrequently in past years. We aimed to provide a comprehensive evaluation of the quality of the data at the Bulgarian National Cancer Registry (BNCR). Quantitative and semi-quantitative methods were applied for cancers diagnosed during the whole period 1993-2010, and also for cases diagnosed in 2006-2010. The methods used include historic data methods, mortality-to-incidence ratios (M:I), capture-recapture and death-certificate methods, proportions of morphologically verified cases (MV%), death-certificate-only cases (DCO%), and cases with missing information (primary site unknown, PSU%; stage unknown, SU%). The BNCR coding and classification systems follow international standards. The overall completeness was estimated at 92.6-94.7% for the period 2006-2010, with variations between cancer sites (86.7-98.5%). During the period 1993-2010, M:I decreased to 0.5 for males and 0.4 for females, MV increased to 87.4%, DCO and SU decreased to 4.8% and 18.8%, respectively, and PSU remained at the same level of about 4% for both sexes together. Sub-analysis revealed differences by site, sex and age groups. The comparison with other registries from the region showed similar incidence rates and directions of trends: M:I, MV% and DCO% that were not significantly different. The underreporting in 2008 and 2009 due to timely publication was estimated at an overall 0.8% and 0.5%, respectively. The present review showed that the BNCR yields internationally comparable data that are reasonably accurate, timely, and close to complete, especially in recent years. This is a prerequisite for the BNCR to expand its role to more areas of cancer control.

  4. [Sociodemographic determinants of access to breast cancer screening in Mexico: a review of national surveys].

    Science.gov (United States)

    Agudelo Botero, Marcela

    2013-04-01

    The aim of this article is to identify factors affecting access to breast cancer screening in Mexico according to the sociodemographic characteristics of the women, using three nationally-representative surveys. Descriptive statistics were performed and multiple classification analysis techniques were used. The dependent variables were that the women had realized: 1) breast self-examination, 2) clinical breast examination, or 3) mammography; the covariates were: age group, education level, type of locality (urban/rural), marital status, number of children, enrollment in social security and socioeconomic status. A low level of screening use was detected and gaps were observed between different groups of women according to sociodemographic characteristics. In general women of lower economic strata, without enrollment in social security and with lower educational levels, showed fewer detection practices than the national average.

  5. Preventing premature deaths from breast and cervical cancer among underserved women in the United States: insights gained from a national cancer screening program.

    Science.gov (United States)

    White, Mary C; Wong, Faye L

    2015-05-01

    This commentary highlights some of the valuable insights gained from a special collection of papers that utilized data from the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) and appear in this special issue. The data and experiences of the NBCCEDP can inform the identification of new opportunities and directions for meeting the cancer screening needs of underserved women in a complex and changing health care environment.

  6. CCR5 conformations are dynamic and modulated by localization, trafficking and G protein association.

    Directory of Open Access Journals (Sweden)

    Ayanna J Flegler

    Full Text Available CCR5 acts as the principal coreceptor during HIV-1 transmission and early stages of infection. Efficient HIV-1 entry requires a series of processes, many dependent on the conformational state of both viral envelope protein and cellular receptor. Monoclonal antibodies (MAbs are able to identify different CCR5 conformations, allowing for their use as probes to distinguish CCR5 populations. Not all CCR5 MAbs are able to reduce HIV-1 infection, suggesting the use of select CCR5 populations for entry. In the U87.CD4.CCR5-GFP cell line, we used such HIV-1-restricting MAbs to probe the relation between localization, trafficking and G protein association for individual CCR5 conformations. We find that CCR5 conformations not only exhibit different localization and abundance patterns throughout the cell, but that they also display distinct sensitivities to endocytosis inhibition. Using chemokine analogs that vary in their HIV-1 inhibitory mechanisms, we also illustrate that responses to ligand engagement are conformation-specific. Additionally, we provide supporting evidence for the select sensitivity of conformations to G protein association. Characterizing the link between the function and dynamics of CCR5 populations has implications for understanding their selective targeting by HIV-1 and for the development of inhibitors that will block CCR5 utilization by the virus.

  7. CCR5 conformations are dynamic and modulated by localization, trafficking and G protein association.

    Science.gov (United States)

    Flegler, Ayanna J; Cianci, Gianguido C; Hope, Thomas J

    2014-01-01

    CCR5 acts as the principal coreceptor during HIV-1 transmission and early stages of infection. Efficient HIV-1 entry requires a series of processes, many dependent on the conformational state of both viral envelope protein and cellular receptor. Monoclonal antibodies (MAbs) are able to identify different CCR5 conformations, allowing for their use as probes to distinguish CCR5 populations. Not all CCR5 MAbs are able to reduce HIV-1 infection, suggesting the use of select CCR5 populations for entry. In the U87.CD4.CCR5-GFP cell line, we used such HIV-1-restricting MAbs to probe the relation between localization, trafficking and G protein association for individual CCR5 conformations. We find that CCR5 conformations not only exhibit different localization and abundance patterns throughout the cell, but that they also display distinct sensitivities to endocytosis inhibition. Using chemokine analogs that vary in their HIV-1 inhibitory mechanisms, we also illustrate that responses to ligand engagement are conformation-specific. Additionally, we provide supporting evidence for the select sensitivity of conformations to G protein association. Characterizing the link between the function and dynamics of CCR5 populations has implications for understanding their selective targeting by HIV-1 and for the development of inhibitors that will block CCR5 utilization by the virus.

  8. Molecular Gymnastics: Mechanisms of HIV-1 Resistance to CCR5 Antagonists and Impact on Virus Phenotypes.

    Science.gov (United States)

    Roche, Michael; Borm, Katharina; Flynn, Jacqueline K; Lewin, Sharon R; Churchill, Melissa J; Gorry, Paul R

    2016-01-01

    Human immunodeficiency virus type 1 (HIV-1) enters host cells through the binding of its envelope glycoproteins (Env) to the host cell receptor CD4 and then subsequent binding to a chemokine coreceptor, either CCR5 or CXCR4. CCR5 antagonists are a relatively recent class addition to the armamentarium of anti-HIV-1 drugs. These compounds act by binding to a hydrophobic pocket formed by the transmembrane helices of CCR5 and altering the conformation of the extracellular domains, such that they are no longer recognized by Env. Maraviroc is the first drug within this class to be licenced for use in HIV-1 therapy regimens. HIV resistance to CCR5 antagonists occurs either through outgrowth of pre-existing CXCR4-using viruses, or through acquisition of the ability of CCR5-using HIV-1 to use the antagonist bound form of CCR5. In the latter scenario, the mechanism underlying resistance is through complex alterations in the way that resistant Envs engage CCR5. These significant changes are unlikely to occur without consequence to the viral entry phenotype and may also open up new avenues to target CCR5 antagonist resistant viruses. This review discusses the mechanism of action of CCR5 antagonists, how HIV resistance to CCR5 antagonists occurs, and the subsequent effects on Env function.

  9. Distinct CCR7 glycosylation pattern shapes receptor signaling and endocytosis to modulate chemotactic responses.

    Science.gov (United States)

    Hauser, Mark A; Kindinger, Ilona; Laufer, Julia M; Späte, Anne-Katrin; Bucher, Delia; Vanes, Sarah L; Krueger, Wolfgang A; Wittmann, Valentin; Legler, Daniel F

    2016-06-01

    The homeostatic chemokines CCL19 and CCL21 and their common cognate chemokine receptor CCR7 orchestrate immune cell trafficking by eliciting distinct signaling pathways. Here, we demonstrate that human CCR7 is N-glycosylated on 2 specific residues in the N terminus and the third extracellular loop. Conceptually, CCR7 glycosylation adds steric hindrance to the receptor N terminus and extracellular loop 3, acting as a "swinging door" to regulate receptor sensitivity and cell migration. We found that freshly isolated human B cells, as well as expanded T cells, but not naïve T cells, express highly sialylated CCR7. Moreover, we identified that human dendritic cells imprint T cell migration toward CCR7 ligands by secreting enzymes that deglycosylate CCR7, thereby boosting CCR7 signaling on T cells, permitting enhanced T cell locomotion, while simultaneously decreasing receptor endocytosis. In addition, dendritic cells proteolytically convert immobilized CCL21 to a soluble form that is more potent in triggering chemotactic movement and does not desensitize the receptor. Furthermore, we demonstrate that soluble CCL21 functionally resembles neither the CCL19 nor the CCL21 phenotype but acts as a chemokine with unique features. Thus, we advance the concept of dendritic cell-dependent generation of micromilieus and lymph node conditioning by demonstrating a novel layer of CCR7 regulation through CCR7 sialylation. In summary, we demonstrate that leukocyte subsets express distinct patterns of CCR7 sialylation that contribute to receptor signaling and fine-tuning chemotactic responses.

  10. CCR7-independent transport of skin antigens occurs in the dermis.

    Science.gov (United States)

    Yoshino, Miya; Okuyama, Kazuki; Murata, Akihiko; Tomura, Michio; Hayashi, Shin-ichi

    2012-06-01

    Under homeostatic conditions, skin DCs migrate to regional LNs transporting self-antigens (self-Ags). The transport of self-Ags is considered to be critical for maintaining peripheral tolerance. Although the chemokine receptor CCR7 potently induces the migration of skin DCs to regional LNs, Ccr7(-/-) (Ccr7-KO) mice do not show skin auto-immune diseases. To resolve this inconsistency, we examined Ccr7-KO epidermis- or dermis-hyperpigmented transgenic (Tg) mice, in which the transport of skin self-Ags is traceable by melanin granules (MGs). Under CCR7-deficient conditions, the transport of epidermal MGs to regional LNs was impaired at 7 weeks of age. However, epidermal MGs could be transported when they had accumulated in the dermis. Ccr7-KO-dermis-pigmented Tg mice confirmed the presence of CCR7-independent transport from the dermis. Compared with WT-dermis-pigmented Tg mice, the amount of transported melanin and number of MG-laden CD11c(+) cells were both approximately 40% of the WT levels, while the number of MG-laden CD205(+) or CD207(+) cells decreased to about 10% in skin regional LNs of Ccr7-KO-dermis-pigmented Tg mice. Cell sorting highlighted the involvement of CD11c(+) cells in the CCR7-independent transport. Here, we show that CCR7-independent transport of skin self-Ags occurs in the dermis. This system might contribute to the continuous transport of self-Ags, and maintain peripheral tolerance.

  11. CCR5△32及CCR5siRNA修饰的人外周血来源的PBMC细胞对HIV-1假病毒的拮抗作用%CCR5A32 and CCR5 siRNA Modified-Human Peripheral Blood-Derived PBMC Cells Resist HIV-1 Psedovirus Infection

    Institute of Scientific and Technical Information of China (English)

    夏承来; 严鹏科; 黄汉辉

    2011-01-01

    目的 研究CCR5△32及CCR5 siRNA修饰的PBMC细胞对HIV-1假病毒的拮抗作用.方法 将CCR5△32和CCR5siRNA的基因连接到腺病毒载体上,用磷酸钙法将其转入人源性PBMC,Westernblot检测CCR5△32稳定表达情况以及CCR5siRNA对CCR5的抑制情况.构建HIV-1假病毒,检测荧光素酶报告基因的活性,判断病毒的感染情况.结果 CCR5△32在PBMC细胞上获得稳定表达,CCR5siRNA抑制PBMC细胞中CCR5的表达;修饰后的PBMC细胞并不能被HIV-1假病毒感染.结论 修饰后的PBMC细胞具有较好的拮抗HIV-1假病毒感染的作用.

  12. Correlation between chemokine receptor CXCR4, CCR7 in gastric cell fines with different invasive potentials%趋化因子受体CXCR4、CCR7在胃癌细胞中的表达及其与胃癌细胞侵袭能力的关系

    Institute of Scientific and Technical Information of China (English)

    姜明; 郑毅雄; 唐湘莲; 孟立峰; 陈力

    2010-01-01

    目的 观察趋化因子受体CXCR4及CCR7在不同侵袭能力人胃癌细胞株中的差异表达.方法 逆转录-聚合酶链反应(RT-PCR)及Western blot分析CXCR4及CCR7在人胃癌细胞株MGC803、AGS、BGC823、SGC7901的表达;体外侵袭实验测定4株胃癌细胞的侵袭能力.结果 MGC803、AGS、BGC823、SGC7901中CXCR4 mRNA相对表达量分别为:1.2556±0.1384、0.7943±0.0913、0.4749±0.0744、0.2463±0.0344,CCR7 mRNA相对表达量分别为:0.6071±0.1404、0.5355±0.0750、0.2549±0.0522、0.2466±0.0342,CXCR4及CCR7蛋白表达趋势同其相对应的基因表达趋势基本一致.4株胃癌细胞侵袭实验测定的侵袭细胞数分别为:400.0±18.2、310.0±4.0、110.0±13.9、85.0±9.5.CXCR4在不同侵袭能力的胃癌细胞株中存在差异性表达(P<0.05).结论 CXCR4的表达与胃癌细胞侵袭能力成正相关,CCR7的表达与胃癌细胞侵袭能力无明显相关.%Objective To compare the differential expression of chemokine receptors CXCR4 and CCR7 in human gastric carcinoma cell lines with different invasion ability. Methods The expression of CXCR4 and CCR7 in MGC803, AGS, BGC823 and SGC7901 cells was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The invasion ability of gastric cancer cell lines was measured using transwell chamber with matrigle. Results The expression of CXCR4 mRNA in MGC803, AGS, BGC823 and SGC790 cells was 1. 2556 ±0. 1384, 0. 7943 ± 0. 0913, 0. 4749 ± 0. 0744, 0. 2463 ± 0. 0344, that of CCR7 mRNA was 0. 6071 ± 0. 1404, 0. 5355 ± 0. 0750, 0. 2549 ± 0. 0522, 0. 2466 ± 0. 0342, respectively. The protein expression of CXCR4 and CCR7 in four human gastric carcino-ma cell lines showed a good agreement with mRNA expression. The penetrating cell number of MGC803, AGS, BGC823 and SGC790 was 400. 0 ± 18. 2, 310. 0 ±4. 0, 110. 0 ±13.9, 85.0 ± 9. 5, respectively. The expression levels of CXCR4 in cancer cells showed a significant positive correlation

  13. The association between regular use of aspirin and the prevalence of prostate cancer: Results from the National Health Interview Survey.

    Science.gov (United States)

    Huang, Wan-Ting; Erickson, Steven R; Hansen, Richard A; Wu, Chung-Hsuen

    2016-06-01

    Prostate cancer is prevalent with significant morbidity in the United States. Aspirin previously has been found to be associated with reduced carcinogenesis of prostate cells. However, it remains unclear whether regularly taking aspirin could lower the risk of prostate cancer. Therefore, our aim was to examine the association between self-reported regular use of aspirin and the prevalence of prostate cancer in a national sample of the US adult population.The National Health Interview Survey is an annual survey conducted by the National Center for Health Statistics to investigate health and healthcare use of the US population. The current study is a population-based cross-sectional study using the 2010 National Health Interview Survey data. Adult male respondents who self-reported regularly taking aspirin at least 3 times per week were grouped as regular users. The prostate cancer prevalence was measured by respondents' self-report of prostate cancer. Multivariable logistic regression models were used to evaluate the association between these 2 factors by adjusting for covariates selected based on Andersen Behavioral Model of Health Services Use.An estimated 23 million (23.7%) males in the United States reported that they took aspirin regularly. Of them, 5.0% had prostate cancer. Regular aspirin use was significantly associated with a lower self-reported prevalence of prostate cancer after adjusting for predisposing, enabling, and need factors (odds ratio 0.60, 95% confidence interval 0.38-0.94).Regular aspirin use was found to be significantly associated with a lower self-reported prevalence of prostate cancer in the United States in 2010. Further clinical trials and longitudinal studies are needed to confirm the causality between regular aspirin use and prostate cancer.

  14. Delineation of target volumes and organs at risk in adjuvant radiotherapy of early breast cancer: national guidelines and contouring atlas by the Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

    Nielsen, Mette H; Berg, Martin; Pedersen, Anders N;

    2013-01-01

    During the past decade planning of adjuvant radiotherapy (RT) of early breast cancer has changed from two-dimensional (2D) to 3D conformal techniques. In the planning computerised tomography (CT) scan both the targets for RT and the organs at risk (OARs) are visualised, enabling an increased focus...... on target dose coverage and homogeneity with only minimal dose to the OARs. To ensure uniform RT in the national prospective trials of the Danish Breast Cancer Cooperative Group (DBCG), a national consensus for the delineation of clinical target volumes (CTVs) and OARs was required....

  15. Trends and variations in breast and colorectal cancer incidence from 1995 to 2011: a comparative study between Texas Cancer Registry and National Cancer Institute's Surveillance, Epidemiology and End Results data.

    Science.gov (United States)

    Liu, Zheyu; Zhang, Yefei; Franzin, Luisa; Cormier, Janice N; Chan, Wenyaw; Xu, Hua; Du, Xianglin L

    2015-04-01

    Few studies have examined the cancer incidence trends in the state of Texas, and no study has ever been conducted to compare the temporal trends of breast and colorectal cancer incidence in Texas with those of the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) in the United States. This study aimed to conduct a parallel comparison between the Texas Cancer Registry and the National Cancer Institute's SEER on cancer incidence from 1995 to 2011. A total of 951,899 breast and colorectal cancer patients were included. Age-adjusted breast cancer incidence was 134.74 per 100,000 in Texas and 131.78 per 100,000 in SEER in 1995-2011, whereas age-adjusted colorectal cancer incidence was 50.52 per 100,000 in Texas and 49.44 per 100,000 in SEER. Breast cancer incidence increased from 1995 to 2001, decreased from 2002 to 2006, and then remained relatively stable from 2007 to 2011. For colorectal cancer, the incidence increased in 1995-1997, and then decreased continuously from 1998 to 2011 in Texas and SEER areas. Incidence rates and relative risks by age, gender and ethnicity were identical between Texas and SEER.

  16. Hypoxia preconditioning of mesenchymal stromal cells enhances PC3 cell lymphatic metastasis accompanied by VEGFR-3/CCR7 activation.

    Science.gov (United States)

    Huang, Xin; Su, Kunkai; Zhou, Limin; Shen, Guofang; Dong, Qi; Lou, Yijia; Zheng, Shu

    2013-12-01

    Mesenchymal stromal cells (MSCs) in bone marrow may enhance tumor metastases through the secretion of chemokines. MSCs have been reported to home toward the hypoxic tumor microenvironment in vivo. In this study, we investigated prostate cancer PC3 cell behavior under the influence of hypoxia preconditioned MSCs and explored the related mechanism of prostate cancer lymphatic metastases in mice. Transwell assays revealed that VEGF-C receptor, VEGFR-3, as well as chemokine CCL21 receptor, CC chemokine receptor 7 (CCR7), were responsible for the migration of PC3 cells toward hypoxia preconditioned MSCs. Knock-in Ccr7 in PC3 cells also improved cell migration in vitro. Furthermore, when PC3 cells were labeled using the hrGfp-lentiviral vector, and were combined with hypoxia preconditioned MSCs for xenografting, it resulted in an enhancement of lymph node metastases accompanied by up-regulation of VEGFR-3 and CCR7 in primary tumors. Both PI3K/Akt/IκBα and JAK2/STAT3 signaling pathways were activated in xenografts in the presence of hypoxia-preconditioned MSCs. Unexpectedly, the p-VEGFR-2/VEGFR-2 ratio was attenuated accompanied by decreased JAK1 expression, indicating a switching-off of potential vascular signal within xenografts in the presence of hypoxia-preconditioned MSCs. Unlike results from other studies, VEGF-C maintained a stable expression in both conditions, which indicated that hypoxia preconditioning of MSCs did not influence VEGF-C secretion. Our results provide the new insights into the functional molecular events and signalings influencing prostate tumor metastases, suggesting a hopeful diagnosis and treatment in new approaches.

