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Sample records for ccr national cancer

  1. CCR Interns | Center for Cancer Research

    Science.gov (United States)

    The Cancer Research Interns (CRI) Summer Program was inaugurated in 2004 to increase the diversity of trainee applicants to the Center for Cancer Research (CCR). We have placed 339 students from 2004 to 2017, in labs and branches across the CCR. The Division provides the training dollars, some Service & Supply funds, and travel support for those students who meet the financial eligibility criteria (View and/or print the 2018 flier).

  2. CCR Interns | Center for Cancer Research

    Science.gov (United States)

    The Cancer Research Interns (CRI) Summer Program was inaugurated in 2004 to provide an open door for students looking for an initial training opportunity. The goal is to enhance diversity within the CCR (Center for Cancer Research) training program and we have placed 338 students from 2004 to 2017, in labs and branches across the division.  The CCR and the Center for Cancer Training’s Office of Training and Education provide stipend support, some Service & Supply funds, and travel support for those students who meet the financial eligibility criteria (

  3. Relationship between genetic polymorphisms in MCP-1, CCR-2, and non-small-cell lung cancer in the Han nationality of Northern China.

    Science.gov (United States)

    Yang, L; Wang, J; Li, F-G; Han, M; Chang, X-J; Wang, Z-T

    2015-04-22

    Lung cancer is a common malignant tumor worldwide and is now the leading cause of cancer-related deaths. Monocyte chemoattractant protein 1 (MCP-1) and its receptor chemokine receptor 2 (CCR-2) are important chemokines. We examined the polymorphisms of 338 unrelated patients with non-small cell lung carcinoma (NSCLC) and 200 unrelated healthy controls of Han nationality in Northern China using polymerase chain reaction-restriction fragment length polymorphism. We found a significant increase in the frequency of the MCP-1 AA genotype [0.293 vs 0.195, odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.13-2.60] and a significant decrease in the frequency of the GG genotype (0.290 vs 0.41, OR = 0.64, 95%CI = 0.47-0.87) in NSCLC patients compared to controls. The frequencies of AA-ww (0.151 vs 0.090, P = 0.041, OR = 1.80, 95%CI = 1.33-2.43) and AA-wm (0.136 vs 0.080, P = 0.049, OR = 1.81, 95%CI = 1.01-3.27) were higher in lung cancer patients than in healthy controls; the frequency of GG-wm (0.121 vs 0.190, P = 0.030, OR = 0.60, 95%CI = 0.38-0.95) was lower in lung cancer patients than in healthy controls. Based on these results, the polymorphism in MCP-1 may be correlated with the development of NSCLC in the Han nationality of Northern China. However, the polymorphism in CCR-2 is not involved in NSCLC.

  4. [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.

  5. CCR presentations at AACR - 2018 | Center for Cancer Research

    Science.gov (United States)

    CCR presentations at AACR Several CCR scientists will present their research at the AACR Annual Meeting in Chicago, IL, between April 14-18, 2018. Selected oral presentations are listed below. A full list of abstracts can be found on the AACR website.

  6. CCR presentations at AACR | Center for Cancer Research

    Science.gov (United States)

    CCR presentations at AACR Several CCR scientists will present their research at the AACR Annual Meeting in Washington, D.C., between April 1-5, 2017. Selected oral presentations are listed below. A full list of abstracts can be found on the AACR website.

  7. 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...

  8. Levo-Corydalmine Alleviates Neuropathic Cancer Pain Induced by Tumor Compression via the CCL2/CCR2 Pathway

    Directory of Open Access Journals (Sweden)

    Yahui Hu

    2017-06-01

    Full Text Available Background: Tumor compression-induced pain (TCIP is a complex pathological cancer pain. Spinal glial cells play a critical role in maintenance of cancer pain by releasing proinflammatory cytokines and chemokines. In this study, we verified the role of levo-corydalmine (l-CDL on TCIP. Methods: Spontaneous pain, paw withdrawal threshold and latency were assessed using TCIP mouse model. Immunofluorescence was used to identify the reactions of glia. RT-PCR and western blot or ELISA were used to determine mRNA or protein expression of tumor necrosis factor-α (TNF-α, interlukin-1β (IL-1β, CC chemokine ligand 2 (CCL2 and chemotactic cytokine receptor 2 (CCR2 in vivo and in vitro. Results: l-CDL significantly attenuated TCIP hypersensitivity, accompanying with downregulation of TNF-α and IL-1β expression levels and declined astrocytes and microglial activation. It also significantly decreased the expression of the mRNA and protein level for CCL2 and CCR2. Further, l-CDL could suppress TNF-α-induced astrocytes activation and IL-1β expression through downregulating the CCL2/CCR2. Besides, CCL2-induced BV-microglia activation and inflammatory factors secretion were suppressed by l-CDL via CCR2. Conclusions: Suppression of CCL2/CCR2 by l-CDL may contribute to alleviate TCIP, offering an alternative medication for TCIP.

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

    Directory of Open Access Journals (Sweden)

    Williamson Anna-Lise

    2010-06-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions 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

  10. 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)

    Chatterjee, Koushik; Dandara, Collet; Hoffman, Margaret; Williamson, Anna-Lise

    2010-01-01

    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

  11. Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: a role for targeting the CCL2/CCR2 axis

    Science.gov (United States)

    Sanford, Dominic E.; Belt, Brian A.; Panni, Roheena Z.; Mayer, Allese; Deshpande, Anjali D.; Carpenter, Danielle; Mitchem, Jonathan B.; Plambeck-Suess, Stacey M.; Worley, Lori A.; Goetz, Brian D.; Wang-Gillam, Andrea; Eberlein, Timothy J.; Denardo, David G.; Goedegebuure, S. Peter; Linehan, David C.

    2013-01-01

    Purpose To determine the role of the CCL2/CCR2 axis and inflammatory monocytes (IM; CCR2+/CD14+) as immunotherapeutic targets in the treatment of pancreatic cancer (PC). Experimental Design Survival analysis was performed to determine if the prevalence of pre-operative blood monocytes correlates with survival in PC patients following tumor resection. IM prevalence in the blood and bone marrow of PC patients and controls was compared. The immunosuppressive properties of IM and macrophages in the blood and tumors, respectively, of PC patients were assessed. CCL2 expression by human PC tumors was compared to normal pancreas. A novel CCR2 inhibitor (PF-04136309) was tested in an orthotopic model of murine PC. Results Monocyte prevalence in the peripheral blood correlates inversely with survival, and low monocyte prevalence is an independent predictor of increased survival in PC patients with resected tumors. IM are increased in the blood and decreased in the bone marrow of PC patients compared to controls. An increased ratio of IM in the blood versus the bone marrow is a novel predictor of decreased patient survival following tumor resection. Human PC produces CCL2, and immunosuppressive CCR2+ macrophages infiltrate these tumors. Patients with tumors that exhibit high CCL2 expression/low CD8 T cell infiltrate have significantly decreased survival. In mice, CCR2 blockade depletes IM and macrophages from the primary tumor and premetastatic liver resulting in enhanced anti-tumor immunity, decreased tumor growth, and reduced metastasis. Conclusions IM recruitment is critical to PC progression, and targeting CCR2 may be an effective immunotherapeutic strategy in this disease. PMID:23653148

  12. [A case of breast cancer postoperative metastases to the liver obtained cCR].

    Science.gov (United States)

    Enomoto, Katsuhisa; Sakurai, Kenichi

    2011-11-01

    A case is a 55-year-old woman. We noticed the right breast lump in May 2006. It was papillotubular carcinoma, ER(-), PgR -), HER2 (3+) by needle biopsy. The patient was introduced to our department in November 2006 for a close inspection and treatment. The palpation showed a mass without a firm flexibility, which was a border indistinctness of about 2 cm in size in the right AB area. We did not find a distant metastasis either. We operated for Bt+Ax (level II) in December. It was T2N0M0, stage IIA papillotubular carcinoma, ER(-), PgR(-), HER2 (3+) with histopathology. We recommended an adjuvant therapy but the patient refused. Since then we followed her up. After two years from the operation, multiple metastases were observed to the liver, FEC therapy was started. CT revealed that metastasized tumors were disappeared after six courses of treatment. Echography obtained cCR. Generally speaking, chemotherapy was effective for breast cancer as we compared it to endemic cancer of other organs. Meanwhile, it has been reported that many kinds of newly developed medicines for the treatment are available and effective. On the other hand, a selection of therapeutic drugs could be a problem for metastasized organs.

  13. CCR1

    African Journals Online (AJOL)

    Chemokine Receptor 1 (CCR1) Derived from Viral ... the potential role and mechanism of peptide C18P derived from viral macrophage inflammatory protein ..... 4. Kauts ML, Pihelgas S, Orro K, Neuman T, Piirsoo A. CCL5/CCR1 axis regulates multipotency of human adipose tissue derived stromal cells. Stem Cell Res. 2013 ...

  14. Association of CXCR4, CCR7, VEGF-C and VEGF-D expression with lymph node metastasis in patients with cervical cancer.

    Science.gov (United States)

    Dai, Yifei; Tong, Rui; Guo, Hui; Yu, Tingting; Wang, Chunyan

    2017-07-01

    We attempted to investigate the expression of CXCR4, CCR7, VEGF-C and VEGF-D in cervical cancer specimens, and the association between CXCR4, CCR7, VEGF-C and VEGF-D expression with the clinicopathological parameters of patients with cervical cancer. 57 tissue microarrays including 9 normal cervical tissues and 48 cervical cancer tissues were purchased from Biomax. The association between CXCR4, CCR7, VEGF-C and VEGF-D expression with the clinicopathological parameters were evaluated. Then immunohistochemistry was used to assess the expression of CXCR4, CCR7, VEGF-C and VEGF-D in cervical cancer specimens. Finally, Spearman correlations were used for the correlation analyses between CXCR4, CCR7, VEGF-C and VEGF-D. We revealed that CXCR4 expression was significantly higher in patients with squamous cell carcinomas (P=0.002) and lymph node metastasis (P=0.038), while CCR7 expression was significantly elevated in patients with lymph node metastasis (P=0.037). VEGF-C expression was markedly up-regulated in patients exhibiting FIGO stage II-III tumors (P=0.015) and lymph node metastasis (P=0.038), while VEGF-D expression was obviously increased in patients displaying FIGO stage II-III tumors (P=0.025), squamous carcinomas (P=0.017) and lymph node metastasis (P=0.037). The correlation analysis indicated that CXCR4, CCR7, VEGF-C and VEGF-D expression have a significant correlation to each other. These results suggested that CXCR4, CCR7, VEGF-C and VEGF-D expression might have synergistic effects on the lymph node metastasis in patients with cervical cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. 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.

  16. Pulmonary metastasectomy in colorectal cancer: a prospective study of demography and clinical characteristics of 543 patients in the Spanish colorectal metastasectomy registry (GECMP-CCR).

    Science.gov (United States)

    Embún, R; Fiorentino, F; Treasure, T; Rivas, J J; Molins, L

    2013-05-28

    To capture an accurate contemporary description of the practice of pulmonary metastasectomy for colorectal carcinoma in one national healthcare system. A national registry set up in Spain by Grupo Español de Cirugía Metástasis Pulmonares de Carcinoma Colo-Rectal (GECMP-CCR). 32 Spanish thoracic units. All patients with one or more histologically proven lung metastasis removed by surgery between March 2008 and February 2010. Pulmonary metastasectomy for one or more pulmonary nodules proven to be metastatic colorectal carcinoma. The age and sex of the patients having this surgery were recorded with the number of metastases removed, the interval between the primary colorectal cancer operation and the pulmonary metastasectomy, and the carcinoembryonic antigen level. Also recorded were the practices with respect to mediastinal lymphadenopathy and coexisting liver metastases. Data were available on 543 patients from 32 units (6-43/unit). They were aged 32-88 (mean 65) years, and 65% were men. In 55% of patients, there was a solitary metastasis. The median interval between the primary cancer resection and metastasectomy was 28 months and the serum carcinoembryonic antigen was low/normal in the majority. Liver metastatic disease was present in 29% of patients at some point prior to pulmonary metastasectomy. Mediastinal lymphadenectomy varied from 9% to 100% of patients. The data represent a prospective comprehensive national data collection on pulmonary metastasectomy. The practice is more conservative than the impression gained when members of the European Society of Thoracic Surgeons were surveyed in 2006/2007 but is more inclusive than would be recommended on the basis of recent outcome analyses. Further analyses on the morbidity associated with this surgery and the correlation between imaging studies and pathological findings are being published separately by GECMP-CCR.

  17. Obesity exacerbates colitis-associated cancer via IL-6-regulated macrophage polarisation and CCL-20/CCR-6-mediated lymphocyte recruitment.

    Science.gov (United States)

    Wunderlich, Claudia M; Ackermann, P Justus; Ostermann, Anna Lena; Adams-Quack, Petra; Vogt, Merly C; Tran, My-Ly; Nikolajev, Alexei; Waisman, Ari; Garbers, Christoph; Theurich, Sebastian; Mauer, Jan; Hövelmeyer, Nadine; Wunderlich, F Thomas

    2018-04-25

    Colorectal cancer (CRC) is one of the most lethal cancers worldwide in which the vast majority of cases exhibit little genetic risk but are associated with a sedentary lifestyle and obesity. Although the mechanisms underlying CRC and colitis-associated colorectal cancer (CAC) remain unclear, we hypothesised that obesity-induced inflammation predisposes to CAC development. Here, we show that diet-induced obesity accelerates chemically-induced CAC in mice via increased inflammation and immune cell recruitment. Obesity-induced interleukin-6 (IL-6) shifts macrophage polarisation towards tumour-promoting macrophages that produce the chemokine CC-chemokine-ligand-20 (CCL-20) in the CAC microenvironment. CCL-20 promotes CAC progression by recruiting CC-chemokine-receptor-6 (CCR-6)-expressing B cells and γδ T cells via chemotaxis. Compromised cell recruitment as well as inhibition of B and γδ T cells protects against CAC progression. Collectively, our data reveal a function for IL-6 in the CAC microenvironment via lymphocyte recruitment through the CCL-20/CCR-6 axis, thereby implicating a potential therapeutic intervention for human patients.

  18. Why CCR: A conversation with Physician Assistant Julia Friend | Center for Cancer Research

    Science.gov (United States)

    "Where else can you make such a profound difference not only for the individual now, but for those who come in the future? It is hard work, good work and worth doing well.” Physician Assistant Julia Friend answers our questions about why she loves working for CCR. Read more...

  19. [A Case of an Older Patient with Metastatic Breast Cancer Effectively Treated with Capecitabine, with Achievement of cCR].

    Science.gov (United States)

    Ono, Yoko; Enomoto, Katsuhisa; Sakurai, Kenichi; Amano, Sadao

    2015-11-01

    A case: An 82-year-old woman underwent Bp plus Ax enforcement for carcinoma of the right breast (T2N1M0, StageⅡB) about 5 years previously. Letrozole was administered, but right pleura tuberculum and pleural dissemination was noted in the fifth postoperative year. The hormone therapy was changed, but mediastinal lymph node metastases were observed with tumor marker elevation and bilateral metastases in the lung and right pleural fluid retention. Capecitabine 1,800 mg/day for 3 weeks was started in the sixth postoperative year. The response to treatment was classified as cCR and no side effects were noted. For approximately 1 year and 6 months, no recurrence or metastasis has been observed. Consecutive therapy such as onset of the side effect or an injection method change, dosage weight loss is difficult though chemotherapies is performed for the recurrence metastasis breast cancer case of the older patient. Because capecitabine is isolated, and a continuous administration is had without a side effect, and it was with cCR for this case, in addition, discussion of the literature is reported because it seemed that it may be in effective therapy for an older patient breast cancer case in future.

  20. 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.

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

    Science.gov (United States)

    2011-01-01

    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. PMID:21539750

  2. 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.

  3. National Ovarian Cancer Coalition

    Science.gov (United States)

    ... History Day – Prepare for a Family Conversation About Genetics and Cancer November 08, 2017 Live Webinar on ... us here . Thanksgiving Day, November 23rd, is National Family ... Read ... Tree Display November 19, 2017 @ 10:00AM Hosted by ...

  4. National Comprehensive Cancer Network

    Science.gov (United States)

    ... Anal Carcinoma B-Cell Lymphomas Basal Cell Skin Cancer Bladder Cancer Bone Cancer Breast Cancer Central Nervous System Cancers ... Breast Cancer Risk Reduction Breast Cancer Screening and Diagnosis Cervical Cancer Screening Colorectal Cancer Screening Genetic/Familial ...

  5. CCR 20th Anniversary Commentary: Divide and Conquer-Breast Cancer Subtypes and Response to Therapy.

    Science.gov (United States)

    Pusztai, Lajos; Rouzier, Roman; Symmans, W Fraser

    2015-08-15

    The article by Rouzier and colleagues, published in the August 15, 2005, issue of Clinical Cancer Research, demonstrated that different molecular subtypes of breast cancer have different degrees of sensitivity to chemotherapy, but the extent of response to neoadjuvant therapy has a different meaning by subtype. Several molecular subtype-specific clinical trials are under way to maximize pathologic complete response rates in triple-negative breast cancer and HER2-positive cancers, and to provide adjuvant treatment options for patients with residual invasive disease. See related article by Rouzier et al., Clin Cancer Res 2005;11(16) Aug 15, 2005;5678-85. ©2015 American Association for Cancer Research.

  6. 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.

  7. CCR 20th Anniversary Commentary: Prospects and Challenges of Therapeutic Nanoparticles in Cancer.

    Science.gov (United States)

    Rahman, Mohammad Aminur; Shin, Dong M

    2015-10-15

    In their review article published in the March 1, 2008, issue of Clinical Cancer Research, Cho and colleagues presented the strong potential of nanotechnology in cancer. This commentary discusses the latest advances in nanotechnology, which provide novel approaches for cancer diagnosis, imaging, drug delivery, and personalized therapy; highlights the perspectives for therapeutic nanoparticles; and describes the advantages and challenges of their multifunctionalities. ©2015 American Association for Cancer Research.

  8. CCR 20th Anniversary Commentary: The Development of Breast Cancer Molecular Subtyping.

    Science.gov (United States)

    Nielsen, Torsten O; Perou, Charles M

    2015-04-15

    In the August 15, 2004, issue of Clinical Cancer Research, Nielsen and colleagues demonstrated how a cancer subtype identified by gene expression profiling could be validated using a widely accessible technology (immunohistochemistry). This opened the door to large-scale studies of archival cohorts and clinical trials, which allowed detailed clinical understanding of a new genomic discovery. Clin Cancer Res; 21(8); 1779-81. ©2015 AACR. See related article by Nielsen et al., Clin Cancer Res 2004;10(16) Aug 15, 2004;5367-74. ©2015 American Association for Cancer Research.

  9. Cell differentiation dependent expressed CCR6 mediates ERK-1/2, SAPK/JNK, and Akt signaling resulting in proliferation and migration of colorectal cancer cells.

    Science.gov (United States)

    Brand, Stephan; Olszak, Torsten; Beigel, Florian; Diebold, Joachim; Otte, Jan-Michel; Eichhorst, Soeren T; Göke, Burkhard; Dambacher, Julia

    2006-03-01

    The expression of CCL20 (MIP-3alpha), which chemoattracts leukocytes to sites of inflammation, has been shown in intestinal epithelial cells (IEC). Aim of this study was to analyze the role of the CCL20 receptor CCR6 in IEC and colorectal cancer (CRC) cells. Expression of CCR6 and CCL20 was analyzed by RT-PCR and immunohistochemistry. Signaling was investigated by Western blotting, proliferation by MTS assays and chemotactic cell migration by wounding assays. The effect of CCL20 on Fas-induced apoptosis was determined by flow cytometry. CCR6 and its ligand CCL20 are expressed in IEC. Moreover, CRC and CRC metastases express CCR6, which is upregulated during IEC differentiation. Stimulation of IEC with CCL20 and proinflammatory stimuli (TNF-alpha, IL-1beta, LPS) significantly upregulates CCL20 mRNA expression. CCL20 expression was significantly increased in inflamed colonic lesions in Crohn's disease and correlated significantly with the IL-8 mRNA expression in these lesions (r = 0.71) but was downregulated in CRC metastases. CCL20 activated Akt, ERK-1/2, and SAPK/JNK MAP kinases and increased IL-8 protein expression. The CCL20 mediated activation of these pathways resulted in a 2.6-fold increase of cell migration (P = 0.001) and in a significant increase of cell proliferation (P differentiation. CCR6 mediated signals result in increased IEC migration and proliferation suggesting an important role in intestinal homeostasis and intestinal inflammation by mediating chemotaxis of IEC but also in mediating migration of CRC cells. 2005 Wiley-Liss, Inc.

  10. CCR 20th Anniversary commentary: stayin' alive-antiapoptotic proteins and breast cancer.

    Science.gov (United States)

    Yee, Douglas

    2015-02-15

    The control of cell death involves a complex interaction of multiple proteins. In a study published in the January 1, 2000, issue of Clinical Cancer Research, Tanaka and colleagues demonstrated that one of the proapoptotic proteins, survivin, was frequently expressed in breast cancer. In the subsequent years, effectors of apoptosis have translated into important prognostic indicators and potential therapeutic targets. ©2015 American Association for Cancer Research.

  11. CCR 20th Anniversary Commentary: Circulating Tumor Cells in Prostate Cancer.

    Science.gov (United States)

    Mehra, Niven; Zafeiriou, Zafeiris; Lorente, David; Terstappen, Leon W M M; de Bono, Johann S

    2015-11-15

    Circulating tumor cells (CTC) have substantial promise for multipurpose biomarker studies in prostate cancer. The IMMC-38 trial conducted by de Bono and colleagues, which was published in the October 1, 2008, issue of Clinical Cancer Research, demonstrated for the first time that CTCs are the most accurate and independent predictor of overall survival in metastatic prostate cancer. Since the publication of prospective trials demonstrating prognostic utility, CTCs have been utilized for nucleic acid analyses, for protein analyses, and in intermediate endpoint studies. CTC studies are also now facilitating the analysis of intrapatient heterogeneity. See related article by de Bono et al., Clin Cancer Res 2008;14(19) October 1, 2008;6302-9. ©2015 American Association for Cancer Research.

  12. CCR 20th anniversary commentary: Preclinical study of proteasome inhibitor bortezomib in head and neck cancer.

    Science.gov (United States)

    Allen, Clint T; Conley, Barbara; Sunwoo, John B; Van Waes, Carter

    2015-03-01

    In a study published in the May 1, 2001, issue of Clinical Cancer Research, Sunwoo and colleagues provided evidence for proteasome inhibition of NF-κB and tumorigenesis, supporting early-phase clinical trials in solid malignancies of the upper aerodigestive tract. Subsequent clinical studies uncovered a dichotomy of responses in patients with hematopoietic and solid malignancies, and the mechanisms of resistance. ©2015 American Association for Cancer Research.

  13. National Cancer Institute News

    Science.gov (United States)

    ... with Cancer Feelings and Cancer Adjusting to Cancer Self-Image & Sexuality Day-to-Day Life Support for Caregivers ... Alternative Medicine Coping Feelings & Cancer Adjusting to Cancer Self Image & Sexuality Day to Day Life Survivorship Support for ...

  14. [Use of micro RNAs in the diagnosis and prognosis of colorectal cancer (CCR)].

    Science.gov (United States)

    Arredondo-Valdez, Abril Reneé; Wence-Chavez, Laura; Rosales-Reynoso, Mónica Alejandra

    2016-01-01

    The aim of this review is to present a general overview about the importance of micro RNAs (miRNAs) in colorectal carcinoma. First, we focused on the mechanisms whereby the miRNAs regulate the expression of target genes, and how an altered regulation of them is associated with several types of cancer, including colorectal carcinoma. Later, examples of some miRNAs that have been associated with cancer development and how the expression patterns of specific miRNAs can be used as potential biomarkers for prognosis, diagnosis and therapeutic outcome in colorectal carcinoma are addressed. Finally, several polymorphisms presents in the miRNAs that have been associated to risk and prognosis in colorectal carcinoma are described.

  15. CCR study: evidence for benefit of TARP vaccine for men with early stage prostate cancer | Center for Cancer Research

    Science.gov (United States)

    Results from a pilot clinical trial found that TARP, or T-cell receptor gamma chain alternate reading frame protein, vaccination slowed prostate-specific antigen (PSA) rise in the majority of patients with early stage prostate cancer.

  16. 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.

  17. CCR 20th Anniversary Commentary: Triple-Negative Breast Cancer in 2015—Still in the Ballpark.

    Science.gov (United States)

    Narod, Steven A; Dent, Rebecca A; Foulkes, William D

    2015-09-01

    The research article by Dent and colleagues, which was published in the August 1, 2007, issue of Clinical Cancer Research, provided a clinical description of metastatic progression of triple-negative breast cancers. Finding successful treatment strategies for women with triple-negative breast cancer remains a challenge. ©2015 American Association for Cancer Research.

  18. CCR 20th Anniversary Commentary: From Regulatory T Cells to Checkpoint Monoclonal Antibodies--Immuno-oncology Advances Clinical Cancer Research.

    Science.gov (United States)

    Wolf, Dominik; Wolf, Anna Maria

    2015-06-15

    Immune escape is a hallmark of cancer development and metastasis. Regulatory T cells (Treg) are potent inhibitors of cancer immune surveillance but also prevent inflammation-driven tumorigenesis. The study by Wolf and colleagues, which was published in the February 2003 issue of Clinical Cancer Research, showed the expansion of Treg in solid cancer patients, providing a deeper understanding of cancer immune escape mechanisms that later set the stage for the development of scientific breakthroughs in cancer immunotherapy. ©2015 American Association for Cancer Research.

  19. CCR 20th Anniversary Commentary: Autologous T Cells-The Ultimate Personalized Drug for the Immunotherapy of Human Cancer.

    Science.gov (United States)

    Rosenberg, Steven A

    2015-12-15

    The article by Rosenberg and colleagues, which was published in the July 1, 2011, issue of Clinical Cancer Research, demonstrated the power of the adoptive transfer of autologous antitumor T cells to mediate the complete, durable, and likely curative regression of cancer in patients with heavily pretreated metastatic melanoma. It also provided a stimulus to the development of cell transfer approaches for other cancer types using both natural and genetically engineered lymphocytes. ©2015 American Association for Cancer Research.

  20. CCR 20th Anniversary commentary: in search of cetuximab's first indication-combination therapy with irinotecan in colorectal cancer.

    Science.gov (United States)

    Hicklin, Daniel J

    2015-04-01

    The research article by Prewett and colleagues, published in the May 1, 2002, issue of Clinical Cancer Research, provided important translational data that extended earlier preclinical and clinical studies with the human-murine chimeric anti-EGFR monoclonal antibody C225. Subsequent clinical trials with C225 led to the demonstration of its efficacy in combination with irinotecan and regulatory approval for the treatment of metastatic colorectal cancer. ©2015 American Association for Cancer Research.

  1. 77 FR 15783 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2012-03-16

    ... personal privacy. Name of Committee: National Cancer Institute Special Emphasis Panel Nanotechnology... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute... proposals. Place: National Institutes of Health, National Cancer Institute, 6116 Executive Blvd., Conference...

  2. 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

  3. TESTICULAR CANCER AT KENYATTA NATIONAL HOSPITAL ...

    African Journals Online (AJOL)

    hi-tech

    2000-02-02

    Feb 2, 2000 ... Objective: To determine the prevalence, clinical characteristics, management methods and prognosis of testicular cancer at ... component of testicular cancer management at Kenyatta National Hospital. INTRODUCTION ..... adenopathy, haemoptysis from lung metastasis, back pain from retroperitoneal ...

  4. 76 FR 576 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-01-05

    ... Committee: National Cancer Institute Special Emphasis Panel; Nanotechnology Sensing Platforms. Date: March 2... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute... Cancer Institute Special Emphasis Panel; SPORE in Mesothelioma, Lung, Breast and Ovarian Cancers. Date...

  5. 76 FR 76981 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-12-09

    ... Cancer Institute Special Emphasis Panel, Nanotechnology Reformulations for Cancer Drugs. Date: April 12... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute... Cancer Institute Special Emphasis Panel, NCI SPORE in Prostate and Gastrointestinal Cancers. Date...

  6. Radiochemotherapy in Anal Cancer: cCR, clinical outcomes and quality of life using two different treatment schedules.

    Science.gov (United States)

    Di Santo, Sara; Trignani, Marianna; Neri, Matteo; Milano, Angelo; Innocenti, Paolo; Taraborrelli, Maria; Augurio, Antonietta; Vinciguerra, Annamaria; Di Tommaso, Monica; Ursini, Lucia Anna; Di Pilla, Angelo; Di Nicola, Marta; Genovesi, Domenico

    2015-01-01

    Main endpoint was a response rate to therapy; secondary endpoints were disease-free survival, overall survival, acute and late toxicities, specially in terms of anorectal and urinary continence. Radiochemotherapy for anal cancer achieves a good clinical response, locoregional control, anal function preservation. However, oncologic outcomes can differ using radiotherapy plus fluorouracil and mytomicin vs. cisplatin and fluorouracil. Between 2000 and 2012, 27 anal cancer patients receiving radiotherapy combined with two different radiochemotherapy schedules, fluorouracil and mytomicin (group A) and cisplatin plus fluorouracil (group B). The Kaplan-Meier method was also used to estimate local control, overall survival and disease free survival. Statistical significance between curves was evaluated using the Log-rank test. Complete pathological response was found in 85.2% of patients, with higher rates of response in the group A (100% vs. 63.6%, p = 0.039). No significantly difference was found between the two groups for the other endpoints. Low rates of both acute and late toxicities were recorded. Radiotherapy plus fluorouracil and mytomicin provide a better complete pathological response than radiotherapy plus cisplatin and fluorouracil and a greater rate of anal sphincter function preservation. Globally, radiochemotherapy of the anal cancer provides excellent clinical outcomes with a good profile of acute and late toxicity, without difference between the two groups studied.

  7. National Coalition for Cancer Survivorship

    Science.gov (United States)

    ... Journey Forward Breakaway from Cancer Lilly Oncology On Canvas Our Sponsors Blog Donate The Stovall Award Cancer ... Journey Forward Breakaway from Cancer Lilly Oncology On Canvas Our Sponsors Blog Donate The Stovall Award NCCS ...

  8. CCR1 and CCR5 expressions on peripheral blood mononuclear ...

    African Journals Online (AJOL)

    Isolated PBMCs from 25 patients with HCC, 10 LC patients and 9 adult healthy controls were stained with monoclonal antibodies against CD4, CD8, CCR1 and CCR5, then detected by using a flow cytometry technique. Patients were diagnosed by abdominal ultrasound (US) and computed tomography (CT) scan findings, ...

  9. Relevance of CCL3/CCR5 axis in oral carcinogenesis.

    Science.gov (United States)

    da Silva, Janine Mayra; Moreira Dos Santos, Tálita Pollyanna; Sobral, Lays Martin; Queiroz-Junior, Celso Martins; Rachid, Milene Alvarenga; Proudfoot, Amanda E I; Garlet, Gustavo Pompermaier; Batista, Aline Carvalho; Teixeira, Mauro Martins; Leopoldino, Andréia Machado; Russo, Remo Castro; Silva, Tarcília Aparecida

    2017-08-01

    The chemokine CCL3 is a chemotactic cytokine crucial for inflammatory cell recruitment in homeostatic and pathological conditions. CCL3 might stimulate cancer progression by promoting leukocyte accumulation, angiogenesis and tumour growth. The expression of CCL3 and its receptors CCR1 and CCR5 was demonstrated in oral squamous cell carcinoma (OSCC), but their role was not defined. Here, the functions of CCL3 were assessed using a model of chemically induced tongue carcinogenesis with 4-nitroquinoline-1-oxide (4NQO). Lineages of OSCC were used to analyse the effects of CCL3 in vitro . The 4NQO-induced lesions exhibited increased expression of CCL3, CCR1 and CCR5. CCL3 -/- and CCR5 -/- mice presented reduced incidence of tongue tumours compared to wild-type (WT) and CCR1 -/- mice. Consistently, attenuated cytomorphological atypia and reduced cell proliferation were observed in lesions of CCL3 -/- and CCR5 -/- mice. OSCC from CCL3 -/- mice exhibited lower infiltration of eosinophils and reduced expression of Egf, Fgf1, Tgf-β1, Vegfa, Vegfb, Itga-4, Vtn, Mmp-1a, Mmp-2 and Mmp-9 than WT mice. In vitro , CCL3 induced invasion and production of CCL5, IL-6, MMP -2, -8, -9. Blockage of CCL3 in vitro using α-CCL3 or Evasin-1 (a CCL3-binding protein) impaired tumour cell invasion. In conclusion, CCL3/CCR5 axis has pro-tumourigenic effects in oral carcinogenesis. The induction of inflammatory and angiogenic pathways and eosinophils recruitment appear to be the underlying mechanism explaining these effects. These data reveal potential protective effects of CCL3 blockade in oral cancer.

  10. A Natural CCR2 Antagonist Relieves Tumor-associated Macrophage-mediated Immunosuppression to Produce a Therapeutic Effect for Liver Cancer

    Directory of Open Access Journals (Sweden)

    Wenbo Yao

    2017-08-01

    Full Text Available Hepatocellular carcinoma (HCC is a common malignant tumor in the digestive tract with limited therapeutic choices. Although sorafenib, an orally administered multikinase inhibitor, has produced survival benefits for patients with advanced HCC, favorable clinical outcomes are limited due to individual differences and resistance. The application of immunotherapy, a promising approach for HCC is urgently needed. Macrophage infiltration, mediated by the CCL2/CCR2 axis, is a potential immunotherapeutic target. Here, we report that a natural product from Abies georgei, named 747 and related in structure to kaempferol, exhibits sensitivity and selectivity as a CCR2 antagonist. The specificity of 747 on CCR2 was demonstrated via calcium flux, the binding domain of CCR2 was identified in an extracellular loop by chimera binding assay, and in vivo antagonistic activity of 747 was confirmed through a thioglycollate-induced peritonitis model. In animals, 747 elevated the number of CD8+ T cells in tumors via blocking tumor-infiltrating macrophage-mediated immunosuppression and inhibited orthotopic and subcutaneous tumor growth in a CD8+ T cell-dependent manner. Further, 747 enhanced the therapeutic efficacy of low-dose sorafenib without obvious toxicity, through elevating the numbers of intra-tumoral CD8+ T cells and increasing death of tumor cells. Thus, we have discovered a natural CCR2 antagonist and have provided a new perspective on development of this antagonist for treatment of HCC. In mouse models of HCC, 747 enhanced the tumor immunosuppressive microenvironment and potentiated the therapeutic effect of sorafenib, indicating that the combination of an immunomodulator with a chemotherapeutic drug could be a new approach for treating HCC.

  11. Role of major resection in pulmonary metastasectomy for colorectal cancer in the Spanish prospective multicenter study (GECMP-CCR).

    Science.gov (United States)

    Hernández, J; Molins, L; Fibla, J J; Heras, F; Embún, R; Rivas, J J

    2016-05-01

    Patients with pulmonary metastases from colorectal cancer (CRC) may benefit from aggressive surgical therapy. The objective of this study was to determine the role of major anatomic resection for pulmonary metastasectomy to improve survival when compared with limited pulmonary resection. Data of 522 patients (64.2% men, mean age 64.5 years) who underwent pulmonary resections with curative intent for CRC metastases over a 2-year period were reviewed. All patients were followed for a minimum of 3 years. Disease-specific survival (DSS) and disease-free survival (DFS) were assessed with the Kaplan-Meier method. Factors associated with DSS and DFS were analyzed using a Cox proportional hazards regression model. A total of 394 (75.6%) patients underwent wedge resection, 19 (3.6%) anatomic segmentectomy, 5 (0.9%) lesser resections not described, 100 (19.3%) lobectomy, and 4 (0.8%) pneumonectomy. Accordingly, 104 (19.9%) patients were treated with major anatomic resection and 418 (80.1%) with lesser resection. Operations were carried out with video-assisted thoracoscopic surgery (VATS) in 93 patients. The overall DSS and DFS were 55 and 28.3 months, respectively. Significant differences in DSS and DFS in favor of major resection versus lesser resection (DSS median not reached versus 52.2 months, P = 0.03; DFS median not reached versus 23.9 months, P < 0.001) were found. In the multivariate analysis, major resection appeared to be a protective factor in DSS [hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.41-0.96, P = 0.031] and DFS (HR 0.5, 95% CI 0.36-0.75, P < 0.001). The surgical approach (VATS versus open surgical resection) had no effect on outcome. Major anatomic resection with lymphadenectomy for pulmonary metastasectomy can be considered in selected CRC patient with sufficient functional reserve to improve the DSS and DFS. Further prospective randomized studies are needed to confirm the present results. © The Author 2016. Published by Oxford University Press

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Chemokine receptors are involved in trafficking of leukocytes and represent targets for autoimmune conditions, inflammatory diseases, viral infections, and cancer. We recently published CCR1, CCR8, and CCR5 agonists and positive modulators based on a three metal-ion chelator series: 2,2'-bipyridine...... 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...

  13. 75 FR 5092 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-02-01

    ... . Name of Committee: National Cancer Institute Special Emphasis Panel, Quantitative Cell-Based Imaging....396, Cancer Biology Research; 93.397, Cancer Centers Support; 93.398, Cancer Research Manpower; 93.399... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute...

  14. National Cancer Center Singapore: the way forward.

    Science.gov (United States)

    Teo, Melissa; Soo, Khee Chee

    2016-02-01

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

  15. Tumor hypoxia modulates podoplanin/CCL21 interactions in CCR7+ NK cell recruitment and CCR7+ tumor cell mobilization.

    Science.gov (United States)

    Tejchman, Anna; Lamerant-Fayel, Nathalie; Jacquinet, Jean-Claude; Bielawska-Pohl, Aleksandra; Mleczko-Sanecka, Katarzyna; Grillon, Catherine; Chouaib, Salem; Ugorski, Maciej; Kieda, Claudine

    2017-05-09

    Podoplanin (PDPN), an O-glycosylated, transmembrane, mucin-type glycoprotein, is expressed by cancer associated fibroblasts (CAFs). In malignant transformation, PDPN is subjected to changes and its role is yet to be established. Here we show that it is involved in modulating the activity of the CCL21/CCR7 chemokine/receptor axis in a hypoxia-dependent manner. In the present model, breast cancer MDA-MB-231 cells and NKL3 cells express the surface CCR7 receptor for CCL21 chemokine which is a potent chemoattractant able to bind to PDPN. The impact of the CCL21/CCR7 axis in the molecular mechanism of the adhesion of NKL3 cells and of MDA-MB-231 breast cancer cells was reduced in a hypoxic tumor environment. In addition to its known effect on migration, CCL21/CCR7 interaction was shown to allow NK cell adhesion to endothelial cells (ECs) and its reduction by hypoxia. A PDPN expressing model of CAFs made it possible to demonstrate the same CCL21/CCR7 axis involvement in the tumor cells to CAFs recognition mechanism through PDPN binding of CCL21. PDPN was induced by hypoxia and its overexpression undergoes a reduction of adhesion, making it an anti-adhesion molecule in the absence of CCL21, in the tumor. CCL21/CCR7 modulated NK cells/ECs and MDA-MB-231 cells/CAF PDPN-dependent interactions were further shown to be linked to hypoxia-dependent microRNAs as miRs: miR-210 and specifically miR-21, miR-29b which influence PDPN expression.

  16. CCR researchers show that blocking the estrogen receptor restores the sensitivity of lung cancer cells to therapy | Center for Cancer Research

    Science.gov (United States)

    Claudia Palena, Ph.D., of CCR’s Laboratory of Tumor Immunology and Biology, and her colleagues wondered if it would be possible to identify compounds that could reverse the therapy resistance imparted by the process called epithelial-mesenchymal transition (EMT) in lung cancer.

  17. 76 FR 9353 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-02-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute.... Place: Bethesda North Marriott Hotel & Conference Center, 5701 Marinelli Road, Bethesda, MD 20852... Branch, Division of Extramural Activities, National Cancer Institute, 6116 Executive Blvd., Room 8101...

  18. Peripheral Blood CCR4+CCR6+ and CXCR3+CCR6+ CD4+ T Cells Are Highly Permissive to HIV-1 Infection

    OpenAIRE

    Gosselin, Annie; Monteiro, Patricia; Chomont, Nicolas; Diaz-Griffero, Felipe; Said, Elias A.; Fonseca, Simone; Wacleche, Vanessa; El-Far, Mohamed; Boulassel, Mohamed-Rachid; Routy, Jean-Pierre; Sekaly, Rafick-Pierre; Ancuta, Petronela

    2009-01-01

    There is limited knowledge on the identity of primary CD4+ T cell subsets selectively targeted by HIV-1 in vivo. In this study, we established a link between HIV permissiveness, phenotype/homing potential, and lineage commitment in primary CD4+ T cells. CCR4+CCR6+, CCR4+CCR6−, CXCR3+CCR6+, and CXCR3+CCR6− T cells expressed cytokines and transcription factors specific for Th17, Th2, Th1Th17, and Th1 lineages, respectively. CCR4+CCR6+ and CXCR3+CCR6+ T cells expressed the HIV coreceptors CCR5 a...

  19. Administrative Assistant | Center for Cancer Research

    Science.gov (United States)

    An administrative assistant position is available immediately in the Laboratory of Genome Integrity (LGI) within the Center for Cancer Research (CCR) in the National Cancer Institute (NCI). The LGI is actively looking for someone with administrative skills who will facilitate personnel, travel and related demands that support the laboratory chief, all principal investigators and postdoctoral fellows and laboratory support staff. 

  20. 78 FR 55750 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-09-11

    ... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed Meetings... Innovative Molecular Analysis Technology Development for Cancer Research (R21). Date: October 24, 2013. Time...: National Cancer Institute Special Emphasis Panel; Integrative Cancer Biology. Date: October 29, 2013. Time...

  1. 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 Meetings...

  2. 76 FR 16431 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-03-23

    ... Committee: National Cancer Institute Special Emphasis Panel; SPORE in Lymphoma, Breast, Ovarian... 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 Meeting...

  3. 75 FR 14172 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-03-24

    ... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed Meetings... Emphasis Panel, Nucleic Acid Analysis for the Molecular Characterization of Cancer. Date: April 6, 2010... Biology Research; 93.397, Cancer Centers Support; 93.398, Cancer Research Manpower; 93.399, Cancer Control...

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

    Science.gov (United States)

    2010-12-17

    ... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed Meetings... Cancer Institute Special Emphasis Panel. Development of Devices for Point of Care Analysis of Circulating... Biology Research; 93.397, Cancer Centers Support; 93.398, Cancer Research Manpower; 93.399, Cancer Control...

  5. 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...; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93.396, Cancer... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed Meetings...

  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..., Cancer Cause and Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed Meetings...

  7. 78 FR 27408 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-05-10

    ... Methods for the Detection of Cancer Recurrence in Post-Therapy Breast Cancer Patients. Date: June 4, 2013... Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed Meetings...

  8. 76 FR 52960 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-08-24

    ... Emphasis Panel, Mechanisms of Cell Signaling in Cancer. Date: October 13-14, 2011. Time: 3 to 5 p.m. Agenda..., Cancer Treatment Research; 93.396, Cancer Biology Research; 93.397, Cancer Centers Support; 93.398... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute...

  9. Involvement of CCR6/CCL20/IL-17 Axis in NSCLC Disease Progression

    Science.gov (United States)

    Amir, Gail; Demma, Jonathan; Vernea, Fiona; Beider, Katia; Shlomai, Zippora; Wald, Hanna; Zamir, Gideon; Shapira, Oz M.; Peled, Amnon; Wald, Ori

    2011-01-01

    Objectives Autocrine and paracrine chemokine/chemokine receptor-based interactions promote non-small-cell-lung-cancer (NSCLC) carcinogenesis. CCL20/CCR6 interactions are involved in prostatic and colonic malignancy pathogenesis. The expression and function of CCL20/CCR6 and its related Th-17 type immune response in NSCLC is not yet defined. We sought to characterize the role of the CCL20/CCR6/IL-17 axis in NSCLC tumor growth. Methods A specialized histopathologist blindly assessed CCL20/CCR6 expression levels in 49 tissue samples of NSCLC patients operated in our department. Results were correlated to disease progression. Colony assays, ERK signaling and chemokine production were measured to assess cancer cell responsiveness to CCL20 and IL-17 stimulation. Results CCL20 was highly expressed in the majority (38/49, 77.5%) of tumor samples. Only a minority of samples (8/49, 16.5%) showed high CCR6 expression. High CCR6 expression was associated with a shorter disease-free survival (P = 0.008) and conferred a disease stage-independent 4.87-fold increased risk for disease recurrence (P = 0.0076, CI 95% 1.52–15.563). Cancerous cell colony-forming capacity was increased by CCL20 stimulation; this effect was dependent in part on ERK phosphorylation and signaling. IL-17 expression was detected in NSCLC; IL-17 potentiated the production of CCL20 by cancerous cells. Conclusion Our findings suggest that the CCL20/CCR6 axis promotes NSCLC disease progression. CCR6 is identified as a potential new prognostic marker and the CCL20/CCR6/IL-17 axis as a potential new therapeutic target. Larger scale studies are required to consolidate these observations. PMID:21949768

  10. 78 FR 44577 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2013-07-24

    ... and AIDS Malignancy priorities. Place: National Cancer Institute, NIH, Building 10, Room 10S255, 10... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute.... App.), notice is hereby given of a meeting of the National Cancer Institute Board of Scientific...

  11. Regulation of CCR7-dependent cell migration through?CCR7 homodimer formation

    OpenAIRE

    Kobayashi, Daichi; Endo, Masataka; Ochi, Hirotaka; Hojo, Hironobu; Miyasaka, Masayuki; Hayasaka, Haruko

    2017-01-01

    The chemokine receptor CCR7 contributes to various physiological and pathological processes including T cell maturation, T cell migration from the blood into secondary lymphoid tissues, and tumor cell metastasis to lymph nodes. Although a previous study suggested that the efficacy of CCR7 ligand-dependent T cell migration correlates with CCR7 homo- and heterodimer formation, the exact extent of contribution of the CCR7 dimerization remains unclear. Here, by inducing or disrupting CCR7 dimers,...

  12. Molecular characterization and expression analysis of four fish-specific CC chemokine receptors CCR4La, CCR4Lc1, CCR4Lc2 and CCR11 in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Qi, Zhitao; Holland, Jason W; Jiang, Yousheng; Secombes, Christopher J; Nie, Pin; Wang, Tiehui

    2017-09-01

    The chemokine and chemokine receptor networks regulate leukocyte trafficking, inflammation, immune cell differentiation, cancer and other biological processes. Comparative immunological studies have revealed that both chemokines and their receptors have expanded greatly in a species/lineage specific way. Of the 10 human CC chemokine receptors (CCR1-10) that bind CC chemokines, orthologues only to CCR6, 7, 9 and 10 are present in teleost fish. In this study, four fish-specific CCRs, termed as CCR4La, CCR4Lc1, CCR4Lc2 and CCR11, with a close link to human CCR1-5 and 8, in terms of amino acid homology and syntenic conservation, have been identified and characterized in rainbow trout (Oncorhynchus mykiss). These CCRs were found to possess the conserved features of the G protein-linked receptor family, including an extracellular N-terminal, seven TM domains, three extracellular loops and three intracellular loops, and a cytoplasmic carboxyl tail with multiple potential serine/threonine phosphorylation sites. Four cysteine residues known to be involved in forming two disulfide bonds are present in the extracellular domains and a DRY motif is present in the second intracellular loop. Signaling mediated by these receptors might be regulated by N-glycosylation, tyrosine sulfation, S-palmitoylation, a PDZ ligand motif and di-leucine motifs. Studies of intron/exon structure revealed distinct fish-specific CCR gene organization in different fish species/lineages that might contribute to the diversification of the chemokine ligand-receptor networks in different fish lineages. Fish-specific trout CCRs are highly expressed in immune tissues/organs, such as thymus, spleen, head kidney and gills. Their expression can be induced by the pro-inflammatory cytokines, IL-1β, IL-6 and IFNγ, by the pathogen associated molecular patterns, PolyIC and peptidoglycan, and by bacterial infection. These data suggest that fish-specific CCRs are likely to have an important role in immune

  13. 76 FR 17930 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-03-31

    ... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed Meetings... Special Emphasis Panel; Innovative Emerging Molecular Analysis Technologies. Date: June 2-3, 2011. Time: 8..., Cancer Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93.396, Cancer Biology...

  14. 78 FR 46357 - National Cancer Institute; Amended Notice of Meeting

    Science.gov (United States)

    2013-07-31

    ... Cancer Institute Board of Scientific Advisors ad hoc Subcommittee on HIV/AIDS Malignancy, August 08, 2013, 10:30 a.m. to 12:00 p.m., National Cancer Institute, NIH, Building 10, Room 10S255, 10 Center Drive... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute...

