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  1. Expression and histopathological correlation of CCR9 and CCL25 in ovarian cancer

    OpenAIRE

    Singh, Rajesh; Cecil R. Stockard; Grizzle, William E.; Lillard, James W.; Singh, Shailesh

    2011-01-01

    Ovarian carcinoma is the most lethal gynecological malignancy among women and its poor prognosis is mainly due to metastasis. Chemokine receptor CCR9 is primarily expressed by a small subset of immune cells. The interactions between CCL25 and CCR9 have been implicated in leukocyte trafficking to the small bowel, a frequent metastatic site for ovarian cancer cells. We have previously shown that ovarian cancer cells express CCR9 and play an important role in cell migration, invasion and surviva...

  2. [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.

  3. Expression and histopathological correlation of CCR9 and CCL25 in ovarian cancer.

    Science.gov (United States)

    Singh, Rajesh; Stockard, Cecil R; Grizzle, William E; Lillard, James W; Singh, Shailesh

    2011-08-01

    Ovarian carcinoma is the most lethal gynecological malignancy among women and its poor prognosis is mainly due to metastasis. Chemokine receptor CCR9 is primarily expressed by a small subset of immune cells. The interactions between CCL25 and CCR9 have been implicated in leukocyte trafficking to the small bowel, a frequent metastatic site for ovarian cancer cells. We have previously shown that ovarian cancer cells express CCR9 and play an important role in cell migration, invasion and survival in the presence of its natural ligand in vitro. In this study, we have evaluated the expression of CCR9 and CCL25 in ovarian cancer cells and clinical samples. Ovarian cancer tissue microarrays from University of Alabama at Birmingham and AccuMax were stained for CCR9 and CCL25. Aperio ScanScope was used to acquire 80X digital images and expression analysis of CCR9 and CCL25. Flow cytometry and the Image stream system were used to conform the expression of CCR9 and CCL25 in ovarian cancer cells. Our results show significantly higher (ptumor, dysgerminoma, transitional cell carcinoma, Brenner tumor, yolk sac tumor, adenocarcinoma and fibroma cases, compared to non-neoplastic ovarian tissue. Similar to tissue expression, CCR9 was also significantly expressed by the ovarian cancer cell lines (OVCAR-3 and SK-OV-3) in comparison to normal adult ovarian epithelial cell. We provide the first evidence that CCR9 and its natural ligand CCL25 are highly expressed by ovarian cancer tissue and their expression correlates with histological subtypes. Expression of this chemokine receptor and its ligand CCL25 within primary tumor tissue further suggests a potential role of this chemokine-receptor axis in ovarian cancer progression. PMID:21637913

  4. 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.

  5. Breast cancer lung metastasis requires expression of chemokine receptor CCR4 and regulatory T cells.

    Science.gov (United States)

    Olkhanud, Purevdorj B; Baatar, Dolgor; Bodogai, Monica; Hakim, Fran; Gress, Ronald; Anderson, Robin L; Deng, Jie; Xu, Mai; Briest, Susanne; Biragyn, Arya

    2009-07-15

    Cancer metastasis is a leading cause of cancer morbidity and mortality. More needs to be learned about mechanisms that control this process. In particular, the role of chemokine receptors in metastasis remains controversial. Here, using a highly metastatic breast cancer (4T1) model, we show that lung metastasis is a feature of only a proportion of the tumor cells that express CCR4. Moreover, the primary tumor growing in mammary pads activates remotely the expression of TARC/CCL17 and MDC/CCL22 in the lungs. These chemokines acting through CCR4 attract both tumor and immune cells. However, CCR4-mediated chemotaxis was not sufficient to produce metastasis, as tumor cells in the lung were efficiently eliminated by natural killer (NK) cells. Lung metastasis required CCR4(+) regulatory T cells (Treg), which directly killed NK cells using beta-galactoside-binding protein. Thus, strategies that abrogate any part of this process should improve the outcome through activation of effector cells and prevention of tumor cell migration. We confirm this prediction by killing CCR4(+) cells through delivery of TARC-fused toxins or depleting Tregs and preventing lung metastasis. PMID:19567680

  6. 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...

  7. 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.

  8. 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.

  9. CCR2-V64I polymorphism is associated with increased risk of cervical cancer but not with HPV infection or pre-cancerous lesions in African women

    International Nuclear Information System (INIS)

    Cervical cancer, caused by specific oncogenic types of human papillomavirus (HPV), is the second most common cancer in women worldwide. A large number of young sexually active women get infected by HPV but only a small fraction of them have persistent infection and develop cervical cancer pointing to co- factors including host genetics that might play a role in outcome of the HPV infection. This study investigated the role of CCR2-V64I polymorphism in cervical cancer, pre-cancers and HPV infection in South African women resident in Western Cape. CCR2-V64I polymorphism has been previously reported to influence the progression to cervical cancer in some populations and has also been associated with decreased progression from HIV infection to AIDS. Genotyping for CCR2-V64I was done by PCR-SSP in a case-control study of 446 women (106 black African and 340 mixed-ancestry) with histologically confirmed invasive cervical cancer and 1432 controls (322 black African and 1110 mixed-ancestry) group-matched (1:3) by age, ethnicity and domicile status. In the control women HPV was detected using the Digene Hybrid Capture II test and cervical disease was detected by cervical cytology. The CCR2-64I variant was significantly associated with cervical cancer when cases were compared to the control group (P = 0.001). Further analysis comparing selected groups within the controls showed that individuals with abnormal cytology and high grade squamous intraepitleial neoplasia (HSIL) did not have this association when compared to women with normal cytology. HPV infection also showed no association with CCR2-64I variant. Comparing SIL positive controls with the cases showed a significant association of CCR2-64I variant (P = 0.001) with cervical cancer. This is the first study of the role of CCR2-V64I polymorphism in cervical cancer in an African population. Our results show that CCR2-64I variant is associated with the risk of cervical cancer but does not affect the susceptibility to HPV

  10. Tumor infiltration by chemokine receptor 7 (CCR7)+ T-lymphocytes is a favorable prognostic factor in metastatic colorectal cancer

    OpenAIRE

    Correale, Pierpaolo; Rotundo, Maria Saveria; Botta, Cirino; del Vecchio, Maria Teresa; Tassone, Pierfrancesco; Tagliaferri, Pierosandro

    2012-01-01

    The immune interactions occurring within the tumor microenvironment have a critical role in determining the outcome of colorectal cancer patients. We carried-out an immunohistochemical analysis of tumor infiltrating T-lymphocytes expressing chemokine receptor 7 (CCR7) in a series of colorectal cancer patients enrolled in a prospective clinical trial. We demonstrated that a high tumor infiltration score of this lymphocyte subset is predictive of longer progression free survival and overall sur...

  11. 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。

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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. PMID:27177471

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 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. PMID:26096680

  20. Haptoglobin and CCR2 receptor expression in ovarian cancer cells that were exposed to ascitic fluid: exploring a new role of haptoglobin in the tumoral microenvironment.

    Science.gov (United States)

    Garibay-Cerdenares, O L; Hernández-Ramírez, V I; Osorio-Trujillo, J C; Gallardo-Rincón, D; Talamás-Rohana, P

    2015-01-01

    Haptoglobin (Hp) is an acute-phase protein that is produced by the liver to capture the iron that is present in the blood circulation, thus avoiding its accumulation in the blood. Moreover, Hp has been detected in a wide variety of tissues, in which it performs various functions. In addition, this protein is considered a potential biomarker in many diseases, such as cancer, including ovarian carcinoma; however, its participation in the cancerous processes has not yet been determined. The objective of this work was to demonstrate the expression of Hp and its receptor CCR2 in the ovarian cancer cells and its possible involvement in the process of cell migration through changes in the rearrangement of the actin cytoskeleton using western blot and wound-healing assays and confirming by confocal microscopy. Ovarian cancer cells express both Hp and its receptor CCR2 but only after exposure to ascitic fluid, inducing moderated cell migration. However, when the cells are exposed to exogenous Hp, the expression of CCR2 is induced together with drastic changes in the actin cytoskeleton rearrangement. At the same time, Hp induced cell migration in a much more efficient manner than did ascitic fluid. These effects were blocked when the CCR2 synthetic antagonist RS102895 was used to pretreat the cells. These results suggest that Hp-induced changes in the cell morphology, actin cytoskeleton structure, and migration ability of tumor cells, is possibly "preparing" these cells for the potential induction of the metastatic phenotype. PMID:26211665

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. National Cancer Institute

    Science.gov (United States)

    ... Español 1-800-4-CANCER Live Chat Publications Dictionary Menu Contact Dictionary Search About Cancer Causes and Prevention Risk Factors ... Contacts Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training ...

  4. 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.

  5. National Ovarian Cancer Coalition

    Science.gov (United States)

    ... 10, 2016 TESARO, Inc., an oncology-focused biopharmaceutical company, and ENGOT, the European Network for Gynecological Oncological Trial groups, today announced the presentation ... Read More NOCC Launches NOCC CancerConnect Community Social Media Network for Women with Ovarian Cancer September ...

  6. 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... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed Meetings... clearly unwarranted invasion of personal privacy. Name of Committee: National Cancer Institute...

  7. 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...

  8. The National Cancer Program: Driving Discovery

    Science.gov (United States)

    An overview of NCI’s role in driving cancer research discoveries: conducting and funding research in challenging areas and providing resources and leadership to national infrastructures for cancer research.

  9. 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

  10. 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.

  11. 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

  12. 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:

  13. 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...

  14. 78 FR 20118 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-04-03

    ... Committee: National Cancer Institute Special Emphasis Panel; Cancer Biology and Therapy. Date: April 17... Research; 93.395, Cancer Treatment Research; 93.396, Cancer Biology Research; 93.397, Cancer Centers... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  15. 78 FR 25459 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-05-01

    ... Committee: National Cancer Institute Special Emphasis Panel; Cancer Therapy (Omnibus). Date: June 27-28....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...

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. 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...

  2. 77 FR 67015 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-11-08

    ... Committee: National Cancer Institute Special Emphasis Panel NCI Omnibus and Cancer Therapy. Date: November... 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...

  3. 78 FR 8157 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-02-05

    ... Committee: National Cancer Institute Special Emphasis Panel; Provocative Questions: Cancer Therapy and... 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...

  4. 78 FR 36200 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-06-17

    ... Committee: National Cancer Institute Special Emphasis Panel; Cancer Biology and Therapy. Date: June 24, 2013... Research; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93.396... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  5. 77 FR 5029 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2012-02-01

    ... 1 p.m. Agenda: 2/29--Drug Shortage--A Critical Challenge for the Cancer Community; Cancer Drug..., 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 Meeting Pursuant...

  6. 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...

  7. 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.

  8. National and international guidelines for rectal cancer

    DEFF Research Database (Denmark)

    Nielsen, Liv Bjerre Juul; Wille-Jørgensen, P

    2014-01-01

    but not all considered the level of evidence. CONCLUSION: The intention of the study was to provide an overview of international guidelines for rectal cancer based on the underlying evidence, but despite hard evidence it was very difficult to reach general conclusions. Despite much knowledge......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...

  9. 78 FR 58321 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-09-23

    ... Emphasis Panel, Provocative Questions: Cancer Therapy & Outcomes. Date: November 7-8, 2013. Time: 8:00 a.m..., 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 Closed...

  10. 77 FR 31030 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2012-05-24

    ...: June 27, 2012--Drug User Fee Programs, Generic Cancer Drug Shortages: Continuing the Dialogue, The Role..., 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...

  11. 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...

  12. 78 FR 27408 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-05-10

    ... Committee: National Cancer Institute Special Emphasis Panel; SBIR Topic 304 ``Development of Blood-based Methods for the Detection of Cancer Recurrence in Post-Therapy Breast Cancer Patients. Date: June 4, 2013... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  13. 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.

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

    OpenAIRE

    Sasaki, Soichiro; Baba, Tomohisa; Nishimura, Tatsunori; Hayakawa, Yoshihiro; Hashimoto, Shin-ichi; GOTO, Noriko(Graduate school of Education,Tokyo Gakugei University); Mukaida, Naofumi

    2016-01-01

    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 ch...

  15. 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...

  16. 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...

  17. 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

    expression was dominated by CCR1, CCR2 and CCR5. However, despite a stronger initial chemokine signal in VSV-infected mice, only LCMV-induced T cell-dependent inflammation was found to be associated with substantially increased expression of CCR genes. Virus-activated CD8+ T cells were found to express CCR2...... and CCR5, whereas activated monocytes/macrophages expressed CCR1 in addition to CCR2 and CCR5. Together, these CCR profiles readily account for the CCR profile prominent during CD8+-dependent CNS inflammation....

  18. 78 FR 55750 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-09-11

    ... Cancer Institute Special Emphasis Panel; NCI Omnibus--Drug and Gene Delivery. Date: November 7, 2013... 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...

  19. 76 FR 76981 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-12-09

    ... Emphasis Panel, NCI SPORE in Prostate and Gastrointestinal Cancers. Date: February 15-16, 2012. Time: 8 a.m... 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...

  20. 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...

  1. 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...

  2. 75 FR 54161 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-09-03

    ... Sarcoma, Brain, Liver, Lung, and Prostate Cancers. Date: September 29-30, 2010. Time: 8 a.m. to 5 p.m... 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...

  3. 75 FR 62297 - National Breast Cancer Awareness Month, 2010

    Science.gov (United States)

    2010-10-08

    ... Documents#0;#0; ] Proclamation 8572 of October 1, 2010 National Breast Cancer Awareness Month, 2010 By the... fight against breast cancer, it remains the most frequently diagnosed type of non-skin cancer and the... will be diagnosed and nearly 40,000 lives will be claimed. During National Breast Cancer...

  4. 78 FR 64507 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-10-29

    ... hereby given of meetings of the Board of Scientific Counselors for Clinical Sciences and Epidemiology National Cancer Institute and the Board of Scientific Counselors for Basic Sciences National Cancer... Counselors for Clinical Sciences and Epidemiology National Cancer Institute. Date: November 12, 2013. Time:...

  5. 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... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed Meetings... Committee: National Cancer Institute Special Emphasis Panel, Novel Imaging Agents to Expand the...

  6. 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... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed Meetings... clearly unwarranted invasion of personal privacy. Name of Committee: National Cancer Institute...

  7. 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... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed Meetings... Committee: National Cancer Institute Special Emphasis Panel, Drug Discovery, Chemoprevention and...

  8. 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...

  9. 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...

  10. 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:...

  11. 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.

  12. 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.

  13. 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

  14. 78 FR 50064 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2013-08-16

    ...: 8:30 a.m. to 3:30 p.m. Agenda: Cancer Communication for Prevention: In the Digital Commons... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Meeting Pursuant to... a meeting of the President's Cancer Panel. The meeting will be open to the public, with...

  15. 78 FR 69432 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2013-11-19

    ...:30 a.m. to 4:00 p.m. Agenda: Cancer Communication in the Digital Era: Opportunities and Challenges... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Meeting Pursuant to... a meeting of the President's Cancer Panel. The meeting will be open to the public, with...

  16. 78 FR 53154 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-08-28

    ... Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93... Emphasis Panel NCI Experimental Therapeutics--Clinical Trials Network with Phase 1 Emphasis. Date: November... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  17. 78 FR 61805 - National Breast Cancer Awareness Month, 2013

    Science.gov (United States)

    2013-10-04

    ... against breast cancer. While we still do not know the exact causes, we do know that some women are at an... Documents#0;#0; ] Proclamation 9028 of September 30, 2013 National Breast Cancer Awareness Month, 2013 By... solidarity with those battling breast cancer and those at risk for breast cancer. This disease touches...

  18. 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...

  19. 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...

  20. 77 FR 55095 - National Ovarian Cancer Awareness Month, 2012

    Science.gov (United States)

    2012-09-06

    ..., who have a family history of ovarian or breast cancer, or who have had certain cancers in the past are... Documents#0;#0; ] Proclamation 8853 of August 31, 2012 National Ovarian Cancer Awareness Month, 2012 By the... their lives to ovarian cancer. They are mothers and daughters, sisters and grandmothers,...

  1. 75 FR 992 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2010-01-07

    ... personal privacy. Name of Committee: National Cancer Advisory Board; Ad Hoc Subcommittee on Experimental Therapeutics. Open: February 8, 2010, 6:30 p.m. to 8 p.m. Agenda: Discussion on cancer experimental... Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93.396, Cancer Biology Research;...

  2. 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...

  3. 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,...

  4. 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)...

  5. 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,...

  6. 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...

  7. 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.

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

    OpenAIRE

    Lillard James W; Grizzle William E; Johnson Erica L; Singh Rajesh; Johnson-Holiday Crystal; Singh Shailesh

    2011-01-01

    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 rece...

  9. 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...

  10. 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.

  11. 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.

  12. 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...

  13. 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...

  14. 76 FR 62285 - National Breast Cancer Awareness Month, 2011

    Science.gov (United States)

    2011-10-07

    ... Documents#0;#0; ] Proclamation 8724 of October 3, 2011 National Breast Cancer Awareness Month, 2011 By the... of our commitment to preventing and treating breast cancer, and to supporting those courageously... recent decades in the prevention, early detection, and treatment of breast cancer. Still, this...

  15. 77 FR 60605 - National Breast Cancer Awareness Month, 2012

    Science.gov (United States)

    2012-10-04

    ... Documents#0;#0; ] Proclamation 8874 of October 1, 2012 National Breast Cancer Awareness Month, 2012 By the President of the United States of America A Proclamation Breast cancer touches the lives of Americans from... combatting this devastating illness, more than 200,000 women will be diagnosed with breast cancer this...

  16. 77 FR 19024 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-03-29

    ... SPORE in Lymphoma, Leukemia, Brain, Esophageal and Gastrointestinal Cancers. Date: May 23-24, 2012. Time...., Scientific Review Officer, National Cancer Institute, Division of Extramural Activities, Research Programs... Development of Emerging Technologies for Cancer Research (R33). Date: June 14, 2012. Time: 8 a.m. to 6...

  17. 76 FR 42719 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-07-19

    ... the treatment of cancer. The outcome of the evaluation will provide information to internal NCI... development of the potential therapeutic to improve the treatment of various forms of cancer. The research... of Committee: National Cancer Institute Special Emphasis Panel, NCI Experimental Therapeutics...

  18. 76 FR 10381 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-02-24

    ... the treatment of cancer. The outcome of the evaluation will provide information to internal NCI... development of the potential therapeutic to improve the treatment of various forms of cancer. The research... of Committee: National Cancer Institute Special Emphasis Panel; NCI Experimental Therapeutics...

  19. 75 FR 33817 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-06-15

    ... the treatment of cancer. The outcome of the evaluation will provide information to internal NCI... development of the potential therapeutic to improve the treatment of various forms of cancer. The research... of Committee: National Cancer Institute Special Emphasis Panel; NCI Experimental Therapeutics...

  20. 75 FR 26267 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2010-05-11

    ... personal privacy. Name of Committee: National Cancer Advisory Board Ad hoc Subcommittee on Experimental Therapeutics. Open: June 21, 2010, 6:30 p.m. to 8 p.m. Agenda: Discussion on Experimental Therapeutics. Place... Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer Treatment Research;...

  1. 76 FR 66733 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-10-27

    ... the treatment of cancer. The outcome of the evaluation will provide information to internal NCI... development of the potential therapeutic to improve the treatment of various forms of cancer. The research... of Committee: National Cancer Institute Special Emphasis Panel, NCI Experimental Therapeutics...

  2. 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...

  3. 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.

  4. 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.

  5. 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.,...

  6. 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.

  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. 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...

  9. Cancer Incidence in Egypt: Results of the National Population-Based Cancer Registry Program

    OpenAIRE

    Amal S. Ibrahim; Khaled, Hussein M.; Nabiel NH Mikhail; Hoda Baraka; Hossam Kamel

    2014-01-01

    Background. This paper aims to present cancer incidence rates at national and regional level of Egypt, based upon results of National Cancer Registry Program (NCRP). Methods. NCRP stratified Egypt into 3 geographical strata: lower, middle, and upper. One governorate represented each region. Abstractors collected data from medical records of cancer centers, national tertiary care institutions, Health Insurance Organization, Government-Subsidized Treatment Program, and death records. Data ...

  10. 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...... analyzed in 109 patients with relapsing-remitting MS treated with IFN-beta who were followed clinically for 1 year. Cellular CCR5 expression was measured by flow cytometry. RESULTS: Patients with MS had a higher percentage of CCR5-positive monocytes than healthy controls. Increased monocyte expression...... of CCR5 correlated weakly with an increased short-term relapse risk but there was no relationship between CCR5 Delta32 allele and CCR5 promoter polymorphism genotypes and relapse risk. CONCLUSIONS: The results do not support a major role of CCR5 in the pathogenesis of relapses in MS patients treated...

  11. 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....

  12. CCR7-SLC/ELC生物学轴对乳腺癌细胞趋化及侵袭活性的影响%CC chemokine receptor-7 and its ligand SLC, ELCS influence on chemotaxis and inyvasion of breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    朱丽华; 谢明均

    2011-01-01

    目的 探讨CCR7-SLC/ELC生物学轴对乳腺癌细胞株MCF-7的趋化及侵袭活性的影响.方法 用Boyden趋化小室测定外源性趋化因子SLC、ELC对MCF-7趋化及侵袭活性的影响.用Westen-Blot法检测所取新鲜乳腺癌转移淋巴结标本中SLC、ELC的表达情况.取转移淋巴结组织匀浆上清液代替外源趋化因子,测定其对MCF-7趋化及侵袭活性.同时测定使用SLC、ELC单克隆抗体后趋化及侵袭活性的改变.结果 不论是外源性SLC、ELC还是转移淋巴结的蛋白上清液均能增加MCF-7趋化及侵袭活性.SLC、ELC单克隆抗体的封闭能明显抑制其活性.结论 CCR7-SLC/ELC 生物学轴增加乳腺癌细胞的趋化和侵袭活性,可能参与乳腺癌的亲嗜性淋巴结转移.%Objective To study the chemotaxis and invasion of breast cancer cells-MCF-7 facilitated by CC chemokine receptor-7(CC7) and its ligand second lymphoid tissue chemokine (SLC) EBII-ligand chemokine (ELC). Methods The chemotaxis and invasion assays were performed on breast cancer cells-MCF-7 in presence of exogenous SLC and ELC. First detect the expression of SLC and ELC in novel lymph node with breast cancer metastasis by Westen-Blot. Second replace the exogenous SLC and ELC with the clear supernatant liquid of novel lymph node with breast cancer metastasis to study the chemotaxis and invasion of breast cancer cells-MCF-7 facilitated by endogenous SLC and ELC and when SLC and ELC was blocked. Results Both exotgenous and endogenous SLC and ELC can facilitate the chemotaxis and invasion of the breast cancer cells-MCF-7, both chemotaxis and invasion could be blocked by neutralazing anti-SLC, ELC antibody. Conclusion Chemotaxis and invasion of breast cance cell can be facilitated by axis of CCR7/SLC ,ELC and the axis may play an important role in the lymph node metastasis of breast cancer.

  13. The National LGBT Cancer Action Plan: A White Paper of the 2014 National Summit on Cancer in the LGBT Communities

    Science.gov (United States)

    Margolies, Liz; Sigurdsson, Hrafn Oli; Walland, Jonathan; Radix, Asa; Rice, David; Buchting, Francisco O.; Sanchez, Nelson F.; Bare, Michael G.; Boehmer, Ulrike; Cahill, Sean; Griebling, Tomas L.; Bruessow, Diane; Maingi, Shail

    2016-01-01

    Abstract Despite growing social acceptance of lesbians, gay men, bisexuals, and transgender (LGBT) persons and the extension of marriage rights for same-sex couples, LGBT persons experience stigma and discrimination, including within the healthcare system. Each population within the LGBT umbrella term is likely at elevated risk for cancer due to prevalent, significant cancer risk factors, such as tobacco use and human immunodeficiency virus infection; however, cancer incidence and mortality data among LGBT persons are lacking. This absence of cancer incidence data impedes research and policy development, LGBT communities' awareness and activation, and interventions to address cancer disparities. In this context, in 2014, a 2-day National Summit on Cancer in the LGBT Communities was convened by a planning committee for the purpose of accelerating progress in identifying and addressing the LGBT communities' concerns and needs in the spheres of cancer research, clinical cancer care, healthcare policy, and advocacy for cancer survivorship and LGBT health equity. Summit participants were 56 invited persons from the United States, United Kingdom, and Canada, representatives of diverse identities, experiences, and knowledge about LGBT communities and cancer. Participants shared lessons learned and identified gaps and remedies regarding LGBT cancer concerns across the cancer care continuum from prevention to survivorship. This white paper presents background on each of the Summit themes and 16 recommendations covering the following: sexual orientation and gender identity data collection in national and state health surveys and research on LGBT communities and cancer, the clinical care of LGBT persons, and the education and training of healthcare providers.

  14. MCP-1/CCR2 axis promotes the homing of human umbilical cord mesenchymal stem cells to lung cancer tissues%MCP-1/CCR2轴促进脐带间充质干细胞向肺癌组织归巢

    Institute of Scientific and Technical Information of China (English)

    宋新苗; 颜次慧; 吕梦果; 于文文; 张新伟; 任秀宝

    2016-01-01

    目的:探讨单核细胞趋化蛋白-l(monocyte chemoatractant protein-1,MCP-1)/趋化因子(C-C模体)受体2[chemokine(C-C motif) receptor 2,CCR2)轴在人脐带间充质干细胞(human umbilical cord mesenchymal stem cells,HUMSCs)向肺癌归巢中的作用.方法:采用组织块培养法从健康新生儿脐带组织中分离HUMSCs并鉴定,构建BALB/c裸鼠皮下移植瘤模型.体外应用Transwell趋化实验、体内应用IVIS Xenogen动物活体成像系统检测HUMSCs是否向肺癌归巢,ELISA法检测肺癌细胞A549培养上清中MCP-1分泌水平,转染shRNA敲低肺癌细胞内MCP-1的表达和用抑制剂RS504393抑制HUMSCs细胞表面的MCP-1受体CCR2后,体内外检测HUMSCs向肺癌归巢能力的改变.结果:成功分离得到HUMSCs并完成鉴定,成功建立BALB/c裸鼠皮下肺癌移植瘤模型.HUMSCs在体内外均能向肺癌归巢(P<0.01),肺癌细胞高表达MCP-1.成功构建稳定低表达MCP-1的肺癌A549细胞系,与对照组相比,shRNA1和shRNA2敲低组趋化HUMSCs的数目明显减少[(80.0±33.0)、(94.0±16.0)vs (167.0±41.0)个,均P<0.05],抑制HUMSCs细胞表面MCP-1受体CCR2后,体内外均显著抑制HUMSCs向肺癌的趋化能力(P<0.05).结论:MCP-1/CCR2轴促进HUMSCs向肺癌归巢.

  15. 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. PMID:15822119

  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. 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

    chemokine receptors, high affinity CCL3 chemokine binding was maintained in the absence of either bridge. In CCR5, the closest homolog to CCR1, a completely different dependency was observed as neither chemokine activation nor binding was retained in the absence of either bridge. In contrast, both bridges...... 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...

  19. 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.

  20. 76 FR 1625 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-01-11

    ... Committee: National Cancer Institute Initial Review Group; Subcommittee I--Career Development, Career Development. Date: February 22-23, 2011. Time: February 22, 2011, 8 a.m. to 6 p.m. Agenda: To review...

  1. 75 FR 48699 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-08-11

    ... Committee: National Cancer Institute Initial Review Group, Subcommittee I--Career Development, NCI-I Career Development. Date: September 21, 2010. Time: 8 a.m. to 6 p.m. Agenda: To review and evaluate...

  2. Cancer Now Leading Killer in 12 European Nations

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_160436.html Cancer Now Leading Killer in 12 European Nations Gains against heart ... has overtaken heart disease and stroke as the leading cause of death in 12 European countries, a ...

  3. 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...

  4. 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...

  5. 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.

  6. 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.

  7. The Rheumatoid Arthritis Risk Variant CCR6DNP Regulates CCR6 via PARP-1.

    Science.gov (United States)

    Li, Gang; Cunin, Pierre; Wu, Di; Diogo, Dorothée; Yang, Yu; Okada, Yukinori; Plenge, Robert M; Nigrovic, Peter A

    2016-09-01

    Understanding the implications of genome-wide association studies (GWAS) for disease biology requires both identification of causal variants and definition of how these variants alter gene function. The non-coding triallelic dinucleotide polymorphism CCR6DNP is associated with risk for rheumatoid arthritis, and is considered likely causal because allelic variation correlates with expression of the chemokine receptor CCR6. Using transcription activator-like effector nuclease (TALEN) gene editing, we confirmed that CCR6DNP regulates CCR6. To identify the associated transcription factor, we applied a novel assay, Flanking Restriction Enhanced Pulldown (FREP), to identify specific association of poly (ADP-ribose) polymerase 1 (PARP-1) with CCR6DNP consistent with the established allelic risk hierarchy. Correspondingly, manipulation of PARP-1 expression or activity impaired CCR6 expression in several lineages. These findings show that CCR6DNP is a causal variant through which PARP-1 regulates CCR6, and introduce a highly efficient approach to interrogate non-coding genetic polymorphisms associated with human disease. PMID:27626929

  8. 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.

  9. 78 FR 50065 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-08-16

    ... Roberson, Ph.D., Scientific Review Officer, Resources and Training Review Branch, Division of Extramural... Rockville Pike, Rockville, MD 20852. Contact Person: Robert Bird, Ph.D., Chief, Resources and Training... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  10. 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...

  11. Developing National Cancer Registration in Developing Countries- Case Study of the Nigerian National System of Cancer Registries

    Directory of Open Access Journals (Sweden)

    Elima E Jedy-Agba

    2015-07-01

    Full Text Available The epidemiologic transition in sub-Saharan Africa (SSA has given rise to a concomitant increase in the incidence of non-communicable diseases including cancers. Worldwide, cancer registries have been shown to be critical for the determination of cancer burden, conduct of research, and in the planning and implementation of cancer control measures. Cancer registration though vital is often neglected in SSA owing to competing demands for resources for healthcare.We report the implementation of a system for representative nation-wide cancer registration in Nigeria - the Nigerian National System of Cancer Registries (NSCR. The NSCR coordinates the activities of cancer registries in Nigeria, strengthens existing registries, establishes new registries, complies and analyses data, and makes these freely available to researchers and policy makers. We highlight the key challenges encountered in implementing this strategy and how they were overcome. This report serves as a guide for other low and middle income countries (LMIC wishing to expand cancer registration coverage in their countries and highlights the training, mentoring, scientific and logistic support, and advocacy that are crucial to sustaining cancer registration programs in LMIC

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

    Science.gov (United States)

    ... Find Out More MedlinePlus: Breast Cancer medlineplus.gov/breastcancer.html National Cancer Institute, NIH, HHS Phone Number(s): ( ... Treatment-Research-Studies MedlinePlus tutorial medlineplus.gov/tutorials/breastcancer/htm/index.htm NIH Senior Health http://nihseniorhealth. ...

  13. National Cancer Centre Singapore Consensus Guidelines for Hepatocellular Carcinoma.

    Science.gov (United States)

    Chow, Pierce K H; Choo, Su Pin; Ng, David C E; Lo, Richard H G; Wang, Michael L C; Toh, Han Chong; Tai, David W M; Goh, Brian K P; Wong, Jen San; Tay, Kiang Hiong; Goh, Anthony S W; Yan, Sean X; Loke, Kelvin S H; Thang, Sue Ping; Gogna, Apoorva; Too, Chow Wei; Irani, Farah Gillian; Leong, Sum; Lim, Kiat Hon; Thng, Choon Hua

    2016-04-01

    Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world, but the second most common cause of cancer death. There is no universally accepted consensus practice guidelines for HCC owing to rapid developments in new treatment modalities, the heterogeneous epidemiology and clinical presentation of HCC worldwide. However, a number of regional and national guidelines currently exist which reflect practice relevant to the epidemiology and collective experience of the consensus group. In 2014, clinicians at the multidisciplinary Comprehensive Liver Cancer Clinic (CLCC) at the National Cancer Centre Singapore (NCCS) reviewed the latest published scientific data and existing international and regional practice guidelines, such as those of the National Comprehensive Cancer Network, American Association for the Study of Liver Diseases and the Asian Pacific Association for the Study of the Liver, and modified them to reflect local practice. These would serve as a template by which treatment outcomes can be collated and benchmarked against international data. The NCCS Consensus Guidelines for HCC have been successfully implemented in the CLCC since their publication online on 26(th) September 2014, and the guidelines allow outcomes of treatment to be compared to international data. These guidelines will be reviewed periodically to incorporate new data. PMID:27386428

  14. Oxazolidinones as novel human CCR8 antagonists.

    Science.gov (United States)

    Jin, Jian; Wang, Yonghui; Wang, Feng; Kerns, Jeffery K; Vinader, Victoria M; Hancock, Ashley P; Lindon, Matthew J; Stevenson, Graeme I; Morrow, Dwight M; Rao, Parvathi; Nguyen, Cuc; Barrett, Victoria J; Browning, Chris; Hartmann, Guido; Andrew, David P; Sarau, Henry M; Foley, James J; Jurewicz, Anthony J; Fornwald, James A; Harker, Andy J; Moore, Michael L; Rivero, Ralph A; Belmonte, Kristen E; Connor, Helen E

    2007-03-15

    High-throughput screening of the corporate compound collection led to the discovery of a novel series of N-substituted-5-aryl-oxazolidinones as potent human CCR8 antagonists. The synthesis, structure-activity relationships, and optimization of the series that led to the identification of SB-649701 (1a), are described. PMID:17267215

  15. 78 FR 69858 - National Cancer Institute; Amended Notice of Meeting

    Science.gov (United States)

    2013-11-21

    ... following agenda topics will be discussed: Proposed organizational change: DEA, Biomedical Cloud Technology, Optimizing Big Data to Advance Research, and Advocate and Organizational Engagement. Dated: November 15, 2013... is hereby given of a change in the meeting of the National Cancer Institute Director's...