  17. CCR5 and CXCR3 are dispensable for liver infiltration, but CCR5 protects against virus-induced T-cell-mediated hepatic steatosis

    DEFF Research Database (Denmark)

    Holst, P J; Orskov, C; Qvortrup, K;

    2007-01-01

    CCR5 and CXCR3 are important molecules in regulating the migration of activated lymphocytes. Thus, the majority of tissue-infiltrating T cells found in the context of autoimmune conditions and viral infections express CCR5 and CXCR3, and the principal chemokine ligands are expressed within inflamed...... tissues. Accordingly, intervention studies have pointed to nonredundant roles of these receptors in models of allograft rejection, viral infection, and autoimmunity. In spite of this, considerable controversy exists, with many studies failing to support a role for CCR5 or CXCR3 in disease pathogenesis....... One possible explanation is that different chemokine receptors may take over in the absence of any individual receptor, thus rendering individual receptors redundant. We have attempted to address this issue by analyzing CCR5(-/-), CXCR3(-/-), and CCR5/CXCR3(-/-) mice with regard to virus-induced liver...

  18. Topotecan inhibits cancer cell migration by down-regulation of chemokine CC motif receptor 7 and matrix metalloproteinases

    Institute of Scientific and Technical Information of China (English)

    Sen-sen LIN; Li SUN; Yan-kai ZHANG; Ren-ping ZHAO; Wen-lu LIANG; Sheng-tao YUAN; Lu-yong ZHANG

    2009-01-01

    Aim: The aim of this study was to investigate the effect of topotecan (TPT) on cancer cell migration.Methods: Growth inhibition of TPT was analyzed by MTT assay, and cancer cell migration was measured by transwell double chamber assay. To verify the effect of TPT on the chemokine receptors CXCR4 and CCR7, quantitative PCR, semi-quantitative PCR and Western blot analysis were performed. The secretion of MMP-2 and MMP-9 was detected by enzyme-linked immunosorbent assay (ELISA) and gelatin zymography. To evaluate possible contributions of CCR7 to MMP secretion, the overexpression vectors pcDNA3.1+-CCR7 and CCR7 siRNA were transiently transfected into MDA-MB-435 cells.Results: TPT inhibited cancer cell migration in a dose-dependent manner. Additionally, TPT significantly decreased the expression of CCR7 in both MDA-MB-435 and MDA-MB-231 cells and moderately reduced the expression of CXCR4 in MDA-MB-435 cells. The secretion of MMPs (MMP-2, MMP-9) was also inhibited by TPT. Overexpression of CCR7 increased the secretion of MMP-2/9 and cancer cell migration, whereas knockdown of CCR7 reduced active MMP-2/9 production and migration of MDA-MB-435 cells.Conclusion: TPT inhibited cancer cell migration by down-regulation of CCR7 and MMPs (MMP-2 and MMP-9).

  19. Matrix metalloproteinase-9 is up-regulated by CCL19/CCR7 interaction via PI3K/Akt pathway and is involved in CCL19-driven BMSCs migration.

    Science.gov (United States)

    Zhang, Wei; Tu, Guanjun; Lv, Chen; Long, Jun; Cong, Lin; Han, Yaxin

    2014-08-22

    C-C chemokine receptor 7 (CCR7) and its ligands CCL19 contributes to the directional migration of certain cancer cell lines, but its role in the migration of BMSCs remains vague. The aim of this study was to determine the possible interaction between CCL19-induced conditions and matrix metalloproteinases-9 (MMP9) expression in BMSCs. Cell migration using Transwell assay indicated that activation of CCR7 by its specific ligand, exogenous chemokine ligand 19 (CCL19), was associated with a significant linear increase. Western blot and real-time PCR indicated that CCL19/CCR7 significantly upregulated expression of MMP9, which is related to metastasis-associated genes. The CCL19/CCR7 interaction significantly enhanced phosphorylation of Akt, as measured by Western blot. P-Akt and MMP9 protein expression exhibited a time-dependent pattern, and the peak was at 48h. LY294002 significantly abolished the effects of exogenous CCL19. These results suggest that CCL19/CCR7 contributes to the migration of BMSCs by upregulating MMP9 potentially via the PI3K/Akt pathway.

  20. Initial results of the National Colorectal Cancer Screening Program in Lithuania.

    Science.gov (United States)

    Poskus, Tomas; Strupas, Kestutis; Mikalauskas, Saulius; Bitinaitė, Dominyka; Kavaliauskas, Augustas; Samalavicius, Narimantas E; Saladzinskas, Zilvinas

    2015-03-01

    The aim of the present study was to review the National Colorectal Cancer Screening Program (the Program) in Lithuania according to the criteria set by the European Union. In Lithuania, screening services are provided free of charge to the population. The National Health Insurance Fund (NHIF) reimburses the institutions for performing each service; each procedure within the Program has its own administrative code. All the information about the performance of the Program is collected in one institution - the NHIF. The results of the Program were retrieved from the database of NHIF from the start of the Program from 1 July 2009 to 1 July 2012. Descriptive analysis of epidemiological indicators was carried out. Results were compared with the references in the guidelines of the European Union for quality assurance in colorectal cancer (CRC) screening and diagnosis. Information service [which involves fecal immunochemical test (FIT)] was provided to 271,396 of 890,309 50-74-year-old residents. The screening uptake was 46.0% over 3 years. During this period, 19,455 (7.2%) FITs were positive and 251,941 (92.8%) FITs were negative. Referral for colonoscopy was performed in 10,190 (52.4%) patients. Colonoscopy was performed in 12,864 (66.1%) patients. Colonoscopy did not indicate any pathological findings in 8613 (67.0%) patients. Biopsies were performed in 4251 (33.0%) patients. The rate of high-grade neoplasia reported by pathologists was 3.9%; the rate of cancer was 3.1% of all colonoscopies. The rate of CRC detected by the Program was 0.2%. The CRC screening program in Lithuania meets most of the requirements for standardized CRC screening programs. The invitation coverage and rate of referral for colonoscopy after positive FIT should be improved.

  1. Preparation of specific polyclonal antibodies to a C-C chemokine receptor, CCR1, and determination of CCR1 expression on various types of leukocytes.

    Science.gov (United States)

    Su, S B; Mukaida, N; Wang, J; Nomura, H; Matsushima, K

    1996-11-01

    cDNA cloning has revealed the presence of at least three distinct human receptors for macrophage inflammatory protein-1alpha (MIP-1alpha) and RANTES: C-C chemokine receptor (CCR) 1, 4, and 5. To clarify the physiological role of CCR1, we prepared specific antibodies to CCR1 by immunizing rabbits with recombinant glutathione-S-transferase (GST) fused with its NH2-terminal portion. The resultant antibodies stained positively 293 cells transfected with CCR1 cDNA but neither parental cells nor cells transfected with CXCR1 [interleukin-8 (IL-8) receptor type A] cDNA, confirming its specificity. Immunofluorescence analysis revealed that peripheral blood lymphocytes and monocytes but not neutrophils express CCR1. Positive staining of transfectants, monocytes, and lymphocytes was inhibited by the GST protein fused with the NH2-terminal portion of CCR1, further indicating that this antibody recognized the NH2-terminal portion of CC CKR1. A majority of CD3+, CD4+, CD8+, or CD16+ peripheral blood lymphocytes but not CD19+ lymphocytes expressed CCR1. Among CD4+ peripheral blood lymphocytes, CD45RO+ cells expressed a larger number of CCR1 compared with CD45RO-. Moreover, CD34+ cells in human bone marrow as well as cord blood were uniformly stained with this antibody. Furthermore, the antibody inhibited calcium mobilization in CCR1 transfectants stimulated with human rMIP-1alpha, suggesting that its NH2-terminal portion is critically involved in ligand binding or signaling. Finally, the antibody partially inhibited monocyte chemotactic activities of human rMIP-1alpha, suggesting that CCR1 is a functional receptor for MIP-1alpha on human peripheral blood monocytes.

  2. HIV-1 resistance to CCR5 antagonists associated with highly efficient use of CCR5 and altered tropism on primary CD4+ T cells.

    Science.gov (United States)

    Pfaff, Jennifer M; Wilen, Craig B; Harrison, Jessamina E; Demarest, James F; Lee, Benhur; Doms, Robert W; Tilton, John C

    2010-07-01

    We previously reported on a panel of HIV-1 clade B envelope (Env) proteins isolated from a patient treated with the CCR5 antagonist aplaviroc (APL) that were drug resistant. These Envs used the APL-bound conformation of CCR5, were cross resistant to other small-molecule CCR5 antagonists, and were isolated from the patient's pretreatment viral quasispecies as well as after therapy. We analyzed viral and host determinants of resistance and their effects on viral tropism on primary CD4(+) T cells. The V3 loop contained residues essential for viral resistance to APL, while additional mutations in gp120 and gp41 modulated the magnitude of drug resistance. However, these mutations were context dependent, being unable to confer resistance when introduced into a heterologous virus. The resistant virus displayed altered binding between gp120 and CCR5 such that the virus became critically dependent on the N' terminus of CCR5 in the presence of APL. In addition, the drug-resistant Envs studied here utilized CCR5 very efficiently: robust virus infection occurred even when very low levels of CCR5 were expressed. However, recognition of drug-bound CCR5 was less efficient, resulting in a tropism shift toward effector memory cells upon infection of primary CD4(+) T cells in the presence of APL, with relative sparing of the central memory CD4(+) T cell subset. If such a tropism shift proves to be a common feature of CCR5-antagonist-resistant viruses, then continued use of CCR5 antagonists even in the face of virologic failure could provide a relative degree of protection to the T(CM) subset of CD4(+) T cells and result in improved T cell homeostasis and immune function.

  3. CCR5 Disruption in Induced Pluripotent Stem Cells Using CRISPR/Cas9 Provides Selective Resistance of Immune Cells to CCR5-tropic HIV-1 Virus.

    Science.gov (United States)

    Kang, HyunJun; Minder, Petra; Park, Mi Ae; Mesquitta, Walatta-Tseyon; Torbett, Bruce E; Slukvin, Igor I

    2015-12-15

    The chemokine (C-C motif) receptor 5 (CCR5) serves as an HIV-1 co-receptor and is essential for cell infection with CCR5-tropic viruses. Loss of functional receptor protects against HIV infection. Here, we report the successful targeting of CCR5 in GFP-marked human induced pluripotent stem cells (iPSCs) using CRISPR/Cas9 with single and dual guide RNAs (gRNAs). Following CRISPER/Cas9-mediated gene editing using a single gRNA, 12.5% of cell colonies demonstrated CCR5 editing, of which 22.2% showed biallelic editing as determined by a Surveyor nuclease assay and direct sequencing. The use of dual gRNAs significantly increased the efficacy of CCR5 editing to 27% with a biallelic gene alteration frequency of 41%. To ensure the homogeneity of gene editing within cells, we used single cell sorting to establish clonal iPSC lines. Single cell-derived iPSC lines with homozygous CCR5 mutations displayed the typical characteristics of pluripotent stem cells and differentiated efficiently into hematopoietic cells, including macrophages. Although macrophages from both wild-type and CCR5-edited iPSCs supported CXCR4-tropic virus replication, macrophages from CCR5-edited iPSCs were uniquely resistant to CCR5-tropic virus challenge. This study demonstrates the feasibility of applying iPSC technology for the study of the role of CCR5 in HIV infection in vitro, and generation of HIV-resistant cells for potential therapeutic applications.

  4. Effects of the CCR5-Delta32 mutation on hepatitis C virus-specific immune responses in patients with haemophilia.

    Science.gov (United States)

    Ahlenstiel, Golo; Woitas, Rainer P; Iwan, Agathe; Nattermann, Jacob; Feldmann, Georg; Rockstroh, Jürgen K; Oldenburg, Johannes; Kupfer, Bernd; Sauerbruch, Tilman; Spengler, Ulrich

    2009-01-01

    In hepatitis C virus (HCV) infection antiviral T cells express the CC chemokine receptor 5 (CCR5). Their recruitment to the liver is an important step in the immune response. A 32 base pair deletion in the CCR5 gene leads to reduced expression and total loss of CCR5 in CCR5-Delta32 heterozygous and homozygous subjects, respectively. However, the role of this mutation for antiviral immunity remains unclear. Here, we analysed proliferation, IFN-gamma and IL-4 secretion (ELISpot) induced by the HCV antigens core, NS3, NS4, and NS5a in 21 anti-HCV-positive haemophiliac patients in relationship to their CCR5 genotypes (CCR5 wildtype n = 10, CCR5-Delta32 heterozygous n = 5 and CCR5-Delta32 homozygous n = 6). Furthermore, T cell migration in response to the CCR5 ligands CCL3, -4 and -5 was studied. Overall IFN-gamma responses to HCV proteins were only slightly greater in CCR5 wild-type patients than in CCR5-Delta32 carriers (0.6 versus 0.24 SFC/10(4) PBMC; p = 0.043). This difference was consistently seen with all tested HCV antigens. In contrast, neither T cell migration, nor PBMC proliferation, nor IL-4 production differed between CCR5 genotypes. Interruption of the CCR5 signalling pathway due to CCR5-Delta32 may potentially result in subtle reduction of HCV specific IFN-gamma responses in anti-HCV-positive haemophiliac patients.

  5. Anti-HIV Target and Resistance to CCR5 Inhibitors%抗HIV药物靶点CCR5及HIV对CCR5抑制剂的抗性

    Institute of Scientific and Technical Information of China (English)

    陈超; 高向东; 顾觉奋

    2012-01-01

    趋化因子受体CCR5是细胞膜表面G蛋白偶联受体中的一员.HIV-1在体内与细胞融合时需要CCR5作为辅助受体介导.因此,CCR5可作为抗HIV-1药物的筛选靶点,目前已筛选出多种CCR5抑制剂.但随着CCR5抑制剂的使用,HIV-1对于这些抑制剂的抗性也逐渐产生,而抗性的产生机制还不明确.本文主要介绍CCR5介导HIV-1与细胞融合的机制及HIV-1对CCR5抑制剂的抗性产生机制.

  6. Limited protective effect of the CCR5Delta32/CCR5Delta32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus

    DEFF Research Database (Denmark)

    Iversen, Astrid K N; Christiansen, Claus Bohn; Attermann, Jørn

    2003-01-01

    The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2% of the Scand......The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2...

  7. Functional characterization of CCR in birch (Betula platyphylla × Betula pendula) through overexpression and suppression analysis.

    Science.gov (United States)

    Zhang, Wenbo; Wei, Rui; Chen, Su; Jiang, Jing; Li, Huiyu; Huang, Haijiao; Yang, Guang; Wang, Shuo; Wei, Hairong; Liu, Guifeng

    2015-06-01

    We cloned a Cinnamoyl-CoA Reductase gene (BpCCR1) from an apical meristem and first internode of Betula platyphylla and characterized its functions in lignin biosynthesis, wood formation and tree growth through transgenic approaches. We generated overexpression and suppression transgenic lines and analyzed them in comparison with the wild-type in terms of lignin content, anatomical characteristics, height and biomass. We found that BpCCR1 overexpression could increase lignin content up to 14.6%, and its underexpression decreased lignin content by 6.3%. Surprisingly, modification of BpCCR1 expression led to conspicuous changes in wood characteristics, including xylem vessel number and arrangement, and secondary wall thickness. The growth of transgenic trees in terms of height was also significantly influenced by the modification of BpCCR1 genes. We discuss the functions of BpCCR1 in the context of a phylogenetic tree built with CCR genes from multiple species.

  8. The expression of periphery blood leucocyte CCR3 and CCR5 in the children with Epstein-Barr virus associated infectious mononucleosis%感染EB病毒的传染性单核细胞增多症患儿外周血白细胞CCR3和CCR5的表达

    Institute of Scientific and Technical Information of China (English)

    齐铁雄; 高国花; 刘世华

    2010-01-01

    目的 探讨感染EB病毒的传染性单核细胞增多症(IM)患儿CCR3和CCR5的表达,以期了解Th1/Th2细胞的分化情况.方法 观察患儿外周血异型淋巴细胞比例,测定患儿的嗜异凝集抗体,用双抗体夹心酶联免疫吸附法(ELISA)测定患儿抗EBV-CA-IgM、抗EBV-CA-IgG及抗EBV-NA-IgG,筛选出符合诊断标准的IM患儿.并用流式细胞检测仪检测淋巴细胞中CCR3和CCR5的表达.结果 IM感染组异型淋巴细胞比例高于对照组(P<0.05).IM感染组CCR3+细胞率高于对照组(P<0.05),CCR5+细胞率低于对照组(P<0.05).CCR3与发热持续时间、异型淋巴细胞百分数呈正相关(P<0.05).CCR5与发热持续时间呈负相关(P<0.05).结论 IM患儿CCR3+表达增高,CCR5+表达降低,存在以Th2细胞优势分化状态为特征的T辅助细胞分化失衡.CCR3和CCR5可以作为判断IM病情轻重的重要参考指标.%Objective To explore the expression of periphery blood leucocyte CCR3 and CCR5 and to comprehend T helper cell in the Children with Epstein-Barr virus associated infectious mononucleosis.Methods We defined the children according to the diagnosis criterion through Paul-Bunnell test inspecting the children's periphery blood unusual lymphocyte and detecting their anti-EBV-CA-IgM, anti-EBV-CA-IgG and anti-EBV-NA-IgG by ELISA and counted the ratio of CCR3 + and CCR5 + cells in lymphocytes with flow cytometry. Results The ratio of unusual lymphocyte in IM was higher than that of the healthy control group (P < O. 05). The ratio of CCR3 + cells in IM group was higher than that of the healthy control group (P < 0.05). The ratio of CCR5 + cells in IM group was significantly lower than that of the healthy control group. CCR3 + had direct interrelation with fever continued time and the ratio of unusual lymphocyte. There was a negative interrelation between CCR5 and fever continued time ( P < 0. 05 ). Conclusions Children infectious of IM expressed higher level of CCR3 + and lower

  9. Epidemiological changes in oesophageal cancer at National Hospital, Bloemfontein: 1995, 2000 and 2005

    Directory of Open Access Journals (Sweden)

    Tian van der Merwe

    2010-03-01

    Full Text Available Background: Oesophageal cancer is a common malignancy with a high mortality rate. The two main histological types are squamous cell and adenocarcinoma. An increase in oesophageal adenocarcinoma has been noted, especially in developed countries.Objectives: The aim of this retrospective study was to investigate the profile of oesophageal cancer by reviewing medical records of patients diagnosed with oesophageal cancer in 1995, 2000 and 2005.Method: The study sample consisted of 474 files of patients diagnosed, for the first time, with oesophageal cancer in 1995, 2000 and 2005, at the National Hospital in Bloemfontein and the outreach clinics in surrounding areas. Information reviewed from patient files included: age, race and gender of the patient, as well as topography, size, histological grade and type of the tumour.Results: The number of newly diagnosed cases of oesophageal carcinoma decreased over the 10-year period. The mean age of patients was > 57 years. The majority of cases were Black patients: 90.5% in 1995, 93.2% in 2000 and 87.7% in 2005. More male patients were seen (71.5% in 1995, 70.1% in 2000 and 64.2% in 2005, although the number of female patients diagnosed with this malignancy increased by 7.3% from 1995 to 2005. The mid- and lower third of the oesophagus were affected most commonly, most lesions were 6 cm – 10 cm in length and classified as Grade II, moderately differentiated tumours. Squamous cell carcinoma was diagnosed in 76.9% of patients in 1995, 90.5% in 2000 and 94.3% in 2005.Conclusion: The number of newly diagnosed cases of oesophageal carcinoma decreased over the 10-year period, but demographic and disease characteristics remained constant.

  10. Quality Improvement in the National Cancer Institute Community Cancer Centers Program: The Quality Oncology Practice Initiative Experience

    Science.gov (United States)

    Siegel, Robert D.; Castro, Kathleen M.; Eisenstein, Jana; Stallings, Holley; Hegedus, Patricia D.; Bryant, Donna M.; Kadlubek, Pam J.; Clauser, Steven B.