  15. 75 FR 7489 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-02-19

    ... Institute Special Emphasis Panel; NCI Cancer Nanotechnology Training (R25) and Career Development Award (K99... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute... personal privacy. Name of Committee: National Cancer Institute Special Emphasis Panel; The Early Detection...

  16. 78 FR 16272 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-03-14

    ...: National Cancer Institute Special Emphasis Panel, Nanotechnology RNA Therapeutics. Date: April 18-19, 2013... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute... Cancer Institute Special Emphasis Panel, NCI Provocative Questions. Date: March 28, 2013. Time: 7:30 a.m...

  17. 76 FR 69744 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-11-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute... personal privacy. Name of Committee: National Cancer Institute Special Emphasis Panel, Cancer Diagnostic and Therapeutic Agents Enabled by Nanotechnology. Date: November 29, 2011. Time: 8 a.m. to 7 p.m...

  18. 75 FR 26968 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-05-13

    ...: National Cancer Institute Special Emphasis Panel; Nanotechnology Imaging and Sensing Platforms. Date: June... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute... Cancer Institute Special Emphasis Panel; Adult Brain Tumor Consortium. Date: May 20, 2010. Time: 1 p.m...

  19. CCR1+/CCR5+ mononuclear phagocytes accumulate in the central nervous system of patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Trebst, C; Sørensen, Torben Lykke; Kivisäkk, P

    2001-01-01

    and macrophage inflammatory protein-1alpha/CCL3. We analyzed expression of CCR1 and CCR5, the monocyte receptors for these chemokines, on circulating and cerebrospinal fluid CD14+ cells, and in MS brain lesions. Approximately 70% of cerebrospinal fluid monocytes were CCR1+/CCR5+, regardless of the presence...... of CNS pathology, compared to less than 20% of circulating monocytes. In active MS lesions CCR1+/CCR5+ monocytes were found in perivascular cell cuffs and at the demyelinating edges of evolving lesions. Mononuclear phagocytes in early demyelinating stages comprised CCR1+/CCR5+ hematogenous monocytes...... and CCR1-/CCR5- resident microglial cells. In later stages, phagocytic macrophages were uniformly CCR1-/CCR5+. Cultured in vitro, adherent monocytes/macrophages up-regulated CCR5 and down-regulated CCR1 expression, compared to freshly-isolated monocytes. Taken together, these findings suggest...

  20. Molekulare Klonierung, stabile Transfektion und funktionelle Expression der murinen Chemokinrezeptoren Ccr2 und Ccr5

    OpenAIRE

    Simonis, Christopher

    2009-01-01

    The two chemokine receptors CCR2 and CCR5 play important roles in the recruitment and activation of monocytes/macrophages and T-lymphocytes at sites of infection and inflammation. To further examine their function, I cloned the two murine chemokine receptors Ccr2 and Ccr5 from genomic mouse DNA by a PCR-based cloning strategy and functionally expressed them in stably transfected CHO-cells. These cells were used to generate the first monoclonal antibodies against Ccr2 and Ccr5.

  1. 76 FR 19257 - National Cancer Control Month, 2011

    Science.gov (United States)

    2011-04-06

    ... April 6, 2011 Part IV The President Proclamation 8644 --National Cancer Control Month, 2011 Proclamation 8645 --National Child Abuse Prevention Month, 2011 Proclamation 8646 --National Financial Literacy... 8644 of March 31, 2011 National Cancer Control Month, 2011 By the President of the United States of...

  2. The Danish National Penile Cancer Quality database

    Directory of Open Access Journals (Sweden)

    Jakobsen JK

    2016-10-01

    Full Text Available Jakob Kristian Jakobsen,1 Buket Öztürk,2 Mette Søgaard2 1Department of Urology, 2Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus Nord, Denmark Aim of database: The Danish National Penile Cancer Quality database (DaPeCa-data aims to improve the quality of cancer care and monitor the diagnosis, staging, and treatment of all incident penile cancer cases in Denmark. The aim is to assure referral practice, guideline adherence, and treatment and development of the database in order to enhance research opportunities and increase knowledge and survival outcomes of penile cancer. Study population: The DaPeCa-data registers all patients with newly diagnosed invasive squamous cell carcinoma of the penis in Denmark since June 2011. Main variables: Data are systematically registered at the time of diagnosis by a combination of automated data-linkage to the central registries as well as online registration by treating clinicians. The main variables registered relate to disease prognosis and treatment morbidity and include the presence of risk factors (phimosis, lichen sclerosus, and human papillomavirus, date of diagnosis, date of treatment decision, date of beginning of treatment, type of treatment, treating hospital, type and time of complications, date of recurrence, date of death, and cause of death. Descriptive data: Registration of these variables correlated to the unique Danish ten-digit civil registration number enables characterization of the cohort, individual patients, and patient groups with respect to age; 1-, 3-, and 5-year disease-specific and overall survival; recurrence patterns; and morbidity profile related to treatment modality. As of August 2015, more than 200 patients are registered with ~65 new entries per year. Conclusion: The DaPeCa-data has potential to provide meaningful, timely, and clinically relevant quality data for quality maintenance, development, and research purposes. Keywords: penile cancer

  3. 78 FR 30933 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-05-23

    .... Time: 1:00 p.m. to 4:00 p.m. Agenda: To review and evaluate contract proposals. Place: National Cancer... Conference Call). Contact Person: Clifford W Schweinfest, Ph.D., Scientific Review Officer, Special Review... Committee: National Cancer Institute Special Emphasis Panel; Nanotech-Biosensor Platforms for Cancer. Date...

  4. 75 FR 44274 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-07-28

    ... Cancer Institute Special Emphasis Panel, Nanotechnology Imaging and Sensing Platforms for Improved Diagnosis of Cancer. Date: August 31, 2010. Time: 12 p.m. to 1:30 p.m. Agenda: To review and evaluate... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute...

  5. 75 FR 62297 - National Breast Cancer Awareness Month, 2010

    Science.gov (United States)

    2010-10-08

    ..., diagnosis, and treatment of breast and other cancers. Screenings and early detection are also essential... 8572 of October 1, 2010 National Breast Cancer Awareness Month, 2010 By the President of the United... nearly 40,000 lives will be claimed. During National Breast Cancer Awareness Month, we reaffirm our...

  6. CCR 20th Anniversary Commentary: Gene-Expression Signature in Breast Cancer--Where Did It Start and Where Are We Now?

    Science.gov (United States)

    Gingras, Isabelle; Desmedt, Christine; Ignatiadis, Michail; Sotiriou, Christos

    2015-11-01

    Desmedt and colleagues published two articles, one in the June 1, 2007 issue, and the other in the August 15, 2008, issue of Clinical Cancer Research, that showed gene-expression signatures to be proliferation driven and time dependent, with their prognostic power decreasing with increasing follow-up years. Moreover, the articles showed that immune response is a crucial determinant of prognosis in the HER2-positive and estrogen receptor-negative/HER2-negative subtypes, providing a rationale to further explore the role of the antitumor immune response in these breast cancer subtypes. ©2015 American Association for Cancer Research.

  7. 77 FR 60605 - National Breast Cancer Awareness Month, 2012

    Science.gov (United States)

    2012-10-04

    ... provider about breast cancer, and to visit www.Cancer.gov to learn more about symptoms, diagnosis, and... 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...

  8. CCR 20th Anniversary Commentary: RAS as a Biomarker for EGFR--Targeted Therapy for Colorectal Cancer-From Concept to Practice.

    Science.gov (United States)

    Camp, E Ramsay; Ellis, Lee M

    2015-08-15

    Clinical data support the use of EGFR mAbs in patients with metastatic colorectal cancer (mCRC) with wild-type RAS status. This notion, hypothesized in the review article by Camp, Ellis, and colleagues in the January 1, 2005, issue of Clinical Cancer Research, serves as an example of the successful application of basic science principles to clinical practice. The exclusion of patients with mCRC with Ras-mutated tumors from therapy with EGFR mAbs has led to improved outcomes while sparing patients unnecessary and potentially harmful therapy. See related article by Camp et al., Clin Cancer Res 2005;11(1): January 1, 2005;397-405. ©2015 American Association for Cancer Research.

  9. 75 FR 54451 - National Ovarian Cancer Awareness Month, 2010

    Science.gov (United States)

    2010-09-07

    ... claim more lives than any other gynecologic cancer. During National Ovarian Cancer Awareness Month, we... Control and Prevention, and the Department of Defense all play vital roles in reducing the burden of this...

  10. CCR+: Metadata Based Extended Personal Health Record Data Model Interoperable with the ASTM CCR Standard.

    Science.gov (United States)

    Park, Yu Rang; Yoon, Young Jo; Jang, Tae Hun; Seo, Hwa Jeong; Kim, Ju Han

    2014-01-01

    Extension of the standard model while retaining compliance with it is a challenging issue because there is currently no method for semantically or syntactically verifying an extended data model. A metadata-based extended model, named CCR+, was designed and implemented to achieve interoperability between standard and extended models. Furthermore, a multilayered validation method was devised to validate the standard and extended models. The American Society for Testing and Materials (ASTM) Community Care Record (CCR) standard was selected to evaluate the CCR+ model; two CCR and one CCR+ XML files were evaluated. In total, 188 metadata were extracted from the ASTM CCR standard; these metadata are semantically interconnected and registered in the metadata registry. An extended-data-model-specific validation file was generated from these metadata. This file can be used in a smartphone application (Health Avatar CCR+) as a part of a multilayered validation. The new CCR+ model was successfully evaluated via a patient-centric exchange scenario involving multiple hospitals, with the results supporting both syntactic and semantic interoperability between the standard CCR and extended, CCR+, model. A feasible method for delivering an extended model that complies with the standard model is presented herein. There is a great need to extend static standard models such as the ASTM CCR in various domains: the methods presented here represent an important reference for achieving interoperability between standard and extended models.

  11. 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.

  12. 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; Zikursh, Melinda J Blood; 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-valuesnew insights regarding CCR5 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. 78 FR 4422 - National Cancer Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-01-22

    ... personal privacy. Name of Committee: National Cancer Institute Special Emphasis Panel; The Role of..., Ph.D., Scientific Review Administrator, Special Review and Logistics Branch, Division of Extramural...

  14. CCL5 and CCR5 interaction promotes cell motility in human osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Shih-Wei Wang

    Full Text Available BACKGROUND: Osteosarcoma is characterized by a high malignant and metastatic potential. CCL5 (previously called RANTES was originally recognized as a product of activated T cells, and plays a crucial role in the migration and metastasis of human cancer cells. It has been reported that the effect of CCL5 is mediated via CCR receptors. However, the effect of CCL5 on migration activity and integrin expression in human osteosarcoma cells is mostly unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we found that CCL5 increased the migration and expression of αvβ3 integrin in human osteosarcoma cells. Stimulation of cells with CCL5 increased CCR5 but not CCR1 and CCR3 expression. CCR5 mAb, inhibitor, and siRNA reduced the CCL5-enhanced the migration and integrin up-regulation of osteosarcoma cells. Activations of MEK, ERK, and NF-κB pathways after CCL5 treatment were demonstrated, and CCL5-induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of MEK, ERK, and NF-κB cascades. In addition, over-expression of CCL5 shRNA inhibited the migratory ability and integrin expression in osteosarcoma cells. CONCLUSIONS/SIGNIFICANCE: CCL5 and CCR5 interaction acts through MEK, ERK, which in turn activates NF-κB, resulting in the activations of αvβ3 integrin and contributing the migration of human osteosarcoma cells.

  15. 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.

  16. Monitoring the delivery of cancer care: Commission on Cancer and National Cancer Data Base.

    Science.gov (United States)

    Williams, Richelle T; Stewart, Andrew K; Winchester, David P

    2012-07-01

    The primary objective of the Commission on Cancer (CoC) is to ensure the delivery of comprehensive, high-quality care that improves survival while maintaining quality of life for patients with cancer. This article examines the initiatives of the CoC toward achieving this goal, utilizing data from the National Cancer Data Base (NCDB) to monitor treatment patterns and outcomes, to develop quality measures, and to benchmark hospital performance. The article also highlights how these initiatives align with the Institute of Medicine's recommendations for improving the quality of cancer care and briefly explores future projects of the CoC and NCDB. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. 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. 

  18. 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...

  19. 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...

  20. 77 FR 55091 - National Childhood Cancer Awareness Month, 2012

    Science.gov (United States)

    2012-09-06

    ... be done, our Nation has come far in the fight to understand, treat, and control childhood cancer... cancer and work to ease the burdens they face. Under the Affordable Care Act, insurance companies can no... they drop coverage because a child is diagnosed with cancer. The law also bans insurers from placing a...

  1. Influence of the CCR2-V64I Polymorphism on Human Immunodeficiency Virus Type 1 Coreceptor Activity and on Chemokine Receptor Function of CCR2b, CCR3, CCR5, and CXCR4

    OpenAIRE

    Lee, Benhur; Doranz, Benjamin J.; Rana, Shalini; Yi, Yanji; Mellado, Mario; Frade, Jose M. R.; Martinez-A., Carlos; O’Brien, Stephen J.; Dean, Michael; Collman, Ronald G.; Doms, Robert W.

    1998-01-01

    The chemokine receptors CCR5 and CXCR4 are used by human immunodeficiency virus type 1 (HIV-1) in conjunction with CD4 to infect cells. In addition, some virus strains can use alternative chemokine receptors, including CCR2b and CCR3, for infection. A polymorphism in CCR2 (CCR2-V64I) is associated with a 2- to 4-year delay in the progression to AIDS. To investigate the mechanism of this protective effect, we studied the expression of CCR2b and CCR2b-V64I, their chemokine and HIV-1 coreceptor ...

  2. Constrained use of CCR5 on CD4+ lymphocytes by R5X4 HIV-1: Efficiency of Env-CCR5 interactions and low CCR5 expression determine a range of restricted CCR5-mediated entry

    OpenAIRE

    Loftin, Lamorris M.; Kienzle, Martha F.; Yi, Yanjie; Lee, Benhur; Lee, Fang-Hua; Gray, Lachlan; Gorry, Paul R.; Collman, Ronald G.

    2010-01-01

    R5X4 HIV-1 have impaired utilization of CCR5 on primary CD4+ lymphocytes but the mechanisms responsible are not well defined. Using a panel of diverse R5X4 Envs we identified a spectrum of CCR5 use on CD4+ lymphocytes. Greater lymphocyte CCR5 use correlated with relative resistance to CCR5 mAbs and small molecule antagonists. Increasing CCR5 expression on lymphocytes increased the proportion of entry mediated by CCR5 for all R5X4 isolates except 89.6. In cell lines with regulated CCR5 express...

  3. 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...

  4. Why CCR2 and CCR5 blockade failed and why CCR1 blockade might still be effective in the treatment of rheumatoid arthritis

    OpenAIRE

    Lebre, M.C.; Vergunst, C.E.; Choi, I.Y.K.; Aarrass, S.; Oliveira, A.S.F.; Wyant, T.; Horuk, R.; Reedquist, K.A.; Tak, P.P.

    2011-01-01

    BACKGROUND: The aim of this study was to provide more insight into the question as to why blockade of CCR1, CCR2, and CCR5 may have failed in clinical trials in rheumatoid arthritis (RA) patients, using an in vitro monocyte migration system model. METHODOLOGY/PRINCIPAL FINDINGS: Monocytes from healthy donors (HD; n = 8) or from RA patients (for CCR2 and CCR5 antibody n = 8; for CCR1 blockade n = 13) were isolated from peripheral blood and pre-incubated with different concentrations of either ...

  5. Increased frequency of CCR4+ and CCR6+ memory T-cells including CCR7+CD45RAmed very early memory cells in granulomatosis with polyangiitis (Wegener's)

    OpenAIRE

    Fagin, Ursula; Pitann, Silke; Gross, Wolfgang L; Lamprecht, Peter

    2012-01-01

    Introduction Chemokine receptors play an important role in mediating the recruitment of T cells to inflammatory sites. Previously, small proportions of circulating Th1-type CCR5+ and Th2-type CCR3+ cells have been shown in granulomatosis with polyangiitis (GPA). Wondering to what extent CCR4 and CCR6 expression could also be implicated in T cell recruitment to inflamed sites in GPA, we investigated the expression of CCR4 and CCR6 on T cells and its association with T cell diversity and polari...

  6. 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....

  7. United States military contributions to the National Cancer Institute.

    Science.gov (United States)

    Sarvis, Jamey A; Thompson, Ian M

    2009-01-01

    To review contributions from the Department of Defense and the United States military to cancer research and the National Cancer Institute. The Department of Defense and the military have a number of programs aimed at cancer research with significant dedication to prostate cancer, such as the Prostate Cancer Research Program and Center for Prostate Disease Research. In addition, the military has significant involvement with the National Cancer Institute (NCI) through the various Cooperative Research Groups. The military has played a critical role in large NCI sponsored multi-institutional clinical trials such as the Prostate Cancer Prevention Trial (PCPT) and the Servicemen's Testicular Tumor Environmental Endocrine Determinants Study (STEED). The Department of Defense has demonstrated a consistent commitment to cancer research.

  8. Validity of the CR-POSSUM model in surgery for colorectal cancer in Spain (CCR-CARESS study) and comparison with other models to predict operative mortality.

    Science.gov (United States)

    Baré, Marisa; Alcantara, Manuel Jesús; Gil, Maria José; Collera, Pablo; Pont, Marina; Escobar, Antonio; Sarasqueta, Cristina; Redondo, Maximino; Briones, Eduardo; Dujovne, Paula; Quintana, Jose Maria

    2018-01-29

    To validate and recalibrate the CR- POSSUM model and compared its discriminatory capacity with other European models such as POSSUM, P-POSSUM, AFC or IRCS to predict operative mortality in surgery for colorectal cancer. Prospective multicenter cohort study from 22 hospitals in Spain. We included patients undergoing planned or urgent surgery for primary invasive colorectal cancers between June 2010 and December 2012 (N = 2749). Clinical data were gathered through medical chart review. We validated and recalibrated the predictive models using logistic regression techniques. To calculate the discriminatory power of each model, we estimated the areas under the curve - AUC (95% CI). We also assessed the calibration of the models by applying the Hosmer-Lemeshow test. In-hospital mortality was 1.5% and 30-day mortality, 1.7%. In the validation process, the discriminatory power of the CR-POSSUM for predicting in-hospital mortality was 73.6%. However, in the recalibration process, the AUCs improved slightly: the CR-POSSUM reached 75.5% (95% CI: 67.3-83.7). The discriminatory power of the CR-POSSUM for predicting 30-day mortality was 74.2% (95% CI: 67.1-81.2) after recalibration; among the other models the POSSUM had the greatest discriminatory power, with an AUC of 77.0% (95% CI: 68.9-85.2). The Hosmer-Lemeshow test showed good fit for all the recalibrated models. The CR-POSSUM and the other models showed moderate capacity to discriminate the risk of operative mortality in our context, where the actual operative mortality is low. Nevertheless the IRCS might better predict in-hospital mortality, with fewer variables, while the CR-POSSUM could be slightly better for predicting 30-day mortality. Registered at: ClinicalTrials.gov Identifier: NCT02488161.

  9. Clinical complete response (cCR) after neoadjuvant chemoradiotherapy and conservative treatment in rectal cancer. Findings from the ACCORD 12/PRODIGE 2 randomized trial.

    Science.gov (United States)

    Gérard, Jean-Pierre; Chamorey, Emmanuel; Gourgou-Bourgade, Sophie; Benezery, Karène; de Laroche, Guy; Mahé, Marc-André; Boige, Valérie; Juzyna, Béata

    2015-05-01

    During the ACCORD 12 randomized trial, an evaluation of the clinical tumor response was prospectively performed after neoadjuvant chemoradiotherapy. The correlations between clinical complete response and patient characteristics and treatment outcomes are reported. Between 2005 and 2008 the Accord 12 trial accrued 598 patients with locally advanced rectal cancer and compared two different neoadjuvant chemoradiotherapies (Capox 50: capecitabine+oxaliplatin+50Gy vs Cap 45: capecitabine+45Gy). An evaluation of the clinical tumor response with rectoscopy and digital rectal examination was planned before surgery. A score to classify tumor response was used adapted from the RECIST definition: complete response: no visible or palpable tumor; partial response, stable and progressive disease. The clinical tumor response was evaluable in 201 patients. Score was: complete response: 8% (16 patients); partial response: 68% (137 patients); stable: 21%; progression: 3%. There was a trend toward more complete response in the Capox 50 group (9.3% vs 6.7% with Cap 45). In the whole cohort of 201 pts complete response was significantly more frequent in T2 tumors (28%; p=0.025); tumors <4cm in diameter (14%; p=0.017), less than half rectal circumference and with a normal CEA level. Clinical complete response observed in 16 patients was associated with more conservative treatment (p=0.008): 2 patients required an abdomino-perineal resection, 11 an anterior resection and 3 patients benefited from organ preservation (2 local excision, 1 "watch and wait". A complete response was associated with more ypT0 (73%; p<0.001); ypNO (92%); R0 circumferential margin (100%). These data support the hypothesis that a clinical complete response assessed using rectoscopy and digital rectal examination after neoadjuvant therapy may increase the chance of a sphincter or organ preservation in selected rectal cancers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. 75 FR 56455 - National Childhood Cancer Awareness Month, 2010

    Science.gov (United States)

    2010-09-15

    ... Part V The President Proclamation 8556--National Childhood Cancer Awareness Month, 2010 Proclamation 8557--National Historically Black Colleges and Universities Week, 2010 Proclamation 8558--National..., and of the Independence of the United States of America the two hundred and thirty-fifth...

  11. 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.

  12. Stimulation of oral fibroblast chemokine receptors identifies CCR3 and CCR4 as potential wound healing targets

    Science.gov (United States)

    Buskermolen, Jeroen K.; Roffel, Sanne

    2017-01-01

    The focus of this study was to determine which chemokine receptors are present on oral fibroblasts and whether these receptors influence proliferation, migration, and/or the release of wound healing mediators. This information may provide insight into the superior wound healing characteristics of the oral mucosa. The gingiva fibroblasts expressed 12 different chemokine receptors (CCR3, CCR4, CCR6, CCR9, CCR10, CXCR1, CXCR2, CXCR4, CXCR5, CXCR7, CX3CR1, and XCR1), as analyzed by flow cytometry. Fourteen corresponding chemokines (CCL5, CCL15, CCL20, CCL22, CCL25, CCL27, CCL28, CXCL1, CXCL8, CXCL11, CXCL12, CXCL13, CX3CL1, and XCL1) were used to study the activation of these receptors on gingiva fibroblasts. Twelve of these fourteen chemokines stimulated gingiva fibroblast migration (all except for CXCL8 and CXCL12). Five of the chemokines stimulated proliferation (CCL5/CCR3, CCL15/CCR3, CCL22/CCR4, CCL28/CCR3/CCR10, and XCL1/XCR1). Furthermore, CCL28/CCR3/CCR10 and CCL22/CCR4 stimulation increased IL‐6 secretion and CCL28/CCR3/CCR10 together with CCL27/CCR10 upregulated HGF secretion. Moreover, TIMP‐1 secretion was reduced by CCL15/CCR3. In conclusion, this in‐vitro study identifies chemokine receptor‐ligand pairs which may be used in future targeted wound healing strategies. In particular, we identified the chemokine receptors CCR3 and CCR4, and the mucosa specific chemokine CCL28, as having an predominant role in oral wound healing by increasing human gingiva fibroblast proliferation, migration, and the secretion of IL‐6 and HGF and reducing the secretion of TIMP‐1. PMID:28387445

  13. 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

    interact with residues in the main binding crevice, we show that the 7TM-conserved bridge is essential for all types of ligand-mediated activation, whereas the chemokine-conserved bridge is dispensable for small-molecule activation in CCR1. However, in striking contrast to previous studies in other...... 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...

  14. CCL5, CCR1 and CCR5 in murine glioblastoma: immune cell infiltration and survival rates are not dependent on individual expression of either CCR1 or CCR5

    OpenAIRE

    Pham, Kien; Luo, Defang; Liu, Che; Harrison, Jeffrey K.

    2012-01-01

    Glioblastoma multiforme (GBM) is the most malignant brain tumor. Microglia/macrophages are found within human GBM where they likely promote tumor progression. We report that CCL5, CCR1, and CCR5 are expressed in glioblastoma. Individual deletion of CCR1 or CCR5 had little to no effect on survival of tumor bearing mice, or numbers of glioblastoma-infiltrated microglia/macrophages or lymphocytes. CCL5 promoted in vitro migration of wild type, CCR1- or CCR5-deficient microglia/macrophages that w...

  15. Colorectal carcinoma metastases: Detection with In-111-labeled monoclonal antibody CCR 086

    Energy Technology Data Exchange (ETDEWEB)

    Abdel-Nabi, H.H.; Levine, G.; Lamki, L.M.; Murray, J.L.; Tauxe, W.N.; Shah, A.N.; Patt, Y.Z.; Doerr, R.J.; Klein, H.A.; Gona, J. (Veterans Administration Medical Center, Buffalo, NY (USA))

    1990-07-01

    A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer.

  16. Colorectal carcinoma metastases: detection with In-111-labeled monoclonal antibody CCR 086.

    Science.gov (United States)

    Abdel-Nabi, H H; Levine, G; Lamki, L M; Murray, J L; Tauxe, W N; Shah, A N; Patt, Y Z; Doerr, R J; Klein, H A; Gona, J

    1990-07-01

    A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer.

  17. Colorectal carcinoma metastases: Detection with In-111-labeled monoclonal antibody CCR 086

    International Nuclear Information System (INIS)

    Abdel-Nabi, H.H.; Levine, G.; Lamki, L.M.; Murray, J.L.; Tauxe, W.N.; Shah, A.N.; Patt, Y.Z.; Doerr, R.J.; Klein, H.A.; Gona, J.

    1990-01-01

    A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer

  18. Evaluating compliance to Kenya national cancer guidelines on ...

    African Journals Online (AJOL)

    Background: In Kenya, breast cancer is one of the most prevalent diseases among women. Early diagnosis and stage-directed treatment are vital in reducing morbidity and mortality associated with it. The Kenya National Cancer Guidelines (KNCG) was developed in 2013. Utility of the guidelines is expected to improve early ...

  19. Evaluation of the national cancer program and proposed reforms.

    Science.gov (United States)

    Epstein, S S

    1993-07-01

    A statement by some 68 prominent national experts in industrial medicine, carcinogenesis, epidemiology, and public health, released at a February 4, 1992 press conference in Washington, D.C., charged that the National Cancer Institute (NCI) has confused the public by repeated claims of winning the war against cancer. In fact, age standardized incidence rates have increased sharply over recent decades, while ability to treat and cure most cancers has not materially improved. Furthermore, the NCI has minimized evidence for increasing cancer rates which are largely attributed to smoking and to diet. In so doing, NCI trivializes the importance of occupational carcinogens as non-smoking-attributable causes of lung and other cancers, and ignores the tenuous and inconsistent evidence for the causal role of diet per se and also the important role of carcinogenic dietary contaminants. Reflecting this near exclusionary blame-the-victim theory of cancer causation, with support from the American Cancer Society and industry, the NCI discounts the role of avoidable involuntary exposures to industrial carcinogens in air, water, food, the home, and the workplace. The NCI has also failed to provide scientific guidance to Congress and regulatory agencies on fundamental principles of carcinogenesis and epidemiology, and on the critical need to reduce avoidable exposures to environmental and occupational carcinogens. Contrary to NCI, analysis of their $2 billion budget reveals very limited allocations for research on primary cancer prevention, and for occupational cancer which receives only $19 million annually, 1% of NCI's total budget. Problems of professional mindsets in NCI leadership--fixation on diagnosis, treatment, and basic research (much of questionable relevance) and the neglect of cancer prevention--are exemplified by the composition of the Executive President's Cancer Panel and the National Cancer Advisory Board. Contrary to the explicit mandate of the National Cancer Act

  20. National and international guidelines for rectal cancer

    DEFF Research Database (Denmark)

    Nielsen, Liv Bjerre Juul; Wille-Jørgensen, P

    2014-01-01

    concerning the definition of rectal cancer. Ten of the 11 guidelines use the TNM staging system and there was general agreement regarding the recommendation of MRI and CT in rectal cancer. There was consensus concerning a multidisciplinary approach, preoperative chemoradiotherapy (CRT) and total mesorectal...... 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...

  1. Trends in intensity modulated radiation therapy use for locally advanced rectal cancer at National Comprehensive Cancer Network centers

    OpenAIRE

    Marsha Reyngold, MD, PhD; Joyce Niland, PhD; Anna ter Veer, MS; Tanios Bekaii-Saab, MD; Lily Lai, MD; Joshua E. Meyer, MD; Steven J. Nurkin, MD, MS; Deborah Schrag, MD, MPH; John M. Skibber, MD, FACS; Al B. Benson, MD; Martin R. Weiser, MD; Christopher H. Crane, MD; Karyn A. Goodman, MD, MS

    2018-01-01

    Purpose: Intensity modulated radiation therapy (IMRT) has been rapidly incorporated into clinical practice because of its technological advantages over 3-dimensional conformal radiation therapy (CRT). We characterized trends in IMRT utilization in trimodality treatment of locally advanced rectal cancer at National Comprehensive Cancer Network cancer centers between 2005 and 2011. Methods and materials: Using the prospective National Comprehensive Cancer Network Colorectal Cancer Database, ...

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

    Science.gov (United States)

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

    2016-10-01

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

  3. 78 FR 8156 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-02-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute... proposals. Place: Bethesda North Marriott Hotel & Conference Center, Montgomery County Conference Center... Institute, NIH, 6116 Executive Blvd., Suite 703, Room 7072, Bethesda, md 20892-8329, 301-594-1408, Stoicaa2...

  4. 77 FR 68136 - National Cancer Institute Amended; Notice of Meeting

    Science.gov (United States)

    2012-11-15

    ... Regency Bethesda Hotel, Old Georgetown Room, One Metro Center, Bethesda, MD 20814. The NCAB ad hoc... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute..., Building 31C, Wing C, Conference Room 10, 31 Center Drive, Bethesda, MD 20892 which was published in the...

  5. Differentiated Thyroid Cancer Multidisciplinary Management at the Colombian National Cancer Institute

    International Nuclear Information System (INIS)

    Garavito, Gloria; Llamas O, Augusto; Cadena, Enrique; De Los Reyes, Amelia

    2009-01-01

    Thyroid cancer is the most common malignant disease of the endocrine system. Two hundred and twenty-one new cases were diagnosed at the National Cancer Institute of Colombia (NCI) in 2006, roughly 4% of all new cancer cases. Weekly multidisciplinary decision-making meetings on thyroid cancer management have been held at the NCI since 1994. This article covers the body of knowledge gathered through 14 years of interdisciplinary collaboration where experience has been combined with the best available evidence.

  6. 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

  7. CCR5 as a treatment target in pulmonary arterial hypertension.

    Science.gov (United States)

    Amsellem, Valérie; Lipskaia, Larissa; Abid, Shariq; Poupel, Lucie; Houssaini, Amal; Quarck, Rozenn; Marcos, Elisabeth; Mouraret, Nathalie; Parpaleix, Aurélien; Bobe, Régis; Gary-Bobo, Guillaume; Saker, Mirna; Dubois-Randé, Jean-Luc; Gladwin, Mark T; Norris, Karen A; Delcroix, Marion; Combadière, Christophe; Adnot, Serge

    2014-09-09

    Pulmonary arterial hypertension (PH), whether idiopathic or related to underlying diseases such as HIV infection, results from complex vessel remodeling involving both pulmonary artery smooth muscle cell (PA-SMC) proliferation and inflammation. CCR5, a coreceptor for cellular HIV-1 entry expressed on macrophages and vascular cells, may be involved in the pathogenesis of PH. Maraviroc is a new CCR5 antagonist designed to block HIV entry. Marked CCR5 expression was found in lungs from patients with idiopathic PH, in mice with hypoxia-induced PH, and in Simian immunodeficiency virus-infected macaques, in which it was localized chiefly in the PA-SMCs. To assess the role for CCR5 in experimental PH, we used both gene disruption and pharmacological CCR5 inactivation in mice. Because maraviroc does not bind to murine CCR5, we used human-CCR5ki mice for pharmacological and immunohistochemical studies. Compared with wild-type mice, CCR5-/- mice or human-CCR5ki mice treated with maraviroc exhibited decreased PA-SMC proliferation and recruitment of perivascular and alveolar macrophages during hypoxia exposure. CCR5-/- mice reconstituted with wild-type bone marrow cells and wild-type mice reconstituted with CCR5-/- bone marrow cells were protected against PH, suggesting CCR5-mediated effects on PA-SMCs and macrophage involvement. The CCR5 ligands CCL5 and the HIV-1 gp120 protein increased intracellular calcium and induced growth of human and human-CCR5ki mouse PA-SMCs; maraviroc inhibited both effects. Maraviroc also reduced the growth-promoting effects of conditioned media from CCL5-activated macrophages derived from human-CCR5ki mice on PA-SMCs from wild-type mice. The CCL5-CCR5 pathway represents a new therapeutic target in PH associated with HIV or with other conditions. © 2014 American Heart Association, Inc.

  8. Electron Microscopist/Structural Biologist | Center for Cancer Research

    Science.gov (United States)

    PROGRAM DESCRIPTION The Cancer Research Technology Program (CRTP) develops and implements emerging technology, cancer biology expertise and research capabilities to accomplish NCI research objectives. The CRTP is an outward-facing, multi-disciplinary hub purposed to enable the external cancer research community and provides dedicated support to NCI’s intramural Center for Cancer Research (CCR). The dedicated units provide electron microscopy, protein characterization, protein expression, optical microscopy and genetics. These research efforts are an integral part of CCR at the Frederick National Laboratory for Cancer Research (FNLCR). CRTP scientists also work collaboratively with intramural NCI investigators to provide research technologies and expertise. KEY ROLES/RESPONSIBILITIES - THIS POSITION IS CONTINGENT UPON FUNDING APPROVAL Develop technologies for application on emerging electron microscopy platforms. Operate and optimize performance of TEM microscopes, specifically Titan Krios and Talos Artctica for high-resolution data collection in single particle studies as well as cryo-electron tomography. Assist with maintenance for the Titan Krios and the Talos Arctica as well as associated instruments. Interact closely with and transfer newly developed technical capabilities to CCR Center for Molecular Microscopy (CMM) and CCR collaborators.

  9. 78 FR 27974 - Proposed Collection; 60-Day Comment Request: National Cancer Institute (NCI) Alliance for...

    Science.gov (United States)

    2013-05-13

    ... Comment Request: National Cancer Institute (NCI) Alliance for Nanotechnology in Cancer Platform... project, contact: Dorothy Farrell, Center for Strategic Scientific Initiatives, Office of Cancer... Institute (NCI) Alliance for Nanotechnology in Cancer Platform Partnership Scientific Progress Reports, 0925...

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

    Directory of Open Access Journals (Sweden)

    Amal S. Ibrahim

    2014-01-01

    Full Text Available 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 entry was online. Incidence rates were calculated at a regional and a national level. Future projection up to 2050 was also calculated. Results. Age-standardized incidence rates per 100,000 were 166.6 (both sexes, 175.9 (males, and 157.0 (females. Commonest sites were liver (23.8%, breast (15.4%, and bladder (6.9% (both sexes: liver (33.6% and bladder (10.7% among men, and breast (32.0% and liver (13.5% among women. By 2050, a 3-fold increase in incident cancer relative to 2013 was estimated. Conclusion. These data are the only available cancer rates at national and regional levels of Egypt. The pattern of cancer indicated the increased burden of liver cancer. Breast cancer occupied the second rank. Study of rates of individual sites of cancer might help in giving clues for preventive programs.

  11. Spatial analyses identify the geographic source of patients at a National Cancer Institute Comprehensive Cancer Center.

    Science.gov (United States)

    Su, Shu-Chih; Kanarek, Norma; Fox, Michael G; Guseynova, Alla; Crow, Shirley; Piantadosi, Steven

    2010-02-01

    We examined the geographic distribution of patients to better understand the service area of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, a designated National Cancer Institute (NCI) comprehensive cancer center located in an urban center. Like most NCI cancer centers, the Sidney Kimmel Comprehensive Cancer Center serves a population beyond city limits. Urban cancer centers are expected to serve their immediate neighborhoods and to address disparities in access to specialty care. Our purpose was to learn the extent and nature of the cancer center service area. Statistical clustering of patient residence in the continental United States was assessed for all patients and by gender, cancer site, and race using SaTScan. Primary clusters detected for all cases and demographically and tumor-defined subpopulations were centered at Baltimore City and consisted of adjacent counties in Delaware, Pennsylvania, Virginia, West Virginia, New Jersey and New York, and the District of Columbia. Primary clusters varied in size by race, gender, and cancer site. Spatial analysis can provide insights into the populations served by urban cancer centers, assess centers' performance relative to their communities, and aid in developing a cancer center business plan that recognizes strengths, regional utility, and referral patterns. Today, 62 NCI cancer centers serve a quarter of the U.S. population in their immediate communities. From the Baltimore experience, we might project that the population served by these centers is actually more extensive and varies by patient characteristics, cancer site, and probably cancer center services offered.

  12. Naturally Occurring Deletional Mutation in the C-Terminal Cytoplasmic Tail of CCR5 Affects Surface Trafficking of CCR5

    OpenAIRE

    Shioda, Tatsuo; Nakayama, Emi E.; Tanaka, Yuetsu; Xin, Xiaomi; Liu, Huanliang; Kawana-Tachikawa, Ai; Kato, Atsushi; Sakai, Yuko; Nagai, Yoshiyuki; Iwamoto, Aikichi

    2001-01-01

    CCR5 is an essential coreceptor for the cellular entry of R5 strains of human immunodeficiency virus type 1 (HIV-1). CCR5-893(−) is a single-nucleotide deletion mutation which is observed exclusively in Asians (M. A. Ansari-Lari, et al., Nat. Genet. 16:221–222, 1997). This mutant gene produces a CCR5 which lacks the entire C-terminal cytoplasmic tail. To assess the effect of CCR5-893(−) on HIV-1 infection, we generated a recombinant Sendai virus expressing the mutant CCR5 and compared its HIV...

  13. The Abrogation of Phosphorylation Plays a Relevant Role in the CCR5 Signalosome Formation with Natural Antibodies to CCR5

    Directory of Open Access Journals (Sweden)

    Assunta Venuti

    2017-12-01

    Full Text Available The exposure to CCR5 (CC chemokine receptor 5 specific natural antibodies in vitro produces a Class B β-arrestin2-dependent CCR5 retention with the aid of ERK1, due to the formation of a CCR5 signalosome, which remains stable for at least 48 h. Considering that β-arrestins and MAPKs are receptive to environmental signals, their signal complexes could be one of the key junction for GPCRs internalization related signal transduction. Here, we demonstrate that, in T cells, the phosphorylation status of either CCR5 receptor or ERK1 protein is necessary to drive the internalized receptor into the early endosomes, forming the CCR5 signalosome. In particular, our data show that β-arrestin2/ERK1 complex is a relevant transducer in the CCR5 signaling pathway. Understanding the mechanism of CCR5 regulation is essential for many inflammatory disorders, tumorigenesis and viral infection such as HIV.

  14. The growth and maturation of the National Cancer Data Base.

    Science.gov (United States)

    Menck, H R; Cunningham, M P; Jessup, J M; Eyre, H J; Winchester, D P; Scott-Conner, C E; Murphy, G P

    1997-12-15

    The National Cancer Data Base (NCDB), a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society, is a cancer management and outcomes data base for health care organizations. It provides a comparative summary of patient care that is used by communities and participating hospitals for self-assessment. The most current (1994) data are described here. Six calls for data have yielded a total of 4,580,000 cases for the years 1985-1994. A total of 1735 hospital cancer registries have each participated in at least one of the calls for data. Summing the last year's report from each of the 1227 hospitals that participated in 1994, the cases represent the equivalent of 57% of the estimated 1994 U.S. cancer cases. These data were received from all six regions of the country, including all 50 states. Ninety-seven percent of patients received all or part of their treatment at the reporting hospital. The four most common cancers are carcinomas of the breast (15.7%), lung (14.3%), prostate (13.1%), and colon (7.7%), and collectively they comprise a majority of new cases. The NCDB is a cancer management and outcomes data base for health care organizations that currently provides data on 57% of the estimated new cases in the U.S. Past data have been used extensively to assess patterns of care and outcomes.

  15. Polymorphism in CCR4 Gene (1014 C/T in Patients with Breast Carcinoma from the South of Iran

    Directory of Open Access Journals (Sweden)

    F Moghaddasi

    2013-04-01

    Full Text Available ABSTRACT Background & aim: CCR4 gene polymorphism at position C/T1014 has been associated with changes in mRNA stability and is involved expression of this molecule. The aim of this study was to investigate CCR4 gene polymorphism at position 1014 C/T in breast carcinoma patients in southern Iran. Methods: In this case-control study, 150 women with breast carcinoma and 160 healthy women as controls were included. PCR-RFLP method was used to genotyping of CCR4, receptor gene. The data were analyzed using chi-square and Fisher. Results: Genotype frequencies of CC, CT and TT, in case group were 57.8, 35.1 & 7.1%, where as in control group showed 54.4, 39.4 & 6.2% respectively. In addition, C and T allele of the cases were, 75.3 & 24.7% and in control group 74.1 & 25.9% respectively (p>0.05. Conclusion: CCR4 gene polymorphism has no role in increasing of susceptibility to breast cancer in the south of Iran population. Key words: Polymorphism, CCR4, Breast cancer

  16. Estimation of National Colorectal-Cancer Incidence Using Claims Databases

    Directory of Open Access Journals (Sweden)

    C. Quantin

    2012-01-01

    Full Text Available Background. The aim of the study was to assess the accuracy of the colorectal-cancer incidence estimated from administrative data. Methods. We selected potential incident colorectal-cancer cases in 2004-2005 French administrative data, using two alternative algorithms. The first was based only on diagnostic and procedure codes, whereas the second considered the past history of the patient. Results of both methods were assessed against two corresponding local cancer registries, acting as “gold standards.” We then constructed a multivariable regression model to estimate the corrected total number of incident colorectal-cancer cases from the whole national administrative database. Results. The first algorithm provided an estimated local incidence very close to that given by the regional registries (646 versus 645 incident cases and had good sensitivity and positive predictive values (about 75% for both. The second algorithm overestimated the incidence by about 50% and had a poor positive predictive value of about 60%. The estimation of national incidence obtained by the first algorithm differed from that observed in 14 registries by only 2.34%. Conclusion. This study shows the usefulness of administrative databases for countries with no national cancer registry and suggests a method for correcting the estimates provided by these data.

  17. Cancer risk factors and screening in First Nations in Ontario

    Directory of Open Access Journals (Sweden)

    Maegan V. Mazereeuw

    2017-06-01

    Full Text Available Introduction: A lack of identifiers in health administrative databases limits our understanding of the cancer burden in First Nations. This study compares cancer risk factors and screening between First Nations in Ontario (on and off reserve and non-Aboriginal Ontarians using two unique health surveys. Methods: We measured age-standardized prevalence estimates using the First Nations Regional Health Survey (RHS Phase 2, 2008/10 (for First Nations on reserve and the Canadian Community Health Survey (CCHS, 2007–2013 (for First Nations off reserve and non-Aboriginal Ontarians. We used prevalence rate ratios (RR and Pearson’s chisquare tests for differences in proportions to compare estimates between First Nations (on and off reserve and non-Aboriginal Ontarians. Results: A higher proportion of First Nation men, women and adolescents on reserve smoked (RR = 1.97, 2.78 and 7.21 respectively and were obese (RR = 1.73, 2.33 and 3.29 respectively compared to their non-Aboriginal counterparts. Similar patterns were observed for First Nations off reserve. Frequent binge drinking was also more prevalent among First Nation men and women living on reserve (RR = 1.28 and 2.22, respectively and off reserve (RR = 1.70 and 1.45, respectively than non-Aboriginal Ontarians. First Nation men and women on reserve were about half as likely to consume fruit at least twice per day and vegetables at least twice per day compared to non-Aboriginal men and women (RR = 0.53 and 0.54, respectively. Pap test uptake was similar across all groups, while First Nation women on reserve were less likely to have had a mammogram in the last five years than non-Aboriginal women (RR = 0.85. Conclusion: First Nations, especially those living on reserve, have an increased risk for cancer and other chronic diseases compared to non-Aboriginal Ontarians. These results provide evidence to support policies and programs to reduce the future burden of cancer and other chronic diseases in

  18. National cancer control programmes: policies and managerial guidelines

    National Research Council Canada - National Science Library

    2002-01-01

    ..., and immunizing against viral hepatitis B. Early detection, and therefore prompt treatment, of a further one-third of cases is possible where resources allow. Effective techniques are sufficiently well established to permit comprehensive palliative care for the remaining, more advanced, cases. The establishment of a national cancer ...

  19. 76 FR 11800 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-03-03

    ... Emphasis Panel; Biosensors for Early Cancer Detection and Risk Assessment. Date: March 29, 2011. Time: 2 p.m. to 5 p.m. Agenda: To review and evaluate contract proposals. Place: National Institutes of Health...: Lalita D. Palekar, PhD, Scientific Review Officer, Special Review and Logistics Branch, Division of...

  20. Owl monkey CCR5 reveals synergism between CD4 and CCR5 in HIV-1 entry.

    Science.gov (United States)

    Nahabedian, John; Sharma, Amit; Kaczmarek, Maryska E; Wilkerson, Greg K; Sawyer, Sara L; Overbaugh, Julie

    2017-12-01

    Studying HIV-1 replication in the presence of functionally related proteins from different species has helped define host determinants of HIV-1 infection. Humans and owl monkeys, but not macaques, encode a CD4 receptor that permits entry of transmissible HIV-1 variants due to a single residue difference. However, little is known about whether divergent CCR5 receptor proteins act as determinants of host-range. Here we show that both owl monkey (Aotus vociferans) CD4 and CCR5 receptors are functional for the entry of transmitted HIV-1 when paired with human versions of the other receptor. By contrast, the owl monkey CD4/CCR5 pair is generally a suboptimal receptor combination, although there is virus-specific variation in infection with owl monkey receptors. Introduction of the human residues 15Y and 16T within a sulfation motif into owl monkey CCR5 resulted in a gain of function. These findings suggest there is cross-talk between CD4 and CCR5 involving the sulfation motif. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Use of National Comprehensive Cancer Network and Other Guidelines and Biomarkers for Colorectal Cancer Screening

    Science.gov (United States)

    Williams, Christina D.; Grady, William M.; Zullig, Leah L.

    2016-01-01

    Colorectal cancer (CRC) remains a common cancer and significant public health burden. CRC-related mortality is declining, in part due to the early detection of CRC through robust screening. The National Comprehensive Cancer Network (NCCN) has established CRC screening guidelines to aid healthcare providers in making appropriate recommendations for screening according to a patient’s risk of developing CRC. The purpose of this review is to describe the evolution of CRC screening guidelines for average risk individuals, discuss the role of NCCN CRC screening guidelines in cancer prevention, and comment on the current and emerging use of biomarkers for CRC screening. PMID:27799515

  2. $200,000 Grants Awarded to CCR Researchers for HIV/AIDS Studies | Poster

    Science.gov (United States)

    By Nancy Parrish, Staff Writer Earlier this year, the Office of AIDS Research (OAR) awarded two, two-year grants of $200,000 each to Anu Puri, Ph.D., and Robert Blumenthal, Ph.D., both of the Center for Cancer Research (CCR) Nanobiology Program, and to Eric Freed, Ph.D., of the HIV Drug Resistance Program, for their research on potential new treatments for HIV.

  3. CCR5 inhibitors in HIV-1 therapy.

    Science.gov (United States)

    Dorr, Patrick; Perros, Manos

    2008-11-01

    The human immunodeficiency virus 1 (HIV-1) is the causative pathogen of AIDS, the world's biggest infectious disease killer. About 33 million people are infected worldwide, with 2.1 million deaths a year as a direct consequence. The devastating nature of AIDS has prompted widespread research, which has led to an extensive array of therapies to suppress viral replication and enable recovery of the immune system to prolong and improve patient life substantially. However, the genetic plasticity and replication rate of HIV-1 are considerable, which has lead to rapid drug resistance. This, together with the need for reducing drug side effects and increasing regimen compliance, has led researchers to identify antiretroviral drugs with new modes of action. This review describes the discovery and clinical development of CCR5 antagonists and the recent approval of maraviroc as a breakthrough in anti-HIV-1 therapy. CCR5 inhibitors target a human cofactor to disable HIV-1 entry into the cells, and thereby provide a new hurdle for the virus to overcome. The status and expert opinion of CCR5 antagonists for the treatment of HIV-1 infection are detailed.