  16. 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

  17. 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

  18. 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.

  19. Autocrine MCP-1/CCR2 signaling stimulates proliferation and migration of renal carcinoma cells

    Science.gov (United States)

    Küper, Christoph; Beck, Franz-Xaver; Neuhofer, Wolfgang

    2016-01-01

    The chemokine monocyte chemoattractant protein-1 [MCP-1; also known as chemokine (C-C motif) ligand 2] is an important mediator of monocyte recruitment during inflammatory processes. Pathologically high expression levels of MCP-1 by tumor cells have been observed in a variety of cancer types. In the majority of cases, high MCP-1 expression is associated with a poor prognosis, as infiltration of the tumor with inflammatory monocytes promotes tumor progression and metastasis. MCP-1 is also expressed in renal cell carcinoma (RCC). In the present study, the function and the regulation of MCP-1 was investigated in two RCC cell lines, CaKi-1 and 786-O. In both cell lines, expression of MCP-1 was significantly enhanced compared with non-cancerous control cells. As expected, secretion of MCP-1 into the medium facilitated the recruitment of peripheral blood monocytes via the chemokine (C-C motif) receptor type 2 (CCR2). As expression of CCR2 was also detected in 786-O and CaKi-1 cells, the effect of autocrine MCP-1/CCR2 signaling was evaluated in these cells. In proliferation assays, administration of an MCP-1 neutralizing antibody or of a CCR2 antagonist to CaKi-1 and 786-O cells significantly decreased cell growth; supplementation of the growth medium with recombinant human MCP-1 had no additional effect on proliferation. The migration ability of RCC cells was impaired by MCP-1 neutralization or pharmacological CCR2 inhibition, while it was stimulated by the addition of recombinant human MCP-1, compared with untreated control cells. Finally, substantial differences in the regulation of MCP-1 expression were observed between RCC cell lines. In CaKi-1 cells, expression of MCP-1 appears to be largely mediated by the transcription factor nuclear factor of activated T cells 5, while in 786-O cells, deletion of the tumor suppressor gene Von-Hippel-Lindau appeared to be responsible for MCP-1 upregulation, as suggested by previous studies. Taken together, the results of the

  20. 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.

  1. Absence of Association between CCR5 rs333 Polymorphism and Childhood Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Coral de Oliveira

    2014-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a malignant disorder that originates from one single hematopoietic precursor committed to B- or T-cell lineage. Ordinarily, these cells express CCR5 chemokine receptor, which directs the immune response to a cellular pattern and is involved in cancer pathobiology. The genetic rs333 polymorphism of CCR5 (Δ32, results in a diminished receptor expression, thus leading to impaired cell trafficking. The objective of the present study was to investigate the effect of CCR5 chemokine receptor rs333 polymorphism in the pathogenesis of ALL. The genotype distribution was studied in 79 patients and compared with 80 control subjects, in a childhood population of Southern Brazil. Genotyping was performed using DNA samples amplified by polymerase chain reaction with sequence-specific primers (PCR-SSP. The homozygous (Δ32/Δ32 deletion was not observed in any subject involved in the study. Heterozygous genotype was not associated with ALL risk (OR 0.7%; 95% CI 0.21–2.32; P>0.05, nor recurrence status of ALL (OR 0.86; 95% CI 0.13–5.48; P>0.05. This work demonstrated, for the first time, no significant differences in the frequency of the CCR5/Δ32 genotype between ALL and control groups, indicating no effect of this genetic variant on the ALL susceptibility and recurrence risk.

  2. 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.

  3. 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...

  4. 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.

  5. 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.

  6. Cooperative research and development opportunities with the National Cancer Institute

    Science.gov (United States)

    Sybert, Kathleen

    1991-01-01

    The Office of Technology Development (OTD) of the National Cancer Institute (NCI) is responsible for negotiating Cooperative Research and Development Agreements (CRADAs), whereby the knowledge resulting from NCI investigators' government-sponsored research is developed in collaboration with universities and/or industry into new products of importance for the diagnosis and treatment of cancer and acquired immunodeficiency syndrome (AIDS). The NCI has recently executed a unique 'clinical trials' CRADA and is developing a model agreement based upon it for the development and commercialization of products for the diagnosis and treatment of cancer and AIDS. NCI drug screening, preclinical testing, clinical trials, and AIDS program capabilities form the basis for this new technology development/technology transfer vehicle. NCI's extensive drug screening program and 'designer foods' program serve as potential sources of investigational new drugs (INDs) and cancer preventatives. Collaborations between NCI and pharmaceutical companies having the facilities, experience, and expertise necessary to develop INDs into approved drugs available to the public are being encouraged where the companies have proprietary rights to INDs, or where NCI has proprietary rights to INDs and invites companies to respond to a collaborator announcement published in the Federal Register. The joint efforts of the NCI and the chosen collaborator are designed to generate the data necessary to obtain pharmaceutic regulatory approval from the Food and Drug Administration (FDA) to market the drugs developed, and thereby make them available to health care providers for the diagnosis and treatment of cancer and AIDS.

  7. Frederick National Lab and the Pancreatic Cancer Action Network Award Fellowships for KRAS Research | Poster

    Science.gov (United States)

    By Nancy Parrish, Staff Writer The Frederick National Laboratory for Cancer Research (FNLCR) recently formed a partnership with the Pancreatic Cancer Action Network (PanCAN) to award a one-year fellowship to two scientists whose research will help lead to new therapies for pancreatic cancer. The scientists will focus on KRAS, a gene in the RAS family that is mutated in 95 percent of pancreatic cancers, according to the National Cancer Institute (NCI).

  8. 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.

  9. The Effect of National Cancer Screening on Disparity Reduction in Cancer Stage at Diagnosis by Income Level.

    Directory of Open Access Journals (Sweden)

    Hye-Min Jung

    Full Text Available Early detection of cancer is an effective and efficient cancer management strategy. In South Korea, the National Health Insurance administers the National Cancer Screening Program to its beneficiaries. We examined the impact of the National Cancer Screening Program on socioeconomic disparities in cancer stage at diagnosis.Cancer patients registered in the Korean Central Cancer Registry from January 1, 2010 to December 31, 2010 with a diagnosis of gastric cancer (n = 22,470, colon cancer (n = 16,323, breast cancer (n = 10,076, or uterine cervical cancer (n = 2,447 were included. Income level was divided into three groups according to their monthly contribution of National Health Insurance. We employed absolute (age-standardized prevalence rate, slope index of inequality and relative (relative index of inequality measures to separately examine social disparities among participants and non-participants of the National Cancer Screening Program in terms of the early-stage rate.Age-standardized prevalence rates of early-stage by income group were always higher in participants than in non-participants. Furthermore, the age-standardized prevalence rate of early-stage in the low income group of the participants was also higher than that of the high income group of the non-participants. The sizes of disparities (both slope index of inequality and relative index of inequality are smaller in participants compared to non-participants.National Cancer Screening Program participation reduced income disparity in cancer stage at diagnosis. Population-based cancer screening programs can be used as an effective measure to reduce income disparity in cancer care.

  10. 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. PMID:27025367

  11. 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.

  12. Linking Tumor Registry and Medicaid Claims to Evaluate Cancer Care Delivery

    OpenAIRE

    Schrag, Deborah; Virnig, Beth A.; Warren, Joan L.

    2009-01-01

    The utility of Medicaid claims for studying cancer care is not known. Our objective was to evaluate how well Medicaid claims capture diagnostic and treatment information recorded by the California Cancer Registry (CCR). We compared cancer treatment from Medicaid claims with CCR data, using 1988-2000 cases matched with 1997-1998 Medicaid enrollment data. Medicaid claims corroborated diagnoses for 73 percent of breast and 68 percent of colorectal cancers in CCR. Medicaid claims confirmed surger...

  13. 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.

  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. 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…

  16. 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

  17. Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion

    International Nuclear Information System (INIS)

    CC chemokine receptor 1 (CCR1) has an important role in the recruitment of leukocytes to the site of inflammation. The migration and metastasis of tumor cells shares many similarities with leukocyte trafficking, which is mainly regulated by chemokine receptor-ligand interactions. CCR1 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues with unknown functions. In this study, we silenced CCR1 expression in the human HCC cell line HCCLM3 using artificial microRNA (miRNA)-mediated RNA interference (RNAi) and examined the invasiveness and proliferation of CCR1-silenced HCCLM3 cells and the matrix metalloproteinase (MMP) activity. The miRNA-mediated knockdown expression of CCR1 significantly inhibited the invasive ability of HCCLM3 cells, but had only a minor effect on the cellular proliferation rate. Moreover, CCR1 knockdown significantly reduced the secretion of MMP-2. Together, these findings indicate that CCR1 has an important role in HCCLM3 invasion and that CCR1 might be a new target of HCC treatment

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    was around or above 90% in most instances. Perfect agreement on the diagnosis of thyroid carcinoma was found, both inter- and intra-observer, and κ values of selected variables showed overall good to excellent agreement. CONCLUSION: In a setup with public health insurance, personal identity numbers...... 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...

  19. 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.

  20. 75 FR 51830 - National Cancer Institute's Best Practices for Biospecimen Resources

    Science.gov (United States)

    2010-08-23

    ... HUMAN SERVICES National Institutes of Health National Cancer Institute's Best Practices for Biospecimen... best practices, the National Cancer Institute (NCI) is seeking public comment on a revised version of the NCI Best Practices for Biospecimen Resources. This revised version of the NCI Best Practices...

  1. 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...

  2. 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.

  3. Breast cancer. National Center for Radiation Therapy. Trinidad and Tobago

    International Nuclear Information System (INIS)

    Was performed a retrospective study of cases registered at the Center National Radiotherapy of Trinidad and Tobago, with histologically or cytological breast cancer in the period from January 1 to July 31, 2007. It 125 cases studied. The aim of this study was to determine the characteristics of breast cancer in these patients, the different treatments used in order to improve prevention, treatment regimens, quality of life and increase survival rates of women suffering from this disease. The risk of cancer increases with age in the age group of 50-59 years was the highest incidence of the disease, an important group of patients suffer disease after 70 years. 64% of the cases were diagnosed in stage 0-II, carcinoma in situ was diagnosed in 4% of the patients, 52.8% of cases had positive lymph nodes. Surgery and chemotherapy were treatments used, the surgery was done in 92.8% of patients, being the the most common radical surgery, chemotherapy was used in 76% of cases, doxorubicin, cyclophosphamide and taxol were the most used drugs. The hormone receptors were positive in 65% of cases and Her 2 negative in 82.02%, the third generation aromatase inhibitors were hormones most used. Our results were compared with other studies. (Author)

  4. The National Cancer Informatics Program (NCIP) Annotation and Image Markup (AIM) Foundation Model

    OpenAIRE

    Mongkolwat, Pattanasak; Kleper, Vladimir; Talbot, Skip; Rubin, Daniel

    2014-01-01

    Knowledge contained within in vivo imaging annotated by human experts or computer programs is typically stored as unstructured text and separated from other associated information. The National Cancer Informatics Program (NCIP) Annotation and Image Markup (AIM) Foundation information model is an evolution of the National Institute of Health’s (NIH) National Cancer Institute’s (NCI) Cancer Bioinformatics Grid (caBIG®) AIM model. The model applies to various image types created by various techn...

  5. 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.

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

    NARCIS (Netherlands)

    F.L.H. Muntinghe; M. Verduijn; M.W. Zuurman; D.C. Grootendorst; J.J. Carrero; A.R. Qureshi; K. Luttropp; L. Nordfors; B. Lindholm; V. Brandenburg; M. Schalling; P. Stenvinkel; E.W. Boeschoten; R.T. Krediet; G. Navis; F.W. Dekker

    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. 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...... targeting CCR5 or treatment with MMP inhibitors may attenuate disease activity in MS...

  9. 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.

  10. 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.

  11. 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

  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. Discovery of indole inhibitors of chemokine receptor 9 (CCR9).

    Science.gov (United States)

    Pandya, Bhaumik A; Baber, Christian; Chan, Audrey; Chamberlain, Brian; Chandonnet, Haoqun; Goss, Jennifer; Hopper, Timothy; Lippa, Blaise; Poutsiaka, Katherine; Romero, Jan; Stucka, Sabrina; Varoglu, Mustafa; Zhang, Jing; Zhang, Xin

    2016-07-15

    Irritable bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC) are serious chronic diseases affecting millions of patients worldwide. Studies of human chemokine biology has suggested C-C chemokine receptor 9 (CCR9) may be a key mediator of pro-inflammatory signaling. Discovery of agents that inhibit CCR9 may lead to new therapies for CD and UC patients. Herein we describe the evolution of a high content screening hit (1) into potent inhibitors of CCR9, such as azaindole 12. PMID:27256913

  14. Cancer Information Seeking and Cancer-Related Health Outcomes: A Scoping Review of the Health Information National Trends Survey Literature.

    Science.gov (United States)

    Wigfall, Lisa T; Friedman, Daniela B

    2016-09-01

    Cancer is a leading cause of death among adults in the United States. Only 54% of U.S. adults reported seeking cancer information in 2014. Cancer information seeking has been positively associated with cancer-related health outcomes such as screening adherence. We conducted a scoping review of studies that used data from the Health Information National Trends Survey (HINTS) in order to examine cancer information seeking in depth and the relationship between cancer information seeking and cancer-related health outcomes. We searched five databases and the HINTS website. The search yielded a total of 274 article titles. After review of 114 de-duplicated titles, 66 abstracts, and 50 articles, 22 studies met inclusion criteria. Cancer information seeking was the outcome in only four studies. The other 18 studies focused on a cancer-related health outcome. Cancer beliefs, health knowledge, and information seeking experience were positive predictors of cancer information seeking. Cancer-related awareness, knowledge, beliefs, preventive behaviors, and screening adherence were higher among cancer information seekers. Results from this review can inform other research study designs and primary data collection focused on specific cancer sites or aimed at populations not represented or underrepresented in the HINTS data (e.g., minority populations, those with lower socioeconomic status). PMID:27466828

  15. [Cancer between infection and heredity: genes, viruses and mice at National Cancer Institute (1937-1977)].

    Science.gov (United States)

    Gaudillière, J P

    1994-01-01

    After World War II, in the United States,viral explanation of cancer replaced a vision of the disease emphasizing genetic factors. From the mid 1950s onwards, experimental oncologists favored the notion that cancer was initiated by infectious agents passed from one generation to the next. In order to analyze this displacement, the present paper focuses on the part played by new experimental systems, i.e. mice showing tumors induced by viruses. Since animal models are agencies which "represent" human diseases, and mediate between different social worlds, their uses often result in opposing views. Mouse models thus provided tractable resources which favored the alternation between heredity and infection. The paper describes the emergence, in the late 1930s, at the Jackson Memorial Laboratory, of an agent enhancing the formation of mammary tumors in mice. This laboratory was then involved in the production of marketable inbred mice as well as in research concerned with genetic factors that may cause cancer. After World War II, loose theories and conflicting results helped turn the agent into a virus. At the National Cancer Institute, the virus was associated with a whole range of particles causing leukemia in mice. Owing to the Virus Cancer Program, the value of mouse tumor viruses increased in the late 1960s. This research effort then aimed at finding human tumor viruses, and at crafting cancer vaccines. It was modeled after the experience of the NCI chemotherapy program stemming from war research. In addition to the fact that biomedical research became a state enterprise, the study emphasizes three parameters. First, loose practices--both theoretical and experimental--helped manage the variability of animal models. Secondly, the standardization and mass production of animals and reagents encouraged the stabilization of research programs. Thirdly, private biotechnology companies working under NCI contracts implemented preclinical work, and mediated between virology

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

    OpenAIRE

    Carlson, Marilyn; Madison, Bernard; 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 administe...

  17. The national cancer institute (NCI) and cancer biology in a 'post genome world'

    International Nuclear Information System (INIS)

    The National Cancer Institute (NCI) exists to reduce the burden of all cancers through research and discovery. Extensive restructuring of the NCI over the past year has been aimed at assuring that the institution functions in all ways to promote opportunities for discovery in the laboratory, in the clinic, and in the community. To do this well requires the difficult and almost paradoxical problem of planning for scientific discovery which, in turn is based on the freedom to pursue the unanticipated. The intellectual and structural landscape of science is changing and it places new challenges, new demands and new opportunities for facilitating discovery. The nature of cancer as a disease of genomic instability and of accumulated genetic change, coupled with a possibility of the development of new technologies for reading, utilizing, interpreting and manipulating the genome of single cells, provides unprecedented opportunities for a new type of high through-put biology that will change the nature of discovery, cancer detection, diagnosis, prognosis, therapeutic decision-making and therapeutic discovery. To capture these new opportunities will require attention to be paid to integrate the development of technology and new scientific discoveries with the ability to apply advances rapidly and efficiently through clinical trials

  18. Communication and Cancer: The Role of Health Communication Specialists in Achieving National Health Goals.

    Science.gov (United States)

    Cline, Rebecca J.

    Proceeding from the implicit message promoted by the National Cancer Institute to the communication profession--expertise in health communication is central to the effort to alleviate the costs of the national burden placed on the economy because of cancer--this paper proposes the development of health communication as a career. Specifically, the…

  19. 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.

  20. Prevalence of bone marrow necrosis in Egyptian cancer patients referring to the National Cancer Institute

    International Nuclear Information System (INIS)

    Bone marrow necrosis; Egyptian cancer patients Abstract Background: Bone marrow necrosis is a relatively rare entity which has been associated with a poor prognosis. It is most commonly found in patients with neoplastic disorders and severe infections. Methods: study comprised examination of 5043 bone marrow biopsy specimens performed at the National Cancer Institute, Cairo University, over 7 years period (March 2004-March 2011). It included 5 years retrospective (2867 archived samples) and 2 years prospective (2176 samples). Results: Bone marrow necrosis was diagnosed in fifteen out of 5043 examined specimens with a percentage of 0.3% and ranged from mild to massive according to semiquantitative estimation. Prognosis of all patients was poor with survival not exceeding 6 months from the date of marrow necrosis diagnosis. Conclusion: In Egyptian patients, bone marrow necrosis in association with malignancy is a rare disorder which is accompanied by a poor outcome

  1. CCR3: Shedding New Light on a Dark Problem?

    Institute of Scientific and Technical Information of China (English)

    A. Brett Mason; Josephine Hoh

    2009-01-01

    A recent work by Ambati et al. represents a bold step towards a more effective diagnosis and treatment of age-related macular degeneration, with the new evidence showing that CCR3, a chemokine receptor, is an early marker of and potential therapeutic target for choroidal neovascularization development. In the wake of such a novel and significant finding, additional illumination to confirm and consolidate the promise shown by CCR3 will soon follow.

  2. The first national public breast cancer screening program in Saudi Arabia

    OpenAIRE

    Abulkhair, Omalkhair A.; Al Tahan, Fatina M.; Young, Susan E.; Musaad, Salma MA.; Jazieh, Abdul-Rahman M.

    2010-01-01

    BACKGROUND AND OBJECTIVES: Despite its relatively low incidence in Saudi Arabia, breast cancer has been the most common cancer among Saudi females for the past 12 consecutive years. The objective of this study was to report the results of the first national public breast cancer screening program in Saudi Arabia. METHODS: Women 40 years of age or older underwent breast cancer screening. Mammograms were scored using the Breast Imaging-Reporting and Data System (BI-RADS). Correlations between im...

  3. The case for selection at CCR5-Delta32.

    Directory of Open Access Journals (Sweden)

    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.

  4. [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.

  5. CCR2 and coronary artery disease: a woscops substudy

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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. PMID:26114311

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

    Science.gov (United States)

    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.

  8. 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

  9. Cancer incidence among workers at the Los Alamos National Laboratory

    International Nuclear Information System (INIS)

    An analysis of cancer incidence among Los Alamos workers was reported at the Sixteenth Mid-Year Topical Symposium of the Health Physics Society. Cancer incidence was especially low among Anglo-American males for cancer of the lung and oral cancer, cancer sites commonly associated with cigarette smoking. No cases of cancer of the lung, oral cavity, pancreas, or bladder were observed among Anglo-American females in the population. Standardized incidence ratios for cancer of the breast and cancer of the uterine corpus exceeded one; however, these findings were not statistically significant. These findings are consistent with expectation for a population of high socioeconomic class, such as the Laboratory work force. Therefore, working conditions at the Laboratory do not appear to have affected cancer incidence in this population. 1 reference, 2 tables

  10. 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.

  11. CCR5 promoter polymorphism determines macrophage CCR5 density and magnitude of HIV-1 propagation in vitro

    OpenAIRE

    Salkowitz, Janelle R.; Bruse, Shannon E.; Meyerson, Howard; Valdez, Hernan; Mosier, Donald E.; Harding, Clifford V.; Peter A Zimmerman; Lederman, Michael M.

    2003-01-01

    The common CCR5 promoter polymorphism at position –2459 (A/G) has been associated with differences in the rate of progression to AIDS, where HIV-1-infected individuals with the CCR5 –2459 G/G genotype exhibit slower disease progression than those with the A/A genotype. Mechanisms underlying the relationship between these polymorphisms and disease progression are not known. Here through in vitro infection of peripheral blood mononuclear cells obtained from healthy Caucasian blood donors with m...

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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... Molecular Diagnostics Assay to Detect Basal- like Breast Cancer. Date: February 15, 2011. Time: 12 p.m. to 5...-Therapy Breast Cancer Patients. Date: March 3, 2011. Time: 12 p.m. to 5 p.m. Agenda: To review...

  19. 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. PMID:25757618

  20. Application of log-linear models to cancer patients: a case study of data from the National Cancer Institute.

    Science.gov (United States)

    Tiensuwan, Montip; Yimprayoon, Pornpis; Lenbury, Yongwimon

    2005-09-01

    Cancer is a noninfectious disease which is on the increase throughout the world and has become a serious problem for public health in many countries, including Thailand. In Thailand, cancer has risen significantly to become a leading cause of death and most patients are admitted to the National Cancer Institute. The objective of this study is to identify the associated factors between personal, cancer/clinical variables of cancer patients using log-linear models. Tests of independence are used (chi-square and Cramer's V-value tests) to find out the relationships between any two variables. In addition two- and three-dimensional log-linear models are used to obtain estimated parameters and expected frequencies for these models. Amongst the models fitted, the best are chosen based on the analysis of deviance. The results of this study show that most paired variables of personal, cancer/clinical variables are significantly related at p-value value. Moreover, the site of cancer also affects the method of diagnostic evidence and treatment. Since the site of cancer in each sex is different, prevention for various sites of cancer should be considered for each specific sex. In addition, for male and female patients, treatment is related to the site of cancer. Consequently, physicians may consider these factors before selecting the appropriate method of treatment. PMID:16438159

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Integrated oncology and palliative care: five years experience at the National Cancer Institute of Mexico.

    Science.gov (United States)

    Allende-Pérez, Silvia; Verástegui-Avilés, Emma; Mohar-Betancourt, Alejandro; Meneses-García, Abelardo; Herrera-Gómez, Angel

    2016-04-01

    Under the national plan for addressing cancer, prevention and detection play important roles. However, the cost of treatments and late diagnosis represent a significant burden on health services. At the National Cancer Institute, more than half of patients present with tumors in advanced stages, and approximately 10% of patients seen for the first time exhibit terminal-stage malignancies, where there are no feasible cancer treatment options, and the patients are instead admitted to the hospital exclusively for palliative symptomatic management. In 2010, the National Cancer Plan began implementing a model of integrative management of palliative care in oncology that has gradually come to include symptomatic palliative care, involving ambulatory, distant and hospitalized management of patients with cancer, in its final stages and, more recently, in earlier stages. PMID:27557392

  6. 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,

  7. 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

  8. 78 FR 27974 - Proposed Collection; 60-Day Comment Request: National Cancer Institute (NCI) Alliance for...

    Science.gov (United States)

    2013-05-13

    ... projects to be submitted to the Office of Management and Budget (OMB) for review and approval. Written... for Strategic Scientific Initiatives, Office of Cancer Nanotechnology Research, National Cancer... Nanotechnology Research (OCNR), part of the Center for Strategic Scientific Initiatives within NCI. OMB...

  9. 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).

  10. 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.

  11. 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.

  12. 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.

  13. 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;...

  14. 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...

  15. The National LGBT Cancer Action Plan: A White Paper of the 2014 National Summit on Cancer in the LGBT Communities

    OpenAIRE

    Burkhalter, Jack E.; Margolies, Liz; Sigurdsson, Hrafn Oli; Walland, Jonathan; Radix, Asa; Rice, David; Buchting, Francisco O.; Sanchez, Nelson F.; Bare, Michael G; Boehmer, Ulrike; Cahill, Sean; Griebling, Tomas L; Bruessow, Diane; Maingi, Shail

    2016-01-01

    Abstract Despite growing social acceptance of lesbians, gay men, bisexuals, and transgender (LGBT) persons and the extension of marriage rights for same-sex couples, LGBT persons experience stigma and discrimination, including within the healthcare system. Each population within the LGBT umbrella term is likely at elevated risk for cancer due to prevalent, significant cancer risk factors, such as tobacco use and human immunodeficiency virus infection; however, cancer incidence and mortality d...

  16. 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

  17. 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

  18. 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)

    International Nuclear Information System (INIS)

    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). 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. 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. Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians

  19. 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.

  20. 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.

  1. 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...

  2. 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.

  3. Guidelines for a national epidemiological surveillance system of thyroid cancer in France

    International Nuclear Information System (INIS)

    At the request of the French Department of Health, a multidisciplinary Thyroid Cancer Committee, coordinated by the French Public Health Agency analysed the observed increase of thyroid cancer incidence in France and outlined the limits of the present case registration system. This Committee set up guidelines to improve the national surveillance system of thyroid cancer. The Committee analysed 4 models for the incidence survey, 3 of which have been excluded: a poor cost-benefit ratio precludes the constitution of a national registry dedicated to thyroid cancer; however, the Committee has recommended this model that still exists for thyroid cancer of the youth(under 19 years old), a national system base exclusively on pathological data would only be relevant after significant improvement of data collection, obligatory of all cases of thyroid cancer is inappropriate considering the fit prognosis of this cancer. A two level system is proposed with continuous registration of incident caes through the National Hospital Discharge survey, specific focused analysis of clinical and pathological data in case of a cluster alert in any given area. Whatever the system, it seems necessary to in general: propose a unique health registration number per patient, improve access to medical data, organize a national standardised collection of pathological findings, follow up the diagnosis practices related to thyroid cancer that have an impact on incidence rates. In conclusion, a reliable incidence survey and a follow up of diagnostic practices and of risk factors may provide a relevant model of epidemiological survey of thyroid cancers in France but such a system requires a long lasting strategic and financial involvement. (author)

  4. 75 FR 79010 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-12-17

    ... Special Emphasis Panel. SPORE in Glioma, Head and Neck, Lymphoma, Myeloid Leukemia, and Myeloma. Date... Program for Cancer Epidemiology. Date: April 28-29, 2011. Time: 8:30 a.m. to 5 p.m. Agenda: To review...

  5. Evaluation of cancer incidence among employees at the Los Alamos National Laboratory

    International Nuclear Information System (INIS)

    As part of the National Plutonium Workers Study, cancer incidence for 1969 to 1978 among employees of the Los Alamos National Laboratory was investigated. Incident cancers were identified by a computer match of the Los Alamos employed roster against New Mexico Tumor Registry files. The resulting numbers of total and site-specific cancers were compared to the numbers expected based on incidence rates for the State of New Mexico, specific for age, sex, ethnicity, and calendar period. For Anglo males, significantly fewer cancers than expected (SIR = 0.60, 95% CI 0.44 to 0.79) were found. This resulted from marked deficits of smoking-related cancers, particularly lung (2 observed, 19.4 expected) and oral (1 observed, 6.5 expected) cancer. Similarly, no smoking-related cancers were detected among Anglo females, though they had a slight nonsignificant excess of breast cancer (14 observed, 9.1 expected) and a suggestive excess of cancer of the uterine corpus (2 observed, 0.25 expected). The pattern of cancerincidence among Anglo employees is typical of high social class populations and not likely related to the Los Alamos working environment

  6. 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.

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

    International Nuclear Information System (INIS)

    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

  8. 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.

  9. 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

  10. Multi-functional regulation of 4E-BP gene expression by the Ccr4-Not complex.

    Directory of Open Access Journals (Sweden)

    Hirokazu Okada

    Full Text Available The mechanistic target of rapamycin (mTOR signaling pathway is highly conserved from yeast to humans. It senses various environmental cues to regulate cellular growth and homeostasis. Deregulation of the pathway has been implicated in many pathological conditions including cancer. Phosphorylation cascades through the pathway have been extensively studied but not much is known about the regulation of gene expression of the pathway components. Here, we report that the mRNA level of eukaryotic translation initiation factor (eIF subunit 4E-binding protein (4E-BP gene, one of the key mTOR signaling components, is regulated by the highly conserved Ccr4-Not complex. RNAi knockdown of Not1, a putative scaffold protein of this protein complex, increases the mRNA level of 4E-BP in Drosophila Kc cells. Examination of the gene expression mechanism using reporter swap constructs reveals that Not1 depletion increases reporter mRNAs with the 3'UTR of 4E-BP gene, but decreases the ones with the 4E-BP promoter region, suggesting that Ccr4-Not complex regulates both degradation and transcription of 4E-BP mRNA. These results indicate that the Ccr4-Not complex controls expression of a single gene at multiple levels and adjusts the magnitude of the total effect. Thus, our study reveals a novel regulatory mechanism of a key component of the mTOR signaling pathway at the level of gene expression.

  11. 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.

  12. Role for CCR5 in Dissemination of Vaccinia Virus In Vivo▿

    OpenAIRE

    Rahbar, Ramtin; Murooka, Thomas T.; Fish, Eleanor N.

    2008-01-01

    In an earlier report, we provided evidence that expression of CCR5 by primary human T cells renders them permissive for vaccinia virus (VACV) replication. This may represent a mechanism for dissemination throughout the lymphatic system. To test this hypothesis, wild-type CCR5+/+ and CCR5 null mice were challenged with VACV by intranasal inoculation. In time course studies using different infective doses of VACV, we identified viral replication in the lungs of both CCR5+/+ and CCR5−/− mice, ye...

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

    OpenAIRE

    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

    2009-01-01

    The CC-chemokine receptor 5 (CCR5) is a receptor for various proinflammatory chemokines, and a deletion variant of the CCR5 gene (CCR5Δ32) leads to deficiency of the receptor. We hypothesized that CCR5Δ32 modulates inflammation-driven mortality in patients with ESRD. We studied the interaction between CCR5 genotype and levels of high-sensitivity C-reactive protein (hsCRP) in 603 incident dialysis patients from the multicenter, prospective NEtherlands COoperative Study on the Adequacy of Dialy...

  14. Insights into the experiences of patients with cancer in London: framework analysis of free-text data from the National Cancer Patient Experience Survey 2012/2013 from the two London Integrated Cancer Systems

    OpenAIRE

    Wiseman, Theresa; Lucas, Grace; Sangha, Amrit; Randolph, Anuska; Stapleton, Sarah; Pattison, Natalie; O'Gara, Geraldine; Harris, Katherine; Pritchard-Jones, Kathy; Dolan, Shelley

    2015-01-01

    Objective To shed light on experiences of patients with cancer in London National Health Service (NHS) trusts that may not be fully captured in national survey data, to inform improvement action plans by these trusts. Design Framework analysis of free-text data from 2012/2013 National Cancer Patient Experience Survey (NCPES) from the 2 London Integrated Cancer Systems. Setting and participants Patients with a cancer diagnosis treated by the NHS across 27 trusts in London. ...