    2015-01-01

    Purpose: The National Cancer Institute (NCI) Community Cancer Centers Program (NCCCP) began in 2007; it is a network of community-based hospitals funded by the NCI. Quality of care is an NCCCP priority, with participation in the American Society of Clinical Oncology Quality Oncology Practice Initiative (QOPI) playing a fundamental role in quality assessment and quality improvement (QI) projects. Using QOPI methodology, performance on quality measures was analyzed two times per year over a 3-year period to enhance our implementation of quality standards at NCCCP hospitals. Methods: A data-sharing agreement allowed individual-practice QOPI data to be electronically sent to the NCI. Aggregated data with the other NCCCP QOPI participants were presented to the network via Webinars. The NCCCP Quality of Care Subcommittee selected areas in which to focus subsequent QI efforts, and high-performing practices shared voluntarily their QI best practices with the network. Results: QOPI results were compiled semiannually between fall 2010 and fall 2013. The network concentrated on measures with a quality score of ≤ 0.75 and planned voluntary group-wide QI interventions. We identified 13 measures in which the NCCCP fell at or below the designated quality score in fall 2010. After implementing a variety of QI initiatives, the network registered improvements in all parameters except one (use of treatment summaries). Conclusion: Using the NCCCP as a paradigm, QOPI metrics provide a useful platform for group-wide measurement of quality performance. In addition, these measurements can be used to assess the effectiveness of QI initiatives. PMID:25538082

  11. CCR5 haplotypes and mother-to-child HIV transmission in Malawi.

    Directory of Open Access Journals (Sweden)

    Bonnie R Pedersen

    Full Text Available BACKGROUND: CCR5 and CCR2 gene polymorphisms (SNPs have been associated with protection against HIV transmission in adults and with delayed progression to AIDS. The CCR5 Delta32 deletion and SNP -2459G are associated with reduced expression of the CCR5 protein. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the association between infant CCR2/CCR5 diplotype and HIV mother to child transmission (MTCT in Malawi. Blood samples from infants (n = 552 of HIV positive women who received nevirapine were genotyped using a post-PCR multiplex ligase detection reaction and haplotypes were identified based on 8 CCR2/CCR5 SNPs and the open reading frame 32 base pair deletion. Following verification of Hardy-Weinberg equilibrium, log linear regression was performed to examine the association between mutations and MTCT. Overall, protection against MTCT was weakly associated with two CCR5 SNPs, -2459G (Risk ratio [RR], 0.78; confidence interval [CI], 0.54-1.12, and the linked CCR5 -2135T (RR, 0.78; CI, 0.54-1.13. No child carried the CCR5 Delta32 SNP. Maternal Viral Load (MVL was found to be an effect measure modifier. Among mothers with low MVL, statistically significant protection against MTCT was observed for -2459G (RR, 0.50; CI, 0.27-0.91, and -2135T (RR, 0.51; CI, 0.28-0.92. Statistically significant protection was not found at high MVL. CONCLUSIONS/SIGNIFICANCE: Results from this study suggest that CCR5 SNPs -2459G and -2135T associated with reduced receptor expression protect against MTCT of HIV at low MVLs, whereas high MVLs may over-ride differences in coreceptor availability.

  12. Induction of Murine Mucosal CCR5-Reactive Antibodies as an Anti-Human Immunodeficiency Virus Strategy

    Science.gov (United States)

    Barassi, C.; Soprana, E.; Pastori, C.; Longhi, R.; Buratti, E.; Lillo, F.; Marenzi, C.; Lazzarin, A.; Siccardi, A. G.; Lopalco, L.

    2005-01-01

    The genital mucosa is the main site of initial human immunodeficiency virus type 1 (HIV-1) contact with its host. In spite of repeated sexual exposure, some individuals remain seronegative, and a small fraction of them produce immunoglobulin G (IgG) and IgA autoantibodies directed against CCR5, which is probably the cause of the CCR5-minus phenotype observed in the peripheral blood mononuclear cells of these subjects. These antibodies recognize the 89-to-102 extracellular loop of CCR5 in its native conformation. The aim of this study was to induce infection-preventing mucosal anti-CCR5 autoantibodies in individuals at high risk of HIV infection. Thus, we generated chimeric immunogens containing the relevant CCR5 peptide in the context of the capsid protein of Flock House virus, a presentation system in which it is possible to engineer conformationally constrained peptide in a highly immunogenic form. Administered in mice via the systemic or mucosal route, the immunogens elicited anti-CCR5 IgG and IgA (in sera and vaginal fluids). Analogous to exposed seronegative individuals, mice producing anti-CCR5 autoantibodies express significantly reduced levels of CCR5 on the surfaces of CD4+ cells from peripheral blood and vaginal washes. In vitro studies have shown that murine IgG and IgA (i) specifically bind human and mouse CD4+ lymphocytes and the CCR5-transfected U87 cell line, (ii) down-regulate CCR5 expression of CD4+ cells from both humans and untreated mice, (iii) inhibit Mip-1β chemotaxis of CD4+ CCR5+ lymphocytes, and (iv) neutralize HIV R5 strains. These data suggest that immune strategies aimed at generating anti-CCR5 antibodies at the level of the genital mucosa might be feasible and represent a strategy to induce mucosal HIV-protective immunity. PMID:15890924

  13. The CCR4-NOT complex physically and functionally interacts with TRAMP and the nuclear exosome.

    Directory of Open Access Journals (Sweden)

    Nowel Azzouz

    Full Text Available BACKGROUND: Ccr4-Not is a highly conserved multi-protein complex consisting in yeast of 9 subunits, including Not5 and the major yeast deadenylase Ccr4. It has been connected functionally in the nucleus to transcription by RNA polymerase II and in the cytoplasm to mRNA degradation. However, there has been no evidence so far that this complex is important for RNA degradation in the nucleus. METHODOLOGY/PRINCIPAL FINDINGS: In this work we point to a new role for the Ccr4-Not complex in nuclear RNA metabolism. We determine the importance of the Ccr4-Not complex for the levels of non-coding nuclear RNAs, such as mis-processed and polyadenylated snoRNAs, whose turnover depends upon the nuclear exosome and TRAMP. Consistently, mutation of both the Ccr4-Not complex and the nuclear exosome results in synthetic slow growth phenotypes. We demonstrate physical interactions between the Ccr4-Not complex and the exosome. First, Not5 co-purifies with the exosome. Second, several exosome subunits co-purify with the Ccr4-Not complex. Third, the Ccr4-Not complex is important for the integrity of large exosome-containing complexes. Finally, we reveal a connection between the Ccr4-Not complex and TRAMP through the association of the Mtr4 helicase with the Ccr4-Not complex and the importance of specific subunits of Ccr4-Not for the association of Mtr4 with the nuclear exosome subunit Rrp6. CONCLUSIONS/SIGNIFICANCE: We propose a model in which the Ccr4-Not complex may provide a platform contributing to dynamic interactions between the nuclear exosome and its co-factor TRAMP. Our findings connect for the first time the different players involved in nuclear and cytoplasmic RNA degradation.

  14. The HIV-1 Gp120/CXCR4 Axis Promotes CCR7 Ligand-Dependent CD4 T Cell Migration: CCR7 Homo- and CCR7/CXCR4 Hetero-Oligomer Formation as a Possible Mechanism for Up-Regulation of Functional CCR7

    OpenAIRE

    Haruko Hayasaka; Daichi Kobayashi; Hiromi Yoshimura; Nakayama, Emi E.; Tatsuo Shioda; Masayuki Miyasaka

    2015-01-01

    During human immunodeficiency virus (HIV) infection, enhanced migration of infected cells to lymph nodes leads to efficient propagation of HIV-1. The selective chemokine receptors, including CXCR4 and CCR7, may play a role in this process, yet the viral factors regulating chemokine-dependent T cell migration remain relatively unclear. The functional cooperation between the CXCR4 ligand chemokine CXCL12 and the CCR7 ligand chemokines CCL19 and CCL21 enhances CCR7-dependent T cell motility in v...

  15. Ubiquitylation of the chemokine receptor CCR7 enables efficient receptor recycling and cell migration

    OpenAIRE

    Schäuble, Karin; Hauser, Mark A.; Rippl, Alexandra; Bruderer, Roland; Otero, Carolina; Gröttrup, Marcus; Legler, Daniel F.

    2012-01-01

    The chemokine receptor CCR7 is essential for lymphocyte and dendritic cell homing to secondary lymphoid organs. Owing to the ability to induce directional migration, CCR7 and its ligands CCL19 and CCL21 are pivotal for the regulation of the immune system. Here, we identify a novel function for receptor ubiquitylation in the regulation of the trafficking process of this G-protein-coupled seven transmembrane receptor. We discovered that CCR7 is ubiquitylated in a constitutive, ligand-independen...

  16. TALEN-Mediated Knockout of CCR5 Confers Protection Against Infection of Human Immunodeficiency Virus.

    Science.gov (United States)

    Shi, Bingjie; Li, Juan; Shi, Xuanling; Jia, Wenxu; Wen, Yi; Hu, Xiongbing; Zhuang, Fengfeng; Xi, Jianzhong; Zhang, Linqi

    2017-02-01

    Transcription activator-like effector nuclease (TALEN) represents a valuable tool for genomic engineering due to its single-nucleotide precision, high nuclease activity, and low cytotoxicity. We report here systematic design and characterization of 28 novel TALENs targeting multiple regions of CCR5 gene (CCR5-TALEN) which encodes the co-receptor critical for entry of human immunodeficiency virus type I (HIV-1). By systemic characterization of these CCR5-TALENs, we have identified one (CCR5-TALEN-515) with higher nuclease activity, specificity, and lower cytotoxicity compared with zinc-finger nuclease (CCR5-ZFN) currently undergoing clinical trials. Sequence analysis of target cell line GHOST-CCR5-CXCR4 and human primary CD4 T cells showed that the double-strand breaks at the TALEN targeted sites resulted in truncated or nonfunctional CCR5 proteins thereby conferring protection against HIV-1 infection in vitro. None of the CCR5-TALENs had detectable levels of off-target nuclease activity against the homologous region in CCR2 although substantial level was identified for CCR5-ZFN in the primary CD4 T cells. Our results suggest that the CCR5-TALENs identified here are highly functional nucleases that produce protective genetic alterations to human CCR5. Application of these TALENs directly to the primary CD4 T cells and CD34 hematopoietic stem cells (HSCs) of infected individuals could help to create an immune system resistant to HIV-1 infection, recapitulating the success of "Berlin patient" and serving as an essential first step towards a "functional" cure of AIDS.

  17. Socioeconomic impact of cancer in member countries of the Association of Southeast Asian Nations (ASEAN): the ACTION study protocol.

    Science.gov (United States)

    Kimman, Merel; Jan, Stephen; Kingston, David; Monaghan, Helen; Sokha, Eav; Thabrany, Hasbullah; Bounxouei, Bounthaphany; Bhoo-Pathy, Nirmala; Khin, Myo; Cristal-Luna, Gloria; Khuhaprema, Thiravud; Hung, Nguyen Chan; Woodward, Mark

    2012-01-01

    Cancer can be a major cause of poverty. This may be due either to the costs of treating and managing the illness as well as its impact upon people's ability to work. This is a concern that particularly affects countries that lack comprehensive social health insurance systems and other types of social safety nets. The ACTION study is a longitudinal cohort study of 10,000 hospital patients with a first time diagnosis of cancer. It aims to assess the impact of cancer on the economic circumstances of patients and their households, patients' quality of life, costs of treatment and survival. Patients will be followed throughout the first year after their cancer diagnosis, with interviews conducted at baseline (after diagnosis), three and 12 months. A cross-section of public and private hospitals as well as cancer centers across eight member countries of the Association of Southeast Asian Nations (ASEAN) will invite patients to participate. The primary outcome is incidence of financial catastrophe following treatment for cancer, defined as out-of-pocket health care expenditure at 12 months exceeding 30% of household income. Secondary outcomes include illness induced poverty, quality of life, psychological distress, economic hardship, survival and disease status. The findings can raise awareness of the extent of the cancer problem in South East Asia and its breadth in terms of its implications for households and the communities in which cancer patients live, identify priorities for further research and catalyze political action to put in place effective cancer control policies.

  18. Prevention, early detection and team management of skin cancer in primary care: contribution to The health of the nation objectives.

    Science.gov (United States)

    Jackson, A

    1995-02-01

    The incidence of all skin cancers is increasing. If The health of the nation targets are to be addressed, incidence figures need to be more accurate. Solar damage is the major causal factor in all skin cancers. Certain individual risk factors also play an important part, especially in the development of malignant melanoma. Prevention and early detection are crucial in reducing morbidity and mortality from skin cancer. This paper considers the role of primary care skin screening clinics and cutaneous surgery facilities in the early detection and management of skin cancer. It also illustrates the value of a team approach in primary care in the prevention and early detection of skin cancer and in the more accurate recording of incidence rates.

  19. CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory

    Science.gov (United States)

    Zhou, Miou; Greenhill, Stuart; Huang, Shan; Silva, Tawnie K; Sano, Yoshitake; Wu, Shumin; Cai, Ying; Nagaoka, Yoshiko; Sehgal, Megha; Cai, Denise J; Lee, Yong-Seok; Fox, Kevin; Silva, Alcino J

    2016-01-01

    Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity. These results suggest that CCR5 is a powerful suppressor for plasticity and memory, and CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits. Consistent with this hypothesis, the HIV V3 peptide caused LTP, signaling and memory deficits that were prevented by Ccr5 knockout or knockdown. Overall, our results demonstrate that CCR5 plays an important role in neuroplasticity, learning and memory, and indicate that CCR5 has a role in the cognitive deficits caused by HIV. DOI: http://dx.doi.org/10.7554/eLife.20985.001 PMID:27996938

  20. HIV-1 exploits CCR5 conformational heterogeneity to escape inhibition by chemokines.

    OpenAIRE

    2013-01-01

    International audience; CC chemokine receptor 5 (CCR5) is a receptor for chemokines and the coreceptor for R5 HIV-1 entry into CD4(+) T lymphocytes. Chemokines exert anti-HIV-1 activity in vitro, both by displacing the viral envelope glycoprotein gp120 from binding to CCR5 and by promoting CCR5 endocytosis, suggesting that they play a protective role in HIV infection. However, we showed here that different CCR5 conformations at the cell surface are differentially engaged by chemokines and gp1...

  1. Effect of CCR5-Δ32 heterozygosity on HIV-1 susceptibility: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Sijie Liu

    Full Text Available BACKGROUND: So far, many studies have investigated the distribution of CCR5 genotype between HIV-1 infected patients and uninfected people. However, no definite results have been put forward about whether heterozygosity for a 32-basepair deletion in CCR5 gene (CCR5-Δ32 can affect HIV-1 susceptibility. METHODS: We performed a meta-analysis of 18 studies including more than 12000 subjects for whom the CCR5-Δ32 polymorphism was genotyped. Odds ratio (OR with 95% confidence interval (CI were employed to assess the association of CCR5-Δ32 polymorphism with HIV-1 susceptibility. RESULTS: Compared with the wild-type CCR5 homozygotes, the pooled OR for CCR5-Δ32 heterozygotes was 1.02 (95%CI, 0.88-1.19 for healthy controls (HC and 0.95 (95%CI, 0.71-1.26 for exposed uninfected (EU controls. Similar results were found in stratified analysis by ethnicity, sample size and method of CCR5-Δ32 genotyping. CONCLUSIONS: The meta-analysis indicated that HIV-1 susceptibility is not significantly affected by heterozygosity for CCR5-Δ32.

  2. Dengue virus requires the CC-chemokine receptor CCR5 for replication and infection development.

    Science.gov (United States)

    Marques, Rafael E; Guabiraba, Rodrigo; Del Sarto, Juliana L; Rocha, Rebeca F; Queiroz, Ana Luiza; Cisalpino, Daniel; Marques, Pedro E; Pacca, Carolina C; Fagundes, Caio T; Menezes, Gustavo B; Nogueira, Maurício L; Souza, Danielle G; Teixeira, Mauro M

    2015-08-01

    Dengue is a mosquito-borne disease that affects millions of people worldwide yearly. Currently, there is no vaccine or specific treatment available. Further investigation on dengue pathogenesis is required to better understand the disease and to identify potential therapeutic targets. The chemokine system has been implicated in dengue pathogenesis, although the specific role of chemokines and their receptors remains elusive. Here we describe the role of the CC-chemokine receptor CCR5 in Dengue virus (DENV-2) infection. In vitro experiments showed that CCR5 is a host factor required for DENV-2 replication in human and mouse macrophages. DENV-2 infection induces the expression of CCR5 ligands. Incubation with an antagonist prevents CCR5 activation and reduces DENV-2 positive-stranded (+) RNA inside macrophages. Using an immunocompetent mouse model of DENV-2 infection we found that CCR5(-/-) mice were resistant to lethal infection, presenting at least 100-fold reduction of viral load in target organs and significant reduction in disease severity. This phenotype was reproduced in wild-type mice treated with CCR5-blocking compounds. Therefore, CCR5 is a host factor required for DENV-2 replication and disease development. Targeting CCR5 might represent a therapeutic strategy for dengue fever. These data bring new insights on the association between viral infections and the chemokine receptor CCR5.

  3. A role for MCP-1/CCR2 in interstitial lung disease in children

    Directory of Open Access Journals (Sweden)

    Reinhardt Dietrich

    2005-08-01

    Full Text Available Abstract Background Interstitial lung diseases (ILD are chronic inflammatory disorders leading to pulmonary fibrosis. Monocyte chemotactic protein 1 (MCP-1 promotes collagen synthesis and deletion of the MCP-1 receptor CCR2 protects from pulmonary fibrosis in ILD mouse models. We hypothesized that pulmonary MCP-1 and CCR2+ T cells accumulate in pediatric ILD and are related to disease severity. Methods Bronchoalveolar lavage fluid was obtained from 25 children with ILD and 10 healthy children. Levels of pulmonary MCP-1 and Th1/Th2-associated cytokines were quantified at the protein and the mRNA levels. Pulmonary CCR2+, CCR4+, CCR3+, CCR5+ and CXCR3+ T cells were quantified by flow-cytometry. Results CCR2+ T cells and MCP-1 levels were significantly elevated in children with ILD and correlated with forced vital capacity, total lung capacity and ILD disease severity scores. Children with lung fibrosis had significantly higher MCP-1 levels and CCR2+ T cells in bronchoalveolar lavage fluid compared to non-fibrotic children. Conclusion The results indicate that pulmonary CCR2+ T cells and MCP-1 contribute to the pathogenesis of pediatric ILD and might provide a novel target for therapeutic strategies.

  4. ERK1-Based Pathway as a New Selective Mechanism To Modulate CCR5 with Natural Antibodies.

    Science.gov (United States)

    Venuti, Assunta; Pastori, Claudia; Siracusano, Gabriel; Riva, Agostino; Sciortino, Maria Teresa; Lopalco, Lucia

    2015-10-01

    Natural human Abs, recognizing an epitope within the first extramembrane loop of CCR5 (the main HIV coreceptor), induce a long-lasting internalization (48 h) of the protein, whereas all known CCR5 modulating molecules show a short-term kinetics (60-90 min). Despite extensive studies on the regulation of CCR5 signaling cascades, which are the effect of concomitant CCR5 internalization by exogenous stimuli such as Abs, downstream signaling continues to be poorly understood. In this article, we report a hitherto unrecognized mechanism of CCR5 modulation mediated by G protein-dependent ERK1 activity. We further demonstrate that ERK1 is localized mainly in the cytoplasmic compartment and that it interacts directly with the CCR5 protein, thus provoking possible CCR5 degradation with a subsequent de novo synthesis, and that re-expression of CCR5 on the cell membrane required several days. In contrast, the RANTES treatment induces a recovery of the receptor on the cell membrane in short-term kinetics without the involvement of de novo protein synthesis. The said new pathway could be relevant not only to better understand the molecular basis of all pathologic conditions in which CCR5 is involved but also to generate new tools to block viral infections, such as the use of recombinant Abs.