  4. Detection of new mutant sites of HIV-1 coreceptor CCR5 among Saudi populations.

    Science.gov (United States)

    Abuelsaad, Abdelaziz S A; Al-Ghamdi, Abdullhamid S; Al-Ghamdi, Ahmed N; Alakkas, Eyad A; Alsulaimani, Adnan A; Al-Harthi, Abdulla A; Abdel-Moneim, Ahmed S

    2013-12-01

    The genetic association of CCR5 with human immunodeficiency virus-1 (HIV-1) pathogenesis is well known. The HIV-1 entry into target cells is initiated by the binding of the viral envelope glycoproteins (gp120-gp41) with the cell surface receptor (CD4) and the coreceptor (CCR5), followed by fusion of the viral and cell membranes. Genetic variants of the gene-encoding HIV-1 coreceptor are implicated in the susceptibility to HIV-1 infection. The prevalence of these mutations may vary according to population ethnicity. In the current study, characterization and frequency distribution of the HIV-related gene variants in 135 samples of the Saudi populations were conducted. Polymerase chain reaction (PCR) of 276 bp amplicons was used to rapidly detect Δ32 deletion in the initial sample of DNA. The direct sequence of 2 overlapping PCR amplicons flanking 1,059 bp was used to detect single-nucleotide polymorphisms. A single hetrozygous Δ32 deletion allele and 6 single-nucleotide polymorphisms were detected. Only one of the identified haplotypes, Taif-1, which was found in the majority of the tested sample, is identical to CCR5 wild-type alleles. Furthermore, the results of this study raised a concern about the prospective role of the mutations detected among Saudi nationals in the HIV pathogenesis and the clinical use of CCR5 antagonists, which are currently being developed as therapeutics for HIV-1 and inflammatory diseases.

  5. Surveillance Evaluation of the National Cancer Registry in Sabah, Malaysia.

    Science.gov (United States)

    Jeffree, Saffree Mohammad; Mihat, Omar; Lukman, Khamisah Awang; Ibrahim, Mohd Yusof; Kamaludin, Fadzilah; Hassan, Mohd Rohaizat; Kaur, Nirmal; Myint, Than

    2016-01-01

    Cancer is the fourth leading cause of death in Sabah Malaysia with a reported agestandardized incidence rate was 104.9 per 100,000 in 2007. The incidence rate depends on nonmandatory notification in the registry. Underreporting will provide the false picture of cancer control program effectiveness. The present study was to evaluate the performance of the cancer registry system in terms of representativeness, data quality, simplicity, acceptability and timeliness and provision of recommendations for improvement. The evaluation was conducted among key informants in the National Cancer Registry (NCR) and reporting facilities from FebMay 2012 and was based on US CDC guidelines. Representativeness was assessed by matching cancer case in the Health Information System (HIS) and state pathology records with those in NCR. Data quality was measured through case finding and reabstracting of medical records by independent auditors. The reabstracting portion comprised 15 data items. Selfadministered questionnaires were used to assess simplicity and acceptability. Timeliness was measured from date of diagnosis to date of notification received and data dissemination. Of 4613 cancer cases reported in HIS, 83.3% were matched with cancer registry. In the state pathology centre, 99.8% was notified to registry. Duplication of notification was 3%. Data completeness calculated for 104 samples was 63.4%. Registrars perceived simplicity in coding diagnosis as moderate. Notification process was moderately acceptable. Median duration of interval 1 was 5.7 months. The performances of registry's attributes are fairly positive in terms of simplicity, case reporting sensitivity, and predictive value positive. It is moderately acceptable, data completeness and inflexible. The usefulness of registry is the area of concern to achieve registry objectives. Timeliness of reporting is within international standard, whereas timeliness to data dissemination was longer up to 4 years. Integration between

  6. Cancer research in India: national priorities, global results.

    Science.gov (United States)

    Sullivan, Richard; Badwe, Rajendra A; Rath, Goura K; Pramesh, C S; Shanta, V; Digumarti, Raghunadharao; D'Cruz, Anil; Sharma, Suresh C; Viswanath, Lokesh; Shet, Arun; Vijayakumar, Manavalan; Lewison, Grant; Chandy, Mammen; Kulkarni, Priyadarshini; Bardia, M R; Kumar, Shaleen; Sarin, Rajiv; Sebastian, Paul; Dhillon, Preet K; Rajaraman, Preetha; Trimble, Edward L; Aggarwal, Ajay; Vijaykumar, D K; Purushotham, Arnie D

    2014-05-01

    Over the past 20 years, cancer research in India has grown in size and impact. Clinicians, scientists, and government and state policy makers in India have championed cancer research, from studies to achieve low-tech, large-scale health outcomes to some of the most advanced areas of fundamental cancer science. In this paper, we frame public policy discussions about cancer with use of an in-depth analysis of research publications from India. Cancer research in India is a complex environment that needs to balance public policy across many competing agendas. We identify major needs across these environments such as those for increased research capacity and training and protected time for clinical researchers; for more support from states and enhanced collaborative funding programmes from government; for development of national infrastructures across a range of domains (ie, clinical trials, tissue banking, registries, etc); and for a streamlined and rational regulatory environment. We also discuss improvements that should be made to translate research into improvements in cancer outcomes and public health. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Analysis of Staphylococcal cassette chromosome mec in Staphylococcus haemolyticus and Staphylococcus sciuri: identification of a novel ccr gene complex with a newly identified ccrA allotype (ccrA7).

    Science.gov (United States)

    Urushibara, Noriko; Paul, Shyamal Kumar; Hossain, Mohammad Akram; Kawaguchiya, Mitsuyo; Kobayashi, Nobumichi

    2011-06-01

    Methicillin resistance in staphylococci is conferred by the acquisition in its chromosome of the mecA gene, which is located on a mobile genetic element called staphylococcal cassette chromosome mec (SCCmec). Genetic type of SCCmec is defined by combination of mec gene complex class and cassette chromosome recombinase gene (ccr) allotype. In this study, we analyzed genetic diversity of the SCCmec in 11 Staphylococcus haemolyticus strains and a Staphylococcus sciuri strain, which were recently isolated from clinical specimens in Bangladesh. Among these strains, only two S. haemolyticus strains were proved to have the known types of SCCmec, that is, SCCmec V (class C2 mec-ccrC) and VII (class C1 mec-ccrC). Five S. haemolyticus strains were assigned two unique mec-ccr gene complexes combination; that is, class C1 mec-ccrA4B4 (four isolates) and class A mec-ccrC (one isolate). In the remaining four S. haemolyticus strains with class C1 mec, no known ccr allotypes could be detected. A single S. sciuri strain with class A mec complex carried a ccrA gene belonging to a novel allotype designated ccrA7, together with ccrB3. The ccrA7 gene in the S. sciuri strain showed 61.7%-82.7% sequence identity to the ccrA gene sequences published so far, and 75.3% identity to ccrA3, which is a component of the type 3 ccr complex (ccrA3-ccrB3) in methicillin-resistant Staphylococcus aureus. The results of the present study indicated that mec gene complex and ccr genes in coagulase-negative staphylococci are highly divergent, and distinct from those of common methicillin-resistant S. aureus. Identification of the novel ccrA7 allotype combined with ccrB3 suggested an occurrence of recombination between different ccr complexes in nature.

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

    Directory of Open Access Journals (Sweden)

    Ericsson-Dahlstrand Anders

    2007-05-01

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

  9. Optimising the expansion of the National Bowel Cancer Screening Program.

    Science.gov (United States)

    Cenin, Dayna R; St John, D James B; Ledger, Melissa J N; Slevin, Terry; Lansdorp-Vogelaar, Iris

    2014-10-20

    To estimate the impact of various expansion scenarios of the National Bowel Cancer Screening Program (NBCSP) on the number of bowel cancer deaths prevented; and to investigate the impact of the expansion scenarios on colonoscopy demand. MISCAN-Colon, a well established, validated computer simulation model for bowel cancer screening, was adjusted to reflect the Australian situation. In July 2013, we simulated the effects of screening over a 50-year period, starting in 2006. The model parameters included rates of participation in screening and follow-up, rates of identification of cancerous and precancerous lesions, bowel cancer incidence, mortality and the outcomes of the NBCSP. Five implementation scenarios, based on biennial screening using an immunochemical faecal occult blood test, were developed and modelled. A sensitivity analysis that increased screening participation to 60% was also conducted. Australian residents aged 50 to 74 years. Comparison of the impact of five implementation scenarios on the number of bowel cancer deaths prevented and demand for colonoscopy. MISCAN-Colon calculated that in its current state, the NBCSP should prevent 35 169 bowel cancer deaths in the coming 40 years. Accelerating the expansion of the program to achieve biennial screening by 2020 would prevent more than 70 000 deaths. If complete implementation of biennial screening results in a corresponding increase in participation to 60%, the number of deaths prevented will increase across all scenarios. The findings strongly support the need for rapid implementation of the NBCSP. Compared with the current situation, achieving biennial screening by 2020 could result in 100% more bowel cancer deaths (about 35 000) being prevented in the coming 40 years.

  10. Population-based geographic access to parent and satellite National Cancer Institute Cancer Center Facilities.

    Science.gov (United States)

    Onega, Tracy; Alford-Teaster, Jennifer; Wang, Fahui

    2017-09-01

    Satellite facilities of National Cancer Institute (NCI) cancer centers have expanded their regional footprints. This study characterized geographic access to parent and satellite NCI cancer center facilities nationally overall and by sociodemographics. Parent and satellite NCI cancer center facilities, which were geocoded in ArcGIS, were ascertained. Travel times from every census tract in the continental United States and Hawaii to the nearest parent and satellite facilities were calculated. Census-based population attributes were used to characterize measures of geographic access for sociodemographic groups. From the 62 NCI cancer centers providing clinical care in 2014, 76 unique parent locations and 211 satellite locations were mapped. The overall proportion of the population within 60 minutes of a facility was 22% for parent facilities and 32.7% for satellite facilities. When satellites were included for potential access, the proportion of some racial groups for which a satellite was the closest NCI cancer center facility increased notably (Native Americans, 22.6% with parent facilities and 39.7% with satellite facilities; whites, 34.8% with parent facilities and 50.3% with satellite facilities; and Asians, 40.0% with parent facilities and 54.0% with satellite facilities), with less marked increases for Hispanic and black populations. Rural populations of all categories had dramatically low proportions living within 60 minutes of an NCI cancer center facility of any type (1.0%-6.6%). Approximately 14% of the population (n = 43,033,310) lived more than 180 minutes from a parent or satellite facility, and most of these individuals were Native Americans and/or rural residents (37% of Native Americans and 41.7% of isolated rural residents). Racial/ethnic and rural populations showed markedly improved geographic access to NCI cancer center care when satellite facilities were included. Cancer 2017;123:3305-11. © 2017 American Cancer Society. © 2017 American

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

    Science.gov (United States)

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

    2014-12-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: Although a prospective national clinical thyroid cancer database (DATHYRCA) has been active in Denmark since January 1, 1996, no assessment of data quality has been performed. The purpose of the study was to evaluate completeness and data validity in the Danish national clinical thyroid...... 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...

  13. Gynecologic Cancer Prevention and Control in the National Comprehensive Cancer Control Program: Progress, Current Activities, and Future Directions

    OpenAIRE

    Stewart, Sherri L.; Lakhani, Naheed; Brown, Phaeydra M.; Larkin, O. Ann; Moore, Angela R.; Hayes, Nikki S.

    2013-01-01

    Gynecologic cancer confers a large burden among women in the United States. Several evidence-based interventions are available to reduce the incidence, morbidity, and mortality from these cancers. The National Comprehensive Cancer Control Program (NCCCP) is uniquely positioned to implement these interventions in the US population. This review discusses progress and future directions for the NCCCP in preventing and controlling gynecologic cancer.

  14. Gynecologic cancer prevention and control in the National Comprehensive Cancer Control Program: progress, current activities, and future directions.

    Science.gov (United States)

    Stewart, Sherri L; Lakhani, Naheed; Brown, Phaeydra M; Larkin, O Ann; Moore, Angela R; Hayes, Nikki S

    2013-08-01

    Gynecologic cancer confers a large burden among women in the United States. Several evidence-based interventions are available to reduce the incidence, morbidity, and mortality from these cancers. The National Comprehensive Cancer Control Program (NCCCP) is uniquely positioned to implement these interventions in the US population. This review discusses progress and future directions for the NCCCP in preventing and controlling gynecologic cancer.

  15. Grape seed extract proanthocyanidins downregulate HIV- 1 entry coreceptors, CCR2b, CCR3 and CCR5 gene expression by normal peripheral blood mononuclear cells

    Directory of Open Access Journals (Sweden)

    MADHAVAN P NAIR

    2002-01-01

    Full Text Available Flavonoids and related polyphenols, in addition to their cardioprotective, anti-tumor, anti-inflammatory, anti-carcinogenic and anti-allergic activities, also possess promising anti-HIV effects. Recent studies documented that the ß-chemokine receptors, CCR2b, CCR3 and CCR5, and the alpha-chemokine receptors, CXCR1, CXCR2 and CXCR4 serve as entry coreceptors for HIV-1. Although flavonoids and polyphenolic compounds elicit anti-HIV effects such as inhibition of HIV-1 expression and virus replication, the molecular mechanisms underlying these effects remain to be clearly elucidated. We hypothesize that flavonoids exert their anti-HIV effects, possibly by interfering at the HIV co-receptor level. We investigated the effect of flavonoid constituents of a proprietary grape seed extract (GSE on the expression of HIV-1 coentry receptors by immunocompetent mononuclear leukocytes. Our results showed that GSE significantly downregulated the expression of the HIV-1 entry co-receptors, CCR2b , CCR3 and CCR5 in normal PBMC in a dose dependent manner. Further , GSE treated cultures showed significantly lower number of CCR3 positive cells as quantitated by flow cytometry analysis which supports RT-PCR gene expression data.Investigations of the mechanisms underlying the anti-HIV-1 effects of grape seed extracts may help to identify promising natural products useful in the prevention and /or amelioration of HIV-1 infection

  16. Compact containment boiling water reactor (CCR)

    International Nuclear Information System (INIS)

    2006-01-01

    The compact containment boiling water reactor (CCR) is a modular boiling water reactor (BWR) designed by the Toshiba Corporation with the support of the Japan Atomic Power Company (JAPC). The current CCR design falls into the category of innovative small and medium size reactors, featuring 300MW electrical output per module. In Japan, increases in nuclear plant unit capacity have been promoted to take advantage of the economies of scale while further enhancing safety and reliability. As a result, more than 50 nuclear units are playing an important role in the domestic electric power generation. The next generation reactor with a 1700 MW(e) capacity is currently under development [IX-1, IX-2]. However, the future of nuclear power generation looks uncertain because of increasing competition with other power sources [IX-3] in the deregulated market, in spite of the general recognition that nuclear power is attractive from the viewpoint of energy security and environmental protection. Furthermore, factors such as stagnant growth in recent electricity demand, limitations in grid capacity and limited initial investment to avoid risk, will not favour large plant outputs. Nuclear plants are required that can easily be adopted in any country to globalize nuclear power generation for the mitigation of greenhouse effects. In the 1980s, the Toshiba Corporation has carried out R and D for BWRs with natural circulation and passive safety features. These R and D included tests and analysis of passive containment cooling systems (PCCS), isolation condensers (IC) and gravity driven cooling systems (GDCS). The results obtained through these tests have been used in the design of a simplified boiling water reactor (SBWR). Based on these activities, the design of a simplified BWR with a long operating cycle (LSBWR) design has been under development since the mid 1990s. The concept of the LSBWR is to provide flexibility to meet site conditions and electricity demands, to mitigate

  17. 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.

  18. On relativistic irreducible quantum fields fulfilling CCR

    International Nuclear Information System (INIS)

    Baumann, K.

    1987-01-01

    Let phi be a relativistic scalar field fulfilling canonical commutation relations (CCR). Furthermore it is assumed that the time zero fields and momenta form an irreducible set. Based on estimates given by Herbst [I. W. Herbst, J. Math. Phys. 17, 1210 (1976)], and by methods developed by Powers [R. T. Powers, Commun. Math. Phys. 4, 145 (1967)], it is shown that phi has to be a free field in n>3 space dimensions. For n = 3 (resp. n = 2) restrictions that look similar to the restriction in a formal :phi 4 : 3 /sub +/ 1 (resp. :phi 6 : 2 /sub +/ 1 ) theory are obtained

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

    Science.gov (United States)

    Falteisek, Lukáš; Cerný, Jan; Janštová, Vanda

    2013-01-01

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

  20. 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)....

  1. 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

  2. Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion

    International Nuclear Information System (INIS)

    Wu Xiaofeng; Fan Jia; Wang Xiaoying; Zhou Jian; Qiu Shuangjian; Yu Yao; Liu Yinkun; Tang Zhaoyou

    2007-01-01

    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

  3. The ins and outs of ligand binding to CCR2

    NARCIS (Netherlands)

    Zweemer, Annelien Jacomina Maria

    2014-01-01

    This thesis provides novel insights in the molecular mechanism of action of antagonists for the chemokine receptor CCR2. CCR2 belongs to the protein family of G protein-coupled receptors (GPCRs). It is involved in several inflammatory diseases and therefore many small molecule antagonists targeting

  4. Treatment deintensification in human papillomavirus-positive oropharynx cancer: Outcomes from the National Cancer Data Base.

    Science.gov (United States)

    Cheraghlou, Shayan; Yu, Phoebe K; Otremba, Michael D; Park, Henry S; Bhatia, Aarti; Zogg, Cheryl K; Mehra, Saral; Yarbrough, Wendell G; Judson, Benjamin L

    2018-02-15

    The growing epidemic of human papillomavirus-positive (HPV+) oropharyngeal cancer and the favorable prognosis of this disease etiology have led to a call for deintensified treatment for some patients with HPV+ cancers. One of the proposed methods of treatment deintensification is the avoidance of chemotherapy concurrent with definitive/adjuvant radiotherapy. To the authors' knowledge, the safety of this form of treatment de-escalation is unknown and the current literature in this area is sparse. The authors investigated outcomes after various treatment combinations stratified by American Joint Committee on Cancer (AJCC) eighth edition disease stage using patients from the National Cancer Data Base. A retrospective study of 4443 patients with HPV+ oropharyngeal cancer in the National Cancer Data Base was conducted. Patients were stratified into AJCC eighth edition disease stage groups. Multivariate Cox regressions as well as univariate Kaplan-Meier analyses were conducted. For patients with stage I disease, treatment with definitive radiotherapy was associated with diminished survival compared with chemoradiotherapy (hazard ratio [HR], 1.798; P = .029), surgery with adjuvant radiotherapy (HR, 2.563; P = .002), or surgery with adjuvant chemoradiotherapy (HR, 2.427; P = .001). For patients with stage II disease, compared with treatment with chemoradiotherapy, patients treated with a single-modality (either surgery [HR, 2.539; P = .009] or radiotherapy [HR, 2.200; P = .030]) were found to have poorer survival. Among patients with stage III disease, triple-modality therapy was associated with improved survival (HR, 0.518; P = .024) compared with treatment with chemoradiotherapy. Deintensification of treatment from chemoradiotherapy to radiotherapy or surgery alone in cases of HPV+ AJCC eighth edition stage I or stage II disease may compromise patient safety. Treatment intensification to triple-modality therapy for patients with stage III disease may improve survival in

  5. National Trends in the Epidemiology of Malignant Pleural Mesothelioma: A National Cancer Data Base Study.

    Science.gov (United States)

    Saddoughi, Sahar A; Abdelsattar, Zaid M; Blackmon, Shanda H

    2018-02-01

    Malignant pleural mesothelioma (MPM) remains an aggressive malignancy that is difficult to cure. However, the treatment paradigm of MPM has evolved, and the national practice patterns are unknown. This study examined the national trends in the epidemiology, national treatment patterns, and survival of patients with this disease. We identified all patients (n = 19,134) with MPM from the National Cancer Data Base from 2004 to 2013. We analyzed patient, tumor characteristics, and treatment patterns using descriptive statistics and used Kaplan-Meier and Cox proportional hazards models to estimate survival stratified by the type of therapy administered. Four histologic subtypes were represented in the National Cancer Data Base, these included sarcomatoid (n = 2,355 [12.3%]), epithelioid (n = 6,858 [35.8%]), biphasic (n = 13,617 [11%]), and not otherwise specified (n = 8,560 [44.7%]). Across all subtypes, the prevalence of mesothelioma was highest among white men. Sarcomatoid had the worst survival (adjusted hazard ratio, 2.2; p Data Base. Although survival remains poor, multimodality therapy with surgical resection is associated with the best survival for MPM. Further research is needed to improve survival and overall patient outcomes. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  6. Metal dusting in CCR platforming unit

    Energy Technology Data Exchange (ETDEWEB)

    Dampc, J. [Lotos Group SA, Gdansk (Poland); Grzesik, Z. [AGH University of Science and Technology, Krakow (Poland); Hucinska, J. [Gdansk University of Technology, Gdansk (Poland)

    2009-03-15

    The mechanism of metal dusting of 9Cr-1Mo steel in CCR platforming unit, based on examinations of a charge heater tube, is presented. The tube operated for 10 years, and the metal skin temperature was about 600 C. The feed was composed of hydrotreated naphtha and hydrogen gas. The mechanism of the corrosion was elucidated using scanning electron microscopy, electron probe microanalysis and X-ray diffraction technique. It has been found that the carbon deposition on the steel surface and its inward diffusion into the steel is accompanied by the outward diffusion of carbide forming elements, i.e. chromium and molybdenum. At an advanced stage of the metal dusting process a thin layer of fine chromium-rich carbides beneath the steel surface exists. The layer is followed by a porous zone composed of big degraded primary carbides and fine carbides instead of alloy ferrite, with chromium and molybdenum content higher than the ferrite inside the tube wall. On the steel surface, a layer of coke composed of graphite, iron and M{sub 7}C{sub 3} carbides is formed and the uniform wastage of the steel takes place. Possible influence of some sulphur additions to the CCR platformer feed during the future service on degradation of the subsurface material has been considered. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

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

    Science.gov (United States)

    2013-07-23

    ... Act of 1995, the National Institutes of Health (NIH), has submitted to the Office of Management and... associated response time, should be directed to the: Office of Management and Budget, Office of Regulatory...: Dorothy Farrell, Center for Strategic Scientific Initiatives, Office of Cancer Nanotechnology Research...

  8. 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...

  9. Development of Tetravalent, Bispecific CCR5 Antibodies with Antiviral Activity against CCR5 Monoclonal Antibody-Resistant HIV-1 Strains▿

    Science.gov (United States)

    Schanzer, Jürgen; Jekle, Andreas; Nezu, Junichi; Lochner, Adriane; Croasdale, Rebecca; Dioszegi, Marianna; Zhang, Jun; Hoffmann, Eike; Dormeyer, Wilma; Stracke, Jan; Schäfer, Wolfgang; Ji, Changhua; Heilek, Gabrielle; Cammack, Nick; Brandt, Michael; Umana, Pablo; Brinkmann, Ulrich

    2011-01-01

    In this study, we describe novel tetravalent, bispecific antibody derivatives that bind two different epitopes on the HIV coreceptor CCR5. The basic protein formats that we applied were derived from Morrison-type bispecific antibodies: whole IgGs to which we connected single-chain antibodies (scFvs) via (Gly4Ser)n sequences at either the C or N terminus of the light chain or heavy chain. By design optimization, including disulfide stabilization of scFvs or introduction of 30-amino-acid linkers, stable molecules could be obtained in amounts that were within the same range as or no less than 4-fold lower than those observed with monoclonal antibodies in transient expression assays. In contrast to monospecific CCR5 antibodies, bispecific antibody derivatives block two alternative docking sites of CCR5-tropic HIV strains on the CCR5 coreceptor. Consequently, these molecules showed 18- to 57-fold increased antiviral activities compared to the parent antibodies. Most importantly, one prototypic tetravalent CCR5 antibody had antiviral activity against virus strains resistant to the single parental antibodies. In summary, physical linkage of two CCR5 antibodies targeting different epitopes on the HIV coreceptor CCR5 resulted in tetravalent, bispecific antibodies with enhanced antiviral potency against wild-type and CCR5 antibody-resistant HIV-1 strains. PMID:21300827

  10. CCR2+ and CCR5+ CD8+ T cells increase during viral infection and migrate to sites of infection

    DEFF Research Database (Denmark)

    Nansen, A; Marker, O; Bartholdy, C

    2000-01-01

    Chemokines and their receptors play a critical role in the selective recruitment of various leukocyte subsets. In this study, we correlated the expression of multiple chemokine and CC chemokine receptor (CCR) genes during the course of intracerebral (i.c.) infection with lymphocytic choriomeningi......Chemokines and their receptors play a critical role in the selective recruitment of various leukocyte subsets. In this study, we correlated the expression of multiple chemokine and CC chemokine receptor (CCR) genes during the course of intracerebral (i.c.) infection with lymphocytic...... a rapidly lethal, T cell-independent encephalitis, and infection resulted in a dramatic early up-regulation of chemokine gene expression. Similar marked up-regulation of chemokine expression was not seen until late after LCMV infection and required the presence of activated T cells. Cerebral CCR gene...... 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...

  11. Systemic MCP1/CCR2 blockade and leukocyte specific MCP1/CCR2 inhibition affect aortic aneurysm formation differently

    NARCIS (Netherlands)

    de Waard, Vivian; Bot, Ilze; de Jager, Saskia C. A.; Talib, Sara; Egashira, Kensuke; de Vries, Margreet R.; Quax, Paul H. A.; Biessen, Erik A. L.; van Berkel, Theo J. C.

    2010-01-01

    Objective: CCR2, the receptor for monocyte chemoattractant protein 1 (MCP1), is involved in atherosclerosis and abdominal aortic aneurysms (AAAs). Here, we explored the potential beneficial blockade of the MCP1/CCR2 pathway. Methods: We applied an AAA model in aging apolipoprotein E deficient mice

  12. 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.

  13. 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.

  14. Chemokine CCL28 induces apoptosis of decidual stromal cells via binding CCR3/CCR10 in human spontaneous abortion.

    Science.gov (United States)

    Sun, Chan; Zhang, Yuan-Yuan; Tang, Chuan-Ling; Wang, Song-Cun; Piao, Hai-Lan; Tao, Yu; Zhu, Rui; Du, Mei-Rong; Li, Da-Jin

    2013-10-01

    Spontaneous abortion is the most common complication of pregnancy. Immune activation and the subsequent inflammation-induced tissue injury are often observed at the maternal-fetal interface as the final pathological assault in recurrent spontaneous abortion. However, the precise mechanisms responsible for spontaneous abortion involving inflammation are not fully understood. Chemokine CCL28 and its receptors CCR3 and CCR10 are important regulators in inflammatory process. Here, we examined the expression of CCL28 and its receptors in decidual stromal cells (DSCs) by immunochemistry and flow cytometry (FCM), and compared their expression level in DSCs from normal pregnancy versus spontaneous abortion, and their relationship to inflammatory cytokines production by DSCs. We further analyzed regulation of the pro-inflammatory cytokines on CCL28 expression in DSCs by real-time polymerase chain reaction, In-cell Western and FCM. The effects of CCL28-CCR3/CCR10 interaction on DSC apoptosis was investigated by Annexin V staining and FCM analysis or DAPI staining and nuclear morphology. Higher levels of the inflammatory cytokines interleukin (IL)-1β, IL-17A and tumor necrosis factor-α, and increased CCR3/CCR10 expression were observed in DSCs from spontaneous abortion compared with normal pregnancy. Treatment with inflammatory cytokines differently affected CCL28 and CCR3/CCR10 expression in DSCs. Human recombinant CCL28 promoted DSC apoptosis, which was eliminated by pretreatment with neutralizing antibodies against CCR3/CCR10 and CCL28. However, CCL28 did not affect DSC growth. These results suggest that the inflammation-promoted up-regulation of CCL28 and its receptors interaction in DSCs is involved in human spontaneous abortion via inducing DSC apoptosis.

  15. Pediatric testicular cancer: Two decades of Saudi national data

    Directory of Open Access Journals (Sweden)

    Mohammed Abomelha

    2017-01-01

    Full Text Available Pediatric testicular cancer is exceedingly rare. There are no data available touching Saudi children. The aim of the study is to determine the trends and patterns of testicular cancer among Saudi children over a period of 20 years. The national database of the Saudi Cancer Registry (SCR on pediatric testicular cancer over the last two decades was examined including epidemiological and histological patterns. From 1994 to 2013, 82 cases of testicular cancer among Saudi children aged 1–14 years were accumulated at the SCR. The annual percentage change rate was 3.3%. Of all cases, 62% appeared within the first 2 years of life. Seminomas were seen in 39%, nonseminomas in 40.3%, and paratesticular tumors in 20.7%. No gonadal stromal tumors observed. About 91% of the seminomas accrued in the first decade (1994–2003, while all nonseminomas fell in the last decade (2004–2013. The most common subtypes of the nonseminomas were yolk sac tumors and mixed tumors. More than 80% of the paratesticular tumors were rhabdomyosarcomas and lymphomas. The SEER summary stage of seminomas was localized in 56%, regional in 22%, and distant in 16%, while of nonseminomas was 56%, 16%, and 28%, respectively, and no stage improvement over the studied period was noted. No temporal trend in incidence rate was observed. The most affected age group was the first 2 years of life. Noteworthy was the high incidence of seminoma and the low rate of teratomas and stromal tumors, when compared to Western data. Notable was the dominance of the seminomas in the first decade and of the nonseminomas in the second decade. At the time of diagnosis, nonseminomas were more advanced than seminomas. No stage improvement noted over the studied period.

  16. Estimated effects of the National Breast and Cervical Cancer Early Detection Program on breast cancer mortality.

    Science.gov (United States)

    Hoerger, Thomas J; Ekwueme, Donatus U; Miller, Jacqueline W; Uzunangelov, Vladislav; Hall, Ingrid J; Segel, Joel; Royalty, Janet; Gardner, James G; Smith, Judith Lee; Li, Chunyu

    2011-04-01

    The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides breast cancer screening to medically underserved, low-income women aged 40-64 years. No study has evaluated NBCCEDP's effect on breast cancer mortality. This study estimates life-years saved by NBCCEDP breast cancer screening compared with screening in the absence of NBCCEDP and with no screening. A breast cancer simulation model based on existing Cancer Intervention and Surveillance Modeling Network models was constructed. The screening module from these models was modified to reflect screening frequency for NBCCEDP participants. Screening data for uninsured women represented what would have happened without the program. Separate simulations were performed for women who received NBCCEDP (Program) screening, women who potentially received screening without the program (No Program), and women who received no screening (No Screening). The impact of NBCCEDP was estimated as the difference in life-years between the Program and No Program, and the Program and No Screening scenarios. The analysis was performed in 2008-2009. Among 1.8 million women who were screened between 1991 and 2006, the Program saved 100,800 life-years compared with No Program and 369,000 life-years compared with No Screening. Per woman screened, the Program saved 0.056 life-years (95% CI=0.031, 0.081) compared with No Program and 0.206 life-years (95% CI=0.177, 0.234) compared with No Screening. Per woman with invasive breast cancer and screen-detected invasive cancer, the Program saved 0.41 and 0.71 life-years, respectively, compared with No Program. These estimates suggest that NBCCEDP breast cancer screening has reduced mortality among medically uninsured and underinsured low-income women. Published by Elsevier Inc.

  17. Effect of hospital volume on processes of breast cancer care: A National Cancer Data Base study.

    Science.gov (United States)

    Yen, Tina W F; Pezzin, Liliana E; Li, Jianing; Sparapani, Rodney; Laud, Purushuttom W; Nattinger, Ann B

    2017-05-15

    The purpose of this study was to examine variations in delivery of several breast cancer processes of care that are correlated with lower mortality and disease recurrence, and to determine the extent to which hospital volume explains this variation. Women who were diagnosed with stage I-III unilateral breast cancer between 2007 and 2011 were identified within the National Cancer Data Base. Multiple logistic regression models were developed to determine whether hospital volume was independently associated with each of 10 individual process of care measures addressing diagnosis and treatment, and 2 composite measures assessing appropriateness of systemic treatment (chemotherapy and hormonal therapy) and locoregional treatment (margin status and radiation therapy). Among 573,571 women treated at 1755 different hospitals, 38%, 51%, and 10% were treated at high-, medium-, and low-volume hospitals, respectively. On multivariate analysis controlling for patient sociodemographic characteristics, treatment year and geographic location, hospital volume was a significant predictor for cancer diagnosis by initial biopsy (medium volume: odds ratio [OR] = 1.15, 95% confidence interval [CI] = 1.05-1.25; high volume: OR = 1.30, 95% CI = 1.14-1.49), negative surgical margins (medium volume: OR = 1.15, 95% CI = 1.06-1.24; high volume: OR = 1.28, 95% CI = 1.13-1.44), and appropriate locoregional treatment (medium volume: OR = 1.12, 95% CI = 1.07-1.17; high volume: OR = 1.16, 95% CI = 1.09-1.24). Diagnosis of breast cancer before initial surgery, negative surgical margins and appropriate use of radiation therapy may partially explain the volume-survival relationship. Dissemination of these processes of care to a broader group of hospitals could potentially improve the overall quality of care and outcomes of breast cancer survivors. Cancer 2017;123:957-66. © 2016 American Cancer Society. © 2016 American Cancer Society.

  18. 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.

  19. Roles of CcrA and CcrB in Excision and Integration of Staphylococcal Cassette Chromosome mec, a Staphylococcus aureus Genomic Island▿

    OpenAIRE

    Wang, Lei; Archer, Gordon L.

    2010-01-01

    The gene encoding resistance to methicillin and other β-lactam antibiotics in staphylococci, mecA, is carried on a genomic island, SCCmec (for staphylococcal cassette chromosome mec). The chromosomal excision and integration of types I to IV SCCmec are catalyzed by the site-specific recombinases CcrA and CcrB, the genes for which are encoded on each element. We sought to identify the relative contributions of CcrA and CcrB in the excision and integration of SCCmec. Purified CcrB but not CcrA ...

  20. Inefficient entry of vicriviroc-resistant HIV-1 via the inhibitor-CCR5 complex at low cell surface CCR5 densities

    OpenAIRE

    Pugach, Pavel; Ray, Neelanjana; Klasse, Per Johan; Ketas, Thomas J.; Michael, Elizabeth; Doms, Robert W.; Lee, Benhur; Moore, John P.

    2009-01-01

    HIV-1 variants resistant to small molecule CCR5 inhibitors such as vicriviroc (VVC) have modified Env complexes that can use both the inhibitor-bound and -free forms of the CCR5 co-receptor to enter target cells. However, entry via the inhibitor-CCR5 complex is inefficient in some, but not all, cell types, particularly cell lines engineered to express CCR5. We investigated the effect of increasing CCR5 expression, and hence the density of the inhibitor-CCR5 complex when a saturating inhibitor...

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

    OpenAIRE

    Ditzel, Henrik J.; Rosenkilde, Mette M.; Garred, Peter; Wang, Meng; Koefoed, Klaus; Pedersen, Court; Burton, Dennis R.; Schwartz, Thue W.

    1998-01-01

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

  2. Cancer Clinical Trials at the National Institutes of Health Clinical Center

    Science.gov (United States)

    ... Questions to Ask about Your Treatment Research Cancer Clinical Trials at the National Institutes of Health Clinical Center ... they are eligible for a clinical trial . NCI Clinical Trials at the NIH Clinical Center Cancer research at ...

  3. 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...

  4. 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.

  5. Metilação e CCR

    OpenAIRE

    Soares, Mónica Sofia Barroso

    2016-01-01

    Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz O Cancro Cólon Retal (CCR) é um dos cancros mais comuns no mundo, sendo o terceiro mais frequente e mortal a nível mundial, com uma incidência de cerca de 9% e provocando a morte de aproximadamente 394000 pessoas/ano. O desenvolvimento desta neoplasia surge maioritariamente associado a uma sequência e acumulação de mutações genéticas, designada sequência adenoma-carcinoma. Esta doença pode tam...

  6. Leveraging National Cancer Institute Programmatic Collaboration for Uterine Cervix Cancer Patient Accrual in Puerto Rico

    Directory of Open Access Journals (Sweden)

    Charles A. Kunos

    2018-04-01

    Full Text Available Women in the U.S. Commonwealth of Puerto Rico (PR have a higher age-adjusted incidence rate for uterine cervix cancer than the U.S. mainland as well as substantial access and economic barriers to cancer care. The National Cancer Institute (NCI funds a Minority/Underserved NCI Community Oncology Research Program in PR (PRNCORP as part of a national network of community-based health-care systems to conduct multisite cancer clinical trials in diverse populations. Participation by the PRNCORP in NCI’s uterine cervix cancer clinical trials, however, has remained limited. This study reports on the findings of an NCI site visit in PR to assess barriers impeding site activation and accrual to its sponsored gynecologic cancer clinical trials. Qualitative, semi-structured individual, and group interviews were conducted at six PRNCORP-affiliated locations to ascertain: long-term trial accrual objectives; key stakeholders in PR that address uterine cervix cancer care; key challenges or barriers to activating and to enrolling patients in NCI uterine cervix cancer treatment trials; and resources, policies, or procedures in place or needed on the island to support NCI-sponsored clinical trials. An NCI-sponsored uterine cervix cancer radiation–chemotherapy intervention clinical trial (NCT02466971, already activated on the island, served as a test case to identify relevant patient accrual and site barriers. The site visit identified five key barriers to accrual: (1 lack of central personnel to coordinate referrals for treatment plans, medical tests, and medical imaging across the island’s clinical trial access points; (2 patient insurance coverage; (3 lack of a coordinated brachytherapy schedule at San Juan-centric service providers; (4 limited credentialed radiotherapy machines island-wide; and (5 too few radiology medical physicists tasked to credential trial-specified positron emission tomography scanners island-wide. PR offers a unique opportunity to

  7. 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....... Genotypes were determined in 119 individuals enrolled in the Copenhagen AIDS Cohort. When including the concurrent effects of the CCR5 Delta32 and CCR2 64I mutations, homozygous carriers of the CCR5 promoter -2459A allele had a significantly faster progression towards death than heterozygous A/G individuals...... (P = 0.03), whereas this adverse effect was not significant when comparing A/A and G/G individuals. However, independent analysis revealed a significant adverse effect of the CCR5 promoter -2459A allele. Homozygous carriers of the -2459A allele that lack the protective effects of the CCR5 Delta32...

  8. Genotyping of CCR5 gene, CCR2b and SDF1 variants related to HIV-1 infection in Gabonese subjects.

    Science.gov (United States)

    Mombo, Landry Erik; Bisseye, Cyrille; Mickala, Patrick; Ossari, Simon; Makuwa, Maria

    2015-01-01

    Given the magnitude of the HIV epidemic infection, many viral and human factors were analyzed, and the most decisive was the variant CCR5-Δ32. The presence of a low HIV prevalence (1.8%) in Gabon in the 1990s, compared to neighboring countries, represents a paradox that led us to search for viral and human genetic variants in this country. In this study, only variants of coreceptors and chemokines were investigated. Variants of the coding region of the CCR5 gene were analyzed by denaturing gradient gel electrophoresis, and then variants of SDF1 and CCR2b were determined by polymerase chain reaction-restriction fragment length polymorphism. Four rare variants of the CCR5 coreceptor were found, while CCR5-Δ32 and CCR5m303 variants were not found. No association with CCR2b-V64I (17%) and SDF1-3'A (2%) variants was determined in relation to HIV-1 infection in Gabonese patients. The paradox of HIV seroprevalence in Gabon, which ended in the 2000s, was not caused by human genetic variants but rather by environmental factors. © 2015 S. Karger AG, Basel.

  9. National Practice Patterns for Clinical T1N0 Nasopharyngeal Cancer in the Elderly: A National Cancer Data Base Analysis.

    Science.gov (United States)

    Post, Carl M; Lin, Chi; Adeberg, Sebastian; Gupta, Mrigank; Zhen, Weining; Verma, Vivek

    2018-03-01

    The standard of care for T1N0 nasopharyngeal cancer (NPC) is definitive radiation therapy (RT). However, practice patterns in the elderly may not necessarily follow national guidelines. Herein, we investigated national practice patterns for T1N0 NPC. The National Cancer Data Base (NCDB) was queried for clinical T1N0 primary NPC cases (2004-2013) in patients ≥70 years old. Patient, tumor, and treatment parameters were extracted. Kaplan-Meier analysis was used to compare overall survival (OS) between patients receiving RT versus those under observation. Logistic regression was used to examine variables associated with receipt of RT. Cox proportional hazards modeling determined variables associated with OS. Landmark analysis of patients surviving 1 year or more was performed to assess survival differences between groups. In total, data of 147 patients were analyzed. RT was delivered to 89 patients (61%), whereas 58 (39%) patients underwent observation. On multivariable analysis, older patients were less likely to receive RT (p=0.003), but there were no differences between groups in terms of Charlson-Deyo comorbidity index. Median and 5-year OS in patients receiving RT versus those under observation were 71 and 33 months, and 59% and 48% (p=0.011), respectively. For patients surviving 1 year or more (n=96), there was a strong trend showing that receipt of RT was associated with better median and 5-year OS. This National Data Base analysis shows that observation is relatively common for T1N0 NPC in the elderly, but is associated with poorer survival. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Variation in lung cancer resources and workload: results from the first national lung cancer organisational audit.

    Science.gov (United States)

    Cusworth, K; O'Dowd, E; Hubbard, R; Beckett, P; Peake, M D; Woolhouse, I

    2015-10-01

    We report the findings of the first national lung cancer organisational audit. The results demonstrate marked variation in service provision and workload of some lung cancer specialists. For example, over half of the clinical nurse specialists report case volumes over recommended numbers. Some trusts have no access to key treatments such as video assisted thoracoscopy (VAT) lobectomy and stereotactic radiotherapy. Multivariate regression analysis demonstrated an association between higher surgical resection rates and the on-site availability of advanced staging and therapeutic modalities, for example, PET scan and VAT lobectomy. We conclude by making a number of recommendations to address the variation in lung cancer care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Trends in intensity modulated radiation therapy use for locally advanced rectal cancer at National Comprehensive Cancer Network centers

    Directory of Open Access Journals (Sweden)

    Marsha Reyngold, MD, PhD

    2018-01-01

    Conclusions: Although most patients with stage II-III rectal cancer at queried National Cancer Institute–designated cancer centers between 2005 and 2011 received 3-dimensional CRT, significant and increasing numbers received IMRT. IMRT utilization is highly variable among institutions and not uniform among sociodemographic groups but may be more consistently embraced in specific clinical settings. Given this trend, comparative-effectiveness research is needed to evaluate the benefits of IMRT for rectal cancer.

  12. Diagnosing cancer in primary care: results from the National Cancer Diagnosis Audit.

    Science.gov (United States)

    Swann, Ruth; McPhail, Sean; Witt, Jana; Shand, Brian; Abel, Gary A; Hiom, Sara; Rashbass, Jem; Lyratzopoulos, Georgios; Rubin, Greg

    2018-01-01

    Continual improvements in diagnostic processes are needed to minimise the proportion of patients with cancer who experience diagnostic delays. Clinical audit is a means of achieving this. To characterise key aspects of the diagnostic process for cancer and to generate baseline measures for future re-audit. Clinical audit of cancer diagnosis in general practices in England. Information on patient and tumour characteristics held in the English National Cancer Registry was supplemented by information from GPs in participating practices. Data items included diagnostic timepoints, patient characteristics, and clinical management. Data were collected on 17 042 patients with a new diagnosis of cancer during 2014 from 439 practices. Participating practices were similar to non-participating ones, particularly regarding population age, urban/rural location, and practice-based patient experience measures. The median diagnostic interval for all patients was 40 days (interquartile range [IQR] 15-86 days). Most patients were referred promptly (median primary care interval 5 days [IQR 0-27 days]). Where GPs deemed diagnostic delays to have occurred (22% of cases), patient, clinician, or system factors were responsible in 26%, 28%, and 34% of instances, respectively. Safety netting was recorded for 44% of patients. At least one primary care-led investigation was carried out for 45% of patients. Most patients (76%) had at least one existing comorbid condition; 21% had three or more. The findings identify avenues for quality improvement activity and provide a baseline for future audit of the impact of 2015 National Institute for Health and Care Excellence guidance on management and referral of suspected cancer. © British Journal of General Practice 2018.

  13. Diagnosing cancer in primary care: results from the National Cancer Diagnosis Audit

    Science.gov (United States)

    Swann, Ruth; McPhail, Sean; Witt, Jana; Shand, Brian; Abel, Gary A; Hiom, Sara; Rashbass, Jem; Lyratzopoulos, Georgios; Rubin, Greg

    2018-01-01

    Background Continual improvements in diagnostic processes are needed to minimise the proportion of patients with cancer who experience diagnostic delays. Clinical audit is a means of achieving this. Aim To characterise key aspects of the diagnostic process for cancer and to generate baseline measures for future re-audit. Design and setting Clinical audit of cancer diagnosis in general practices in England. Method Information on patient and tumour characteristics held in the English National Cancer Registry was supplemented by information from GPs in participating practices. Data items included diagnostic timepoints, patient characteristics, and clinical management. Results Data were collected on 17 042 patients with a new diagnosis of cancer during 2014 from 439 practices. Participating practices were similar to non-participating ones, particularly regarding population age, urban/rural location, and practice-based patient experience measures. The median diagnostic interval for all patients was 40 days (interquartile range [IQR] 15–86 days). Most patients were referred promptly (median primary care interval 5 days [IQR 0–27 days]). Where GPs deemed diagnostic delays to have occurred (22% of cases), patient, clinician, or system factors were responsible in 26%, 28%, and 34% of instances, respectively. Safety netting was recorded for 44% of patients. At least one primary care-led investigation was carried out for 45% of patients. Most patients (76%) had at least one existing comorbid condition; 21% had three or more. Conclusion The findings identify avenues for quality improvement activity and provide a baseline for future audit of the impact of 2015 National Institute for Health and Care Excellence guidance on management and referral of suspected cancer. PMID:29255111

  14. Cloning and expression analysis of cinnamoyl-CoA reductase (CCR) genes in sorghum.

    Science.gov (United States)

    Li, Jieqin; Fan, Feifei; Wang, Lihua; Zhan, Qiuwen; Wu, Peijin; Du, Junli; Yang, Xiaocui; Liu, Yanlong

    2016-01-01

    Cinnamoyl-CoA reductase (CCR) is the first enzyme in the monolignol-specific branch of the lignin biosynthetic pathway. In this research, three sorghum CCR genes including SbCCR1, SbCCR2-1 and SbCCR2-2 were cloned and characterized. Analyses of the structure and phylogeny of the three CCR genes showed evolutionary conservation of the functional domains and divergence of function. Transient expression assays in Nicotiana benthamiana leaves demonstrated that the three CCR proteins were localized in the cytoplasm. The expression analysis showed that the three CCR genes were induced by drought. But in 48 h, the expression levels of SbCCR1 and SbCCR2-2 did not differ between CK and the drought treatment; while the expression level of SbCCR2-1 in the drought treatment was higher than in CK. The expression of the SbCCR1 and SbCCR2-1 genes was not induced by sorghum aphid [Melanaphis sacchari (Zehntner)] attack, but SbCCR2-2 was significantly induced by sorghum aphid attack. It is suggested that SbCCR2-2 is involved in the process of pest defense. Absolute quantitative real-time PCR revealed that the three CCR genes were mainly expressed in lignin deposition organs. The gene copy number of SbCCR1 was significantly higher than those of SbCCR2-1 and SbCCR2-2 in the tested tissues, especially in stem. The results provide new insight into the functions of the three CCR genes in sorghum.

  15. The chemokine receptor CCR5 in the central nervous system.

    Science.gov (United States)

    Sorce, Silvia; Myburgh, Renier; Krause, Karl-Heinz

    2011-02-01

    The expression and the role of the chemokine receptor CCR5 have been mainly studied in the context of HIV infection. However, this protein is also expressed in the brain, where it can be crucial in determining the outcome in response to different insults. CCR5 expression can be deleterious or protective in controlling the progression of certain infections in the CNS, but it is also emerging that it could play a role in non-infectious diseases. In particular, it appears that, in addition to modulating immune responses, CCR5 can influence neuronal survival. Here, we summarize the present knowledge about the expression of CCR5 in the brain and highlight recent findings suggesting its possible involvement in neuroprotective mechanisms. Copyright © 2011. Published by Elsevier Ltd.

  16. Quality of life among breast cancer patients undergoing treatment in national cancer centers in Nepal.

    Science.gov (United States)

    Manandhar, Sajani; Shrestha, Deepak Sundar; Taechaboonsermsk, Pimsurang; Siri, Sukhontha; Suparp, Jarueyporn

    2014-01-01

    To study the quality of life and to identify associated factors among breast cancer patients undergoing treatment in national cancer centers in Nepal. One hundred breast cancer patients were selected and interviewed using a structured questionnaire. European Organization of Research and Treatment of Cancer EORTC-QLQ-C30 and EORTC-QLQ-BR23 were used to assess quality of life and modified Medical Outcome Study -Social Support survey(mMOS-SS) was used to assess social support. Only multi-item scales of EORTC C30 and BR23 were analyzed for relationships. Independent sample T-tests and ANOVA were applied to analyze differences in mean scores. The score of global health status/quality of life (GHS/GQoL) was marginally above average (mean=52.8). The worst performed scales in C-30 were emotional and social function while best performed scales were physical and role function. In BR-23, most of the patients fell into the problematic group regarding sexual function and enjoyment. Almost 90% had financial difficulties. Symptom scales did not demonstrate many problems. Older individuals, patients with stage I breast cancer and thosewith good social support were found to have good GHS/GQoL. Of all the influencing factors, social support was established to have strong statistical associations with most of the functional scales: GHS/GQoL (0.003), emotional function (system.