  15. Insights into the experiences of patients with cancer in London: framework analysis of free-text data from the National Cancer Patient Experience Survey 2012/2013 from the two London Integrated Cancer Systems

    OpenAIRE

    Wiseman, Theresa; Lucas, Grace; Sangha, Amrit; Randolph, Anuska; Stapleton, Sarah; Pattison, Natalie; O'Gara, Geraldine; Harris, Katherine; Pritchard-Jones, Kathy; Dolan, Shelley

    2015-01-01

    Objective To shed light on experiences of patients with cancer in London National Health Service (NHS) trusts that may not be fully captured in national survey data, to inform improvement action plans by these trusts. Design Framework analysis of free-text data from 2012/2013 National Cancer Patient Experience Survey (NCPES) from the 2 London Integrated Cancer Systems. Setting and participants Patients with a cancer diagnosis treated by the NHS across 27 trusts in London. Main outcome measure...

  16. 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

  17. 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.

  18. 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.

  19. The chemokine receptor CCR5 Δ32 allele in natalizumab-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Møller, M; Søndergaard, Helle B; Koch-Henriksen, N;

    2014-01-01

    OBJECTIVE: The chemokine receptor CCR5 may be important for the recruitment of pathogenic T cells to the CNS in multiple sclerosis (MS). We hypothesized that this chemokine receptor might still be important for T-cell migration during treatment with anti-very late antigen (VLA)-4 antibody. We...... therefore analysed whether natalizumab-treated MS patients carrying the CCR5 Δ32 deletion allele, which results in reduced expression of CCR5 on the cell surface, had lower disease activity. METHODS: CCR5 Δ32 was analysed in 212 natalizumab-treated MS patients. RESULTS: CCR5 Δ32 status had no significant...... impact on the frequency of relapses 1 year prior to natalizumab treatment or during the first 48 weeks of treatment. The multiple sclerosis severity score (MSSS) was significantly lower at baseline in patients carrying CCR5 Δ32 (P = 0.031). CONCLUSIONS: CCR5 Δ32 is not associated with lower disease...

  20. 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,...

  1. Cancer - resources

    Science.gov (United States)

    Resources - cancer ... The following organizations are good resources for information on cancer : American Cancer Society -- www.cancer.org Cancer Care -- www.cancercare.org National Cancer Institute -- www.cancer.gov

  2. Hepatitis B vaccinations among Koreans: Results from 2005 Korea National Cancer Screening Survey

    Directory of Open Access Journals (Sweden)

    Kwak Min-Son

    2009-11-01

    Full Text Available Abstract Background Liver cancer is one of most commonly diagnosed cancers among Koreans. Chronic hepatitis B virus (HBV infection is a major risk factor for liver cancer. HBV infection can be prevented by effective screening and vaccination programs. The purpose of this study is to examine the status of HBV infection and the predictors associated with HBV vaccination. Methods The study population was derived from the 2005 Korea National Cancer Screening Survey (KNCSS. The KNCSS is an annual cross-sectional survey that uses a nationally-representative random sampling to investigate cancer screening rates. A total of 1,786 Koreans over 40 years of age participated in this study. Results Of all the participants, 5.9% reported HBV positive (HBsAg+, HBsAb-, 41.8% were HBV negative but protected (HBsAg-, HBsAb+, and 52.3% were unprotected (HBsAg-, HBsAb-. Among unprotected individuals (n = 934, 23.1% reported to have received the vaccination. About half of those who had vaccinations completed the 3-shot vaccine series. In multiple analyses, education, having private cancer insurance, alcohol use, having regular check-up, and doing regular exercise were associated with completed HBV vaccination. Conclusion This study result suggests that we need a liver cancer education program to increase HBV awareness and to increase the liver cancer prevention message among low educated populations.

  3. 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

  4. 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.

  5. 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. PMID:26307764

  6. 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.

  7. Screening mammography. A missed clinical opportunity? Results of the NCI [National Cancer Institute] Breast Cancer Screening Consortium and national health interview survey studies

    International Nuclear Information System (INIS)

    Data from seven studies sponsored by the National Cancer Institute (NCI) were used to determine current rates of breast cancer screening and to identify the characteristics of and reasons for women not being screened. All seven studies were population-based surveys of women aged 50 to 74 years without breast cancer. While over 90% of non-Hispanic white respondents had regular sources of medical care, 46% to 76% had a clinical breast examination within the previous year, and only 25% to 41% had a mammogram. Less educated and poorer women had fewer mammograms. The two most common reasons women gave for never having had a mammogram were that they did not known they needed it and that their physician had not recommended it. Many physicians may have overlooked the opportunity to recommend mammography for older women when performing a clinical breast examination and to educate their patients about the benefit of screening mammography

  8. Parameter estimates for invasive breast cancer progression in the Canadian National Breast Screening Study

    OpenAIRE

    Taghipour, S.; Banjevic, D; Miller, A.B.; Montgomery, N; A K S Jardine; Harvey, B. J.

    2013-01-01

    Background: The aim of screening is to detect a cancer in the preclinical state. However, a false-positive or a false-negative test result is a real possibility. Methods: We describe invasive breast cancer progression in the Canadian National Breast Screening Study and construct progression models with and without covariates. The effect of risk factors on transition intensities and false-negative probability is investigated. We estimate the transition rates, the sojourn time and sensitivity o...

  9. Trends in Research on Energy Balance Supported by the National Cancer Institute

    OpenAIRE

    Ballard-Barbash, Rachel; Siddiqi, Sameer M.; Berrigan, David A.; Ross, Sharon A.; Nebeling, Linda C.; Dowling, Emily C.

    2013-01-01

    Over the past decade, the body of research linking energy balance to the incidence, development, progression and treatment of cancer has grown substantially. No prior NIH portfolio analyses have focused on energy balance within one institute. This portfolio analysis describes the growth of National Cancer Institute (NCI) grant research on energy balance–related conditions and behaviors from 2004 to 2010 following the release of an NCI research priority statement in 2003 on energy balance and ...

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

    Directory of Open Access Journals (Sweden)

    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

  11. Utilization of breast cancer screening methods in a developing nation: results from a nationally representative sample of Malaysian households.

    Science.gov (United States)

    Dunn, Richard A; Tan, Andrew K G

    2011-01-01

    As is the case in many developing nations, previous studies of breast cancer screening behavior in Malaysia have used relatively small samples that are not nationally representative, thereby limiting the generalizability of results. Therefore, this study uses nationally representative data from the Malaysia Non-Communicable Disease Surveillance-1 to investigate the role of socio-economic status on breast cancer screening behavior in Malaysia, particularly differences in screening behaviour between ethnic groups. The decisions of 816 women above age 40 in Malaysia to screen for breast cancer using mammography, clinical breast exams (CBE), and breast self-exams (BSE) are modeled using logistic regression. Results indicate that after adjusting for differences in age, education, household income, marital status, and residential location, Malay women are less likely than Chinese and Indian women to utilize mammography, but more likely to perform BSE. Education level and urban residence are positively associated with utilization of each method, but these relationships vary across ethnicity. Higher education levels are strongly related to using each screening method among Chinese women, but have no statistically significant relationship to screening among Malays. PMID:21615819

  12. 75 FR 62547 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-10-12

    ... consideration of personnel qualifications and performance, and the competence of individual investigators, the... performance, and competence of individual investigators. Place: Double Tree Hotel, 8120 Wisconsin Avenue... qualifications and performance, and competence of individual investigators. Place: National Institutes of...

  13. 75 FR 62552 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-10-12

    ... Institute, including consideration of personnel qualifications and performance, and the competence of... personal qualifications and performance, and competence of individual investigators. Place: National... performance, and competence of individual investigators. Place: Double Tree Hotel, 8120 Wisconsin...

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

    Science.gov (United States)

    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.

  15. 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.

  16. 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. PMID:26324043

  17. 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.

  18. 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.

  19. Low Frequencies of CCR5-△32 and CCR5-m303, but High Frequencies of CCR2-641 and SDF1-3'A Alleles in Indigenous Ethnic Groups in Mainland China

    Institute of Scientific and Technical Information of China (English)

    WANG Fusheng (王福生); WANG zhe(王哲); Feng Tiejian (冯铁建); HOU Jing(侯静); LI Guanghani(李光汉); CAO Yunzhen(曹韵贞); JIN Lei(金磊); HONG Weiguo(洪卫国); LIU Mingxu (刘明旭); ZHOU YueSu (周越塑); ZHANG Bing (张冰); SHI Ming (施明); WANG JiMing(王吉明); LEI Zhouyun (雷周云)

    2002-01-01

    Objective:The aim in this study was to identify the allelicfrequencies of the chemokine (SDF1-3'A) and chemokinereceptor (CCR5A32, CCR5m303 and CCR2-64I) genesresistant to HIV-1 infection and/or disease progression inindigenous Chinese populations.Methods: By using QIAamp DNA Blood Mini Kit, thegenomic DNA samples were purified from whole peripheralblood of healthy individuals (n=2067) from Han, Uygur,Mongolian and Tibetan ethnic groups, as well as Han patientsincluding HIV-1 carriers (n=330), patients with other sexuallytransmitted diseases (STDs, n=259) and intravenous drugusers (IVDUs, n=125). The allelic polymorphisms wereidentified by means of PCR or PCR-RFLP analyses. Thesequences of randomly selected amplified PCR products werefurther confirmed by direct DNA sequencing.Results: The mutant frequencies were identified to be0%~3.48% for CCR5A32, 0% for CCR5m303,19.15%~28.79% for CCR2-64 and 19.10%~28.73% for SDF1-3'A alleles, respectively, in Chinese healthy individuals fromfour ethnic groups. Our findings indicated the allelicfrequencies vary among the different ethnic groups.Furthermore, the HIV-1 carriers, STD cases and IVDUs (all ofHan ethnicity) were found to have the allelic frequencies of0%~0.19% (CCR5A32), 0% (CCR5m303), 19.31%~20.45%(CCR2-64) and 25.61%~26.83% (SDF1-3'A) with minorvariations in their frequencies between the patients andhealthy Han groups. There was no CCR5-m303 mutationfound in any subject in this study.Conclusion: The examined subjects of four Chinese ethnicorigins showed lower frequencies of CCR5A32 andCCR5m303 alleles, but higher frequencies of mutant CCR2-64I and SDF1-3'A alleles compared to those identified innorthern-European and American Caucasians. Thesignificance of the different frequencies and polymorphisms of the above alleles in Chinese populations needs to be furtherexamined in HIV-1/AIDS diseases.

  20. 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...... insufficient, with only two of 21 countries and territories having achieved coverage of cervical cancer screening above 40%. Ten of 21 countries and territories had included HPV vaccination in their immunization schedule, but only two countries reported coverage of HPV vaccination above 60% among the targeted...... population. Key barriers to the introduction and continuation of HPV vaccination were reported to be: (i) Lack of sustainable financing for HPV vaccine programs; (ii) Lack of visible government endorsement; (iii) Critical public perception of the value and safety of the HPV vaccine; and (iv) Lack of clear...

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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...

  3. 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.

  4. 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.

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

    Science.gov (United States)

    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...

  7. Tregs细胞CCR4、CCR6表达异常在类风湿关节炎患者发病时的意义%The pathogenic significance of increased CCR4,CCR6 expression on Tregs cells in rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    魏巍; 刘葵葵; 韩捷

    2013-01-01

    Objective To explore the role of CCR4 andCCR6 abnormal expression on Tregs in RA and the mechanism that may be involved. Methods Peripheral blood mononuclear cel s (PBMC) were isolated from blood in RA patients. Im-munofluorescence staining and flow cytometry assay were used to detect the expression of CCR4, CCR6 on Tregs surface. The correlation analysis between expression level of CCR4 and CCR6 on Tregs and the clinical activity parameters was performed. Results The expression of Tregs in peripheral blood of RA patients was lower than healthy control(P<0.05). The expression levels of chemokine receptor of CCR4, CCR6 on Tregs cell in peripheral blood of RA patients in active phase were higher than healthy control(P<0.05).The expression levels of chemokine receptor CCR4, CCR6 on Tregs cel in RA patients who were in active phase was positively correlated with the level of the DAS28 score (P<0.05).Conclusion The increased expression of CCR4, CCR6 on Tregs surface in rheumatoid arthritis patients not only means Tregs cell obtain the capability to directional migrate to joint, but also represents feedback regulation in the body's inflammatory response.%  目的探讨Tregs细胞CCR4、CCR6受体在类风湿关节炎(RA)患者发病时的意义。方法选择45例活动期RA患者(RA组)及30例健康体检者(对照组),从外周血分离单个核细胞(PBMC),采用流式细胞分析法检测RA患者外周血中CD4+Foxp3+细胞(Tregs)占比及其该类细胞上CCR4、CCR6的表达水平,并对Tregs上CCR4、CCR6水平与RA临床活动指标进行相关性分析。结果与对照组比较,RA活动期患者外周血Tregs细胞数量明显减少,差异有统计学意义(P<0.05);RA活动期患者外周血Tregs细胞表面趋化因子受体CCR4、CCR6表达水平与对照组的差异有统计学意义(P<0.05);RA活动期患者外周血Tregs细胞CCR4、CCR6表达水平与DAS28评分呈正相关(P<0.05)。结论 RA患

  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. CTV delineation for rectal cancer treatment: ambiguities defined by a national review project

    OpenAIRE

    Joye, Ines; Van Herck, Hans; Slagmolen, Pieter; Defraene, Gilles; Hortobagyi, Eszter; Maes, Frederik; Haustermans, Karin

    2014-01-01

    Joye I., Van Herck H., Slagmolen P., Defraene G., Hortobagyi E., Maes F., Haustermans K., ''CTV delineation for rectal cancer treatment: ambiguities defined by a national review project'', Radiotherapy and oncology, vol. 111 suppl. 1, pp. S195, April 2014 (European Society for Radiotherapy & Oncology - ESTRO 33, April 4-8, 2014, Vienna, Austria).

  10. 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...

  11. Quantifying important risk factors and survival following treatment in people with lung cancer using routinely collected national data

    OpenAIRE

    Powell, Helen

    2014-01-01

    Background: Survival for people with lung cancer is poor and inequalities in access to care have been demonstrated. Methods: Primary care data from The Health Improvement Network, secondary care data from Hospital Episodes Statistics and the National Lung Cancer Audit, and death records from the Office for National Statistics, were used to investigate clinical questions in lung cancer. Matched case-control methodology was used to investigate the association between sex, smoking quantity,...

  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. Experimental Autoimmune Encephalomyelitis (EAE) in CCR2−/− Mice: Susceptibility in Multiple Strains

    OpenAIRE

    Gaupp, Stefanie; Pitt, David; Kuziel, William A.; Cannella, Barbara; Raine, Cedric S.

    2003-01-01

    Chemokines are low molecular weight cytokines which act as chemoattractants for infiltrating cells bearing appropriate receptors (CCR) to sites of inflammation. It has been proposed that CCR2 on monocytes is responsible for their recruitment into the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, and two previous reports have described resistance of CCR2−/− mice to EAE. The present study examined three different mouse strains w...

  15. CCR5 Expression and β-Chemokine Production During Placental Neonatal Monocyte Differentiation

    OpenAIRE

    Zylla, Dylan; Li, Yuan; BERGENSTAL, EMILY; Merrill, Jeffrey D.; Douglas, Steven D.; MOONEY, KATHY; GUO, CHANG-JIANG; Song, Li; Ho, Wen-Zhe

    2003-01-01

    The stage of maturation of monocytes affects their susceptibility to HIV infection. The β-chemokines and their receptor CCR5 play a crucial role in inflammatory reactions and HIV infection. We therefore examined the correlation between the expression of CCR5 and β-chemokine production and the susceptibility to HIV infection during cord monocyte (CM) differentiation into macrophages. CM and CM-derived macrophages (CMDM) were examined for β-chemokine and CCR5 expression. The susceptibility of t...

  16. Challenges in the development and implementation of the National Comprehensive Cancer Control Program in Mexico.

    Science.gov (United States)

    Reynoso-Noverón, Nancy; Meneses-García, Abelardo; Erazo-Valle, Aura; Escudero-de Los Ríos, Pedro; Kuri-Morales, Pablo Antonio; Mohar-Betancourt, Alejandro

    2016-04-01

    Chronic noncommunicable diseases (NCDs), including cancer, have become the leading cause of human morbidity and mortality. In Mexico, cancer is the third leading cause of death, with a high incidence among the economically active population, a high proportion of advanced stages at diagnosis and limited care coverage for patients. However, no public policy aimed at managing this important public health problem has been developed and implemented to date. This manuscript describes the first interinstitutional proposal of a National Program for Cancer Control, considering the known risk factors, early detection, treatment, palliative care and patient rehabilitation. This manuscript also outlines a series of thoughts on the difficulties and needs that the Mexican health system faces in achieving the main objectives of the program: to decrease the incidence of cancer, to increase survival and to improve the quality of life for this group of patients. PMID:27557393

  17. Chemokine receptor CCR8 is required for lipopolysaccharide-triggered cytokine production in mouse peritoneal macrophages.

    Directory of Open Access Journals (Sweden)

    Tomoyuki Oshio

    Full Text Available Chemokine (C-C motif receptor 8 (CCR8, the chemokine receptor for chemokine (C-C motif ligand 1 (CCL1, is expressed in T-helper type-2 lymphocytes and peritoneal macrophages (PMφ and is involved in various pathological conditions, including peritoneal adhesions. However, the role of CCR8 in inflammatory responses is not fully elucidated. To investigate the function of CCR8 in macrophages, we compared cytokine secretion from mouse PMφ or bone marrow-derived macrophages (BMMφ stimulated with various Toll-like receptor (TLR ligands in CCR8 deficient (CCR8-/- and wild-type (WT mice. We found that CCR8-/- PMφ demonstrated attenuated secretion of tumor necrosis factor (TNF-α, interleukin (IL-6, and IL-10 when stimulated with lipopolysaccharide (LPS. In particular, LPS-induced IL-10 production absolutely required CCR8. CCR8-dependent cytokine secretion was characteristic of PMφ but not BMMφ. To further investigate this result, we selected the small molecule compound R243 from a library of compounds with CCR8-antagonistic effects on CCL1-induced Ca2+ flux and CCL1-driven PMφ aggregation. Similar to CCR8-/- PMφ, R243 attenuated secretion of TNF-α, IL-6, and most strikingly IL-10 from WT PMφ, but not BMMφ. CCR8-/- PMφ and R243-treated WT PMφ both showed suppressed c-jun N-terminal kinase activity and nuclear factor-κB signaling after LPS treatment when compared with WT PMφ. A c-Jun signaling pathway inhibitor also produced an inhibitory effect on LPS-induced cytokine secretion that was similar to that of CCR8 deficiency or R243 treatment. As seen in CCR8-/- mice, administration of R243 attenuated peritoneal adhesions in vivo. R243 also prevented hapten-induced colitis. These results are indicative of cross talk between signaling pathways downstream of CCR8 and TLR-4 that induces cytokine production by PMφ. Through use of CCR8-/- mice and the new CCR8 inhibitor, R243, we identified a novel macrophage innate immune response pathway that

  18. Chemokine receptor Ccr1 drives neutrophil-mediated kidney immunopathology and mortality in invasive candidiasis.

    Directory of Open Access Journals (Sweden)

    Michail S Lionakis

    Full Text Available 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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...

  6. Strategies for Increasing Cervical Cancer Screening Amongst First Nations Communities in Northwest Ontario, Canada.

    Science.gov (United States)

    Maar, Marion; Wakewich, Pamela; Wood, Brianne; Severini, Alberto; Little, Julian; Burchell, Ann N; Ogilvie, Gina; Zehbe, Ingeborg

    2016-04-01

    The high burden of cervical cancer in Indigenous populations worldwide is due to underscreening and inadequate follow-up. Using qualitative, participatory action research, we interviewed health care staff to identify ways to increase screening recruitment in First Nations communities in Northwest Ontario, Canada. Our findings suggest the value of a multilevel social-ecological model to promote behavioral changes at the community, health care service and stakeholder, and decision-maker level. Participants emphasized the central role of First Nations women as nurturers of life and for the well-being of their family members. They stressed the importance of building awareness and motivation for cervical cancer screening through various activities including continuous education, hosting screening events specifically for women, improving the attitude and service of health care providers, and promoting screening tools and policies that complement and are respectful of First Nations women. PMID:25375661

  7. 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.

  8. 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.

  9. 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.

  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. 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.

  12. 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.

  13. 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.

  14. Improving quality of breast cancer surgery through development of a national breast cancer surgical outcomes (BRCASO) research database

    International Nuclear Information System (INIS)

    Common measures of surgical quality are 30-day morbidity and mortality, which poorly describe breast cancer surgical quality with extremely low morbidity and mortality rates. Several national quality programs have collected additional surgical quality measures; however, program participation is voluntary and results may not be generalizable to all surgeons. We developed the Breast Cancer Surgical Outcomes (BRCASO) database to capture meaningful breast cancer surgical quality measures among a non-voluntary sample, and study variation in these measures across providers, facilities, and health plans. This paper describes our study protocol, data collection methods, and summarizes the strengths and limitations of these data. We included 4524 women ≥18 years diagnosed with breast cancer between 2003-2008. All women with initial breast cancer surgery performed by a surgeon employed at the University of Vermont or three Cancer Research Network (CRN) health plans were eligible for inclusion. From the CRN institutions, we collected electronic administrative data including tumor registry information, Current Procedure Terminology codes for breast cancer surgeries, surgeons, surgical facilities, and patient demographics. We supplemented electronic data with medical record abstraction to collect additional pathology and surgery detail. All data were manually abstracted at the University of Vermont. The CRN institutions pre-filled 30% (22 out of 72) of elements using electronic data. The remaining elements, including detailed pathology margin status and breast and lymph node surgeries, required chart abstraction. The mean age was 61 years (range 20-98 years); 70% of women were diagnosed with invasive ductal carcinoma, 20% with ductal carcinoma in situ, and 10% with invasive lobular carcinoma. The BRCASO database is one of the largest, multi-site research resources of meaningful breast cancer surgical quality data in the United States. Assembling data from electronic

  15. 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.

  16. Connecting the Dots: Linking the National Program of Cancer Registries and the Needs of Survivors and Clinicians.

    Science.gov (United States)

    Ryerson, A Blythe; Eheman, Christie; Styles, Timothy; Rycroft, Randi; Snyder, Claire

    2015-12-01

    Cancer survivors, the medical community, public health professionals, researchers, and policymakers all need information about newly diagnosed cancer cases and deaths to better understand and address the disease burden. CDC collects cancer data on 96% of the U.S. population through the National Program of Cancer Registries. The National Program of Cancer Registries routinely collects data on all cancer occurrences, deaths, and the types of initial treatment received by the patients, and recently CDC has made advances in its cancer surveillance activities that have direct applicability to cancer survivorship research and care. This article examines CDC's innovative uses of the National Program of Cancer Registries infrastructure and data as a recruitment source for survivorship research studies and behavioral interventions; comparative effectiveness and patient-centered outcomes research; and the collection, consolidation, and dissemination of treatment summaries for cancer survivors and their providers. This paper also discusses long-term, idealistic plans for additional data linkages and sharing among public health, providers, and the cancer survivor through innovative concepts such as patient portals and rapid-learning health care. PMID:26590648

  17. 75 FR 26266 - National Cancer Institute (NCI); National Institute of Allergy and Infectious Diseases (NIAID...

    Science.gov (United States)

    2010-05-11

    ... Allergy and Infectious Diseases (NIAID); National Institute of Arthritis and Musculoskeletal and Skin...: From Mouse Models to Human Disease and Treatment.'' Dates: September 2-3, 2010. Location: Lister Hill... treatment. It is hoped that one consequence of this meeting might be some consensus as to what is...

  18. Functional health literacy in Spanish-speaking Latinas seeking breast cancer screening through the National Breast and Cervical Cancer Screening Program

    OpenAIRE

    Samantha Garbers; Karen Schmitt; Anne Marie Rappa; Mary Ann Chiasson

    2010-01-01

    Samantha Garbers1, Karen Schmitt2, Anne Marie Rappa2, Mary Ann Chiasson11Public Health Solutions, New York, NY, USA; 2Columbia University Breast Cancer Screening Program, New York, NY, USABackground: This analysis examines the association between functional health literacy and follow-up after mammography among women receiving breast cancer screening at a National Breast and Cervical Cancer Early Detection Program site in New York City that provides universal bilingual case management.Methods:...

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. 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...

  4. 77 FR 5471 - Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review

    Science.gov (United States)

    2012-02-03

    ... regulations (63 FR 44511, August 19, 1998) to provide to its customers each year. Community water systems... 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...

  5. CCR4 is critically involved in effective antitumor immunity in mice bearing intradermal B16 melanoma.

    Science.gov (United States)

    Matsuo, Kazuhiko; Itoh, Tatsuki; Koyama, Atsushi; Imamura, Reira; Kawai, Shiori; Nishiwaki, Keiji; Oiso, Naoki; Kawada, Akira; Yoshie, Osamu; Nakayama, Takashi

    2016-08-01

    CCR4 is a major chemokine receptor expressed by Treg cells and Th17 cells. While Treg cells are known to suppress antitumor immunity, Th17 cells have recently been shown to enhance the induction of antitumor cytotoxic T lymphocytes. Here, CCR4-deficient mice displayed enhanced tumor growth upon intradermal inoculation of B16-F10 melanoma cells. In CCR4-deficient mice, while IFN-γ+CD8+ effector T cells were decreased in tumor sites, IFN-γ+CD8+ T cells and Th17 cells were decreased in regional lymph nodes. In wild-type mice, CD4+IL-17A+ cells, which were identified as CCR4+CD44+ memory Th17, were found to be clustered around dendritic cells expressing MDC/CCL22, a ligand for CCR4, in regional lymph nodes. Compound 22, a CCR4 antagonist, also enhanced tumor growth and decreased Th17 cells in regional lymph nodes in tumor-bearing mice treated with Dacarbazine. In contrast, CCR6 deficiency did not affect the tumor growth and the numbers of Th17 cells in regional lymph nodes. These findings indicate that CCR4 is critically involved in regional lymph node DC-Th17 cell interactions that are necessary for Th17 cell-mediated induction of antitumor CD8+ effector T cells in mice bearing B16 melanoma. PMID:27132989

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. Circulating human CD4 and CD8 T cells do not have large intracellular pools of CCR5

    OpenAIRE

    Pilch-Cooper, Heather A.; Sieg, Scott F.; Hope, Thomas J.; Koons, Ann; Escola, Jean-Michel; Offord, Robin; Veazey, Ronald S.; Mosier, Donald E.; Clagett, Brian; Medvik, Kathy; Jadlowsky, Julie K; Chance, Mark R.; Kiselar, Janna G.; Hoxie, James A.; Collman, Ronald G.

    2011-01-01

    CC Chemokine Receptor 5 (CCR5) is an important mediator of chemotaxis and the primary coreceptor for HIV-1. A recent report by other researchers suggested that primary T cells harbor pools of intracellular CCR5. With the use of a series of complementary techniques to measure CCR5 expression (antibody labeling, Western blot, quantitative reverse transcription polymerase chain reaction), we established that intracellular pools of CCR5 do not exist and that the results obtained by the other rese...

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. DMPD: Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12960231 Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited sign...82. Epub 2003 Jul 22. (.png) (.svg) (.html) (.csml) Show Macrophage activation through CCR5- and CXCR4-media...on through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. Authors Lee C, Liu QH, Tomkowicz B, Yi

  20. 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.

  1. 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

  2. CCR10基因的克隆与序列分析%Molecular Cloning and Sequence Analysis of Oryctolagus cuniculus CCR10

    Institute of Scientific and Technical Information of China (English)

    贾海丽; 乔新安; 韩立强; 惠参军; 王月影; 王艳玲; 杨国宇

    2008-01-01

    克隆并分析兔CCR10基因.基于电子延伸序列,设计1对克隆引物,兔盲肠黏膜组织提取总RNA,进行RT-PCR,将PCR产物与pMD19-T载体连接后转化E.coli JM109感受态细胞、检测阳性克隆、测序并进行序列分析.克隆的兔CCR10基因长为723bp,编码由241个氨基酸残基组成的CCR10前体蛋白,三级结构预测表明CCR10具有一个多克隆免疫球蛋白区(PIG-X).克隆的兔CCR10基因与绵羊、人的同源性分别为89.6%、89.9%,推导的氨基酸序列与绵羊、人的同源性分别为94.2%、93.8%,结构特征与绵羊、人的相一致.克隆了兔CCR10基因并注册GenBank(登录号:EU348829).

  3. 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.

  4. CCL20/CCR6 Signaling Regulates Bone Mass Accrual in Mice.

    Science.gov (United States)

    Doucet, Michele; Jayaraman, Swaathi; Swenson, Emily; Tusing, Brittany; Weber, Kristy L; Kominsky, Scott L

    2016-07-01

    CCL20 is a member of the macrophage inflammatory protein family and is reported to signal monogamously through the receptor CCR6. Although studies have identified the genomic locations of both Ccl20 and Ccr6 as regions important for bone quality, the role of CCL20/CCR6 signaling in regulating bone mass is unknown. By micro-computed tomography (μCT) and histomorphometric analysis, we show that global loss of Ccr6 in mice significantly decreases trabecular bone mass coincident with reduced osteoblast numbers. Notably, CCL20 and CCR6 were co-expressed in osteoblast progenitors and levels increased during osteoblast differentiation, indicating the potential of CCL20/CCR6 signaling to influence osteoblasts through both autocrine and paracrine actions. With respect to autocrine effects, CCR6 was found to act as a functional G protein-coupled receptor in osteoblasts and although its loss did not appear to affect the number or proliferation rate of osteoblast progenitors, differentiation was significantly inhibited as evidenced by delays in osteoblast marker gene expression, alkaline phosphatase activity, and mineralization. In addition, CCL20 promoted osteoblast survival concordant with activation of the PI3K-AKT pathway. Beyond these potential autocrine effects, osteoblast-derived CCL20 stimulated the recruitment of macrophages and T cells, known facilitators of osteoblast differentiation and survival. Finally, we generated mice harboring a global deletion of Ccl20 and found that Ccl20(-/-) mice exhibit a reduction in bone mass similar to that observed in Ccr6(-/-) mice, confirming that this phenomenon is regulated by CCL20 rather than alternate CCR6 ligands. Collectively, these data indicate that CCL20/CCR6 signaling may play an important role in regulating bone mass accrual, potentially by modulating osteoblast maturation, survival, and the recruitment of osteoblast-supporting cells. © 2016 American Society for Bone and Mineral Research. PMID:26890063

  5. 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.

  6. 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. PMID:26997201

  7. 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.

  8. 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.

  9. 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. PMID:26970137

  10. 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.

  11. Cancer incidence estimates at the national and district levels in Colombia Incidencia estimada de cáncer en Colombia a nivel departamental y nacional

    OpenAIRE

    Marion Piñeros; Jacques Ferlay; Raúl Murill

    2006-01-01

    OBJECTIVE: To estimate national and district cancer incidence for 18 major cancer sites in Colombia. MATERIAL AND METHODS: National and district incidence was estimated by applying a set of age, sex and site-specific incidence/mortality ratios, obtained from a population-based cancer registry, to national and regional mortality. The work was done in Bogotá (Colombia) and Lyon (France) between May 2003 and August 2004. RESULTS: The annual total number of cases expected (all cancers but skin) w...

  12. Plant collecting program in Southeast Asia under the sponsorship of the United States National Cancer Institute (NCI) (1986-1991)

    NARCIS (Netherlands)

    Soejarto, D.D.

    1992-01-01

    Under the funding from the United States National Cancer Institute (NCI)¹, a program was undertaken to collect plant samples in Southeast Asia to be tested for their cancer- and AIDS-arresting properties, for the period of September 1, 1986 through August 31, 1991. The program was implemented with t

  13. 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.

  14. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Role in Cancer Research Intramural Research Extramural Research Bioinformatics and Cancer NCI-Designated Cancer Centers Frederick National ... Role in Cancer Research Intramural Research Extramural Research Bioinformatics and Cancer NCI-Designated Cancer Centers Frederick National ...

  15. Critical roles of chemokine receptor CCR5 in regulating glioblastoma proliferation and invasion.

    Science.gov (United States)

    Zhao, Lanfu; Wang, Yuan; Xue, Yafei; Lv, Wenhai; Zhang, Yufu; He, Shiming

    2015-11-01

    Glioblastoma (GBM) is the most prevalent malignant primary brain tumor in adults and exhibits a spectrum of aberrantly aggressive phenotype. Tumor cell proliferation and invasion are critically regulated by chemokines and their receptors. Recent studies have shown that the chemokine CCL5 and its receptor CCR5 play important roles in tumor invasion and metastasis. Nonetheless, the roles of the CCR5 in GBM still remain unclear. The present study provides the evidence that the chemokine receptor CCR5 is highly expressed and associated with poor prognosis in human GBM. Mechanistically, CCL5-CCR5 mediates activation of Akt, and subsequently induces proliferation and invasive responses in U87 and U251 cells. Moreover, down-regulation of CCR5 significantly inhibited the growth of glioma in U87 tumor xenograft mouse model. Finally, high CCR5 expression in GBM is correlated with increased p-Akt expression in patient samples. Together, these findings suggest that the CCR5 is a critical molecular event associated with gliomagenesis.