  5. Chemokine receptor Ccr1 drives neutrophil-mediated kidney immunopathology and mortality in invasive candidiasis.

    Science.gov (United States)

    Lionakis, Michail S; Fischer, Brett G; Lim, Jean K; Swamydas, Muthulekha; Wan, Wuzhou; Richard Lee, Chyi-Chia; Cohen, Jeffrey I; Scheinberg, Phillip; Gao, Ji-Liang; Murphy, Philip M

    2012-01-01

    Invasive candidiasis is the 4(th) leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1(lo) to Ccr1(high) at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1∶1 mixture of Ccr1(+/+) and Ccr1(-/-) donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1(+/+) recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1(+/+) cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ.

  6. CCR7 Maintains Nonresolving Lymph Node and Adipose Inflammation in Obesity.

    Science.gov (United States)

    Hellmann, Jason; Sansbury, Brian E; Holden, Candice R; Tang, Yunan; Wong, Blenda; Wysoczynski, Marcin; Rodriguez, Jorge; Bhatnagar, Aruni; Hill, Bradford G; Spite, Matthew

    2016-08-01

    Accumulation of immune cells in adipose tissue promotes insulin resistance in obesity. Although innate and adaptive immune cells contribute to adipose inflammation, the processes that sustain these interactions are incompletely understood. Here we show that obesity promotes the accumulation of CD11c(+) adipose tissue immune cells that express C-C chemokine receptor 7 (CCR7) in mice and humans, and that CCR7 contributes to chronic inflammation and insulin resistance. We identified that CCR7(+) macrophages and dendritic cells accumulate in adipose tissue in close proximity to lymph nodes (LNs) (i.e., perinodal) and visceral adipose. Consistent with the role of CCR7 in regulating the migration of immune cells to LNs, obesity promoted the accumulation of CD11c(+) cells in LNs, which was prevented by global or hematopoietic deficiency of Ccr7 Obese Ccr7(-/-) mice had reduced accumulation of CD8(+) T cells, B cells, and macrophages in adipose tissue, which was associated with reduced inflammatory signaling. This reduction in maladaptive inflammation translated to increased insulin signaling and improved glucose tolerance in obesity. Therapeutic administration of an anti-CCR7 antibody phenocopied the effects of genetic Ccr7 deficiency in mice with established obesity. These results suggest that CCR7 plays a causal role in maintaining innate and adaptive immunity in obesity.

  7. CCR7 Controls Thymus Recirculation, but Not Production and Emigration, of Foxp3(+) T Cells.

    Science.gov (United States)

    Cowan, Jennifer E; McCarthy, Nicholas I; Anderson, Graham

    2016-02-09

    Current models of Foxp3(+) regulatory T cell (Treg) development involve CCR7-mediated migration of thymocytes into the thymus medulla to enable essential interactions with medullary epithelium. However, increased Foxp3(+) thymic Treg numbers in Ccr7(-/-) mice challenge this view, and the role of CCR7 in Treg development, emigration, and/or recirculation is unknown. Here, we have examined CCR7 and Rag2pGFP levels during Treg development and generated Rag2pGFPCcr7(-/-) mice to study its impact on the intrathymic Treg pool. We reveal surprising developmental heterogeneity in thymocytes described as Treg precursors, showing that they contain recirculating CCR6(+)CCR7(-)Rag2pGFP(-) T cells. Although CCR7 defines bona fide Rag2GFP(+) Treg precursors, it is not required for Treg production and emigration. Rather, we show that lack of CCR7 renders the thymus more receptive to Treg thymus homing. Our study reveals a role for CCR7 in limiting Treg recirculation back to the thymus and enables separation of the mechanisms controlling Treg production and thymic recirculation.

  8. CCR5-CCL Axis in PDL during Orthodontic Biophysical Force Application.

    Science.gov (United States)

    Lee, S Y; Yoo, H I; Kim, S H

    2015-12-01

    Tooth movement by application of orthodontic biophysical force primarily reflects the role of soluble molecules released from the periodontal ligament (PDL). Thus far, many factors have been reported to be involved in orthodontic tooth movement (OTM), but key molecules that orchestrate responses of periodontal tissues to biophysical force are still enigmatic. In this in vivo study, in which the upper first molars in rats were moved, differential display-polymerase chain reaction revealed that CC chemokine receptor 5 (CCR5) level was differentially increased during OTM. Strong immunoreactivity for CCR5 was found in the PDL undergoing force application. Moreover, the in vitro compression or tension force application to primary cultured human PDL cells increased the expression of CCR5 and CCR5 ligands. In vitro tension force on human PDL cells did not induce RANKL, an osteoclastogenesis-inducing factor, but did induce the upregulation of IL12, an osteoclast inhibitory factor, and osteoblast differentiation factors, including Runx2, which was attenuated under tension by CCR5 gene silencing whereas augmented with CCR5 ligands. In contrast, in vitro compression force did not induce the expression of osteoprotegerin, a decoy receptor for RANKL and Runx2, but did induce the upregulation of RANKL, which was attenuated under compression by CCR5 gene silencing. These results suggest that the CCR5-CCR5 ligands axis in PDL cells may play a crucial role in the remodeling of periodontal tissues and can be a therapeutic target for achieving efficient OTM.

  9. CCR5 Expression Levels in HIV-Uninfected Women Receiving Hormonal Contraception.

    Science.gov (United States)

    Sciaranghella, Gaia; Wang, Cuiwei; Hu, Haihong; Anastos, Kathryn; Merhi, Zaher; Nowicki, Marek; Stanczyk, Frank Z; Greenblatt, Ruth M; Cohen, Mardge; Golub, Elizabeth T; Watts, D Heather; Alter, Galit; Young, Mary A; Tsibris, Athe M N

    2015-11-01

    Human immunodeficiency virus (HIV) infectivity increases as receptor/coreceptor expression levels increase. We determined peripheral CD4, CCR5, and CXCR4 expression levels in HIV-uninfected women who used depot medroxyprogesterone acetate (DMPA; n = 32), the levonorgestrel-releasing intrauterine device (LNG-IUD; n = 27), oral contraceptive pills (n = 32), or no hormonal contraception (n = 33). The use of LNG-IUD increased the proportion of CD4(+) and CD8(+) T cells that expressed CCR5; increases in the magnitude of T-cell subset CCR5 expression were observed with DMPA and LNG-IUD use (P CCR5 expression.

  10. Deficient Fas expression by CD4+ CCR5+ T cells in multiple sclerosis

    DEFF Research Database (Denmark)

    Julià, Eva; Montalban, Xavier; Al-Zayat, Hammad;

    2006-01-01

    OBJECTIVE: To evaluate whether T cells expressing CCR5 and CXCR3 from multiple sclerosis (MS) patients are more resistant to apoptosis. METHODS: Expression of CD69, TNF-R1, Fas, FasL, bcl-2, and bax was investigated in 41 MS patients and 12 healthy controls by flow cytometry in CD4+ and CD8+ T...... cells expressing CCR5 and CXCR3. RESULTS: In MS patients, the percentage of CD69 was increased and Fas expression decreased in CD4+ CCR5+ T cells. INTERPRETATION: The lower Fas expression in activated CD4+ CCR5+ T cells might contribute to disease pathogenesis by prolonging cell survival and favoring...

  11. Transition from film to digital mammography: Impact for breast cancer screening through the national breast and cervical cancer early detection program

    NARCIS (Netherlands)

    N.T. van Ravesteyn (Nicolien); L. Van Lier (Lisanne); C.B. Schechter (Clyde); D.U. Ekwueme (Donatus U.); J. Royalty (Janet); J.W. Miller (Jacqueline W.); A.M. Near (Aimee); K.A. Cronin (Kathleen); E.A.M. Heijnsdijk (Eveline); J.S. Mandelblatt (Jeanne); H.J. de Koning (Harry)

    2015-01-01

    textabstractIntroduction The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides mammograms and diagnostic services for low-income, uninsured women aged 40-64 years. Mammography facilities within the NBCCEDP gradually shifted from plain-film to digital mammography. The pur

  12. Risk Prediction Model for Colorectal Cancer: National Health Insurance Corporation Study, Korea

    OpenAIRE

    Aesun Shin; Jungnam Joo; Hye-Ryung Yang; Jeongin Bak; Yunjin Park; Jeongseon Kim; Jae Hwan Oh; Byung-Ho Nam

    2014-01-01

    PURPOSE: Incidence and mortality rates of colorectal cancer have been rapidly increasing in Korea during last few decades. Development of risk prediction models for colorectal cancer in Korean men and women is urgently needed to enhance its prevention and early detection. METHODS: Gender specific five-year risk prediction models were developed for overall colorectal cancer, proximal colon cancer, distal colon cancer, colon cancer and rectal cancer. The model was developed using data from a po...

  13. Frequency of polymorphisms of genes coding for HIV-1 co-receptors CCR5 and CCR2 in a Brazilian population

    Directory of Open Access Journals (Sweden)

    Munerato Patrícia

    2003-01-01

    Full Text Available Entry of human immunodeficiency type 1 virus (HIV-1 into target cells requires both CD4and one of the chemokine receptors. Viruses predominantly use one, or occasionally both, of the major co-receptors CCR5 and CXCR4, although other receptors, including CCR2B and CCR3, function as minor co-receptors. A 32-nucleotide deletion (delta32 within the beta-chemokine receptor 5 gene (CCR5 has been described in subjects who remain uninfected despite extensive exposition to HIV-1. The heterozygous genotype delays disease progression. This allele is common among Caucasians, but has not been found in people of African or Asian ancestry. A more common transition involving a valine to isoleucine switch in transmembrane domain I of CCR2B (64I, with unknown functional consequences, was found to delay disease progression but not to reduce infection risk. As the Brazilian population consists of a mixture of several ethnic groups, we decided to examine the genotype frequency of these polymorphisms in this country. There were 11.5% CCR5 heterozygotes among the HIV-1 infected population and 12.5% among uninfected individuals, similar to data from North America and Western Europe. The prevalence of CCR2-64I homozygotes and heterozygotes was 0.06 and 15.2%, respectively, also similar to what is known for North America and Western Europe.

  14. Progress in the Research of Small Molecule CCR5 Antagonists%小分子CCR5拮抗剂研究进展

    Institute of Scientific and Technical Information of China (English)

    陈文文; 刘新泳

    2012-01-01

    C-C chemokine receptor type 5 (CCR5) has been recognized as a major co-receptor in the HIV-1 entry process. Currently, many kinds of novel small molecule CCR5 antagonists for the treatment of AIDS have been identified and progressed into clinical trials. In this article, after brief introduction of the mechanism of action, current progress in drug research for various small molecule CCR5 antagonists is reviewed.%趋化因子受体5(CCR5)是HIV-1侵入宿主细胞的主要辅助受体之一.目前已发现许多小分子CCR5拮抗剂,其中一些化合物已进入临床研究和应用.本文介绍了小分子CCR5拮抗剂的作用机制,综述了近几年来各种不同结构类型的小分子CCR5拮抗剂的研究进展.

  15. Treatment of chronically Trypanosoma cruzi-infected mice with a CCR1/CCR5 antagonist (Met-RANTES) results in amelioration of cardiac tissue damage.

    Science.gov (United States)

    Medeiros, Gabriela A; Silvério, Jaline C; Marino, Ana Paula M P; Roffê, Ester; Vieira, Valeska; Kroll-Palhares, Karina; Carvalho, Cristiano E; Silva, Andréa Alice; Teixeira, Mauro M; Lannes-Vieira, Joseli

    2009-02-01

    The comprehension of the molecular mechanisms leading to Trypanosoma cruzi-elicited heart dysfunction might contribute to design novel therapeutic strategies aiming to ameliorate chronic Chagas disease cardiomyopathy. In C3H/He mice infected with the low virulence T. cruzi Colombian strain, the persistent cardiac inflammation composed mainly of CCR5(+) T lymphocytes parallels the expression of CC-chemokines in a pro-inflammatory IFN-gamma and TNF-alpha milieu. The chronic myocarditis is accompanied by increased frequency of peripheral CCR5(+)LFA-1(+) T lymphocytes. The treatment of chronically T. cruzi-infected mice with Met-RANTES, a selective CCR1/CCR5 antagonist, led to a 20-30% decrease in CD4(+) cell numbers as well as IL-10, IL-13 and TNF-alpha expression. Further, Met-RANTES administration impaired the re-compartmentalization of the activated CD4(+)CCR5(+) lymphocytes. Importantly, Met-RANTES treatment resulted in significant reduction in parasite load and fibronectin deposition in the heart tissue. Moreover, Met-RANTES treatment significantly protected T. cruzi-infected mice against connexin 43 loss in heart tissue and CK-MB level enhancement, markers of heart dysfunction. Thus, our results corroborate that therapeutic strategies based on the modulation of CCR1/CCR5-mediated cell migration and/or effector function may contribute to cardiac tissue damage limitation during chronic Chagas disease.

  16. Quality of venous thromboembolism diagnoses among prostate cancer patients in the Danish National Registry of Patients

    Directory of Open Access Journals (Sweden)

    Drljevic A

    2014-10-01

    Full Text Available Aska Drljevic,1 Michael Borre,2 Morten Høyer,3 Vera Ehrenstein,4 Mary Nguyen-Nielsen4 1Department of Pharmacology, 2Department of Urology, 3Department of Oncology, 4Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Background and aim: It is well established that cancer patients have an increased risk of venous thromboembolism (VTE. However, no previous study has examined the quality of VTE diagnoses related to cancer patients in the Danish National Registry of Patients (DNRP. To support future studies on cancer and risk of VTE, this study aimed to estimate the positive predictive value (PPV of VTE diagnoses among prostate cancer (PC patients registered in the DNRP. Materials and methods: We conducted a validation study using data from hospitals within the Central Denmark Region, which covers a population of 1.3 million people. Using the DNRP, we identified a total of 120 PC patients registered with VTE within the period 1995–2012. We also identified a random sample of 120 PC patients with no VTE registration within the same period. Therefore, a total of 240 patients were selected for medical chart review. We compared data from the DNRP to data collected from medical record review (ie, reference standard. We then computed PPV, sensitivity, and specificity with corresponding 95% confidence intervals (CIs using the Jeffreys method. Results: The final study sample included 232 PC patients, of which 115 were registered with VTE and 117 had no registration of VTE in the DNRP. We found the overall PPV of VTE diagnoses in the DNRP to be 86.1% (95% CI 78.9%–91.5%. Sensitivity was 98.0% (95% CI 93.8%–99.6%, and specificity was 87.8% (95% CI 81.4%–92.6%. We also found the PPV of incident PC diagnoses in the DNRP to be 98.3% (95% CI 96.1%–99.4%. Conclusion: For PC patients, the registration of VTE diagnoses in the DNRP is associated with a high PPV. We provide evidence that data from the DNRP are valid for studies

  17. K-ras genetic mutation and influencing factor analysis for Han and Uygur nationality colorectal cancer patients.

    Science.gov (United States)

    Eli, Mayinur; Mollayup, Ablikim; Muattar; Liu, Chao; Zheng, Chao; Bao, Yong-Xing

    2015-01-01

    To investigate the K-ras genetic mutation status in colorectal cancer patients, compare the difference of K-ras genetic mutation rate in Han and Uygur nationality and analyze the influencing factor. 91 cases (52 cases of Han nationality and 39 cases of Uygur nationality) of colorectal biopsy or surgical ablation pathology specimen from the first affiliated hospital of Xinjiang Medical University during January, 2010 to March, 2013 were collected to detect the 12th and 13th code mutation status of K-ras gene exon 2 with pyrosequencing method and compare the difference of K-ras gene mutation rate between Han and Uygur nationality patients. Single factor analysis and multiple factor logistic regression analysis were utilized to analyze the influencing factor for K-ras genetic mutation. 33 cases of patients with K-ras genetic mutation were found from the 91 cases colorectal cancer patients and the total mutation rate was 36.3%. Among them, 24 cases (72.7%) were found with mutation only in the 12th code, 9 cases (27.3%) were found with mutation only in the 13th code and no one case was found with mutation in both the two codes. Mutation rate of the 12th code in the Uygur nationality was significantly higher than that in the Han nationality (P0.05). There were no associativity (P>0.05) between the K-ras genetic mutation and sex, age, smoking history, drinking history, tumor location, macropathology type, differentiation level, staging, invasive depth, lymph nodes transferring and metastasis in colorectal cancer patients (P>0.05). K-ras genetic mutation rate is high in colorectal cancer patients. The mutation rate of 12th code in Uygur nationality is higher than that in Han nationality. There is no significant associativity between K-ras genetic mutation rate and patients' clinical pathology characteristic.

  18. CCR4 frameshift mutation identifies a distinct group of adult T cell leukaemia/lymphoma with poor prognosis.

    Science.gov (United States)

    Yoshida, Noriaki; Miyoshi, Hiroaki; Kato, Takeharu; Sakata-Yanagimoto, Mamiko; Niino, Daisuke; Taniguchi, Hiroaki; Moriuchi, Yukiyoshi; Miyahara, Masaharu; Kurita, Daisuke; Sasaki, Yuya; Shimono, Joji; Kawamoto, Keisuke; Utsunomiya, Atae; Imaizumi, Yoshitaka; Seto, Masao; Ohshima, Koichi

    2016-04-01

    Adult T cell leukaemia/lymphoma (ATLL) is an intractable T cell neoplasm caused by human T cell leukaemia virus type 1. Next-generation sequencing-based comprehensive mutation studies have revealed recurrent somatic CCR4 mutations in ATLL, although clinicopathological findings associated with CCR4 mutations remain to be delineated. In the current study, 184 cases of peripheral T cell lymphoma, including 113 cases of ATLL, were subjected to CCR4 mutation analysis. This sequence analysis identified mutations in 27% (30/113) of cases of ATLL and 9% (4/44) of cases of peripheral T cell lymphoma not otherwise specified. Identified mutations included nonsense (NS) and frameshift (FS) mutations. No significant differences in clinicopathological findings were observed between ATLL cases stratified by presence of CCR4 mutation. All ATLL cases with CCR4 mutations exhibited cell-surface CCR4 positivity. Semi-quantitative CCR4 protein analysis of immunohistochemical sections revealed higher CCR4 expression in cases with NS mutations of CCR4 than in cases with wild-type (WT) CCR4. Furthermore, among ATLL cases, FS mutation was significantly associated with a poor prognosis, compared with NS mutation and WT CCR4. These results suggest that CCR4 mutation is an important determinant of the clinical course in ATLL cases, and that NS and FS mutations of CCR4 behave differently with respect to ATLL pathophysiology.

  19. The surgical management of male breast cancer: Time for an easy access national reporting database?

    Directory of Open Access Journals (Sweden)

    Robert M.T. Staruch

    2016-08-01

    Discussion: We report a series of seven cases of male breast cancer encountered over three years, evaluating patient demographics as well as treatment and outcomes. In our series patients were managed with mastectomy. New evidence is questioning the role of mastectomy against breast conserving surgery in male patients. Furthermore there is a lack of reporting infrastructure for national data capture of the benefits of surgical modalities. Literature review highlights the varied clinical experience between units that remains reported as podium presentation but not published. The establishment of an online international reporting registry would allow for efficient analysis of surgical outcomes to improve patient care from smaller single centres. This would facilitate large scale meta analysis by larger academic surgical centres.