  17. Disparities in Geographic Accessibility of National Cancer Institute Cancer Centers in the United States.

    Science.gov (United States)

    Xu, Yanqing; Fu, Cong; Onega, Tracy; Shi, Xun; Wang, Fahui

    2017-11-11

    The National Cancer Institute (NCI) Cancer Centers form the backbone of the cancer care system in the United States since their inception in the early 1970s. Most studies on their geographic accessibility used primitive measures, and did not examine the disparities across urbanicity or demographic groups. This research uses an advanced accessibility method, termed "2-step floating catchment area (2SFCA)" and implemented in Geographic Information Systems (GIS), to capture the degree of geographic access to NCI Cancer Centers by accounting for competition intensity for the services and travel time between residents and the facilities. The results indicate that urban advantage is pronounced as the average accessibility is highest in large central metro areas, declines to large fringe metro, medium metro, small metro, micropolitan and noncore rural areas. Population under the poverty line are disproportionally concentrated in lower accessibility areas. However, on average Non-Hispanic White have the lowest geographic accessibility, followed by Hispanic, Non-Hispanic Black and Asian, and the differences are statistically significant. The "reversed racial disadvantage" in NCI Cancer Center accessibility seems counterintuitive but is consistent with an influential prior study; and it is in contrast to the common observation of co-location of concentration of minority groups and people under the poverty line.

  18. Comparing Local TV News with National TV News in Cancer Coverage: An Exploratory Content Analysis

    Science.gov (United States)

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

    2014-01-01

    We compared local TV news with national TV news in terms of cancer coverage using a nationally representative sample of local nightly TV and national network TV (i.e., ABC, CBS, NBC, and CNN) cancer news stories that aired during 2002 and 2003. Compared to national TV news, local TV cancer stories were (a) much shorter in length, (b) less likely to report on cancer prevention (i.e., preventive behaviors and screening tests), and (c) less likely to reference national organizations (i.e., NCI, ACS, NIH, CDC, FDA) that have made clear recommendations about ways to prevent cancer. The implications of these findings for health communication research and cancer education were discussed. PMID:24750022

  19. The case for selection at CCR5-Delta32.

    Directory of Open Access Journals (Sweden)

    2005-11-01

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

  20. 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.

  1. Genetic Variation Linked to Lung Cancer Survival in White Smokers | Center for Cancer Research

    Science.gov (United States)

    CCR investigators have discovered evidence that links lung cancer survival with genetic variations (called single nucleotide polymorphisms) in the MBL2 gene, a key player in innate immunity. The variations in the gene, which codes for a protein called the mannose-binding lectin, occur in its promoter region, where the RNA polymerase molecule binds to start transcription, and in the first exon that is responsible for the correct structure of MBL. The findings appear in the September 19, 2007, issue of the Journal of the National Cancer Institute.

  2. 75 FR 42449 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2010-07-21

    ... Research Programs and Updates of the Implementation of the Clinical Trials and Translational Research....395, Cancer Treatment Research; 93.396, Cancer Biology Research; 93.397, Cancer Centers Support; 93...

  3. 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.

  4. 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).

  5. 3 CFR 8407 - Proclamation 8407 of August 31, 2009. National Ovarian Cancer Awareness Month, 2009

    Science.gov (United States)

    2010-01-01

    .... National Ovarian Cancer Awareness Month helps educate women and men about the importance of knowing common... me by the Constitution and laws of the United States, do hereby proclaim September 2009 as National Ovarian Cancer Awareness Month. I encourage citizens, Government agencies, private businesses, nonprofit...

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

    International Nuclear Information System (INIS)

    Klausner, Richard D.

    1996-01-01

    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

  7. Translational Partnership Development Lead | Center for Cancer Research

    Science.gov (United States)

    PROGRAM DESCRIPTION The Frederick National Laboratory for Cancer Research (FNLCR) is a Federally Funded Research and Development Center operated by Leidos Biomedical Research, Inc on behalf of the National Cancer Institute (NCI). The staff of FNLCR support the NCI’s mission in the fight against cancer and HIV/AIDS. Currently we are seeking a Translational Partnership Development Lead (TPDL) who will work closely with the Office of Translational Resources (OTR) within the Office of the Director (OD) of NCI’s Center for Cancer Research (CCR) to facilitate the successful translation of CCR’s basic and preclinical research advances into new therapeutics and diagnostics. The TPDL with be strategically aligned within FNLCR’s Partnership Development Office (PDO), to maximally leverage the critical mass of expertise available within the PDO. CCR comprises the basic and clinical components of the NCI’s Intramural Research Program (IRP) and consists of ~230 basic and clinical Investigators located at either the NIH main campus in Bethesda or the NCI-Frederick campus. CCR Investigators are focused primarily on cancer and HIV/AIDS, with special emphasis on the most challenging and important high-risk/high-reward problems driving the fields. (See https://ccr.cancer.gov for a full delineation of CCR Investigators and their research activities.) The process of developing research findings into new clinical applications is high risk, complex, variable, and requires multiple areas of expertise seldom available within the confines of a single Investigator’s laboratory. To accelerate this process, OTR serves as a unifying force within CCR for all aspects of translational activities required to achieve success and maintain timely progress. A key aspect of OTR’s function is to develop and strengthen essential communications and collaborations within NIH, with extramural partners and with industry to bring together experts in chemistry, human subjects research

  8. Analysis of esophagogastric cancer patients enrolled in the National Cancer Institute Cancer Therapy Evaluation Program sponsored phase 1 trials.

    Science.gov (United States)

    Bando, Hideaki; Rubinstein, Larry; Harris, Pamela; Yoshino, Takayuki; Doi, Toshihiko; Ohtsu, Atsushi; Welch, John; Takebe, Naoko

    2017-05-01

    In phase 1 trials, an important entry criterion is life expectancy predicted to be more than 90 days, which is generally difficult to predict. The Royal Marsden Hospital (RMH) prognostic score that is determined by lactate dehydrogenase level, albumin level, and number of metastatic sites of disease was developed to help project patient outcomes. There have been no systematic analyses to evaluate the utility of the RMH prognostic score for esophagogastric cancer patients. All nonpediatric phase 1 oncology trials sponsored by the National Cancer Institute Cancer Therapy Evaluation Program that began between 2001 and 2013 were considered in this review. Of 4722 patients with solid tumors, 115 patients were eligible for our analysis; 54 (47 %) with cancer of the esophagus, 14 (12 %) with cancer of the esopagogastric junction, and 47 (41 %) with stomach cancer. Eighty-six patients (75 %) had a good RMH prognostic score (0 or 1) and 29 patients (25 %) had a poor RMH prognostic score (2 or 3). Disease control rates were significantly different between patients with good and poor RMH prognostic scores (49 % vs 17 %; two-sided Fisher's exact test P = 0.004). The median treatment duration and overall survival for good and poor RMH prognostic score patients were significantly different (median treatment duration 2.1 months vs 1.2 months respectively, P = 0.016; median overall survival 10.9 months vs 2.1 months respectively, P cancer patients who might participate in a phase 1 trial.

  9. Cancer of the penis at Kenyatta National Hospital | Magoha | East ...

    African Journals Online (AJOL)

    most common was prostate cancer (56.0%), followed by bladder cancer (25.0%), kidney cancer (7.9%), and testicular cancer (6.1%). Thirty eight ... Twenty five patients had partial penectomy with radiotherapy and or chemotherapy. ... Eleven other patients had radiotherapy either alone or combined with chemotherapy.

  10. 75 FR 20370 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-04-19

    ... Cancer Institute Special Emphasis Panel, Assay Systems for Drug Efficacy in Cancer Stem Cells. Date..., Rockville, MD 20852. Contact Person: David G. Ransom, PhD, Scientific Review Officer, Research Programs... Domestic Assistance Program Nos. 93.392, Cancer Construction; 93.393, Cancer Cause and Prevention Research...

  11. Locally advance breast cancer survival after radiotherapy following mastectomy at the National Cancer Institute of Colombia

    International Nuclear Information System (INIS)

    Ospino, Rosalba; Cendales, Ricardo; Cifuentes, Javier; Sanchez, Zayda; Galvis, Juan; Bobadilla, Ivan

    2010-01-01

    Objective: To evaluate survival after treatment with mastectomy and teletherapy for locally advance breast cancer at the National Cancer Institute of Colombia. Methods: A case serie analysis was conducted. Frequencies and measures of central tendency were applied. Locoregional relapse free survival, disease free survival and overall survival were determined with Kaplan-Meyer and Cox regression analyses. Results: 174 patiens were included. Most of the patients corresponded to ductal tumors with positive axillary nodes and hormone receptors. The treatment was neoadjuvant chemotherapy, mastectomy, axillary nodes resection, radiotherapy, and adjuvant hormone therapy. The 5-years locoregional relapse free survival was 88.8%, disease free survival was 63.3%, and overall survival 84.4%. Conclusions: The results are similar to previous reports. Breast reconstruction was associated with a greater chance of locoregional relapse. The node rate is a relevant predictor for overall survival, disease free survival, and locoregional relapse free survival, and tumor grade for the former two.

  12. Locally advance breast cancer survival after radiotherapy following mastectomy at the National Cancer Institute of Colombia

    International Nuclear Information System (INIS)

    Ospino, Rosalba; Cendales, Ricardo; Cifuentes, Javier; Sanchez, Zayda; Galvis, Juan; Bobadilla, Ivan

    2009-01-01

    Objective: To evaluate survival after treatment with mastectomy and teletherapy for locally advance breast cancer at the National Cancer Institute of Colombia. Methods: A case serie analysis was conducted. Frequencies and measures of central tendency were applied. Locoregional relapse free survival, disease free survival and overall survival were determined with Kaplan-Meyer and Cox regression analyses. Results: 174 patients were included. Most of the patients corresponded to ductal tumors with positive axillary nodes and hormone receptors. The treatment was neoadjuvant chemotherapy, mastectomy, axillary nodes resection, radiotherapy, and adjuvant hormone therapy. The 5-years locoregional relapse free survival was 88.8%, disease free survival was 63.3%, and overall survival 84.4%. Conclusions: The results are similar to previous reports. Breast reconstruction was associated with a greater chance of locoregional relapse. The node rate is a relevant predictor for overall survival, disease free survival, and locoregional relapse free survival, and tumor grade for the former two.

  13. Survival As a Quality Metric of Cancer Care: Use of the National Cancer Data Base to Assess Hospital Performance.

    Science.gov (United States)

    Shulman, Lawrence N; Palis, Bryan E; McCabe, Ryan; Mallin, Kathy; Loomis, Ashley; Winchester, David; McKellar, Daniel

    2018-01-01

    Survival is considered an important indicator of the quality of cancer care, but the validity of different methodologies to measure comparative survival rates is less well understood. We explored whether the National Cancer Data Base (NCDB) could serve as a source of unadjusted and risk-adjusted cancer survival data and whether these data could be used as quality indicators for individual hospitals or in the aggregate by hospital type. The NCDB, an aggregate of > 1,500 hospital cancer registries, was queried to analyze unadjusted and risk-adjusted hazards of death for patients with stage III breast cancer (n = 116,787) and stage IIIB or IV non-small-cell lung cancer (n = 252,392). Data were analyzed at the individual hospital level and by hospital type. At the hospital level, after risk adjustment, few hospitals had comparative risk-adjusted survival rates that were statistically better or worse. By hospital type, National Cancer Institute-designated comprehensive cancer centers had risk-adjusted survival ratios that were statistically significantly better than those of academic cancer centers and community hospitals. Using the NCDB as the data source, survival rates for patients with stage III breast cancer and stage IIIB or IV non-small-cell lung cancer were statistically better at National Cancer Institute-designated comprehensive cancer centers when compared with other hospital types. Compared with academic hospitals, risk-adjusted survival was lower in community hospitals. At the individual hospital level, after risk adjustment, few hospitals were shown to have statistically better or worse survival, suggesting that, using NCDB data, survival may not be a good metric to determine relative quality of cancer care at this level.

  14. Epitope Switching as a Novel Escape Mechanism of HIV to CCR5 Monoclonal Antibodies▿

    OpenAIRE

    Jekle, Andreas; Chhabra, Milloni; Lochner, Adriane; Meier, Sonja; Chow, Eugene; Brandt, Michael; Sankuratri, Surya; Cammack, Nick; Heilek, Gabrielle

    2009-01-01

    In passaging experiments, we isolated HIV strains resistant to MAb3952, a chemokine (C-C motif) receptor 5 (CCR5) monoclonal antibody (MAb) that binds to the second extracellular domain (extracellular loop 2 [ECL-2]) of CCR5. MAb3952-resistant viruses remain CCR5-tropic and are cross-resistant to a second ECL-2-specific antibody. Surprisingly, MAb3952-resistant viruses were more susceptible to RoAb13, a CCR5 antibody binding to the N terminus of CCR5. Using CCR5 receptor mutants, we show that...

  15. National Cancer Institute and American Association for Clinical Chemistry Partner to Bridge the Gap | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The National Cancer Institute, through its Clinical Proteomic Technologies for Cancer (CPTC) initiative has entered into a memorandum of understanding with the American Association for Clinical Chemistry (AACC) to join forces to promote and educate the clinical chemistry community in the area of proteomic standards and technology advances.

  16. National assessment of HPV and Pap tests: Changes in cervical cancer screening, National Health Interview Survey.

    Science.gov (United States)

    Watson, Meg; Benard, Vicki; King, Jessica; Crawford, Anatasha; Saraiya, Mona

    2017-07-01

    Major organizations recommend cytology screening (Pap test) every 3years for women aged 21-65; women aged 30 to 65 have the option of adding the HPV test (co-test) every 5years. We examined national percentages of cervical cancer screening, and we examined use of co-testing as an option for screening. We used 2015 U.S. National Health Interview Survey (NHIS) data to examine recent cervical cancer screening (Pap test within 3years among women aged 21-65 without a hysterectomy; N=10,596) and co-testing (N=9,125). We also conducted a multivariable analysis to determine odds of having had a Pap test or co-test by demographic variables. To evaluate changes in screening over time, we examined Pap testing during the years 2000, 2005, 2008, 2010, 2013 and 2015. Analysis completed in Atlanta, GA during 2016. Overall, 81.1% of eligible women reported having a Pap test within 3years; percentages declined over time among all age groups. An estimated 14 million women aged 21-65 had not been screened within the past 3years. Recent immigrants to the United States, women without insurance, and women without a usual source of healthcare had lower odds of being up to date with screening. About 1/3 of women up to date on Pap testing reported having a co-test with their most recent Pap test. Declines in screening among women aged 21-65 are cause for concern. More research is needed on co-testing practices. Provider and patient education efforts may be needed to clarify recommended use of HPV tests. Published by Elsevier Inc.

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

    International Nuclear Information System (INIS)

    Acquavella, J.J.; Wilkinson, G.S.; Wiggs, L.D.; Reyes-Waxweiler, M.; Key, C.R.; Tietjen, G.L.

    1985-01-01

    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

  18. Depletion of Gut-Resident CCR5+Cells for HIV Cure Strategies.

    Science.gov (United States)

    Merriam, David; Chen, Connie; Méndez-Lagares, Gema; Rogers, Kenneth A; Michaels, Anthony J; Yan, Jiangli; Casaz, Paul; Reimann, Keith A; Villinger, François; Hartigan-O'Connor, Dennis J

    2017-11-01

    The HIV reservoir forming at the earliest stages of infection is likely composed of CCR5 + cells, because these cells are the targets of transmissible virus. Restriction of the CCR5 + reservoir, particularly in the gut, may be needed for subsequent cure attempts. Strategies for killing or depleting CCR5 + cells have been described, but none have been tested in vivo in nonhuman primates, and the extent of achievable depletion from tissues is not known. In this study we investigate the efficacy of two novel cytotoxic treatments for targeting and eliminating CCR5 + cells in young rhesus macaques. The first, an immunotoxin consisting of the endogenous CCR5 ligand RANTES fused with Pseudomonas exotoxin (RANTES-PE38), killed CCR5 + lamina propria lymphocytes (LPLs) ex vivo, but had no detectable effect on CCR5 + LPLs in vivo. The second, a primatized bispecific antibody for CCR5 and CD3, depleted all CCR5 + cells from blood and the vast majority of such cells from the colonic mucosa (up to 96% of CD4 + CCR5 + ). Absence of CCR5-expressing cells from blood endured for at least 1 week, while CCR5 + cells in colon were substantially replenished over the same time span. These data open an avenue to investigation of combined early ART treatment and CCR5 + reservoir depletion for cure of HIV-infected infants.

  19. Early outcomes for rectal cancer surgery in the republic of ireland following a national centralization program.

    Science.gov (United States)

    Burke, John P; Coffey, J Calvin; Boyle, Emily; Keane, Frank; McNamara, Deborah A

    2013-10-01

    Following a national audit of rectal cancer management in 2007, a national centralization program in the Republic of Ireland was initiated. In 2010, a prospective evaluation of rectal cancer treatment and early outcomes was conducted. A total of 29 colorectal surgeons in 14 centers prospectively collated data on all patients with rectal cancer who underwent curative surgery in 2010. Data were available on 447 patients who underwent proctectomy with curative intent for rectal cancer in 2010; 23.7 % of patients underwent abdominoperineal excision. The median number of lymph nodes identified was 12. The 30-day mortality rate was 1.1 %. Compared with 2007, there was a reduction in positive circumferential margin rate (15.8 vs 4.5 %, P rectal cancer. Patients undergoing rectal cancer surgery in hospitals following a national centralization initiative received high-quality surgery. Significant heterogeneity exists in radiotherapy administration, and evidence-based guidelines should be developed and implemented.

  20. Fox Chase Cancer Center's Genitourinary Division: a national resource for research, innovation and patient care.

    Science.gov (United States)

    Uzzo, Robert G; Horwitz, Eric M; Plimack, Elizabeth R

    2016-04-01

    Founded in 1904, Fox Chase Cancer Center remains committed to its mission. It is one of 41 centers in the country designated as a Comprehensive Cancer Center by the National Cancer Institute, is a founding member of the National Comprehensive Cancer Network, holds the magnet designation for nursing excellence, is one of the first to establish a family cancer risk assessment program, and has achieved national distinction because of the scientific discoveries made there that have advanced clinical care. Two of its researchers have won Nobel prizes. The Genitourinary Division is nationally recognized and viewed as one of the top driving forces behind the growth of Fox Chase due to its commitment to initiating and participating in clinical trials, its prolific contributions to peer-reviewed publications and presentations at scientific meetings, its innovations in therapies and treatment strategies, and its commitment to bringing cutting-edge therapies to patients.

  1. Impact of national cancer policies on cancer survival trends and socioeconomic inequalities in England, 1996-2013: population based study

    Science.gov (United States)

    Rachet, Bernard; Belot, Aurélien; Maringe, Camille; Coleman, Michel P

    2018-01-01

    Abstract Objective To assess the effectiveness of the NHS Cancer Plan (2000) and subsequent national cancer policy initiatives in improving cancer survival and reducing socioeconomic inequalities in survival in England. Design Population based cohort study. Setting England. Population More than 3.5 million registered patients aged 15-99 with a diagnosis of one of the 24 most common primary, malignant, invasive neoplasms between 1996 and 2013. Main outcome measures Age standardised net survival estimates by cancer, sex, year, and deprivation group. These estimates were modelled using regression model with splines to explore changes in the cancer survival trends and in the socioeconomic inequalities in survival. Results One year net survival improved steadily from 1996 for 26 of 41 sex-cancer combinations studied, and only from 2001 or 2006 for four cancers. Trends in survival accelerated after 2006 for five cancers. The deprivation gap observed for all 41 sex-cancer combinations among patients with a diagnosis in 1996 persisted until 2013. However, the gap slightly decreased for six cancers among men for which one year survival was more than 65% in 1996, and for cervical and uterine cancers, for which survival was more than 75% in 1996. The deprivation gap widened notably for brain tumours in men and for lung cancer in women. Conclusions Little evidence was found of a direct impact of national cancer strategies on one year survival, and no evidence for a reduction in socioeconomic inequalities in cancer survival. These findings emphasise that socioeconomic inequalities in survival remain a major public health problem for a healthcare system founded on equity. PMID:29540358

  2. 77 FR 55095 - National Ovarian Cancer Awareness Month, 2012

    Science.gov (United States)

    2012-09-06

    ... Proclamation This year, thousands of American women will lose their lives to ovarian cancer. They are mothers... campaign, we are working to raise awareness about the signs and symptoms of ovarian cancer. The Affordable...

  3. 75 FR 54453 - National Prostate Cancer Awareness Month, 2010

    Science.gov (United States)

    2010-09-07

    ... several factors that may increase a man's risk of developing prostate cancer, including age, race, and..., husbands, and sons battling prostate cancer, as well as their families and the health care providers...

  4. 76 FR 62285 - National Breast Cancer Awareness Month, 2011

    Science.gov (United States)

    2011-10-07

    ... cancer, and too many will be lost. African-American women bear a particularly large burden, experiencing higher death rates from breast cancer than other racial or ethnic groups in the United States. Too many...

  5. Pattern of Skin cancer at the National Orthopaedic Hospital, Enugu ...

    African Journals Online (AJOL)

    ... should be undertaken by albinos. Public enlightenment towards early recognition of skin cancer will enhance early presentation and ensure adequate and curative treatment. Keywords: Skin cancers, squamous cell carcinoma, late presentation of skin cancer. Nigerian Journal of Plastic Surgery Vol. 4 (1) 2008: pp. 13-18 ...

  6. Oral cancer at Kenyatta National Hospital, Nairobi | Onyango | East ...

    African Journals Online (AJOL)

    Background: The epidemiology of oral cancer in the African population is still uncertain. Earlier reports suggested a relatively low incidence of oral cancer among Africans. However, there have been recent reports of an upward trend in the incidence of oral cancers in developing countries as a consequence of changes in ...

  7. Cervical cancer in women diagnosed at the National Health ...

    African Journals Online (AJOL)

    Background: Cancer of the cervix is the second most prevalent cancer of women to date in the Sudan, in a concerted review of the records of the hospital-based cancer registry of the Radiation & Isotope Centre of Khartoum (RICK). However, in spite of a wealth of data, this is the first study to date describing the ...

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

    OpenAIRE

    Camargo, Jose F.; Quinones, Marlon P.; Mummidi, Srinivas; Srinivas, Sowmya; Gaitan, Alvaro A.; Begum, Kazi; Jimenez, Fabio; VanCompernolle, Scott; Unutmaz, Derya; Ahuja, Seema S.; Ahuja, Sunil K.

    2009-01-01

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

  9. National Cancer Institute’s Cancer Disparities Research Partnership Program: Experience and Lessons Learned

    Directory of Open Access Journals (Sweden)

    Rosemary S. L. Wong

    2014-11-01

    Full Text Available Purpose: To increase access of underserved/health disparities communities to National Cancer Institute (NCI clinical trials, the Radiation Research Program (RRP piloted a unique model - the Cancer Disparities Research Partnership (CDRP program. CDRP targeted community hospitals with a limited past NCI funding history and provided funding to establish the infrastructure for their clinical research program.Methods: Initially, 5-year planning phase funding was awarded to six CDRP institutions through a cooperative agreement (U56. Five were subsequently eligible to compete for 5-year implementation phase (U54 funding and three received a second award. Additionally, the NCI Center to Reduce Cancer Health Disparities supported their U56 Patient Navigation programs.Results: Community-based hospitals with little or no clinical trials experience required at least a year to develop the infrastructure and establish community outreach/education and Patient Navigation programs before accrual to clinical trials could begin. Once established, CDRP sites increased their yearly patient accrual mainly to NCI-sponsored cooperative group trials (~60% and Principal Investigator (PI/mentor-initiated trials (~30%. The total number of patients accrued on all types of trials was 2,371, while 5,147 patients received navigation services. Conclusions: Despite a historical gap in participation in clinical cancer research, underserved communities are willing/eager to participate. Since a limited number of cooperative group trials address locally advanced diseases seen in health disparities populations, this shortcoming needs to be rectified. Sustainability for these programs remains a challenge. Addressing these gaps through research and public health mechanisms may have an important impact on their health, scientific progress and efforts to increase diversity in NCI clinical trials.

  10. Epitope Switching as a Novel Escape Mechanism of HIV to CCR5 Monoclonal Antibodies▿

    Science.gov (United States)

    Jekle, Andreas; Chhabra, Milloni; Lochner, Adriane; Meier, Sonja; Chow, Eugene; Brandt, Michael; Sankuratri, Surya; Cammack, Nick; Heilek, Gabrielle

    2010-01-01

    In passaging experiments, we isolated HIV strains resistant to MAb3952, a chemokine (C-C motif) receptor 5 (CCR5) monoclonal antibody (MAb) that binds to the second extracellular domain (extracellular loop 2 [ECL-2]) of CCR5. MAb3952-resistant viruses remain CCR5-tropic and are cross-resistant to a second ECL-2-specific antibody. Surprisingly, MAb3952-resistant viruses were more susceptible to RoAb13, a CCR5 antibody binding to the N terminus of CCR5. Using CCR5 receptor mutants, we show that MAb3952-resistant virus strains preferentially use the N terminus of CCR5, while the wild-type viruses preferentially use ECL-2. We propose this switch in the CCR5 binding site as a novel mechanism of HIV resistance. PMID:19995923

  11. CCR Certification Form for Wyoming or EPA R8 Tribal Community Water Systems

    Science.gov (United States)

    The CCR Certification Form can be used to certify that community water systems in Wyoming or on Tribal Lands in EPA Region 8 have completed and distributed their annual Consumer Confidence Report (CCR) or water quality report.

  12. In-silico guided discovery of novel CCR9 antagonists

    Science.gov (United States)

    Zhang, Xin; Cross, Jason B.; Romero, Jan; Heifetz, Alexander; Humphries, Eric; Hall, Katie; Wu, Yuchuan; Stucka, Sabrina; Zhang, Jing; Chandonnet, Haoqun; Lippa, Blaise; Ryan, M. Dominic; Baber, J. Christian

    2018-03-01

    Antagonism of CCR9 is a promising mechanism for treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. There is limited experimental data on CCR9 and its ligands, complicating efforts to identify new small molecule antagonists. We present here results of a successful virtual screening and rational hit-to-lead campaign that led to the discovery and initial optimization of novel CCR9 antagonists. This work uses a novel data fusion strategy to integrate the output of multiple computational tools, such as 2D similarity search, shape similarity, pharmacophore searching, and molecular docking, as well as the identification and incorporation of privileged chemokine fragments. The application of various ranking strategies, which combined consensus and parallel selection methods to achieve a balance of enrichment and novelty, resulted in 198 virtual screening hits in total, with an overall hit rate of 18%. Several hits were developed into early leads through targeted synthesis and purchase of analogs.

  13. The chemokine receptor CCR2 maintains plasmacytoid dendritic cell homeostasis

    DEFF Research Database (Denmark)

    Cédile, Oriane; Østerby Jørgensen, Line; Frank, Ida

    2017-01-01

    Thymic dendritic cells (DC) play a role in central tolerance. Three thymic DC subtypes have been described: plasmacytoid DC (pDC) and two conventional DC (cDC), CD8α+ Sirpα- DC and Sirpα+ CD8α- cDC. Both pDC and Sirpα+ cDC can take up antigen in periphery and migrate into the thymus in response t...... by CCL2 or CCR2 deficiency. Although some thymic progenitors expressed CCR2, this did not include those that give rise to pDC. Based on these results, we propose that CCR2 is involved in pDC homeostasis but its ligand CCL2 does not play a major role....

  14. National and Subnational Population-Based Incidence of Cancer in Thailand: Assessing Cancers with the Highest Burdens

    Directory of Open Access Journals (Sweden)

    Shama Virani

    2017-08-01

    Full Text Available In Thailand, five cancer types—breast, cervical, colorectal, liver and lung cancer—contribute to over half of the cancer burden. The magnitude of these cancers must be quantified over time to assess previous health policies and highlight future trajectories for targeted prevention efforts. We provide a comprehensive assessment of these five cancers nationally and subnationally, with trend analysis, projections, and number of cases expected for the year 2025 using cancer registry data. We found that breast (average annual percent change (AAPC: 3.1% and colorectal cancer (female AAPC: 3.3%, male AAPC: 4.1% are increasing while cervical cancer (AAPC: −4.4% is decreasing nationwide. However, liver and lung cancers exhibit disproportionately higher burdens in the northeast and north regions, respectively. Lung cancer increased significantly in northeastern and southern women, despite low smoking rates. Liver cancers are expected to increase in the northern males and females. Liver cancer increased in the south, despite the absence of the liver fluke, a known factor, in this region. Our findings are presented in the context of health policy, population dynamics and serve to provide evidence for future prevention strategies. Our subnational estimates provide a basis for understanding variations in region-specific risk factor profiles that contribute to incidence trends over time.

  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. PMID:24955252

  16. 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.

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

    Science.gov (United States)

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

    2013-06-04

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

  18. Use of G-Protein-Coupled and -Uncoupled CCR5 Receptors by CCR5 Inhibitor-Resistant and -Sensitive Human Immunodeficiency Virus Type 1 Variants

    Science.gov (United States)

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

    2013-01-01

    Small-molecule CCR5 inhibitors such as vicriviroc (VVC) and maraviroc (MVC) are allosteric modulators that impair HIV-1 entry by stabilizing a CCR5 conformation that the virus recognizes inefficiently. Viruses resistant to these compounds are able to bind the inhibitor-CCR5 complex while also interacting with the free coreceptor. CCR5 also interacts intracellularly with G proteins, as part of its signal transduction functions, and this process alters its conformation. Here we investigated whether the action of VVC against inhibitor-sensitive and -resistant viruses is affected by whether or not CCR5 is coupled to G proteins such as Gαi. Treating CD4+ T cells with pertussis toxin to uncouple the Gαi subunit from CCR5 increased the potency of VVC against the sensitive viruses and revealed that VVC-resistant viruses use the inhibitor-bound form of Gαi-coupled CCR5 more efficiently than they use uncoupled CCR5. Supportive evidence was obtained by expressing a signaling-deficient CCR5 mutant with an impaired ability to bind to G proteins, as well as two constitutively active mutants that activate G proteins in the absence of external stimuli. The implication of these various studies is that the association of intracellular domains of CCR5 with the signaling machinery affects the conformation of the external and transmembrane domains and how they interact with small-molecule inhibitors of HIV-1 entry. PMID:23468486

  19. Enriquecimento com calda do CCR para face de barragens

    OpenAIRE

    Wendler,A. P.; Marques Filho,J.; Franco Filho,J. M. M.; Bianchini,M.

    2014-01-01

    A construção de barragens de CCR prioriza a minimização de interferências, como a execução da face de montante, para garantia da produtividade. O estudo procurou avaliar as propriedades físicas do CCR enriquecido com calda, em substituição ao concreto convencional usualmente empregado na face, utilizando os mesmos materiais, central de concreto, mão de obra e equipamentos, empregados na construção da Usina Hidrelétrica Mauá. Para tanto foram feitos prismas experimentais de campo (com diferent...

  20. Solution Structure of LC4 Transmembrane Segment of CCR5

    OpenAIRE

    Miyamoto, Kazuhide; Togiya, Kayo

    2011-01-01

    CC-chemokine receptor 5 (CCR5) is a specific co-receptor allowing the entry of human immunodeficiency virus type 1 (HIV-1). The LC4 region in CCR5 is required for HIV-1 entry into the cells. In this study, the solution structure of LC4 in SDS micelles was elucidated by using standard 1H two-dimensional NMR spectroscopy, circular dichroism, and fluorescdence quenching. The LC4 structure adopts two helical structures, whereas the C-terminal part remains unstructured. The positions in which LC4 ...

  1. Postdoctoral Fellows | Center for Cancer Research

    Science.gov (United States)

    The Oncogenomics section of the Genetics Branch is a multidisciplinary and interdisciplinary translational research programmatic effort with the goal of utilizing genomics to develop novel immunotherapies for cancer. Our group is applying high throughput applied genomics methods including single cell RNAseq, single cell TCR sequencing, DNA sequencing, CRISPR/Cas9, bioinformatics combined with T cell based therapeutics to identify and develop novel immunotherapeutics for human cancer. We work with other investigators within the intramural program as well as industrial and pharmaceutical partners to rapidly translate our findings to the clinic. The program takes advantage of the uniqueness of the National Cancer Institute, (NCI), Center for Cancer Research (CCR) intramural program in that it spans high-risk basic discovery research in immunology, genomics and tumor biology, through preclinical translational research, to paradigm-shifting clinical trials. The position is available immediately. The appointment duration is up to 5 years. Stipends are commensurate with education and experience. Additional information can be found on Dr. Khan’s profile page: https://ccr.cancer.gov/Genetics-Branch/javed-khan

  2. Research Associate | Center for Cancer Research

    Science.gov (United States)

    PROGRAM DESCRIPTION The Cancer Research Technology Program (CRTP) develops and implements emerging technology, cancer biology expertise and research capabilities to accomplish NCI research objectives.  The CRTP is an outward-facing, multi-disciplinary hub purposed to enable the external cancer research community and provides dedicated support to NCI’s intramural Center for Cancer Research (CCR).  The dedicated units provide electron microscopy, protein characterization, protein expression, optical microscopy and nextGen sequencing. These research efforts are an integral part of CCR at the Frederick National Laboratory for Cancer Research.  CRTP scientists also work collaboratively with intramural NCI investigators to provide research technologies and expertise. KEY ROLES/RESPONSIBILITIES We are seeking a highly motivated Research Associate II to join the newly established Single Cell Analysis Facility (SCAF) of the CCR at NCI.  The SCAF will house state of the art single cell sequencing technologies including 10xGenomics Chromium, BD Genomics Rhapsody, DEPPArray, and other emerging single cell technologies. This person will work under the guidance of SCAF senior staff to carry out single cell sequencing experiments.

  3. Neuropathic pain inhibitor, RAP-103, is a potent inhibitor of microglial CCL1/CCR8.

    Science.gov (United States)

    Noda, Mami; Tomonaga, Daichi; Kitazono, Kota; Yoshioka, Yusaku; Liu, Jiadai; Rousseau, Jean-Philippe; Kinkead, Richard; Ruff, Michael R; Pert, Candace B

    2017-12-14

    Chemokine signaling is important in neuropathic pain, with microglial cells expressing chemokine (C-C motif) receptor CCR2, CCR5 and CCR8, all playing key roles. In the previous report (Padi et al., 2012), oral administration of a short peptide, RAP-103, for 7 days fully prevents mechanical allodynia and inhibits the development of thermal hyperalgesia after partial ligation of the sciatic nerve in rodents. As for the mechanism of the inhibiting effect of RAP-103, it was speculated to be due to dual blockade of CCR2 and CCR5. We report here that RAP-103 exhibits stronger antagonism for CCR8 (half maximal inhibitory concentration [IC 50 ] 7.7 fM) compared to CCR5 (IC 50  < 100 pM) in chemotaxis using primary cultured mouse microglia. In addition, RAP-103 at a concentration of 0.1 pM completely inhibits membrane ruffling and phagocytosis induced by chemokine (C-C motif) ligand 1 (CCL1), an agonist for CCR8. It has been shown that CCL1/CCR8 signaling is important in tactile allodynia induced by nerve ligation. Therefore, CCR8, among other chemokine receptors such as CCR2/CCR5, could be the most potent target for RAP-103. Inhibitory effects of RAP-103 on plural chemokine receptors may play important roles for broad clinical use in neuropathic pain treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    2012-02-03

    ... Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review AGENCY... stakeholder input on the Consumer Confidence Report (CCR) Rule as part of the agency's Retrospective Review of... implementing CCR delivery certification, use of CCRs to meet Tier 3 Public Notification requirements, and how...

  5. 77 FR 55833 - Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review...

    Science.gov (United States)

    2012-09-11

    ... on the Consumer Confidence Report (CCR) Rule Retrospective Review and Request for Public Comment on Potential Approaches to Electronic Delivery of the CCR AGENCY: Environmental Protection Agency (EPA). ACTION... potential approaches for providing Consumer Confidence Reports (CCR) via electronic delivery. EPA plans to...

  6. Molecular requirements for inhibition of the chemokine receptor CCR8--probe-dependent allosteric interactions

    DEFF Research Database (Denmark)

    Rummel, Pia Cwarzko; Arfelt, K N; Baumann, L

    2012-01-01

    Here we present a novel series of CCR8 antagonists based on a naphthalene-sulfonamide structure. This structure differs from the predominant pharmacophore for most small-molecule CC-chemokine receptor antagonists, which in fact activate CCR8, suggesting that CCR8 inhibition requires alternative...

  7. Breast and Cervical Cancer Screening Behavior in Female Cancer Survivors: The Korea National Health and Nutrition Examination Survey, 2007-2012.

    Science.gov (United States)

    Lee, Eun-Ae; Shin, Jinyoung; Hwang, Eun-Joo; Lee, Jung-Woong

    2017-05-01

    The aim of this study was to compare breast and cervical cancer screening rates between female cancer survivors and a population without cancer to identify factors related to cervical and breast cancer screening in cancer survivors. We included 17,765 adults (738 cancer survivors and 17,027 individuals without cancer) in this study, all of whom who were 30 years of age or older and participated in the Fourth and Fifth Korean National Health and Nutritional Examination Surveys from 2007-2012. Multiple logistic regression analysis was performed to identify factors related to cervical and breast cancer screening uptake in female cancer survivors. The screening rate for breast cancer was 56.6%, which was higher than that in the non-cancer control group (P=0.001). The screening rate for cervical cancer was 51.4%, which was not different from that of the non-cancer control group. In terms of breast cancer screening, cancer survivors showed no significant difference in the rate of screening 5 years after their cancer diagnosis. However, cervical cancer survivors were less likely to have cervical cancer screening 10 years after their cancer diagnosis. There was no significant association between cancer screening and sociodemographic factors. Breast and cervical cancer screening rates in Korean female cancer survivors are low. Secondary primary cancer screening of female cancer survivors needs to be planned in a comprehensive manner, with the consideration of influences beyond sociodemographic factors.

  8. From Cancer Screening to Treatment: Service Delivery and Referral in the National Breast and Cervical Cancer Early Detection Program

    Science.gov (United States)

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

    2015-01-01

    The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides breast and cervical cancer screening and diagnostic services to low-income and underserved women through a network of providers and health care organizations. Although the program serves women 40-64 years old for breast cancer screening and 21-64 years old for cervical cancer screening, the priority populations are women 50-64 years old for breast cancer and women who have never or rarely been screened for cervical cancer. From 1991 through 2011, the NBCCEDP provided screening and diagnostic services to more than 4.3 million women, diagnosing 54,276 breast cancers, 2554 cervical cancers, and 123,563 precancerous cervical lesions. A critical component of providing screening services is to ensure that all women with abnormal screening results receive appropriate and timely diagnostic evaluations. Case management is provided to assist women with overcoming barriers that would delay or prevent follow-up care. Women diagnosed with cancer receive treatment through the states' Breast and Cervical Cancer Treatment Programs (a special waiver for Medicaid) if they are eligible. The NBCCEDP has performance measures that serve as benchmarks to monitor the completeness and timeliness of care. More than 90% of the women receive complete diagnostic care and initiate treatment less than 30 days from the time of their diagnosis. Provision of effective screening and diagnostic services depends on effective program management, networks of providers throughout the community, and the use of evidence-based knowledge, procedures, and technologies. PMID:25099897

  9. 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

    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.

  10. Gene polymorphisms in CCR5, CCR2, SDF1 and RANTES among Chinese Han population with HIV-1 infection.

    Science.gov (United States)

    Li, Hui; Liu, Ting-Jun; Hong, Ze-Hui

    2014-06-01

    Chemokines and chemokine receptors are crucial for immune response in HIV-1 infection. Although many studies have been done to investigate the relationship between chemokines and chemokine receptor gene polymorphisms and host's susceptibility to HIV-1 infection, the conclusions are under debate. In the present study, a cohort of 287 HIV-1 seropositive patients, 388 ethnically age-matched healthy controls and 49 intravenous drug users (IDUs) HIV-1 exposed seronegative individuals (HESN) from Chinese Han population were enrolled in order to determine the influence of host genetic factors on HIV-1 infection. Seven polymorphisms on four known chemokines/chemokine receptor genes (CCR5Δ32, CCR5 m303, CCR5 59029A/G, CCR2 64I, RANTES -403A/G, RANTES -28C/G and SDF1 3'-A) were screened. CCR5Δ32 and CCR5 m303 were absent or infrequent in Chinese Han population, which may not be hosts' genetic protective factors for HIV-1 infection. Our results showed the CCR5 59029A/G, CCR2 64I and SDF1 3'-A were not associated with host's resistance to HIV-1 infection. The frequency of RANTES -403A allele was significantly lower in HIV-1 patients than in healthy blood donors (p=0.0005) and HESN group (p=0.035), which implied the association between A allele and reduced HIV-1 infection risk. Different genetic models were assessed to investigate this association (AA vs. GG+AG, OR=0.38 95% CI, 0.22-0.65 p=0.0004; A vs. G, OR=0.66 95% CI, 0.52-0.84 p=0.0006), which supported this association, either. The genotype and allele distribution of RANTES -28 between HIV-1 patients and healthy controls (genotype profile: p=0.072; allele profile: p=0.027) or HIV-1 seronegative group (genotype profile: p=0.036; allele profile: p=0.383) were both at the marginal level of significance, which were not observed after Bonferroni correction. All these results suggest the RANTES -403A may be associated with reduced susceptibility to HIV-1 infection, while the RANTES -28 locus not. By lack of the patients

  11. Renal cell cancer stage migration: analysis of the National Cancer Data Base.

    Science.gov (United States)

    Kane, Christopher J; Mallin, Katherine; Ritchey, Jamie; Cooperberg, Matthew R; Carroll, Peter R

    2008-07-01

    Evidence exists to suggest a pattern of increasing early diagnosis of renal cell carcinoma (RCC). The aim of the study was to analyze patterns of disease presentation and outcome of RCC by AJCC stage using data from the National Cancer Data Base (NCDB) over a 12-year period. The NCDB was queried for adults diagnosed between 1993 and 2004 presenting with ICD-O-2 of 3 renal cell tumors arising in the kidney. Cases were classified by demographics, 2002 AJCC stage (6th edition), and histology. The Cochran-Armitage Test for Trend was used to determine statistical significance of trends over time. Cox regression multivariate analysis was used to evaluate the impact of stage and histology on relative survival. SPSS 14.0 was used for analyses. Between 1993 and 2004 a total of 205,963 patients from the NCDB fit our case definition of RCC. Comparisons between 1993 and 2004 data show an increase in stage I disease and decrease in stage II, III, and IV disease (P < or = .001). The size of stage I tumors also decreased from a mean of 4.1 cm in 1993 to 3.6 cm in 2003. In multivariate analysis, stage, but not histology, predicted relative survival. A 3.3% increase in survival was found for patients diagnosed in 1998 compared with patients diagnosed in 1993. A greater proportion of newly diagnosed patients with RCC currently present with stage I disease compared with earlier years. Stage predicts relative survival for patients with kidney cancer. More recently diagnosed patients have improved relative survival. (Copyright) 2008 American Cancer Society.

  12. National Cancer Institute Formulary: A Public-Private Partnership Providing Investigators Access to Investigational Anticancer Agents.

    Science.gov (United States)

    Cristofaro, J V; Ansher, S S; Zwiebel, J A; Ivy, P; Conley, B; Abrams, J S; Doroshow, J H

    2017-05-01

    As part of the White House Cancer Moonshot Initiative, the National Cancer Institute (NCI) has developed a drug formulary to provide investigational anticancer agents to the extramural research community. This article describes how the NCI Formulary functions, how researchers may apply for access to drugs in the formulary, and the NCI's initial goals for formulary participation. Approved investigators may apply for access to formulary agents at: https://nciformulary.cancer.gov. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  13. 3 CFR 8354 - Proclamation 8354 of April 1, 2009. National Cancer Control Month, 2009

    Science.gov (United States)

    2010-01-01

    ... America A Proclamation We have achieved remarkable progress in the fight against cancer. Miracles in... Prevention, and academic and other institutions. The Federal Government plays an indispensable role in... 3 The President 1 2010-01-01 2010-01-01 false Proclamation 8354 of April 1, 2009. National Cancer...

  14. Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on HIV-1 disease progression

    DEFF Research Database (Denmark)

    Ioannidis, J P; Rosenberg, P S; Goedert, J J

    2001-01-01

    seroconversion. Data were combined with fixed-effects and random-effects models. RESULTS: Both the CCR5-Delta32 and CCR2-64I alleles were associated with a decreased risk for progression to AIDS (relative hazard among seroconverters, 0.74 and 0.76, respectively; P = 0.01 for both), a decreased risk for death...... (relative hazard among seroconverters, 0.64 and 0.74; P CCR5-Delta32 or CCR2-64I allele had no clear protective effect on the risk for death.......00), or death after development of AIDS (relative hazard, 0.81 and 0.97; P > 0.5 for all). CONCLUSIONS: The CCR5-Delta32 and CCR2-64I alleles had a strong protective effect on progression of HIV-1 infection, but SDF-1 3'A homozygosity carried no such protection....

  15. 77 FR 5029 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2012-02-01

    ... Community; Cancer Drug Shortages: Economic, Regulatory, and Manufacturing Issues; The Role of the Cancer... security, NIH has instituted stringent procedures for entrance onto the NIH campus. All visitor vehicles, including taxicabs, hotel, and airport shuttles will be inspected before being allowed on campus. Visitors...

  16. 77 FR 20491 - National Cancer Control Month, 2012

    Science.gov (United States)

    2012-04-05

    ... unlock new therapies. Innovative studies are paving the way for effective treatments to deadly cancers..., women, and children we have lost to cancer, and we look ahead to a future in which more Americans have..., April 5, 2012 / Presidential Documents#0;#0; #0; #0;Title 3-- #0;The President [[Page 20491...

  17. 75 FR 17839 - National Cancer Control Month, 2010

    Science.gov (United States)

    2010-04-07

    ... Institutes of Health to develop more effective treatments. While cancer affects people of every background... from cancer. Americans should discuss preventive care with a health professional. Getting regular check... limiting sun exposure and alcohol consumption, avoiding tobacco, exercising regularly, and maintaining a...

  18. 77 FR 55848 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2012-09-11

    ... Clinical Trials and Strategic Planning Subcommittee. Date: September 24, 2012. Time: 5 p.m. to 6 p.m... Trials Strategic Planning Subcommittee. Dial in number: 1-866-652-9542 and Passcode: 4596704. Place... Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93.396, Cancer Biology Research; 93.397...

  19. 78 FR 5190 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2013-01-24

    ... Clinical Trials and Strategic Planning Subcommittee. Date: February 25, 2013. Time: 5:00 p.m. to 6:00 p.m... Trials Strategic Planning Subcommittee. Dial in number: 1-866-652-9542 and Passcode: 4596704. Place... Research; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93.396...

  20. 77 FR 36564 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2012-06-19

    ... Prevention Method: State of the, Science and Evidence. Place: Hilton San Francisco Financial District, 750... applicable, the business or professional affiliation of the interested person. Information is also available... Research; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93.396...

  1. Central extensions for the Weyl CCR in Curved space

    International Nuclear Information System (INIS)

    Emch, G.G.

    1993-01-01

    For non-necessarily flat homogeneous configuration spaces, we illustrate how the cohomological choices made in the definition a Weyl group of the CCR are reflected in the momentum map for the action of this group on its co-adjoint orbit of maximal dimension. (Author) 8 refs

  2. Gene editing using a zinc-finger nuclease mimicking the CCR5Δ32 mutation induces resistance to CCR5-using HIV-1.

    Science.gov (United States)

    Badia, Roger; Riveira-Muñoz, Eva; Clotet, Bonaventura; Esté, José A; Ballana, Ester

    2014-07-01

    To characterize a new zinc-finger nuclease (ZFN) that targets close to the sequence of the 32 bp deletion polymorphism in the CCR5 gene, and to generate cells resistant to HIV-1 strains that use CCR5. CCR5Δ32 is a naturally occurring deletion that provides genetic resistance to R5-tropic HIV-1. The specificity and efficacy of a newly identified target for CCR5 gene editing, near the CCR5Δ32 sequence (ZFNCCR5Δ32), was assessed as well as its ability to generate cells resistant to HIV infection with reduced off-target effects. ZFNCCR5Δ32 activity was evaluated by heteroduplex formation in human K562 cells. Assessment of ZFNCCR5Δ32 specificity was analysed in silico. The yield of ZFNCCR5Δ32 in cell culture was improved by fluorescence-activated cell sorting, and the anti-HIV potency of ZFNCCR5Δ32 was measured in vitro in TZM-bl cells against HIV-1 strains. ZFNCCR5Δ32 effectively recognized the CCR5Δ32 region, inducing a frameshift of the CCR5 coding region that resulted in the complete absence of CCR5 expression of mRNA and of protein at the cell surface. CCR5 knockout cells were refractory to HIV-1 infection by the R5-using strain BaL. Unlike previous CCR5 ZFN studies, the new ZFN has no detectable off-target activity. ZFNCCR5Δ32 is a specific and efficient tool for the generation of CCR5 knockouts. Its ability to mimic the natural CCR5Δ32 phenotype in the absence of relevant off-site cutting events suggests that ZFNCCR5Δ32 might be safe in clinical research. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Development of National Program of Cancer Registries SAS Tool for Population-Based Cancer Relative Survival Analysis.