  16. HEK293T Cells Are Heterozygous for CCR5 Delta 32 Mutation.

    Science.gov (United States)

    Qi, Chunxia; Jia, Xiaopeng; Lu, Lingling; Ma, Ping; Wei, Min

    2016-01-01

    C-C chemokine receptor 5 (CCR5) is a receptor for chemokines and a co-receptor for HIV-1 entry into the target CD4+ cells. CCR5 delta 32 deletion is a loss-of-function mutation, resistant to HIV-1 infection. We tried to induce the CCR5 delta 32 mutation harnessing the genome editing technique, CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR and CRISPR associated protein 9, Cas9) in the commonly used cell line human embryonic kidney HEK 293T cells. Surprisingly, we found that HEK293T cells are heterozygous for CCR5 delta 32 mutation, in contrast to the wild type CCR5 cells, human acute T cell leukemia cell line Jurkat and human breast adenocarcinoma cell line MDA-MB-231 cells. This finding indicates that at least one human cell line is heterozygous for the CCR5 delta 32 mutation. We also found that in PCR amplification, wild type CCR5 DNA and mutant delta 32 DNA can form mismatched heteroduplex and move slowly in gel electrophoresis.

  17. HEK293T Cells Are Heterozygous for CCR5 Delta 32 Mutation

    Science.gov (United States)

    Qi, Chunxia; Jia, Xiaopeng; Lu, Lingling; Ma, Ping; Wei, Min

    2016-01-01

    C-C chemokine receptor 5 (CCR5) is a receptor for chemokines and a co-receptor for HIV-1 entry into the target CD4+ cells. CCR5 delta 32 deletion is a loss-of-function mutation, resistant to HIV-1 infection. We tried to induce the CCR5 delta 32 mutation harnessing the genome editing technique, CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR and CRISPR associated protein 9, Cas9) in the commonly used cell line human embryonic kidney HEK 293T cells. Surprisingly, we found that HEK293T cells are heterozygous for CCR5 delta 32 mutation, in contrast to the wild type CCR5 cells, human acute T cell leukemia cell line Jurkat and human breast adenocarcinoma cell line MDA-MB-231 cells. This finding indicates that at least one human cell line is heterozygous for the CCR5 delta 32 mutation. We also found that in PCR amplification, wild type CCR5 DNA and mutant delta 32 DNA can form mismatched heteroduplex and move slowly in gel electrophoresis. PMID:27042825

  18. 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.

  19. DISTRIBUTION OF CCR2-64I GENE AMONG THE TRIBES AND CASTE POPULATION OF VIDARBHA, INDIA.

    Directory of Open Access Journals (Sweden)

    Arvind B Chavhan

    2013-08-01

    Results: The genotyping for the CCR2-64I mutation among the selected tribe and a caste reveal that all of the tribes and a caste was found to be heterozygous for the CCR2-64I mutation. Among the tribes Gonds showed highest genotype frequency (29.28% and (11.76% for heterozygous (CCR2/64I and Homozygous (64I/64I respectively, having an allelic frequency (0.233. A pooled allelic frequencies of the wild-type allele CCR2 and CCR2 64I the variant were found to be 0.854 and 0.146, respectively. No significant deviations from the HWE were observed for tribes and a caste population for the CCR2- 64I mutant χ2=2.76. The study reports the presence of mutant CCR2- 64I gene in tribes and caste population from Vidarbha region.

  20. CCR2 regulates the uptake of bone marrow-derived fibroblasts in renal fibrosis.

    Directory of Open Access Journals (Sweden)

    Yunfeng Xia

    Full Text Available Recent studies have shown that bone marrow-derived fibroblasts contribute significantly to the pathogenesis of renal fibrosis. However, the molecular mechanisms underlying the recruitment of bone marrow-derived fibroblasts into the kidney are incompletely understood. Bone marrow-derived fibroblasts express the chemokine receptor--CCR2. In this study, we tested the hypothesis that CCR2 participates in the recruitment of fibroblasts into the kidney during the development of renal fibrosis. Bone marrow-derived collagen-expressing GFP⁺ fibroblasts were detected in the obstructed kidneys of chimeric mice transplanted with donor bone marrow from collagen α1(I-GFP reporter mice. These bone marrow-derived fibroblasts expressed PDGFR-β and CCR2. CCR2 knockout mice accumulated significantly fewer bone marrow-derived fibroblast precursors expressing the hematopoietic marker-CD45 and the mesenchymal markers-PDGFR-β or procollagen I in the obstructed kidneys compared with wild-type mice. Furthermore, CCR2 knockout mice displayed fewer bone marrow-derived myofibroblasts and expressed less α-SMA or FSP-1 in the obstructed kidneys compared with wild-type mice. Consistent with these findings, genetic deletion of CCR2 inhibited total collagen deposition and suppressed expression of collagen I and fibronectin. Moreover, genetic deletion of CCR2 inhibits MCP-1 and CXCL16 gene expression associated with a reduction of inflammatory cytokine expression and macrophage infiltration, suggesting a linear interaction between two chemokines/ligand receptors in tubular epithelial cells. Taken together, our results demonstrate that CCR2 signaling plays an important role in the pathogenesis of renal fibrosis through regulation of bone marrow-derived fibroblasts. These data suggest that inhibition of CCR2 signaling could constitute a novel therapeutic approach for fibrotic kidney disease.

  1. Localized CCR2 Activation in the Bone Marrow Niche Mobilizes Monocytes by Desensitizing CXCR4.

    Directory of Open Access Journals (Sweden)

    Hosung Jung

    Full Text Available Inflammatory (classical monocytes residing in the bone marrow must enter the bloodstream in order to combat microbe infection. These monocytes express high levels of CCR2, a chemokine receptor whose activation is required for them to exit the bone marrow. How CCR2 is locally activated in the bone marrow and how their activation promotes monocyte egress is not understood. Here, we have used double transgenic lines that can visualize CCR2 activation in vivo and show that its chemokine ligand CCL2 is acutely released by stromal cells in the bone marrow, which make direct contact with CCR2-expressing monocytes. These monocytes also express CXCR4, whose activation immobilizes cells in the bone marrow, and are in contact with stromal cells expressing CXCL12, the CXCR4 ligand. During the inflammatory response, CCL2 is released and activates the CCR2 on neighboring monocytes. We demonstrate that acutely isolated bone marrow cells co-express CCR2 and CXCR4, and CCR2 activation desensitizes CXCR4. Inhibiting CXCR4 by a specific receptor antagonist in mice causes CCR2-expressing cells to exit the bone marrow in absence of inflammatory insults. Taken together, these results suggest a novel mechanism whereby the local activation of CCR2 on monocytes in the bone marrow attenuates an anchoring signalling provided by CXCR4 expressed by the same cell and mobilizes the bone marrow monocyte to the blood stream. Our results also provide a generalizable model that cross-desensitization of chemokine receptors fine-tunes cell mobility by integrating multiple chemokine signals.

  2. 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

  3. Changes in acute response to radiation after implementation of new national guidelines for head and neck cancer

    DEFF Research Database (Denmark)

    Hansen, C. R.; Bertelsen, Anders; Zukauskaite, R.;

    2015-01-01

    Purpose/Objective: New national guidelines (GL) for radiotherapy (RT) of head and neck cancer (HNC) were implemented at the beginning of 2013. One purpose of the new GL was to nationally standardise the expansion from GTV to high risk CTV (CTV1). This standardisation has resulted in change...

  4. Teaching Tools to Engage Anishinaabek First Nations Women in Cervical Cancer Screening: Report of an Educational Workshop

    Science.gov (United States)

    Zehbe, Ingeborg; Wood, Brianne; Wakewich, Pamela; Maar, Marion; Escott, Nicholas; Jumah, Naana; Little, Julian

    2016-01-01

    Objective: To explore educational strategies for engaging First Nations women in Canada to attend cervical cancer screening. Design: Within a participatory action research framework, semi-structured interviews with health-care providers in First Nations communities revealed that education about the value of screening is perceived as being a key…

  5. CCR6 marks regulatory T cells as a colon-tropic, interleukin-10-producing phenotype1

    OpenAIRE

    Kitamura, Kazuya; Farber, Joshua M; Kelsall, Brian L.

    2010-01-01

    Expression of CCR6 and its ligand, CCL20, are increased in the colon of humans with inflammatory bowel diseases and mice with experimental colits, however their role in disease pathogenesis remains obscure. Here we demonstrate a role for CCR6 on regulatory T (Treg)3 cells in the T cell-transfer model of colitis. Rag2−/− mice given Ccr6−/− CD4+CD45RBhigh T cells had more severe colitis with increased IFN-γ-producing T cells, compared to the mice given WT cells. While equivalent frequency of in...

  6. CD4-independent use of the CCR5 receptor by sequential primary SIVsm isolates

    Directory of Open Access Journals (Sweden)

    Thorstensson Rigmor

    2007-07-01

    Full Text Available Abstract Background CD4-independence has been taken as a sign of a more open envelope structure that is more accessible to neutralizing antibodies and may confer altered cell tropism. In the present study, we analyzed SIVsm isolates for CD4-independent use of CCR5, mode of CCR5-use and macrophage tropism. The isolates have been collected sequentially from 13 experimentally infected cynomolgus macaques and have previously been shown to use CCR5 together with CD4. Furthermore, viruses obtained early after infection were neutralization sensitive, while neutralization resistance appeared already three months after infection in monkeys with progressive immunodeficiency. Results Depending whether isolated early or late in infection, two phenotypes of CD4-independent use of CCR5 could be observed. The inoculum virus (SIVsm isolate SMM-3 and reisolates obtained early in infection often showed a pronounced CD4-independence since virus production and/or syncytia induction could be detected directly in NP-2 cells expressing CCR5 but not CD4 (CD4-independent-HIGH. Conversely, late isolates were often more CD4-dependent in that productive infection in NP-2/CCR5 cells was in most cases weak and was revealed only after cocultivation of infected NP-2/CCR5 cells with peripheral blood mononuclear cells (CD4-independent-LOW. Considering neutralization sensitivity of these isolates, newly infected macaques often harbored virus populations with a CD4-independent-HIGH and neutralization sensitive phenotype that changed to a CD4-independent-LOW and neutralization resistant virus population in the course of infection. Phenotype changes occurred faster in progressor than long-term non-progressor macaques. The phenotypes were not reflected by macrophage tropism, since all isolates replicated efficiently in macrophages. Infection of cells expressing CCR5/CXCR4 chimeric receptors revealed that SIVsm used the CCR5 receptor in a different mode than HIV-1. Conclusion Our

  7. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, H.B.; Timm, S.; Wang, A.G.;

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission...... of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without...

  8. The herpesvirus 8-encoded chemokine vMIP-II, but not the poxvirus-encoded chemokine MC148, inhibits the CCR10 receptor

    DEFF Research Database (Denmark)

    Lüttichau, H R; Lewis, I C; Gerstoft, J;

    2001-01-01

    chemokines are expressed in the skin we suspected MC148 to block CCR10. However, in calcium mobilization assays we found MC148 unable to block CCR10 in micromolar concentrations in contrast to vMIP-II. (125)I-MC148 was only able to bind to CCR8, but not to CCR10, CCR11, CXCR6 / BONZO, APJ, DARC or the orphan...

  9. 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.

  10. Sociodemographic factors and delays in the diagnosis of six cancers: analysis of data from the ‘National Survey of NHS Patients: Cancer'

    OpenAIRE

    Neal, R D; Allgar, V L

    2005-01-01

    This paper aims to explore the relationship between sociodemographic factors and the components of diagnostic delay (total, patient and primary care, referral, secondary care) for these six cancers (breast, colorectal, lung, ovarian, prostate, or non-Hodgkin's lymphoma). Secondary analysis of patient-reported data from the ‘National Survey of NHS patients: Cancer' was undertaken (65 192 patients). Data were analysed using univariate analysis and Generalised Linear Modelling. With regard to to...

  11. Gene Cloning and Characterization of the Geobacillus thermoleovorans CCR11 Carboxylesterase CaesCCR11, a New Member of Family XV.

    Science.gov (United States)

    Espinosa-Luna, Graciela; Sánchez-Otero, María Guadalupe; Quintana-Castro, Rodolfo; Matus-Toledo, Rodrigo Eloir; Oliart-Ros, Rosa María

    2016-01-01

    A gene encoding a carboxylesterase produced by Geobacillus thermoleovoras CCR11 was cloned in the pET-3b cloning vector, sequenced and expressed in Escherichia coli BL21(DE3). Gene sequence analysis revealed an open reading frame of 750 bp that encodes a polypeptide of 250 amino acid residues (27.3 kDa) named CaesCCR11. The enzyme showed its maximum activity at 50 °C and pH 5-8, with preference for C4 substrates, confirming its esterase nature. It displayed good resistance to temperature, pH, and the presence of organic solvents and detergents, that makes this enzyme biotechnologically applicable in the industries such as fine and oleo-chemicals, cosmetics, pharmaceuticals, organic synthesis, biodiesel production, detergents, and food industries. A 3D model of CaesCCR11 was predicted using the Bacillus sp. monoacyl glycerol lipase bMGL H-257 structure as template (PBD code 3RM3, 99 % residue identity with CaesCCR11). Based on its canonical α/β hydrolase fold composed of 7 β-strands and 6 α-helices, the α/β architecture of the cap domain, the GLSTG pentapeptide, and the formation of distinctive salt bridges, we are proposing CaesCCR11 as a new member of family XV of lipolytic enzymes.

  12. Molecular Cloning and Sequence Analysis of Gene CCR9 in Oryctolagus cuniculus%兔CCR9基因的克隆与序列分析

    Institute of Scientific and Technical Information of China (English)

    贾海丽; 惠参军; 乔新安; 韩立强; 王月影; 王艳玲; 杨国宇

    2008-01-01

    设计1对克隆引物,从兔十二指肠黏膜组织提取总RNA,进行RT-PCR,将PCR产物与pMD19-T载体连接后转化E.coli JM109感受态细胞,检测阳性克隆、测序并进行序列分析.结果表明:克隆的兔CCR9基因长为624 bp,编码由208个氨基酸残基组成的CCR9前体蛋白,预测CCR9具有多个跨膜区.克隆的兔CCR9基因与绵羊、人的同源性分别为82.9%、82.7%;推导的兔CCR9氨基酸序列与绵羊、人的同源性分别为80.1%、82.2%,其结构特征与绵羊、人的相一致.

  13. 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.

  14. Insulin glargine and risk of cancer: a cohort study in the French National Healthcare Insurance Database

    OpenAIRE

    Blin, P.; Lassalle, R.; Dureau-Pournin, C.; Ambrosino, B.; Bernard, M. A.; Abouelfath, A.; Gin, H; Le Jeunne, C; Pariente, A.; Droz, C.; Moore, N

    2012-01-01

    Aims/hypothesis Using the Echantillon Généraliste de Bénéficiaires: random 1/97 permanent sample of the French national healthcare insurance system database (EGB), we investigated whether, as previously suspected, the risk of cancer in insulin glargine (A21Gly,B31Arg,B32Arg human insulin) users is higher than in human insulin users. The investigation period was from 1 January 2003 to 30 June 2010. Methods We used Cox proportional hazards time-dependent models that were stratified on propensit...

  15. 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. PMID:27577410

  16. 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.

  17. Colorectal cancer screening of high-risk populations: A national survey of physicians

    Directory of Open Access Journals (Sweden)

    White Pascale M

    2012-01-01

    Full Text Available Abstract Background The incidence of colorectal cancer can be decreased by appropriate use of screening modalities. Patients with a family history of colon cancer and of African-American ethnicity are known to be at higher risk of developing colorectal cancer. We aimed to determine if there is a lack of physician knowledge for colorectal cancer screening guidelines based on family history and ethnicity. Between February and April 2009 an anonymous web-based survey was administered to a random sample selected from a national list of 25,000 internists, family physicians and gastroenterologists. A stratified sampling strategy was used to include practitioners from states with high as well as low CRC incidence. All data analyses were performed following data collection in 2009. Results The average knowledge score was 37 ± 18% among the 512 respondents. Gastroenterologists averaged higher scores compared to internists, and family physicians, p = 0.001. Only 28% of physicians correctly identified the screening initiation point for African-Americans while only 12% of physicians correctly identified the screening initiation point and interval for a patient with a family history of CRC. The most commonly cited barriers to referring high-risk patients for CRC screening were "patient refusal" and "lack of insurance reimbursement." Conclusions There is a lack of knowledge amongst physicians of the screening guidelines for high-risk populations, based on family history and ethnicity. Educational programs to improve physician knowledge and to reduce perceived barriers to CRC screening are warranted to address health disparities in colorectal cancer.

  18. CCR5基因真核表达质粒的构建及其鉴定%Construction and characterization of plasmid expressing human CCR5 gene in eukaryotes

    Institute of Scientific and Technical Information of China (English)

    程林; 宋红勇; 吴喜林; 吴稚伟

    2012-01-01

    目的:构建人CCR5基因的真核表达质粒并对其进行功能鉴定.方法:PCR扩增人CCR5基因,将其克隆入真核表达载体pcDNA3.1内,构建含人CCR5基因的真核表达质粒pcDNA3.1-CCR5.使用RT-PCR、流式细胞术和HIV假病毒感染实验的方法,鉴定CCR5在真核细胞中的表达和功能.结果:克隆的人CCR5基因与GenBank中已登记的基因序列100%同源.瞬时转染真核细胞后,RT-PCR在预期的位置检测出目的条带,流式细胞术检测到约25.6%的细胞表达CCR5蛋白,且该蛋白能介导HIV假病毒的感染.结论:成功构建了含人CCR5基因的真核表达质粒.%Objective:To construct and characterize a eukaryotic system for expressing human CCR5 gene. Methods; Human CCR5 gene was amplified by PCR, and subcloned into pcDNA3.1 vector to construct a recombinant plasmid pcDNA3. 1-CCR5. The expression of human CCR5 gene in eukaryotic cells was verified by RT-PCR and flow cytometry. HIV-1 env pseudotyped virus infection assay was used to detect the function of CCR5 gene in eukaryotic cells. Results:The sequence of inserted CCR5 gene fragment was 100% homology compared to human CCR5 gene registered in GenBank. After transfection of eukaryotic cells with pcDNA3. 1-CCR5, the target band was identified by RT-PCR and about 25. 6% of the CCR5 protein was detected by flow cytometry. Furthermore, the protein could mediate HIV pseudotype virus infection. Conclusion:A functional eukaryotic expression plasmid pcDNA3. 1-CCR5 has been established successfully.

  19. Prostate cancer - resources

    Science.gov (United States)

    Resources - prostate cancer ... The following organizations are good resources for information on prostate cancer : American Cancer Society -- www.cancer.org/cancer/prostatecancer/index National Cancer Institute -- www.cancer.gov/cancertopics/ ...

  20. Establishment of a novel CCR5 and CXCR4 expressing CD4+ cell line which is highly sensitive to HIV and suitable for high-throughput evaluation of CCR5 and CXCR4 antagonists

    Directory of Open Access Journals (Sweden)

    De Clercq Erik

    2004-03-01

    Full Text Available Abstract Background CCR5 and CXCR4 are the two main coreceptors essential for HIV entry. Therefore, these chemokine receptors have become important targets in the search for anti-HIV agents. Here, we describe the establishment of a novel CD4+ cell line, U87.CD4.CCR5.CXCR4, stably expressing both CCR5 and CXCR4 at the cell surface. Results In these cells, intracellular calcium signalling through both receptors can be measured in a single experiment upon the sequential addition of CXCR4- and CCR5-directed chemokines. The U87.CD4.CCR5.CXCR4 cell line reliably supported HIV-1 infection of diverse laboratory-adapted strains and primary isolates with varying coreceptor usage (R5, X4 and R5/X4 and allows to investigate the antiviral efficacy of combined CCR5 and CXCR4 blockade. The antiviral effects recorded in these cells with the CCR5 antagonist SCH-C and the CXCR4 antagonist AMD3100 were similar to those noted in the single CCR5- or CXCR4-transfected U87.CD4 cells. Furthermore, the combination of both inhibitors blocked the infection of all evaluated HIV-1 strains and isolates. Conclusions Thus, the U87.CD4.CCR5.CXCR4 cell line should be useful in the evaluation of CCR5 and CXCR4 antagonists with therapeutic potential and combinations thereof.

  1. 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...

  2. 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 focu...... 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....

  3. Association of two functional polymorphisms in the CCR5 gene with juvenile rheumatoid arthritis.

    Science.gov (United States)

    Prahalad, S; Bohnsack, J F; Jorde, L B; Whiting, A; Clifford, B; Dunn, D; Weiss, R; Moroldo, M; Thompson, S D; Glass, D N; Bamshad, M J

    2006-09-01

    Juvenile rheumatoid arthritis (JRA) is mediated by Th1-immune responses. In children with JRA, synovial T cells express high levels of the Th1-chemokine receptor CC chemokine receptor 5 (CCR5), which has been implicated in susceptibility to rheumatoid arthritis. To test the hypothesis that genetic variation in CCR5 is associated with susceptibility to JRA, we analyzed patterns of variation in the 5'cis-regulatory region of CCR5 in 124 multiplex families from a JRA-affected sibpair registry. After sequencing the upstream region of CCR5, variants were tested for association with JRA by transmission disequilibrium testing. A single nucleotide polymorphism, C-1835T, was significantly undertransmitted to children with early-onset JRA (PJRA (PJRA (PJRA (PJRA.

  4. CCR5 blockade for neuroinflammatory diseases--beyond control of HIV.

    Science.gov (United States)

    Martin-Blondel, Guillaume; Brassat, David; Bauer, Jan; Lassmann, Hans; Liblau, Roland S

    2016-02-01

    Chemokine receptors have been implicated in a wide range of CNS inflammatory diseases and have important roles in the recruitment and positioning of immune cells within tissues. Among them, the chemokine (C-C motif) receptor 5 (CCR5) can be targeted by maraviroc, a readily available and well-tolerated drug that was developed for the treatment of HIV. Correlative evidence implicates the CCR5-chemokine axis in multiple sclerosis, Rasmussen encephalitis, progressive multifocal leukoencephalopathy-associated immune reconstitution inflammatory syndrome, and infectious diseases, such as cerebral malaria and HIV-associated neurocognitive disorders. On the basis of this evidence, we postulate in this Review that CCR5 antagonists, such as maraviroc, offer neuroprotective benefits in settings in which CCR5 promotes deleterious neuroinflammation, particularly in diseases in which CD8(+) T cells seem to play a pivotal role.

  5. Development of maraviroc, a CCR5 antagonist for treatment of HIV, using a novel tropism assay.

    Science.gov (United States)

    van der Ryst, Elna; Heera, Jayvant; Demarest, James; Knirsch, Charles

    2015-06-01

    Assays to identify infectious organisms are critical for diagnosis and enabling the development of therapeutic agents. The demonstration that individuals with a 32-bp deletion within the CCR5 locus were resistant to human immunodeficiency virus (HIV) infection, while those heterozygous for the mutation progressed more slowly, led to the discovery of maraviroc (MVC), a CCR5 antagonist. As MVC is only active against CCR5-tropic strains of HIV, it was critical to develop a diagnostic assay to identify appropriate patients. Trofile™, a novel phenotypic tropism assay, was used to identify patients with CCR5-tropic virus for the MVC development program. Results of these clinical studies demonstrated that the assay correctly identified patients likely to respond to MVC. Over time, the performance characteristics of the phenotypic assay were enhanced, necessitating retesting of study samples. Genotypic tropism tests that have the potential to allow for local use and more rapid turnaround times are also being developed.

  6. Structure of the CCR5 Chemokine Receptor-HIV Entry Inhibitor Maraviroc Complex

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Qiuxiang; Zhu, Ya; Li, Jian; Chen, Zhuxi; Han, Gye Won; Kufareva, Irina; Li, Tingting; Ma, Limin; Fenalti, Gustavo; Li, Jing; Zhang, Wenru; Xie, Xin; Yang, Huaiyu; Jiang, Hualiang; Cherezov, Vadim; Liu, Hong; Stevens, Raymond C.; Zhao, Qiang; Wu, Beili [Scripps; (Chinese Aca. Sci.); (UCSD)

    2013-10-21

    The CCR5 chemokine receptor acts as a co-receptor for HIV-1 viral entry. Here we report the 2.7 angstrom–resolution crystal structure of human CCR5 bound to the marketed HIV drug maraviroc. The structure reveals a ligand-binding site that is distinct from the proposed major recognition sites for chemokines and the viral glycoprotein gp120, providing insights into the mechanism of allosteric inhibition of chemokine signaling and viral entry. A comparison between CCR5 and CXCR4 crystal structures, along with models of co-receptor–gp120-V3 complexes, suggests that different charge distributions and steric hindrances caused by residue substitutions may be major determinants of HIV-1 co-receptor selectivity. These high-resolution insights into CCR5 can enable structure-based drug discovery for the treatment of HIV-1 infection.

  7. Quantifying CD4/CCR5 Usage Efficiency of HIV-1 Env Using the Affinofile System.

    Science.gov (United States)

    Webb, Nicholas E; Lee, Benhur

    2016-01-01

    Entry of HIV-1 into target cells involves the interaction of the HIV envelope (Env) with both a primary receptor (CD4) and a coreceptor (CXCR4 or CCR5). The relative efficiency with which a particular Env uses these receptors is a major component of cellular tropism in the context of entry and is related to a variety of pathological Env phenotypes (Chikere et al. Virology 435:81-91, 2013). The protocols outlined in this chapter describe the use of the Affinofile system, a 293-based dual-inducible cell line that expresses up to 25 distinct combinations of CD4 and CCR5, as well as the associated Viral Entry Receptor Sensitivity Assay (VERSA) metrics used to summarize the CD4/CCR5-dependent infectivity results. This system allows for high-resolution profiling of CD4 and CCR5 usage efficiency in the context of unique viral phenotypes.

  8. CCR5∆32及CCR5 siRNA共修饰的树突状细胞抗HIV-1的初步研究%The preliminary study of CCR5∆32 and CCR5 siRNA modiifed dendritic cells resistant HIV-1 infection

    Institute of Scientific and Technical Information of China (English)

    夏承来; 李书华

    2014-01-01

    目的:分析CCR5∆32及CCR5 siRNA共修饰的树突状细胞抗人类免疫缺陷病毒Ⅰ型(HIV-1)的作用。方法采用Adeasy系统构建携带CCR5∆32及CCR5 siRNA的重组腺病毒载体;在体外将人外周血单个核细胞(PBMC)发育成树突状细胞;采用免疫印迹法分析细胞内CCR5∆32、CCR5及HIV-1 p24的表达情况;采用酶联免疫吸附测定(ELISA)分析HIV-1 p24含量。结果重组腺病毒载体感染人源性PBMC后,细胞内CCR5表达下降,CCR5Δ32表达增加。HIV-1感染PBMC后,经修饰后的细胞中p24含量较低,而未修饰的细胞中p24含量持续上升。HIV-1感染PBMC来源的树突状细胞后,经修饰后的细胞中p24含量较低,而未修饰的细胞中p24含量持续上升。结论 CCR5∆32及CCR5 siRNA共修饰的树突状细胞具有抗HIV-1的功能。但将修饰后的细胞回输入体内能否重建机体免疫系统功能以及载体的安全性和高效性如何评价,尚需要进一步研究。%Objective To identify the characteristics of recombinant adenovirus modiifed PBMC-derived dendritic cells to resist the HIV-1 infection. Method The recombinant adenovirus vector was integrated with CCR5∆32 and CCR5 siRNA genes by using Adeasy system. The human PBMC from healthy donor blood was isolated in order to get dendritic cells. The expression of CCR5∆32, CCR5 and HIV-1 p24 in PBMC or modified cells was measured by Western blot, and ELISA. Result After the cells had been modified by recombinant adenovirus vector, the expression of CCR5∆32 was increased while the expression of CCR5 was decreased. The expression of p24 was decreased when the cells had been modified by recombinant adenovirus vector compared to the un-modiifed cells. The modiifed cells showed resistance to HIV-1 infection. Conclusion The recombinant adenovirus-modiifed cells show good resistance to HIV-1 infection. The effect and safety of modiifed cells need to be explored by further researches.

  9. Radon Control Activities for Lung Cancer Prevention in National Comprehensive Cancer Control Program Plans, 2005–2011

    OpenAIRE

    Antonio Neri, MD, MPH; Sherri L. Stewart, PhD; William Angell, MS

    2013-01-01

    Introduction Radon is the second leading cause of lung cancer among smokers and the leading cause among nonsmokers. The US Environmental Protection Agency recommends that every home be tested for radon. Comprehensive Cancer Control (CCC) programs develop cancer coalitions that coordinate funding and resources to focus on cancer activities that are recorded in cancer plans. Radon tests, remediation, and radon mitigation techniques are relatively inexpensive, but it is unclear whether coalition...

  10. Inhibition of Human Immunodeficiency Virus Replication by a Dual CCR5/CXCR4 Antagonist

    Science.gov (United States)

    Princen, Katrien; Hatse, Sigrid; Vermeire, Kurt; Aquaro, Stefano; De Clercq, Erik; Gerlach, Lars-Ole; Rosenkilde, Mette; Schwartz, Thue W.; Skerlj, Renato; Bridger, Gary; Schols, Dominique

    2004-01-01

    Here we report that the N-pyridinylmethyl cyclam analog AMD3451 has antiviral activity against a wide variety of R5, R5/X4, and X4 strains of human immunodeficiency virus type 1 (HIV-1) and HIV-2 (50% inhibitory concentration [IC50] ranging from 1.2 to 26.5 μM) in various T-cell lines, CCR5- or CXCR4-transfected cells, peripheral blood mononuclear cells (PBMCs), and monocytes/macrophages. AMD3451 also inhibited R5, R5/X4, and X4 HIV-1 primary clinical isolates in PBMCs (IC50, 1.8 to 7.3 μM). A PCR-based viral entry assay revealed that AMD3451 blocks R5 and X4 HIV-1 infection at the virus entry stage. AMD3451 dose-dependently inhibited the intracellular Ca2+ signaling induced by the CXCR4 ligand CXCL12 in T-lymphocytic cells and in CXCR4-transfected cells, as well as the Ca2+ flux induced by the CCR5 ligands CCL5, CCL3, and CCL4 in CCR5-transfected cells. The compound did not interfere with chemokine-induced Ca2+ signaling through CCR1, CCR2, CCR3, CCR4, CCR6, CCR9, or CXCR3 and did not induce intracellular Ca2+ signaling by itself at concentrations up to 400 μM. In freshly isolated monocytes, AMD3451 inhibited the Ca2+ flux induced by CXCL12 and CCL4 but not that induced by CCL2, CCL3, CCL5, and CCL7. The CXCL12- and CCL3-induced chemotaxis was also dose-dependently inhibited by AMD3451. Furthermore, AMD3451 inhibited CXCL12- and CCL3L1-induced endocytosis in CXCR4- and CCR5-transfected cells. AMD3451, in contrast to the specific CXCR4 antagonist AMD3100, did not inhibit but enhanced the binding of several anti-CXCR4 monoclonal antibodies (such as clone 12G5) at the cell surface, pointing to a different interaction with CXCR4. AMD3451 is the first low-molecular-weight anti-HIV agent with selective HIV coreceptor, CCR5 and CXCR4, interaction. PMID:15542651

  11. Colon cancer in Luxembourg: a national population-based data report, 1988–1998

    International Nuclear Information System (INIS)

    Over the last two decades time trends in incidence rates of colorectal cancer, changes in the proportions of stage at diagnosis and changes in the anatomic sub-site distribution of colon cancers have been reported in some European countries. In order to determine a strategy for early detection of colon cancer in the Grand-Duchy of Luxembourg, all consecutive colon adenocarcinomas diagnosed during the period 1988–1998 at a nation-wide level were reviewed. The population-based data of the national Morphologic Tumour Registry report all new high-grade adenomas (i.e. high-grade intraepithelial adenomatous neoplasias) and all consecutive new invasive adenocarcinomas of the colon diagnosed in the central department of pathology. Attention has been focused on variations in incidence, stage, anatomical site distribution and survival rates. Rectal cancers were excluded. Over the study period, 254 new colonic high-grade adenomas and 1379 new invasive adenocarcinomas were found; the crude incidence rates of colon adenocarcinomas grew steadily by 30%. Comparing the two 5-year periods 1988–1992 and 1994–1998, the crude incidence rates of high-grade adenomas (stage 0) rose by 190%, that of stage I cases by 14.3%, stage II cases 12.9% and stage III cases 38.5%, whereas the crude incidence rates of stage IV cases decreased by 11.8%. The high-grade adenoma/adenocarcinoma ratio increased. The right-sided colonic adenocarcinomas in elderly patients (>69 years) increased by 76%. The observed survival rates correlated with tumour stages. The overall observed 5-year survival rate (stage I-IV) was 51 ± 3% (95% confidence interval). The increasing incidence rates of colon adenocarcinomas, the persistence of advanced tumour stages (stage III), the mortality rates which remain stable, and the changing trends in the age- and sub-site distribution underline the need for preventive measures at the age of 50 in asymptomatic patients to reduce mortality from colo(rectal) cancer

  12. 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

    for an intracellular binding site for CCR2-RA-[R], JNJ-27141491, and SD-24. For CCR2-RA-[R] the most important residues for binding were found to be the highly conserved tyrosine Y(7.53) and phenylalanine F(8.50) of the NPxxYx(5,6)F motif, as well as V(6.36) at the bottom of TM-VI and K(8.49) in helix...