  20. Pioneering the Transdisciplinary Team Science Approach: Lessons Learned from National Cancer Institute Grantees.

    Science.gov (United States)

    Vogel, Amanda L; Stipelman, Brooke A; Hall, Kara L; Nebeling, Linda; Stokols, Daniel; Spruijt-Metz, Donna

    2014-01-01

    The National Cancer Institute has been a leader in supporting transdisciplinary (TD) team science. From 2005-2010, the NCI supported Transdisciplinary Research on Energetic and Cancer I (TREC I), a center initiative fostering the TD integration of social, behavioral, and biological sciences to examine the relationships among obesity, nutrition, physical activity and cancer. In the final year of TREC I, we conducted qualitative in-depth-interviews with 31 participating investigators and trainees to learn more about their experiences with TD team science, including challenges, facilitating factors, strategies for success, and impacts. Five main challenges emerged: (1) limited published guidance for how to engage in TD team science, when TREC I was implemented; (2) conceptual and scientific challenges inherent to efforts to achieve TD integration; (3) discipline-based differences in values, terminology, methods, and work styles; (4) project management challenges involved in TD team science; and (5) traditional incentive and reward systems that do not recognize or reward TD team science. Four main facilitating factors and strategies for success emerged: (1) beneficial attitudes and beliefs about TD research and team science; (2) effective team processes; (3) brokering and bridge-building activities by individuals holding particular roles in a research center; and (4) funding initiative characteristics that support TD team science. Broad impacts of participating in TD team science in the context of TREC I included: (1) new positive attitudes about TD research and team science; (2) new boundary-crossing collaborations; (3) scientific advances related to research approaches, findings, and dissemination; (4) institutional culture change and resource creation in support of TD team science; and (5) career advancement. Funding agencies, academic institutions, and scholarly journals can help to foster TD team science through funding opportunities, institutional policies on

  1. National Cancer Institute-supported chemotherapy-induced peripheral neuropathy trials: outcomes and lessons

    Science.gov (United States)

    Majithia, Neil; Temkin, Sarah M.; Ruddy, Kathryn J.; Beutler, Andreas S.; Hershman, Dawn L.; Loprinzi, Charles L.

    2016-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common and debilitating complications of cancer treatment. Due to a lack of effective management options for patients with CIPN, the National Cancer Institute (NCI) sponsored a series of trials aimed at both prevention and treatment. A total of 15 such studies were approved, evaluating use of various neuro-modulatory agents which have shown benefit in other neuropathic pain states. Aside from duloxetine, none of the pharmacologic methods demonstrated therapeutic benefit for patients with CIPN. Despite these disappointing results, the series of trials revealed important lessons that have informed subsequent work. Some examples of this include the use of patient-reported symptom metrics, the elimination of traditional—yet unsubstantiated—practice approaches, and the discovery of molecular genetic predictors of neuropathy. Current inquiry is being guided by the results from these large-scale trials, and as such, stands better chance of identifying durable solutions for this treatment-limiting toxicity. PMID:26686859

  2. Radiation-Therapeutic Agent Clinical Trials: Leveraging Advantages of a National Cancer Institute Programmatic Collaboration.

    Science.gov (United States)

    Takebe, Naoko; Ahmed, Mansoor M; Vikram, Bhadrasain; Bernhard, Eric J; Zwiebel, James; Norman Coleman, C; Kunos, Charles A

    2016-10-01

    A number of oncology phase II radiochemotherapy trials with promising results have been conducted late in the overall experimental therapeutic agent development process. Accelerated development and approval of experimental therapeutic agents have stimulated further interest in much earlier radiation-agent studies to increase the likelihood of success in phase III trials. To sustain this interest, more forward-thinking preclinical radiobiology experimental designs are needed to improve discovery of promising radiochemotherapy plus agent combinations for clinical trial testing. These experimental designs should better inform next-step radiation-agent clinical trial dose, schedule, exposure, and therapeutic effect. Recognizing the need for a better strategy to develop preclinical data supporting radiation-agent phase I or II trials, the National Cancer Institute (NCI)-Cancer Therapy Evaluation Program (CTEP) and the NCI-Molecular Radiation Therapeutics Branch of the Radiation Research Program have partnered to promote earlier radiobiology studies of CTEP portfolio agents. In this Seminars in Radiation Oncology article, four key components of this effort are discussed. First, we outline steps for accessing CTEP agents for preclinical testing. Second, we propose radiobiology studies that facilitate transition from preclinical testing to early phase trial activation. Third, we navigate steps that walk through CTEP agent strategic development paths available for radiation-agent testing. Fourth, we highlight a new NCI-sponsored cooperative agreement grant supporting in vitro and in vivo radiation-CTEP agent testing that informs early phase trial designs. Throughout the article, we include contemporary examples of successful radiation-agent development initiatives.

  3. New insights into the mechanisms whereby low molecular weight CCR5 ligands inhibit HIV-1 infection.

    Science.gov (United States)

    Garcia-Perez, Javier; Rueda, Patricia; Staropoli, Isabelle; Kellenberger, Esther; Alcami, Jose; Arenzana-Seisdedos, Fernando; Lagane, Bernard

    2011-02-18

    CC chemokine receptor 5 (CCR5) is a G-protein-coupled receptor for the chemokines CCL3, -4, and -5 and a coreceptor for entry of R5-tropic strains of human immunodeficiency virus type 1 (HIV-1) into CD4(+) T-cells. We investigated the mechanisms whereby nonpeptidic, low molecular weight CCR5 ligands block HIV-1 entry and infection. Displacement binding assays and dissociation kinetics demonstrated that two of these molecules, i.e. TAK779 and maraviroc (MVC), inhibit CCL3 and the HIV-1 envelope glycoprotein gp120 binding to CCR5 by a noncompetitive and allosteric mechanism, supporting the view that they bind to regions of CCR5 distinct from the gp120- and CCL3-binding sites. We observed that TAK779 and MVC are full and weak inverse agonists for CCR5, respectively, indicating that they stabilize distinct CCR5 conformations with impaired abilities to activate G-proteins. Dissociation of [(125)I]CCL3 from CCR5 was accelerated by TAK779, to a lesser extent by MVC, and by GTP analogs, suggesting that inverse agonism contributes to allosteric inhibition of the chemokine binding to CCR5. TAK779 and MVC also promote dissociation of [(35)S]gp120 from CCR5 with an efficiency that correlates with their ability to act as inverse agonists. Displacement experiments revealed that affinities of MVC and TAK779 for the [(35)S]gp120-binding receptors are in the same range (IC(50) ∼6.4 versus 22 nm), although we found that MVC is 100-fold more potent than TAK779 for inhibiting HIV infection. This suggests that allosteric CCR5 inhibitors not only act by blocking gp120 binding but also alter distinct steps of CCR5 usage in the course of HIV infection.

  4. CCR5 small interfering RNA ameliorated joint inflammation in rats with adjuvant-induced arthritis.

    Science.gov (United States)

    Duan, Hongmei; Yang, Pingting; Fang, Fang; Ding, Shuang; Xiao, Weiguo

    2014-12-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disease. C-C chemokine receptor type 5 (CCR5) is found in inflamed synovium of RA patients and is necessary for formation of RA. We aimed to check whether delivery of CCR5-specific small interfering RNA (siRNA) via electroporation suppresses local inflammation in arthritis rats. Vectors encoding siRNA that target CCR5 or negative control siRNA were constructed for gene silencing and the silencing effects of suppressing CCR5 expression in synovium examined by western blot. The vector with strongest effect was delivered into the knee joint of adjuvant-induced arthritis (AIA) rats by the in vivo electroporation method 7, 10, 13, and 16 days after immunization with Complete Freund's adjuvant. During an observation of 28 days, behavior, paw swelling, arthritis and histopathologic scoring were estimated. The expression level of CCR5 in synovium was evaluated by western blot and real-time PCR. Anti-CCR5 D1 siRNA was effectively inhibited CCR5 expression in vitro. Moreover, delivery of the siRNA into inflammatory joint also suppressed the expression of CCR5 in vivo and markedly suppressed paw swelling and inflammation. Local electroporation of anti-CCR5 siRNA into the left inflamed joints could achieve the silencing of CCR5 gene and alleviate local inflammation just in the knee joint injected with siRNA other than the opposite joint. Inhibition of CCR5 expression may provide a potential for treatment of RA.

  5. Reduced colon cancer incidence and mortality in postmenopausal women treated with an oral bisphosphonate-Danish National Register Based Cohort Study

    DEFF Research Database (Denmark)

    Pazianas, M; Abrahamsen, B; Eiken, Pia Agnete;

    2012-01-01

    In this Danish national register-based cohort study, we examined the effects of alendronate on the development of colon cancers and survival. The incidence of colon cancer and mortality rate, once colon cancer had been diagnosed, were lower in patients treated with alendronate, posing the questio...

  6. HIV-1 predisposed to acquiring resistance to maraviroc (MVC and other CCR5 antagonists in vitro has an inherent, low-level ability to utilize MVC-bound CCR5 for entry

    Directory of Open Access Journals (Sweden)

    Westby Mike

    2011-11-01

    Full Text Available Abstract Background Maraviroc (MVC and other CCR5 antagonists are HIV-1 entry inhibitors that bind to- and alter the conformation of CCR5, such that CCR5 is no longer recognized by the viral gp120 envelope (Env glycoproteins. Resistance to CCR5 antagonists results from HIV-1 Env acquiring the ability to utilize the drug-bound conformation of CCR5. Selecting for HIV-1 resistance to CCR5-antagonists in vitro is relatively difficult. However, the CCR5-using CC1/85 strain appears to be uniquely predisposed to acquiring resistance to several CCR5 antagonists in vitro including MVC, vicriviroc and AD101. Findings Here, we show that Env derived from the parental CC1/85 strain is inherently capable of a low affinity interaction with MVC-bound CCR5. However, this phenotype was only revealed in 293-Affinofile cells and NP2-CD4/CCR5 cells that express very high levels of CCR5, and was masked in TZM-bl, JC53 and U87-CD4/CCR5 cells as well as PBMC, which express comparatively lower levels of CCR5 and which are more commonly used to detect resistance to CCR5 antagonists. Conclusions Env derived from the CC1/85 strain of HIV-1 is inherently capable of a low-affinity interaction with MVC-bound CCR5, which helps explain the relative ease in which CC1/85 can acquire resistance to CCR5 antagonists in vitro. The detection of similar phenotypes in patients may identify those who could be at higher risk of virological failure on MVC.

  7. What Does the Public Know about Preventing Cancer? Results from the Health Information National Trends Survey (HINTS)

    Science.gov (United States)

    Hawkins, Nikki A.; Berkowitz, Zahava; Peipins, Lucy A.

    2010-01-01

    This study provides information about the public's familiarity with cancer prevention strategies and examines the association between this familiarity and actual prevention behavior. Data from interviews with 5,589 adults included in the 2003 Health Information National Trends Survey (HINTS) were analyzed. Most respondents were able to cite one or…

  8. Annual national direct and indirect cost estimates of the prevention and treatment of cervical cancer in Brazil

    Science.gov (United States)

    Novaes, Hillegonda Maria Dutilh; Itria, Alexander; Silva, Gulnar Azevedo e; Sartori, Ana Marli Christovam; Rama, Cristina Helena; de Soárez, Patrícia Coelho

    2015-01-01

    OBJECTIVE: To estimate the annual direct and indirect costs of the prevention and treatment of cervical cancer in Brazil. METHODS: This cost description study used a "gross-costing" methodology and adopted the health system and societal perspectives. The estimates were grouped into sets of procedures performed in phases of cervical cancer care: the screening, diagnosis and treatment of precancerous lesions and the treatment of cervical cancer. The costs were estimated for the public and private health systems, using data from national health information systems, population surveys, and literature reviews. The cost estimates are presented in 2006 USD. RESULTS: From the societal perspective, the estimated total costs of the prevention and treatment of cervical cancer amounted to USD $1,321,683,034, which was categorized as follows: procedures (USD $213,199,490), visits (USD $325,509,842), transportation (USD $106,521,537) and productivity losses (USD $676,452,166). Indirect costs represented 51% of the total costs, followed by direct medical costs (visits and procedures) at 41% and direct non-medical costs (transportation) at 8%. The public system represented 46% of the total costs, and the private system represented 54%. CONCLUSION: Our national cost estimates of cervical cancer prevention and treatment, indicating the economic importance of cervical cancer screening and care, will be useful in monitoring the effect of the HPV vaccine introduction and are of interest in research and health care management. PMID:26017797

  9. Results of National Colorectal Cancer Screening Program in Croatia (2007-2011)

    Institute of Scientific and Technical Information of China (English)

    Miroslava Kati(c)i(c); Nata(s)a Antoljak; Milan Kujund(z)i(c); Valerija Stameni(c); Dunja Skoko Poljak; Danica Kramari(c); Davor (S)timac

    2012-01-01

    AIM:To study the epidemiologic indicators of uptake and characteristic colonoscopic findings in the Croatian National Colorectal Cancer Screening Program.METHODS:Colorectal cancer (CRC) was the second leading cause of cancer mortality in men (n =1063,49.77/100 000),as well as women (n =803,34.89/100 000) in Croatia in 2009.The Croatian National CRC Screening Program was established by the Ministry of Health and Social Welfare,and its implementation started in September,2007.The coordinators were recruited in each county institute of public health with an obligation to provide fecal occult blood testing (FOBT) to the participants,followed by colonoscopy in all positive cases.The FOBT was performed by hypersensitive guaiac-based Hemognost card test (Biognost,Zagreb).The test and short questionnaire were delivered to the home addresses of all citizens aged 50-74years consecutively during a 3-year period.Each participant was required to complete the questionnaire and send it together with the stool specimen on three test cards back to the institute for further analysis.About 4% FOBT positive cases are expected in normal risk populations.A descriptive analysis was performed.RESULTS:A total of 1 056 694 individuals (born between 1933-1945 and 1952-1957) were invited to screening by the end of September 2011.In total,210 239 (19.9%) persons returned the envelope with a completed questionnaire,and 181 102 of them returned it with a correctly placed stool specimen on FOBT cards.Until now,12 477 (6.9%),FOBT-positive patients have been found,which is at the upper limit of the expected values in European Guidelines for Quality Assurance in CRC Screening and Diagnosis [European Union (EU) Guidelines].Colonoscopy was performed in 8541 cases (uptake 66%).Screening has identified CRC in 472 patients (5.5% of colonoscopied,3.8% of FOBT-positive,and 0.26% of all screened individuals).This is also in the expected range according to EU Guidelines.Polyps were found and

  10. Limited protective effect of the CCR5Δ32/CCR5Δ32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus

    DEFF Research Database (Denmark)

    Iversen, Astrid K. N.; Christiansen, Claus Bohn; Attermann, Jørn

    2003-01-01

    The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)–infected patients with hemophilia. One patient (0.6%) had the CCR5Δ32/CCR5Δ32 genotype (which occurs in ∼2% of the Scandinavian population...

  11. Elucidation of the CCR1- and CCR5-binding modes of MIP-1α by application of an NMR spectra reconstruction method to the transferred cross-saturation experiments

    Energy Technology Data Exchange (ETDEWEB)

    Yoshiura, Chie; Ueda, Takumi; Kofuku, Yutaka; Matsumoto, Masahiko; Okude, Junya; Kondo, Keita; Shiraishi, Yutaro; Shimada, Ichio, E-mail: shimada@iw-nmr.f.u-tokyo.ac.jp [The University of Tokyo, Graduate School of Pharmaceutical Sciences (Japan)

    2015-12-15

    C–C chemokine receptor 1 (CCR1) and CCR5 are involved in various inflammation and immune responses, and regulate the progression of the autoimmune diseases differently. However, the number of residues identified at the binding interface was not sufficient to clarify the differences in the CCR1- and CCR5-binding modes to MIP-1α, because the NMR measurement time for CCR1 and CCR5 samples was limited to 24 h, due to their low stability. Here we applied a recently developed NMR spectra reconstruction method, Conservation of experimental data in ANAlysis of FOuRier, to the amide-directed transferred cross-saturation experiments of chemokine receptors, CCR1 and CCR5, embedded in lipid bilayers of the reconstituted high density lipoprotein, and MIP-1α. Our experiments revealed that the residues on the N-loop and β-sheets of MIP-1α are close to both CCR1 and CCR5, and those in the C-terminal helix region are close to CCR5. These results suggest that the genetic influence of the single nucleotide polymorphisms of MIP-1α that accompany substitution of residues in the C-terminal helix region, E57 and V63, would provide clues toward elucidating how the CCR5–MIP-1α interaction affects the progress of autoimmune diseases.

  12. Elucidation of the CCR1- and CCR5-binding modes of MIP-1α by application of an NMR spectra reconstruction method to the transferred cross-saturation experiments.

    Science.gov (United States)

    Yoshiura, Chie; Ueda, Takumi; Kofuku, Yutaka; Matsumoto, Masahiko; Okude, Junya; Kondo, Keita; Shiraishi, Yutaro; Shimada, Ichio

    2015-12-01

    C-C chemokine receptor 1 (CCR1) and CCR5 are involved in various inflammation and immune responses, and regulate the progression of the autoimmune diseases differently. However, the number of residues identified at the binding interface was not sufficient to clarify the differences in the CCR1- and CCR5-binding modes to MIP-1α, because the NMR measurement time for CCR1 and CCR5 samples was limited to 24 h, due to their low stability. Here we applied a recently developed NMR spectra reconstruction method, Conservation of experimental data in ANAlysis of FOuRier, to the amide-directed transferred cross-saturation experiments of chemokine receptors, CCR1 and CCR5, embedded in lipid bilayers of the reconstituted high density lipoprotein, and MIP-1α. Our experiments revealed that the residues on the N-loop and β-sheets of MIP-1α are close to both CCR1 and CCR5, and those in the C-terminal helix region are close to CCR5. These results suggest that the genetic influence of the single nucleotide polymorphisms of MIP-1α that accompany substitution of residues in the C-terminal helix region, E57 and V63, would provide clues toward elucidating how the CCR5-MIP-1α interaction affects the progress of autoimmune diseases.

  13. Summary and Recommendations from the National Cancer Institute’s Clinical Trials Planning Meeting on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer

    Science.gov (United States)

    Lerner, Seth P.; Bajorin, Dean F.; Dinney, Colin P.; Efstathiou, Jason A.; Groshen, Susan; Hahn, Noah M.; Hansel, Donna; Kwiatkowski, David; O’Donnell, Michael; Rosenberg, Jonathan; Svatek, Robert; Abrams, Jeffrey S.; Al-Ahmadie, Hikmat; Apolo, Andrea B.; Bellmunt, Joaquim; Callahan, Margaret; Cha, Eugene K.; Drake, Charles; Jarow, Jonathan; Kamat, Ashish; Kim, William; Knowles, Margaret; Mann, Bhupinder; Marchionni, Luigi; McConkey, David; McShane, Lisa; Ramirez, Nilsa; Sharabi, Andrew; Sharpe, Arlene H.; Solit, David; Tangen, Catherine M.; Amiri, Abdul Tawab; Van Allen, Eliezer; West, Pamela J.; Witjes, J. A.; Quale, Diane Zipursky

    2016-01-01

    The NCI Bladder Cancer Task Force convened a Clinical Trials Planning Meeting (CTPM) Workshop focused on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer (NMIBC). Meeting attendees included a broad and multi-disciplinary group of clinical and research stakeholders and included leaders from NCI, FDA, National Clinical Trials Network (NCTN), advocacy and the pharmaceutical and biotech industry. The meeting goals and objectives were to: 1) create a collaborative environment in which the greater bladder research community can pursue future optimally designed novel clinical trials focused on the theme of molecular targeted and immune-based therapies in NMIBC; 2) frame the clinical and translational questions that are of highest priority; and 3) develop two clinical trial designs focusing on immunotherapy and molecular targeted therapy. Despite successful development and implementation of large Phase II and Phase III trials in bladder and upper urinary tract cancers, there are no active and accruing trials in the NMIBC space within the NCTN. Disappointingly, there has been only one new FDA approved drug (Valrubicin) in any bladder cancer disease state since 1998. Although genomic-based data for bladder cancer are increasingly available, translating these discoveries into practice changing treatment is still to come. Recently, major efforts in defining the genomic characteristics of NMIBC have been achieved. Aligned with these data is the growing number of targeted therapy agents approved and/or in development in other organ site cancers and the multiple similarities of bladder cancer with molecular subtypes in these other cancers. Additionally, although bladder cancer is one of the more immunogenic tumors, some tumors have the ability to attenuate or eliminate host immune responses. Two trial concepts emerged from the meeting including a window of opportunity trial (Phase 0) testing an FGFR3 inhibitor and a second multi-arm multi-stage trial testing combinations

  14. CCR7 is required for the in vivo function of CD4+ CD25+ regulatory T cells

    OpenAIRE

    Schneider, M. A.; Meingassner, J. G.; Lipp, M.; Moore, H D; Rot, A.