    Science.gov (United States)

    Dong, Xing; Zhang, Kevin; Ren, Yuan; Wilson, Reda; O'Neil, Mary Elizabeth

    2016-01-01

    Studying population-based cancer survival by leveraging the high-quality cancer incidence data collected by the Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR) can offer valuable insight into the cancer burden and impact in the United States. We describe the development and validation of a SASmacro tool that calculates population-based cancer site-specific relative survival estimates comparable to those obtained through SEER*Stat. The NPCR relative survival analysis SAS tool (NPCR SAS tool) was developed based on the relative survival method and SAS macros developed by Paul Dickman. NPCR cancer incidence data from 25 states submitted in November 2012 were used, specifically cases diagnosed from 2003 to 2010 with follow-up through 2010. Decennial and annual complete life tables published by the National Center for Health Statistics (NCHS) for 2000 through 2009 were used. To assess comparability between the 2 tools, 5-year relative survival rates were calculated for 25 cancer sites by sex, race, and age group using the NPCR SAS tool and the National Cancer Institute's SEER*Stat 8.1.5 software. A module to create data files for SEER*Stat was also developed for the NPCR SAS tool. Comparison of the results produced by both SAS and SEER*Stat showed comparable and reliable relative survival estimates for NPCR data. For a majority of the sites, the net differences between the NPCR SAS tool and SEER*Stat-produced relative survival estimates ranged from -0.1% to 0.1%. The estimated standard errors were highly comparable between the 2 tools as well. The NPCR SAS tool will allow researchers to accurately estimate cancer 5-year relative survival estimates that are comparable to those produced by SEER*Stat for NPCR data. Comparison of output from the NPCR SAS tool and SEER*Stat provided additional quality control capabilities for evaluating data prior to producing NPCR relative survival estimates.

  4. An anti-CCR5 monoclonal antibody and small molecule CCR5 antagonists synergize by inhibiting different stages of human immunodeficiency virus type 1 entry

    International Nuclear Information System (INIS)

    Safarian, Diana; Carnec, Xavier; Tsamis, Fotini; Kajumo, Francis; Dragic, Tatjana

    2006-01-01

    HIV-1 coreceptors are attractive targets for novel antivirals. Here, inhibition of entry by two classes of CCR5 antagonists was investigated. We confirmed previous findings that HIV-1 isolates vary greatly in their sensitivity to small molecule inhibitors of CCR5-mediated entry, SCH-C and TAK-779. In contrast, an anti-CCR5 monoclonal antibody (PA14) similarly inhibited entry of diverse viral isolates. Sensitivity to small molecules was V3 loop-dependent and inversely proportional to the level of gp120 binding to CCR5. Moreover, combinations of the MAb and small molecules were highly synergistic in blocking HIV-1 entry, suggesting different mechanisms of action. This was confirmed by time course of inhibition experiments wherein the PA14 MAb and small molecules were shown to inhibit temporally distinct stages of CCR5 usage. We propose that small molecules inhibit V3 binding to the second extracellular loop of CCR5, whereas PA14 preferentially inhibits subsequent events such as CCR5 recruitment into the fusion complex or conformational changes in the gp120-CCR5 complex that trigger fusion. Importantly, our findings suggest that combinations of CCR5 inhibitors with different mechanisms of action will be central to controlling HIV-1 infection and slowing the emergence of resistant strains

  5. Development of experimental autoimmune uveitis: efficient recruitment of monocytes is independent of CCR2.

    Science.gov (United States)

    Dagkalis, Athanasios; Wallace, Carol; Xu, Heping; Liebau, Sebastian; Manivannan, Ayyakkannu; Stone, Michael A; Mack, Matthias; Liversidge, Janet; Crane, Isabel J

    2009-09-01

    Macrophages are major contributors to the damage occurring in the retina in experimental autoimmune uveitis (EAU). CCR2 may be needed for efficient recruitment of monocytes to an inflammatory site, and the aim of this study was to determine whether this was the case in EAU. EAU was induced and graded in C57BL/6J and CCR2(-/-) mice. Macrophage infiltration and CCR2 expression were assessed using immunohistochemistry. Retinas were examined for MCP-1 expression using RT-PCR. Rolling and infiltration of labeled bone marrow monocytes at the inflamed retinal vasculature were examined by scanning laser ophthalmoscopy and confocal microscopy, respectively. Effect of CCR2 deletion or blockade by antibody and antagonist was determined. Expression of mRNA for MCP-1 increased as EAU developed and was localized to the retina. CCR2 was associated with infiltrating macrophages. However, EAU induced in CCR2(-/-) mice was not reduced in severity, and neither was the percentage of macrophages in the retina. CCR2(-/-) monocytes, 48 hours after adoptive transfer to mice with EAU, showed no significant difference in percentage rolling or infiltration into the retina compared to WT. CCR2-independent rolling of monocytes was confirmed by CCR2 neutralizing antibody and antagonist treatment. CCR2 does not have a primary role in the recruitment of monocytes to the inflammatory site across the blood-retina barrier in well-developed EAU. Therapeutics targeting CCR2 are unlikely to be of value in treating human posterior uveitis.

  6. Marked differences in CCR5 expression and activation levels in two South African populations

    Science.gov (United States)

    Picton, Anabela C P; Shalekoff, Sharon; Paximadis, Maria; Tiemessen, Caroline T

    2012-01-01

    The chemokine receptor CCR5 is pivotal in determining an individual’s susceptibility to HIV-1 infection and rate of disease progression. To establish whether population-based differences exist in cell surface expression of CCR5 we evaluated the extent of CCR5 expression across all peripheral blood cell types in individuals from two populations, South African Africans (SAA) and South African Caucasians (SAC). Significant differences in CCR5 expression, both in number of CCR5 molecules per cell (density) and the percentage of CCR5-expressing cells, were observed between the two study groups, within all cell subsets. Most notably, the percentage of all CCR5+ cell subsets was significantly lower in SAC compared with SAA individuals (P CCR5 density was significantly higher in SAC compared with SAA individuals in CCR5+ CD8+ T-cell subsets and CCR5+ NK-cell subsets (CD56+, CD16+ CD56+ and CD56dim) (all P CCR5 expression, which are likely to impact on both susceptibility to HIV-1 infection and the rate of HIV-1 disease progression. PMID:22509959

  7. 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...... time were seen for CCR5/CCR5 patients. Surprisingly, no protective effect of the CCR5/CCR5Delta32 genotype on disease progression or survival was seen for children but was evident for adults. Age group-related immunologic differences might explain this variation, and transmission route and/or viral...... phenotype variation within donor virus may be related to the limited protection of the CCR5Delta32/CCR5Delta32 genotype. Sequence comparisons indicate that X4 virus can be selected in vivo due to either absence of CCR5 receptors or relative increase of CXCR4 receptors....

  8. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV.

    Science.gov (United States)

    Tebas, Pablo; Stein, David; Tang, Winson W; Frank, Ian; Wang, Shelley Q; Lee, Gary; Spratt, S Kaye; Surosky, Richard T; Giedlin, Martin A; Nichol, Geoff; Holmes, Michael C; Gregory, Philip D; Ando, Dale G; Kalos, Michael; Collman, Ronald G; Binder-Scholl, Gwendolyn; Plesa, Gabriela; Hwang, Wei-Ting; Levine, Bruce L; June, Carl H

    2014-03-06

    CCR5 is the major coreceptor for human immunodeficiency virus (HIV). We investigated whether site-specific modification of the gene ("gene editing")--in this case, the infusion of autologous CD4 T cells in which the CCR5 gene was rendered permanently dysfunctional by a zinc-finger nuclease (ZFN)--is safe. We enrolled 12 patients in an open-label, nonrandomized, uncontrolled study of a single dose of ZFN-modified autologous CD4 T cells. The patients had chronic aviremic HIV infection while they were receiving highly active antiretroviral therapy. Six of them underwent an interruption in antiretroviral treatment 4 weeks after the infusion of 10 billion autologous CD4 T cells, 11 to 28% of which were genetically modified with the ZFN. The primary outcome was safety as assessed by treatment-related adverse events. Secondary outcomes included measures of immune reconstitution and HIV resistance. One serious adverse event was associated with infusion of the ZFN-modified autologous CD4 T cells and was attributed to a transfusion reaction. The median CD4 T-cell count was 1517 per cubic millimeter at week 1, a significant increase from the preinfusion count of 448 per cubic millimeter (PCCR5-modified CD4 T cells at 1 week was 250 cells per cubic millimeter. This constituted 8.8% of circulating peripheral-blood mononuclear cells and 13.9% of circulating CD4 T cells. Modified cells had an estimated mean half-life of 48 weeks. During treatment interruption and the resultant viremia, the decline in circulating CCR5-modified cells (-1.81 cells per day) was significantly less than the decline in unmodified cells (-7.25 cells per day) (P=0.02). HIV RNA became undetectable in one of four patients who could be evaluated. The blood level of HIV DNA decreased in most patients. CCR5-modified autologous CD4 T-cell infusions are safe within the limits of this study. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00842634.).

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

    DEFF Research Database (Denmark)

    Møller, M; Søndergaard, H 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...

  10. Coverage of common cancer types in UK national newspapers: a content analysis.

    Science.gov (United States)

    Konfortion, Julie; Jack, Ruth H; Davies, Elizabeth A

    2014-07-11

    To determine whether recent newspaper coverage of the four most common cancer types relates to their relative burden and national awareness months, and to identify the subject focus during high-coverage periods. Content analysis using the Nexis newspaper article database. UK 2011-2012. Annual number and ranking, monthly proportions and subject of articles on breast, lung, bowel and prostate cancers. 9178 articles were identified during 2011 and 2012 featuring breast (4237), prostate (1757), lung (1746) and bowel (1438) cancer. Peaks in monthly proportions above the 99% upper confidence limit were identified for each. Breast cancer had the highest coverage of 12% and 17% during its awareness month. Smaller peaks (11%) were identified during Bowel Cancer Awareness month. Prostate cancer received high coverage in relation to the case of the man convicted of the Lockerbie bombing who had been diagnosed with the cancer, and lung cancer in relation to the deaths of celebrities. Breast cancer was covered most often overall and by newspaper category while the lower coverage of other cancer types did not consistently mirror the relative number of new cases each year. The peaks by newspaper category were similar to the overall coverage with few exceptions. UK newspaper coverage of common cancer types other than of the breast appears under-represented relative to their population burden. Coverage of breast cancer and bowel cancer appears to be influenced by their awareness months, while that of prostate cancer and lung cancer is influenced by other media stories. Health-promoting public bodies and campaigners could learn from the success of Breast Cancer Awareness Month and work more closely with journalists to ensure that the relevant messages reach wider audiences. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. 76 FR 55209 - National Ovarian Cancer Awareness Month, 2011

    Science.gov (United States)

    2011-09-07

    ... month, we remember the mothers, sisters, and daughters we have lost to ovarian cancer, and we extend our... the women, families, and professionals working to end this disease. The Centers for Disease Control...

  12. 77 FR 19674 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-04-02

    ... commercial property such as patentable material, and personal information concerning individuals associated... and evaluate grant applications. Place: Doubletree Hotel Bethesda, 8120 Wisconsin Avenue, Bethesda, MD... Institute Special Emphasis Panel; Innovative Molecular Analysis Technologies for Cancer (R21). Date: June 26...

  13. 76 FR 20693 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2011-04-13

    ... special assistance, such as sign language interpretation or other reasonable accommodations, should notify... Dialogue, Nonprofit Conveners Driving Implementation of Research Outcomes, Barriers to Implementation of Research Outcomes, Presentations Highlighting Local Academic Research in Cancer. Place: Rizzo Conference...

  14. 78 FR 54737 - National Childhood Cancer Awareness Month, 2013

    Science.gov (United States)

    2013-09-06

    ... death by disease for American children under 15. For those children and their families, and in memory of... trial, including clinical trials that treat childhood cancer. All children deserve the chance to dream...

  15. Delivering prostate cancer prevention messages to the public: how the National Cancer Institute (NCI) effectively spread the word about the Prostate Cancer Prevention Trial (PCPT) results.

    Science.gov (United States)

    Croker, Kara Smigel; Ryan, Anne; Morzenti, Thuy; Cave, Lynn; Maze-Gallman, Tamara; Ford, Leslie

    2004-01-01

    The Prostate Cancer Prevention Trial was the first clinical trial to show that a direct intervention (5 mg of finasteride daily for 7 years) could reduce a man's risk of developing prostate cancer. Initial results also suggested that men taking finasteride had an increased risk of developing what appeared to be higher-grade disease (Gleason score 7-10). The National Cancer Institute has a congressional mandate to communicate health information to the public and has established methods to reach the public directly and to reach information intermediaries in the media, professional societies, and advocacy groups. The groundbreaking yet complicated results of the Prostate Cancer Prevention Trial were widely disseminated by National Cancer Institute using the social marketing and public-relations strategies and tactics detailed here. Copyright 2004 Elsevier Inc.

  16. 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

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

    International Nuclear Information System (INIS)

    2002-10-01

    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)

  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

    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.

  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)

    International Nuclear Information System (INIS)

    Canzian, Federico; Calle, Eugenia E; Chanock, Stephen; Clavel-Chapelon, Francoise; Dossus, Laure; Feigelson, Heather Spencer; Haiman, Christopher A; Hankinson, Susan E; Hoover, Robert; Hunter, David J; Isaacs, Claudine; Kaaks, Rudolf; Lenner, Per; Lund, Eiliv; Overvad, Kim; Palli, Domenico; Pearce, Celeste Leigh; Quiros, Jose R; Riboli, Elio; Stram, Daniel O; Thomas, Gilles; Thun, Michael J; Cox, David G; Trichopoulos, Dimitrios; Gils, Carla H van; Ziegler, Regina G; Henderson, Katherine D; Henderson, Brian E; Berg, Christine; Bingham, Sheila; Boeing, Heiner; Buring, Julie

    2009-01-01

    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

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

    International Nuclear Information System (INIS)

    Acquavella, J.F.; Wilkinson, G.S.; Wiggs, L.D.; Tietjen, G.L.; Key, C.R.

    1983-01-01

    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

  1. 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.

  2. Role of CCL-2, CCR-2 and CCR-4 in cerulein-induced acute pancreatitis and pancreatitis-associated lung injury.

    Science.gov (United States)

    Frossard, Jean Louis; Lenglet, Sébastien; Montecucco, Fabrizio; Steffens, Sabine; Galan, Katia; Pelli, Graziano; Spahr, Laurent; Mach, Francois; Hadengue, Antoine

    2011-05-01

    Acute pancreatitis is an inflammatory process of variable severity. Leucocytes are thought to play a key role in the development of pancreatitis and pancreatitis-associated lung injury. The interactions between inflammatory cells and their mediators are crucial for determining tissue damage. Monocyte chemoattractant protein-1 (or CCL-2), CCR-2 and CCR-4 are chemokines and chemokine receptors involved in leucocyte trafficking. The aim of the study was to evaluate the role of the CCL-2, CCR-2 and CCR-4 chemokine receptors in the pathogenesis of cerulein-induced pancreatitis and pancreatitis-associated lung injury. To address the role of CCL-2, CCR-2 and CCR-4 that attracts leucocytes cells in inflamed tissues, pancreatitis was induced by administering supramaximal doses of cerulein in mice that do not express CCL-2, CCR-2 or CCR-4. The severity of pancreatitis was measured by serum amylase, pancreatic oedema and acinar cell necrosis. Lung injury was quantitated by evaluating lung microvascular permeability and lung myeloperoxidase activity. Chemokine and chemokine-receptor expression were quantitated by real-time PCR. The nature of inflammatory cells invading the pancreas and lungs was studied by immunostaining. The authors have found that pancreas CCL-2 and CCR-2 levels rise during pancreatitis. Both pancreatitis and the associated lung injury are blunted, but not completely prevented, in mice deficient in CCL-2, whereas the deficiency in either CCR-2 or CCR-4 does not reduce the severity of both the pancreatitis and the lung injury. The amounts of neutrophils and monocyte/macrophages (MOMA)-2 cells were significantly lower in mice deficient in CCL-2 compared with their sufficient littermates. These results suggest that CCL-2 plays a key role in pancreatitis by modulating the infiltration by neutrophils and MOMA-2 cells, and that its deficiency may improve the outcome of the disease.

  3. HIV-1 Escape from the CCR5 Antagonist Maraviroc Associated with an Altered and Less-Efficient Mechanism of gp120-CCR5 Engagement That Attenuates Macrophage Tropism▿

    Science.gov (United States)

    Roche, Michael; Jakobsen, Martin R.; Sterjovski, Jasminka; Ellett, Anne; Posta, Filippo; Lee, Benhur; Jubb, Becky; Westby, Mike; Lewin, Sharon R.; Ramsland, Paul A.; Churchill, Melissa J.; Gorry, Paul R.

    2011-01-01

    Maraviroc (MVC) inhibits the entry of human immunodeficiency virus type 1 (HIV-1) by binding to and modifying the conformation of the CCR5 extracellular loops (ECLs). Resistance to MVC results from alterations in the HIV-1 gp120 envelope glycoproteins (Env) enabling recognition of the drug-bound conformation of CCR5. To better understand the mechanisms underlying MVC resistance, we characterized the virus-cell interactions of gp120 from in vitro-generated MVC-resistant HIV-1 (MVC-Res Env), comparing them with those of gp120 from the sensitive parental virus (MVC-Sens Env). In the absence of the drug, MVC-Res Env maintains a highly efficient interaction with CCR5, similar to that of MVC-Sens Env, and displays a relatively modest increase in dependence on the CCR5 N terminus. However, in the presence of the drug, MVC-Res Env interacts much less efficiently with CCR5 and becomes critically dependent on the CCR5 N terminus and on positively charged elements of the drug-modified CCR5 ECL1 and ECL2 regions (His88 and His181, respectively). Structural analysis suggests that the Val323 resistance mutation in the gp120 V3 loop alters the secondary structure of the V3 loop and the buried surface area of the V3 loop–CCR5 N terminus interface. This altered mechanism of gp120-CCR5 engagement dramatically attenuates the entry of HIV-1 into monocyte-derived macrophages (MDM), cell-cell fusion activity in MDM, and viral replication capacity in MDM. In addition to confirming that HIV-1 escapes MVC by becoming heavily dependent on the CCR5 N terminus, our results reveal novel interactions with the drug-modified ECLs that are critical for the utilization of CCR5 by MVC-Res Env and provide additional insights into virus-cell interactions that modulate macrophage tropism. PMID:21345957

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

    Science.gov (United States)

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

    2014-08-15

    The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides breast and cervical cancer screening and diagnostic services to low-income and underserved women through a network of providers and health care organizations. Although the program serves women 40-64 years old for breast cancer screening and 21-64 years old for cervical cancer screening, the priority populations are women 50-64 years old for breast cancer and women who have never or rarely been screened for cervical cancer. From 1991 through 2011, the NBCCEDP provided screening and diagnostic services to more than 4.3 million women, diagnosing 54,276 breast cancers, 2554 cervical cancers, and 123,563 precancerous cervical lesions. A critical component of providing screening services is to ensure that all women with abnormal screening results receive appropriate and timely diagnostic evaluations. Case management is provided to assist women with overcoming barriers that would delay or prevent follow-up care. Women diagnosed with cancer receive treatment through the states' Breast and Cervical Cancer Treatment Programs (a special waiver for Medicaid) if they are eligible. The NBCCEDP has performance measures that serve as benchmarks to monitor the completeness and timeliness of care. More than 90% of the women receive complete diagnostic care and initiate treatment less than 30 days from the time of their diagnosis. Provision of effective screening and diagnostic services depends on effective program management, networks of providers throughout the community, and the use of evidence-based knowledge, procedures, and technologies. © 2014 American Cancer Society.

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

    Science.gov (United States)

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

    2016-05-01

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

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

    International Nuclear Information System (INIS)

    Wang, Elyn H.; Mougalian, Sarah S.; Soulos, Pamela R.; Rutter, Charles E.; Evans, Suzanne B.; Haffty, Bruce G.; Gross, Cary P.; Yu, James B.

    2014-01-01

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

  7. Variation in Locoregional Prostate Cancer Care and Treatment Trends at Commission on Cancer Designated Facilities: A National Cancer Data Base Analysis 2004 to 2013.

    Science.gov (United States)

    Löppenberg, Björn; Sood, Akshay; Dalela, Deepansh; Karabon, Patrick; Sammon, Jesse D; Vetterlein, Malte W; Noldus, Joachim; Peabody, James O; Trinh, Quoc-Dien; Menon, Mani; Abdollah, Firas

    2017-12-01

    Contemporary treatment trends for prostate cancer show increased rates of active surveillance. However, nationwide applicability of these reports is limited. Additionally, the effect of Commission on Cancer facility type on prostate cancer treatment patterns is unknown. We used the National Cancer Data Base to identify men diagnosed with prostate cancer, between 2004 and 2013. Our cohort was stratified on the basis of the National Comprehensive Cancer Network prostate cancer risk classes. Cochran-Armitage tests were used to evaluate temporal trends. Random effects hierarchical logit models were used to assess treatment variation at Commission on Cancer facility and institution level. In 825,707 men, utilization of radiation therapy declined and utilization of radical prostatectomy increased for all prostate cancer risk groups between 2004 and 2013 (P Commission on Cancer facility type. Across all risk groups, the lowest rates of radical prostatectomy and highest rates of external beam radiation therapy were observed in community cancer programs. The highest rates of observation for low-risk disease were observed in academic centers. Treatment variation according to institution ranged from 14% (95% confidence interval, 0.12-0.15) for androgen deprivation therapy up to 59% (95% confidence interval, 0.45-0.73) for cryotherapy. The increased utilization of observation in low-risk prostate cancer is an encouraging finding, which appears to be mainly derived by a decrease in radiotherapy utilization in this risk group. Regardless of tumor characteristics, significant variations in treatment modality exist among different facility types and institutions. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    ... Cancer and Environment Research Centers (BCERCs) to conduct interdisciplinary research on the effects of early environmental exposures ... more than 20 cancers using state-of-the art genomic analysis technologies. Recent findings suggest that there ...

  9. The molecular cloning and functional expression of the dog CCR5.

    Science.gov (United States)

    Mosley, Michael; Pullen, Sarah; Botham, Andrew; Gray, Andrew; Napier, Carolyn; Mansfield, Roy; Holbrook, Mark

    2006-10-15

    Activation of CCR5 by specific chemokines is involved in the regulation of the immunological response of leukocytes at sites of inflammation. In addition, CCR5 serves as a fusion co-factor for macrophage-tropic strains of human immunodeficiency virus type 1 (HIV-1). Consequently, several CCR5 antagonists are currently in development for the treatment of HIV-1 infection. The dog CCR5 gene was cloned in order to characterise the chemokine binding site of the dog receptor for comparison across species. The deduced amino acid sequence of the dog CCR5 has close homology to the human receptor (80% identity). A HEK-293 cell line expressing the dog recombinant receptor was generated and immunoblot analysis with an anti-human CCR5 antibody revealed a 58kDa band in the cell lysate. In functional calcium signalling assays, the CCR5 endogenous ligands MIP-1alpha, MIP-1beta and RANTES evoked a robust response in the dog recombinant CCR5 cells. In a CRE-Luc (cAMP response element-luciferase) reporter gene assay, MIP-1beta (0.01-30nM) produced concentration-dependent inhibition of forskolin induced elevation in cAMP levels, and was equipotent in dog, human and macaque recombinant CCR5 cells (EC(50) 0.4, 0.21 and 0.47nM, respectively). These data suggest that chemokine signalling is conserved in the dog CCR5.

  10. Suppression of CCR impacts metabolite profile and cell wall composition in Pinus radiata tracheary elements.

    Science.gov (United States)

    Wagner, Armin; Tobimatsu, Yuki; Goeminne, Geert; Phillips, Lorelle; Flint, Heather; Steward, Diane; Torr, Kirk; Donaldson, Lloyd; Boerjan, Wout; Ralph, John

    2013-01-01

    Suppression of the lignin-related gene cinnamoyl-CoA reductase (CCR) in the Pinus radiata tracheary element (TE) system impacted both the metabolite profile and the cell wall matrix in CCR-RNAi lines. UPLC-MS/MS-based metabolite profiling identified elevated levels of p-coumaroyl hexose, caffeic acid hexoside and ferulic acid hexoside in CCR-RNAi lines, indicating a redirection of metabolite flow within phenylpropanoid metabolism. Dilignols derived from coniferyl alcohol such as G(8-5)G, G(8-O-4)G and isodihydrodehydrodiconiferyl alcohol (IDDDC) were substantially depleted, providing evidence for CCR's involvement in coniferyl alcohol biosynthesis. Severe CCR suppression almost halved lignin content in TEs based on a depletion of both H-type and G-type lignin, providing evidence for CCR's involvement in the biosynthesis of both lignin types. 2D-NMR studies revealed minor changes in the H:G-ratio and consequently a largely unchanged interunit linkage distribution in the lignin polymer. However, unusual cell wall components including ferulate and unsaturated fatty acids were identified in TEs by thioacidolysis, pyrolysis-GC/MS and/or 2D-NMR in CCR-RNAi lines, providing new insights into the consequences of CCR suppression in pine. Interestingly, CCR suppression substantially promoted pyrolytic breakdown of cell wall polysaccharides, a phenotype most likely caused by the incorporation of acidic compounds into the cell wall matrix in CCR-RNAi lines.

  11. CCR5 Conformations Are Dynamic and Modulated by Localization, Trafficking and G Protein Association

    Science.gov (United States)

    Flegler, Ayanna J.; Cianci, Gianguido C.; Hope, Thomas J.

    2014-01-01

    CCR5 acts as the principal coreceptor during HIV-1 transmission and early stages of infection. Efficient HIV-1 entry requires a series of processes, many dependent on the conformational state of both viral envelope protein and cellular receptor. Monoclonal antibodies (MAbs) are able to identify different CCR5 conformations, allowing for their use as probes to distinguish CCR5 populations. Not all CCR5 MAbs are able to reduce HIV-1 infection, suggesting the use of select CCR5 populations for entry. In the U87.CD4.CCR5-GFP cell line, we used such HIV-1-restricting MAbs to probe the relation between localization, trafficking and G protein association for individual CCR5 conformations. We find that CCR5 conformations not only exhibit different localization and abundance patterns throughout the cell, but that they also display distinct sensitivities to endocytosis inhibition. Using chemokine analogs that vary in their HIV-1 inhibitory mechanisms, we also illustrate that responses to ligand engagement are conformation-specific. Additionally, we provide supporting evidence for the select sensitivity of conformations to G protein association. Characterizing the link between the function and dynamics of CCR5 populations has implications for understanding their selective targeting by HIV-1 and for the development of inhibitors that will block CCR5 utilization by the virus. PMID:24586501

  12. 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.

  13. Effects of CCR5-Delta32 and CCR2-64I alleles on HIV-1 disease progression: the protection varies with duration of infection

    NARCIS (Netherlands)

    Mulherin, Stephanie A.; O'Brien, Thomas R.; Ioannidis, John P.; Goedert, James J.; Buchbinder, Susan P.; Coutinho, Roel A.; Jamieson, Beth D.; Meyer, Laurence; Michael, Nelson L.; Pantaleo, Giuseppe; Rizzardi, G. Paolo; Schuitemaker, Hanneke; Sheppard, Haynes W.; Theodorou, Ioannis D.; Vlahov, David; Rosenberg, Philip S.

    2003-01-01

    OBJECTIVE: To examine temporal variation in the effects of CCR5-Delta32 and CCR2-64I chemokine receptor gene polymorphisms on HIV-1 disease progression. DESIGN: Pooled analysis of individual patient data from 10 cohorts of HIV-1 seroconverters from the United States, Europe, and Australia. METHODS:

  14. Causal pathways of the effects of age and the CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on AIDS development

    NARCIS (Netherlands)

    Geskus, Ronald B.; Meyer, Laurence; Hubert, Jean-Baptiste; Schuitemaker, Hanneke; Berkhout, Ben; Rouzioux, Christine; Theodorou, Ioannis D.; Delfraissy, Jean-François; Prins, Maria; Coutinho, Roel A.

    2005-01-01

    OBJECTIVE: To investigate the causal pathways by which age and the CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles influence progression to AIDS. DESIGN: Analysis of follow-up data from 2 cohort studies among homosexual men (n=400), having >10 years of follow-up. METHODS: The effects of the 4

  15. CANCER OF THE PENIS AT KENYATTA NATIONAL HOSPITAL ...

    African Journals Online (AJOL)

    hi-tech

    2000-10-10

    Oct 10, 2000 ... It is however widely reported that squamous cell cancer of the penis is commoner in men in their sixth and seventh decades with an abrupt increase in incidence at 60 years and peaking at 80 years of age(23). In two such studies the mean age was reported as being 55 and 58 years(24,25) respectively.

  16. 77 FR 4052 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-01-26

    ... Person: Marvin L. Salin, Ph.D., Scientific Review Officer, Special Review and Logistics Branch, Division... Special Emphasis Panel, The Role of Microbial Metabolites in Cancer Prevention and Etiology. Date: March... Soldatenkov, M.D., Ph.D., Scientific Review Officer, Special Review and Logistics Branch, Division of...

  17. 78 FR 54745 - National Prostate Cancer Awareness Month, 2013

    Science.gov (United States)

    2013-09-06

    ... increase a man's chances of developing prostate cancer. It is more common among older men and men with a... placing lifetime dollar limits on essential health benefits and from dropping coverage because of mistakes... dollar limits on vital benefits, and insurers will no longer be able to deny coverage or charge higher...

  18. 76 FR 55551 - National Prostate Cancer Awareness Month, 2011

    Science.gov (United States)

    2011-09-07

    ..., studies show certain factors--including age, race, and family history--may increase the likelihood of.... I encourage all men, especially those who are at an increased risk, to talk to their doctors about... dollar limits on health benefits. These changes free cancer patients to focus on getting better instead...

  19. ORAL CANCER AT KENYATTA NATIONAL HOSPITAL, NAIROBI JF ...

    African Journals Online (AJOL)

    hi-tech

    2004-06-06

    Jun 6, 2004 ... However, there was a very wide age range with occurrences reported as early as the first decade. The tongue was the most frequent site for oral cancer in both males and females (Table 3). This was followed by the mandible and the maxilla. The floor of the mouth was the fourth most common site followed.

  20. 77 FR 49450 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-08-16

    ... Executive Blvd., Rockville, MD 20852, (Telephone Conference Call). Contact Person: Gerald G. Lovinger, Ph.D... and R01 applications in Lung, Skin, Ovarian, Pancreatic and Gastrointestinal Cancers. Date: September... Washington/Rockville, 1750 Rockville Pike, Rockville, MD 20852. Contact Person: Caron A Lyman, Ph.D...

  1. 78 FR 20213 - National Cancer Control Month, 2013

    Science.gov (United States)

    2013-04-04

    ... tomorrow's breakthroughs. My Administration is committed to supporting the kind of medical research that.... This month, we rededicate ourselves to securing better outcomes, reducing new cases, and advancing cancer research. To beat this disease, we must continue our efforts to prevent it. Each of us can reduce...

  2. 78 FR 50068 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2013-08-16

    ... be open to the public, with attendance limited to space available. Individuals who plan to attend and.../Default.aspx . Directions/Parking For a map and directions, please visit http://ncifrederick.cancer.gov... (three flag poles in this lot). Space in the parking lot is somewhat limited, and street parking on...

  3. 78 FR 54741 - National Ovarian Cancer Awareness Month, 2013

    Science.gov (United States)

    2013-09-06

    ... options, protections, and benefits. Thanks to this law, insurance companies can no longer set lifetime dollar limits on coverage or cancel coverage because of errors on paperwork. By 2014, the health care law... understanding of ovarian cancer and develop better methods for diagnosis and treatment. As we continue to...

  4. Distribution of CCR5-Delta32, CCR5 promoter 59029 A/G, CCR2-64I and SDF1-3'A genetic polymorphisms in HIV-1 infected and uninfected patients in the west region of Cameroon.

    Science.gov (United States)

    Nkenfou, Céline Nguefeu; Mekue, Linda Chapdeleine Mouafo; Nana, Christelle Tafou; Kuiate, Jules Roger

    2013-07-23

    Genetic variants of the genes encoding human immunodeficiency virus-1 (HIV-1) co-receptors and their ligands, like CC-chemokine receptor 5 delta 32 mutation (CCR5-Delta32), CCR5 promoter A/G (Adenine/Guanine), CC-chemokine receptor 2 mutation 64 isoleucine (CCR2-64I) and the stromal cell-derived factor 3'A mutation (SDF1-3'A), are involved in the susceptibility to HIV-1 infection and progression. The prevalence of these mutations varies by region. However, little is known about their distribution in the population of Dschang, located in the west region of Cameroon. The prevalence of HIV in the west region of Cameroon is lower than elsewhere in Cameroon. The objectives of this study were to determine the distribution of four AIDS Related Gene (ARG) variants in HIV-infected and non-infected population of Cameroon especially in the west region and to estimate the contribution of these variants to the susceptibility or resistance to HIV infection. We also aimed to evaluate the effectiveness of genotyping using dried blood spot (DBS) samples. A total of 179 participants were recruited from two hospitals in Dschang in the west region of Cameroon. Their genotypes for CCR5-Delta32, CCR5 promoter 59029A/G, CCR2-64I and SDF1-3'A were analyzed using polymerase chain reaction (PCR) and restriction fragment length polymorphisms. A total of 179 participants were enrolled in the study. Among them, 32 (17.9%) were HIV positive and 147 (82.1%) were HIV negative. The allelic frequencies of these genes were: 0%, 49.72%, 17.6% and 100% respectively for CCR5-Delta32, CCR5 promoter 59029A/G, CCR2-64I and SDF1-3'A. No individual was found to carry the CCR5-Delta 32 mutation. All participants recruited were heterozygous for the SDF1-3'A allele. Our data suggest that the CCR5-Delta32 cannot account for the protection as it was completely absent in our population. SDF1-3'A variants, may be in association with other polymorphisms, may account for the overall protection from HIV-1 infection

  5. [Histologic and endoscopic characteristics of gastric cancer diagnosed in a national hospital of Callao, Peru].

    Science.gov (United States)

    Rodríguez-Vargas, Briny; Arévalo-Suarez, Fernando; Monge-Salgado, Eduardo; Montes-Teves, Pedro

    2013-03-01

    To describe the histologic and endoscopic characteristics reported among patients diagnosed with gastric cancer in Daniel Alcides Carrion National Hospital in Callao. We performed a case series including all patients with histological diagnosis of gastric cancer from January 2009 to December 2011. Data were obtained from the registers of the pathology service of Daniel Alcides Carrion National Hospital. Factors such as age and gender of patients, histologic type, endoscopic location, presence of intestinal metaplasia, histologic degree, and cancer morphology were evaluated. 120 patients were included. Mean age was 65.4 ± 13.6 years; 59 (49%) were male. Based on the histologic type, intestinal type was found among 68 (56%); diffuse type among 45 (38%), and a mixed type in 7 (6%). Regarding the site, 23 (19%) of gastric cancers were located in the fundus; 52 (43%) in the body; 39 (33%) in the antrum, and 6 (5%) in the pylorus. Patients with gastric cancer of the intestinal type were in average older than those with a diffuse type (69.1 ± 10.3 versus 59.3 ± 15.3). 60.3% of intestinal-type gastric cancers were located proximally, versus 66.6% of diffuse-type cancers. Among the studied population, diffuse-type gastric cancer appears at an earlier age than the intestinal type, and its most common location is proximal.

  6. 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.

  7. 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. © 2011 Wiley Periodicals, Inc.

  8. International Framework for Cancer Patient Advocacy: Empowering Organizations and Patients to Create a National Call to Action on Cancer

    Science.gov (United States)

    Manasco, Leigh; McGoldrick, Devon; Kajana, Kiti; Rosenthal, Lauren; McMikel, Ann; Lins, Nancy

    2015-01-01

    Purpose With the rate of cancer and other noncommunicable diseases (NCDs) growing globally, cancer prevention and control efforts are critical internationally. Moreover, since the 2011 United Nations High-Level Meeting on NCDs, the international health and development community has shifted its awareness to include NCDs as a global health priority, especially in developing countries where mortality rates are disproportionately high. Simultaneously, with the dissemination of the World Cancer Declaration and the evolution of cancer control policies, the international cancer community has recognized the value of engaging patients in reducing the global cancer burden. Cancer advocacy programs that involve patients, survivors, and nongovernmental organizations (NGOs) have increasing opportunities for global impact. Methods We developed a framework over 4 years through implementation of two pilot projects. We created a series of trainings and tools to build the capacity of local NGOs and patients to plan and implement a forum for patients with cancer and to create and disseminate a national call to action. The framework was piloted in South Africa from 2009 to 2011 and Japan from 2012 to 2014, and results were measured through postproject surveys completed by members of the collaborative working group and interviews with the in-country partner. Results The framework is globally relevant and could be adapted and implemented in low- and middle-income countries to amplify patient voices in the policymaking process, increase grassroots mobilization, and improve health systems and infrastructure through addressing patient needs. Conclusion With the dominant paradigm of global health in developing countries—which has previously focused on HIV/AIDS, maternal and child health, tuberculosis, and malaria—shifting to adapt to the burgeoning NCD burden, effective patient-centered advocacy frameworks are critical to the success of NCD control. PMID:28804777

  9. International Framework for Cancer Patient Advocacy: Empowering Organizations and Patients to Create a National Call to Action on Cancer.

    Science.gov (United States)

    Schear, Rebekkah M; Manasco, Leigh; McGoldrick, Devon; Kajana, Kiti; Rosenthal, Lauren; McMikel, Ann; Lins, Nancy

    2015-12-01

    With the rate of cancer and other noncommunicable diseases (NCDs) growing globally, cancer prevention and control efforts are critical internationally. Moreover, since the 2011 United Nations High-Level Meeting on NCDs, the international health and development community has shifted its awareness to include NCDs as a global health priority, especially in developing countries where mortality rates are disproportionately high. Simultaneously, with the dissemination of the World Cancer Declaration and the evolution of cancer control policies, the international cancer community has recognized the value of engaging patients in reducing the global cancer burden. Cancer advocacy programs that involve patients, survivors, and nongovernmental organizations (NGOs) have increasing opportunities for global impact. We developed a framework over 4 years through implementation of two pilot projects. We created a series of trainings and tools to build the capacity of local NGOs and patients to plan and implement a forum for patients with cancer and to create and disseminate a national call to action. The framework was piloted in South Africa from 2009 to 2011 and Japan from 2012 to 2014, and results were measured through postproject surveys completed by members of the collaborative working group and interviews with the in-country partner. The framework is globally relevant and could be adapted and implemented in low- and middle-income countries to amplify patient voices in the policymaking process, increase grassroots mobilization, and improve health systems and infrastructure through addressing patient needs. With the dominant paradigm of global health in developing countries-which has previously focused on HIV/AIDS, maternal and child health, tuberculosis, and malaria-shifting to adapt to the burgeoning NCD burden, effective patient-centered advocacy frameworks are critical to the success of NCD control.

  10. Solution structure of LC4 transmembrane segment of CCR5.

    Directory of Open Access Journals (Sweden)

    Kazuhide Miyamoto

    Full Text Available CC-chemokine receptor 5 (CCR5 is a specific co-receptor allowing the entry of human immunodeficiency virus type 1 (HIV-1. The LC4 region in CCR5 is required for HIV-1 entry into the cells. In this study, the solution structure of LC4 in SDS micelles was elucidated by using standard 1H two-dimensional NMR spectroscopy, circular dichroism, and fluorescence quenching. The LC4 structure adopts two helical structures, whereas the C-terminal part remains unstructured. The positions in which LC4 binds to the HIV-1 inhibitory peptide LC5 were determined by docking calculations in addition to NMR data. The poses showed the importance of the hydrophobic interface of the assembled structures. The solution structure of LC4 elucidated in the present work provides a structural basis for further studies on the HIV-1 inhibitory function of the LC4 region.

  11. Solution structure of LC4 transmembrane segment of CCR5.

    Science.gov (United States)

    Miyamoto, Kazuhide; Togiya, Kayo

    2011-01-01

    CC-chemokine receptor 5 (CCR5) is a specific co-receptor allowing the entry of human immunodeficiency virus type 1 (HIV-1). The LC4 region in CCR5 is required for HIV-1 entry into the cells. In this study, the solution structure of LC4 in SDS micelles was elucidated by using standard 1H two-dimensional NMR spectroscopy, circular dichroism, and fluorescence quenching. The LC4 structure adopts two helical structures, whereas the C-terminal part remains unstructured. The positions in which LC4 binds to the HIV-1 inhibitory peptide LC5 were determined by docking calculations in addition to NMR data. The poses showed the importance of the hydrophobic interface of the assembled structures. The solution structure of LC4 elucidated in the present work provides a structural basis for further studies on the HIV-1 inhibitory function of the LC4 region.

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

    Science.gov (United States)

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

    1977-10-01

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

  13. NCI RNA Biology 2017 symposium recap | Center for Cancer Research

    Science.gov (United States)

    The recent discovery of new classes of RNAs and the demonstration that alterations in RNA metabolism underlie numerous human cancers have resulted in enormous interest among CCR investigators in RNA biology. In order to share the latest research in this exciting field, the CCR Initiative in RNA Biology held its second international symposium April 23-24, 2017, in Natcher Auditorium. Learn more...

  14. 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...

  15. Cellular Imaging | Center for Cancer Research

    Science.gov (United States)

    Innovative imaging methods developed and refined within CCR revealed atomic-level structures of biological molecules and unveiled dynamic views of a cell’s interior that are driving the design of new treatments and diagnostics for cancer.

  16. Breast cancer among Yemeni women using the National Oncology Centre Registry 2004-2010.

    Science.gov (United States)

    El-Zaemey, S; Nagi, N; Fritschi, L; Heyworth, J

    2012-06-01

    In developing countries including Arab countries breast cancer is one of the most common cancers found in women. Even though breast cancer incidence is lower in Arab developing countries than in western countries, Arabic women are more likely to be diagnosed at an earlier age than the women in western countries. A descriptive study was undertaken to investigate the type of breast cancer, lymph node involvement, side of breast and, region and age distribution of breast cancer patients registered in the National Oncology Centre in Yemen. From September 2004 to December 2010, 2654 women across Yemen diagnosed with breast cancer were registered in the National Oncology Centre for treatment. Between the years 2004 and 2010, breast cancer represented 22% of all cancers registered in women. Seventy-one per cent of the women were aged 50 or younger at the time of diagnosis. The most common age group affected was women aged 41-50 years, with (35%) of cases occurring in this age. Invasive ductal carcinoma was the most common pathology (76%) and 79% of the patients had lymph node involvement at the time of diagnosis. Approximately 2% had bilateral disease and the frequency of left (44%) and right breast cancer (42%) were similar. This study has shown that breast cancer is a disease of young women in Yemen. The majority of women presented with lymph node involvement. Hence efforts are needed to increase breast cancer awareness in Yemen for early detection at all age groups, and to target women living in areas that have lower access to health care services. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. 76 FR 26310 - National Cancer Institute; Notice of Meeting

    Science.gov (United States)

    2011-05-06

    ... Group(s); and Budget Presentations. Place: National Institutes of Health, Building 31, 31 Center Drive... entrance onto the NIH campus. All visitor vehicles, including taxicabs, hotel, and airport shuttles will be...

  18. Use of the National Cancer Institute Community Cancer Centers Program screening and accrual log to address cancer clinical trial accrual.

    Science.gov (United States)

    St Germain, Diane; Denicoff, Andrea M; Dimond, Eileen P; Carrigan, Angela; Enos, Rebecca A; Gonzalez, Maria M; Wilkinson, Kathy; Mathiason, Michelle A; Duggan, Brenda; Einolf, Shaun; McCaskill-Stevens, Worta; Bryant, Donna M; Thompson, Michael A; Grubbs, Stephen S; Go, Ronald S

    2014-03-01

    Screening logs have the potential to help oncology clinical trial programs at the site level, as well as trial leaders, address enrollment in real time. Such an approach could be especially helpful in improving representation of racial/ethnic minority and other underrepresented populations in clinical trials. The National Cancer Institute Community Cancer Centers Program (NCCCP) developed a screening log. Log data collected from March 2009 through May 2012 were analyzed for number of patients screened versus enrolled, including for demographic subgroups; screening methods; and enrollment barriers, including reasons for ineligibility and provider and patient reasons for declining to offer or participate in a trial. User feedback was obtained to better understand perceptions of log utility. Of 4,483 patients screened, 18.4% enrolled onto NCCCP log trials. Reasons for nonenrollment were ineligibility (51.6%), patient declined (25.8%), physician declined (15.6%), urgent need for treatment (6.6%), and trial suspension (0.4%). Major reasons for patients declining were no desire to participate in trials (43.2%) and preference for standard of care (39%). Major reasons for physicians declining to offer trials were preference for standard of care (53%) and concerns about tolerability (29.3%). Enrollment rates onto log trials did not differ between white and black (P = .15) or between Hispanic and non-Hispanic patients (P = .73). Other races had lower enrollment rates than whites and blacks. Sites valued the ready access to log data on enrollment barriers, with some sites changing practices to address those barriers. Use of screening logs to document enrollment barriers at the local level can facilitate development of strategies to enhance clinical trial accrual.

  19. Validity of new methods to evaluate renal function in cancer patients treated with cisplatin.

    Science.gov (United States)

    Funakoshi, Yohei; Fujiwara, Yutaka; Kiyota, Naomi; Mukohara, Toru; Shimada, Takanobu; Toyoda, Masanori; Imamura, Yoshinori; Chayahara, Naoko; Tomioka, Hideo; Umezu, Michio; Otsuki, Naoki; Nibu, Ken-ichi; Minami, Hironobu

    2016-02-01

    Creatinine clearance (Ccr) is used as a marker of renal function in cancer chemotherapy, but it is not correlated with glomerular filtration rate (GFR) after high-dose cisplatin treatment. In addition to Ccr, measured using 24-h urine collection (24-h Ccr) or Cockcroft-Gault formula (CGF), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the Japanese GFR estimation equation (the Japanese equation) have been recently developed to estimate GFR for predicting renal function. However, these equations remain to be evaluated, particularly in cancer patients treated with cisplatin. Therefore, we investigated the validity of these equations for predicting the GFR in cancer patients treated with cisplatin. GFR was measured by inulin clearance (Cin) in 50 cancer patients and compared with GFR estimated by the CKD-EPI equation, the Japanese equation, and Ccr estimated by CGF or measured by 24-h Ccr before the first and third cisplatin-containing chemotherapy cycles (considered pretreatment and posttreatment, respectively). Before treatment, the CKD-EPI and the Japanese equations estimated GFR with higher accuracy than Ccr. Posttreatment bias values for GFR estimation using the CKD-EPI and the Japanese equations were lower than those for Ccr. The CKD-EPI and the Japanese equations were also more precise than Ccr. However, for patients with low renal function, these equations still overestimated Cin. The CKD-EPI and the Japanese equations estimated GFR with lower bias and higher precision than Ccr pre- and postcisplatin treatment. This study is registered at UMIN: 000002167.

  20. The architecture of the Schizosaccharomyces pombe CCR4-NOT complex

    Science.gov (United States)

    Ukleja, Marta; Cuellar, Jorge; Siwaszek, Aleksandra; Kasprzak, Joanna M.; Czarnocki-Cieciura, Mariusz; Bujnicki, Janusz M.; Dziembowski, Andrzej; M. Valpuesta, Jose

    2016-01-01

    CCR4-NOT is a large protein complex present both in cytoplasm and the nucleus of eukaryotic cells. Although it is involved in a variety of distinct processes related to expression of genetic information such as poly(A) tail shortening, transcription regulation, nuclear export and protein degradation, there is only fragmentary information available on some of its nine subunits. Here we show a comprehensive structural characterization of the native CCR4-NOT complex from Schizosaccharomyces pombe. Our cryo-EM 3D reconstruction of the complex, combined with techniques such as immunomicroscopy, RNA-nanogold labelling, docking of the available high-resolution structures and models of different subunits and domains, allow us to propose its full molecular architecture. We locate all functionally defined domains endowed with deadenylating and ubiquitinating activities, the nucleus-specific RNA-interacting subunit Mmi1, as well as surfaces responsible for protein–protein interactions. This information provides insight into cooperation of the different CCR4-NOT complex functions. PMID:26804377

  1. 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.