  13. Nf1+/- monocytes/macrophages induce neointima formation via CCR2 activation.

    Science.gov (United States)

    Bessler, Waylan K; Kim, Grace; Hudson, Farlyn Z; Mund, Julie A; Mali, Raghuveer; Menon, Keshav; Kapur, Reuben; Clapp, D Wade; Ingram, David A; Stansfield, Brian K

    2016-03-15

    Persons with neurofibromatosis type 1 (NF1) have a predisposition for premature and severe arterial stenosis. Mutations in the NF1 gene result in decreased expression of neurofibromin, a negative regulator of p21(Ras), and increases Ras signaling. Heterozygous Nf1 (Nf1(+/-)) mice develop a marked arterial stenosis characterized by proliferating smooth muscle cells (SMCs) and a predominance of infiltrating macrophages, which closely resembles arterial lesions from NF1 patients. Interestingly, lineage-restricted inactivation of a single Nf1 allele in monocytes/macrophages is sufficient to recapitulate the phenotype observed in Nf1(+/-) mice and to mobilize proinflammatory CCR2+ monocytes into the peripheral blood. Therefore, we hypothesized that CCR2 receptor activation by its primary ligand monocyte chemotactic protein-1 (MCP-1) is critical for monocyte infiltration into the arterial wall and neointima formation in Nf1(+/-) mice. MCP-1 induces a dose-responsive increase in Nf1(+/-) macrophage migration and proliferation that corresponds with activation of multiple Ras kinases. In addition, Nf1(+/-) SMCs, which express CCR2, demonstrate an enhanced proliferative response to MCP-1 when compared with WT SMCs. To interrogate the role of CCR2 activation on Nf1(+/-) neointima formation, we induced neointima formation by carotid artery ligation in Nf1(+/-) and WT mice with genetic deletion of either MCP1 or CCR2. Loss of MCP-1 or CCR2 expression effectively inhibited Nf1(+/-) neointima formation and reduced macrophage content in the arterial wall. Finally, administration of a CCR2 antagonist significantly reduced Nf1(+/-) neointima formation. These studies identify MCP-1 as a potent chemokine for Nf1(+/-) monocytes/macrophages and CCR2 as a viable therapeutic target for NF1 arterial stenosis. PMID:26740548

  14. CCR5Δ32 variant and cardiovascular disease in patients with rheumatoid arthritis: a cohort study

    OpenAIRE

    Rodríguez Rodríguez, Luis; González Juanatey, Carlos; García Bermúdez, Mercedes; Vázquez Rodríguez, Tomás R.; Miranda Filloy, José Alberto; Fernández Gutiérrez, Benjamín; Llorca Díaz, Javier; Martín Ibáñez, Javier; González-Gay Mantecón, Miguel Ángel

    2011-01-01

    Introduction The aim of our study was to analyze the influence of the CCR5Δ32 polymorphism in the risk of cardiovascular (CV) events and subclinical atherosclerosis among patients with rheumatoid arthritis (RA). Methods A total of 645 patients fulfilling the American Rheumatism Association 1987 revised classification criteria for RA were studied. Patients were genotyped for the CCR5 rs333 polymorphism using predesigned TaqMan assays. Also, HLA DRB1 genotyping was performed using mo...

  15. Measures for Optimization of Aromatic-type and Gasoline-type CCR Technology

    Institute of Scientific and Technical Information of China (English)

    Bao Wei

    2006-01-01

    This article based on the target products manufactured by the gasoline-type and aromatic-type continuous catalytic reforming (CCR) units makes an assessment on the technical indicators of these catalytic reforming units. This article also explores the technical measures for maximizing the target products delivered by the gasoline-type and aromatic-type CCR units with respect to the selection of catalysts, the optimization of feedstock and the optimized operating regime.

  16. Environmental dose in the Nuclear Medicine Department of the National Institute of Cancer

    International Nuclear Information System (INIS)

    The dosimeters TLD-100 and TLD-900 were used to know the levels of environmental dose in areas of the Nuclear Medicine Department of the National Institute of Cancer. The dosimeters calibration was carried out in the Metrology Department of the National Institute of Nuclear Research. The radioisotopes used in the studied areas are 131I, 18F, 67Ga, 99mTc, 111In, 201Tl and 137Cs with gamma energies between 93 and 662 KeV. Dosimeters were placed during five months in the diagnostic, injection, waiting and PET rooms as well as hot room, waste room, enclosed corridors to patient rooms treated with 131I and 137Cs and witness dosimeters to know the bottom. The values found vary between 0.3 and 70 major times that those of bottom. The maximum doses were measured in the waste room and in the enclosed corridor to the patient rooms with cervical uterine cancer treated with 137Cs. (Author)

  17. Development and Commercial Application of High-Platinum CCR Catalyst with Low Coke Deposition Rate

    Institute of Scientific and Technical Information of China (English)

    Ma Aizeng; Pan Jincheng; Yang Sennian

    2007-01-01

    By means of selecting proper additives and optimizing catalyst composition and preparation procedures,a high-platinum and low coke deposition catalyst PS-Ⅶ for continuous catalytic reforming (CCR)without reducing its specific surface area has been successfully developed.This catalyst PS-Ⅶ was evaluated in a 100-mL pilot test unit.Study results showed that under the same reaction conditions the newly developed catalyst PS-Ⅶ achieved a 26%reduction in coke deposition as compared to the existing high-platinum CCR catalyst.This catalyst upon its first commercial application in a 1.39Mt/a CCR unit had exhibited good anti-attrition performance and good stability in terms of its specific surface area.Compared to the original CCR catalyst this PS-Ⅶ type catalyst could reduce the coke deposition by 27.32%when operating on feedstock with low potential aromatic content,along with apparent increase in C6+liquid yield,hydrogen yield and aromatics yield,which could grapple with the problem associated with the catalyst regeneration constraints after CCR capacity expansion to ensure the longcycle high-load operation of the CCR unit.

  18. CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape

    Directory of Open Access Journals (Sweden)

    Gero Hütter

    2015-07-01

    Full Text Available Allogeneic transplantation with CCR5-delta 32 (CCR5-d32 homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a wider population. There are two cellular ways to do this. The first one is to use a CCR5 negative cell source e.g., hematopoietic stem cells (HSC to copy the initial finding. However, a recent case of a second allogeneic transplantation with CCR5-d32 homozygous stem cells suffered from viral escape of CXCR4 quasi-species. The second way is to knock down CCR5 expression by gene therapy. Currently, there are five promising techniques, three of which are presently being tested clinically. These techniques include zinc finger nucleases (ZFN, clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9, transcription activator-like effectors nuclease (TALEN, short hairpin RNA (shRNA, and a ribozyme. While there are multiple gene therapy strategies being tested, in this review we reflect on our current knowledge of inhibition of CCR5 specifically and whether this approach allows for consequent viral escape.

  19. CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape.

    Science.gov (United States)

    Hütter, Gero; Bodor, Josef; Ledger, Scott; Boyd, Maureen; Millington, Michelle; Tsie, Marlene; Symonds, Geoff

    2015-07-27

    Allogeneic transplantation with CCR5-delta 32 (CCR5-d32) homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a wider population. There are two cellular ways to do this. The first one is to use a CCR5 negative cell source e.g., hematopoietic stem cells (HSC) to copy the initial finding. However, a recent case of a second allogeneic transplantation with CCR5-d32 homozygous stem cells suffered from viral escape of CXCR4 quasi-species. The second way is to knock down CCR5 expression by gene therapy. Currently, there are five promising techniques, three of which are presently being tested clinically. These techniques include zinc finger nucleases (ZFN), clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9), transcription activator-like effectors nuclease (TALEN), short hairpin RNA (shRNA), and a ribozyme. While there are multiple gene therapy strategies being tested, in this review we reflect on our current knowledge of inhibition of CCR5 specifically and whether this approach allows for consequent viral escape.

  20. Roles of RUNX1 and PU.1 in CCR3 Transcription.

    Science.gov (United States)

    Kong, Su-Kang; Kim, Byung Soo; Hwang, Sae Mi; Lee, Hyune Hwan; Chung, Il Yup

    2016-06-01

    CCR3 is a chemokine receptor that mediates the accumulation of allergic inflammatory cells, including eosinophils and Th2 cells, at inflamed sites. The regulatory sequence of the CCR3 gene, contains two Runt-related transcription factor (RUNX) 1 sites and two PU.1 sites, in addition to a functional GATA site for transactivation of the CCR3 gene. In the present study, we examined the effects of the cis-acting elements of RUNX1 and PU.1 on transcription of the gene in EoL-1 eosinophilic cells and Jurkat T cells, both of which expressed functional surface CCR3 and these two transcription factors. Introduction of RUNX1 siRNA or PU.1 siRNA resulted in a modest decrease in CCR3 reporter activity in both cell types, compared with transfection of GATA-1 siRNA. Cotransfection of the two siRNAs led to inhibition in an additive manner. EMSA analysis showed that RUNX1, in particular, bound to its binding motifs. Mutagenesis analysis revealed that all point mutants lacking RUNX1- and PU.1-binding sites exhibited reduced reporter activities. These results suggest that RUNX1 and PU.1 participate in transcriptional regulation of the CCR3 gene.

  1. 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

  2. The National Breast and Cervical Cancer Early Detection Program: 25 Years of public health service to low-income women.

    Science.gov (United States)

    Lantz, Paula M; Mullen, Jewel

    2015-05-01

    This article presents an overview of the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), a valuable and successful national public health program in the USA that will soon celebrate its 25th anniversary. Simulation modeling and other analyses have demonstrated that the NBCCEDP has significantly reduced breast and cervical cancer mortality among low-income uninsured and underinsured women in the USA, a major goal of the original legislation. The NBCCEDP has also served to build cancer prevention and control capacity in state and local health agencies and created strong and unique public-private partnerships aimed at improving women's health. As such, the impact of NBCCEDP extends beyond the millions of women served by the program to include increased public health system capacity and effectiveness regarding cancer early detection and control for all women.

  3. Prognostic value of the expression of C-Chemokine Receptor 6 and 7 and their ligands in non-metastatic breast cancer

    International Nuclear Information System (INIS)

    Chemokines and chemokine receptors are major actors of leukocytes trafficking and some have been shown to play an important role in cancer metastasis. Chemokines CCL19, CCL20 and CCL21 and their receptors CCR6 and CCR7, were assessed as potential biomarkers of metastatic dissemination in primary breast cancer. Biomarker expression levels were evaluated using immunohistochemistry on paraffin-embedded tissue sections of breast cancer (n = 207). CCR6 was expressed by tumor cells in 35% of cases. CCR7 was expressed by spindle shaped stromal cells in 43% of cases but not by tumor cells in this series. CCL19 was the only chemokine found expressed in a significant number of breast cancers and was expressed by both tumor cells and dendritic cells (DC). CCR6, CCL19 and CCR7 expression correlated with histologic features of aggressive disease. CCR6 expression was associated with shorter relapse-free survival (RFS) in univariate and but not in multivariate analysis (p = 0.0316 and 0.055 respectively), and was not associated with shorter overall survival (OS). Expression of CCR7 was not significantly associated with shorter RFS or OS. The presence of CCL19-expressing DC was associated with shorter RFS in univariate and multivariate analysis (p = 0.042 and 0.020 respectively) but not with shorter OS. These results suggest a contribution of CCR6 expression on tumor cells and CCL19-expressing DC in breast cancer dissemination. In our series, unlike what was previously published, CCR7 was exclusively expressed on stromal cells and was not associated with survival

  4. Exploring research participation among cancer patients: analysis of a national survey and an in-depth interview study

    OpenAIRE

    Mc Grath-Lone, Louise; Day, Sophie; Schoenborn, Claudia; Ward, Helen

    2015-01-01

    Background Inequalities in cancer research participation are thought to exist with certain groups under-represented in research populations; however, much of the evidence is based on small-scale studies. The aim of this study was to explore data from in-depth interviews with cancer patients and a large national survey to investigate variation in who is asked to participate in research and who takes part. Methods Factors associated with research discussion and participation were explored in Na...

  5. Plant collecting program in Southeast Asia under the sponsorship of the United States National Cancer Institute (NCI) (1986-1991)

    OpenAIRE

    Soejarto, D. D.

    1992-01-01

    Under the funding from the United States National Cancer Institute (NCI)¹, a program was undertaken to collect plant samples in Southeast Asia to be tested for their cancer- and AIDS-arresting properties, for the period of September 1, 1986 through August 31, 1991. The program was implemented with the collaboration of the Arnold Arboretum and the Bishop Museum. Botanists from these and other institutions collaborated in the field work operation for the program, among others: J.S. BURLEY (A), ...

  6. AtCCR4a and AtCCR4b are Involved in Determining the Poly(A) Length of Granule-bound starch synthase 1 Transcript and Modulating Sucrose and Starch Metabolism in Arabidopsis thaliana.

    Science.gov (United States)

    Suzuki, Yuya; Arae, Toshihiro; Green, Pamela J; Yamaguchi, Junji; Chiba, Yukako

    2015-05-01

    Removing the poly(A) tail is the first and rate-limiting step of mRNA degradation and apparently an effective step not only for modulating mRNA stability but also for translation of many eukaryotic transcripts. Carbon catabolite repressor 4 (CCR4) has been identified as a major cytoplasmic deadenylase in Saccharomyces cerevisiae. The Arabidopsis thaliana homologs of the yeast CCR4, AtCCR4a and AtCCR4b, were identified by sequence-based analysis; however, their role and physiological significance in plants remain to be elucidated. In this study, we revealed that AtCCR4a and AtCCR4b are localized to cytoplasmic mRNA processing bodies, which are specific granules consisting of many enzymes involved in mRNA turnover. Double mutants of AtCCR4a and AtCCR4b exhibited tolerance to sucrose application but not to glucose. The levels of sucrose in the seedlings of the atccr4a/4b double mutants were reduced, whereas no difference was observed in glucose levels. Further, amylose levels were slightly but significantly increased in the atccr4a/4b double mutants. Consistent with this observation, we found that the transcript encoding granule-bound starch synthase 1 (GBSS1), which is responsible for amylose synthesis, is accumulated to a higher level in the atccr4a/4b double mutant plants than in the control plants. Moreover, we revealed that GBSS1 has a longer poly(A) tail in the double mutant than in the control plant, suggesting that AtCCR4a and AtCCR4b can influence the poly(A) length of transcripts related to starch metabolism. Our results collectively suggested that AtCCR4a and AtCCR4b are involved in sucrose and starch metabolism in A. thaliana.

  7. 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

  8. 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...

  9. 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.

  10. 人趋化因子受体CCR6的克隆、表达及其功能分析%Cloning and expression and function analysis of human chemokine receptor CCR6

    Institute of Scientific and Technical Information of China (English)

    沈大斌; 龚小云; 顾涛; 罗福康; 郑红

    2006-01-01

    目的 构建人趋化因子受体6(CCR6)cDNA序列的真核表达载体,并在HEK293细胞中表达,为研究CCR6生物学功能和筛选CCR6拮抗剂奠定基础.方法 采用RT-PCR方法从人扁桃体克隆CCR6受体的DNA片段,并将该片段插入真核表达质粒pcDNA3.1(+)中,构建重组真核表达质粒pcDNA3.1(+)-CCR6;将该质粒pcDNA3.1(+)-CCR6转染HEK293细胞,用流式细胞术检测转染pcDNA3.1(+)-CCR6质粒的HEK293细胞;采用体外趋化实验、钙流实验,验证转染pcDNA3.1(+)-CCR6质粒的HEK293细胞表面表达的CCR6的生物学活性.结果 经RT-PCR获得了编码人CCR6受体的DNA片段,构建了重组真核表达质粒pcDNA3.1(+)-CCR6;转染HEK293细胞,经流式细胞仪检测、趋化实验、钙流实验证实,表达CCR6的HEK293细胞具有趋化因子受体CCR6的生物学活性.结论 重组人趋化因子受体CCR6克隆成功,并在HEK293细胞中获得了表达,为研究CCR6的生物学功能及筛选CCR6拮抗剂奠定了基础.

  11. CCR5为靶点的小分子抗艾滋病药物的研究与开发%Research and Development of CCR5-targeted Small Molecule Anti-AIDS Drugs

    Institute of Scientific and Technical Information of China (English)

    甘海峰; 查晓明; 吉民

    2005-01-01

    综述趋化因子受体5(CCR5)拮抗剂的作用机制,介绍若干具代表性的小分子CCR5拮抗剂,并探讨其构效关系.CCR5属于G蛋白偶联受体超家族,是HIV-1入侵机体细胞的主要辅助受体之一.以CCR5为为靶点的小分子抗艾滋病药物的研究与开发备受关注.

  12. 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

  13. IL-23 induces atopic dermatitis-like inflammation instead of psoriasis-like inflammation in CCR2-deficient mice.

    Directory of Open Access Journals (Sweden)

    Shannon K Bromley

    Full Text Available Psoriasis is an immune-mediated chronic inflammatory skin disease, characterized by epidermal hyperplasia and infiltration of leukocytes into the dermis and epidermis. IL-23 is expressed in psoriatic skin, and IL-23 injected into the skin of mice produces IL-22-dependent dermal inflammation and acanthosis. The chemokine receptor CCR2 has been implicated in the pathogenesis of several inflammatory diseases, including psoriasis. CCR2-positive cells and the CCR2 ligand, CCL2 are abundant in psoriatic lesions. To examine the requirement of CCR2 in the development of IL-23-induced cutaneous inflammation, we injected the ears of wild-type (WT and CCR2-deficient (CCR2(-/- mice with IL-23. CCR2(-/- mice had increased ear swelling and epidermal thickening, which was correlated with increased cutaneous IL-4 levels and increased numbers of eosinophils within the skin. In addition, TSLP, a cytokine known to promote and amplify T helper cell type 2 (Th2 immune responses, was also increased within the inflamed skin of CCR2(-/- mice. Our data suggest that increased levels of TSLP in CCR2(-/- mice may contribute to the propensity of these mice to develop increased Th2-type immune responses.

  14. Biophysical and structural investigation of bacterially expressed and engineered CCR5, a G protein-coupled receptor

    Energy Technology Data Exchange (ETDEWEB)

    Wiktor, Maciej; Morin, Sebastien; Sass, Hans-Juergen [University of Basel, Focal Area Structural Biology and Biophysics, Biozentrum (Switzerland); Kebbel, Fabian [University of Basel, Center for Cellular Imaging and NanoAnalytics (C-CINA), Biozentrum (Switzerland); Grzesiek, Stephan, E-mail: stephan.grzesiek@unibas.ch [University of Basel, Focal Area Structural Biology and Biophysics, Biozentrum (Switzerland)

    2013-01-15

    The chemokine receptor CCR5 belongs to the class of G protein-coupled receptors. Besides its role in leukocyte trafficking, it is also the major HIV-1 coreceptor and hence a target for HIV-1 entry inhibitors. Here, we report Escherichia coli expression and a broad range of biophysical studies on E. coli-produced CCR5. After systematic screening and optimization, we obtained 10 mg of purified, detergent-solubilized, folded CCR5 from 1L culture in a triply isotope-labeled ({sup 2}H/{sup 15}N/{sup 13}C) minimal medium. Thus the material is suitable for NMR spectroscopic studies. The expected {alpha}-helical secondary structure content is confirmed by circular dichroism spectroscopy. The solubilized CCR5 is monodisperse and homogeneous as judged by transmission electron microscopy. Interactions of CCR5 with its ligands, RANTES and MIP-1{beta} were assessed by surface plasmon resonance yielding K{sub D} values in the nanomolar range. Using size exclusion chromatography, stable monomeric CCR5 could be isolated. We show that cysteine residues affect both the yield and oligomer distribution of CCR5. HSQC spectra suggest that the transmembrane domains of CCR5 are in equilibrium between several conformations. In addition we present a model of CCR5 based on the crystal structure of CXCR4 as a starting point for protein engineering.

  15. Cytokine-induced killer cells interact with tumor lysate-pulsed dendritic cells via CCR5 signaling.

    Science.gov (United States)

    Lee, Hong Kyung; Kim, Yong Guk; Kim, Ji Sung; Park, Eun Jae; Kim, Boyeong; Park, Ki Hwan; Kang, Jong Soon; Hong, Jin Tae; Kim, Youngsoo; Han, Sang-Bae

    2016-08-10

    The antitumor activity of cytokine-induced killer (CIK) cells can be increased by co-culturing them with tumor lysate-pulsed dendritic cells (tDCs); this phenomenon has been studied mainly at the population level. Using time-lapse imaging, we examined how CIK cells gather information from tDCs at the single-cell level. tDCs highly expressed CCL5, which bound CCR5 expressed on CIK cells. tDCs strongly induced migration of Ccr5(+/+) CIK cells, but not that of Ccr5(-/-) CIK cells or Ccr5(+/+) CIK cells treated with the CCR5 antagonist Maraviroc. Individual tDCs contacted Ccr5(+/+) CIK cells more frequently and lengthily than with Ccr5(-/-) CIK cells. Consequently, tDCs increased the antitumor activity of Ccr5(+/+) CIK cells in vitro and in vivo, but did not increase that of Ccr5(-/-) CIK cells. Taken together, our data provide insight into the mechanism of CIK cell activation by tDCs at the single-cell level.

  16. CCR5:抗HIV-1药物的新靶点%CCR5, a New Target of Anti-HIV Drugs

    Institute of Scientific and Technical Information of China (English)

    韩燕星; 蒋建东

    2003-01-01

    CCR5为细胞膜蛋白,属于G蛋白偶联受体家族的成员,是HIV-1入侵机体细胞的主要辅助受体之一.在过去的几年中,对CCR5的生物学特性以及在HIV感染过程中所起作用的研究取得了明显的进展,以CCR5为靶点的HIV受体拮抗剂倍受关注,主要有以下4种:(1)趋化因子衍生物;(2)低分子量非肽类;(3)单克隆抗体;(4)肽类化合物.本文综述了近年来CCR5和以其为靶点的HIV受体拮抗剂的研究进展.

  17. Recent Research on CCR5 and Its Antagonists%CCR5及其拮抗剂的研究进展

    Institute of Scientific and Technical Information of China (English)

    吴英萍; 吴文言

    2008-01-01

    趋化因子CCR5,作为G蛋白偶联因子超家族(GPCR)成员的细胞膜蛋白,是HIV-1入侵机体细胞的主要辅助受体之一.以CCR5为靶点的HIV-1受体拮抗剂越来越受关注,主要有趋化因子衍生物、非肽类小分子化合物、单克隆抗体、肽类化合物等4类.这些抗病毒活性强、高亲和力的CCR5拮抗剂,已有一部分进入了临床试验阶段.就近年来CCR5拮抗剂的相关研究进展进行了综述.

  18. Heroin use in Indonesia is associated with higher expression of CCR5 on CD4+ cells and lower ex-vivo production of CCR5 ligands

    NARCIS (Netherlands)

    Meijerink, H.; Indrati, A.R.; Soedarmo, S.; Utami, F.; Jong, C.A.J. de; Alisjahbana, B.; Crevel, R. van; Wisaksana, R.; Ven, A.J.A.M. van der

    2015-01-01

    Opioid use may affect HIV infection through altered expression of HIV co-receptors. This was examined in Indonesia among antiretroviral therapy-naive HIV patients, many of whom use drugs. C-C chemokine receptor type 5 (CCR5) expression on CD4+ cells was higher in heroin (P = 0.007), methadone (P = 0

  19. Exacerbation of facial motoneuron loss after facial nerve axotomy in CCR3-deficient mice

    Directory of Open Access Journals (Sweden)

    Derek A Wainwright

    2009-12-01

    Full Text Available We have previously demonstrated a neuroprotective mechanism of FMN (facial motoneuron survival after facial nerve axotomy that is dependent on CD4+ Th2 cell interaction with peripheral antigen-presenting cells, as well as CNS (central nervous system-resident microglia. PACAP (pituitary adenylate cyclase-activating polypeptide is expressed by injured FMN and increases Th2-associated chemokine expression in cultured murine microglia. Collectively, these results suggest a model involving CD4+ Th2 cell migration to the facial motor nucleus after injury via microglial expression of Th2-associated chemokines. However, to respond to Th2-associated chemokines, Th2 cells must express the appropriate Th2-associated chemokine receptors. In the present study, we tested the hypothesis that Th2-associated chemokine receptors increase in the facial motor nucleus after facial nerve axotomy at timepoints consistent with significant T-cell infiltration. Microarray analysis of Th2-associated chemokine receptors was followed up with real-time PCR for CCR3, which indicated that facial nerve injury increases CCR3 mRNA levels in mouse facial motor nucleus. Unexpectedly, quantitative- and co-immunofluorescence revealed increased CCR3 expression localizing to FMN in the facial motor nucleus after facial nerve axotomy. Compared with WT (wild-type, a significant decrease in FMN survival 4 weeks after axotomy was observed in CCR3−/− mice. Additionally, compared with WT, a significant decrease in FMN survival 4 weeks after axotomy was observed in Rag2−/− (recombination activating gene-2-deficient mice adoptively transferred CD4+ T-cells isolated from CCR3−/− mice, but not in CCR3−/− mice adoptively transferred CD4+ T-cells derived from WT mice. These results provide a basis for further investigation into the co-operation between CD4+ T-cell- and CCR3-mediated neuroprotection after FMN injury.

  20. CCR5 controls immune and metabolic functions during Toxoplasma gondii infection.

    Directory of Open Access Journals (Sweden)

    Giuliano Bonfá

    Full Text Available CCR5, an important receptor related to cell recruitment and inflammation, is expressed during experimental Toxoplasma gondii infection. However, its role in the immunopathology of toxoplasmosis is not clearly defined yet. Thus, we inoculated WT and CCR5(-/- mice with a sub lethal dose of the parasite by oral route. CCR5(-/- mice were extremely susceptible to infection, presenting higher parasite load and lower tissue expression of IL-12p40, IFN-γ, TNF, IL-6, iNOS, Foxp3, T-bet, GATA-3 and PPARα. Although both groups presented inflammation in the liver with prominent neutrophil infiltration, CCR5(-/- mice had extensive tissue damage with hepatocyte vacuolization, steatosis, elevated serum triglycerides and transaminases. PPARα agonist Gemfibrozil improved the vacuolization but did not rescue CCR5(-/- infected mice from high serum triglycerides levels and enhanced mortality. We also found intense inflammation in the ileum of CCR5(-/- infected mice, with epithelial ulceration, augmented CD4 and decreased frequency of NK cells in the gut lamina propria. Most interestingly, these findings were accompanied by an outstanding accumulation of neutrophils in the ileum, which seemed to be involved in the gut immunopathology, once the depletion of these cells was accompanied by reduced local damage. Altogether, these data demonstrated that CCR5 is essential to the control of T. gondii infection and to maintain the metabolic, hepatic and intestinal integrity. These findings add novel information on the disease pathogenesis and may be relevant for directing future approaches to the treatment of multi-deregulated diseases.

  1. 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.

  2. 76 FR 66932 - The National Cancer Institute (NCI) Announces the Initiation of a Public Private Industry...

    Science.gov (United States)

    2011-10-28

    ... Initiation of a Public Private Industry Partnership on Translation of Nanotechnology in Cancer (TONIC) To Promote Translational Research and Development Opportunities of Nanotechnology-Based Cancer Solutions... industry partnership called TONIC (Translation Of Nanotechnology In Cancer) to promote...

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

    Science.gov (United States)

    ... pharynx, and larynx) and increased for four others (cancer of the pancreas, liver, melanoma, and soft tissue including heart) (see ... cavity and pharynx, and gallbladder) and increased for cancers of the pancreas, liver, and uterus. 9. If cancer death rates ...

  4. Lung cancer multidisciplinary team meetings: a survey of participants at a national conference

    International Nuclear Information System (INIS)

    Full text: Multidisciplinary meetings (MDMs) are a useful aid for the development of comprehensive treatment plans for cancer patients. However, little is known about the requirements for effective MDM function. Attendees at a national lung cancer conference who participated at least weekly in lung cancer MDMs were surveyed. The survey addressed the attendees' perceptions regarding the aims of MDMs, and for their own institutional MDMs, the importance and need for improvement for each of: (i) the attendance of nine discipline groups; and (ii) 15 aspects related to MDM function derived from the literature. The survey also asked participants if MDMs met their needs. There was a general agreement on the aims of the meetings. There was also an agreement on the importance of various groups' attendance and each of the examined aspects of MDMs. However, many respondents reported their meetings required moderate or substantial improvements in one or more areas. More than 20% of the respondents indicated improvement was required for the attendance of three discipline groups (palliative care physicians, pathologists and cardiothoracic surgeons) and 10 of the 15 examined aspects (more than half in the case of computerised databases). Only 9% of the respondents reported that none of the features surveyed needed either moderate or substantial improvement. MDMs met the needs of 79% of the respondents. We found general agreement on the aims of the meetings, the importance of various groups' attendance at MDMs and each of the examined aspects of MDMs. However, moderate or substantial improvements were thought to be required by many respondents. The performance of individual institutions' MDMs and the resources they have available to achieve their aims should be assessed and periodically reviewed. The survey applied here may provide a framework for MDM members to do this.

  5. 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

  6. 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.

  7. Staging cancer of the uterus: A national audit of MRI accuracy

    International Nuclear Information System (INIS)

    Aim: To report the results of a nationwide audit of the accuracy of magnetic resonance imaging (MRI) staging in uterine body cancer when staging myometrial invasion, cervical extension, and lymph node spread. Materials and methods: All UK radiology departments were invited to participate using a web-based tool for submitting anonymized data for a 12 month period. MRI staging was compared with histopathological staging using target accuracies of 85, 86, and 70% respectively. Results: Of the departments performing MRI staging of endometrial cancer, 37/87 departments contributed. Targets for MRI staging were achieved for two of the three standards nationally with diagnostic accuracy for depth of myometrial invasion, 82%; for cervical extension, 90%; and for pelvic nodal involvement, 94%; the latter two being well above the targets. However, only 13/37 (35%) of individual centres met the target for assessing depth of myometrial invasion, 31/36 (86%) for cervical extension and 31/34 (91%) for pelvic nodal involvement. Statistical analysis demonstrated no significant difference for the use of intravenous contrast medium, but did show some evidence of increasing accuracy in assessment of depth of myometrial invasion with increasing caseload. Conclusion: Overall performance in the UK was good, with only the target for assessment of depth of myometrial invasion not being met. Inter-departmental variation was seen. One factor that may improve performance in assessment of myometrial invasion is a higher caseload. No other clear factor to improve performance were identified.