    2007-01-01

    CCR7-mediated migration of naive T cells into the secondary lymphoid organs is a prerequisite for their encounter with mature dendritic cells, the productive presentation of cognate antigen, and consequent T cell proliferation and effector differentiation. Therefore, CCR7 was suggested to play an important role in the initiation of adaptive immune responses. In this study, we show that primary immunity can also develop in the absence of CCR7. Moreover, CCR7-deficient knockout (KO) mice displa...

  15. CCR5 susceptibility to ligand-mediated down-modulation differs between human T lymphocytes and myeloid cells.

    Science.gov (United States)

    Fox, James M; Kasprowicz, Richard; Hartley, Oliver; Signoret, Nathalie

    2015-07-01

    CCR5 is a chemokine receptor expressed on leukocytes and a coreceptor used by HIV-1 to enter CD4(+) T lymphocytes and macrophages. Stimulation of CCR5 by chemokines triggers internalization of chemokine-bound CCR5 molecules in a process called down-modulation, which contributes to the anti-HIV activity of chemokines. Recent studies have shown that CCR5 conformational heterogeneity influences chemokine-CCR5 interactions and HIV-1 entry in transfected cells or activated CD4(+) T lymphocytes. However, the effect of CCR5 conformations on other cell types and on the process of down-modulation remains unclear. We used mAbs, some already shown to detect distinct CCR5 conformations, to compare the behavior of CCR5 on in vitro generated human T cell blasts, monocytes and MDMs and CHO-CCR5 transfectants. All human cells express distinct antigenic forms of CCR5 not detected on CHO-CCR5 cells. The recognizable populations of CCR5 receptors exhibit different patterns of down-modulation on T lymphocytes compared with myeloid cells. On T cell blasts, CCR5 is recognized by all antibodies and undergoes rapid chemokine-mediated internalization, whereas on monocytes and MDMs, a pool of CCR5 molecules is recognized by a subset of antibodies and is not removed from the cell surface. We demonstrate that this cell surface-retained form of CCR5 responds to prolonged treatment with more-potent chemokine analogs and acts as an HIV-1 coreceptor. Our findings indicate that the regulation of CCR5 is highly specific to cell type and provide a potential explanation for the observation that native chemokines are less-effective HIV-entry inhibitors on macrophages compared with T lymphocytes.

  16. Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5

    DEFF Research Database (Denmark)

    Berg, Christian; Spiess, Katja; von Lüttichau, Hans Rudolf;

    2016-01-01

    Since the discovery of HIV's use of CCR5 as the primary coreceptor in fusion, the focus on developing small-molecule receptor antagonists for inhibition hereof has only resulted in one single drug, Maraviroc. We therefore investigated the possibility of using small-molecule CCR5 agonists as HIV-1...

  17. 77 FR 5471 - Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review

    Science.gov (United States)

    2012-02-03

    ... AGENCY 40 CFR Parts 141 and 142 Announcement of Public Meeting on the Consumer Confidence Report (CCR... Internet on February 23, 2012, to obtain stakeholder input on the Consumer Confidence Report (CCR) Rule as.... Background: Consumer Confidence Reports are a key part of the public's right-to-know as established in...

  18. Immunohistochemical detection of CCR2 and CX3CR1 in sepsis-induced lung injury.

    Science.gov (United States)

    An, Jun-Ling; Ishida, Yuko; Kimura, Akihiko; Tsokos, Michael; Kondo, Toshikazu

    2009-11-20

    Sepsis is a systemic inflammatory disease with high mortality. In the present study, we immunohistochemically examined CCR2 and CX3CR1 expression in sepsis-induced lung injury, and discussed its availability for the postmortem diagnosis of sepsis. Lung samples were obtained from different lung lobes of nine sepsis and eight control cases with postmortem intervals between 12 and 48h. Immunohistochemically, mononuclear cells recruited into the lungs expressed CCR2 and CX3CR1 in both sepsis and non-septic groups. In double-color immunofluorescence analysis, CCR2- or CX3CR1-positive cells could be identified as CD68-positive macrophages. Moreover, most of CD68-positive macrophages expressed both CCR2 and CX3CR1. Morphometrically, the average of CCR2- and CX3CR1-positive macrophages was significantly increased in sepsis group, compared with control group (sepsis vs. control: 41.6+/-1.3% vs. 8.0+/-0.4% in CCR2; 36.2+/-1.3% vs. 9.2+/-0.4% in CX3CR1). These observations implied that CCR2- or CX3CR1-positive macrophages were recruited into the lungs under several pathological conditions. In particular, their recruitment might be more evident in sepsis. Moreover, from the forensic aspects, immunohistochemical detection of CCR2 and CX3CR1 expression in the lungs can be considered as valuable diagnostic tools for the postmortem diagnosis of sepsis.

  19. Discovery of the CCR1 antagonist, BMS-817399, for the treatment of rheumatoid arthritis.

    Science.gov (United States)

    Santella, Joseph B; Gardner, Daniel S; Duncia, John V; Wu, Hong; Dhar, Murali; Cavallaro, Cullen; Tebben, Andrew J; Carter, Percy H; Barrish, Joel C; Yarde, Melissa; Briceno, Stephanie W; Cvijic, Mary Ellen; Grafstrom, R Robert; Liu, Richard; Patel, Sima R; Watson, Andrew J; Yang, Guchen; Rose, Anne V; Vickery, Rodney D; Caceres-Cortes, Janet; Caporuscio, Christian; Camac, Daniel M; Khan, Javed A; An, Yongmi; Foster, William R; Davies, Paul; Hynes, John

    2014-09-25

    High-affinity, functionally potent, urea-based antagonists of CCR1 have been discovered. Modulation of PXR transactivation has revealed the selective and orally bioavailable CCR1 antagonist BMS-817399 (29), which entered clinical trials for the treatment of rheumatoid arthritis.

  20. Chemokine receptor CCR5 antagonist maraviroc: medicinal chemistry and clinical applications.

    Science.gov (United States)

    Xu, Guoyan G; Guo, Jia; Wu, Yuntao

    2014-01-01

    The human immunodeficiency virus (HIV) causes acquired immumodeficiency syndrome (AIDS), one of the worst global pandemic. The virus infects human CD4 T cells and macrophages, and causes CD4 depletion. HIV enters target cells through the binding of the viral envelope glycoprotein to CD4 and the chemokine coreceptor, CXCR4 or CCR5. In particular, the CCR5-utilizing viruses predominate in the blood during the disease course. CCR5 is expressed on the surface of various immune cells including macrophages, monocytes, microglia, dendric cells, and active memory CD4 T cells. In the human population, the CCR5 genomic mutation, CCR5Δ32, is associated with relative resistance to HIV. These findings paved the way for the discovery and development of CCR5 inhibitors to block HIV transmission and replication. Maraviroc, discovered as a CCR5 antagonist, is the only CCR5 inhibitor that has been approved by both US FDA and the European Medicines Agency (EMA) for treating HIV/AIDS patients. In this review, we summarize the medicinal chemistry and clinical studies of Maraviroc.

  1. The Effects of the Recombinant CCR5 T4 Lysozyme Fusion Protein on HIV-1 Infection.

    Directory of Open Access Journals (Sweden)

    Qingwen Jin

    Full Text Available Insertion of T4 lysozyme (T4L into the GPCR successfully enhanced GPCR protein stability and solubilization. However, the biological functions of the recombinant GPCR protein have not been analyzed.We engineered the CCR5-T4L mutant and expressed and purified the soluble recombinant protein using an E.coli expression system. The antiviral effects of this recombinant protein in THP-1 cell lines, primary human macrophages, and PBMCs from different donors were investigated. We also explored the possible mechanisms underlying the observed antiviral effects.Our data showed the biphasic inhibitory and promotion effects of different concentrations of soluble recombinant CCR5-T4L protein on R5 tropic human immunodeficiency virus-1 (HIV-1 infection in THP-1 cell lines, human macrophages, and PBMCs from clinical isolates. We demonstrated that soluble recombinant CCR5-T4L acts as a HIV-1 co-receptor, interacts with wild type CCR5, down-regulates the surface CCR5 expression in human macrophages, and interacts with CCL5 to inhibit macrophage migration. Using binding assays, we further determined that recombinant CCR5-T4L and [125I]-CCL5 compete for the same binding site on wild type CCR5.Our results suggest that recombinant CCR5-T4L protein marginally promotes HIV-1 infection at low concentrations and markedly inhibits infection at higher concentrations. This recombinant protein may be helpful in the future development of anti-HIV-1 therapeutic agents.

  2. TNF-alpha levels are not increased in inflamed patients carrying the CCR5 deletion 32

    NARCIS (Netherlands)

    Muntinghe, Friso L. H.; Carrero, Juan Jesus; Navis, Gerjan; Stenvinkel, Peter

    2011-01-01

    Background and aims: Recently we reported on a genetically predisposed protection from C-reactive protein (CRP) related mortality in dialysis patients carrying the functional CC-chemokine receptor 5 deletion 32 allele (CCR5 Delta 32) mutation. Since CCR5 Delta 32 is associated with a less pro-inflam

  3. Unexpected Regulatory Role of CCR9 in Regulatory T Cell Development.

    Directory of Open Access Journals (Sweden)

    Heather L Evans-Marin

    Full Text Available T cells reactive to microbiota regulate the pathogenesis of inflammatory bowel disease (IBD. As T cell trafficking to intestines is regulated through interactions between highly specific chemokine-chemokine receptors, efforts have been made to develop intestine-specific immunosuppression based on blocking these key processes. CCR9, a gut-trophic chemokine receptor expressed by lymphocytes and dendritic cells, has been implicated in the regulation of IBD through mediating recruitment of T cells to inflamed sites. However, the role of CCR9 in inducing and sustaining inflammation in the context of IBD is poorly understood. In this study, we demonstrate that CCR9 deficiency in effector T cells and Tregs does not affect the development of colitis in a microbiota antigen-specific, T cell-mediated model. However, Treg cells express higher levels of CCR9 compared to those in effector T cells. Interestingly, CCR9 inhibits Treg cell development, in that CCR9-/- mice demonstrate a high level of Foxp3+ Tregs, and ligation of CCR9 by its ligand CCL25 inhibits Treg cell differentiation in vitro. Collectively, our data indicate that in addition to acting as a gut-homing molecule, CCR9 signaling shapes immune responses by inhibiting Treg cell development.

  4. Role of CCR5 Delta 32 bp deletion in RA and SLE

    NARCIS (Netherlands)

    Martens, H. A.; Kallenberg, C. G. M.; Bijl, M.

    2009-01-01

    CCR5 and its ligands play important roles in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). A deletion of 32 bp in its gene leads to the production of a non-functional receptor. Although a protective effect of CCR5 Delta 32 for the development of RA has been suggested, future stud

  5. CCR5 blockade in rheumatoid arthritis: a randomised, double-blind, placebo-controlled clinical trial

    NARCIS (Netherlands)

    A.W.R. van Kuijk; C.E. Vergunst; D.M. Gerlag; B. Bresnihan; J.J. Gomez-Reino; R. Regine; P.C. Verschueren; C. van der Leij; M. Maas; M.C. Kraan; P.P. Tak

    2010-01-01

    Objective C-C chemokine receptor type 5 (CCR5), a chemokine receptor expressed on T cells and macrophages, and its ligands are found in inflamed synovial tissue (ST) of patients with rheumatoid arthritis (RA). The rationale for testing CCR5 blockade in patients with RA was supported by the effects o

  6. A Picture Really is Worth a Thousand Words: Public Engagement with the National Cancer Institute on Social Media.

    Science.gov (United States)

    Strekalova, Yulia A; Krieger, Janice L

    2017-03-01

    The National Cancer Institute (NCI) provides pertinent information about cancer prevention, treatment, and research advancements that is considered objective and accurate. NCI's presence on social media is an example of a growing effort in promoting and facilitating audience engagement with evidence-based information about health and cancer. However, it is unknown what strategies are most effective for engaging audiences via this communication platform. To evaluate this important question, we analyzed data on posts, associated comments, and meta-data from official NCI Facebook page between July 2010 and February 2015 (end of data collection). Results show that audience engagement is associated with the format of cancer-related social media posts. Specifically, posts with photos received significantly more likes, comments, and shares than videos, links, and status updates. The findings have important implications for how social media can be more effectively utilized to promote public engagement with important public health issues.

  7. Provincial distribution of three HIV-1 resistant polymorphisms (CCR5-Δ32, CCR2-64I, and SDF1-3’ A) in China

    Institute of Scientific and Technical Information of China (English)

    肖君华; 胡芳; 徐红岩; 苏兵; 蒋跃明; 罗竞春; 张蔚翎; 谈家桢; 金力; 卢大儒

    2000-01-01

    CCR5-Δ2, CCR2-641, mutants in two chemokine receptors and SDF1-3’ A, mutant in a ligand gene, can delay AIDS pathogenesis. The distribution of the three polymorphic loci was studied in 1 046 DNA samples from 26 provinces (cities) in China. No CCR5-Δ32 was observed. CCR2-64I and SDF1-3’ A had reverse distribution cline from south to north in China, with average frequency of 20.8% and 24.8% respectively. Relative hazard was evaluated. Important information to the epidemiology of AIDS and the origin and spread of these polymorphic loci in Chinese was provided.

  8. Provincial distribution of three HIV-1 resistant polymorphisms (CCR5-Δ32,CCR2-64I,and SDF1-3′A) in China

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    CCR5-Δ32,CCR2-64I,mutants in two chemokine receptors and SDF1-3′A,mutant in a ligand gene,can delay AIDS pathogenesis.The distribution of the three polymorphic loci was studied in 1 046 DNA samples from 26 provinces (cities) in China.No CCR5-Δ32 was observed.CCR2-64I and SDF1-3′A had reverse distribution cline from south to north in China,with average frequency of 20.8% and 24.8% respectively.Relative hazard was evaluated.Important information to the epidemiology of AIDS and the origin and spread of these polymorphic loci in Chinese was provided.

  9. Relationship between CCR5 Gene Polymorphism and Condyloma Acuminata%CCR5基因多态性与尖锐湿疣的关系

    Institute of Scientific and Technical Information of China (English)

    左亚刚; 王宝玺; 刘秀荣; 赵芃; 阎倩姝

    2008-01-01

    目的 探讨CCR5△32基因多态性与尖锐湿疣的关系.方法 收集60例尖锐湿疣患者和50例健康对照者的DNA标本,采用PCR方法 扩增CCR5基因片段,比较两组的基因型差别.结果 60例尖锐湿疣和50例健康对照者中均未发现突变型CCR5 △32基因型.结论 CCR5 △32基因多态性与尖锐湿疣无相关性.

  10. Effect of CO2 pneumoperitoneum on the expression of the chemokine receptors CXCR4 and CCR7 in colorectal carcinoma cells in vitro

    Institute of Scientific and Technical Information of China (English)

    YANG Chun-kang; LI Guo-dong; YING Min-gang; XU Ke

    2013-01-01

    Background The ability of pneumoperitoneum in laparoscopic surgery to promote proliferation and metastasis of colorectal cancer has become a focus of research in the field of minimally invasive surgery.The aim of this research was to investigate the effect of CO2 pneumoperitoneum under different pressures and exposed times on the expression of chemokine receptors in colorectal carcinoma cells.Methods We constructed an in vitro pneumoperitoneum model.SW480 colon carcinoma cells were exposed to CO2 pneumoperitoneum under different pressures (6,9,12,and 15 mmHg) for 1,2,and 4 hours.These cells were then cultivated under the same conditions as normal SW480 colon carcinoma cells without CO2 pneumoperitoneum (control group),treated at 37℃,and 5% CO2.The expression of the chemokine receptors CXC receptor 4 (CXCR4) and chemokine C receptor 7 (CCR7) was detected by immunocytochemistry and reverse transcriptase polymerase chain reaction after being cultivated for 0,24,48,and 72 hours.Results Immunocytochemistry showed that CXCR4 expression in SW480 cells was significantly decreased in the 6,9,12,and 15 mmHg CO2 pneumoperitoneum-treated groups for the same exposure times compared with controls (P<0.05).CCR7 expression in SW480 cells was significantly decreased in the 12 and 15 mmHg CO2 pneumoperitoneumtreated groups compared with controls (P <0.05).CXCR4 and CCR7 expression increased up to the level of the control group after 24 and 48 hours (P >0.05).If the CO2 pneumoperitoneum pressure increased,CXCR4 and CCR7 expression decreased at all exposure times.If the CO2 pneumoperitoneum exposure time prolonged,there were no significant differences in CXCR4 and CCR7 expression under the same pressure.Under all exposure times,CXCR4 and CCR7 mRNA expression was significantly decreased in the 6,9,12,and 15 mmHg CO2 pneumoperitoneum-treated groups (P<0.05) compared with controls,and it increased up to the level of controls after being cultivated for 48 hours (P >0.05).If

  11. Host inflammatory response and development of complications of Chlamydia trachomatis genital infection in CCR5-deficient mice and subfertile women with the CCR5delta32 gene deletion.

    Science.gov (United States)

    Barr, Erika L; Ouburg, Sander; Igietseme, Joseph U; Morré, Servaas A; Okwandu, Edith; Eko, Francis O; Ifere, Godwin; Belay, Tesfaye; He, Qing; Lyn, Deborah; Nwankwo, Gift; Lillard, James W; Black, Carolyn M; Ananaba, Godwin A

    2005-08-01

    T cell immunity protects against diseases caused by the obligate intracellular bacterium Chlamydia trachomatis. Incidentally, host inflammatory response that includes T cells appears to also contribute to the pathogenesis of chlamydial diseases such as trachoma and tubal factor infertility (TFI). Therefore, designing effective prevention strategies requires a delineation of immune processes responsible for pathology and those mediating immunity, and identification of the immunogenetic factors predisposing to complication development. The chemokine receptor CCR5 is crucial for T cell activation and function since its deficiency causes suppression of T cell response. We investigated the hypothesis that the clearance of genital chlamydial infection in CCR5-deficient mice could be delayed in the short term; however, a beneficial effect could include protection against inflammation-related complications such as TFI. In a translational study in humans, we investigated the effect of a functional 32 bp deletion in the CCR5 gene on the risk of developing tubal pathology in Dutch Caucasian women with immunologic evidence [i.e., immunoglobulin G (IgG) responses] of chlamydial infection. When genitally-infected wild-type (WT) and CCR5 knockout (CCR5KO) mice were evaluated for microbiologic shedding of chlamydiae, there was a greater intensity of infection and delayed resolution in the knockout mice. However, compared to WT mice, the fertility of infected CCR5KO mice (measured by pregnancy rate) was only mildly affected in the short term and unaffected in the long term (70% vs 30% reduction in the short term, and 50 vs 0% in the long term, respectively). Immunobiologic analysis revealed that the diminished capacity of CCR5KO to control acute chlamydial infection correlated with the relatively low chemokine [interferon-inducible protein 10 (IP-10) and regulated upon activation normal cell expressed and secreted (RANTES)] and cytokine (mainly interferon-gamma and tumor necrosis

  12. Analysis of CCR5 and SDF-1 genetic variants and HIV infection in Indian population.

    Science.gov (United States)

    Gupta, A; Padh, Harish

    2015-08-01

    HIV-1 infection and progression exhibits interindividual variation. The polymorphism in the chemokine receptors CCR5 and CXCR4, the principal coreceptors for HIV-1 and their ligands like SDF-1 have a profound effect in altering the HIV-1 disease progression rate. A single nucleotide polymorphism designated SDF1-3'UTR-801G-A has been associated with resistance to HIV-1 infection or delayed progression to AIDS. In this study, the SDF1-3'A polymorphism, CCR5∆32 polymorphism and CCR5 promoter polymorphism at positions 58934 G/T, 59029 G/A, 59353 T/C, 59356 C/T, 59402 A/G and 59653 C/T were analysed in Indian population. The polymorphisms in HIV-1 patients and healthy individuals were evaluated by conventional PCR, RFLP-PCR and direct sequencing techniques. The CCR5∆32 mutant allele was found to be almost absent in Indian population. The analysis of the CCR5-59356C/T polymorphism revealed a trend towards an association of the C allele with an increased risk of HIV-1 infection. The frequency of allele CCR5-59356C was higher in HIV-1 patients (100%) as compared to healthy control subjects (89%, P = 0.003). The correlation of SDF1-3'A and CCR5 promoter CCR5-58934G/T, CCR5-59029G/A, CCR5-59353T/C, CCR5-59402 A/G and CCR5-59653C/T polymorphisms and protection to HIV-1 infection and progression to AIDS was found to be nonsignificant. Nine haplotypes with more than 1% frequency were detected but were not significant in their protective role against HIV. Comparative analysis with global populations showed a noteworthy difference in CCR5 and SDF-1 polymorphisms' frequency distribution, indicating the ethnic variability of Indians. Although susceptibility to infections cannot be completely dependent on one or few genetic variants, it is important to remember that SDF-1 and CCR5 variants have been correlated globally with HIV-1 infection and disease progression. In the light of that, higher frequency of SDF-1 variants in the Indian population is noteworthy.