  2. CCR5 Disruption in Induced Pluripotent Stem Cells Using CRISPR/Cas9 Provides Selective Resistance of Immune Cells to CCR5-tropic HIV-1 Virus

    Directory of Open Access Journals (Sweden)

    HyunJun Kang

    2015-01-01

    Full Text Available 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.

  3. Coverage of common cancer types in UK national newspapers: a content analysis

    OpenAIRE

    Konfortion, Julie; Jack, Ruth H; Davies, Elizabeth A

    2014-01-01

    Objective To determine whether recent newspaper coverage of the four most common cancer types relates to their relative burden and national awareness months, and to identify the subject focus during high-coverage periods. Design Content analysis using the Nexis newspaper article database. Setting UK 2011–2012. Outcome measures Annual number and ranking, monthly proportions and subject of articles on breast, lung, bowel and prostate cancers. Results 9178 articles were identified during 2011 an...

  4. Implication of Ccr4-Not complex function in mRNA quality control in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Assenholt, Jannie; Mouaikel, John; Saguez, Cyril

    2011-01-01

    RNPs are exported to the cytoplasm. The Ccr4-Not complex, which constitutes the major S. cerevisiae cytoplasmic deadenylase, has recently been implied in nuclear exosome–related processes. Consistent with a possible nuclear function of the complex, the deletion or mutation of Ccr4-Not factors also elicits...... transcription phenotypes. Here we use genetic depletion of the Mft1p protein of the THO transcription/mRNP packaging complex as a model system to link the Ccr4-Not complex to nuclear mRNP QC. We reveal strong genetic interactions between alleles of the Ccr4-Not complex with both the exosomal RRP6 and MFT1 genes....... Moreover, Rrp6p-dependent in vivo QC phenotypes of Δmft1 cells can be rescued by codeletion of several Ccr4-Not components. We discuss how the Ccr4-Not complex may connect with the mRNP QC pathway...

  5. Biased signaling of G protein-coupled receptors - From a chemokine receptor CCR7 perspective

    DEFF Research Database (Denmark)

    Jørgensen, Astrid Sissel; Rosenkilde, Mette M; Hjortø, Gertrud M

    2018-01-01

    findings related to ligand- and tissue-biased signaling of CCR7 and summarize what is known about bias at other chemokine receptors. CCR7 is expressed by a subset of T-cells and by mature dendritic cells (DCs). Together with its two endogenous ligands CCL19 and CCL21, of which the carboxy terminal tail...... of CCL21 displays an extraordinarily strong glycosaminoglycan (GAG) binding, CCR7 plays a central role in coordinating the meeting between mature antigen presenting DCs and naïve T-cells which normally takes place in the lymph nodes (LNs). This process is a prerequisite for the initiation of an antigen......-specific T-cell mediated immune response. Thus CCR7 and its ligands are key players in initiating cell-based immune responses. CCL19 and CCL21 display differential interaction- and docking-modes for CCR7 leading to stabilization of different CCR7 conformations and hereby preferential activation of distinct...

  6. A highly selective CCR2 chemokine agonist encoded by human herpesvirus 6

    DEFF Research Database (Denmark)

    Lüttichau, Hans R; Clark-Lewis, Ian; Jensen, Peter Østrup

    2003-01-01

    calcium mobilization as efficiently as the endogenous chemokine ligand CCL2 through the CCR2 receptor, whereas the virally encoded chemokine did not affect any of the other 17 human chemokine receptors tested. Mutual cross-desensitization between CCL2 and vCCL4 was demonstrated in the CCR2-transfected...... cells. The affinity of vCCL4 for the CCR2 receptor was 79 nm as determined in competition binding against radioactively labeled CCL2. In the murine pre-B lymphocyte cell line L1.2 stably transfected with the CCR2 receptor, vCCL4 acted as a relatively low potency but highly efficacious chemoattractant...... being equally or more efficacious in causing cell migration than CCL2 and CCL7 and considerably more efficacious than CCL8 and CCL13. It is concluded that human herpesvirus 6 encodes a highly selective and efficacious CCR2 agonist, which will attract CCR2 expressing cells, for example macrophages...

  7. 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

    The chemokine receptor CCR2 is a G protein-coupled receptor that is involved in many diseases characterized by chronic inflammation, and therefore a large variety of CCR2 small molecule antagonists has been developed. On the basis of their chemical structures these antagonists can roughly...... be divided into two groups with most likely two topographically distinct binding sites. The aim of the current study was to identify the binding site of one such group of ligands, exemplified by three allosteric antagonists, CCR2-RA-[R], JNJ-27141491, and SD-24. We first used a chimeric CCR2/CCR5 receptor...... approach to obtain insight into the binding site of the allosteric antagonists and additionally introduced eight single point mutations in CCR2 to further characterize the putative binding pocket. All constructs were studied in radioligand binding and/or functional IP turnover assays, providing evidence...

  8. Structural refinement and prediction of potential CCR2 antagonists through validated multi-QSAR modeling studies.

    Science.gov (United States)

    Amin, Sk Abdul; Adhikari, Nilanjan; Baidya, Sandip Kumar; Gayen, Shovanlal; Jha, Tarun

    2018-01-03

    Chemokines trigger numerous inflammatory responses and modulate the immune system. The interaction between monocyte chemoattractant protein-1 and chemokine receptor 2 (CCR2) may be the cause of atherosclerosis, obesity, and insulin resistance. However, CCR2 is also implicated in other inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, asthma, and neuropathic pain. Therefore, there is a paramount importance of designing potent and selective CCR2 antagonists despite a number of drug candidates failed in clinical trials. In this article, 83 CCR2 antagonists by Jhonson and Jhonson Pharmaceuticals have been considered for robust validated multi-QSAR modeling studies to get an idea about the structural and pharmacophoric requirements for designing more potent CCR2 antagonists. All these QSAR models were validated and statistically reliable. Observations resulted from different modeling studies correlated and validated results of other ones. Finally, depending on these QSAR observations, some new molecules were proposed that may exhibit higher activity against CCR2.

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

    Science.gov (United States)

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

    2016-05-01

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

  10. Well-directed inclusion of hematology in African national cancer control plans.

    Science.gov (United States)

    Weaver, Meaghann; Yao, Atteby J J; Renner, Lorna; Harif, Mhamed; Lam, Catherine G

    2017-07-01

    In the context of a convergent call for noncommunicable disease integration in the global agenda, recognizing cross-cutting needs and opportunities in national strategies across disease fields with shared priorities in low- and middle-income settings can enhance sustainable development approaches. We reviewed publicly available cancer control plans in Africa to evaluate for inclusion of hematology needs and shared service priorities. Pediatric data remain sparse in cancer control plans. While continental Africa represents incredible diversity, recognizing shared priorities and opportunity for collaboration between oncology and hematology services and across age groups may guide prioritized cancer control efforts and reduce programmatic redundancies in resource-limited settings. © 2017 Wiley Periodicals, Inc.

  11. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis.

    Directory of Open Access Journals (Sweden)

    Eric Lefebvre

    Full Text Available Interactions between C-C chemokine receptor types 2 (CCR2 and 5 (CCR5 and their ligands, including CCL2 and CCL5, mediate fibrogenesis by promoting monocyte/macrophage recruitment and tissue infiltration, as well as hepatic stellate cell activation. Cenicriviroc (CVC is an oral, dual CCR2/CCR5 antagonist with nanomolar potency against both receptors. CVC's anti-inflammatory and antifibrotic effects were evaluated in a range of preclinical models of inflammation and fibrosis.Monocyte/macrophage recruitment was assessed in vivo in a mouse model of thioglycollate-induced peritonitis. CCL2-induced chemotaxis was evaluated ex vivo on mouse monocytes. CVC's antifibrotic effects were evaluated in a thioacetamide-induced rat model of liver fibrosis and mouse models of diet-induced non-alcoholic steatohepatitis (NASH and renal fibrosis. Study assessments included body and liver/kidney weight, liver function test, liver/kidney morphology and collagen deposition, fibrogenic gene and protein expression, and pharmacokinetic analyses.CVC significantly reduced monocyte/macrophage recruitment in vivo at doses ≥20 mg/kg/day (p < 0.05. At these doses, CVC showed antifibrotic effects, with significant reductions in collagen deposition (p < 0.05, and collagen type 1 protein and mRNA expression across the three animal models of fibrosis. In the NASH model, CVC significantly reduced the non-alcoholic fatty liver disease activity score (p < 0.05 vs. controls. CVC treatment had no notable effect on body or liver/kidney weight.CVC displayed potent anti-inflammatory and antifibrotic activity in a range of animal fibrosis models, supporting human testing for fibrotic diseases. Further experimental studies are needed to clarify the underlying mechanisms of CVC's antifibrotic effects. A Phase 2b study in adults with NASH and liver fibrosis is fully enrolled (CENTAUR Study 652-2-203; NCT02217475.

  12. Second primary cancers after adjuvant radiotherapy in early breast cancer patients: A national population based study under the Danish Breast Cancer Cooperative Group (DBCG)

    International Nuclear Information System (INIS)

    Grantzau, Trine; Mellemkjær, Lene; Overgaard, Jens

    2013-01-01

    Background and purpose: To analyze the long-term risk of second primary solid non-breast cancer in a national population-based cohort of 46,176 patients treated for early breast cancer between 1982 and 2007. Patients and methods: All patients studied were treated according to the national guidelines of the Danish Breast Cancer Cooperative Group. The risk of second primary cancers was estimated by Standardised incidence ratios (SIRs) and multivariate Cox regression models were used to estimate adjusted hazard ratios (HR) among irradiated women compared to non-irradiated. All irradiated patients were treated on linear accelerators. Second cancers were a priori categorized into two groups; radiotherapy-associated- (oesophagus, lung, heart/mediastinum, pleura, bones, and connective tissue) and non-radiotherapy-associated sites (all other cancers). Results: 2358 second cancers had occurred during the follow-up. For the radiotherapy-associated sites the HR among irradiated women was 1.34 (95% CI 1.11–1.61) with significantly increased HRs for the time periods of 10–14 years (HR 1.55; 95% CI 1.08–2.24) and ⩾15 years after treatment (HR 1.79; 95% CI 1.14–2.81). There was no increased risk for the non-radiotherapy-associated sites (HR 1.04; 95% CI 0.94–1.1). The estimated attributable risk related to radiotherapy for the radiotherapy-associated sites translates into one radiation-induced second cancer in every 200 women treated with radiotherapy. Conclusions: Radiotherapy treated breast cancer patients have a small but significantly excess risk of second cancers

  13. Relationship between the chemokine receptor CCR5 and microglia in neurological disorders: consequences of targeting CCR5 on neuroinflammation, neuronal death and regeneration in a model of epilepsy.

    Science.gov (United States)

    Louboutin, Jean-Pierre; Strayer, David S

    2013-09-01

    Chemokines may play a role in leukocyte migration across the blood-brain barrier (BBB) during neuroinflammation and other neuropathological processes, such as epilepsy. The CC chemokine receptor 5 (CCR5) is a member of CC-chemokine receptor family that binds several chemokines, including CCL3 (macrophage inflammatory protein-1alpha, MIP-1alpha), CCL4 (macrophage inflammatory protein-1beta, MIP-1beta) and CCL5 (RANTES). The current review examines the relationship between CCR5 and the microglia in different neurological disorders and models of CNS injury. CCR5 expression is upregulated in different neurological diseases, where it is often immunolocalized in microglial cells. A multistep cascade couples CCR5 activation by chemokines to Ca(2+) increases in human microglia. Because changes in [Ca(2+)] (i) affect chemotaxis, secretion, and gene expression, pharmacologic modulation of this pathway may alter inflammatory and degenerative processes in the CNS. Consequently, targeting CCR5 by using CCR5 antagonists may attenuate critical aspects of neuroinflammation in different models of neurological disorders. To illustrate the interaction between CCR5 and microglia in the CNS, we used a model of excitotoxicity, and demonstrate the intimate involvement of CCR5 in neuron injury and inflammation attendant to kainic acid (KA)-induced neurotoxicity. CCR5 participates in neuronal injury caused by the excitotoxin, KA, brings inflammatory cells to the sites of KA-induced CNS injury, defines the extent of tissue loss after KA exposure and limits reparative responses. We used a SV40-derived vector carrying an interfering RNA (RNAi) that targets CCR5. Delivered directly to the bone marrow, this vector decreased CCR5 expression in circulating cells. Animals so treated showed greatly reduced expression of CCR5 and its ligands (MIP-1alpha and RANTES) in the CNS, including in the brain vasculature, decreased BBB leakage, demonstrated greater KA-stimulated neurogenesis and increased

  14. CCR2 mediates Helicobacter pylori-induced immune tolerance and contributes to mucosal homeostasis.

    Science.gov (United States)

    Sun, Xia; Zhang, Min; El-Zaatari, Mohamad; Huffnagle, Gray B; Kao, John Y

    2017-04-01

    We previously demonstrated that H. pylori infection leads to increased induction of regulatory T cells in local and systemic immune compartments. Here, we investigate the role of CCR2 in the tolerogenic programing of dendritic cells in a mouse model of H. pylori infection. CCR2 deficient (CCR2KO) mice and wild-type (Wt) mice infected with H. pylori SS1 strain were analyzed by qPCR and FACS analysis. In vitro, bone marrow-derived DC on day 6 from CCR2KO and Wt mice cocultured with or without H. pylori were examined to determine the impact of CCR2 signaling on dendritic cells function by qPCR, ELISA, and FACS analyses. Acute H. pylori infection was associated with a threefold increase in CCR2 mRNA expression in the gastric mucosa. H. pylori-infected CCR2KO mice exhibited a higher degree of mucosal inflammation, that is, increased gastritis scores and pro-inflammatory cytokine mRNA levels, but lower degree of H. pylori gastric colonization compared to infected Wt mice. Peripheral H. pylori-specific immune response measured in the CCR2KO spleen was characterized by a higher Th17 response and a lower Treg response. In vitro, CCR2KO bone marrow-derived DC was less mature and shown a lower Treg/Th17 ratio. Moreover, blockade of CCR2 signaling by MCP-1 neutralizing antibody inhibited H. pylori-stimulated bone marrow-derived DC maturation. Our results indicate that CCR2 plays an essential role in H. pylori-induced immune tolerance and shed light on a novel mechanism of CCR2-dependent DC Treg induction, which appears to be important in maintaining mucosal homeostasis during H. pylori infection. © 2016 John Wiley & Sons Ltd.

  15. CCL2 recruits T cells into the brain in a CCR2-independent manner

    DEFF Research Database (Denmark)

    Cédile, Oriane; Wlodarczyk, Agnieszka; Owens, Trevor

    2017-01-01

    CCR2, a receptor for CCL2. Expression of another receptor for CCL2, CCR4, and CXCR3, a receptor for CXCL10, which was also induced, were both increased in CCL2-treated CNS. CCR4 was expressed by neurons and astrocytes as well as CD4 T cells, and CXCR3 was expressed by CD4 and CD8 T cells. Chemokine...

  16. Pulmonary CCR2+CD4+T cells are immune regulatory and attenuate lung fibrosis development.

    Science.gov (United States)

    Milger, Katrin; Yu, Yingyan; Brudy, Eva; Irmler, Martin; Skapenko, Alla; Mayinger, Michael; Lehmann, Mareike; Beckers, Johannes; Reichenberger, Frank; Behr, Jürgen; Eickelberg, Oliver; Königshoff, Melanie; Krauss-Etschmann, Susanne

    2017-11-01

    Animal models have suggested that CCR2-dependent signalling contributes to the pathogenesis of pulmonary fibrosis, but global blockade of CCL2 failed to improve the clinical course of patients with lung fibrosis. However, as levels of CCR2 + CD4 + T cells in paediatric lung fibrosis had previously been found to be increased, correlating with clinical symptoms, we hypothesised that distinct CCR2 + cell populations might either increase or decrease disease pathogenesis depending on their subtype. To investigate the role of CCR2 + CD4 + T cells in experimental lung fibrosis and in patients with idiopathic pulmonary fibrosis and other fibrosis. Pulmonary CCR2 + CD4 + T cells were analysed using flow cytometry and mRNA profiling, followed by in silico pathway analysis, in vitro assays and adoptive transfer experiments. Frequencies of CCR2 + CD4 + T cells were increased in experimental fibrosis-specifically the CD62L - CD44 + effector memory T cell phenotype, displaying a distinct chemokine receptor profile. mRNA profiling of isolated CCR2 + CD4 + T cells from fibrotic lungs suggested immune regulatory functions, a finding that was confirmed in vitro using suppressor assays. Importantly, adoptive transfer of CCR2 + CD4 + T cells attenuated fibrosis development. The results were partly corroborated in patients with lung fibrosis, by showing higher percentages of Foxp3 + CD25 + cells within bronchoalveolar lavage fluid CCR2 + CD4 + T cells as compared with CCR2 - CD4 + T cells. Pulmonary CCR2 + CD4 + T cells are immunosuppressive, and could attenuate lung inflammation and fibrosis. Therapeutic strategies completely abrogating CCR2-dependent signalling will therefore also eliminate cell populations with protective roles in fibrotic lung disease. This emphasises the need for a detailed understanding of the functions of immune cell subsets in fibrotic lung disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights

  17. 77 FR 64526 - National Cancer Institute; Notice of Meetings

    Science.gov (United States)

    2012-10-22

    ... issues. Place: National Institutes of Health, 9000 Rockville Pike, Building 31, C Wing, 6th Floor... professional affiliation of the interested person. In the interest of security, NIH has instituted stringent procedures for entrance onto the NIH campus. All visitor vehicles, including taxicabs, hotel, and airport...

  18. Incidence and histological patterns of thyroid cancer in Sri Lanka 2001-2010: an analysis of national cancer registry data.

    Science.gov (United States)

    Jayarajah, Umesh; Fernando, Ashan; Prabashani, Saumyakala; Fernando, Eshani A; Seneviratne, Sanjeewa A

    2018-02-07

    An increasing incidence of thyroid cancer is observed in many developed countries. Increasing incidence may also reflect better reporting or increased diagnostic scrutiny. We conducted this study to examine trends in thyroid cancer incidence and histological patterns in Sri Lanka. A retrospective cohort evaluation of patients with thyroid cancer during 2001-2010 was performed using population based data published from the Sri Lanka National Cancer Registry. Trends in incidence and histological patterns were analysed by age and gender. The age-standardized incidence of thyroid cancer increased from 2.44 per 100,000 in 2001 (95% confidence interval [95% CI]: 2.21-2.67) to 5.16 per 100,000 in 2010 (95% CI: 4.85-5.47); a 2.1-fold increase (p < 0.05 for trend). A greater part of this increase is attributable to increase in incidence of papillary thyroid cancer, which increased from 1.64 to 3.61 per 100,000; a 2.2-fold increase (p < 0.05 for trend). Follicular cancer showed lesser, yet a significant increase from 0.56 to 0.95 per 100,000 (p < 0.05). Other varieties of thyroid cancer showed no significant increases in incidence. Trends in the increases in incidence of papillary cancer in females showed a much greater increase compared with males (from 2.45 to 5.60 per 100,000, a 2.28-fold increase in females compared with from 0.82 to 1.55; a 1.89-fold increase in males, p < 0.001). Highest incidence of papillary cancer was observed in 30-39-year age group, which has increased from 5.56 to 12.9 per 100,000; a 2.32-fold increase (p < 0.001). The increasing incidence of thyroid cancer in Sri Lanka is predominantly due to the increasing incidence of papillary cancers. These trends may reflect increased detection and better reporting, although an inherent increase in the incidence is the likely main contributor. Further studies including tumour stage and mortality may help answer these questions.

  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. 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...

  1. Inhibition of human immunodeficiency virus replication by a dual CCR5/CXCR4 antagonist

    DEFF Research Database (Denmark)

    Princen, Katrien; Hatse, Sigrid; Vermeire, Kurt

    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 [IC(50)] ranging from 1.2 to 26.5 microM) in various T-cell lines, CCR5...... at the virus entry stage. AMD3451 dose-dependently inhibited the intracellular Ca(2+) signaling induced by the CXCR4 ligand CXCL12 in T-lymphocytic cells and in CXCR4-transfected cells, as well as the Ca(2+) flux induced by the CCR5 ligands CCL5, CCL3, and CCL4 in CCR5-transfected cells. The compound did...... not interfere with chemokine-induced Ca(2+) signaling through CCR1, CCR2, CCR3, CCR4, CCR6, CCR9, or CXCR3 and did not induce intracellular Ca(2+) signaling by itself at concentrations up to 400 microM. In freshly isolated monocytes, AMD3451 inhibited the Ca(2+) flux induced by CXCL12 and CCL4...

  2. A role for MCP-1/CCR2 in interstitial lung disease in children

    Directory of Open Access Journals (Sweden)

    Reinhardt Dietrich

    2005-08-01

    Full Text Available Abstract Background Interstitial lung diseases (ILD are chronic inflammatory disorders leading to pulmonary fibrosis. Monocyte chemotactic protein 1 (MCP-1 promotes collagen synthesis and deletion of the MCP-1 receptor CCR2 protects from pulmonary fibrosis in ILD mouse models. We hypothesized that pulmonary MCP-1 and CCR2+ T cells accumulate in pediatric ILD and are related to disease severity. Methods Bronchoalveolar lavage fluid was obtained from 25 children with ILD and 10 healthy children. Levels of pulmonary MCP-1 and Th1/Th2-associated cytokines were quantified at the protein and the mRNA levels. Pulmonary CCR2+, CCR4+, CCR3+, CCR5+ and CXCR3+ T cells were quantified by flow-cytometry. Results CCR2+ T cells and MCP-1 levels were significantly elevated in children with ILD and correlated with forced vital capacity, total lung capacity and ILD disease severity scores. Children with lung fibrosis had significantly higher MCP-1 levels and CCR2+ T cells in bronchoalveolar lavage fluid compared to non-fibrotic children. Conclusion The results indicate that pulmonary CCR2+ T cells and MCP-1 contribute to the pathogenesis of pediatric ILD and might provide a novel target for therapeutic strategies.

  3. CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory

    Science.gov (United States)

    Zhou, Miou; Greenhill, Stuart; Huang, Shan; Silva, Tawnie K; Sano, Yoshitake; Wu, Shumin; Cai, Ying; Nagaoka, Yoshiko; Sehgal, Megha; Cai, Denise J; Lee, Yong-Seok; Fox, Kevin; Silva, Alcino J

    2016-01-01

    Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity. These results suggest that CCR5 is a powerful suppressor for plasticity and memory, and CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits. Consistent with this hypothesis, the HIV V3 peptide caused LTP, signaling and memory deficits that were prevented by Ccr5 knockout or knockdown. Overall, our results demonstrate that CCR5 plays an important role in neuroplasticity, learning and memory, and indicate that CCR5 has a role in the cognitive deficits caused by HIV. DOI: http://dx.doi.org/10.7554/eLife.20985.001 PMID:27996938

  4. CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory.

    Science.gov (United States)

    Zhou, Miou; Greenhill, Stuart; Huang, Shan; Silva, Tawnie K; Sano, Yoshitake; Wu, Shumin; Cai, Ying; Nagaoka, Yoshiko; Sehgal, Megha; Cai, Denise J; Lee, Yong-Seok; Fox, Kevin; Silva, Alcino J

    2016-12-20

    Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity. These results suggest that CCR5 is a powerful suppressor for plasticity and memory, and CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits. Consistent with this hypothesis, the HIV V3 peptide caused LTP, signaling and memory deficits that were prevented by Ccr5 knockout or knockdown. Overall, our results demonstrate that CCR5 plays an important role in neuroplasticity, learning and memory, and indicate that CCR5 has a role in the cognitive deficits caused by HIV.

  5. CCR5 internalisation and signalling have different dependence on membrane lipid raft integrity.

    Science.gov (United States)

    Cardaba, Clara Moyano; Kerr, Jason S; Mueller, Anja

    2008-09-01

    The chemokine receptor, CCR5, acts as a co-receptor for human immunodeficiency virus entry into cells. CCR5 has been shown to be targeted to cholesterol- and sphingolipid-rich membrane microdomains termed lipid rafts or caveolae. Cholesterol is essential for CCL4 binding to CCR5 and for keeping the conformational integrity of the receptor. Filipin treatment leads to loss of caveolin-1 from the membrane and therefore to a collapse of the caveolae. We have found here that sequestration of membrane cholesterol with filipin did not affect receptor signalling, however a loss of ligand-induced internalisation of CCR5 was observed. Cholesterol extraction with methyl-beta-cyclodextrin (MCD) reduced signalling through CCR5 as measured by release of intracellular Ca(2+) and completely abolished the inhibition of forskolin-stimulated cAMP accumulation with no effect on internalisation. Pertussis toxin (PTX) treatment inhibited the intracellular release of calcium that is transduced via Galphai G-proteins. Depletion of cholesterol destroyed microdomains in the membrane and switched CCR5/G-protein coupling to a PTX-independent G-protein. We conclude that cholesterol in the membrane is essential for CCR5 signalling via the Galphai G-protein subunit, and that integrity of lipid rafts is not essential for effective CCR5 internalisation however it is crucial for proper CCR5 signal transduction via Galphai G-proteins.

  6. 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. © 2015 John Wiley & Sons Ltd.

  7. 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.

  8. Targeting spare CC chemokine receptor 5 (CCR5) as a principle to inhibit HIV-1 entry.

    Science.gov (United States)

    Jin, Jun; Colin, Philippe; Staropoli, Isabelle; Lima-Fernandes, Evelyne; Ferret, Cécile; Demir, Arzu; Rogée, Sophie; Hartley, Oliver; Randriamampita, Clotilde; Scott, Mark G H; Marullo, Stefano; Sauvonnet, Nathalie; Arenzana-Seisdedos, Fernando; Lagane, Bernard; Brelot, Anne

    2014-07-04

    CCR5 binds the chemokines CCL3, CCL4, and CCL5 and is the major coreceptor for HIV-1 entry into target cells. Chemokines are supposed to form a natural barrier against human immunodeficiency virus, type 1 (HIV-1) infection. However, we showed that their antiviral activity is limited by CCR5 adopting low-chemokine affinity conformations at the cell surface. Here, we investigated whether a pool of CCR5 that is not stabilized by chemokines could represent a target for inhibiting HIV infection. We exploited the characteristics of the chemokine analog PSC-RANTES (N-α-(n-nonanoyl)-des-Ser(1)-[l-thioprolyl(2), l-cyclohexylglycyl(3)]-RANTES(4-68)), which displays potent anti-HIV-1 activity. We show that native chemokines fail to prevent high-affinity binding of PSC-RANTES, analog-mediated calcium release (in desensitization assays), and analog-mediated CCR5 internalization. These results indicate that a pool of spare CCR5 may bind PSC-RANTES but not native chemokines. Improved recognition of CCR5 by PSC-RANTES may explain why the analog promotes higher amounts of β-arrestin 2·CCR5 complexes, thereby increasing CCR5 down-regulation and HIV-1 inhibition. Together, these results highlight that spare CCR5, which might permit HIV-1 to escape from chemokines, should be targeted for efficient viral blockade. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Adaptation of HIV-1 to cells with low expression of the CCR5 coreceptor.

    Science.gov (United States)

    Espy, Nicole; Pacheco, Beatriz; Sodroski, Joseph

    2017-08-01

    The binding of the human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer ((gp120/gp41) 3 ) to the receptors CD4 and CCR5 triggers virus entry into host cells. To identify Env regions that respond to CCR5 binding, HIV-1 was serially passaged on a CD4-positive canine cell line expressing progressively lower levels of CCR5. HIV-1 replication was observed in cells expressing ~1300 CCR5 molecules/cell. Env changes that conferred this low-CCR5 replication phenotype were located outside of the known CCR5-binding region of the gp120 Env subunit and did not apparently increase CCR5 binding affinity. The adaptation-associated changes, located in the gp120 α1 helix and in the gp41 HR1 heptad repeat and membrane-proximal external region (MPER), enhanced HIV-1 replication in cells at all levels of CCR5 expression. The adapted Envs exhibited a greater propensity to undergo conformational changes, as evidenced by increased exposure of conserved regions near the CD4- and CCR5-binding sites. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Clinical and epidemiological profile of cases of deaths from stomach cancer in the National Cancer Institute, Brazil.

    Science.gov (United States)

    Guedes, Maria Teresa Dos Santos; de Jesus, José Paulo; de Souza Filho, Odilon; Fontenele, Raquel Malta; Sousa, Ana Inês

    2014-01-01

    Stomach cancer is the third most common cause of death worldwide, mainly affecting people with low socioeconomic status. In Brazil, we expect 20,390 new cases of stomach cancer in 2014, in both sexes, and according to the proportional distribution of the ten most prevalent types of cancer (except non-melanoma skin cancer) expected for 2014, this type of cancer was estimated to be the fourth most common in men and sixth in women. To investigate and analyse the clinical and epidemiological profile of deaths caused by stomach adenocarcinoma in patients enrolled in the National Cancer Institute, Brazil. Cross-sectional study, with samples which consisted of data from the medical records of deaths from stomach cancer, enrolled in the period from 1 February 2009 to 31 March 2012 and who had died as of 30 April 2012. The Epi Info ®, version 7. We included 264 cases, mostly male. The mean age was 61.7 years. They were smokers, drinkers, white, and married, with elementary education and an income of one minimum salary. They had advanced stage disease (E IV), with symptoms characteristic of this phase, and the majority died within six months. The findings are similar to other studies. The advanced stage of the disease at the time of admission of the patients reflects the difficulty for users of the Unified Health System to access early diagnosis, demonstrating the need for efforts to identify groups and risk factors for the development of gastric cancer. Training of health professionals will facilitate planning and implementation of programmes for the prevention and control of disease, considering socioeconomic conditions, as seen in the sample, which is common among most users.

  11. The National Cancer Data Base report on recent hospital cancer program progress toward complete American Joint Committee on Cancer/TNM staging.

    Science.gov (United States)

    Fleming, I D; Phillips, J L; Menck, H R; Murphy, G P; Winchester, D P

    1997-12-15

    American Joint Committee on Cancer (AJCC) staging procedures were first published in 1977. Since 1991 the Commission on Cancer (COC) has required AJCC staging of all nonpediatric cancers. The National Cancer Data Base (NCDB) encouraged recording of AJCC staging through analyses of selected aspects of staging completeness. We reviewed the trend toward the adoption of routine AJCC staging by hospitals for the 5-year period 1990-1994. NCDB reports for nearly 2 million stageable cancers diagnosed from 1990 through 1994 were examined with emphasis on the hospital cancer program environment. Staging was complete if the hospital submitted stage codes for > or =90% of stageable cases or absent if stage codes were submitted for <5%. Hospitals were classified by ownership and type of cancer program. Regional staging practices also were reviewed. Overall staging increased from 78% to 88%, with increases for every site except carcinomas of the skin, cancers of the extrahepatic bile ducts and urethra, melanoma of the eyelid, and retinoblastoma The percent of hospitals staging completely increased from 49% to 61%, and the percent not routinely staging decreased from 6% to 3%. Complete staging increased in all hospital categories except For-Profit. The trend toward complete staging was uneven among states and regions. Hospital staging policies were affected by activities of the AJCC, COC, NCDB, clinical protocol procedures, and state policies. The varied completeness of staging at the hospital level by state, region, and type of hospital indicates that the adoption of routine staging is ongoing.

  12. 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.

  13. Risk prediction model for colorectal cancer: National Health Insurance Corporation study, Korea.

    Science.gov (United States)

    Shin, Aesun; Joo, Jungnam; Yang, Hye-Ryung; Bak, Jeongin; Park, Yunjin; Kim, Jeongseon; Oh, Jae Hwan; Nam, Byung-Ho

    2014-01-01

    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. 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 population of 846,559 men and 479,449 women who participated in health examinations by the National Health Insurance Corporation. Examinees were 30-80 years old and free of cancer in the baseline years of 1996 and 1997. An independent population of 547,874 men and 415,875 women who participated in 1998 and 1999 examinations was used to validate the model. Model validation was done by evaluating its performance in terms of discrimination and calibration ability using the C-statistic and Hosmer-Lemeshow-type chi-square statistics. Age, body mass index, serum cholesterol, family history of cancer, and alcohol consumption were included in all models for men, whereas age, height, and meat intake frequency were included in all models for women. Models showed moderately good discrimination ability with C-statistics between 0.69 and 0.78. The C-statistics were generally higher in the models for men, whereas the calibration abilities were generally better in the models for women. Colorectal cancer risk prediction models were developed from large-scale, population-based data. Those models can be used for identifying high risk groups and developing preventive intervention strategies for colorectal cancer.

  14. Risk prediction model for colorectal cancer: National Health Insurance Corporation study, Korea.

    Directory of Open Access Journals (Sweden)

    Aesun Shin

    Full Text Available 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 population of 846,559 men and 479,449 women who participated in health examinations by the National Health Insurance Corporation. Examinees were 30-80 years old and free of cancer in the baseline years of 1996 and 1997. An independent population of 547,874 men and 415,875 women who participated in 1998 and 1999 examinations was used to validate the model. Model validation was done by evaluating its performance in terms of discrimination and calibration ability using the C-statistic and Hosmer-Lemeshow-type chi-square statistics. RESULTS: Age, body mass index, serum cholesterol, family history of cancer, and alcohol consumption were included in all models for men, whereas age, height, and meat intake frequency were included in all models for women. Models showed moderately good discrimination ability with C-statistics between 0.69 and 0.78. The C-statistics were generally higher in the models for men, whereas the calibration abilities were generally better in the models for women. CONCLUSIONS: Colorectal cancer risk prediction models were developed from large-scale, population-based data. Those models can be used for identifying high risk groups and developing preventive intervention strategies for colorectal cancer.

  15. Preferential HIV infection of CCR6+ Th17 cells is associated with higher levels of virus receptor expression and lack of CCR5 ligands.

    Science.gov (United States)

    Alvarez, Yelina; Tuen, Michael; Shen, Guomiao; Nawaz, Fatima; Arthos, James; Wolff, Martin J; Poles, Michael A; Hioe, Catarina E

    2013-10-01

    Th17 cells are enriched in the gut mucosa and play a critical role in maintenance of the mucosal barrier and host defense against extracellular bacteria and fungal infections. During chronic human immunodeficiency virus (HIV) infection, Th17 cells were more depleted compared to Th1 cells, even when the patients had low or undetectable viremia. To investigate the differential effects of HIV infection on Th17 and Th1 cells, a culture system was used in which CCR6(+) CD4(+) T cells were sorted from healthy human peripheral blood and activated in the presence of interleukin 1β (IL-1β) and IL-23 to drive expansion of Th17 cells while maintaining Th1 cells. HIV infection of these cultures had minimal effects on Th1 cells but caused depletion of Th17 cells. Th17 loss correlated with greater levels of virus-infected cells and cell death. In identifying cellular factors contributing to higher susceptibility of Th17 cells to HIV, we compared Th17-enriched CCR6(+) and Th17-depleted CCR6(-) CD4 T cell cultures and noted that Th17-enriched CCR6(+) cells expressed higher levels of α4β7 and bound HIV envelope in an α4β7-dependent manner. The cells also had greater expression of CD4 and CXCR4, but not CCR5, than CCR6(-) cells. Moreover, unlike Th1 cells, Th17 cells produced little CCR5 ligand, and transfection with one of the CCR5 ligands, MIP-1β (CCL4), increased their resistance against HIV. These results indicate that features unique to Th17 cells, including higher expression of HIV receptors and lack of autocrine CCR5 ligands, are associated with enhanced permissiveness of these cells to HIV.

  16. Evaluation of the cost of cervical cancer at the National Institute of ...

    African Journals Online (AJOL)

    Introduction: The Cervical Cancer (CC) is one of the heavy and costly diseases for the population and the health system. We want to know through this study, the first in Morocco, the annual cost of the treatment of this disease at the National Institute of Oncology (NIO) in Rabat, we also want to explore the possibility of ...

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

    Science.gov (United States)

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

  18. Estimating cancer incidence, prevalence, and the number of cancer patients treated with antitumor therapy in 2015 and 2020 -  analysis of the Czech National Cancer Registry.

    Science.gov (United States)

    Dusek, L; Pavlík, T; Májek, O; Büchler, T; Muzik, J; Maluskova, D; Koptíková, J; Bortlicek, Z; Abrahámová, J

    2015-01-01

    Cancer burden in the Czech population ranks among the highest worldwide, which introduces a strong need for a prospective modelling of cancer incidence and prevalence rates. Moreover, a prediction of number of cancer patients requiring active antitumor therapy is also an important issue. This paper presents the stage-specific predictions of cancer incidence and prevalence, and the stage- and region-specific patients requiring active antitumor therapy for the most common cancer diagnoses in the Czech Republic for years 2015 and 2020. The stage-specific estimates are also presented with regard to the treatment phase as newly diagnosed patients, patients treated for non-terminal recurrence, and patients treated for terminal recurrence. Data of the Czech National Cancer Registry from 1977 to 2011 has been used for the analysis, omitting the records of patients diagnosed as death certificate only or at autopsy. In total, 1,777,775 incidences have been considered for the estimation using a statistical model utilizing solely the population-based cancer registry data. All estimates have been calculated with respect to the changing demographic structure of the Czech population and the clinical stage at diagnosis. Considering year 2011 as the baseline, we predict 89%, 15%, 31% and 32% increase in prostate, colorectal, female breast and lung cancer incidence, respectively, in 2020 resulting in 13,153, 9,368, 8,695, and 8,604 newly dia-g--nosed cancer patients in that year, respectively. Regarding cancer prevalence in 2020, the estimated increase is 140%, 40%, 51%, and 17% for prostate, colorectal, female breast and lung cancer, respectively, meaning that more than 100,000 prevalent female breast cancer patients as well as more than 100,000 prevalent prostate cancer patients are expected in the Czech Republic. The estimated numbers of patients requiring active antitumor therapy for prostate, colorectal, female breast and lung cancer in the Czech Republic in 2020 are 23,652, 14

  19. Compliance with national nutrition recommendations among breast cancer survivors in "stepping stone".

    Science.gov (United States)

    Dennis Parker, Elizabeth A; Sheppard, Vanessa B; Adams-Campbell, Lucile

    2014-03-01

    Compared with White breast cancer survivors, African American survivors are more likely to be overweight and obese. Differences in weight status may be attributed to differences in dietary intake; however, there is limited research pertaining to the dietary habits of African American breast cancer survivors. We compared baseline dietary intakes of 31 overweight and obese African American breast cancer survivors enrolled in a healthy lifestyle intervention to national dietary guidelines and also examined beverage intake habits. Dietary intake was assessed using the National Cancer Institute's Diet History Questionnaire and beverage intake was assessed using 3-day food intake records. Overall, the majority of survivors consumed the recommended daily servings of fruits and vegetables (71.0%) and red meat (83.9%); however, survivors exceeded national recommendations for energy intake from fat (64.5%), saturated fat (87.1%), and added sugars (77.4%). Few women met the guidelines for whole grain and fiber intake (6.5% and 35.5%, respectively). Additionally, survivors consumed ~10% of total energy intake from beverages alone and drank only ~3.5 cups of water daily. Current dietary guidelines for cancer survivors recommend consuming >5 servings per day of fruits and vegetables and broad guidelines regarding limiting discretionary fat and added sugars but do not specify beverage intake recommendations. Future dietary interventions in African American breast cancer survivors should focus on reducing intake from dietary fat and added sugar, as well as increasing whole grain consumption as a means for increasing daily fiber intake. Furthermore, substituting caloric beverages with water or noncaloric beverages may be a strategy to decrease caloric intake in African American breast cancer survivors. Nutrition information targeting these nutrients could be administered during treatments or doctor's visits as a means to prevent weight gain that often occurs following diagnosis.

  20. Narcolepsy susceptibility gene CCR3 modulates sleep-wake patterns in mice.

    Science.gov (United States)

    Toyoda, Hiromi; Honda, Yoshiko; Tanaka, Susumu; Miyagawa, Taku; Honda, Makoto; Honda, Kazuki; Tokunaga, Katsushi; Kodama, Tohru

    2017-01-01

    Narcolepsy is caused by the loss of hypocretin (Hcrt) neurons and is associated with multiple genetic and environmental factors. Although abnormalities in immunity are suggested to be involved in the etiology of narcolepsy, no decisive mechanism has been established. We previously reported chemokine (C-C motif) receptor 3 (CCR3) as a novel susceptibility gene for narcolepsy. To understand the role of CCR3 in the development of narcolepsy, we investigated sleep-wake patterns of Ccr3 knockout (KO) mice. Ccr3 KO mice exhibited fragmented sleep patterns in the light phase, whereas the overall sleep structure in the dark phase did not differ between Ccr3 KO mice and wild-type (WT) littermates. Intraperitoneal injection of lipopolysaccharide (LPS) promoted wakefulness and suppressed both REM and NREM sleep in the light phase in both Ccr3 KO and WT mice. Conversely, LPS suppressed wakefulness and promoted NREM sleep in the dark phase in both genotypes. After LPS administration, the proportion of time spent in wakefulness was higher, and the proportion of time spent in NREM sleep was lower in Ccr3 KO compared to WT mice only in the light phase. LPS-induced changes in sleep patterns were larger in Ccr3 KO compared to WT mice. Furthermore, we quantified the number of Hcrt neurons and found that Ccr3 KO mice had fewer Hcrt neurons in the lateral hypothalamus compared to WT mice. We found abnormalities in sleep patterns in the resting phase and in the number of Hcrt neurons in Ccr3 KO mice. These observations suggest a role for CCR3 in sleep-wake regulation in narcolepsy patients.

  1. Narcolepsy susceptibility gene CCR3 modulates sleep-wake patterns in mice.

    Directory of Open Access Journals (Sweden)

    Hiromi Toyoda

    Full Text Available Narcolepsy is caused by the loss of hypocretin (Hcrt neurons and is associated with multiple genetic and environmental factors. Although abnormalities in immunity are suggested to be involved in the etiology of narcolepsy, no decisive mechanism has been established. We previously reported chemokine (C-C motif receptor 3 (CCR3 as a novel susceptibility gene for narcolepsy. To understand the role of CCR3 in the development of narcolepsy, we investigated sleep-wake patterns of Ccr3 knockout (KO mice. Ccr3 KO mice exhibited fragmented sleep patterns in the light phase, whereas the overall sleep structure in the dark phase did not differ between Ccr3 KO mice and wild-type (WT littermates. Intraperitoneal injection of lipopolysaccharide (LPS promoted wakefulness and suppressed both REM and NREM sleep in the light phase in both Ccr3 KO and WT mice. Conversely, LPS suppressed wakefulness and promoted NREM sleep in the dark phase in both genotypes. After LPS administration, the proportion of time spent in wakefulness was higher, and the proportion of time spent in NREM sleep was lower in Ccr3 KO compared to WT mice only in the light phase. LPS-induced changes in sleep patterns were larger in Ccr3 KO compared to WT mice. Furthermore, we quantified the number of Hcrt neurons and found that Ccr3 KO mice had fewer Hcrt neurons in the lateral hypothalamus compared to WT mice. We found abnormalities in sleep patterns in the resting phase and in the number of Hcrt neurons in Ccr3 KO mice. These observations suggest a role for CCR3 in sleep-wake regulation in narcolepsy patients.

  2. Association between HIV-1 tropism and CCR5 human haplotype E in a Caucasian population.

    Science.gov (United States)

    Huik, Kristi; Avi, Radko; Uibopuu, Helen; Pauskar, Merit; Margus, Tõnu; Karki, Tõnis; Krispin, Tõnu; Kool, Piret; Rüütel, Kristi; Talu, Ave; Abel-Ollo, Katri; Uusküla, Anneli; Carrillo, Andrew; He, Weijing; Ahuja, Sunil K; Lutsar, Irja

    2014-07-01

    The influence of the diversity of CCR5 on HIV susceptibility and disease progression has been clearly demonstrated but how the variability of this gene influences the HIV tropism is poorly understood. We investigated whether CCR5 haplotypes are associated with HIV tropism in a Caucasian population. We evaluated 161 HIV-positive subjects in a cross-sectional study. CCR5 haplotypes were derived after genotyping 9 CCR2-CCR5 polymorphisms. The HIV subtype was determined by phylogenetic analysis using the maximum likelihood method and viral tropism by the genotypic tropism assay (geno2pheno). Associations between CCR5 haplotypes and viral tropism were determined using logistic regression analyses. Samples from 500 blood donors were used to evaluate the representativeness of HIV-positives in terms of CCR5 haplotype distribution. The distribution of CCR5 haplotypes was similar in HIV-positive subjects and blood donors. The majority of viruses (93.8%) belonged to HIV-1 CRF06_cpx; 7.5% were X4, and the remaining were R5 tropic. X4 tropic viruses were over represented among people with CCR5 human haplotype E (HHE) compared with those without this haplotype (13.0% vs 1.4%; P = 0.006). People possessing CCR5 HHE had 11 times increased odds (odds ratio = 11.00; 95% confidence interval: 1.38 to 87.38) of having X4 tropic viruses than those with non-HHE. After adjusting for antiretroviral (ARV) therapy, neither the presence of HHE nor the use of ARV was associated with X4 tropic viruses. Our results suggest that CCR5 HHE and ARV treatment might be associated with the presence of HIV-1 X4 tropic viruses.

  3. Increased brain damage after ischaemic stroke in mice lacking the chemokine receptor CCR5

    Science.gov (United States)

    Sorce, S; Bonnefont, J; Julien, S; Marq-Lin, N; Rodriguez, I; Dubois-Dauphin, M; Krause, KH

    2010-01-01

    Background and purpose: The chemokine receptor CCR5 is well known for its function in immune cells; however, it is also expressed in the brain, where its specific role remains to be elucidated. Because genetic factors may influence the risk of developing cerebral ischaemia or affect its clinical outcome, we have analysed the role of CCR5 in experimental stroke. Experimental approach: Permanent cerebral ischaemia was performed by occlusion of the middle cerebral artery in wild-type and CCR5-deficient mice. Locomotor behaviour, infarct size and histochemical alterations were analysed at different time points after occlusion. Key results: The cerebral vasculature was comparable in wild-type and CCR5-deficient mice. However, the size of the infarct and the motor deficits after occlusion were markedly increased in CCR5-deficient mice as compared with wild type. No differences between wild-type and CCR5-deficient mice were elicited by occlusion with respect to the morphology and abundance of astrocytes and microglia. Seven days after occlusion the majority of CCR5-deficient mice displayed neutrophil invasion in the infarct region, which was not observed in wild type. As compared with wild type, the infarct regions of CCR5-deficient mice were characterized by increased neuronal death. Conclusions and implications: Lack of CCR5 increased the severity of brain injury following occlusion of the middle cerebral artery. This is of particular interest with respect to the relatively frequent occurrence of CCR5 deficiency in the human population (1–2% of the Caucasian population) and the advent of CCR5 inhibitors as novel drugs. PMID:20423342

  4. Association of race/ethnicity, socioeconomic status, and breast cancer subtypes in the National Cancer Data Base (2010-2011).

    Science.gov (United States)

    Sineshaw, Helmneh M; Gaudet, Mia; Ward, Elizabeth M; Flanders, W Dana; Desantis, Carol; Lin, Chun Chieh; Jemal, Ahmedin

    2014-06-01

    To estimate the odds of breast cancer subtypes in minority populations versus non-Hispanic (NH) whites stratified by socioeconomic status (SES) [a composite of individual-level SES (insurance status) and area-level SES (median household income quartile from 2000 U.S. Census data)] using a large nationwide cancer database. We used the National Cancer Data Base to identify breast cancer cases diagnosed in 2010 and 2011, the only 2 years since U.S. cancer registries uniformly began collecting HER2 results. Breast cancer cases were classified into five subtypes based on hormone receptor (HR) and HER2 status: HR+/HER2-, HR+/HER2+, HR-/HER2+ (HER2-overexpressing), HR-/HER2- (TN), and unknown. A polytomous logistic regression was used to estimate odds ratios (ORs) comparing the odds of non-HR+/HER2-subtypes to HR+/HER2- for racial/ethnic groups controlling for and stratifying by SES, using a composite of insurance status and area-level income. Compared with NH whites, NH blacks and Hispanics were 84 % (OR = 1.84; 95 % CI 1.77-1.92) and 17 % (OR = 1.17; 95 % CI 1.11-1.24) more likely to have TN subtype versus HR+/HER2-, respectively. Asian/Pacific Islanders (API) had 1.45 times greater odds of being diagnosed with HER2-overexpressing subtype versus HR+/HER2- compared with NH whites (OR = 1.45; 95 % CI 1.31-1.61). We found similar ORs for race in high and low strata of SES. In a large nationwide hospital-based dataset, we found higher odds of having TN breast cancer in black women and of HER2-overexpressing in API compared with white women in every level of SES.