  8. Treatment of T3 laryngeal cancer in the Netherlands: a national survey

    International Nuclear Information System (INIS)

    Treatment strategies for T3 laryngeal carcinoma include radiotherapy (RT) with or without chemotherapy (CT) and sometimes surgery. We conducted a national survey to determine how T3 laryngeal carcinoma is currently being managed in the Netherlands. A questionnaire on general treatment policy, also inquiring details on RT and CT, was sent to all 13 radiotherapy departments accredited for treatment of head and neck cancer (HNC) in the Netherlands. Twelve centers completed the questionnaire. All centers reported using RT with or without CT. Upfront laryngectomy is rarely performed. At 9/12 centers, CT is added to RT in cases with large tumors in T3N0 disease. Three centers use a volume criterion (3–6 cc); 6 centers don’t specify “large” with such criteria. CT consists of cisplatin 3-weekly (7 centers) or weekly (2 centers), unless contra-indicated or age; 6 centers use an age limit of 70 years. RT is given concomitantly with CT 5×/week except at the 2 centers where cisplatin weekly is combined with 6 fractions/week. In case of RT only, treatment is accelerated. Lymph node levels II-IV are treated electively. In T3N+ disease, 11/12 centers treat non-bulky T3N1 with RT only. Volume criteria for combined CT-RT are the same as above. Two centers perform an upfront neck dissection in case of (resectable) N3 disease; 10 centers treat T3N2-3 cancer with primary CT-RT, 2 centers don’t use the N-stage criterion. Total RT dose is 68–70 Gy, the elective dose varies between 46 and 57.75 Gy. Eight centers use a simultaneous integrated boost technique. Treatment of T3 laryngeal cancer in the Netherlands is generally comparable, with CT-RT for voluminous T3N0 and most T3N+ tumors, but there are some differences between the centers in the use of chemotherapy and the dose-fractionation schemes. Therefore, the aim of the National Platform RT HNC is further standardization of RT dose, fractionation and delivery techniques

  9. Prevalence and Predictors of Neoadjuvant Therapy for Stage IIIA Non-Small Cell Lung Cancer in the National Cancer Database: Importance of Socioeconomic Status and Treating Institution

    International Nuclear Information System (INIS)

    Purpose: The optimal locoregional therapy for stage IIIA non-small cell lung cancer (NSCLC) is controversial, with definitive chemoradiation therapy (CRT) and neoadjuvant therapy followed by surgery (NT-S) serving as competing strategies. In this study, we used the National Cancer Database to determine the prevalence and predictors of NT in a large, modern cohort of patients. Methods and Materials: Patients with stage IIIA NSCLC treated with CRT or NT-S between 2003 and 2010 at programs accredited by the Commission on Cancer were included. Predictors were categorized as clinical, time/geographic, socioeconomic, and institutional. In accord with the National Cancer Database, institutions were classified as academic/research program and as comprehensive and noncomprehensive community cancer centers. Logistic regression and random effects multilevel logistic regression were performed for univariable and multivariable analyses, respectively. Results: The cohort consisted of 18,581 patients, 3,087 (16.6%) of whom underwent NT-S (10.6% induction CRT, 6% induction chemotherapy). The prevalence of NT-S was constant over time, but there were significant relative 31% and 30% decreases in pneumonectomy and right-sided pneumonectomy, respectively, over time (P trend <.02). In addition to younger age, lower T stage, and favorable comorbidity score, indicators of higher socioeconomic status were strong independent predictors of NT-S, including white race, higher income, and private/managed insurance. The type of institution (academic/research program vs comprehensive or noncomprehensive community cancer centers, odds ratio 1.54 and 2.08, respectively) strongly predicted NT-S, but treatment volume did not. Conclusions: Neoadjuvant therapy followed by surgery was an uncommon treatment approach in Commission on Cancer programs, and the prevalence of postinduction pneumonectomy decreased over time. Higher socioeconomic status and treatment at academic institutions were significant

  10. Colon cancer - resources

    Science.gov (United States)

    Resources - colon cancer ... The following organizations are good resources for information on colon cancer : American Cancer Society -- www.cancer.org/cancer/colonandrectumcancer/index Colon Cancer Alliance -- www.ccalliance.org National ...

  11. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Types Adolescents and Young Adults with Cancer Reports, Research, and Literature Quiz Cancers by Body Location/ ... the Precision Medicine Initiative® Cancer Moonshot Progress Annual Report to the Nation Cancer Snapshots Milestones in Cancer ...

  12. Evaluation of the Definitions of “High-Risk” Cutaneous Squamous Cell Carcinoma Using the American Joint Committee on Cancer Staging Criteria and National Comprehensive Cancer Network Guidelines

    OpenAIRE

    Melinda B. Chu; Slutsky, Jordan B.; Dhandha, Maulik M.; Beal, Brandon T.; Armbrecht, Eric S.; Walker, Ronald J.; Varvares, Mark A.; Fosko, Scott W.

    2014-01-01

    Recent guidelines from the American Joint Committee on Cancer (AJCC) and National Comprehensive Cancer Network (NCCN) have been proposed for the assessment of “high-risk” cutaneous squamous cell carcinomas (cSCCs). Though different in perspective, both guidelines share the common goals of trying to identify “high-risk” cSCCs and improving patient outcomes. Thus, in theory, both definitions should identify a similar proportion of “high-risk” tumors. We sought to evaluate the AJCC and NCCN d...

  13. 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…

  14. NCI QuitPal, an App from the National Cancer Institute | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... page please turn Javascript on. NCI QuitPal, an App from the National Cancer Institute Past Issues / Winter ... a cigarette? NCI QuitPal is a free, interactive app for iPhone or iPad that uses proven quit ...

  15. The National Cancer Institute of Canada Clinical Trials Group MAP.3 trial: an international breast cancer prevention trial

    OpenAIRE

    Pater, J.; Richardson, H.; Johnston, D.; Goss, Paul E.

    2007-01-01

    Several large phase iii trials have demonstrated that tamoxifen—and more recently, raloxifene—can effectively reduce the incidence of invasive breast cancer by 50%. However, these selective estrogen receptor modulators can also be associated with several rare, but serious, adverse events. Recently, the third-generation aromatase inhibitors (AIS) have demonstrated excellent efficacy in adjuvant breast cancer trials, and they show particular promise in the breast cancer prevention setting. The ...

  16. Design of a Base Station for MEMS CCR Localization in an Optical Sensor Network

    Directory of Open Access Journals (Sweden)

    Chan Gook Park

    2014-05-01

    Full Text Available This paper introduces a design and implementation of a base station, capable of positioning sensor nodes using an optical scheme. The base station consists of a pulse laser module, optical detectors and beam splitter, which are mounted on a rotation-stage, and a Time to Digital Converter (TDC. The optical pulse signal transmitted to the sensor node with a Corner Cube Retro-reflector (CCR is reflected to the base station, and the Time of Flight (ToF data can be obtained from the two detectors. With the angle and flight time data, the position of the sensor node can be calculated. The performance of the system is evaluated by using a commercial CCR. The sensor nodes are placed at different angles from the base station and scanned using the laser. We analyze the node position error caused by the rotation and propose error compensation methods, namely the outlier sample exception and decreasing the confidence factor steadily using the recursive least square (RLS methods. Based on the commercial CCR results, the MEMS CCR is also tested to demonstrate the compatibility between the base station and the proposed methods. The result shows that the localization performance of the system can be enhanced with the proposed compensation method using the MEMS CCR.

  17. Design of a base station for MEMS CCR localization in an optical sensor network.

    Science.gov (United States)

    Park, Chan Gook; Jeon, Hyun Cheol; Kim, Hyoun Jin; Kim, Jae Yoon

    2014-01-01

    This paper introduces a design and implementation of a base station, capable of positioning sensor nodes using an optical scheme. The base station consists of a pulse laser module, optical detectors and beam splitter, which are mounted on a rotation-stage, and a Time to Digital Converter (TDC). The optical pulse signal transmitted to the sensor node with a Corner Cube Retro-reflector (CCR) is reflected to the base station, and the Time of Flight (ToF) data can be obtained from the two detectors. With the angle and flight time data, the position of the sensor node can be calculated. The performance of the system is evaluated by using a commercial CCR. The sensor nodes are placed at different angles from the base station and scanned using the laser. We analyze the node position error caused by the rotation and propose error compensation methods, namely the outlier sample exception and decreasing the confidence factor steadily using the recursive least square (RLS) methods. Based on the commercial CCR results, the MEMS CCR is also tested to demonstrate the compatibility between the base station and the proposed methods. The result shows that the localization performance of the system can be enhanced with the proposed compensation method using the MEMS CCR. PMID:24815681

  18. The functions of DNA methylation by CcrM in Caulobacter crescentus: a global approach.

    Science.gov (United States)

    Gonzalez, Diego; Kozdon, Jennifer B; McAdams, Harley H; Shapiro, Lucy; Collier, Justine

    2014-04-01

    DNA methylation is involved in a diversity of processes in bacteria, including maintenance of genome integrity and regulation of gene expression. Here, using Caulobacter crescentus as a model, we exploit genome-wide experimental methods to uncover the functions of CcrM, a DNA methyltransferase conserved in most Alphaproteobacteria. Using single molecule sequencing, we provide evidence that most CcrM target motifs (GANTC) switch from a fully methylated to a hemi-methylated state when they are replicated, and back to a fully methylated state at the onset of cell division. We show that DNA methylation by CcrM is not required for the control of the initiation of chromosome replication or for DNA mismatch repair. By contrast, our transcriptome analysis shows that >10% of the genes are misexpressed in cells lacking or constitutively over-expressing CcrM. Strikingly, GANTC methylation is needed for the efficient transcription of dozens of genes that are essential for cell cycle progression, in particular for DNA metabolism and cell division. Many of them are controlled by promoters methylated by CcrM and co-regulated by other global cell cycle regulators, demonstrating an extensive cross talk between DNA methylation and the complex regulatory network that controls the cell cycle of C. crescentus and, presumably, of many other Alphaproteobacteria.

  19. CCR5 deficiency predisposes to fatal outcome in influenza virus infection.

    Science.gov (United States)

    Falcon, A; Cuevas, M T; Rodriguez-Frandsen, A; Reyes, N; Pozo, F; Moreno, S; Ledesma, J; Martínez-Alarcón, J; Nieto, A; Casas, I

    2015-08-01

    Influenza epidemics affect all age groups, although children, the elderly and those with underlying medical conditions are the most severely affected. Whereas co-morbidities are present in 50% of fatal cases, 25-50% of deaths are in apparently healthy individuals. This suggests underlying genetic determinants that govern infection severity. Although some viral factors that contribute to influenza disease are known, the role of host genetic factors remains undetermined. Data for small cohorts of influenza-infected patients are contradictory regarding the potential role of chemokine receptor 5 deficiency (CCR5-Δ32 mutation, a 32 bp deletion in the CCR5 gene) in the outcome of influenza virus infection. We tested 171 respiratory samples from influenza patients (2009 pandemic) for CCR5-Δ32 and evaluated its correlation with patient mortality. CCR5-Δ32 patients (17.4%) showed a higher mortality rate than WT individuals (4.7%; P = 0.021), which indicates that CCR5-Δ32 patients are at higher risk than the normal population of a fatal outcome in influenza infection.

  20. HIV-1 adaptation to low levels of CCR5 results in V3 and V2 loop changes that increase envelope pathogenicity, CCR5 affinity and decrease susceptibility to Maraviroc.

    Science.gov (United States)

    Garg, Himanshu; Lee, Raphael T C; Maurer-Stroh, Sebastian; Joshi, Anjali

    2016-06-01

    Variability in CCR5 levels in the human population is suggested to affect virus evolution, fitness and the course of HIV disease. We previously demonstrated that cell surface CCR5 levels directly affect HIV Envelope mediated bystander apoptosis. In this study, we attempted to understand HIV evolution in the presence of low levels of CCR5, mimicking the limiting CCR5 levels inherent to the host. HIV-1 adaptation in a T cell line expressing low levels of CCR5 resulted in two specific mutations; N302Y and E172K. The N302Y mutation led to accelerated virus replication, increase in Maraviroc IC50 and an increase in Envelope mediated bystander apoptosis in low CCR5 expressing cells. Analysis of subtype B sequences showed that N302Y is over-represented in CXCR4 tropic viruses in comparison to CCR5 tropic isolates. Considering the variability in CCR5 levels between individuals, our findings have implications for virus evolution, MVC susceptibility as well as HIV pathogenesis.

  1. Detection and analysis of mutation of CCR5 in the Kazak population in Xinjiang%新疆哈萨克族人群CCR5基因多态性的调查及分析

    Institute of Scientific and Technical Information of China (English)

    盛磊; 殷勤; 常生军; 曹文疆; 杨军; 谭晓华; 周迪

    2012-01-01

    目的 研究新疆哈萨克族人群中,艾滋病病毒(HIV)辅助趋化因子受体CCR5△32、CCR5-894C等位基因突变的频率和多态性的特点.方法 以143例哈萨克族健康人群为研究对象,应用聚合酶链反应(Polymerase chain reaction,PCR)及脱氧核糖核酸(Deoxyribonucleic acid,DNA)直接测序等方法,检测CCR5和CCR5△32、CCR5-894C突变体.结果 143例个体中,CCR5△32扩增分析和CCR5-894C缺失扩增分析结果,均未发现有等位基因突变,均为野生型CCR5.结论 由于例数过少,有必要进一步增加样本量,以确定哈萨克族人群是否对HIV有较高的遗传易感性,为有关部门制定相关政策提供准确的依据.%Objective To study the frequency and polymorphism of HIV co-receptor CCR5 delta 32, CCR5-894C in the Xinjiang Kazak population. Methods CCR5 and CCR5 delta 32 and CCR5-894C mutation were tested among 143 Kazak healthy subjects by using PCR and were further confirmed by DNA sequencing analyses. Results No mutant of allele in CCR5 delta 32 was found in the 143 tested units, and all belonged to the wild type. Conclusion The sample size tested is too small. It is necessary to further increase sample size in order to identify whether the Kazak population has a high genetic susceptibility.

  2. Cellular based cancer vaccines

    DEFF Research Database (Denmark)

    Hansen, Morten; Met, O; Svane, I M;

    2012-01-01

    Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor...... in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....

  3. Detection for mutation of HIV coreceptor CCR5 in Zhuang population from Guangxi Zhuang Autonomous Region of China%广西壮族人群HIV协同受体CCR5基因突变的检测

    Institute of Scientific and Technical Information of China (English)

    杨海波; 樊晓晖; 陆海融; 赖振屏; 梁纲

    2005-01-01

    目的了解广西壮族人群中HIV协同受体CCR5△32等位基因突变频率和多态性的特点,为评估广西壮族人群对HIV的遗传易感性和艾滋病的防治提供理论依据.方法以152例壮族大学生为研究对象,应用PCR和DNA直接测序等方法检测CCR5及CCR5△32突变体.结果未发现CCR5△32等位基因.结论由于未发现CCR5△32,推测广西壮族人群对HIV-1病毒感染可能具有较大的遗传易感性.

  4. Analysis of Hypoxic regulated CCR5 chemokine receptor promoter region expression%缺氧调控人趋化因子受体CCR5启动子区的表达分析

    Institute of Scientific and Technical Information of China (English)

    万抒颖; 张陆勇; 袁胜涛

    2009-01-01

    目的:分析人趋化因子受体5(CCR5)基因启动子区序列在缺氧条件下的表达.方法:构建CCR5基因启动子区萤光素酶报告基因载体,转染入MDA-MB-435细胞中,检测分析其双萤光素酶活性.结果:CCR5基因启动子区的pGL3重组质粒在缺氧条件下的MDA-MB-435细胞中能表现出明显的萤光素酶海性.结论:CCR5基因启动区序列中存在缺氧诱导CCR5基因转录的主要上调元件.

  5. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Timm, Sally; Wang, August G;

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission......-onset schizophrenia) and healthy subjects differed significantly. This was reflected in an increased frequency of the deletion allele in the patient subgroup. Patients with ages at first admission below and above 40 years significantly differed in distribution of genotypes and alleles, with an overrepresentation...... of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without...

  6. Resistance to the CCR5 inhibitor 5P12-RANTES requires a difficult evolution from CCR5 to CXCR4 coreceptor use.

    Directory of Open Access Journals (Sweden)

    Rebecca Nedellec

    Full Text Available Viral resistance to small molecule allosteric inhibitors of CCR5 is well documented, and involves either selection of preexisting CXCR4-using HIV-1 variants or envelope sequence evolution to use inhibitor-bound CCR5 for entry. Resistance to macromolecular CCR5 inhibitors has been more difficult to demonstrate, although selection of CXCR4-using variants might be expected. We have compared the in vitro selection of HIV-1 CC1/85 variants resistant to either the small molecule inhibitor maraviroc (MVC or the macromolecular inhibitor 5P12-RANTES. High level resistance to MVC was conferred by the same envelope mutations as previously reported after 16-18 weeks of selection by increasing levels of MVC. The MVC-resistant mutants were fully sensitive to inhibition by 5P12-RANTES. By contrast, only transient and low level resistance to 5P12-RANTES was achieved in three sequential selection experiments, and each resulted in a subsequent collapse of virus replication. A fourth round of selection by 5P12-RANTES led, after 36 weeks, to a "resistant" variant that had switched from CCR5 to CXCR4 as a coreceptor. Envelope sequences diverged by 3.8% during selection of the 5P12-RANTES resistant, CXCR4-using variants, with unique and critical substitutions in the V3 region. A subset of viruses recovered from control cultures after 44 weeks of passage in the absence of inhibitors also evolved to use CXCR4, although with fewer and different envelope mutations. Control cultures contained both viruses that evolved to use CXCR4 by deleting four amino acids in V3, and others that maintained entry via CCR5. These results suggest that coreceptor switching may be the only route to resistance for compounds like 5P12-RANTES. This pathway requires more mutations and encounters more fitness obstacles than development of resistance to MVC, confirming the clinical observations that resistance to small molecule CCR5 inhibitors very rarely involves coreceptor switching.

  7. Exploring a model of human chemokine receptor CCR2 in presence of TAK779: A membrane based molecular dynamics study

    Science.gov (United States)

    Balupuri, Anand; Sobhia, M. Elizabeth

    2014-04-01

    Chemokine receptor 2 (CCR2) is a G-protein coupled receptor (GPCR) and a crucial target for various inflammation-driven diseases. In the present study, molecular docking and molecular dynamics simulations were performed on a CCR2 homology model. This work includes the comparative MD simulations of uncomplexed and ‘antagonist-complexed’ CCR2 models. These simulations yield insights into the binding mechanism of antagonist TAK779 and improve the understanding of various structural changes induced by the ligand in the CCR2 protein. Here, one 20 ns MD simulation was carried out on the uncomplexed CCR2 model in lipid bilayer to explore the effects of lipid membrane on the protein. Another 20 ns MD simulation was performed under the similar conditions on the docked CCR2-TAK779 complex. An alteration in the position and orientation of the ligand in binding site was observed after the simulation. Examination of protein-ligand complex suggested that TAK779 produced a greater structural change on the TM-III, TM-IV, TM-V and TM-VI than TM-I, TM-II and TM-VII. Interaction networks involving the conserved residues of uncomplexed and ‘antagonist-complexed’ CCR2 models were also examined. The major difference was observed to be the role of conserved residues of the DRY motif of TM-III and the NPxxY motif of TM-VII of CCR2.

  8. R5 human immunodeficiency virus type 1 infection of fetal thymic organ culture induces cytokine and CCR5 expression.

    NARCIS (Netherlands)

    Choudhary, S.K.; Choudhary, N.R.; Kimbrell, K.C.; Colasanti, J.; Ziogas, A.; Kwa, D.; Schuitemaker, H.; Camerini, D.

    2005-01-01

    Late-stage CCR5 tropic human immunodeficiency virus type 1 (HIV-1) isolates (R5 HIV-1) can deplete nearly all CD4+ thymocytes from human thymus/liver grafts, despite the fact that fewer than 5% of these cells express CCR5. To resolve this paradox, we studied the replication and cytopathic effects (C

  9. Evidence favoring the involvement of CC chemokine receptor (CCR) 5 in T-lymphocyte accumulation in optic neuritis

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Ransohoff, R M; Jensen, J;

    2003-01-01

    To define the relationships between levels of chemokine receptor (CCR)5+ T-cells in blood and cerebrospinal fluid (CSF) of optic neuritis (ON) and control patients (CON).......To define the relationships between levels of chemokine receptor (CCR)5+ T-cells in blood and cerebrospinal fluid (CSF) of optic neuritis (ON) and control patients (CON)....

  10. CANCER

    Directory of Open Access Journals (Sweden)

    N. Kavoussi

    1973-09-01

    Full Text Available There are many carcinogenetic elements in industry and it is for this reason that study and research concerning the effect of these materials is carried out on a national and international level. The establishment and growth of cancer are affected by different factors in two main areas:-1 The nature of the human or animal including sex, age, point and method of entry, fat metabolism, place of agglomeration of carcinogenetic material, amount of material absorbed by the body and the immunity of the body.2 The different nature of the carcinogenetic material e.g. physical, chemical quality, degree of solvency in fat and purity of impurity of the element. As the development of cancer is dependent upon so many factors, it is extremely difficult to determine whether a causative element is principle or contributory. Some materials are not carcinogenetic when they are pure but become so when they combine with other elements. All of this creates an industrial health problem in that it is almost impossible to plan an adequate prevention and safety program. The body through its system of immunity protects itself against small amounts of carcinogens but when this amount increases and reaches a certain level the body is not longer able to defend itself. ILO advises an effective protection campaign against cancer based on the Well –equipped laboratories, Well-educated personnel, the establishment of industrial hygiene within factories, the regular control of safety systems, and the implementation of industrial health principles and research programs.

  11. 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. PMID:27619249

  12. 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.

  13. A Role for the Chemokine Receptor CCR6 in Mammalian Sperm Motility and Chemotaxis

    Science.gov (United States)

    Caballero-Campo, Pedro; Buffone, Mariano G.; Benencia, Fabian; Conejo-García, José R.; Rinaudo, Paolo F.; Gerton, George L.

    2013-01-01

    Although recent evidence indicates that several chemokines and defensins, well-known as inflammatory mediators, are expressed in the male and female reproductive tracts, the location and functional significance of chemokine networks in sperm physiology and sperm reproductive tract interactions are poorly understood. To address this deficiency in our knowledge, we examined the expression and function in sperm of CCR6, a receptor common to several chemoattractant peptides, and screened several reproductive tract fluids for the presence of specific ligands. CCR6 protein is present in mouse and human sperm and mainly localized in the sperm tail with other minor patterns in sperm from mice (neck and acrosomal region) and men (neck and midpiece regions). As expected from the protein immunoblotting and immunofluorescence results, mouse Ccr6 mRNA is expressed in the testis. Furthermore, the Defb29 mRNA encoding the CCR6 ligand, β-defensin DEFB29, is expressed at high levels in the epididymis. As determined by protein chip analysis, several chemokines (including some that act through CCR6, such as CCL20/MIP-3α (formerly Macrophage Inflammatory Protein 3α) and protein hormones were present in human follicular fluid, endometrial secretions, and seminal plasma. In functional chemotaxis assays, capacitated human sperm exhibited a directional movement towards CCL20, and displayed modifications in motility parameters. Our data indicate that chemokine ligand/receptor interactions in the male and female genital tracts promote sperm motility and chemotaxis under non-inflammatory conditions. Therefore, some of the physiological reactions mediated by CCR6 ligands in male reproduction extend beyond a pro-inflammatory response and might find application in clinical reproduction and/or contraception. PMID:23765988

  14. Brain imaging in lung cancer patients without symptoms of brain metastases: a national survey of current practice in England

    International Nuclear Information System (INIS)

    Aim: To determine current practice regarding brain imaging for newly diagnosed lung cancer patients without symptoms of brain metastases. Materials and methods: A survey questionnaire was sent by e-mail to all the lung cancer lead clinicians in England currently on the National Cancer Intelligence Network database. The survey asked whether brain imaging was used in new lung cancer patients without symptoms or signs to suggest brain metastases; and if so, which patient subgroups were imaged according to cell type, stage of disease, and intention to treat, and which techniques were used to image these patients. Responses were received between February and May 2014. Results: Fifty-nine of 154 centres replied to the survey (38%). Thirty of the 59 centres (51%) did not image the brain in these patients. Twenty-nine of the 59 (49%) centres imaged the brain in at least certain subgroups. Of those centres that did image the brain 21 (72%) used CT as the first-line imaging technique and six (20%) used MRI. Twenty-five of 59 (42%) centres stated that the 2011 NICE guidelines had led to a change in their practice. Conclusion: There is wide variation in practice regarding brain imaging in this patient group in England, with no brain imaging at all in approximately half of centres and a spectrum of imaging in the other half. When the brain is imaged, CT is the technique most commonly used. The 2011 NICE guidelines have led to some change in practice but not to national uniformity. - Highlights: • Ascertain current practice in brain imaging for staging asymptomatic lung cancer patients. • Survey questionnaire sent to all the lung cancer lead clinicians in England. • Wide variation in practice with regard to brain imaging in this patient group. • No brain imaging at all in approximately half of centres and a spectrum of imaging in the other half • The 2011 NICE guidelines have led to some change in practice but not to national uniformity

  15. CCR1, an enzyme required for lignin biosynthesis in Arabidopsis, mediates cell proliferation exit for leaf development

    DEFF Research Database (Denmark)

    Xue, Jingshi; Luo, Dexian; Xu, Deyang;

    2015-01-01

    exit in leaves. CCR1 is expressed basipetally in the leaf, and ccr1 mutants exhibited multiple abnormalities, including increased cell proliferation. The ccr1 phenotypes are not due to the reduced lignin content, but instead are due to the dramatically increased level of ferulic acid (FeA......), an intermediate in lignin biosynthesis. FeA is known to have antioxidant activity, and the levels of reactive oxygen species (ROS) in ccr1 were markedly reduced. We also characterized another double mutant in CAFFEIC ACID O-METHYLTRANSFERASE (comt) and CAFFEOYL CoA 3-O-METHYLTRANSFERASE (ccoaomt), in which the FeA...... level was dramatically reduced. Cell proliferation in comt ccoaomt leaves was decreased, accompanied by elevated ROS levels, and the mutant phenotypes were partially rescued by treatment with FeA or another antioxidant (N-acetyl-L-cysteine). Taken together, our results suggest that CCR1, FeA and ROS...

  16. 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.

  17. Extracellular HIV Tat and Tat cysteine rich peptide increase CCR5 expression in monocytes

    Institute of Scientific and Technical Information of China (English)

    ZHENG Lin; YANG Yi-da; LU Guo-cai; SALVATO Maria S

    2005-01-01

    In our previous work we reported that HIV Tat and 6 cysteine rich peptides of Tat induce tumor necrosis factor-related apoptosis-induced ligand (TRAIL) in human monocytes (Yang et al., 2003). Here our results showed that HIV Tat and Tat cysteine rich peptide increase CCR5 expression in human monocytes, and this activity is inhibited by rabbit anti-Tat. Boiled Tat does not increase CCR5 expression in monocytes. These results provide insight into a new mechanism by which HIV Tat plays a key role in the pathogenesis of HIV-1 infection.

  18. 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

    better accommodated in the receptors than polar groups. The new analog brominated terpyridine (29) resulted in the highest chelator potencies observed so far CCR1 (EC50: 0.49 μM) and CCR8 (EC50: 0.28 μM). Furthermore, we identified the first selective CCR5 agonist chelator, meta dithiomethylated...

  19. Common promoter deletion is associated with 3.9-fold differential transcription of ovine CCR5 and reduced proviral level of ovine progressive pneumonia virus

    Science.gov (United States)

    CCR5 is a chemokine receptor that regulates immune cell recruitment in inflammation and serves as a coreceptor for human immunodeficiency virus (HIV). A human CCR5 coding deletion (termed delta-32) results in strong resistance to HIV infection, and polymorphisms in CCR5 regulatory regions have been ...

  20. 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.

  1. The Bone Marrow Transplantation Center of the National Cancer Institute - its resources to assist patients with bone marrow failure

    International Nuclear Information System (INIS)

    This paper describes the bone marrow transplantation center of the brazilian National Cancer Institute, which is responsible for the cancer control in Brazil. The document also describes the resources available in the Institute for assisting patients presenting bone marrow failures. The Center provides for allogeneic and autologous bone marrow transplants, peripheral stem cell transplants, umbilical cord collections and transplants, and a small experience with unrelated bone marrow transplants. The Center receives patient from all over the country and provides very sophisticated medical care at no direct cost to the patients

  2. Teenagers and young adults with cancer in Europe: from national programmes to a European integrated coordinated project

    DEFF Research Database (Denmark)

    Stark, D; Bielack, S; Brugieres, L;

    2016-01-01

    Over 14 000 patients aged 15-24 are estimated to be diagnosed with cancer in the European Union (EU) each year. Teenagers and young adults (TYA) often fall down gaps between children's and adults cancer services. The specific challenges of providing optimal care to them are described, but we...... present a summary of recent progress. Progress to overcome these challenges is happening at different rates across Europe. We summarise the European national projects in this field but more recently we have seen the beginnings of European coordination. Within the EU 7th Funding Programme (FP7) European...

  3. The role of the N-terminal segment of CCR5 in HIV-1 Env-mediated membrane fusion and the mechanism of virus adaptation to CCR5 lacking this segment

    Directory of Open Access Journals (Sweden)

    Kabat David

    2007-08-01

    Full Text Available Abstract Background HIV-1 envelope glycoprotein (Env induces membrane fusion as a result of sequential binding to CD4 and chemokine receptors (CCR5 or CXCR4. The critical determinants of CCR5 coreceptor function are the N-terminal domain (Nt and the second extracellular loop. However, mutations in gp120 adapt HIV-1 to grow on cells expressing the N-terminally truncated CCR5(Δ18 (Platt et al., J. Virol. 2005, 79: 4357–68. Results We have functionally characterized the adapted Env (designated Env(NYP using a quantitative cell-cell fusion assay. The rate of fusion with target cells expressing wild-type CCR5 and the resistance to fusion inhibitors was virtually identical for wild-type Env and Env(NYP, implying that the coreceptor affinity had not increased as a result of adaptation. In contrast, Env(NYP-induced fusion with cells expressing CCR5(Δ18 occurred at a slower rate and was extremely sensitive to the CCR5 binding inhibitor, Sch-C. Resistance to Sch-C drastically increased after pre-incubation of Env(NYP- and CCR5(Δ18-expressing cells at a temperature that was not permissive to fusion. This indicates that ternary Env(NYP-CD4-CCR5(Δ18 complexes accumulate at sub-threshold temperature and that low-affinity interactions with the truncated coreceptor are sufficient for triggering conformational changes in the gp41 of Env(NYP but not in wild-type Env. We also demonstrated that the ability of CCR5(Δ18 to support fusion and infection mediated by wild-type Env can be partially reconstituted in the presence of a synthetic sulfated peptide corresponding to the CCR5 Nt. Pre-incubation of wild-type Env- and CCR5(Δ18-expressing cells with the sulfated peptide at sub-threshold temperature markedly increased the efficiency of fusion. Conclusion We propose that, upon binding the Nt region of CCR5, wild-type Env acquires the ability to productively engage the extracellular loop(s of CCR5 – an event that triggers gp41 refolding and membrane merger

  4. Regional cancer centre demonstrates voluntary conformity with the national Radiation Oncology Practice Standards

    Energy Technology Data Exchange (ETDEWEB)

    Manley, Stephen, E-mail: stephen.manley@ncahs.health.nsw.gov.au; Last, Andrew; Fu, Kenneth; Greenham, Stuart; Kovendy, Andrew; Shakespeare, Thomas P [North Coast Cancer Institute, Lismore, New South Wales (Australia)

    2015-06-15

    Radiation Oncology Practice Standards have been developed over the last 10 years and were published for use in Australia in 2011. Although the majority of the radiation oncology community supports the implementation of the standards, there has been no mechanism for uniform assessment or governance. North Coast Cancer Institute's public radiation oncology service is provided across three main service centres on the north coast of NSW. With a strong focus on quality management, we embraced the opportunity to demonstrate conformity with the Radiation Oncology Practice Standards. The Local Health District's Clinical Governance units were engaged to perform assessments of our conformity with the standards and this was signed off as complete on 16 December 2013. The process of demonstrating conformity with the Radiation Oncology Practice Standards has enhanced the culture of quality in our centres. We have demonstrated that self-assessment utilising trained auditors is a viable method for centres to demonstrate conformity. National implementation of the Radiation Oncology Practice Standards will benefit individual centres and the broader radiation oncology community to improve the service delivered to our patients.

  5. Regional cancer centre demonstrates voluntary conformity with the national Radiation Oncology Practice Standards

    International Nuclear Information System (INIS)

    Radiation Oncology Practice Standards have been developed over the last 10 years and were published for use in Australia in 2011. Although the majority of the radiation oncology community supports the implementation of the standards, there has been no mechanism for uniform assessment or governance. North Coast Cancer Institute's public radiation oncology service is provided across three main service centres on the north coast of NSW. With a strong focus on quality management, we embraced the opportunity to demonstrate conformity with the Radiation Oncology Practice Standards. The Local Health District's Clinical Governance units were engaged to perform assessments of our conformity with the standards and this was signed off as complete on 16 December 2013. The process of demonstrating conformity with the Radiation Oncology Practice Standards has enhanced the culture of quality in our centres. We have demonstrated that self-assessment utilising trained auditors is a viable method for centres to demonstrate conformity. National implementation of the Radiation Oncology Practice Standards will benefit individual centres and the broader radiation oncology community to improve the service delivered to our patients

  6. Genetic variation at chemokine receptor CCR5 in leporids: alteration at the 2nd extracellular domain by gene conversion with CCR2 in Oryctolagus, but not in Sylvilagus and Lepus species.