  13. The distribution of lung cancer across sectors of society in the United Kingdom: a study using national primary care data

    Directory of Open Access Journals (Sweden)

    Iyen-Omofoman Barbara

    2011-11-01

    Full Text Available Abstract Background There is pressing need to diagnose lung cancer earlier in the United Kingdom (UK and it is likely that research using computerised general practice records will help this process. Linkage of these records to area-level geo-demographic classifications may also facilitate case ascertainment for public health programmes, however, there have as yet been no extensive studies of data validity for such purposes. Methods To first address the need for validation, we assessed the completeness and representativeness of lung cancer data from The Health Improvement Network (THIN national primary care database by comparing incidence and survival between 2000 and 2009 with the UK National Cancer Registry and the National Lung Cancer Audit Database. Secondly, we explored the potential of a geo-demographic social marketing tool to facilitate disease ascertainment by using Experian's Mosaic Public Sector ™ classification, to identify detailed profiles of the sectors of society where lung cancer incidence was highest. Results Overall incidence of lung cancer (41.4/100, 000 person-years, 95% confidence interval 40.6-42.1 and median survival (232 days were similar to other national data; The incidence rate in THIN from 2003-2006 was found to be just over 93% of the national cancer registry rate. Incidence increased considerably with area-level deprivation measured by the Townsend Index and was highest in the North-West of England (65.1/100, 000 person-years. Wider variations in incidence were however identified using Mosaic classifications with the highest incidence in Mosaic Public Sector ™types 'Cared-for pensioners, ' 'Old people in flats' and 'Dignified dependency' (191.7, 174.2 and 117.1 per 100, 000 person-years respectively. Conclusions Routine electronic data in THIN are a valid source of lung cancer information. Mosaic ™ identified greater incidence differentials than standard area-level measures and as such could be used as a tool

  14. A consensus plan for action to improve access to cancer care in the association of Southeast Asian Nations (ASEAN) region.

    Science.gov (United States)

    Woodward, Mark

    2014-01-01

    In many countries of the Association of Southeast Asian Nations (ASEAN), cancer is an increasing problem due to ageing and a transition to Western lifestyles. Governments have been slow to react to the health consequences of these socioeconomic changes, leading to the risk of a cancer epidemic overwhelming the region. A major limitation to motivating change is the paucity of high-quality data on cancer, and its socioeconomic repercussions, in ASEAN. Two initiatives have been launched to address these issues. First, a study of over 9000 new cancer patients in ASEAN - the ACTION study - which records information on financial difficulties, as well as clinical outcomes, subsequent to the diagnosis. Second, a series of roundtable meetings of key stakeholders and experts, with the broad aim of producing advice for governments in ASEAN to take appropriate account of issues relating to cancer, as well as to generate knowledge and interest through engagement with the media. An important product of these roundtables has been the Jakarta Call to Action on Cancer Control. The growth and ageing of populations is a global challenge for cancer services. In the less developed parts of Asia, and elsewhere, these problems are compounded by the epidemiological transition to Western lifestyles and lack of awareness of cancer at the government level. For many years, health services in less developed countries have concentrated on infectious diseases and mother-and-child health; despite a recent wake-up call (United Nations, 2010), these health services have so far failed to allow for the huge increase in cancer cases to come. It has been estimated that, in Asia, the number of new cancer cases per year will grow from 6.1 million in 2008 to 10.6 million in 2030 (Sankaranarayanan et al., 2014). In the countries of the Association of Southeast Asian Nations (ASEAN), corresponding figures are 770 thousand in 2012 (Figure 1), rising to 1.3 million in 2030 (Ferlay et al., 2012). ASEAN

  15. The burden of cancer in member countries of the Association of Southeast Asian Nations (ASEAN).

    Science.gov (United States)

    Kimman, Merel; Norman, Rosana; Jan, Stephen; Kingston, David; Woodward, Mark

    2012-01-01

    This paper presents the most recent data on cancer rates and the burden of cancer in the ASEAN region. Epidemiological data were sourced from GLOBOCAN 2008 and disability adjusted life years (DALYs) lost were estimated using the standard methodology developed within the World Health Organization's Global Burden of Disease study. Overall, it was estimated there were over 700,000 new cases of cancer and 500,000 cancer deaths in ASEAN in the year 2008, leading to approximately 7.5 million DALYs lost in one year. The most commonly diagnosed cancers were lung (98,143), breast (86,842) and liver cancers (74,777). The most common causes of cancer death were lung cancer (85,772), liver cancer (69,115) and colorectal cancer (44,280). The burden of cancer in terms of DALYs lost was highest in Laos, Viet Nam and Myanmar and lowest in Brunei, Singapore and the Philippines. Significant differences in the patterns of cancer from country to country were observed. Another key finding was the major impact played by population age distribution on cancer incidence and mortality. Cancer rates in ASEAN are expected to increase with ageing of populations and changes in lifestyles associated with economic development. Therefore, ASEAN member countries are strongly encouraged to put in place cancer-control health care policies, focussed on strengthening the health systems to cope with projected increases in cancer prevention, treatment and management needs.

  16. Expression of regulated upon activation normal T-cell expressed and secreted and its receptors CCR1 and CCR5 in rat epididymis%受激活调节正常T细胞表达和分泌因子及其受体CCR1、CCR5在大鼠附睾的表达与定位

    Institute of Scientific and Technical Information of China (English)

    冯潇; 程胖; 赵洁; 肖岚; 李臻

    2013-01-01

    Objective:To observe the expression and the cellular localization of regulated upon activation normal T-cell expressed and secreted (RANTES) as well as its receptors CCR1 and CCR5 in the rat epididymis.Methods:Reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the expression of RANTES and its receptors mRNA in rat epididymis.The presence of RANTES and its receptors protein was assayed by Western blotting.Paraffin-embedded sections were prepared from rat epididymis,and immunohistochemical staining was carried out to detect cellular location of RANTES and its receptors.Colocalization of RANTES,CCR1,and CCR5 in rat epididymis was detected by immunofluorescence.Results:RT-PCR analysis showed the specific expression of RANTES and its receptors in the segments of adult rat epididymis.The distinctive single band of RANTES protein and its receptors protein was identified in the segments of rat epididymis with Western blotting.The positive staining of RANTES and its receptors were mainly observed in the basal cells of the epididymal epithelium.The immunofluorescence of RANTES coincided with CCR1 and CCR5 in the basal cells of epididymis.Conclusion:The expressions of RANTES and its receptors CCR1 and CCR5 were found restricted in the basal cells of the rat epididymis.These results revealed that RANTES may play a role in the physiological function of the basal cells of rat epididymis through autocrine or/and paracrine way.%目的:观察受激活调节正常T细胞表达和分泌因子(RANTES)与其受体CCR1、CCR5在大鼠附睾中的表达和定位.方法:采用免疫组织化学法检测成年大鼠附睾上皮RANTES及其受体的细胞定位,免疫荧光双标染色分别显示RANTES与CCR1、CCR5的细胞共定位情况.RT-PCR检测RANTES及其受体mRNA表达水平,免疫印迹检测RANTES及其受体的蛋白量.结果:RANTES与其受体CCR1、CCR5在大鼠附睾各段呈特异性表达.免疫印迹在大鼠附睾各段检测到RANTES及其受体CCR

  17. Differential requirement for CCR4 and CCR7 during the development of innate and adaptive αβT cells in the adult thymus.

    Science.gov (United States)

    Cowan, Jennifer E; McCarthy, Nicholas I; Parnell, Sonia M; White, Andrea J; Bacon, Andrea; Serge, Arnauld; Irla, Magali; Lane, Peter J L; Jenkinson, Eric J; Jenkinson, William E; Anderson, Graham

    2014-08-01

    αβT cell development depends upon serial migration of thymocyte precursors through cortical and medullary microenvironments, enabling specialized stromal cells to provide important signals at specific stages of their development. Although conventional αβT cells are subject to clonal deletion in the medulla, entry into the thymus medulla also fosters αβT cell differentiation. For example, during postnatal periods, the medulla is involved in the intrathymic generation of multiple αβT cell lineages, notably the induction of Foxp3(+) regulatory T cell development and the completion of invariant NKT cell development. Although migration of conventional αβT cells to the medulla is mediated by the chemokine receptor CCR7, how other T cell subsets gain access to medullary areas during their normal development is not clear. In this study, we show that combining a panel of thymocyte maturation markers with cell surface analysis of CCR7 and CCR4 identifies distinct stages in the development of multiple αβT cell lineages in the thymus. Although Aire regulates expression of the CCR4 ligands CCL17 and CCL22, we show that CCR4 is dispensable for thymocyte migration and development in the adult thymus, demonstrating defective T cell development in Aire(-/-) mice is not because of a loss of CCR4-mediated migration. Moreover, we reveal that CCR7 controls the development of invariant NKT cells by enabling their access to IL-15 trans-presentation in the thymic medulla and influences the balance of early and late intrathymic stages of Foxp3(+) regulatory T cell development. Collectively, our data identify novel roles for CCR7 during intrathymic T cell development, highlighting its importance in enabling multiple αβT cell lineages to access the thymic medulla.

  18. Molecular cloning, structure and expressional profiles of two novel single-exon genes (PoCCR6A and PoCCR6B) in the Japanese flounder (Paralichthys olivaceus).

    Science.gov (United States)

    Wang, Lei; Zhang, Yong-zhen; Xu, Wen-teng; Jia, Xiao-dong; Chen, Song-lin

    2016-05-01

    CCR6 is an important binding receptor of CCL20 and beta-defensins, and has multiple functions in the innate and acquired immune responses. In this study, we cloned the PoCCR6A and PoCCR6B genes of the Japanese flounder and studied the gene structure and expression patterns of these two genes in bacterial infection. The full-length PoCCR6A cDNA is 1415 bp and the open reading frame (ORF) is 1113 bp, encoding a 370-amino-acid peptide. The full-length PoCCR6B cDNA is 2193 bp and the ORF is 1029 bp, encoding a 363-amino-acid peptide. The structures of PoCCR6A and PoCCR6B indicate that they are single-exon genes. The predicted proteins encoded by PoCCR6A and PoCCR6B have the typical G-protein-coupled receptor (GPCR) family signature of seven transmembrane domains and several conserved structural features. A tissue distribution analysis showed that PoCCR6A is predominately expressed in the intestine, gill, and blood, and PoCCR6B in the gill, spleen, and liver. The expression patterns of the two chemokine receptors were analyzed during bacterial infection. In spleen and kidney, the expression of PoCCR6A was significantly upregulated at 24 h after infection, whereas the expression of PoCCR6B was steady at these time points. While in intestine, both of them were upregulated at 6 h-12 h after infection, and in gill the expression levels of them were upregulated at 24 h. The patterns of expression suggested that PoCCR6A and PoCCR6B play an important role in the immune response of the Japanese flounder, especially in the mucosal tissues.

  19. Outcomes of Induction Chemotherapy for Head and Neck Cancer Patients: A Combined Study of Two National Cohorts in Taiwan.

    Science.gov (United States)

    Chen, Jin-Hua; Yen, Yu-Chun; Liu, Shing-Hwa; Yuan, Sheng-Po; Wu, Li-Li; Lee, Fei-Peng; Lin, Kuan-Chou; Lai, Ming-Tang; Wu, Chia-Che; Chen, Tsung-Ming; Chang, Chia-Lun; Chow, Jyh-Ming; Ding, Yi-Fang; Lin, Ming-Chin; Wu, Szu-Yuan

    2016-02-01

    The use of induction chemotherapy (CT) is controversial. We compared the survival of head and neck cancer patients receiving docetaxel- or platinum-based induction CT before concomitant chemoradiotherapy (CCRT) with the survival of those receiving upfront CCRT alone. Data from the National Health Insurance and cancer registry databases in Taiwan were linked and analyzed. We enrolled patients who had head and neck cancer between January 1, 2002 and December 31, 2011. Follow-up was from the index date to December 31, 2013. We included head and neck patients diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0-148.9 who were aged >20 years, at American Joint Committee on Cancer clinical cancer stage III or IV, and receiving induction CT or platinum-based CCRT. The exclusion criteria were a cancer history before head and neck cancer diagnosis, distant metastasis, AJCC clinical cancer stage I or II, receipt of platinum and docetaxel before radiotherapy, an age induction CT for >8 weeks before RT, induction CT alone before RT, cetuximab use, adjuvant CT within 90 days after RT completion, an RT dose cancer surgery before RT, nasopharyngeal cancer, in situ carcinoma, sarcoma, and head and neck cancer recurrence. We enrolled 10,721 stage III-IV head and neck cancer patients, with a median follow-up of 4.18 years (interquartile range, 3.25 years). The CCRT (arm 1), docetaxel-based induction CT (arm 2), and platinum-based CCRT (arm 3; control arm) groups comprised 7968, 503, and 2232 patients, respectively. Arm 3 was used to investigate mortality risk after induction CT. After adjustment for age, sex, clinical stage, and comorbidities, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) for overall death were 1.37 (1.22-1.53) and 1.44 (1.36-1.52) in arms 2 and 3, respectively. In a disease-specific survival rate analysis, aHRs (95% CI) of head and neck cancer-related death were 1.29 (1

  20. Amino- and Carboxyl-Terminal CCR5 Mutations in Brazilian HIV-1-Infected Women and Homology Model of p.L55Q CCR5 Mutant.

    Science.gov (United States)

    Costa, Giselle Calasans de Souza; Nunes, Marcio Roberto T; Jesus, Jaqueline Goes; Novaes, Thiago; Cardoso, Jedson Ferreira; Sousa Júnior, Edivaldo Costa; Santos, Edson de Souza; Galvão-Castro, Bernardo; Zanette, Dalila Luciola; Gonçalves, Marilda de Souza; Alcantara, Luiz Carlos Junior

    2015-07-01

    Genetic factors from an HIV-1 host can affect the rate of progression to AIDS and HIV infection. To investigate the frequency of mutations in the CCR5 gene, HIV-1 samples from infected women and uninfected individuals were selected for sequencing of the CCR5 gene regions encoding the N- and C-terminal protein domains. Physicochemical CCR5 modeling and potential protein domain analysis were performed in order to evaluate the impact of the mutations found in the properties and structure of CCR5. The p.L55Q mutation in the N-terminal protein domain was observed only in uninfected individuals, with an allelic frequency of 1.8%. Physicochemical analysis revealed that the p.L55Q mutation magnified the flexibility and accessibility profiles and the modeling of CCR5 structures showed resulting in a small deviation to the right, as well as a hydrophobic to hydrophilic property alteration. The p.L55Q mutation also resulted in a slight modification of the electrostatic load of this region. Additionally, three novel silent mutations were found at the C-terminal coding region among HIV-1-infected women. The results suggest that the p.L55Q mutation might alter CCR5 conformation. Further studies should be conducted to verify the role of this mutation in HIV-1 susceptibility.

  1. Variation in promptness of presentation among 10,297 patients subsequently diagnosed with one of 18 cancers: evidence from a National Audit of Cancer Diagnosis in Primary Care.

    Science.gov (United States)

    Keeble, Stuart; Abel, Gary A; Saunders, Catherine L; McPhail, Sean; Walter, Fiona M; Neal, Richard D; Rubin, Gregory P; Lyratzopoulos, Georgios

    2014-09-01

    Cancer awareness public campaigns aim to shorten the interval between symptom onset and presentation to a doctor (the 'patient interval'). Appreciating variation in promptness of presentation can help to better target awareness campaigns. We explored variation in patient intervals recorded in consultations with general practitioners among 10,297 English patients subsequently diagnosed with one of 18 cancers (bladder, brain, breast, colorectal, endometrial, leukaemia, lung, lymphoma, melanoma, multiple myeloma, oesophageal, oro-pharyngeal, ovarian, pancreatic, prostate, renal, stomach, and unknown primary) using data from of the National Audit of Cancer Diagnosis in Primary Care (2009-2010). Proportions of patients with 'prompt'/'non-prompt' presentation (0-14 or 15+ days from symptom onset, respectively) were described and respective odds ratios were calculated by multivariable logistic regression. The overall median recorded patient interval was 10 days (IQR 0-38). Of all patients, 56% presented promptly. Prompt presentation was more frequent among older or housebound patients (p presentation was most frequent for bladder and renal cancer (74% and 70%, respectively); and least frequent for oro-pharyngeal and oesophageal cancer (34% and 39%, respectively, p presentation were 2.26 (95% confidence interval 1.57-3.25) and 0.42 (0.34-0.52) for oro-pharyngeal and bladder cancer, respectively. Sensitivity analyses produced similar findings. Routinely recorded patient interval data reveal considerable variation in the promptness of presentation. These findings can help to prioritise public awareness initiatives and research focusing on symptoms of cancers associated with greater risk of non-prompt presentation, such as oro-pharyngeal and oesophageal cancer.

  2. Body mass index and survival after diagnosis of invasive breast cancer: a study based on the Japanese National Clinical Database-Breast Cancer Registry.

    Science.gov (United States)

    Kawai, Masaaki; Tomotaki, Ai; Miyata, Hiroaki; Iwamoto, Takayuki; Niikura, Naoki; Anan, Keisei; Hayashi, Naoki; Aogi, Kenjiro; Ishida, Takanori; Masuoka, Hideji; Iijima, Kotaro; Masuda, Shinobu; Tsugawa, Koichiro; Kinoshita, Takayuki; Nakamura, Seigo; Tokuda, Yutaka

    2016-06-01

    Few studies have reported the association between body mass index (BMI) and outcome among Asian breast cancer patients. We analyzed data for 20,090 female invasive breast cancer patients who had been followed-up for a median period of 6.7 years entered in the National Clinical Database-Breast Cancer Registry between 2004 and 2006. We used mainly the WHO criteria for BMI (kg/m(2) ) categories; cause, 937 breast cancer-specific deaths, and 2433 recurrences were observed. Obesity was associated with an increased risk of all-cause (HR: 1.46; 95% CI: 1.16-1.83) and breast cancer-specific death (HR: 1.47; 95% CI: 1.11-1.93) for all patients, and with all-cause (HR: 1.47; 95% CI: 1.13-1.92) and breast cancer-specific death (HR: 1.58; 95% CI: 1.13-2.20) for postmenopausal patients. Being underweight was associated with an increased risk of all-cause death for all (HR: 1.41; 95% CI: 1.16-1.71) and for postmenopausal patients (HR: 1.45; 95% CI: 1.15-1.84). With regard to subtype and menopausal status, obesity was associated with an increased risk of breast cancer-specific death for all cases of luminal B tumor (HR: 2.59; 95% CI: 1.51-4.43; Pheterogeneity of Luminal B vs. Triple negative = 0.016) and for postmenopausal patients with luminal B tumor (HR: 3.24; 95% CI: 1.71-6.17). Being obese or underweight is associated with a higher risk of death among female breast cancer patients in Japan.