  5. Evaluation of the National Skin Cancer Campaign: a Swiss experience of Euromelanoma.

    Science.gov (United States)

    Lieberherr, Sven; Seyed Jafari, S Morteza; Cazzaniga, Simone; Bianchi, Enrica; Schlagenhauff, Bettina; Tscharner, Gion; Hafner, Jürg; Mainetti, Carlo; Lapointe, Anne-Karine; Hunger, Robert E

    2017-10-24

    Skin cancer is a burden to healthcare and patients worldwide. The incidence of skin cancer has been rising during recent decades and this trend is expected to continue in the future. Numerous risk factors have been identified and prevention strategies developed. The Euromelanoma campaign is a pan-European skin cancer prevention programme, targeted to both primary and secondary prevention of malignant melanoma. The current study aimed to evaluate the results of the Swiss skin cancer screening day 2016. A questionnaire was used to obtain data on characteristics and suspected skin cancers of all participants. Follow-up of patients with suspicious lesions was performed 3 to 6 months later. During the campaign, 2795 people were screened. Of the screened individuals, 157 participants (58% female, 42% male; mean age 58.8 years) underwent further evaluations; 6 cutaneous malignant melanomas, 21 basal cell carcinomas and 2 squamous cell carcinomas were detected. Detection rates were 0.21% for cutaneous melanoma, 0.75% for basal cell carcinoma and 0.07% for squamous cell carcinoma. Our study provides an up-to-date evaluation of the Swiss Euromelanoma campaign 2016. The results are mostly in line with data from other European studies. Considering the morbidity, mortality and financial and social impact of skin cancer, the capacity to raise awareness of risk factors, skin cancer prevention methods and educating high-risk and at-risk individuals, we may assume that a National Screening Day has a crucial impact on the public health system.

  6. Enrollment Trends and Disparity Among Patients With Lung Cancer in National Clinical Trials, 1990 to 2012.

    Science.gov (United States)

    Pang, Herbert H; Wang, Xiaofei; Stinchcombe, Thomas E; Wong, Melisa L; Cheng, Perry; Ganti, Apar Kishor; Sargent, Daniel J; Zhang, Ying; Hu, Chen; Mandrekar, Sumithra J; Redman, Mary W; Manola, Judith B; Schilsky, Richard L; Cohen, Harvey J; Bradley, Jeffrey D; Adjei, Alex A; Gandara, David; Ramalingam, Suresh S; Vokes, Everett E

    2016-11-20

    Purpose Under-representation of elderly, women, and racial/ethnic minority patients with cancer in clinical trials is of national concern. The goal of this study was to characterize enrollment trends and disparities by age, sex, and race/ethnicity in lung cancer trials. Methods We analyzed data for 23,006 National Cancer Institute cooperative group lung cancer trial participants and 578,476 patients with lung cancer from the SEER registry from 1990 to 2012. The enrollment disparity difference (EDD) and enrollment disparity ratio (EDR) were calculated on the basis of the proportion of each subgroup in the trial population and the US lung cancer population. Annual percentage changes (APCs) in the subgroup proportions in each population were compared over time. Results Enrollment disparity for patients ≥ 70 years of age with non-small-cell lung cancer improved from 1990 to 2012 (test of parallelism, P = .020), with a remaining EDD of 0.22 (95% CI, 0.19 to 0.25) and EDR of 1.65 (95% CI, 1.51 to 1.82) in 2010 to 2012. No improvement was seen for elderly patients with small-cell lung cancer (SCLC), with an APC of 0.20 ( P = .714) among trial participants, despite a rising proportion of elderly patients with SCLC in the US population (APC, 0.32; P = .020). Enrollment disparity for women with lung cancer improved overall, with the gap closing by 2012 (EDD, 0.03 [95% CI, 0.00 to 0.06]; EDR, 1.07 [95% CI, 1.00 to 1.16]). Enrollment disparities persisted without significant improvement for elderly women, blacks, Asians/Pacific Islanders, and Hispanics. Conclusion Under-representation in lung cancer trials improved significantly from 1990 to 2012 for elderly patients with non-small-cell lung cancer and for women, but ongoing efforts to improve the enrollment of elderly patients with SCLC and minorities are needed. Our study highlights the importance of addressing enrollment disparities by demographic and disease subgroups to better target under-represented groups of patients

  7. Norepinephrine inhibits macrophage migration by decreasing CCR2 expression.

    Directory of Open Access Journals (Sweden)

    Fangming Xiu

    Full Text Available Increased incidences of infectious and septic complications during post-burn courses represent the main contributor to burn injury mortality. Sustained increases in catecholamine levels, especially norepinephrine (NE, contribute to immune disturbances in severely burned patients. The precise mechanisms underlying NE-mediated immunoregulation are not fully understood. Here we hypothesize that persistently elevated NE levels are associated with immunodysfunctions. We examined the effects of NE on the phenotype and functions of bone marrow-derived macrophages (BMMs. Whole mouse bone marrow cells were treated in vitro with 40 ng/mL of M-CSF and with 1 x 10(-6 M or 1 x 10(-8 M of NE or without NE for 7 days; cells were collected and stained with antibodies for CD11b, F4/80, MHC II and the inflammatory CC chemokine receptor 2 (CCR2. We found 1 x 10(-6 M of NE inhibited MHC II and CCR2 expression on CD11b(+/F4/80(+ BMM cells. It also inhibited BMM proliferation by inhibiting CSF-1R expression. On the contrary, 1 x 10(-8 M of NE slightly increased both MHC II and CCR2 expression on CD11b(+/F4/80(+ BMM cells but inhibited CD11b(+/F4/80(+ BMM proliferation. MCP-1 based migration assay showed that the migration of 1 x 10(-6 M of NE-treated BMM toward MCP-1 was significantly decreased compared to BMM without NE treatment. Both 1 x 10(-8 M and 1 x 10(-6 M of NE enhanced TNF-α production and phagocytosis of FITC-Dextran. Intracellular staining of transcriptional factor MafB showed that 1 x 10(-6 M of NE treatment enhanced its expression, whereas 1 x 10(-8 M of NE decreased expression. Stimulation with LPS in the last 24-hours of BMM culture further decreased CCR2 and MHC II expression of these BMM, suggesting the synergistic effect of LPS and NE on macrophage. Our results demonstrate that NE regulates macrophage differentiation, proliferation and function, and may play a critical role in the dysfunctional immune response post-burn.

  8. Breast and cervical cancers diagnosed and stage at diagnosis among women served through the National Breast and Cervical Cancer Early Detection Program.

    Science.gov (United States)

    Miller, Jacqueline W; Royalty, Janet; Henley, Jane; White, Arica; Richardson, Lisa C

    2015-05-01

    To assess cancers diagnosed and the stage of cancer at the time of diagnosis among low-income, under-insured, or uninsured women who received services through the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). Using the NBCCEDP database, we examined the number and percent of women diagnosed during 2009-2011 with in situ breast cancer, invasive breast cancer, and invasive cervical cancer by demographic and clinical characteristics, including age, race and ethnicity, test indication (screening or diagnostic), symptoms (for breast cancer), and screening history (for cervical cancer). We examined these characteristics by stage at diagnosis, a new variable included in the database obtained by linking with state-based central cancer registries. There were 11,569 women diagnosed with invasive breast cancer, 1,988 with in situ breast cancer, and 583 with invasive cervical cancer through the NBCCEDP. Women who reported breast symptoms or who had diagnostic mammography were more likely to be diagnosed with breast cancer, and at a later stage, than those who did not have symptoms or who had screening mammography. Women who had been rarely or never screened for cervical cancer were more likely to be diagnosed with cervical cancer, and at a later stage, than women who received regular screenings. Women served through the NBCCEDP who have not had prior screening or who have symptoms were more often diagnosed with late-stage disease.

  9. A national survey of lung cancer specialists' views on low-dose CT screening for lung cancer in Korea.

    Directory of Open Access Journals (Sweden)

    Dong Wook Shin

    Full Text Available Lung cancer specialists play an important role in designing and implementing lung cancer screening. We aimed to describe their 1 attitudes toward low-dose lung computed tomography (LDCT screening, 2 current practices and experiences of LDCT screening and 3 attitudes and opinions towards national lung cancer screening program (NLCSP. We conducted a national web-based survey of pulmonologists, thoracic surgeons, medical oncologists, and radiological oncologists who are members of Korean Association for Lung Cancer (N = 183. Almost all respondents agreed that LDCT screening increases early detection (100%, improves survival (95.1%, and gives a good smoking cessation counseling opportunity (88.6%. Most were concerned about its high false positive results (79.8% and the subsequent negative effects. Less than half were concerned about radiation hazard (37.2%. Overall, most (89.1% believed that the benefits outweigh the risks and harms. Most (79.2% stated that they proactively recommend LDCT screening to those who are eligible for the current guidelines, but the screening propensity varied considerably. The majority (77.6% agreed with the idea of NLCSP and its beneficial effect, but had concerns about the quality control of CT devices (74.9%, quality assurance of radiologic interpretation (63.3%, poor access to LDCT (56.3%, and difficulties in selecting eligible population using self-report history (66.7%. Most (79.2% thought that program need to be funded by a specialized fund rather than by the National Health Insurance. The opinions on the level of copayment for screening varied. Our findings would be an important source for health policy decision when considering for NLCSP in Korea.

  10. Chemokine Receptor CCR5 Antagonist Maraviroc: Medicinal Chemistry and Clinical Applications

    Science.gov (United States)

    Xu, Guoyan G.; Guo, Jia; Wu, Yuntao

    2015-01-01

    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. PMID:25159165

  11. Profile of State College and Career Readiness Assessments (CCR) Policy. Florida

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Florida's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  12. Profile of State College and Career Readiness Assessments (CCR) Policy. Arkansas

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Arkansas' college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  13. Profile of State College and Career Readiness Assessments (CCR) Policy. Minnesota

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Minnesota's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  14. Profile of State College and Career Readiness Assessments (CCR) Policy. Alaska

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Alaska's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  15. Profile of State College and Career Readiness Assessments (CCR) Policy. South Carolina

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on South Carolina's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  16. 77 FR 57566 - Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review...

    Science.gov (United States)

    2012-09-18

    ... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OW-2012-0035; FRL-9730-7] Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review and Request for Public Comment on Potential Approaches to Electronic Delivery of the CCR; Correction AGENCY: Environmental Protection Agency...

  17. Profile of State College and Career Readiness Assessments (CCR) Policy. Kentucky

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Kentucky's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  18. Profile of State College and Career Readiness Assessments (CCR) Policy. Georgia

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Georgia's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  19. Profile of State College and Career Readiness Assessments (CCR) Policy. North Dakota

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on North Dakota's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  20. Profile of State College and Career Readiness Assessments (CCR) Policy. Alabama

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Alabama's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  1. Profile of State College and Career Readiness Assessments (CCR) Policy. New Mexico

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on New Mexico's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  2. Profile of State College and Career Readiness Assessments (CCR) Policy. Tennessee

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Tennessee's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  3. Profile of State College and Career Readiness Assessments (CCR) Policy. California

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on California's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  4. Profile of State College and Career Readiness Assessments (CCR) Policy. West Virginia

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on West Virginia's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  5. 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.

  6. The Effects of the Recombinant CCR5 T4 Lysozyme Fusion Protein on HIV-1 Infection.

    Science.gov (United States)

    Jin, Qingwen; Chen, Hong; Wang, Xingxia; Zhao, Liandong; Xu, Qingchen; Wang, Huijuan; Li, Guanyu; Yang, Xiaofan; Ma, Hongming; Wu, Haoquan; Ji, Xiaohui

    2015-01-01

    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.

  7. CCR5 receptor antagonists in preclinical to phase II clinical development for treatment of HIV.

    Science.gov (United States)

    Kim, Michelle B; Giesler, Kyle E; Tahirovic, Yesim A; Truax, Valarie M; Liotta, Dennis C; Wilson, Lawrence J

    2016-12-01

    The chemokine receptor CCR5 has garnered significant attention in recent years as a target to treat HIV infection largely due to the approval and success of the drug Maraviroc. The side effects and inefficiencies with other first generation agents led to failed clinical trials, prompting the development of newer CCR5 antagonists. Areas covered: This review aims to survey the current status of 'next generation' CCR5 antagonists in the preclinical pipeline with an emphasis on emerging agents for the treatment of HIV infection. These efforts have culminated in the identification of advanced second-generation agents to reach the clinic and the dual CCR5/CCR2 antagonist Cenicriviroc as the most advanced currently in phase II clinical studies. Expert opinion: The clinical success of CCR5 inhibitors for treatment of HIV infection has rested largely on studies of Maraviroc and a second-generation dual CCR5/CCR2 antagonist Cenicriviroc. Although research efforts identified several promising preclinical candidates, these were dropped during early clinical studies. Despite patient access to Maraviroc, there is insufficient enthusiasm surrounding its use as front-line therapy for treatment of HIV. The non-HIV infection related development activities for Maraviroc and Cenicriviroc may help drive future interests.

  8. 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.

  9. 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...

  10. Descriptive Epidemiology in Mexican children with cancer under an open national public health insurance program.

    Science.gov (United States)

    Rivera-Luna, Roberto; Shalkow-Klincovstein, Jaime; Velasco-Hidalgo, Liliana; Cárdenas-Cardós, Rocio; Zapata-Tarrés, Marta; Olaya-Vargas, Alberto; Aguilar-Ortiz, Marco R; Altamirano-Alvarez, Eduardo; Correa-Gonzalez, Cecilia; Sánchez-Zubieta, Fernando; Pantoja-Guillen, Francisco

    2014-10-29

    All the children registered at the National Council for the Prevention and Treatment of Childhood Cancer were analyzed. The rationale for this Federal Government Council is to financially support the treatment of all children registered into this system. All patients are within a network of 55 public certified hospitals nationwide. In the current study, data from 2007 to 2012 are presented for all patients (0-18 years) with a pathological diagnosis of leukemia, lymphoma and solid tumors. The parameters analyzed were prevalence, incidence, mortality, and abandonment rate. A diagnosis of cancer was documented in 14,178 children. The incidence was of 156.9/million/year (2012). The median age was 4.9. The most common childhood cancer is leukemia, which occurs in 49.8% of patients (2007-2012); and has an incidence rate of 78.1/million/year (2012). The national mortality rate was 5.3/100,000 in 2012, however in the group between 15 to 18 years it reaches a level of 8.6. The study demonstrates that there is a high incidence of childhood cancer in Mexico. In particular, the results reveal an elevated incidence and prevalence of leukemia especially from 0 to 4 years. Only 4.7% of these patients abandoned treatment. The clinical outcome for all of the children studied improved since the establishment of this national program.

  11. 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.

  12. Lack of shared decision making in cancer screening discussions: results from a national survey.

    Science.gov (United States)

    Hoffman, Richard M; Elmore, Joann G; Fairfield, Kathleen M; Gerstein, Bethany S; Levin, Carrie A; Pignone, Michael P

    2014-09-01

    Clinicians are encouraged to support patients in achieving shared decision making (SDM) for cancer screening. To describe decision making processes and outcomes for cancer screening discussions. A 2011 national Internet survey of adults aged ≥50 years who made cancer screening decisions (breast, BrCa; colorectal, CRC; prostate, PCa) within the previous 2 years was conducted. Participants were asked about their perceived cancer risk; how informed they felt about cancer tests; whether their healthcare provider addressed pros/cons of testing, presented the option of no testing, and elicited their input; whether they were tested; and their confidence in the screening decision. Data were analyzed in 2013-2014 with descriptive statistics and logistic regression. Overall, 1,134 participants (477 men, 657 women) aged ≥50 years made cancer screening decisions, and 1,098 (354, BrCa; 598, CRC; 146, PCa) decisions were discussed with a healthcare provider. Most discussions (51%-67%) addressed pros of screening some or a lot, but few (7%-14%) similarly addressed cons. For all cancer screening decisions, providers usually (63%-71%) explained that testing was optional, but less often asked women (43%-57%) than men (70%-71%) whether they wanted testing. Only 27%-38% of participants reported SDM, 69%-93% underwent screening, and 55%-76% would definitely make the same decision again. Perceived high/average cancer risk and feeling highly informed were associated with confidence in the screening decision. Discussions often failed to provide balanced information and meet SDM criteria. Supporting SDM could potentially improve the quality of cancer screening decisions. Published by Elsevier Inc.

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

    Directory of Open Access Journals (Sweden)

    Leonard K. Katalambula

    2016-01-01

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

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

    Science.gov (United States)

    Katalambula, Leonard K; Ntwenya, Julius Edward; Ngoma, Twalib; Buza, Joram; Mpolya, Emmanuel; Mtumwa, Abdallah H; Petrucka, Pammla

    2016-01-01

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

  15. Nutritional status of cancer patients admitted for chemotherapy at the National Kidney and Transplant Institute.

    Science.gov (United States)

    Montoya, J E; Domingo, F; Luna, C A; Berroya, R M; Catli, C A; Ginete, J K; Sanchez, O S; Juat, N J; Tiangco, B J; Jamias, J D

    2010-11-01

    Malnutrition is common among cancer patients. This study aimed to determine the overall prevalence of malnutrition among patients undergoing chemotherapy and to determine the predictors of malnutrition among cancer patients. A cross-sectional study was conducted on 88 cancer patients admitted for chemotherapy at the National Kidney and Transplant Institute, Philippines, from October to November 2009. Subjective Global Assessment (SGA), anthropometric data and demographic variables were obtained. Descriptive statistics, ANOVA and logistic regression analysis were performed between the outcome and variables. A total of 88 cancer patients were included in the study. The mean age of the patients was 55.7 +/- 14.8 years. The mean duration of illness was 9.7 +/- 8.7 months and the mean body mass index (BMI) was 22.9 kg/m2. The mean Karnofsky performance status was 79.3. 29.55 percent of the patients had breast cancer as the aetiology of their illness. 38 patients (43.2 percent) had SGA B and four (4.5 percent) had SGA C, giving a total malnutrition prevalence of 47.7 percent. The patients were statistically different with regard to their cancer stage (p is less than 0.001), weight (p is 0.01), BMI (p is 0.004), haemoglobin level (p is 0.001) and performance status by Karnofsky score (p is less than 0.001), as evaluated by ANOVA. Logistic regression analysis showed that cancer stage and Karnofsky performance score were predictors of malnutrition. About 47.7 percent of cancer patients suffer from malnutrition, as classified by SGA. Only cancer stage and Karnofsky performance status scoring were predictive of malnutrition in this select group of patients.

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

    Science.gov (United States)

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

    2016-11-16

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

  17. The dual CCR5 and CCR2 inhibitor cenicriviroc does not redistribute HIV into extracellular space: implications for plasma viral load and intracellular DNA decline.

    Science.gov (United States)

    Kramer, Victor G; Hassounah, Said; Colby-Germinario, Susan P; Oliveira, Maureen; Lefebvre, Eric; Mesplède, Thibault; Wainberg, Mark A

    2015-03-01

    Cenicriviroc is a potent antagonist of the chemokine coreceptors 5 and 2 (CCR5/CCR2) and blocks HIV-1 entry. The CCR5 inhibitor maraviroc has been shown in tissue culture to be able to repel cell-free virions from the cell surface into extracellular space. We hypothesized that cenicriviroc might exhibit a similar effect, and tested this using clinical samples from the Phase IIb study 652-2-202, by measuring rates of intracellular DNA decline. We also monitored viral RNA levels in culture fluids. We infected PM-1 cells with CCR5-tropic HIV-1 BaL in the presence or absence of inhibitory concentrations of cenicriviroc (20 nM) or maraviroc (50 nM) or controls. Viral load levels and p24 were measured by ELISA, quantitative PCR and quantitative real-time reverse transcription PCR at 4 h post-infection. Frozen PBMC DNA samples from 30 patients with virological success in the Phase IIb study were studied, as were early and late reverse transcript levels. Docking studies compared binding between cenicriviroc/CCR5 and maraviroc/CCR5. Unlike maraviroc, cenicriviroc did not cause an increase in the amount of virus present in culture fluids at 4 h compared with baseline. The use of cenicriviroc did, however, result in lower levels of intracellular viral DNA after 4 h. Structural modelling indicates that cenicriviroc binds more deeply than maraviroc to the hydrophobic pocket of CCR5, providing an explanation for the absence of viral rebound with cenicriviroc. In contrast to maraviroc, cenicriviroc does not repel virus back into extracellular space. Differences in results may be due to superior binding of cenicriviroc to CCR5 compared with maraviroc. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  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. © 2015 John

  19. Development of Tetravalent, Bispecific CCR5 Antibodies with Antiviral Activity against CCR5 Monoclonal Antibody-Resistant HIV-1 Strains▿

    OpenAIRE

    Schanzer, Jürgen; Jekle, Andreas; Nezu, Junichi; Lochner, Adriane; Croasdale, Rebecca; Dioszegi, Marianna; Zhang, Jun; Hoffmann, Eike; Dormeyer, Wilma; Stracke, Jan; Schäfer, Wolfgang; Ji, Changhua; Heilek, Gabrielle; Cammack, Nick; Brandt, Michael

    2011-01-01

    In this study, we describe novel tetravalent, bispecific antibody derivatives that bind two different epitopes on the HIV coreceptor CCR5. The basic protein formats that we applied were derived from Morrison-type bispecific antibodies: whole IgGs to which we connected single-chain antibodies (scFvs) via (Gly4Ser)n sequences at either the C or N terminus of the light chain or heavy chain. By design optimization, including disulfide stabilization of scFvs or introduction of 30-amino-acid linker...

  20. National evaluation of multidisciplinary quality metrics for head and neck cancer.

    Science.gov (United States)

    Cramer, John D; Speedy, Sedona E; Ferris, Robert L; Rademaker, Alfred W; Patel, Urjeet A; Samant, Sandeep

    2017-11-15

    The National Quality Forum has endorsed quality-improvement measures for multiple cancer types that are being developed into actionable tools to improve cancer care. No nationally endorsed quality metrics currently exist for head and neck cancer. The authors identified patients with surgically treated, invasive, head and neck squamous cell carcinoma in the National Cancer Data Base from 2004 to 2014 and compared the rate of adherence to 5 different quality metrics and whether compliance with these quality metrics impacted overall survival. The metrics examined included negative surgical margins, neck dissection lymph node (LN) yield ≥ 18, appropriate adjuvant radiation, appropriate adjuvant chemoradiation, adjuvant therapy within 6 weeks, as well as overall quality. In total, 76,853 eligible patients were identified. There was substantial variability in patient-level adherence, which was 80% for negative surgical margins, 73.1% for neck dissection LN yield, 69% for adjuvant radiation, 42.6% for adjuvant chemoradiation, and 44.5% for adjuvant therapy within 6 weeks. Risk-adjusted Cox proportional-hazard models indicated that all metrics were associated with a reduced risk of death: negative margins (hazard ratio [HR] 0.73; 95% confidence interval [CI], 0.71-0.76), LN yield ≥ 18 (HR, 0.93; 95% CI, 0.89-0.96), adjuvant radiation (HR, 0.67; 95% CI, 0.64-0.70), adjuvant chemoradiation (HR, 0.84; 95% CI, 0.79-0.88), and adjuvant therapy ≤6 weeks (HR, 0.92; 95% CI, 0.89-0.96). Patients who received high-quality care had a 19% reduced adjusted hazard of mortality (HR, 0.81; 95% CI, 0.79-0.83). Five head and neck cancer quality metrics were identified that have substantial variability in adherence and meaningfully impact overall survival. These metrics are appropriate candidates for national adoption. Cancer 2017;123:4372-81. © 2017 American Cancer Society. © 2017 American Cancer Society.

  1. 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.

  2. Enriquecimento com calda do CCR para face de barragens

    Directory of Open Access Journals (Sweden)

    A. P. Wendler

    Full Text Available A construção de barragens de CCR prioriza a minimização de interferências, como a execução da face de montante, para garantia da produtividade. O estudo procurou avaliar as propriedades físicas do CCR enriquecido com calda, em substituição ao concreto convencional usualmente empregado na face, utilizando os mesmos materiais, central de concreto, mão de obra e equipamentos, empregados na construção da Usina Hidrelétrica Mauá. Para tanto foram feitos prismas experimentais de campo (com diferentes relações água/cimento e quantidades de calda e posterior extração de testemunhos, os quais foram submetidos a ensaios mecânicos e de permeabilidade. Os resultados mostraram que para relações água/cimento 0,74, o material resultante atendeu às especificações de projeto, para consumos de cimento notadamente menores (entre 70 e 85% do CCV.

  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. [Variations in a 24-year period of colorectal and gastric cancer in Mexico].

    Science.gov (United States)

    González Trujillo, José Luis; Vargas, Florencia; Torres Villalobos, Gonzalo; Milke, Pilar; Villalobos Pérez, José de Jesús

    2003-01-01

    Gastric cancer (CG) and colorectal cancer (CCR) are the two most common neoplasms of the digestive system in the world. We performed a study to determine incidence and relation between CG and CCR in five hospitals in Mexico City. Patients with admitted diagnosis of CG and CCR at Hospital General de Mexico, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Hospital Español de México, Centro Médico Nacional "20 de Noviembre" from the Instituto de Salud y Seguridad Social para Trabajadores del Estado, and Hospital Central Militar from January 1978 to December 2001 were studied. A total of 7,136 patients were studied. (CG 3,830, CCR 3,306). At Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" CG was the most common digestive neoplasm; from 1999, ratio was inverted to 2, and later had an average of 1.31. For Hospital Español, ratio always was Nacional "20 de Noviembre", initially CCR was more frequent, then CG, and finally CCR. At Hospital Central Militar ratio was constant, > CG. At the beginning, was global behavior > CG, ratio seemed to invert, but since 1998 CG/CCR ratio was < 1 and continued that way. In this study, we found that changes of CG/CCR ratio in a period of 24 years showed elevation of CCR incidence at five Mexican hospitals.

  5. 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...ted gp120-elicited signalingpathways. PubmedID 12960231 Title Macrophage activation through CCR

  6. Consumer attitudes towards the establishment of a national Australian familial cancer research database by the Inherited Cancer Connect (ICCon) Partnership.

    Science.gov (United States)

    Forrest, Laura; Mitchell, Gillian; Thrupp, Letitia; Petelin, Lara; Richardson, Kate; Mascarenhas, Lyon; Young, Mary-Anne

    2018-01-01

    Clinical genetics units hold large amounts of information which could be utilised to benefit patients and their families. In Australia, a national research database, the Inherited Cancer Connect (ICCon) database, is being established that comprises clinical genetic data held for all carriers of mutations in cancer predisposition genes. Consumer input was sought to establish the acceptability of the inclusion of clinical genetic data into a research database. A qualitative approach using a modified nominal group technique was used to collect data through consumer forums conducted in three Australian states. Individuals who had previously received care from Familial Cancer Centres were invited to participate. Twenty-four consumers participated in three forums. Participants expressed positive attitudes about the establishment of the ICCon database, which were informed by the perceived benefits of the database including improved health outcomes for individuals with inherited cancer syndromes. Most participants were comfortable to waive consent for their clinical information to be included in the research database in a de-identified format. As major stakeholders, consumers have an integral role in contributing to the development and conduct of the ICCon database. As an initial step in the development of the ICCon database, the forums demonstrated consumers' acceptance of important aspects of the database including waiver of consent.

  7. Disparities in the Care of Differentiated Thyroid Cancer in the United States: Exploring the National Cancer Database.

    Science.gov (United States)

    Jaap, Kathryn; Campbell, Rebekah; Dove, James; Fluck, Marcus; Hunsinger, Marie; Wild, Jeffrey; Arora, Tania; Shabahang, Mohsen; Blansfield, Joseph

    2017-07-01

    Differentiated thyroid cancer (DTC) treatment is multifaceted, and may be influenced by socioeconomic factors. The goal of this study is to examine disparities in DTC treatment. DTC patients from 1998 to 2012 were identified using the National Cancer Database. DTC was identified in 262,041 patients. The mean age was 48.2. The majority of patients (52%) received care at Comprehensive Community Cancer Programs (CCCPs). Total thyroidectomy was less common at Community Cancer Programs (CCPs) [odds ratio (OR): 0.735; 95% confidence interval (CI): 0.707-0.764), and more common at academic centers (OR: 1.129; 95% CI: 1.102-1.157) compared with CCCP. A central neck dissection was performed most often at academic center (20.6%) versus CCP (10.0%). Black patients were less likely to undergo central neck dissection compared with white patients (OR: 0.468; 95% CI: 0.452-0.484). Patients more likely to receive radioactive iodine were white compared with black patients (hazard ratio: 0.833; 95% CI: 0.806-0.861), privately insured compared with uninsured patients (hazard ratio: 1.272; 95% CI: 1.210-1.341), and patients treated at CCCP. Disparities exist in DTC treatment. Individuals at risk for under-treatment are black patients, uninsured patients, and those treated at CCP. As the Affordable Care Act changes access to health care, future studies will be needed to readdress disparities.

  8. The functional antagonist Met-RANTES: a modified agonist that induces differential CCR5 trafficking.

    Science.gov (United States)

    Kiss, Debra L; Longden, James; Fechner, Gregory A; Avery, Vicky M

    2009-01-01

    CC chemokine receptor 5 (CCR5) is a pro-inflammatory chemokine receptor that is expressed on cells of the immune system, and specializes in cell migration in response to inflammation and tissue damage. Due to its key role in cell communication and migration, this receptor is involved in various inflammatory and autoimmune diseases, in addition to HIV infection. Met-RANTES is a modified CCR5 ligand that has previously been shown to antagonize CCR5 activation and function in response to its natural ligands in vitro. In vivo, Met-RANTES is able to reduce inflammation in models of induced inflammatory and autoimmune diseases. However, due to the fact that Met-RANTES is also capable of partial agonist activity regarding receptor signaling and internalization, it is clear that Met-RANTES does not function as a conventional receptor antagonist. To further elucidate the effect of Met-RANTES on CCR5, receptor trafficking was investigated in a CHO-CCR5-GFP cell line using the Opera confocal plate reader. The internalization response of CCR5 was quantified, and showed that Met-RANTES internalized CCR5 in a slower, less potent manner than the agonists CCL3 and CCL5. Fluorescent organelle labeling and live cell imaging showed CCL3 and CCL5 caused CCR5 to traffic through sorting endosomes, recycling endosomes and the Golgi apparatus. In contrast, Met-RANTES caused CCR5 to traffic through sorting endosomes and the Golgi apparatus in a manner that was independent of recycling endosomes. As receptor trafficking impacts on cell surface expression and the ability of the receptor to respond to more ligand, this information may indicate an alternative regulation of CCR5 by Met-RANTES that allows the modified ligand to reduce inflammation through stimulation of a pro-inflammatory receptor.

  9. CCR5 Haplotypes Influence HCV Serostatus in Caucasian Intravenous Drug Users

    Science.gov (United States)

    Huik, Kristi; Avi, Radko; Carrillo, Andrew; Harper, Nathan; Pauskar, Merit; Sadam, Maarja; Karki, Tõnis; Krispin, Tõnu; Kongo, Ulvi-Kaire; Jermilova, Tatiana; Rüütel, Kristi; Talu, Ave; Abel-Ollo, Katri; Uusküla, Anneli; Ahuja, Sunil K.; He, Weijing; Lutsar, Irja

    2013-01-01

    Background Up to 90% HIV-1 positive intravenous drug users (IDUs) are co-infected with HCV. Although best recognized for its function as a major co-receptor for cell entry of HIV, CC chemokine receptor 5 (CCR5) has also been implicated in the pathogenesis of HCV infection. Here, we investigated whether CCR5 haplotypes influence HIV-1 and HCV seropositivity among 373 Caucasian IDUs from Estonia. Methods Of these IDUs, 56% and 44% were HIV and HCV seropositive, respectively, and 47% were coinfected. 500 blood donors seronegative for HIV and HCV were also evaluated. CCR5 haplotypes (HHA to HHG*2) were derived after genotyping nine CCR2–CCR5 polymorphisms. The association between CCR5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis. Co-variates included in the models were length of intravenous drug use, HBV serostatus and copy number of CCL3L1, the gene encoding the most potent HIV-suppressive chemokine and ligand for CCR5. Results Compared to IDUs seronegative for both HCV and HIV (HCV−/HIV-), IDUs who were HCV+/HIV- and HCV+/HIV+were 92% and 82%, respectively, less likely to possess the CCR5-HHG*1 haplotype, after controlling for co-variates (Padjusted = 1.89×10−4 and 0.003, respectively). This association was mostly due to subjects bearing the CCR5 HHE and HHG*1 haplotype pairs. Approximately 25% andHIV- IDUs and HCV−/HIV- blood donors, respectively, possessed the HHE/HHG*1 genotype. Conclusions Our findings suggest that HHG*1-bearing CCR5 genotypes influence HCV seropositivity in a group of Caucasian IDUs. PMID:23936229

  10. Oncologists' perspectives on concurrent palliative care in a National Cancer Institute-designated comprehensive cancer center.

    Science.gov (United States)

    Bakitas, Marie; Lyons, Kathleen Doyle; Hegel, Mark T; Ahles, Tim

    2013-10-01

    The purpose of this study was to understand oncology clinicians' perspectives about the care of advanced cancer patients following the completion of the ENABLE II (Educate, Nurture, Advise, Before Life Ends) randomized clinical trial (RCT) of a concurrent oncology palliative care model. This was a qualitative interview study of 35 oncology clinicians about their approach to patients with advanced cancer and the effect of the ENABLE II RCT. Oncologists believed that integrating palliative care at the time of an advanced cancer diagnosis enhanced patient care and complemented their practice. Self-assessment of their practice with advanced cancer patients comprised four themes: (1) treating the whole patient, (2) focusing on quality versus quantity of life, (3) “some patients just want to fight,” and (4) helping with transitions; timing is everything. Five themes comprised oncologists' views on the complementary role of palliative care: (1) “refer early and often,” (2) referral challenges: “Palliative” equals “hospice”; “Heme patients are different,” (3) palliative care as consultants or co-managers, (4) palliative care “shares the load,” and (5) ENABLE II facilitated palliative care integration. Oncologists described the RCT as holistic and complementary, and as a significant factor in adopting concurrent care as a standard of care.

  11. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Colorectal cancer in Saudi Arabia: incidence, survival, demographics and implications for national policies.

    Science.gov (United States)

    Alsanea, Nasser; Abduljabbar, Alaa S; Alhomoud, Samar; Ashari, Luai H; Hibbert, Denise; Bazarbashi, Shouki

    2015-01-01

    The national data on colorectal cancer in Saudi Arabia has not been analyzed. The objective of this study is to describe the demographics, incidence and survival rates for colorectal cancer in Saudi Arabia for the period 1994-2010. Retrospective analysis of the Saudi Cancer Registry data for the period 1994-2010. Data from the Saudi Cancer Registry was analyzed by stage at presentation (local, regional, distal, unknown) and survival rates were calculated using the Kaplan-Meier method. From 9889 colorectal cancer cases, a sample of 549 (5.6%) patients was selected and their living status ascertained to assess survival. Colorectal cancer has been the most common cancer among men and the third commonest among women since 2002 in Saudi Arabia. There has been a slight predominance among men with an average ratio of 116:100 over the years (range: 99:100-132:100). The overall age-standardized rate (ASR) approached a plateau of 9.6/100000 in 2010. The incidence of the disease has been highest in the capital, Riyadh, where it reached 14.5/100000 in 2010. Median age at presentation has been stable at around 60 years (95% confidence Interval (CI): 57-61 years) for men and 55 years (95% CI: 53-58 years) for women. Distant metastasis was diagnosed in 28.4% of patients at the time of presentation and rectal cancer represented 41% of all colorectal cancers diagnosed in 2010. The overall 5-year survival was 44.6% for the period 1994-2004. The ASR for all age groups below 45 years of age was lower than that for the United States. The study was retrospective with a possibility of bias from inaccurate staging of patients, and inaccurate survival information and patient demographics due to the underdeveloped census system prior to 2001. Survival data for the period 2005-2010 are lacking. Colorectal cancer presents at a younger age in Saudis, especially in women. This has a major implication for decisions about the threshold age for screening. The ASR has increased, but is still much

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

    Directory of Open Access Journals (Sweden)

    Aiello Bowles Erin J

    2012-04-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions The BRCASO database is one of the largest, multi-site research resources of meaningful breast cancer surgical quality data

  14. 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...

  15. Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012

    Energy Technology Data Exchange (ETDEWEB)

    Brower, Jeffrey V. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Chen, Shuai [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Bassetti, Michael F. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Yu, Menggang [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Harari, Paul M.; Ritter, Mark A. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Baschnagel, Andrew M., E-mail: baschnagel@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States)

    2016-12-01

    Purpose: To evaluate the effect of radiation dose escalation on overall survival (OS) for patients with nonmetastatic esophageal cancer treated with concurrent radiation and chemotherapy. Methods and Materials: Patients diagnosed with stage I to III esophageal cancer treated from 2004 to 2012 were identified from the National Cancer Data Base. Patients who received concurrent radiation and chemotherapy with radiation doses of ≥50 Gy and did not undergo surgery were included. OS was compared using Cox proportional hazards regression and propensity score matching. Results: A total of 6854 patients were included; 3821 (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received doses >50.4 Gy. Univariate analysis revealed no significant difference in OS between patients receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis, binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses investigating the effect of dose escalation by histologic type and in the setting of intensity modulated radiation therapy also failed to reveal a benefit. Propensity score matching confirmed the absence of a statistically significant difference in OS among the dose levels. The factors associated with improved OS on multivariable analysis included female sex, lower Charlson-Deyo comorbidity score, private insurance, cervical/upper esophagus location, squamous cell histologic type, lower T stage, and node-negative status (P<.01 for all analyses). Conclusions: In this large national cohort, dose escalation >50.4 Gy did not result in improved OS among patients with stage I to III esophageal cancer treated with definitive concurrent radiation and chemotherapy. These data suggest that despite advanced contemporary treatment techniques, OS for patients with esophageal cancer remains unaltered by escalation of radiation dose >50.4 Gy, consistent with the results of

  16. Time trends, improvements and national auditing of rectal cancer management over an 18-year period.

    Science.gov (United States)

    Kodeda, K; Johansson, R; Zar, N; Birgisson, H; Dahlberg, M; Skullman, S; Lindmark, G; Glimelius, B; Påhlman, L; Martling, A

    2015-09-01

    The main aims were to explore time trends in the management and outcome of patients with rectal cancer in a national cohort and to evaluate the possible impact of national auditing on overall outcomes. A secondary aim was to provide population-based data for appraisal of external validity in selected patient series. Data from the Swedish ColoRectal Cancer Registry with virtually complete national coverage were utilized in this cohort study on 29 925 patients with rectal cancer diagnosed between 1995 and 2012. Of eligible patients, nine were excluded. During the study period, overall, relative and disease-free survival increased. Postoperative mortality after 30 and 90 days decreased to 1.7% and 2.9%. The 5-year local recurrence rate dropped to 5.0%. Resection margins improved, as did peri-operative blood loss despite more multivisceral resections being performed. Fewer patients underwent palliative resection and the proportion of non-operated patients increased. The proportions of temporary and permanent stoma formation increased. Preoperative radiotherapy and chemoradiotherapy became more common as did multidisciplinary team conferences. Variability in rectal cancer management between healthcare regions diminished over time when new aspects of patient care were audited. There have been substantial changes over time in the management of patients with rectal cancer, reflected in improved outcome. Much indirect evidence indicates that auditing matters, but without a control group it is not possible to draw firm conclusions regarding the possible impact of a quality control registry on faster shifts in time trends, decreased variability and improvements. Registry data were made available for reference. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

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

    International Nuclear Information System (INIS)

    Torres U, C. L.; Avila A, O. L.; Medina V, L. A.; Buenfil B, A. E.; Brandan S, M. E.; Trujillo Z, F. E.; Gamboa de Buen, I.

    2009-01-01

    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 131 I, 18 F, 67 Ga, 99m Tc, 111 In, 201 Tl and 137 Cs 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 131 I and 137 Cs 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 137 Cs. (Author)

  18. Expression pattern of Ccr2 and Cx3cr1 in inherited retinal degeneration.

    Science.gov (United States)

    Kohno, Hideo; Koso, Hideto; Okano, Kiichiro; Sundermeier, Thomas R; Saito, Saburo; Watanabe, Sumiko; Tsuneoka, Hiroshi; Sakai, Tsutomu

    2015-10-12

    Though accumulating evidence suggests that microglia, resident macrophages in the retina, and bone marrow-derived macrophages can cause retinal inflammation which accelerates photoreceptor cell death, the details of how these cells are activated during retinal degeneration (RD) remain uncertain. Therefore, it is important to clarify which cells play a dominant role in fueling retinal inflammation. However, distinguishing between microglia and macrophages is difficult using conventional techniques such as cell markers (e.g., Iba-1). Recently, two mouse models for visualizing chemokine receptors were established, Cx3cr1 (GFP/GFP) and Ccr2 (RFP/RFP) mice. As Cx3cr1 is expressed in microglia and Ccr2 is reportedly expressed in activated macrophages, these mice have the potential to distinguish microglia and macrophages, yielding novel information about the activation of these inflammatory cells and their individual roles in retinal inflammation. In this study, c-mer proto-oncogene tyrosine kinase (Mertk) (-/-) mice, which show photoreceptor cell death due to defective retinal pigment epithelium phagocytosis, were employed as an animal model of RD. Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice were established by breeding Mertk (-/-) , Cx3cr1 (GFP/GFP) , and Ccr2 (RFP/RFP) mice. The retinal morphology and pattern of inflammatory cell activation and invasion of Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice were evaluated using retina and retinal pigment epithelium (RPE) flat mounts, retinal sections, and flow cytometry. Four-week-old Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice showed Cx3cr1-GFP-positive microglia in the inner retina. Cx3cr1-GFP and Ccr2-RFP dual positive activated microglia were observed in the outer retina and subretinal space of 6- and 8-week-old animals. Ccr2-RFP single positive bone marrow-derived macrophages were observed to migrate into the retina of Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice. These invading cells were still observed in the

  19. Association of TGFβ1, TNFα, CCR2 and CCR5 gene polymorphisms in type-2 diabetes and renal insufficiency among Asian Indians

    Directory of Open Access Journals (Sweden)

    Gupta Arvind

    2007-04-01

    Full Text Available Abstract Background Cytokines play an important role in the development of diabetic chronic renal insufficiency (CRI. Transforming growth factor β1 (TGF β1 induces renal hypertrophy and fibrosis, and cytokines like tumor necrosis factor-alpha (TNFα, chemoattractant protein-1 (MCP-1, and regulated upon activation and normal T cell expressed and secreted (RANTES mediate macrophage infiltration into kidney. Over expression of these chemokines leads to glomerulosclerosis and interstitial fibrosis. The effect of MCP-1 and RANTES on kidney is conferred by their receptors i.e., chemokine receptor (CCR-2 and CCR-5 respectively. We tested association of nine single nucleotide polymorphisms (SNPs from TGFβ1, TNFα, CCR2 and CCR5 genes among individuals with type-2 diabetes with and without renal insufficiency. Methods Type-2 diabetes subjects with chronic renal insufficiency (serum creatinine ≥ 3.0 mg/dl constituted the cases, and matched individuals with diabetes of duration ≥ 10 years and normoalbuminuria were evaluated as controls from four centres in India. Allelic and genotypic contributions of nine SNPs from TGFβ1, TNFα, CCR2 and CCR5 genes to diabetic CRI were tested by computing odds ratio (OR and 95% confidence intervals (CI. Sub-analysis of CRI cases diabetic retinopathy status as dependent variable and SNP genotypes as independent variable in a univariate logistic regression was also performed. Results SNPs Tyr81His and Thr263Ile in TGF β1 gene were monomorphic, and Arg25Pro in TGF β1 gene and Δ32 polymorphism in CCR5 gene were minor variants (minor allele frequency A SNP of CCR5 gene has been observed and the allele 59029A seems to confer predisposition to development of diabetic CRI (OR 1.39; CI 1.04–1.84. In CRI subjects a compound group of genotypes "GA and AA" of SNP G>A -800 was found to confer predisposition for proliferative retinopathy (OR 3.03; CI 1.08–8.50, p = 0.035. Conclusion Of the various cytokine gene

  20. Evaluation of data quality at the National Cancer Registry of Ukraine.

    Science.gov (United States)

    Ryzhov, Anton; Bray, Freddie; Ferlay, Jacques; Fedorenko, Zoya; Goulak, Liudmyla; Gorokh, Yevgeniy; Soumkina, Olena; Znaor, Ariana

    2018-04-01

    Cancer notification has been mandatory in Ukraine since 1953, with the National Cancer Registry of Ukraine (NCRU) established in 1996. The aim of this study was to provide a comprehensive evaluation of the data quality at the NCRU. Qualitative and semi-quantitative methods were used to assess the comparability, completeness, validity and timeliness of cancer incidence data from the NCRU for the period 2002-2012. Cancer registration procedures at the NCRU are in accordance with international standards and recommendations. Semi-quantitative methods suggested the NCRU's data was reasonably complete, although decreases in age-specific incidence and mortality rates in the elderly indicated some missing cases at older ages. The proportion of microscopically-verified cases increased from 73.6% in 2002 to 82.3% in 2012, with death-certificate-only (DCO) proportions stable at around 0.1% and unknown stage recorded in 9.6% of male and 7.5% of female solid tumours. Timeliness was considered acceptable, with reporting >99% complete within a turn-around time of 15 months. While timely reporting of national data reflects the advantages of a mandatory data collection system, a low DCO% and observed age-specific declines suggest possible underreporting of incidence and mortality data, particularly at older ages. Overall, the evaluation indicates that the data are reasonably comparable and thus may be used to describe the magnitude of the cancer burden in Ukraine. Given its central role in monitoring and evaluation of cancer control activities, ensuring the sustainability of NCRU operations throughout the process of healthcare system reform is of utmost importance. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. National Trends and Predictors of Androgen Deprivation Therapy Use in Low-Risk Prostate Cancer.