    Science.gov (United States)

    Carmo, C R; Esteves, P J; Ferrand, N; van der Loo, W

    2006-06-01

    Whereas in its natural host (Sylvilagus sps.) the effects of myxoma virus infections are benign, in European rabbit (Oryctolagus cuniculus), it causes a highly infectious disease with very high mortality rate, known as myxomatosis. There is evidence that, as with HIV-1 virus in human, myxoma virus may use chemokine receptors such as CCR5 of the host target cell for entry and activation of pathways of immune avoidance. We have characterized and compared CCR5 genes of leporid species with different susceptibility levels to myxomatosis. The CCR5 protein of O. cuniculus differs markedly from all those known from other species. The most striking was the replacement of a specific peptide motif of the second extracellular loop (ECL2) by a motif, which in other species characterizes the CCR2 molecules. While absent in Sylvilagus and Lepus species, this CCR2 imposed CCR5-ECL2 alteration was observed in all genomes of 25 European rabbits, representing the subspecies O. cuniculus algirus and O. cuniculus cuniculus. Allelic variation at the rabbit CCR5 locus confirmed that the gene conversion predates the subspecies split (1-2 Ma). PMID:16596402

  7. Regional variations in mortality rates of pancreatic cancer in China:Results from 1990-1992 national mortality survey

    Institute of Scientific and Technical Information of China (English)

    Ke-Xin Chen; Peizhong Peter Wang; Si-Wei Zhang; Lian-Di Li; Feng-Zhu Lu; Xi-Shan Hao

    2003-01-01

    AIM: To examine the regional variations in mortality rates of pancreatic cancer in China.METHODS: Aggregated mortality data of pancreatic cancer were extracted from the 1990-1992 national death of all causes and its mortality survey in China. Age specific and standardized mortality rates were calculated at both national and provincial levels with selected characteristics including sex and residence status.RESULTS: Mortality of pancreatic cancer ranked the ninth and accounted for 1.38 percent of the total malignancy deaths. The crude and age standardized mortality rates of pancreatic cancer in China in the period of 1990-1992 were 1.48/100 000 and 1.30/100 000, respectively. Substantial regional variations in mortality rates across China were observed with adjusted mortality rates ranging from 0.43/100 000 to 3.70/100 000 with an extremal value of 8.7.Urban residents had significant higher pancreatic mortality than rural residents.CONCLUSION: The findings of this study show different mortality rates of this disease and highlight the importance of further investigation on factors, which might contribute to the observed epidemiological patterns.

  8. Cloning and Sequence Analysis of CCR Gene from Mango%芒果 CCR 基因的克隆及其序列分析

    Institute of Scientific and Technical Information of China (English)

    张宇; 张波; 赵志常; 高爱平; 陈业渊; 黄建峰; 党志国; 罗睿雄

    2014-01-01

    为了研究芒果CCR基因在芒果对芒果树抗性的功能。采用传统的RT-PCR和RACE方法从芒果的枝梢中克隆得到了1个参与木质素生物合成的肉桂酰辅酶-A还原酶基因( CCR)的全长cDNA序列,进而对得到的序列采用TMHMM、DNAMAN等软件进行生物信息学分析,发现芒果CCR基因包含编码区、3′和5′非翻译区的长度为1292 bp的cDNA序列,编码305个氨基酸;对跨膜结构域进行了预测,发现该基因无跨膜结构域;蛋白二级结构元件以无规则卷曲和β-螺旋为主;聚类分析发现,该基因与美洲山杨木、油茶等植物的亲缘关系较近,而与百合、橡胶树等亲缘关系较远。从芒果中克隆得到了一个CCR基因,并对其生物信息学进行了分析,为后续转基因工作打下了基础。%In order to study the resistance function of mango of a cinnamoy-CoA reducase ( CCR) gene.CCR was cloned from mango with 3′RACE and 5′RACE method.The characteristics of cDNA sequence was analyzed by software such as DNAMAN ,TMHMM.The bioinformatics analysis on the obtained sequence was showed:CCR gene of mango contains coding region ,3′and 5′untranslated region of length cDNA sequence of 1 292 bp,encoding 305 a-mino acid.The gene without transmembrance by transmembrance domains predicted .The secondary structure of CCR protein had random coil and beta helix .It was found that the gene encoding for the protein had close relation-ship with American aspen wood ,oil-tea camellia ,other distantly relationship with lily ,and rubber tree through phy-logenetic analysis .The CCR gene was cloned from mango and the bioinformatics analysis , laid the groundwork for the follow-up work of transgenic .

  9. 77 FR 57566 - Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review...

    Science.gov (United States)

    2012-09-18

    ...) 250-8793. Correction In the Federal Register of September 11, 2012, in FR Doc. FRL-9726- 8; on page... 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...

  10. 77 FR 55833 - Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review...

    Science.gov (United States)

    2012-09-11

    ... community water system is required by Federal regulations (63 FR 44512, August 19, 1998) to provide to its... AGENCY Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review..., 2012, to listen to stakeholder comments on potential approaches for providing Consumer...

  11. Molecular interaction of a potent nonpeptide agonist with the chemokine receptor CCR8

    DEFF Research Database (Denmark)

    Jensen, Pia C; Nygaard, Rie; Thiele, Stefanie;

    2007-01-01

    ), and N-(1-(3-(2-methoxyphenoxy)benzyl)piperidin-4-yl)-1,2,3,4-tetrahydro-2-oxoquinoline-4-carboxamide (LMD-174)] included several key-residues for nonpeptide antagonists targeting CCR1, -2, and -5. It is noteworthy that a decrease in potency of nearly 1000-fold was observed for all five compounds for...

  12. Association analysis of a CCR5 variant with ewe lifetime production.

    Science.gov (United States)

    A deletion in the promoter region of CCR5 associates with a 50% reduction in proviral concentration (log10 env copies/microgram DNA) of ovine progressive pneumonia virus (OPPV) in sheep blood. Because OPP provirus blood concentrations correlate with the degree of histological lesions in affected ti...

  13. IFN-alpha-induced upregulation of CCR5 leads to expanded HIV tropism in vivo.

    Directory of Open Access Journals (Sweden)

    Cheryl A Stoddart

    2010-02-01

    Full Text Available Chronic immune activation and inflammation (e.g., as manifest by production of type I interferons are major determinants of disease progression in primate lentivirus infections. To investigate the impact of such activation on intrathymic T-cell production, we studied infection of the human thymus implants of SCID-hu Thy/Liv mice with X4 and R5 HIV. X4 HIV was observed to infect CD3(-CD4(+CD8(-CXCR4(+CCR5(- intrathymic T-cell progenitors (ITTP and to abrogate thymopoiesis. R5 HIV, by contrast, first established a nonpathogenic infection of thymic macrophages and then, after many weeks, began to replicate in ITTP. We demonstrate here that the tropism of R5 HIV is expanded and pathogenicity enhanced by upregulation of CCR5 on these key T-cell progenitors. Such CCR5 induction was mediated by interferon-alpha (IFN-alpha in both thymic organ cultures and in SCID-hu mice, and antibody neutralization of IFN-alpha in R5 HIV-infected SCID-hu mice inhibited both CCR5 upregulation and infection of the T-cell progenitors. These observations suggest a mechanism by which IFN-alpha production may paradoxically expand the tropism of R5 HIV and, in so doing, accelerate disease progression.

  14. Association analysis of a CCR5 variant with ewe lifetime production in 3 breeds of sheep.

    Science.gov (United States)

    A deletion in the promoter region of CCR5 associates with a 50% reduction in proviral concentration (log10 env copies/microgram DNA) of ovine progressive pneumonia virus (OPPV) in blood. Nearly half of all flocks in the U.S. have at least one sheep infected with OPPV. Because OPP provirus concentr...

  15. Up-Regulation of CCR5 and CXCR4 Expression on Human Monocytes by Interferon Gamma

    Institute of Scientific and Technical Information of China (English)

    陆韵; 刘祖强; 陈应华

    2003-01-01

    Chemokine receptors, mainly CCR5 and CXCR4, have been proved to be the important coreceptors in HIV-1 entry.HIV-1 disease progression is, in general, characterized by an initial predominance of CCR5 using macrophage tropic, non-syncytium-inducing (NSI) isolates, switching later to CXCR4 using T-cell tropic, syncytium-inducing (SI) isolates.How this shift occurs and how the shift can be controlled are still unclear.Since patients with rapid decline of T cell counts have constantly high levels of IFN-γ in the sera and lymphoid nodes, we investigated the influence of this cytokine on the expression of the HIV-1 coreceptors CCR5 and CXCR4 on the cell surfaces of human monocytic cell line U937 and promonocyte NB4.IFN-γ could intensively enhance the expression of both, while a low level of CCR5 expression was detected in two cell lines before stimulation.The results of semiquantitative RT-PCR also confirm the up-regulation.As the newly generated X4-strains have been demonstrated to be insensitive to chemokine in some reports, IFN-γ may play an important role in selecting CXCR4-used strains.

  16. Science Letters: Assignment of CCR 7 gene to chicken chromosome 27 by radiation hybrid panel mapping

    Institute of Scientific and Technical Information of China (English)

    TIAN Yong; LU Li-zhi; FU Yan; TAO Zheng-rong; SHEN Jun-da; WANG De-qian; YUAN Ai-ping; YIN Zhao-zheng

    2007-01-01

    The protein encoded by CC chemokine receptor 7 (CCR7) is a member of the G protein-coupled receptor family. This receptor was identified as a gene induced by the Epstein-Barr virus (EBV), and is thought to be a mediator of EBV effects on B lymphocytes. This receptor is expressed in various lymphoid tissues and activates B and T lymphocytes. It has been shown to control the migration of memory T cells to inflamed tissues, as well as stimulate dendritic cell maturation. To map the CCR7 gene in chicken chromosome, a 6000 rads chicken-hamster radiation hybrid panel (ChickRH6) was used. PCR of samples from ChickRH6 revealed that the location of CCR7 gene is linked to the maker SEQ0347 (6 cR away) with LOD score of 16.6 and that the marker SEQ0347 is located on chromosome 27 at 27 cR of RH (radiation hydrid) map. We compared the corresponding human mRNA sequence with the predicted coding sequence of chicken CCR7 gene, and found that the assembled contig shared a high percentage of similarity with that of the human gene.

  17. Jak3 is involved in dendritic cell maturation and CCR7-dependent migration.

    Directory of Open Access Journals (Sweden)

    Ana Rivas-Caicedo

    Full Text Available BACKGROUND: CCR7-mediated signalling is important for dendritic cell maturation and homing to the lymph nodes. We have previously demonstrated that Jak3 participates in the signalling pathway of CCR7 in T lymphocytes. METHODOLOGY AND PRINCIPAL FINDINGS: Here, we used Jak3(-/- mice to analyze the role of Jak3 in CCR7-mediated dendritic cells migration and function. First, we found no differences in the generation of DCs from Jak3(-/- bone marrow progenitors, when compared to wild type cells. However, phenotypic analysis of the bone marrow derived DCs obtained from Jak3(-/- mice showed reduced expression of co-stimulatory molecules compared to wild type (Jak3(+/+. In addition, when we analyzed the migration of Jak3(-/- and Jak3(+/+ mature DCs in response to CCL19 and CCL21 chemokines, we found that the absence of Jak3 results in impaired chemotactic responses both in vitro and in vivo. Moreover, lymphocyte proliferation and contact hypersensitivity experiments showed that DC-mediated T lymphocyte activation is reduced in the absence of Jak3. CONCLUSION/SIGNIFICANCE: Altogether, our data provide strong evidence that Jak3 is important for DC maturation, migration and function, through a CCR7-mediated signalling pathway.

  18. Strengthening breast and cervical cancer control through partnerships: American Indian and Alaska Native Women and the National Breast and Cervical Cancer Early Detection Program.

    Science.gov (United States)

    Espey, David; Castro, Georgina; Flagg, T'Ronda; Landis, Kate; Henderson, Jeffrey A; Benard, Vicki B; Royalty, Janet E

    2014-08-15

    The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) has played a critical role in providing cancer screening services to American Indian and Alaska Native (AI/ANs) women and strengthening tribal screening capacity. Since 1991, the NBCCEDP has funded states, tribal nations, and tribal organizations to develop and implement organized screening programs. The ultimate goal is to deliver breast and cervical cancer screening to women who do not have health insurance and cannot afford to pay for these services. The delivery of clinical services is supported through complementary program efforts such as professional development, public education and outreach, and patient navigation. This article seeks to describe the growth of NBCCEDP's tribal commitment and the unique history and aspects of serving the AI/AN population. The article describes: 1) how this program has demonstrated success in improving screening of AI/AN women; 2) innovative partnerships with the Indian Health Service, state programs, and other organizations that have improved tribal public health infrastructure; and 3) the evolution of Centers for Disease Control and Prevention work with tribal communities. PMID:25099898

  19. Bone Cancer

    Science.gov (United States)

    ... cancer. Surgery is often the main treatment for bone cancer. Other treatments may include amputation, chemotherapy, and radiation therapy. Because bone cancer can come back after treatment, regular follow-up visits are important. NIH: National ...

  20. Expression of CCR5 in peripheral blood mononuclear cells in patients with psoriasis%银屑病患者外周血单个核细胞CCR5的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    黄远忠; 董正蓉; 林伯盛; 马丹晓

    2011-01-01

    目的 研究银屑病患者外周血单个核细胞趋化因子受体5(CCR5)的表达及其与银屑病皮损面积和严重程度指数(PASI)的关系.方法 分离35例中重度寻常型银屑病患者及30例健康对照者外周血单个核细胞(PBMCs),用RT-PCR法测定PBMCs培养前后CCR5 mRNA的表达水平,免疫荧光标记一流式细胞仪检测CCR5阳性细胞比率.结果 治疗前银屑病患者外周血单个核细胞中CCR5 mRNA表达水平明显高于治疗后及健康对照组,并与PASI呈正相关(r=0.516,P<0.05).结论 CCR5可能通过活化与趋化单个核细胞到银屑病皮损而参与了银屑病的发病.%Objective To investigate the expression of CCR5 in the peripheral blood mononuclear cells (PBMCs) in patients with psoriasis and the correlation between CCR5 expression and psoriasis area and severity index (PASI).Methods PBMCs were isolated from 35 moderate to severe psoriasis patients and 30 health control. Expression of CCR5 mRNA and the rate of CCR5 positive cells on PBMC before and after culture was respectively detected by RT-PCR and immunofluorescence marker flow cytometry. Results CCR5 mRNA level in PBMCs from untreated psoriasis patients was higher than those in treated patients and normal controls. CCR5 mRNA expression was positively correlated with PASI (r=0.516,P<0.05). Conclusion Our study suggests that CCR5 may be involved in the pathogenesis of the progression of psoriasis by activating and aggregating mononuclear cells into psoriasis lesions.

  1. Small molecular CCR5 antagonists as HIV inhibitors:a review of recent research%CCR5小分子拮抗剂类抗艾滋病药物研究进展

    Institute of Scientific and Technical Information of China (English)

    刘瑶; 苏靖; 李松

    2007-01-01

    趋化因子受体CCR5是抗艾滋病药物作用的重要靶点之一.目前,已经开发了许多活性强、选择性高的CCR5拮抗剂,其中一部分已进入临床试验阶段.本文对近年来文献报道的CCR5小分子拮抗剂进行综述.

  2. Stillbirth and neonatal death among female cancer survivors: A national cohort study.

    Science.gov (United States)

    Ji, Jianguang; Sundquist, Jan; Sundquist, Kristina

    2016-09-01

    The number of cancer survivors continues to increase worldwide. Many of these survivors have had children of their own. It is less well-known whether radiation therapy or chemotherapy could affect the risk of stillbirth and neonatal death for these children. To explore this research questions, we identified all women diagnosed with cancer between 1958 and 2012 from the Swedish Cancer Register and they were further linked to the Swedish Medical Birth Register to identify their subsequent child birth between 1973 and 2012. Multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals for the association between stillbirth and neonatal death and maternal cancer diagnosis. As compared to the children without maternal cancer, the risk of stillbirth was significantly higher among children of female cancer survivors born within three years after cancer diagnosis with an OR of 1.92 (95% CI 1.03-3.57). The incidence of neonatal death did not show a significant change. For women with more than one pregnancy after cancer diagnosis, the risk of stillbirth and neonatal death was lower for the second child birth compared to the first child birth. Our study suggested that the risk of stillbirth was negatively associated with the time after cancer diagnosis, providing evidence that the adverse effect associated with cancer treatment may diminish with time. PMID:27101797

  3. Possible Association Between the Chemokine Receptor Gene CCR5-Delta32 Mutation and Hepatitis C Virus Pathogenesis

    Directory of Open Access Journals (Sweden)

    Kouka Saad Eldin Abdel-Wahab, **Mohamed Foda, *Magda Abdel

    2004-12-01

    Full Text Available Background: CCR5-Delta32, a 32-base pair deletion of the CC chemokine receptor (CCR5 gene, is associated with slowed human immunodeficiency virus disease progression in heterozygotes and protection against infection in homozygotes between carriers and non-carriers of each genetic variant. The present study investigated the frequency and clinical consequence of the CCR%-Delta32 mutation in Egyptian HCV infected patients. Genomic DNA samples from 150 patients with chronic HCV infection were screened by PCR for the presence of the CCR5-Delta32 polymorphism. One hundred blood donors were used as control population. Results: The frequency of CCR5-Delta32 heterozygosity was 0.67% in chronic hepatitis C virus and 0% in controls. The CCR5-Delta32 allele was not associated with any of the clinical parameters of hepatitis C virus infection. Conclusion: In this study, the frequency of CCR5-Delta32 homozygosity in patients with hepatitis C was similar to controls.

  4. CCR5 Blockade Suppresses Melanoma Development Through Inhibition of IL-6-Stat3 Pathway via Upregulation of SOCS3.

    Science.gov (United States)

    Tang, Qiu; Jiang, Jun; Liu, Jian

    2015-12-01

    In order to understand how tumor cells can escape immune surveillance mechanisms and thus develop antitumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. In our current study, we found that chemokine receptor 5 (CCR5) neutralization resulted in reduced melanoma tumor size, decreased percentage of CD11b+ Gr-1(+) myeloid-derived suppressor cells (MDSCs), and increased proportion of cluster of differentiation (CD)3+ T cells in tumor tissues. Suppressive activity of MDSCs on CD4+ T cells and CD8+ T cell proliferation is significantly inhibited by anti-CCR5 antibody. CCR5 blockade also suppresses interleukin (IL)-6 induction, which in turn deactivates signal transducer and activator of transcription 3 (Stat3) in tumors. Furthermore, the suppressed B16 tumor growth induced by CCR5 blockade is abolished with additional administration of recombinant IL-6. CCR5 blockade also induces suppressor of cytokine signaling 3 (SOCS3) upregulations, and anti-CCR5 antibody fails to suppress expression of phospho-Stat3 (p-Stat3), matrix metallopeptidase 9 (MMP9), and IL-6 in cells transfected with SOCS3 short-interfering RNA (SiRNA). All these data suggest that CCR5 blockade suppresses melanoma development through inhibition of IL-6-Stat3 pathway via upregulation of SOCS3.

  5. Cell-specific RNA aptamer against human CCR5 specifically targets HIV-1 susceptible cells and inhibits HIV-1 infectivity.

    Science.gov (United States)

    Zhou, Jiehua; Satheesan, Sangeetha; Li, Haitang; Weinberg, Marc S; Morris, Kevin V; Burnett, John C; Rossi, John J

    2015-03-19

    The C-C chemokine receptor type 5 (CCR5) is a receptor expressed by T cells and macrophages that serves as a coreceptor for macrophage-tropic HIV-1. Loss of CCR5 is associated with resistance to HIV-1. Here, we combine the live-cell-based SELEX with high-throughput sequencing technology to generate CCR5 RNA aptamers capable of specifically targeting HIV-1 susceptible cells (as small interfering RNA [siRNA] delivery agent) and inhibiting HIV-1 infectivity (as antiviral agent) via block of the CCR5 required for HIV-1 to enter cells. One of the best candidates, G-3, efficiently bound and was internalized into human CCR5-expressing cells. The G-3 specifically neutralized R5 virus infection in primary peripheral blood mononuclear cells, and in vivo generated human CD4(+) T cells with a nanomolar inhibitory concentration 50%. G-3 was also capable of transferring functional siRNAs to CCR5-expressing cells. Collectively, the cell-specific, internalizing, CCR5-targeted aptamers and aptamer-siRNA conjugates offer promise for overcoming some of the current challenges of drug resistance in HIV-1 by providing cell-type- or tissue-specific delivery of various therapeutic moieties.

  6. CCR5-Δ32 Heterozygosity, HIV-1 Reservoir Size, and Lymphocyte Activation in Individuals Receiving Long-term Suppressive Antiretroviral Therapy.

    Science.gov (United States)

    Henrich, Timothy J; Hanhauser, Emily; Harrison, Linda J; Palmer, Christine D; Romero-Tejeda, Marisol; Jost, Stephanie; Bosch, Ronald J; Kuritzkes, Daniel R

    2016-03-01

    We conducted a case-controlled study of the associations of CCR5-Δ32 heterozygosity with human immunodeficiency virus type 1 (HIV-1) reservoir size, lymphocyte activation, and CCR5 expression in 114 CCR5(Δ32/WT) and 177 wild-type CCR5 AIDS Clinical Trials Group participants receiving suppressive antiretroviral therapy. Overall, no significant differences were found between groups for any of these parameters. However, higher levels of CCR5 expression correlated with lower amounts of cell-associated HIV-1 RNA. The relationship between CCR5-Δ32 heterozygosity, CCR5 expression, and markers of HIV-1 persistence is likely to be complex and may be influenced by factors such as the duration of ART.

  7. The effect of the CCR5-delta32 deletion on global gene expression considering immune response and inflammation

    Directory of Open Access Journals (Sweden)

    Hütter Gero

    2011-10-01

    Full Text Available Abstract Background The natural function of the C-C chemokine receptor type 5 (CCR5 is poorly understood. A 32 base pair deletion in the CCR5 gene (CCR5-delta32 located on chromosome 3 results in a non-functional protein. It is supposed that this deletion causes an alteration in T-cell response to inflammation. For example, the presence of the CCR5-delta32 allele in recipients of allografts constitutes as an independent and protective factor associated with a decreased risk of graft-versus-host disease (GVHD and graft rejection. However, the mechanism of this beneficial effect of the deletion regarding GVHD is unknown. In this survey we searched for a CCR5-delta32 associated regulation of critical genes involved in the immune response and the development of GVHD. Methods We examined CD34+ hematopoietic progenitor cells derived from bone marrow samples from 19 healthy volunteers for the CCR5-delta32 deletion with a genomic PCR using primers flanking the site of the deletion. Results 12 individuals were found to be homozygous for CCR5 WT and 7 carried the CCR5-delta32 deletion heterozygously. Global gene expression analysis led to the identification of 11 differentially regulated genes. Six of them are connected with mechanisms of immune response and control: LRG1, CXCR2, CCRL2, CD6, CD7, WD repeat domain, and CD30L. Conclusions Our data indicate that the CCR5-delta32 mutation may be associated with differential gene expression. Some of these genes are critical for immune response, in the case of CD30L probably protective in terms of GVHD.

  8. Expression of chemokine receptors CCR3,CCR5 and CXCR3 on CD4+ T cells in CBA/JxDBA/2 mouse model,selectively induced by IL-4 and IL-10,regulates the embryo resorption rate

    Institute of Scientific and Technical Information of China (English)

    JIANG Pei-juan; ZHAO Ai-min; BAO Shi-min; XIAO Shi-jin; XIONG Miao

    2009-01-01

    Background Chemokines and their receptors have been a research focus in transplantation immunology.Chemokines and their receptors play a role in lymphocyte recruitment and differentiation process.This study aimed to observe whether IL-4 and IL-10 may regulate the expression of chemokine receptors CCR3,CCR5 and CXCR3 on CD4+ T cells in CBA/JxDBA/2 mouse model and to explore the role of CCR3,CCR5,CXCR3 in immune tolerance in pregnancy.Methods The mouse model of spontaneous abortion (CBA/JxDBA/2) and the normal pregnant mouse model (CBA/JxBALB/c) were used.CBA/JxDBA/2 mice were injected with IL-4 (CBA/JxDBA/2-1L-4),IL-4 and IL-10 (CBA/JxDBA/2-1L-4+IL-10),or normal saline (CBA/JxDBA/2-NS) as a control.The expression of CCR3,CCR5 and CXCR3 on CD4+ T cells from mouse peripheral blood was measured by the double-labelled FCM method,and the embryo resorption rate was also examined.Results The embryo resorption rate in the CBA/JxDBA/2 group without any treatment was significantly higher than that in the CBA/JxBALB/c group (17.9% vs 3.7%,P<0.01).The embryo resorption rate in the CBA/JxDBA/2 group immunized with IL-4 or IL-4 together with IL-10 was significantly decreased,compared with that in the control and NS groups respectively.CCR3 expression on CD4+ T cells in the CBA/JxDBA/2 group without any treatment was significantly lower than that in the CBA/JxBALB/c group (0.3738±0.3575 vs 1.2190±0.2772,P<0.01 );both CCR5 (3.0900±1.5603 vs 1.2390±0.6361,P <0.01)and CXCR3 (2.4715±0.9074 vs 0.9200±0.5585,P <0.01 ) expressions on CD4+ T cells of the CBA/JxDBA/2 group without any treatment were significantly higher than those of the CBA/JxBALB/c group.Significant up-regulation of CCR3 and down-regulation of CXCR3 were found in the CBA/JxDBA/2 group treated with IL-4 (CCR3:2.0360±0.6944,CXCR3:1.3510±0.5263,P <0.01) or IL-4 and IL-10 (CCR3:1.8160±1.0947,CXCR3:1.0940±0.7168,P<0.01).Because of the CCR5,IL-4 and IL-10 (1.9400±0.8504 vs 3.0900±1.5603,P <0.05),but

  9. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Laboratory for Cancer Research Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of ... Centers Frederick National Lab Partners & Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes ...

  10. Thyroid cancer in Luxembourg: a national population-based data report (1983–1999)

    International Nuclear Information System (INIS)

    Twenty years after the nuclear accident in Chernobyl (Eastern Europe), there is still a controversial debate concerning a possible effect of the radioactive iodines, especially I-131, on the increase of thyroid carcinomas (TCs) in Western Europe. Time trends in incidence rates of TC in Luxembourg in comparison with other European countries and its descriptive epidemiology were investigated. The population-based data of the national Morphologic Tumour Registry collecting new thyroid cancers diagnosed between 1983 and 1999 at a nation-wide level in the central division of pathology were reviewed and focused on incidence rates of TC. Data from 1990 to 1999 were used to evaluate the distribution by gender, age, histological type, tumour size and the outcome. Out of 310 new thyroid carcinomas diagnosed between 1990 and 1999, 304 differentiated carcinomas (A: 80% papillary; B: 14.5% follicular; C: 3.5% medullary) and 6 anaplastic/undifferentiated TCs (D: 2%) were evaluated. The M/F-ratio was 1:3.2, the mean age 48.3 years (range: 13–92). The overall age-standardized (world population) incidence rates over the two 5-year periods 1990–1994 and 1995–1999 increased from 7.4 per 100,000 to 10.1 per 100,000 in females, from 2.3 per 100,000 to 3.6 per 100,000 in males. Only 3 patients were children or adolescents (1%), the majority of the patients (50%) were between 45 and 69 years of age. The percentage of microcarcinomas (<1 cm) was A: 46.4%, (115/248); B: 13.3%, (6/45); C: 27.3%, (3/11). The unexpected increase of TCs in 1997 was mainly due to the rise in the number of microcarcinomas. The observed 5-year survival rates for both genders were A: 96.0+/-2%; B: 88.9%; C: 90.9%; D: 0%. Prognosis was good in younger patients, worse in males and elderly, and extremely poor for undifferentiated TCs. The increasing incidence rates of TC, especially of the papillary type, seem mainly due to a rise in diagnosed microcarcinomas due to some extent to a change in histologic

  11. Involvement of chemokine receptors in breast cancer metastasis

    Science.gov (United States)

    Müller, Anja; Homey, Bernhard; Soto, Hortensia; Ge, Nianfeng; Catron, Daniel; Buchanan, Matthew E.; McClanahan, Terri; Murphy, Erin; Yuan, Wei; Wagner, Stephan N.; Barrera, Jose Luis; Mohar, Alejandro; Verástegui, Emma; Zlotnik, Albert

    2001-03-01

    Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1α and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells.

  12. 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....

  13. Functional health literacy in Spanish-speaking Latinas seeking breast cancer screening through the National Breast and Cervical Cancer Screening Program

    Directory of Open Access Journals (Sweden)

    Samantha Garbers

    2009-03-01

    Full Text Available Samantha Garbers1, Karen Schmitt2, Anne Marie Rappa2, Mary Ann Chiasson11Public Health Solutions, New York, NY, USA; 2Columbia University Breast Cancer Screening Program, New York, NY, USABackground: This analysis examines the association between functional health literacy and follow-up after mammography among women receiving breast cancer screening at a National Breast and Cervical Cancer Early Detection Program site in New York City that provides universal bilingual case management.Methods: A total of 707 Latinas who spoke Spanish as their primary language completed a survey of health and demographic characteristics and the Test of Functional Health Literacy in Spanish (TOFHLA-S. Survey results were matched with clinical outcome data.Results: Among the survey participants, 98% were foreign-born and 99% had no health insurance. While the study found significant differences in access to health information and past screening behavior, women without adequate health literacy in Spanish were no less likely to receive clinical resolution of abnormal mammograms within 60 days (81.8% overall; n = 110 or to return for a repeat mammogram within 18 months (57.2% overall; n = 697. In fact, among those referred for a Pap test (n = 310, women without adequate health literacy were more likely to receive a Pap test within 60 days of their mammogram than those with adequate health literacy (82% compared to 71%, OR: 1.83, 95% CI: 1.04–3.22.Discussion: The lack of significantly lower follow-up outcomes among women with inadequate and marginal functional health literacy in this population of primary Spanish-speaking Latinas suggests that, once women have accessed screening services, programmatic approaches may exist to mitigate barriers to follow-up and to ensure optimal cancer screening outcomes for women of all literacy levels.Keywords: health literacy, mammography, Latinas, case management, cancer screening

  14. Bringing Breast Cancer Technologies to Market | Poster

    Science.gov (United States)

    CCR research is recognized in novel competition to encourage the commercialization of breast cancer inventions. Editor’s note: This article was originally published in CCR Connections (Volume 8, No. 1). The Breast Cancer Startup Challenge was named one of six finalists in the HHS Innovates Award Competition, and was one of three finalists recognized by HHS Secretary Sylvia Mathews Burwell and Deputy Secretary Bill Corr. For more information on the Challenge, see previous article on the Poster website. Start-up companies are instrumental in bringing the fruits of scientific research to market. Recognizing an opportunity to bring entrepreneurial minds to bear on the diagnosis and treatment of breast cancer, the Avon Foundation for Women partnered with NCI and the Center for Advancing Innovation to launch the Breast Cancer Startup Challenge.

  15. HIV-infected individuals with the CCR delta32/CCR5 genotype have lower HIV RNA levels and higher CD4 cell counts in the early years of the infection than do patients with the wild type. Copenhagen AIDS Cohort Study Group

    DEFF Research Database (Denmark)

    Katzenstein, T L; Eugen-Olsen, J; Hofmann, B;

    1997-01-01

    The relations among serum HIV RNA levels, CD4 cell counts, presence of the mutant CCR5-allele in heterozygous form, and clinical outcome was analyzed in 96 patients from the Copenhagen AIDS Cohort. In the early years of the infection, patients with the CCR5 delta32/CCR5 genotype had significantly...

  16. 稳定表达人CCR5基因CHO细胞系的建立及鉴定%Establishment and characterization of CHO cell line stably expressing human CCR5 gene

    Institute of Scientific and Technical Information of China (English)

    程林; 吴喜林; 袁钟平; 吴稚伟

    2012-01-01

    CCR5 is one of the most important co-receptors required for HIV-I infection and a potential target for anti viral agents. In this study,the eukaryotic expression plasmid pcDNA3.1 CCR5 carrying human CCR5 gene was stably transfected into CHO-K1 cells. After 2 weeks selection by G418, cell clones were selected from limited dilution in 96-well plates,and 22 clones were obtained. All the clones were analyzed for cell surface CCR5 expression using flow cytometry, and clone 10 was identified as a high expression clone. The CCR5 gene transcription of the clone 10 was further analyzed using RT PCR and gel electrophoresis,and the target band was visible in the expected location. Cellular ELISA indicated that the surface CCR5 expression of clone 10 was 13. 6 fold higher than the control cells. Our results indicated that the CHO cell line stably expressing human CCR5 can be a useful tool for study viral co receptor,specific antibody screening and anti-viral agents.%CC型趋化因子受体5(CCR5)是HIV-1感染机体所需的最重要的辅助受体和潜在的抗病毒药物靶点之一.将含有人CCR5基因的真核表达质粒pcDNA3.1CCR5稳定转染CHOK1细胞,G418筛选2周后,在96孔板内通过有限稀释法培养细胞单克隆,最后得到22个细胞克隆,用流式细胞术检测细胞表面CCR5蛋白,发现克隆10能够高表达人CCR5基因.使用RT—PCR鉴定克隆10CCR5基因转录情况,结果在预期的位置检测出目的条带.采用细胞ELISA的方法进一步鉴定克隆10细胞表面CCR5的表达,结果该克隆的405nm光密度值是对照组的13.6倍.结果表明,本研究建立的稳定转染人CCR5的CHO细胞系能够高效表达CCR5基因,为研究HIV—1共受体、筛选病毒中和抗体、以及抗病毒药物奠定了基础.