  3. The actin-bundling protein L-plastin dissociates CCR7 proximal signaling from CCR7-induced motility1

    OpenAIRE

    Morley, Sharon Celeste; Wang, Chen; Lo, Wan-Lin; Lio, Chan-Wang J.; Zinselmeyer, Bernd H.; Miller, Mark J.; Brown, Eric J.; Paul M Allen

    2010-01-01

    Chemokines promote lymphocyte motility by triggering F-actin rearrangements and inducing cellular polarization. Chemokines can also enhance cell-cell adhesion and co-stimulate T cells. Here we establish a requirement for the actin-bundling protein L-plastin (LPL) in CCR7- and S1P1-mediated T cell chemotaxis using LPL−/− mice. Disrupted motility of mature LPL−/− thymocytes manifested in vivo as diminished thymic egress. Two-photon microscopy of LPL−/− lymphocytes revealed reduced velocity and ...

  4. The preclinical new drug research program of the National Cancer Institute.

    Science.gov (United States)

    Driscoll, J S

    1984-01-01

    The discovery and development of anticancer drugs with clinical potential are the responsibility of the Developmental Therapeutics Program (DTP), Division of Cancer Treatment, National Cancer Institute (NCI). Approximately 10,000 compounds/year are selectively acquired and screened against murine tumor models in order to discover new, active materials. The program required to accomplish this objective, as well as the subsequent tasks of formulation development and toxicology testing, is described. Since its inception in 1955, the preclinical new drug research program of the NCI has played a major role in the discovery and development of new agents which have been entered into clinical trial. The NCI has been responsible for the discovery of eight of the 16 commercially available drugs discovered since 1955. In addition, the NCI has played an important role in the clinical evaluation of all 16 of these New Drug Application (NDA)-approved drugs. During 1977-1982, the NCI filed Investigational New Drug Applications (INDA) for 33 cytotoxic agents. It was responsible for the discovery of the antitumor activity of 73% of these compounds. Most of the INDA compounds were acquired directly through NCI efforts. The DTP active acquisition program was responsible for obtaining 69% of these materials, with an additional 12% coming from the DTP intramural research program. Only 19% were received as voluntary submissions. The DTP active acquisition and screening effort is shown to have played even a larger role in identifying and obtaining those compounds which are currently in earlier stages of the NCI drug discovery and development process.

  5. Tumor induction following intraoperative radiotherapy: Late results of the National Cancer Institute canine trials

    Energy Technology Data Exchange (ETDEWEB)

    Barnes, M.; Duray, P.; DeLuca, A.; Anderson, W.; Sindelar, W.; Kinsella, T. (Fox Chase Cancer Center, Philadelphia, PA (USA))

    1990-09-01

    Intraoperative radiotherapy has been employed in human cancer research for over a decade. Since 1979, trials to assess the acute and late toxicity of IORT have been carried out at the National Cancer Institute in an adult dog model in an attempt to establish dose tolerance guidelines for a variety of organs. Of the 170 animals entered on 12 studies with a minimum follow-up of 2 years, 148 dogs received IORT; 22 control animals received only surgery. Animals were sacrificed at designated intervals following IORT, usually at 1, 6, 12, 24, and 60 month intervals. 102 of 148 irradiated dogs were sacrificed less than 24 months; 46 dogs were followed greater than or equal to 24 months after IORT. To date, 34 of the 46 animals have been sacrificed; the 12 remaining animals are to be followed to 5 years. These 12 animals have minimum follow-up of 30 months. In the irradiated group followed for greater than or equal to 24 months, 10 tumors have arisen in 9 animals. One animal developed an incidental spontaneous breast carcinoma outside the IORT port, discovered only at scheduled post-mortem exam. The remaining nine tumors arose within IORT ports. Two tumors were benign neural tumors--a neuroma and a neurofibroma. One animal had a collision tumor comprised of grade I chondrosarcoma adjacent to grade III osteosarcoma arising in lumbar vertebrae. Two other grade III osteosarcomas, one grade III fibrosarcoma, and one grade III malignant fibrous histiocytoma arose in retroperitoneal/paravertebral sites. An embryonal rhabdomyosarcoma (sarcoma botryoides) arose within the irradiated urinary bladder of one animal. No sham irradiated controls nor IORT animals sacrificed less than 24 months have developed any spontaneous or radiation-induced tumors. The time range of diagnoses of tumors was 24-58 months. The IORT dose range associated with tumor development was 20-35 Gy.

  6. Structure prediction of GPCRs using piecewise homologs and application to the human CCR5 chemokine receptor: validation through agonist and antagonist docking.

    Science.gov (United States)

    Arumugam, Karthik; Crouzy, Serge; Chevigne, Andy; Seguin-Devaux, Carole; Schmit, Jean-Claude

    2014-01-01

    This article describes the construction and validation of a three-dimensional model of the human CC chemokine receptor 5 (CCR5) receptor using multiple homology modeling. A new methodology is presented where we built each secondary structural model of the protein separately from distantly related homologs of known structure. The reliability of our approach for G-protein coupled receptors was assessed through the building of the human C-X-C chemokine receptor type 4 (CXCR4) receptor of known crystal structure. The models are refined using molecular dynamics simulations and energy minimizations using CHARMM, a classical force field for proteins. Finally, docking models of both the natural agonists and the antagonists of the receptors CCR5 and CXCR4 are proposed. This study explores the possible binding process of ligands to the receptor cavity of chemokine receptors at molecular and atomic levels. We proposed few crucial residues in receptors binding to agonist/antagonist for further validation through experimental analysis. In particular, our study provides better understanding of the blockage mechanism of the chemokine receptors CCR5 and CXCR4, and may help the identification of new lead compounds for drug development in HIV infection, inflammatory diseases, and cancer metastasis.

  7. Nation

    DEFF Research Database (Denmark)

    Østergaard, Uffe

    2014-01-01

    Nation er et gammelt begreb, som kommer af det latinske ord for fødsel, natio. Nationalisme bygger på forestillingen om, at mennesker har én og kun én national identitet og har ret til deres egen nationalstat. Ordet og forestillingen er kun godt 200 år gammel, og i 1900-tallet har ideologien bredt...... sig over hele verden. Nationalisme er blevet global....

  8. eGFR is a reliable preoperative renal function parameter in patients with gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Takayuki; Kosuge; Tokihiko; Sawada; Yoshimi; Iwasaki; Junji; Kita; Mitsugi; Shimoda; Nobumi; Tagaya; Keiichi; Kubota

    2010-01-01

    AIM: To evaluate the validity of the estimated glomerular filtration rate (eGFR) as a preoperative renal function parameter in patients with gastric cancer. METHODS: A retrospective study was conducted in 147 patients with gastric cancer. Preoperative creatinine clearance (Ccr), eGFR, and preand postoperative serum creatinine (sCr) data were examined. Preoperative Ccr and eGFR were then compared for their reliability in predicting postoperative renal dysfunction. RESULTS: Among 110 patients with normal preo...

  9. Utilization of Radiation Therapy in Norway After the Implementation of The National Cancer Plan—A National, Population-Based Study

    Energy Technology Data Exchange (ETDEWEB)

    Åsli, Linn M., E-mail: linn.merete.asli@kreftregisteret.no [Department of Registration, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo (Norway); Kvaløy, Stein O. [Division of Cancer, Surgery, and Transplantation, Oslo University Hospital and University of Oslo, Oslo (Norway); Jetne, Vidar [Department of Medical Physics, Oslo University Hospital, Oslo (Norway); Myklebust, Tor Å. [Department of Registration, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo (Norway); Levernes, Sverre G. [Department of Medical Physics, Oslo University Hospital, Oslo (Norway); The Norwegian Radiation Protection Authority, Østerås (Norway); Tveit, Kjell M. [Department of Oncology, Oslo University Hospital and University of Oslo, Oslo (Norway); Green, Tor O. [Department of Medical Physics, Oslo University Hospital, Oslo (Norway); Johannesen, Tom B. [Department of Registration, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo (Norway)

    2014-11-01

    Purpose: To estimate actual utilization rates of radiation therapy (RT) in Norway, describe time trends (1997-2010), and compare these estimates with corresponding optimal RT rates. Methods and Materials: Data from the population-based Cancer Registry of Norway was used to identify all patients diagnosed with cancer and/or treated by RT for cancer in 1997-2010. Radiation therapy utilization rates (RURs) were calculated as (1) the proportion of incident cancer cases who received RT at least once within 1 year of diagnosis (RUR{sub 1Y}); and (2) the proportion who received RT within 5 years of diagnosis (RUR{sub 5Y}). The number of RT treatment courses per incident cancer case (TCI) was also calculated for all cancer sites combined. The actual RURs were compared with corresponding Australian and Canadian epidemiologic- and evidence-based model estimates and criterion-based benchmark estimates of optimal RURs. The TCIs were compared with TCI estimates from the 1997 Norwegian/National Cancer Plan (NCP). Joinpoint regression was used to identify changes in trends and to estimate annual percentage change (APC) in actual RUR{sub 1Y} and actual TCI. Results: The actual RUR{sub 5Y} (all sites) increased significantly to 29% in 2005 but still differed markedly from the Australian epidemiologic- and evidence-based model estimate of 48%. With the exception of RUR{sub 5Y} for breast cancer and RUR{sub 1Y} for lung cancers, all actual RURs were markedly lower than optimal RUR estimates. The actual TCI increased significantly during the study period, reaching 42.5% in 2010, but was still lower than the 54% recommended in the NCP. The trend for RUR{sub 1Y} (all sites) and TCI changed significantly, with the annual percentage change being largest during the first part of the study period. Conclusions: Utilization rates of RT in Norway increased after the NCP was implemented and RT capacity was increased, but they still seem to be lower than optimal levels.

  10. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancers Metastatic Cancer Recurrent Cancer Research NCI’s Role in Cancer Research Intramural Research Extramural Research Bioinformatics and ... Annual Report to the Nation Cancer Snapshots Milestones in Cancer Research and Discovery Stories of Discovery R& ...

  11. Enriquecimento com calda do CCR para face de barragens

    Directory of Open Access Journals (Sweden)

    A. P. Wendler

    Full Text Available A construção de barragens de CCR prioriza a minimização de interferências, como a execução da face de montante, para garantia da produtividade. O estudo procurou avaliar as propriedades físicas do CCR enriquecido com calda, em substituição ao concreto convencional usualmente empregado na face, utilizando os mesmos materiais, central de concreto, mão de obra e equipamentos, empregados na construção da Usina Hidrelétrica Mauá. Para tanto foram feitos prismas experimentais de campo (com diferentes relações água/cimento e quantidades de calda e posterior extração de testemunhos, os quais foram submetidos a ensaios mecânicos e de permeabilidade. Os resultados mostraram que para relações água/cimento 0,74, o material resultante atendeu às especificações de projeto, para consumos de cimento notadamente menores (entre 70 e 85% do CCV.

  12. Frequency of CCR5delta32 in Brazilian populations

    Directory of Open Access Journals (Sweden)

    A.E. Vargas

    2006-03-01

    Full Text Available A sample of 103 randomly chosen healthy individuals from Alegrete, RS, Brazil, was tested for the CCR5delta32 allele, which is known to influence susceptibility to HIV-1 infection. The CCR5delta32 allele was identified by PCR amplification using specific primers flanking the region of deletion, followed by electrophoresis on a 3% agarose gel. The data obtained were compared to those reported for other populations and interpreted in terms of Brazilian history. The individuals studied came from a highly admixed population. Most of them were identified as white (N = 59, while blacks and browns (mulattoes were N = 13 and N = 31, respectively. The observed frequencies, considering the white, black and brown samples (6.8, 3.8, and 6.4%, respectively, suggest an important European parental contribution, even in populations identified as black and brown. However, in Brazil as a whole, this allele shows gradients indicating a relatively good correlation with the classification based on skin color and other physical traits, used here to define major Brazilian population groups.

  13. Frequent infiltration of S-100 protein+ CCR5+ immature dendritic cells in damaged bile ducts of primary biliary cirrhosis compared to cholangiocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Mitsui H

    2013-04-01

    Full Text Available Hiroko Mitsui,1,2 Hiroya Ohtake,1 Rintaro Ohe,1 Mitsunori Yamakawa1 1Department of Pathological Diagnostics, 2Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan Abstract: Dendritic cells (DCs are professional antigen presenting cells that initiate immune responses. We evaluated the relationship between DC infiltration, chemokines/chemokine receptors, and bile duct damage in primary biliary cirrhosis (PBC, compared to cases of cholangiocellular carcinoma arising from the bile duct. Immunohistochemistry revealed significantly more S-100 protein+ DCs infiltrating the epithelial layer of bile ducts in PBC than in chronic hepatitis C or control neonatal livers. Furthermore, a higher number of S-100 protein+ DCs, but not fascin+ or DC lysosomal associated membrane protein+ mature DCs, were found in the epithelial layer of the damaged bile ducts of the PBC liver. CC-chemokine receptor (CCR 5+ immature DCs frequently accumulated in the portal area in PBC. CCR5 mRNA was also detected in liver tissues from PBC patients by reverse transcription polymerase chain reaction. In situ hybridization revealed the expression of macrophage inflammatory protein (MIP-1α and MIP-1ß mRNA in the epithelial cells of damaged bile ducts. However, no CD1a+ immature DCs were found in any of the PBC or chronic hepatitis C specimens or in neonatal liver, whereas they occurred frequently in the cancer nests of cholangiocellular carcinoma, which expressed MIP-3α and were frequently infiltrated by CCR6+ DCs. These results indicate that bile ducts damaged by PBC secrete MIP-1α and MIP-1ß, while neoplastic ones secrete MIP-3α. They also suggest that CCR5+ immature DCs attracted by MIP-1α and MIP-1ß may play an important role in the pathogenesis of chronic nonsuppurative destructive cholangitis in PBC. Keywords: chemokines, cholangiocellular carcinoma, chronic nonsuppurative destructive cholangitis, dendritic cell, primary biliary

  14. CCR5 genotype and plasma ß-chemokine concentration of Brazilian HIV-infected individuals

    Directory of Open Access Journals (Sweden)

    Mikawa A.Y.

    2002-01-01

    Full Text Available The 32-bp deletion in the HIV-1 co-receptor CCR5 confers a high degree of resistance to HIV-1 infection in homozygous individuals for the deleted allele and partial protection against HIV-1 during disease progression in heterozygotes. Natural ligands for CCR5, MIP-1alpha, MIP-1ß and RANTES, have been shown to inhibit HIV replication in CD4+ T cells. In the present study, we examined the CCR5 genotype by PCR and the plasma levels of RANTES and MIP-1alpha by ELISA among blood donors (N = 26 and among HIV-1-infected individuals (N = 129. The control group consisted of healthy adult volunteers and HIV-1-infected subjects were an asymptomatic and heterogeneous group of individuals with regard to immunologic and virologic markers of HIV-1 disease. The frequency of the CCR5 mutant allele (delta32ccr5 in this population was 0.032; however, no delta32ccr5 homozygote was detected. These results could be related to the intense ethnic admixture of the Brazilian population. There was no correlation between circulating ß-chemokines (MIP-1alpha, RANTES and viral load in HIV-infected individuals. RANTES concentrations in plasma samples from HIV+ patients carrying the homozygous CCR5 allele (CCR5/CCR5 (28.23 ng/ml were higher than in the control samples (16.07 ng/ml; P<0.05; however, this HIV+ patient group (mean 26.23 pg/ml had significantly lower concentrations of MIP-1alpha than those observed in control samples (mean 31.20 pg/ml; P<0.05. Both HIV-1-infected and uninfected individuals heterozygous for the delta32ccr5 allele had significantly lower concentrations of circulating RANTES (mean 16.07 and 6.11 ng/ml, respectively than CCR5/CCR5 individuals (mean 28.23 and 16.07 ng/ml, respectively; P<0.05. These findings suggest that the CCR5 allele and ß-chemokine production may affect the immunopathogenesis of HIV-1.

  15. CCR5Δ32 Protein Expression and Stability Are Critical for Resistance to Human Immunodeficiency Virus Type 1 In Vivo▿

    OpenAIRE

    2007-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection of individuals carrying the two alleles of the CCR5Δ32 mutation (CCR5−/−) has rarely been reported, but how the virus overcomes the CCR5Δ32 protective effect in these cases has not been delineated. We have investigated this in 6 infected (HIV+) and 25 HIV− CCR5−/− individuals. CD4+ T lymphocytes isolated from HIV− CCR5−/− peripheral blood mononuclear cells (PBMCs) showed lower levels of CXCR4 expression that correlated with lower X4 Env-me...

  16. Association of TGFβ1, TNFα, CCR2 and CCR5 gene polymorphisms in type-2 diabetes and renal insufficiency among Asian Indians

    Directory of Open Access Journals (Sweden)

    Gupta Arvind

    2007-04-01

    Full Text Available Abstract Background Cytokines play an important role in the development of diabetic chronic renal insufficiency (CRI. Transforming growth factor β1 (TGF β1 induces renal hypertrophy and fibrosis, and cytokines like tumor necrosis factor-alpha (TNFα, chemoattractant protein-1 (MCP-1, and regulated upon activation and normal T cell expressed and secreted (RANTES mediate macrophage infiltration into kidney. Over expression of these chemokines leads to glomerulosclerosis and interstitial fibrosis. The effect of MCP-1 and RANTES on kidney is conferred by their receptors i.e., chemokine receptor (CCR-2 and CCR-5 respectively. We tested association of nine single nucleotide polymorphisms (SNPs from TGFβ1, TNFα, CCR2 and CCR5 genes among individuals with type-2 diabetes with and without renal insufficiency. Methods Type-2 diabetes subjects with chronic renal insufficiency (serum creatinine ≥ 3.0 mg/dl constituted the cases, and matched individuals with diabetes of duration ≥ 10 years and normoalbuminuria were evaluated as controls from four centres in India. Allelic and genotypic contributions of nine SNPs from TGFβ1, TNFα, CCR2 and CCR5 genes to diabetic CRI were tested by computing odds ratio (OR and 95% confidence intervals (CI. Sub-analysis of CRI cases diabetic retinopathy status as dependent variable and SNP genotypes as independent variable in a univariate logistic regression was also performed. Results SNPs Tyr81His and Thr263Ile in TGF β1 gene were monomorphic, and Arg25Pro in TGF β1 gene and Δ32 polymorphism in CCR5 gene were minor variants (minor allele frequency A SNP of CCR5 gene has been observed and the allele 59029A seems to confer predisposition to development of diabetic CRI (OR 1.39; CI 1.04–1.84. In CRI subjects a compound group of genotypes "GA and AA" of SNP G>A -800 was found to confer predisposition for proliferative retinopathy (OR 3.03; CI 1.08–8.50, p = 0.035. Conclusion Of the various cytokine gene

  17. Cancer trends in Kashmir; common types, site incidence and demographic profiles: National Cancer Registry 2000-2012

    Directory of Open Access Journals (Sweden)

    M A Wani

    2014-01-01

    Full Text Available Background: An assessment of cancer incidence in population is required for prevention, early diagnosis, treatment and resource allocation. This will also guide in the formation of facilities for diagnosis, treatment, rehabilitation and follow-up for these patients. The demographic trend of cancer will help to identify common types and etiological factors. Efforts at clinical, research and administrative levels are needed to overcome this problem. Settings and Design: Present retro prospective study was conducted in regional cancer center of a tertiary care hospital. Materials and Methods: After permission from ethics committee, a retro prospective study of 1 year duration was undertaken to study the profile of cancer patients and to compare it with other cancer registries in India. Statistical Analysis: Pearson′s Chi-square test and simple linear regression were used. Statistical Package for the Social Sciences version-16 (University of Bristol information services (www.bristol.ac.uk/is/learning/resources was used. RESULTS: The overall incidence of cancer in Kashmir is on the increase and common sites of cancer are esophagus and gastroesophageal (GE junction, lung, stomach, colorectal, lymphomas, skin, laryngopharynx, acute leukemias, prostate and brain in males.In females common sites are breast, esophagus and GE junction, ovary, colorectal, stomach, lung, gallbladder, lymphomas, acute leukemias and brain. Conclusion: Cancers of esophagus, stomach and lungs have a high incidence both in men and women in Kashmir. Future studies on sources and types of environmental pollution and exposures in relation to these cancers may improve our understanding of risk factors held responsible for causation of these malignancies in this region. This will help in the allocation of available resources for prevention and treatment strategies.

  18. Regional cancer centre demonstrates vol