  17. 趋化因子受体CCR5亲和短肽的活性分析%Activity Analysis of Peptide Binding to Chemokine Receptor CCR5

    Institute of Scientific and Technical Information of China (English)

    王芳宇; 潘忠诚

    2006-01-01

    趋化因子受体CCR5与许多人类免疫疾病有关,而CCR5功能的缺失似乎并不会对人体产生很大的影响.通过对CCR5亲和短肽(AFDWTFVPSLIL)的活性分析,发现该短肽能抑制RANTES与PBMCs的结合,也能降低PBMCs对RANTES的趋化作用,并且能抑制RANTES引起的胞内Ca2+的升高,初步认为该短肽可作为CCR5的拮抗剂而受到进一步研究.

  18. Structure and regulative function of the 5′end flanking sequence of gene CCR5%CCR5基因5′侧翼区的克隆及调控功能初步研究

    Institute of Scientific and Technical Information of China (English)

    沙新平; 胡国龄; 谢玉桃; 陈曦; 刘映霞; 龚环宇; 侯珏; 李萍

    2002-01-01

    目的:研究CCR5基因5′侧翼区的调控序列.方法:分段构建CCR5基因5′侧翼区的pCAT报告基因载体;分析各片段在Hela细胞中的CAT调节活性.结果:CCR5基因5′侧翼区基因-1~-486 bp序列的pCAT重组质粒在Hela细胞中能明显表现CAT上调活性,其活性比pCAT enhancer vector的活性高3倍.结论:CCR5基因5′侧翼区基因-1~-486 bp序列中存在基因转录上调元件.

  19. A Nation-Wide multicenter 10-year (1999-2008) retrospective clinical epidemiological study of female breast cancer in china

    International Nuclear Information System (INIS)

    According to the very limited cancer registry, incidence and mortality rates for female breast cancer in China are regarded to be increasing especially in the metropolitan areas. Representative data on the breast cancer profile of Chinese women and its time trend over years are relatively rare. The aims of the current study are to illustrate the breast cancer profile of Chinese women in time span and to explore the current treatment approaches to female breast cancer. This was a hospital-based nation-wide and multi-center retrospective study of female primary breast cancer cases. China was divided into 7 regions according to the geographic distribution; from each region, one tertiary hospital was selected. With the exception of January and February, one month was randomly selected to represent each year from year 1999 to 2008 at every hospital. All inpatient cases within the selected month were reviewed and related information was collected based on the designed case report form (CRF). The Cancer Hospital/Institute, Chinese Academy of Medical Sciences (CICAMS) was the leading hospital in this study. Four-thousand two-hundred and eleven cases were randomly selected from the total pool of 45,200 patients and were included in the analysis. The mean age at diagnosis was 48.7 years (s.d. = 10.5 yrs) and breast cancer peaked in age group 40-49 yrs (38.6%). The most common subtype was infiltrating ductal carcinoma (86.5%). Clinical stage I & II accounted for 60.6% of 4,211 patients. Three-thousand five-hundred and thirty-four cases had estrogen receptor (ER) and progestin receptor (PR) tests, among them, 47.9% were positive for both. Two-thousand eight-hundred and forty-nine cases had human epidermal growth factor receptor 2(HER-2) tests, 25.8% of them were HER-2 positive. Among all treatment options, surgery (96.9% (4,078/4,211)) was predominant, followed by chemotherapy (81.4% (3,428/4,211). Much less patients underwent radiotherapy (22.6% (952/4,211)) and endocrine

  20. Lung Cancer: A survival analysis using data from the National Cancer Registry Uruguay of patients diagnosed in 2008

    International Nuclear Information System (INIS)

    Full text: Objective: To analyze survival (S V)from cancer in a cohort of patients Uruguayan drawn from the population-based registry and its association with clinical predictors and welfare. Materials and Methods: Retrospective analysis of patients in which there has been diagnosis of lung cancer in 2008. From the data base incidence and mortality of the 2008 RNC observed S V is calculated and constructed Kaplan Meier curves. We compare the S V as clinical variables (sex, age, extent lesion, histological type)and health care (patients seen in mutual and services health state in Montevideo and the Interior)by log rank test. Analysis is performed multivariate (Cox regression). Excluded from analysis identified patients only by death certificate (D CO)Results: We analyzed 1077 cases. The median S V entire cohort was 293 days (approx 9 months). In univariate analysis were statistically significantly sex, age, disease extension and some histological types. There were statistically S V significantly among patients treated at public and private centers assisted in Montevideo and the inside. In multivariate analysis, significant persists association with age, disease extension and assistance in public or private centers. Conclusions: In this cohort demonstrates S V comparable lung cancer to international series and an association with clinical variables consistent with them. Statistically significant differences were observed between patients assisted in public and private, which warrants further deeper analysis to determine the cause of this difference,

  1. 白藜芦醇对人外周血单核/巨噬细胞CCR5表达的影响%Efforts of resveratrol regulating the expression of CCR5 in human peripheral blood monocyte macrophage

    Institute of Scientific and Technical Information of China (English)

    郭继强; 孙爱萍

    2008-01-01

    目的:观察白藜芦醇对人外周血单核/巨噬细胞CC型趋化因子受体5(CCR5) 表达的调节作用.方法:采用Ficoll-Hypaque密度梯度离心法分离人外周血单个核细胞,再经贴壁法纯化单核/巨噬细胞.采用IFN-γ(1×105U/L)诱导单核/巨噬细胞表达CCR5,再分别加入不同浓度的白藜芦醇(0.5,5,25,50和100 μmol/L)进行干预.培养24 h后收集细胞,RT-PCR法检测外周血单核/巨噬细胞CCR5 mRNA表达水平;流式检测单核/巨噬细胞CCR5表达阳性率.同时将CCR5荧光素酶报告基因(pGL3-Basic-CCR5)转染各组细胞,检测各转染组的荧光素酶相对活性.结果:中、高浓度白藜芦醇处理组(25,50和100 μmol/L)的CCR5 mRNA表达水平、CCR5阳性细胞率和CCR5-luc报告基因的荧光素酶相对活性比对照组均有所降低,低浓度白藜芦醇处理(0.5和5 μmol/L)对单核/巨噬细胞CCR5的表达无明显影响.结论:中、高浓度白藜芦醇可抑制外周血单核/巨噬细胞CCR5的表达.

  2. Social Networks and Physical Activity Behaviors Among Cancer Survivors: Data From the 2005 Health Information National Trends Survey

    Science.gov (United States)

    KIM, BANG HYUN; WALLINGTON, SHERRIE F.; MAKAMBI, KEPHER H.; ADAMS-CAMPBELL, LUCILE L.

    2015-01-01

    The study examined the relation between social networks and physical activity behaviors among cancer survivors. The authors examined 873 cancer survivors (596 women, 277 men) 50 years of age or older who participated in the 2005 Health Information National Trends Survey. Multivariate logistic regression analysis showed that survivors who talked about health with friends/family were more likely to pay attention to new physical activity recommendations (OR = 2.89, CI [1.01, 8.33]). Female survivors were more likely to pay attention to new physical activity recommendations (OR = 2.65, CI [1.55, 4.53]) and more likely to have seen, heard, or read physical activity/exercise and cancer information within the past 12 months (OR = 2.09, CI [1.13, 3.85]) compared with their male counterparts. For male survivors, those who were a member of at least one community organization were more likely to pay attention to new physical activity/exercise recommendations (OR = 5.31, CI [1.32, 21.22]) than the men who were not members. Overall, cancer survivors with a social network (i.e., talking to family/friends about health) were more likely to pay attention to new exercise recommendations compared with those who did not have a social network. Significant differences were also observed by gender with physical activity levels, knowledge, and attitudes. Social networking is an important component in cancer survivorship and further research is needed to encourage social networking strategies that might facilitate in increasing physical activity behaviors among cancer survivors. PMID:25978562

  3. Localization and Expression of CCR3 and CCR5 by Interleukin-1ß in the RIN-5AH Insulin-Producing Model System: A Protective Mechanism Involving Down-Regulation of Chemokine Receptors

    Directory of Open Access Journals (Sweden)

    Vassiliadis S

    2002-05-01

    Full Text Available CONTEXT AND OBJECTIVE: The inflammatory cytokine interleukin-1beta has been considered to be an immune effector molecule in insulin dependent diabetes mellitus. As such, we examined its role on chemokine receptors which, when expressed in the pancreas, have also been associated with the development of type I autoimmune diabetes. DESIGN AND MAIN OUTCOME MEASURES: The presence of membrane and cytoplasmic levels of CCR3 and CCR5 expression is assessed by immunofluorescence in control and interleukin-1beta-treated RIN-5AH cells. The cytoplasmic expression is also shown by confocal microscopy as assessed by the brightness of the cells whereas enzyme-linked immunosorbent assay detects secreted CCR3 and CCR5 molecules by comparing optical density values as these derive from the control and the treated cells. Cell-fractionation experiments show the exact location of the intracellular pools of the chemokine receptors by using the rab7 monoclonal antibody as a guiding molecule. RESULTS: Interleukin-1beta down-regulates constitutively expressed surface CCR3 and CCR5 levels implying receptor internalization for re-utilization or destruction, secretion or both. Cytoplasmic immunofluorescence and confocal microscopy demonstrate cellular retention of chemokine receptors by interleukin-1beta which may be released in the absence of interleukin-1beta as assessed by enzyme-linked immunosorbent assay. Finally, cell-fractionation shows the presence of both receptors in endosomes exhibiting an increasing density after interleukin-1beta treatment. CONCLUSIONS: Given the association of chemokine receptors with progression to diabetes, it appears that interleukin-1beta-induced down-regulation of CCR3 and CCR5 promotes a protective mechanism against cellular destruction. The major role of interleukin-1beta is to maintain these molecules within the endosomes. Thus, interleukin-1beta modulates the movement and the expression of constitutively expressed chemokine receptors

  4. Developing of CCR5 as Target for HIV-1 Gene Therapy%基于修饰CCR5基因的艾滋病基因治疗进展

    Institute of Scientific and Technical Information of China (English)

    郭思达; 周艳; 姜春来

    2014-01-01

    艾滋病药物治疗主要障碍是难以彻底清除病毒、副作用大、成本高且需长期用药.CCR5是HIV侵染的主要辅助受体,缺陷型CCR5(CCR5△32)的CD4+T细胞对R5嗜性HIV-1病毒感染有高度抵抗力.通过骨髓移植CCR5△32干细胞到患者体内可以降低HIV病毒载量至无法检出水平,同时可维持T细胞数目在正常范围内.但由于CCR5△32基因缺失的人群所占比例少、配型困难等问题,CCR5△32干细胞移植无法广泛用于艾滋病的临床治疗.通过锌指核酸酶(ZFNs)或类转录激活因子效应物核酸酶(TALENs)两种方法可以将自体细胞CCR5基因人为部分缺失,将产生的CCR5缺陷细胞回输体内可阻断HIV-1入侵途径,稳定CD4细胞群体并最终清除病毒.而脐带血干细胞具有对配型要求低等优点,使其作为修饰的靶细胞具有广阔的应用前景.

  5. Cenicriviroc, a Novel CCR5 (R5 and CCR2 Antagonist, Shows In Vitro Activity against R5 Tropic HIV-2 Clinical Isolates.

    Directory of Open Access Journals (Sweden)

    Benoit Visseaux

    Full Text Available Maraviroc activity against HIV-2, a virus naturally resistant to different HIV-1 antiretroviral drugs, has been recently demonstrated. The aim of this study was to assess HIV-2 susceptibility to cenicriviroc, a novel, once-daily, dual CCR5 and CCR2 antagonist that has completed Phase 2b development in HIV-1 infection.Cenicriviroc phenotypic activity has been tested using a PBMC phenotypic susceptibility assay against four R5-, one X4- and one dual-tropic HIV-2 clinical primary isolates. All isolates were obtained by co-cultivation of PHA-activated PBMC from distinct HIV-2-infected CCR5-antagonist-naïve patients included in the French HIV-2 cohort and were previously tested for maraviroc susceptibility using the same protocol. HIV-2 tropism was determined by phenotypic assay using Ghost(3 cell lines.Regarding the 4 R5 HIV-2 clinical isolates tested, effective concentration 50% EC50 for cenicriviroc were 0.03, 0.33, 0.45 and 0.98 nM, similar to those observed with maraviroc: 1.13, 0.58, 0.48 and 0.68 nM, respectively. Maximum percentages of inhibition (MPI of cenicriviroc were 94, 94, 93 and 98%, similar to those observed with maraviroc (93, 90, 82, 100%, respectively. The dual- and X4-tropic HIV-2 strains were resistant to cenicriviroc with EC50 >1000 nM and MPI at 33% and 4%, respectively.In this first study assessing HIV-2 susceptibility to cenicriviroc, we observed an in vitro activity against HIV-2 R5-tropic strains similar to that observed with maraviroc. Thus, cenicriviroc may offer a once-daily treatment opportunity in the limited therapeutic arsenal for HIV-2. Clinical studies are warranted.

  6. Differences in Patient Outcomes of Prevalence, Interval, and Screen-Detected Lung Cancers in the CT Arm of the National Lung Screening Trial

    Science.gov (United States)

    Massion, Pierre P.; Thompson, Zachary J.; Eschrich, Steven A.; Balagurunathan, Yoganand; Goldof, Dmitry; Aberle, Denise R.; Gillies, Robert J.

    2016-01-01

    Lung cancer screening identifies cancers with heterogeneous behaviors. Some lung cancers will be identified among patients who had prior negative CT screens and upon follow-up scans develop a de novo nodule that was determined to be cancerous. Other lung cancers will be identified among patients who had one or more prior stable positive scans that were not determined to be lung cancer (indeterminate pulmonary nodules), but in follow-up scans was diagnosed with an incidence lung cancer. Using data from the CT arm of the National Lung Screening Trial, this analysis investigated differences in patient characteristics and survival endpoints between prevalence-, interval-, and screen-detected lung cancers, characterized based on sequence of screening results. Lung cancers immediately following a positive baseline (T0), and prior to the T1 screen, formed the prevalence cohort. Interval cancers were diagnosed following a negative screen at any time point prior to the next screening round. Two cohorts of screen-detected lung cancers (SDLC) were identified that had a baseline positive screen that was that was not determined to be lung cancer (i.e., an indeterminate pulmonary nodule), but in follow-up scans was diagnosed with an incidence lung cancer 12 (SDLC1) or 24 (SDLC2) months later. Two other incidence cohorts had screen-detected lung cancers that had baseline negative screen and upon follow-up scans developed a de novo nodule determined to be cancerous at 12 (SDLC3) or 24 (SDLC4) months later. Differences in patient characteristics, progression-free survival (PFS), and overall survival (OS) were assessed. The lung cancer-specific death rate was higher for SDLC3/SDLC4 compared to SDLC1/SDLC2 lung cancers (136.6/1,000 person-years vs. 71.3/1,000 person-years, P lung cancers (HR = 1.00). Lung cancer patients who develop a de novo nodule that determined to be cancerous (i.e., at least one negative CT screen prior to cancer diagnosis) had poorer survival outcomes compared

  7. Monocytes infiltrate the pancreas via the MCP-1/CCR2 pathway and differentiate into stellate cells.

    Directory of Open Access Journals (Sweden)

    Kazuko Ino

    Full Text Available Recent studies have shown that monocytes possess pluripotent plasticity. We previously reported that monocytes could differentiate into hepatic stellate cells. Although stellate cells are also present in the pancreas, their origin remains unclear. An accumulation of enhanced green fluorescent protein (EGFP(+CD45(- cells was observed in the pancreases and livers of chimeric mice, which were transplanted with a single hematopoietic stem cell isolated from EGFP-transgenic mice and treated with carbon tetrachloride (CCl4. Because the vast majority of EGFP(+CD45(- cells in the pancreas expressed stellate cell-associated antigens such as vimentin, desmin, glial fibrillary acidic protein, procollagen-I, and α-smooth muscle actin, they were characterized as pancreatic stellate cells (PaSCs. EGFP(+ PaSCs were also observed in CCl4-treated mice adoptively transferred with monocytes but not with other cell lineages isolated from EGFP-transgenic mice. The expression of monocyte chemoattractant protein-1 (MCP-1 and angiotensin II (Ang II increased in the pancreas of CCl4-treated mice and their respective receptors, C-C chemokine receptor 2 (CCR2 and Ang II type 1 receptor (AT1R, were expressed on Ly6C(high monocytes isolated from EGFP-transgenic mice. We examined the effect of an AT1R antagonist, irbesartan, which is also a CCR2 antagonist, on the migration of monocytes into the pancreas. Monocytes migrated toward MCP-1 but not Ang II in vitro. Irbesartan inhibited not only their in vitro chemotaxis but also in vivo migration of adoptively transferred monocytes from peripheral blood into the pancreas. Irbesartan treatment significantly reduced the numbers of EGFP(+F4/80(+CCR2(+ monocytic cells and EGFP(+ PaSCs in the pancreas of CCl4-treated chimeric mice receiving EGFP(+ bone marrow cells. A specific CCR2 antagonist RS504393 inhibited the occurrence of EGFP(+ PaSCs in injured mice. We propose that CCR2(+ monocytes migrate into the pancreas possibly via the

  8. C-C chemokine receptor type five (CCR5: An emerging target for the control of HIV infection

    Directory of Open Access Journals (Sweden)

    Fatima Barmania

    2013-12-01

    Full Text Available When HIV was initially discovered as the causative agent of AIDS, many expected to find a vaccine within a few years. This has however proven to be elusive; it has been approximately 30 years since HIV was first discovered, and a suitable vaccine is still not in effect. In 2009, a paper published by Hutter et al. reported on a bone marrow transplant performed on an HIV positive individual using stem cells that were derived from a donor who was homozygous for a mutation in the CCR5 gene known as CCR5 delta-32 (Δ32 (Hütter et al., 2009. The HIV positive individual became HIV negative and remained free of viral detection after transplantation despite having halted anti-retroviral (ARV treatment. This review will focus on CCR5 as a key component in HIV immunity and will discuss the role of CCR5 in the control of HIV infection.

  9. Down-regulation of the chemokine receptor CCR5 by activation of chemotactic formyl peptide receptor in human monocytes.

    Science.gov (United States)

    Shen, W; Li, B; Wetzel, M A; Rogers, T J; Henderson, E E; Su, S B; Gong, W; Le, Y; Sargeant, R; Dimitrov, D S; Oppenheim, J J; Wang, J M

    2000-10-15

    Interactions between cell surface receptors are important regulatory elements in the complex host responses to infections. In this study, it is shown that a classic chemotactic factor, the bacterial chemotactic peptide N-formyl-methionyl-leucylphenyl-alanine (fMLF), rapidly induced a protein-kinase-C-mediated serine phosphorylation and down-regulation of the chemokine receptor CCR5, which serves as a major human immunodeficiency virus (HIV)-1 coreceptor. The fMLF binding to its receptor, formyl peptide receptor (FPR), resulted in significant attenuation of cell responses to CCR5 ligands and in inhibition of HIV-1-envelope-glycoprotein-mediated fusion and infection of cells expressing CD4, CCR5, and FPR. The finding that the expression and function of CCR5 can be regulated by peptides that use an unrelated receptor may provide a novel approach to the design of anti-inflamatory and antiretroviral agents. (Blood. 2000;96:2887-2894)

  10. HIV辅助受体CCR5基因多态性及其研究进展

    Institute of Scientific and Technical Information of China (English)

    邓小玲; 李克

    2003-01-01

    辅助受体是HIV病毒感染人体所必须的,CCR5是HIV-1感染初期的主要辅助受体.本文主要讲述了CCR5的基因多态性,及基因多态性对HIV感染和AIDS病程进展的影响和作用原理,并讨论了CCR5与其它辅助受体和配体的相互作用,以及CCR5在治疗艾滋病药物开发中的应用前景.

  11. HIV辅助受体CCR5基因多态性及其研究进展

    Institute of Scientific and Technical Information of China (English)

    邓小玲; 李克

    2004-01-01

    辅助受体是HIV病毒感染人体所必需的,CCR5是HIV-1感染初期的主要辅助受体.本文主要讲述了CCR5的基因多态性及基因多态性对HIV感染和AIDS病程进展的影响和作用原理,并讨论了CCR5与其他辅助受体和配体的相互作用,以及CCR5在治疗艾滋病药物开发中的应用前景.

  12. Folding of newly translated membrane protein CCR5 is assisted by the chaperonin GroEL-GroES

    Science.gov (United States)

    Chi, Haixia; Wang, Xiaoqiang; Li, Jiqiang; Ren, Hao; Huang, Fang

    2015-11-01

    The in vitro folding of newly translated human CC chemokine receptor type 5 (CCR5), which belongs to the physiologically important family of G protein-coupled receptors (GPCRs), has been studied in a cell-free system supplemented with the surfactant Brij-35. The freshly synthesized CCR5 can spontaneously fold into its biologically active state but only slowly and inefficiently. However, on addition of the GroEL-GroES molecular chaperone system, the folding of the nascent CCR5 was significantly enhanced, as was the structural stability and functional expression of the soluble form of CCR5. The chaperonin GroEL was partially effective on its own, but for maximum efficiency both the GroEL and its GroES lid were necessary. These results are direct evidence for chaperone-assisted membrane protein folding and therefore demonstrate that GroEL-GroES may be implicated in the folding of membrane proteins.

  13. Expression of LL-37, Human beta Defensin-2, and CCR6 mRNA in Patients with Psoriasis Vulgaris

    Institute of Scientific and Technical Information of China (English)

    李东升; 李家文; 段逸群; 周小勇

    2004-01-01

    To investigate whether LL-37 and human beta defensin-2 (hBD-2) is related to the patients with psoriasis seldom having skin infections and explore the role of the two peptides and CCR6 (the receptor of hBD-2) in the pathogenesis of psoriasis, the expression levels of mRNA of LL-37, hBD-2, and CCR6 in skin lesions of patients with psoriasis vulgaris were detected by using RT-PCR. The results showed that the mRNA expression levels of the two peptides and CCR6 in psoriatic lesions all increased compared with the normal skin (P<0. 001). It was suggested that upregulated expression of LL-37 and hBD-2 might be the main reason that result in the the skin of patients with psoriasis being seldom infected, and the two peptides and CCR6 might play crucial roles in the pathogenesis of psoriasis.

  14. Distribution of HIV-1 resistance-conferring polymorphic alleles SDF-1-3′A, CCR2-64I and CCR5-32 in diverse populations of Andhra Pradesh, South India

    Indian Academy of Sciences (India)

    G. V. Ramana; A. Vasanthi; M. Khaja; B. Su; V. Govindaiah; L. Jin; L. Singh; R. Chakraborty

    2001-12-01

    Polymorphic allelic variants of chemokine receptors CCR2 and CCR5, as well as of stromal-derived factor-1 SDF-1, the ligand for the chemokine receptor CXCR4, are known to have protective effects against HIV-1 infection and to be involved with delay in disease progression. We have studied the DNA polymorphisms at the loci that encode these proteins in 525 healthy individuals without any history of HIV-1 infection from 11 diverse populations of Andhra Pradesh, South India. The two protective alleles SDF-1-3′A and CCR2-64I at the SDF-1 and CCR2 loci, respectively, are present in all populations studied, although their frequencies differ considerably across populations (from 17% to 35% for the SDF-1-3′A allele, and from 3% to 17% for CCR2-64I). In contrast the CCR5-32 allele is observed only in three populations (Yamani, Pathan and Kamma), all in low frequencies (i.e. 1% to 3%). The mean number of mutant alleles (for the three loci together) carried by each individual varies from 0.475 (in Vizag Brahmins) to 0.959 (in Bohra Muslims). The estimated relative hazard values for the populations, computed from the three-locus genotype data, are comparable to those from Africa and Southeast Asia, where AIDS is known to be widespread.

  15. Colorectal cancer screening practices of primary care providers: results of a national survey in Malaysia.

    Science.gov (United States)

    Norwati, Daud; Harmy, Mohamed Yusoff; Norhayati, Mohd Noor; Amry, Abdul Rahim

    2014-01-01

    The incidence of colorectal cancer has been increasing in many Asian countries including Malaysia during the past few decades. A physician recommendation has been shown to be a major factor that motivates patients to undergo screening. The present study objectives were to describe the practice of colorectal cancer screening by primary care providers in Malaysia and to determine the barriers for not following recommendations. In this cross sectional study involving 132 primary care providers from 44 Primary Care clinics in West Malaysia, self-administered questionnaires which consisted of demographic data, qualification, background on the primary care clinic, practices on colorectal cancer screening and barriers to colorectal cancer screening were distributed. A total of 116 primary care providers responded making a response rate of 87.9%. About 21% recommended faecal occult blood test (FOBT) in more than 50% of their patients who were eligible. The most common barrier was "unavailability of the test". The two most common patient factors are "patient in a hurry" and "poor patient awareness". This study indicates that colorectal cancer preventive activities among primary care providers are still poor in Malaysia. This may be related to the low availability of the test in the primary care setting and poor awareness and understanding of the importance of colorectal cancer screening among patients. More awareness programmes are required for the public. In addition, primary care providers should be kept abreast with the latest recommendations and policy makers need to improve colorectal cancer screening services in health clinics.

  16. Prostate Cancer Screening in Jamaica: Results of the Largest National Screening Clinic

    Directory of Open Access Journals (Sweden)

    Belinda F. Morrison

    2016-01-01

    Full Text Available Prostate cancer is highly prevalent in Jamaica and is the leading cause of cancer-related deaths. Our aim was to evaluate the patterns of screening in the largest organized screening clinic in Jamaica at the Jamaica Cancer Society. A retrospective analysis of all men presenting for screening at the Jamaica Cancer Society from 1995 to 2005 was done. All patients had digital rectal examinations (DRE and prostate specific antigen (PSA tests done. Results of prostate biopsies were noted. 1117 men of mean age 59.9 ± 8.2 years presented for screening. The median documented PSA was 1.6 ng/mL (maximum of 5170 ng/mL. Most patients presented for only 1 screen. There was a gradual reduction in the mean age of presentation for screening over the period. Prostate biopsies were requested on 11% of screening visits; however, only 59% of these were done. 5.6% of all persons screened were found to have cancer. Of the cancers diagnosed, Gleason 6 adenocarcinoma was the commonest grade and median PSA was 8.9 ng/mL (range 1.5–1059 ng/mL. Older men tend to screen for prostate cancer in Jamaica. However, compliance with regular maintenance visits and requests for confirmatory biopsies are poor. Screening needs intervention in the Jamaican population.

  17. Colorectal cancer screening practices of primary care providers: results of a national survey in Malaysia.

    Science.gov (United States)

    Norwati, Daud; Harmy, Mohamed Yusoff; Norhayati, Mohd Noor; Amry, Abdul Rahim

    2014-01-01

    The incidence of colorectal cancer has been increasing in many Asian countries including Malaysia during the past few decades. A physician recommendation has been shown to be a major factor that motivates patients to undergo screening. The present study objectives were to describe the practice of colorectal cancer screening by primary care providers in Malaysia and to determine the barriers for not following recommendations. In this cross sectional study involving 132 primary care providers from 44 Primary Care clinics in West Malaysia, self-administered questionnaires which consisted of demographic data, qualification, background on the primary care clinic, practices on colorectal cancer screening and barriers to colorectal cancer screening were distributed. A total of 116 primary care providers responded making a response rate of 87.9%. About 21% recommended faecal occult blood test (FOBT) in more than 50% of their patients who were eligible. The most common barrier was "unavailability of the test". The two most common patient factors are "patient in a hurry" and "poor patient awareness". This study indicates that colorectal cancer preventive activities among primary care providers are still poor in Malaysia. This may be related to the low availability of the test in the primary care setting and poor awareness and understanding of the importance of colorectal cancer screening among patients. More awareness programmes are required for the public. In addition, primary care providers should be kept abreast with the latest recommendations and policy makers need to improve colorectal cancer screening services in health clinics. PMID:24761922

  18. Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors: a possible protective effect against disease progression

    Science.gov (United States)

    Pastori, Claudia; Weiser, Barbara; Barassi, Claudia; Uberti-Foppa, Caterina; Ghezzi, Silvia; Longhi, Renato; Calori, Giliola; Burger, Harold; Kemal, Kimdar; Poli, Guido; Lazzarin, Adriano; Lopalco, Lucia

    2006-01-01

    Exposure to HIV-1 does not necessarily result in infection and progression toward disease, thus suggesting that the control of viral infection may be achieved. Antibodies to CCR5 have been detected in HIV-exposed but uninfected subjects (ESNs); thus, these antibodies could be involved in HIV protection. To assess whether anti-CCR5 antibodies may also contribute to slow HIV disease progression, we searched for anti-CCR5 antibodies in 497 subjects, including 85 long-term nonprogressors (LTNPs), 70 progressors, 135 HIV+ patients treated with highly active antiretroviral therapy (HAART), and 207 seronegative donors. We found anti-CCR5 antibodies in a fraction of the LTNPs(23.5%) but not in the other populations studied (P < .001). These antibodies recognized a conformational epitope within the first extramembrane loop of CCR5, and they induced a stable and long-lasting downregulation of CCR5 on the surface of T lymphocytes, which inhibited HIV entry. In addition, CD4+ lymphocytes from LTNPs having anti-CCR5 antibodies are resistance to R5 strains of HIV-1. Follow-up studies showed that the loss of anti-CCR5 antibodies occurred in some subjects, and this loss was significantly associated with a progression toward disease, whereas subjects who retained anti-CCR5 Abs maintained their LTNP status. Induction of anti-CCR5 Abs could be relevant to vaccine design and therapeutics. PMID:16522810

  19. Expression and function analysis of chemokine receptor CCR6 in HEK293 cells%人趋化因子受体CCR6在HEK293细胞内的稳定表达及其功能分析

    Institute of Scientific and Technical Information of China (English)

    魏巍; 高岚; 张菲菲; 崔礼鑫; 谢欣

    2011-01-01

    AIM: To construct a cell line which stably expresses human chemokine receptor 6 (CCR6).METHODS: The human CCR6 cDNA and plasmid G were cotransfected into HEK 293 cells and the clones stably expressing CCR6 were picked out.The expression of CCR6 in HEK293 cells was detected by RT-PCR, Westem blotting,immunofluorescence test, calcium mobilization and in vitro chemotaxis assay.RESULTS: The transfected HEK293 cells could stably express functional human CCR6.CONCLUSION: Successfully establish a cell line which stably express human CCR6 and lays the foundation for its biological functions study and specific antagonist screening.%目的:构建稳定表达人趋化因子受体6(CCR6)的HEK293细胞株.方法:将CCR6基因和Gα16质粒共转到HEK293细胞中,并挑取稳定表达CCR6基因的HEK293细胞克隆.采用体外趋化实验、钙流实验、RT-PCR、Western blot及免疫荧光染色法,检测CCR6在HEK293细胞表面的表达.结果:经上述实验证实,CCR6基因和Cα16质粒共转染的HEK293细胞上,可稳定表达CCR6,且具有生物学活性.结论:成功地在HEK293细胞表面稳定表达具有生物学活性的CCR6,为研究CCR6的生物学功能及筛选CCR6的拮抗剂奠定了基础.

  20. Development and Current Status of National Cancer Center for Chinese Medicine

    Institute of Scientific and Technical Information of China (English)

    LI Jie; LIN Hong-sheng; HOU Wei; ZHANG Pei-tong; HUA Bao-jin

    2011-01-01

    @@ Chinese medicine (CM) is an important feature of cancer treatment in China.Especially in the last 10years, the effect of CM in cancer treatment has been of high concern and has been accepted by experts and patients locally and overseas.The oncology department (OD) of Guang'anmen Hospital (GAMH) of China Academy of Chinese Medical Sciences (CATCM),which will mark its 50th anniversary in 2013, is one of China's most-respected centers devoted exclusively to cancer patient care, research, education, and prevention through CM.It is located at the campus of GAMH,central Beijing.