    Science.gov (United States)

    Yang, David D; Muralidhar, Vinayak; Mahal, Brandon A; Labe, Shelby A; Nezolosky, Michelle D; Vastola, Marie E; King, Martin T; Martin, Neil E; Orio, Peter F; Choueiri, Toni K; Trinh, Quoc-Dien; Spratt, Daniel E; Hoffman, Karen E; Feng, Felix Y; Nguyen, Paul L

    2017-06-01

    Androgen deprivation therapy (ADT) is not recommended for low-risk prostate cancer because of its lack of benefit and potential for harm. We evaluated the incidence and predictors of ADT use in low-risk disease. Using the National Cancer Database, we identified 197,957 patients with low-risk prostate cancer (Gleason score of 3 + 3 = 6, prostate-specific antigen level used multiple logistic regression to evaluate predictors of ADT use and Cox regression to examine its association with all-cause mortality. Overall ADT use decreased from 17.6% in 2004 to 3.5% in 2012. In 2012, 11.5% of low-risk brachytherapy patients and 7.6% of external beam radiation therapy patients received ADT. Among 82,352 irradiation-managed patients, predictors of ADT use included treatment in a community versus academic cancer program (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.50-1.71; Puse versus external beam radiation therapy (AOR, 1.32; 95% CI, 1.27-1.37; Puse included a Charlson-Deyo comorbidity score of ≥2 versus 0 (AOR, 1.42; 95% CI, 1.06-1.91; P=.018); treatment in a community versus academic cancer program (AOR, 1.61; 95% CI, 1.37-1.90; Puse was associated with increased all-cause mortality in patients who did not receive local therapy (adjusted hazard ratio, 1.28; 95% CI, 1.14-1.43; Puse in low-risk prostate cancer has declined nationally but may remain an issue of concern in certain populations and regions. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Clinical auditing as an instrument for quality improvement in breast cancer care in the Netherlands : The national NABON Breast Cancer Audit

    NARCIS (Netherlands)

    van Bommel, Annelotte C.M.; Spronk, Pauline E.R.; Vrancken Peeters, Marie-Jeanne T.F.D.; Jager, Agnes; Lobbes, Marc; Maduro, John H.; Mureau, Marc A.M.; Schreuder, Kay; Smorenburg, Carolien; Verloop, Janneke; Westenend, Pieter J.; Wouters, Michel W.J.M.; Siesling, Sabine; Tjan-Heijnen, Vivianne C.G.; van Dalen, Thijs

    2017-01-01

    Background In 2011, the NABON Breast Cancer Audit (NBCA) was instituted as a nation-wide audit to address quality of breast cancer care and guideline adherence in the Netherlands. The development of the NBCA and the results of 4 years of auditing are described. Methods Clinical and pathological

  3. Australia's National Bowel Cancer Screening Program: does it work for Indigenous Australians?

    Directory of Open Access Journals (Sweden)

    Katzenellenbogen Judith M

    2010-06-01

    Full Text Available Abstract Background Despite a lower incidence of bowel cancer overall, Indigenous Australians are more likely to be diagnosed at an advanced stage when prognosis is poor. Bowel cancer screening is an effective means of reducing incidence and mortality from bowel cancer through early identification and prompt treatment. In 2006, Australia began rolling out a population-based National Bowel Cancer Screening Program (NBCSP using the Faecal Occult Blood Test. Initial evaluation of the program revealed substantial disparities in bowel cancer screening uptake with Indigenous Australians significantly less likely to participate in screening than the non-Indigenous population. This paper critically reviews characteristics of the program which may contribute to the discrepancy in screening uptake, and includes an analysis of organisational, structural, and socio-cultural barriers that play a part in the poorer participation of Indigenous and other disadvantaged and minority groups. Methods A search was undertaken of peer-reviewed journal articles, government reports, and other grey literature using electronic databases and citation snowballing. Articles were critically evaluated for relevance to themes that addressed the research questions. Results The NBCSP is not reaching many Indigenous Australians in the target group, with factors contributing to sub-optimal participation including how participants are selected, the way the screening kit is distributed, the nature of the test and comprehensiveness of its contents, cultural perceptions of cancer and prevailing low levels of knowledge and awareness of bowel cancer and the importance of screening. Conclusions Our findings suggest that the population-based approach to implementing bowel cancer screening to the Australian population unintentionally excludes vulnerable minorities, particularly Indigenous and other culturally and linguistically diverse groups. This potentially contributes to exacerbating

  4. Lumboaortic radiotherapy in patients with cervical cancer. Experience of the National Cancer Institute

    International Nuclear Information System (INIS)

    Santini B, Alejandro; Becerra S, Sergio; Gayan G, Patricio; Carcamo I, Marcela; Bianchi G, Benjamin

    2010-01-01

    Background: Uterine cancer is still a prevalent disease in Chile. Is common to treat patients with tumors in stages IIB and IIIB where the risk of pelvic and paraortic limph node involvement is very high. Its treatment is radio-chemotherapy. Objective: To present a retrospective analysis of patients that suffered cervix-uterine cancer who were treated with radiotherapy including the aortic-lumbar area. Methods: From the revision of patients who were treated of cervix-uterine cancer between the years 1995 and 2007, 39 were treated including aortic-lumbar chains. Evolution and toxicity were analyzed. Two radiotherapy techniques were used. The first one, during the nineties, included two parallel previous and later and opposed fields, and a second technique, currently used, where pelvis and paraortic are radiated at the same time through four lateral (AP-PA) fields. Results: The dosimeter analysis of both techniques shows that there is a higher volume of radiated normal tissue with the two fields techniques, mainly in the small bowel. On the other hand, the toxicity was significantly different being today's technique less toxic and showing low gastrointestinal

  5. 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

  6. Breast cancer in the elderly

    African Journals Online (AJOL)

    JhfBK: A I'ccr-mvicw Journal of liiomeclical Scicnccs. July 2002, Vol. 1 No. 1 pp 33-42. Breast cancer in the elderly. ABSTRACT. Between Janua~y 1997 and December 2001,107 patients were admitted and treated for breast cancer at the University of Benin Teaching Hospital, Nigeria. Of these, 27. (25.2%) were aged 60 ...

  7. The coreceptor mutation CCR5Δ32 influences the dynamics of HIV epidemics and is selected for by HIV

    OpenAIRE

    Sullivan, Amy D.; Wigginton, Janis; Kirschner, Denise

    2001-01-01

    We explore the impact of a host genetic factor on heterosexual HIV epidemics by using a deterministic mathematical model. A protective allele unequally distributed across populations is exemplified in our models by the 32-bp deletion in the host-cell chemokine receptor CCR5, CCR5Δ32. Individuals homozygous for CCR5Δ32 are protected against HIV infection whereas those heterozygous for CCR5Δ32 have lower pre-AIDS viral loads and delayed progression to AIDS. CCR5Δ32 may limit HIV spread by decre...

  8. CCR5 susceptibility to ligand-mediated down-modulation differs between human T lymphocytes and myeloid cells

    OpenAIRE

    Fox, James M.; Kasprowicz, Richard; Hartley, Oliver; Signoret, Nathalie

    2015-01-01

    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. Howeve...

  9. Effects of chemokine receptor signalling on cognition-like, emotion-like and sociability behaviours of CCR6 and CCR7 knockout mice.

    Science.gov (United States)

    Jaehne, E J; Baune, B T

    2014-03-15

    Inflammation is regarded as an important mechanism of neuropsychiatric disorders. Chemokines, which are a part of the immune system, have effects on various aspects of brain function, but little is known about their effects on behaviour. We have compared the cognition-like behaviour (learning and spatial memory) of CCR6(-/-) and CCR7(-/-) mice with wild type (WT) C57BL/6 mice, in the Barnes maze, as well as a range of other behaviours, including exploratory, anxiety and depression-like behaviour, using a battery of tests. Levels of cytokines TNF-α, IL-1β and IL-6 were also measured. In the Barnes maze, CCR7(-/-) mice were shown to take longer to learn the location of the escape box on the 1st of 4 days of training. In the behavioural battery, CCR6(-/-) mice showed higher locomotor activity and lower anxiety in the open field test, and a lack of preference for social novelty in a sociability test. CCR7(-/-) mice behaved much like WT mice, although showed higher anxiety in Elevated Zero Maze. While baseline saccharin preference in a 2-bottle choice test, a test for anhedonia depression-like behaviour, was equal in all strains at baseline, weekly tests showed that both CCR6(-/-) and CCR7(-/-) mice developed a decreased preference for saccharin compared to WT over time. There were no differences between strains in any of the cytokines measured. These results suggest that chemokine receptors may play a role in cognition and learning behaviour, as well as anxiety and other behaviours, although the biological mechanisms are still unclear. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. CCR5 down-regulates osteoclast function in orthodontic tooth movement.

    Science.gov (United States)

    Andrade, I; Taddei, S R A; Garlet, G P; Garlet, T P; Teixeira, A L; Silva, T A; Teixeira, M M

    2009-11-01

    During orthodontic tooth movement, there is local production of chemokines and an influx of leukocytes into the periodontium. CCL5 plays an important role in osteoclast recruitment and activation. This study aimed to investigate whether the CCR5-receptor influences these events and, consequently, orthodontic tooth movement. An orthodontic appliance was placed in wild-type mice (WT) and CCR5-deficient mice (CCR5(-/-)). The expression of mediators involved in bone remodeling was evaluated in periodontal tissues by Real-time PCR. The number of TRAP-positive osteoclasts and the expression of cathepsin K, RANKL, and MMP13 were significantly higher in CCR5(-/-). Meanwhile, the expression of two osteoblastic differentiation markers, RUNX2 and osteocalcin, and that of bone resorption regulators, IL-10 and OPG, were lower in CCR5(-/-). Analysis of the data also showed that CCR5(-/-) exhibited a greater amount of tooth movement after 7 days of mechanical loading. The results suggested that CCR5 might be a down-regulator of alveolar bone resorption during orthodontic movement.

  11. Molecular recognition of CCR5 by an HIV-1 gp120 V3 loop.

    Science.gov (United States)

    Tamamis, Phanourios; Floudas, Christodoulos A

    2014-01-01

    The binding of protein HIV-1 gp120 to coreceptors CCR5 or CXCR4 is a key step of the HIV-1 entry to the host cell, and is predominantly mediated through the V3 loop fragment of HIV-1 gp120. In the present work, we delineate the molecular recognition of chemokine receptor CCR5 by a dual tropic HIV-1 gp120 V3 loop, using a comprehensive set of computational tools predominantly based on molecular dynamics simulations and free energy calculations. We report, what is to our knowledge, the first complete HIV-1 gp120 V3 loop : CCR5 complex structure, which includes the whole V3 loop and the N-terminus of CCR5, and exhibits exceptional agreement with previous experimental findings. The computationally derived structure sheds light into the functional role of HIV-1 gp120 V3 loop and CCR5 residues associated with the HIV-1 coreceptor activity, and provides insights into the HIV-1 coreceptor selectivity and the blocking mechanism of HIV-1 gp120 by maraviroc. By comparing the binding of the specific dual tropic HIV-1 gp120 V3 loop with CCR5 and CXCR4, we observe that the HIV-1 gp120 V3 loop residues 13-21, which include the tip, share nearly identical structural and energetic properties in complex with both coreceptors. This result paves the way for the design of dual CCR5/CXCR4 targeted peptides as novel potential anti-AIDS therapeutics.

  12. 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. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. 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.

  14. Nanotechnology: Emerging Developments and Early Detection of Cancer. A Two-Day Workshop Sponsored by the National Cancer Institute and the National Institute of Standards and Technology, August 30–31 2001, on the National Institute of Standards and Technology Campus, Gaithersburg, MD, USA

    Science.gov (United States)

    Zullo, Steven J.; Srivastava, Sudhir; Looney, J. Patrick; Barker, Peter E.

    2002-01-01

    A recent meeting jointly sponsored by the National Cancer Institute (NCI) and National Institute of Standards and Technology (NIST) brought together researchers active in nanotechnology and cancer molecular biology to discuss and evaluate the interface between disciplines. Emerging areas where nanotechnologies may impact cancer prevention and early cancer detection were elaborated by key researchers who catalyzed interdisciplinary dialogue aimed at fostering cross-discipline communications and future collaboration. PMID:12590168

  15. [Single nucleotide polymorphisms of HIV coreceptor CCR5 gene in Chinese Yi ethnic group and its association with HIV infection].

    Science.gov (United States)

    Ma, Li-ying; Hong, Kun-xue; Lu, Xiao-zhi; Qin, Guang-ming; Chen, Jian-ping; Chen, Kang-lin; Ruan, Yu-hua; Xing, Hui; Zhu, Jia-hong; Shao, Yi-ming

    2005-11-30

    To investigate the single nucleotide polymorphism (SNP) of HIV-1 coreceptor CCR5 gene in Chinese Yi ethnic group and the association between these SNPs and HIV/AIDS. Peripheral blood samples of 102 HIV negative persons of Chinese Yi nationality, 87 males amd 15 females, aged 23 (12-37), and 68 HIV carriers, 61 males and 7 females, aged 27 (17-51). The regulatory and structural regions of the HIV coreceptor CCR5 gene were amplified from the genomic DNA by nested PCR, each of the two regions was divided into three gene fragments which were overlapped. High throughput DHPLC was used for screening of unknown mutations in each gene fragment. The PCR products showing different peak traces from wild types in DHPLC were sequenced by forward and reverse primers respectively. The sequences were analyzed with the help of Sequence Navigator software to search for SNP loci. Statistical analysis by SPSS and PPAP softwares were made to study the association between these SNPs and HIV infection. Five SNPs (A77G, G316A, T532C, C921T, and G668A) and a AGA deletion of the 686-688 nucleotides were discovered in the coding region of this gene in Chinese Yi ethnic group. C921T mutation was a nonsense mutation, and the other SNPs (A77G, G316A, T532C, and G668A) are sense mutation, with the amino acid changes of K26R, G106R, C178R, and R223Q. Only the frequency of R223Q allelic gene was high (0.08) but those of the others were low (less than 0.01). There was no significant difference in the allele frequency between the HIV negative and HIV positive groups (all P > 0.05). Five SNP loci (T58934G, G59029A, T59353C, G59402A, and C59653T) were found in the regulatory region of CCR5 gene with high allelic frequencies of 0.1912-0.2941. Between the HIV negative and HIV positive groups, there were no differences in the SNP loc (all P > 0.05). Statistical analysis of the association between the linkage of mutation loci with HIV infection suggested a significant difference in the haplotype frequency

  16. Flow Cytometry Scientist | Center for Cancer Research

    Science.gov (United States)

    The Basic Science Program (BSP) pursues independent, multidisciplinary research in basic and applied molecular biology, immunology, retrovirology, cancer biology, and human genetics. Research efforts and support are an integral part of the Center for Cancer Research (CCR) at the Frederick National Laboratory for Cancer Research (FNLCR). KEY ROLES/RESPONSIBILITIES The Flow Cytometry Core (Flow Core) in the Cancer and Inflammation Program (CIP) is a service core which supports the research efforts of the CCR by providing expertise in the field of flow cytometry (fluorescence cell sorting) with the goal of gaining a more thorough understanding of the biology of the immune system, cancer, and inflammation processes. The Flow Core provides service to 12-15 CIP laboratories and more than 22 non-CIP laboratories. Flow core staff provide technical advice on the experimental design of applications, which include immunological phenotyping, cell function assays, and cell cycle analysis. Work is performed per customer requirements, and no independent research is involved. Flow Cytometry Scientist - The individual will be responsible for: Daily management of the Flow Cytometry Core, to include the supervision and guidance of technical staff members Monitor performance of and maintain high-dimensional flow cytometer analyzers and cell sorters Operate high-dimensional flow cytometer analyzers and cell sorters Provide scientific expertise to the user community and facilitate the development of cutting-edge technologies Interact with Flow Core users and customers, and provide technical and scientific advice, and guidance regarding their experiments, including possible collaborations Train staff and scientific end users on the use of flow cytometry in their research, as well as teach them how to operate and troubleshoot the bench-top analyzer instruments Prepare and deliver lectures, as well as one-on-one training sessions, with customers/users Ensure that protocols are up

  17. 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.

  18. Variation in primary site resection practices for advanced colon cancer: a study using the National Cancer Data Base.

    Science.gov (United States)

    Healy, Mark A; Pradarelli, Jason C; Krell, Robert W; Regenbogen, Scott E; Suwanabol, Pasithorn A

    2016-10-01

    Treatment of metastatic colon cancer may be driven as much by practice patterns as by features of disease. To optimize management, there is a need to better understand what is determining primary site resection use. We evaluated all patients with stage IV cancers in the National Cancer Data Base from 2002 to 2012 (50,791 patients, 1,230 hospitals). We first identified patient characteristics associated with primary tumor resection. Then, we assessed nationwide variation in hospital resection rates. Overall, 27,387 (53.9%) patients underwent primary site resection. Factors associated with resection included younger age, having less than 2 major comorbidities, and white race (P < .001). Nationwide, hospital-adjusted primary tumor resection rates ranged from 26.0% to 87.8% with broad differences across geographical areas and hospital accreditation types. There is statistically significant variation in hospital rates of primary site resection. This demonstrates inconsistent adherence to guidelines in the presence of conflicting evidence regarding resection benefit. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Epigenetic control of Ccr7 expression in distinct lineages of lung dendritic cells.

    Science.gov (United States)

    Moran, Timothy P; Nakano, Hideki; Kondilis-Mangum, Hrisavgi D; Wade, Paul A; Cook, Donald N

    2014-11-15

    Adaptive immune responses to inhaled allergens are induced following CCR7-dependent migration of precursor of dendritic cell (pre-DC)-derived conventional DCs (cDCs) from the lung to regional lymph nodes. However, monocyte-derived (moDCs) in the lung express very low levels of Ccr7 and consequently do not migrate efficiently to LN. To investigate the molecular mechanisms that underlie this dichotomy, we studied epigenetic modifications at the Ccr7 locus of murine cDCs and moDCs. When expanded from bone marrow precursors, moDCs were enriched at the Ccr7 locus for trimethylation of histone 3 lysine 27 (H3K27me3), a modification associated with transcriptional repression. Similarly, moDCs prepared from the lung also displayed increased levels of H3K27me3 at the Ccr7 promoter compared with migratory cDCs from that organ. Analysis of DC progenitors revealed that epigenetic modification of Ccr7 does not occur early during DC lineage commitment because monocytes and pre-DCs both had low levels of Ccr7-associated H3K27me3. Rather, Ccr7 is gradually silenced during the differentiation of monocytes to moDCs. Thus, epigenetic modifications of the Ccr7 locus control the migration and therefore the function of DCs in vivo. These findings suggest that manipulating epigenetic mechanisms might be a novel approach to control DC migration and thereby improve DC-based vaccines and treat inflammatory diseases of the lung. Copyright © 2014 by The American Association of Immunologists, Inc.

  20. 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.

  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. Quantum continual measurements and a posteriori collapse on CCR

    International Nuclear Information System (INIS)

    Belavkin, V.P.

    1992-01-01

    A quantum stochastic model for the Markovian dynamics of an open system under the nondemolition unsharp observation which is continuous in time, is given. A stochastic equation for the posterior evolution of a quantum continuously observed system is derived and the spontaneous collapse (stochastically continuous reduction of the wave packet) is described. The quantum Langevin evolution equation is solved for the case of a quasi-free Hamiltonian in the initial CCR algebra with a linear output channel, and the posterior dynamics corresponding to an initial Gaussian state is found. It is shown for an example of the posterior dynamics of a quantum oscillator that any mixed state under a complete nondemolition measurement collapses exponentially to a pure Gaussian one. (orig.)

  3. Reimbursements and frequency of tests in privately insured testicular cancer patients in the United States: Implications to national guidelines

    Directory of Open Access Journals (Sweden)

    Mohamed H Kamel

    2017-01-01

    Conclusions: Testicular cancer is not an inexpensive disease. Surgery is the less utilized than radiation and chemotherapy despite lower cost. This may have implications to national guidelines and training since these treatments often carry the same grade of recommendation.

  4. 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.

  5. National Cancer Database Analysis of Proton Versus Photon Radiation Therapy in Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Higgins, Kristin A., E-mail: kristin.higgins@emory.edu [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); O' Connell, Kelli [Rollins School of Public Health, Emory University, Atlanta, Georgia (United States); Liu, Yuan [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Rollins School of Public Health, Emory University, Atlanta, Georgia (United States); Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia (United States); Gillespie, Theresa W. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Surgery, Emory University, Atlanta, Georgia (United States); McDonald, Mark W. [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Pillai, Rathi N. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia (United States); Patel, Kirtesh R.; Patel, Pretesh R. [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Robinson, Clifford G. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); Simone, Charles B. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Owonikoko, Taofeek K. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia (United States); Belani, Chandra P. [Penn State Hershey Cancer Institute, Pennsylvania University, Hershey, Pennsylvania (United States); and others

    2017-01-01

    Purpose: To analyze outcomes and predictors associated with proton radiation therapy for non-small cell lung cancer (NSCLC) in the National Cancer Database. Methods and Materials: The National Cancer Database was queried to capture patients with stage I-IV NSCLC treated with thoracic radiation from 2004 to 2012. A logistic regression model was used to determine the predictors for utilization of proton radiation therapy. The univariate and multivariable association with overall survival were assessed by Cox proportional hazards models along with log–rank tests. A propensity score matching method was implemented to balance baseline covariates and eliminate selection bias. Results: A total of 243,822 patients (photon radiation therapy: 243,474; proton radiation therapy: 348) were included in the analysis. Patients in a ZIP code with a median income of <$46,000 per year were less likely to receive proton treatment, with the income cohort of $30,000 to $35,999 least likely to receive proton therapy (odds ratio 0.63 [95% confidence interval (CI) 0.44-0.90]; P=.011). On multivariate analysis of all patients, non-proton therapy was associated with significantly worse survival compared with proton therapy (hazard ratio 1.21 [95% CI 1.06-1.39]; P<.01). On propensity matched analysis, proton radiation therapy (n=309) was associated with better 5-year overall survival compared with non-proton radiation therapy (n=1549), 22% versus 16% (P=.025). For stage II and III patients, non-proton radiation therapy was associated with worse survival compared with proton radiation therapy (hazard ratio 1.35 [95% CI 1.10-1.64], P<.01). Conclusions: Thoracic radiation with protons is associated with better survival in this retrospective analysis; further validation in the randomized setting is needed to account for any imbalances in patient characteristics, including positron emission tomography–computed tomography staging.

  6. Clinical–Pathologic Stage Discrepancy in Bladder Cancer Patients Treated With Radical Cystectomy: Results From the National Cancer Data Base

    Energy Technology Data Exchange (ETDEWEB)

    Gray, Phillip J. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Lin, Chun Chieh; Jemal, Ahmedin [Surveillance and Health Services Research Program, American Cancer Society, Atlanta, Georgia (United States); Shipley, William U. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Fedewa, Stacey A. [Surveillance and Health Services Research Program, American Cancer Society, Atlanta, Georgia (United States); Kibel, Adam S. [Division of Urology, Brigham and Women' s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Rosenberg, Jonathan E. [Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kamat, Ashish M. [Division of Surgery, Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Virgo, Katherine S. [Department of Health Policy and Management, Emory University, Atlanta, Georgia (United States); Blute, Michael L. [Department of Urology, Massachusetts General Hospital, Boston, Massachusetts (United States); Zietman, Anthony L. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Efstathiou, Jason A., E-mail: jefstathiou@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2014-04-01

    Purpose: To examine the accuracy of clinical staging and its effects on outcome in bladder cancer (BC) patients treated with radical cystectomy (RC), using a large national database. Methods and Materials: A total of 16,953 patients with BC without distant metastases treated with RC from 1998 to 2009 were analyzed. Factors associated with clinical–pathologic stage discrepancy were assessed by multivariate generalized estimating equation models. Survival analysis was conducted for patients treated between 1998 and 2004 (n=7270) using the Kaplan-Meier method and Cox proportional hazards models. Results: At RC 41.9% of patients were upstaged, whereas 5.9% were downstaged. Upstaging was more common in females, the elderly, and in patients who underwent a more extensive lymphadenectomy. Downstaging was less common in patients treated at community centers, in the elderly, and in Hispanics. Receipt of preoperative chemotherapy was highly associated with downstaging. Five-year overall survival rates for patients with clinical stages 0, I, II, III, and IV were 67.2%, 62.9%, 50.4%, 36.9%, and 27.2%, respectively, whereas those for the same pathologic stages were 70.8%, 75.8%, 63.7%, 41.5%, and 24.7%, respectively. On multivariate analysis, upstaging was associated with increased 5-year mortality (hazard ratio [HR] 1.80, P<.001), but downstaging was not associated with survival (HR 0.88, P=.160). In contrast, more extensive lymphadenectomy was associated with decreased 5-year mortality (HR 0.76 for ≥10 lymph nodes examined, P<.001), as was treatment at an National Cancer Institute–designated cancer center (HR 0.90, P=.042). Conclusions: Clinical–pathologic stage discrepancy in BC patients is remarkably common across the United States. These findings should be considered when selecting patients for preoperative or nonoperative management strategies and when comparing the outcomes of bladder sparing approaches to RC.

  7. Variation in Definitive Therapy for Localized Non-Small Cell Lung Cancer Among National Comprehensive Cancer Network Institutions

    Energy Technology Data Exchange (ETDEWEB)

    Valle, Luca F. [Geisel School of Medicine at Dartmouth College, Dartmouth College, Hanover, New Hampshire (United States); Jagsi, Reshma [Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan (United States); Bobiak, Sarah N.; Zornosa, Carrie [National Comprehensive Cancer Network, Fort Washington, Pennsylvania (United States); D' Amico, Thomas A. [Department of Surgery, Division of Thoracic Surgery, Duke Cancer Institute, Durham, North Carolina (United States); Pisters, Katherine M. [Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dexter, Elisabeth U. [Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, New York (United States); Niland, Joyce C. [Department of Information Sciences, City of Hope Comprehensive Cancer Center, Duarte, California (United States); Hayman, James A. [Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan (United States); Kapadia, Nirav S., E-mail: Nirav.S.Kapadia@hitchcock.org [Department of Radiation Oncology, Dartmouth-Hitchcock Norris Cotton Cancer Center, Lebanon, New Hampshire (United States); Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire (United States)

    2016-02-01

    Purpose: This study determined practice patterns in the staging and treatment of patients with stage I non-small cell lung cancer (NSCLC) among National Comprehensive Cancer Network (NCCN) member institutions. Secondary aims were to determine trends in the use of definitive therapy, predictors of treatment type, and acute adverse events associated with primary modalities of treatment. Methods and Materials: Data from the National Comprehensive Cancer Network Oncology Outcomes Database from 2007 to 2011 for US patients with stage I NSCLC were used. Main outcome measures included patterns of care, predictors of treatment, acute morbidity, and acute mortality. Results: Seventy-nine percent of patients received surgery, 16% received definitive radiation therapy (RT), and 3% were not treated. Seventy-four percent of the RT patients received stereotactic body RT (SBRT), and the remainder received nonstereotactic RT (NSRT). Among participating NCCN member institutions, the number of surgeries-to-RT course ratios varied between 1.6 and 34.7 (P<.01), and the SBRT-to-NSRT ratio varied between 0 and 13 (P=.01). Significant variations were also observed in staging practices, with brain imaging 0.33 (0.25-0.43) times as likely and mediastinoscopy 31.26 (21.84-44.76) times more likely for surgical patients than for RT patients. Toxicity rates for surgical and for SBRT patients were similar, although the rates were double for NSRT patients. Conclusions: The variations in treatment observed among NCCN institutions reflects the lack of level I evidence directing the use of surgery or SBRT for stage I NSCLC. In this setting, research of patient and physician preferences may help to guide future decision making.

  8. Internalization of the chemokine receptor CCR4 can be evoked by orthosteric and allosteric receptor antagonists

    OpenAIRE

    Ajram, Laura; Begg, Malcolm; Slack, Robert; Cryan, Jenni; Hall, David; Hodgson, Simon; Ford, Alison; Barnes, Ashley; Swieboda, Dawid; Mousnier, Aurelie; Solari, Roberto

    2014-01-01

    The chemokine receptor CCR4 has at least two natural agonist ligands, MDC (CCL22) and TARC (CCL17) which bind to the same orthosteric site with a similar affinity. Both ligands are known to evoke chemotaxis of CCR4-bearing T cells and also elicit CCR4 receptor internalization. A series of small molecule allosteric antagonists have been described which displace the agonist ligand, and inhibit chemotaxis. The aim of this study was to determine which cellular coupling pathways are involved in in...

  9. A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo

    DEFF Research Database (Denmark)

    Motley, Michael P; Madsen, Daniel H; Jürgensen, Henrik J

    2016-01-01

    cellular endocytosis and lysosomal targeting, revealing a novel intracellular pathway for extravascular fibrin degradation. A C-C chemokine receptor type 2 (CCR2)-positive macrophage subpopulation constituted the majority of fibrin-uptaking cells. Consequently, cellular fibrin uptake was diminished...... by elimination of CCR2-expressing cells. The CCR2-positive macrophage subtype was different from collagen-internalizing M2-like macrophages. Cellular fibrin uptake was strictly dependent on plasminogen and plasminogen activator. Surprisingly, however, fibrin endocytosis was unimpeded by the absence of the fibrin...

  10. 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...... 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...

  11. Synergistic combinations of the CCR5 inhibitor VCH-286 with other classes of HIV-1 inhibitors.

    Science.gov (United States)

    Asin-Milan, Odalis; Sylla, Mohamed; El-Far, Mohamed; Belanger-Jasmin, Geneviève; Haidara, Alpha; Blackburn, Julie; Chamberland, Annie; Tremblay, Cécile L

    2014-12-01

    Here, we evaluated the in vitro anti-HIV-1 activity of the experimental CCR5 inhibitor VCH-286 as a single agent or in combination with various classes of HIV-1 inhibitors. Although VCH-286 used alone had highly inhibitory activity, paired combinations with different drug classes led to synergistic or additive interactions. However, combinations with other CCR5 inhibitors led to effects ranging from synergy to antagonism. We suggest that caution should be exercised when combining CCR5 inhibitors in vivo. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  12. 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

  13. Gene-environment interactions in cancer epidemiology: a National Cancer Institute Think Tank report.

    Science.gov (United States)

    Hutter, Carolyn M; Mechanic, Leah E; Chatterjee, Nilanjan; Kraft, Peter; Gillanders, Elizabeth M

    2013-11-01

    Cancer risk is determined by a complex interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified hundreds of common (minor allele frequency [MAF] > 0.05) and less common (0.01 Think Tank" on January 10-11, 2012. The objective of the Think Tank was to facilitate discussions on (1) the state of the science, (2) the goals of G × E interaction studies in cancer epidemiology, and (3) opportunities for developing novel study designs and analysis tools. This report summarizes the Think Tank discussion, with a focus on contemporary approaches to the analysis of G × E interactions. Selecting the appropriate methods requires first identifying the relevant scientific question and rationale, with an important distinction made between analyses aiming to characterize the joint effects of putative or established genetic and environmental factors and analyses aiming to discover novel risk factors or novel interaction effects. Other discussion items include measurement error, statistical power, significance, and replication. Additional designs, exposure assessments, and analytical approaches need to be considered as we move from the current small number of success stories to a fuller understanding of the interplay of genetic and environmental factors. © 2013 WILEY PERIODICALS, INC.

  14. New National Cryo-EM Facility Provides Access to Cutting-Edge Technology for Cancer Research Community | FNLCR

    Science.gov (United States)

    Cancer researchers nationwide now have access to the latest technology in the field of cryo-electron microscopy (cryo-EM)—the study of protein structures at atomic resolution—at the Frederick National Lab for Cancer Research. The emerging technol

  15. Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis.

    Science.gov (United States)

    Bregar, Amy J; Alejandro Rauh-Hain, J; Spencer, Ryan; Clemmer, Joel T; Schorge, John O; Rice, Laurel W; Del Carmen, Marcela G

    2017-04-01

    To examine patterns of care and survival for Hispanic women compared to white and African American women with high-grade endometrial cancer. We utilized the National Cancer Data Base (NCDB) to identify women diagnosed with uterine grade 3 endometrioid adenocarcinoma, carcinosarcoma, clear cell carcinoma and papillary serous carcinoma between 2003 and 2011. The effect of treatment on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. 43,950 women were eligible. African American and Hispanic women had higher rates of stage III and IV disease compared to white women (36.5% vs. 36% vs. 33.5%, p<0.001). African American women were less likely to undergo surgical treatment for their cancer (85.2% vs. 89.8% vs. 87.5%, p<0.001) and were more likely to receive chemotherapy (36.8% vs. 32.4% vs. 32%, p<0.001) compared to white and Hispanic women. Over the entire study period, after adjusting for age, time period of diagnosis, region of the country, urban or rural setting, treating facility type, socioeconomic status, education, insurance, comorbidity index, pathologic stage, histology, lymphadenectomy and adjuvant treatment, African American women had lower overall survival compared to white women (Hazard Ratio 1.21, 95% CI 1.16-1.26). Conversely, Hispanic women had improved overall survival compared to white women after controlling for the aforementioned factors (HR 0.87, 95% CI 0.80-0.93). Among women with high-grade endometrial cancer, African American women have lower all-cause survival while Hispanic women have higher all-cause survival compared to white women after controlling for treatment, sociodemographic, comorbidity and histopathologic variables. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Reaching and treating Spanish-speaking smokers through the National Cancer Institute's Cancer Information Service. A randomized controlled trial.

    Science.gov (United States)

    Wetter, David W; Mazas, Carlos; Daza, Patricia; Nguyen, Lynne; Fouladi, Rachel T; Li, Yisheng; Cofta-Woerpel, Ludmila

    2007-01-15

    Although the prevalence of smoking is lower among Hispanics than among the general population, smoking still levies a heavy public health burden on this underserved group. The current study, Adiós al Fumar (Goodbye to Smoking), was designed to increase the reach of the Spanish-language smoking cessation counseling service provided by the National Cancer Institute's Cancer Information Service (CIS) and to evaluate the efficacy of a culturally sensitive, proactive, behavioral treatment program among Spanish-speaking smokers. Adiós was a 2-group randomized clinical trial evaluating a telephone-based smoking cessation intervention. Spanish-speaking smokers (N = 297) were randomized to receive either standard counseling or enhanced counseling (EC). Paid media was used to increase the reach of the Spanish-language smoking cessation services offered by the CIS. The Adiós sample was of very low socioeconomic status (SES), and more than 90% were immigrants. Calls to the CIS requesting smoking cessation help in Spanish increased from 0.39 calls to 17.8 calls per month. The unadjusted effect of EC only approached significance (OR = 2.4, P = .077), but became significant after controlling for demographic and tobacco-related variables (OR = 3.8, P = .048). Adiós al Fumar demonstrated that it is possible to reach, retain, and deliver an adequate dose of treatment to a very low SES population that has traditionally been viewed as difficult to reach and hard to follow. Moreover, the findings suggest that a proactive, telephone-counseling program, based on the Treating Tobacco Use and Dependence Clinical Practice Guideline and adapted to be culturally appropriate for Hispanics, is effective. Cancer 2007. (c) 2006 American Cancer Society.

  17. Working to Eliminate Cancer Health Disparities from Tobacco: A Review of the National Cancer Institute’s Community Networks Program

    Science.gov (United States)

    Fagan, Pebbles; Cooper, Leslie; Canto, Maria; Carroll, William; Foster-Bey, John; Hébert, James R.; Lopez-Class, Maria; Ma, Grace X.; Nez Henderson, Patricia; Pérez-Stable, Eliseo J.; Santos, LorrieAnn; Smith, Justin H.; Tan, Yin; Tsoh, Janice; Chu, Kenneth

    2015-01-01

    Introduction: In 2005, the National Cancer Institute funded the Community Networks Program (CNP), which aimed to reduce cancer health disparities in minority racial/ethnic and underserved groups through community-based participatory research, education, and training. The purpose of this study was to describe the CNP model and their tobacco-related work in community-based research, education, and training using a tobacco disparities research framework. Methods: We conducted a comprehensive review of the CNP tobacco-related activities including publications, published abstracts, research activities, trainee pilot studies, policy-related activities, educational outreach, and reports produced from 2005–2009. Two authors categorized the tobacco-related activities and publications within the framework. Results: Although there was no mandate to address tobacco, the CNPs produced 103 tobacco-related peer-reviewed publications, which reflects the largest proportion (12%) of all CNP cancer-related publications. Selected publications and research activities were most numerous under the framework areas “Psychosocial Research,” “Surveillance,” “Epidemiology,” and “Treatment of Nicotine Addiction.” Thirteen CNPs participated in tobacco control policymaking in mainstream efforts that affected their local community and populations, and 24 CNPs conducted 1147 tobacco-related educational outreach activities. CNP activities that aimed to build research and infrastructure capacity included nine tobacco-related pilot projects representing 16% of all CNP cancer-related pilot projects, and 17 publications acknowledging leveraged partnerships with other organizations, a strategy encouraged by the CNP. Conclusions: The CNP is a promising academic-community model for working to eliminate tobacco-related health disparities. Future efforts may address scientific gaps, consider collaboration across groups, assess the extent of operationalizing community-based participatory

  18. Staphylococcus aureus Leukocidin LukED and HIV-1 gp120 Target Different Sequence Determinants on CCR5.

    Science.gov (United States)

    Tam, Kayan; Schultz, Megan; Reyes-Robles, Tamara; Vanwalscappel, Bénédicte; Horton, Joshua; Alonzo, Francis; Wu, Beili; Landau, Nathaniel R; Torres, Victor J

    2016-12-13

    Leukocidin ED (LukED) is a bicomponent pore-forming toxin produced by Staphylococcus aureus that lyses host cells by targeting the chemokine receptors CC chemokine receptor type 5 (CCR5), CXCR1, CXCR2, and DARC. In addition to its role as a receptor for LukED, CCR5 is the major coreceptor for primary isolates of human immunodeficiency virus type 1 (HIV-1) and has been extensively studied. To compare how LukED and HIV-1 target CCR5, we analyzed their respective abilities to use CCR5/CCR2b chimeras to mediate cytotoxicity and virus entry. These analyses showed that the second and third extracellular loops (ECL) of CCR5 are necessary and sufficient for LukED to target the receptor and promote cell lysis. In contrast, the second ECL of CCR5 is necessary but not sufficient for HIV-1 infectivity. The analysis of CCR5 point mutations showed that glycine-163 is critical for HIV-1 infectivity, while arginine-274 and aspartic acid-276 are critical for LukED cytotoxicity. Point mutations in ECL2 diminished both HIV-1 infectivity and LukED cytotoxicity. Treatment of cells with LukED did not interfere with CCR5-tropic HIV-1 infectivity, demonstrating that LukED and the viral envelope glycoprotein use nonoverlapping sites on CCR5. Analysis of point mutations in LukE showed that amino acids 64 to 69 in the rim domain are required for CCR5 targeting and cytotoxicity. Taking the results together, this study identified the molecular basis by which LukED targets CCR5, highlighting the divergent molecular interactions evolved by HIV-1 and LukED to interact with CCR5. The bicomponent pore-forming toxins are thought to play a vital role in the success of Staphylococcus aureus as a mammalian pathogen. One of the leukocidins, LukED, is necessary and sufficient for lethality in mice. At the molecular level, LukED causes cell lysis through binding to specific cellular receptors. CCR5 is one of the receptors targeted by LukED and is the major coreceptor for CCR5-tropic HIV-1. While the

  19. Annulus fibrosus cells express and utilize C-C chemokine receptor 5 (CCR5) for migration.

    Science.gov (United States)

    Liu, Weijun; Liu, David; Zheng, Justin; Shi, Peng; Chou, Po-Hsin; Oh, Chundo; Chen, Di; An, Howard S; Chee, Ana

    2017-05-01

    Disc degeneration is associated with the progressive loss of the proteoglycan content of the intervertebral disc, decreased matrix synthesis, higher concentrations of proteolytic enzymes, and increased levels of proinflammatory cytokines. In previous studies, we have shown that C-C chemokine ligand (CCL)2, CCL3, and CCL5 are highly expressed by cultured nucleus pulposus (NP) and annulus fibrosus (AF) cells that have been treated by interleukin-1. The major function of these chemokines is to recruit immune cells into the disc. It is unclear if disc cells can respond to these chemokines. Recent studies by Phillips et al. (2015) showed that NP cells express a number of cytokines and chemokine receptors. The purpose of this study is to determine the gene and protein expression of C-C chemokine receptor (CCR)1, CCR2, and CCR5 in NP and AF cells, and to test if these receptors can respond to their ligands in these cells by cell signaling and migration. This is an in vitro study. For RNA, surface expression, and cell signaling studies, human cells were isolated from the NP and AF tissues collected after spine surgery or from donated spine segments (Gift of Hope Human Donor & Tissue Network of Illinois) and cultured in monolayer. The gene expression of human CCR1, CCR2, and CCR5 was analyzed using real-time polymerase chain reaction. The surface expression of CCR1, CCR2, and CCR5 was analyzed using flow cytometry and fluorescently tagged antibodies specific for these proteins. Extracellular signal-regulated kinase (ERK) phosphorylation was analyzed from the cell lysates of NP and AF cells treated with CCL2 and CCL5 for 1 hour using enzyme-linked immunosorbent assay. Migration of primary rabbit AF cells was assayed using 8-µm Corning Transwell inserts in the presence or absence of CCL5. This study was partially funded by a North American Spine Society 2014 Basic Research Grant Award ($50,000). RNA analysis showed that gene expression of CCR1, CCR2, and CCR5 was evident in

  20. Racial Differences in Information Needs During and After Cancer Treatment: a Nationwide, Longitudinal Survey by the University of Rochester Cancer Center National Cancer Institute Community Oncology Research Program.

    Science.gov (United States)

    Asare, Matthew; Peppone, Luke J; Roscoe, Joseph A; Kleckner, Ian R; Mustian, Karen M; Heckler, Charles E; Guido, Joseph J; Sborov, Mark; Bushunow, Peter; Onitilo, Adedayo; Kamen, Charles

    2018-02-01

    Before treatment, cancer patients need information about side effects and prognosis, while after treatment they need information to transition to survivorship. Research documenting these needs is limited, especially among racial and ethnic minorities. This study evaluated cancer patients' needs according to race both before and after treatment. We compared white (n = 904) to black (n = 52) patients receiving treatment at 17 National Cancer Institute Community Oncology Research Program (NCORP) sites on their cancer-related concerns and need for information before and after cancer treatment. Two-sample t test and chi-squared analyses were used to assess group differences. Compared to white patients, black patients reported significantly higher concerns about diet (44.3 vs. 25.4 %,) and exercise (40.4 vs. 19.7 %,) during the course of treatment. Compared to whites, blacks also had significantly higher concern about treatment-related issues (white vs. black mean, 25.52 vs. 31.78), self-image issues (7.03 vs. 8.60), family-related issues (10.44 vs. 12.84), and financial concerns (6.42 vs. 8.90, all p information needs regarding follow-up tests (8.17 vs. 9.44), stress management (4.12 vs. 4.89), and handling stigma after cancer treatment (4.21 vs. 4.89) [all p information needs differed by race, with black patients reporting greater information needs and concerns. In clinical practice, tailored approaches may work particularly well in addressing the needs and concerns of black patients.

  1. Apples and pears? A comparison of two sources of national lung cancer audit data in England

    Directory of Open Access Journals (Sweden)

    Aamir Khakwani

    2017-07-01

    Full Text Available In 2014, the method of data collection from NHS trusts in England for the National Lung Cancer Audit (NLCA was changed from a bespoke dataset called LUCADA (Lung Cancer Data. Under the new contract, data are submitted via the Cancer Outcome and Service Dataset (COSD system and linked additional cancer registry datasets. In 2014, trusts were given opportunity to submit LUCADA data as well as registry data. 132 NHS trusts submitted LUCADA data, and all 151 trusts submitted COSD data. This transitional year therefore provided the opportunity to compare both datasets for data completeness and reliability. We linked the two datasets at the patient level to assess the completeness of key patient and treatment variables. We also assessed the interdata agreement of these variables using Cohen's kappa statistic, κ. We identified 26 001 patients in both datasets. Overall, the recording of sex, age, performance status and stage had more than 90% agreement between datasets, but there were more patients with missing performance status in the registry dataset. Although levels of agreement for surgery, chemotherapy and external-beam radiotherapy were high between datasets, the new COSD system identified more instances of active treatment. There seems to be a high agreement of data between the datasets, and the findings suggest that the registry dataset coupled with COSD provides a richer dataset than LUCADA. However, it lagged behind LUCADA in performance status recording, which needs to improve over time.

  2. 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.

  3. Chemokine CCL2 and chemokine receptor CCR2 in early active multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Ransohoff, R M; Strieter, R M

    2004-01-01

    The chemokine monocyte chemoattractant protein (MCP)-1/CCL2 and its receptor CCR2 have been strongly implicated in disease pathogenesis in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS), whereas data on the CCL2-CCR2 axis are scarce in MS. We studied...... the expression of CCR2 on leukocytes in blood and cerebrospinal fluid (CSF) from patients with monosymptomatic optic neuritis and MS, and the concentration of CCL2 in the CSF from these patients. Results were compared with the results in non-inflammatory neurological controls and were correlated with other...... parameters (magnetic resonance imaging and CSF data). Our findings suggest a limited role for CCL2/CCR2 in early active MS....

  4. Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5

    DEFF Research Database (Denmark)

    Berg, Christian; Spiess, Katja; von Lüttichau, Hans Rudolf

    2016-01-01

    Since the discovery of HIV's use of CCR5 as the primary coreceptor in fusion, the focus on developing small-molecule receptor antagonists for inhibition hereof has only resulted in one single drug, Maraviroc. We therefore investigated the possibility of using small-molecule CCR5 agonists as HIV-1...... fusion inhibitors. A virus-free cell-based fusion reporter assay, based on mixing "effector cells" (expressing HIV Env and luciferase activator) with "target cells" (expressing CD4, CCR5 wild type or a selection of well-described mutations, and luciferase reporter), was used as fusion readout. Receptor...... expression was evaluated by ELISA and fluorescence microscopy. On CCR5 WT, Maraviroc and Aplaviroc inhibited fusion with high potencies (EC 50 values of 91 and 501 nM, respectively), whereas removal of key residues for both antagonists (Glu283Ala) or Maraviroc alone (Tyr251Ala) prevented fusion inhibition...

  5. [Novel echogenic needle for ultrasound-guided peripheral nerve block "Hakko type CCR"].

    Science.gov (United States)

    Takayama, Wataru; Yasumura, Rie; Kaneko, Takehiko; Kobayashi, Yoshiro; Kamada, Takaaki; Yoshikawa, Tamotsu; Aoyama, Yasuhiko

    2009-04-01

    A novel echogenic insulated nerve block needle (CCR-needle: Echogenic Needle Type CCR; Hakko, Japan) is commercially available since 2006 in Japan. This needle has three echogenic dimples, namely corner cube reflectors (CCR) on its tip. The CCR-needle will potentially provide a significant advantage for detecting the needle tip. In this report, we firstly evaluated this new disposable echogenic needle in simulation phantom, and demonstrated improved visibility of the needle tip. Afterwards, an interscalene brachial plexus block was performed on a male patient undergoing shoulder surgery. The needle insertion procedure was the "out of plane" ultrasound-guided technique using simultaneous electrical nerve stimulation. The surgery was successfully conducted without any complications.

  6. Study progress of CCR3 in wet age-related macular degeneration

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    Xian-Wei Wu

    2014-03-01

    Full Text Available According to the study, chemokine receptor 3(CCR3in the eye is mainly distributed in retinal pigment epithelial cells, and also expressed in the choroidal vascular endothelial cells(CECs. The specificity of CCR3's high expression in wet age-related macular degeneration(AMDwas found, and it is proved that in wet-AMD patients, it plays an important role in the formation of choroidal neovascularization(CNV. In this paper, the structure, function, the problem of current research and the future direction of CCR3 were summarized. It is believed that with the further research on CCR3, it will not only help us to find a new method of wet-AMD diagnosis and treatment, but also may provide an important reference for other CNV disease research and new anti-CNV drugs.

  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 as a natural and modulated target for inhibition of HIV.

    Science.gov (United States)

    Burke, Bryan P; Boyd, Maureen P; Impey, Helen; Breton, Louis R; Bartlett, Jeffrey S; Symonds, Geoff P; Hütter, Gero

    2013-12-30

    Human immunodeficiency virus type 1 (HIV-1) infection of target cells requires CD4 and a co-receptor, predominantly the chemokine receptor CCR5. CCR5-delta32 homozygosity results in a truncated protein providing natural protection against HIV infection-this without detrimental effects to the host-and transplantation of CCR5-delta32 stem cells in a patient with HIV ("Berlin patient") achieved viral eradication. As a more feasible approach gene-modification strategies are being developed to engineer cellular resistance to HIV using autologous cells. We have developed a dual therapeutic anti-HIV lentiviral vector (LVsh5/C46) that down-regulates CCR5 and inhibits HIV-1 fusion via cell surface expression of the gp41-derived peptide, C46. This construct, effective against multiple strains of both R5- and X4-tropic HIV-1, is being tested in Phase I/II trials by engineering HIV-resistant hematopoietic cells.

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

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    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.

  10. CCR5 limits cortical viral loads during West Nile virus infection of the central nervous system.

    Science.gov (United States)

    Durrant, Douglas M; Daniels, Brian P; Pasieka, TracyJo; Dorsey, Denise; Klein, Robyn S

    2015-12-15

    Cell-mediated immunity is critical for clearance of central nervous system (CNS) infection with the encephalitic flavivirus, West Nile virus (WNV). Prior studies from our laboratory have shown that WNV-infected neurons express chemoattractants that mediate recruitment of antiviral leukocytes into the CNS. Although the chemokine receptor, CCR5, has been shown to play an important role in CNS host defense during WNV infection, regional effects of its activity within the infected brain have not been defined. We used CCR5-deficient mice and an established murine model of WNV encephalitis to determine whether CCR5 activity impacts on WNV levels within the CNS in a region-specific fashion. Statistical comparisons between groups were made with one- or two-way analysis of variance; Bonferroni's post hoc test was subsequently used to compare individual means. Survival was analyzed by the log-rank test. Analyses were conducted using Prism software (GraphPad Prism). All data were expressed as means ± SEM. Differences were considered significant if P ≤ 0.05. As previously shown, lack of CCR5 activity led to increased symptomatic disease and mortality in mice after subcutaneous infection with WNV. Evaluation of viral burden in the footpad, draining lymph nodes, spleen, olfactory bulb, and cerebellum derived from WNV-infected wild-type, and CCR5(-/-) mice showed no differences between the genotypes. In contrast, WNV-infected, CCR5(-/-) mice exhibited significantly increased viral burden in cortical tissues, including the hippocampus, at day 8 post-infection. CNS regional studies of chemokine expression via luminex analysis revealed significantly increased expression of CCR5 ligands, CCL4 and CCL5, within the cortices of WNV-infected, CCR5(-/-) mice compared with those of similarly infected WT animals. Cortical elevations in viral loads and CCR5 ligands in WNV-infected, CCR5(-/-) mice, however, were associated with decreased numbers of infiltrating mononuclear cells

  11. Sunitinib treatment in patients with advanced renal cell cancer: the Brazilian National Cancer Institute (INCA experience

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    Rafael Corrêa Coelho

    Full Text Available ABSTRACT Purpose: The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC treated by the Brazilian Unified Health System (SUS at a single reference institution. Material and Methods: Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. Results: Fifty-eight patients were eligible. Most patients were male 41 (71%, with a median age of 58 years. Nephrectomy was performed in 41 (71% patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2% patients. In 50 patients (86%, sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%, hypothyroidism (43%, mucositis (33% and diarrhea (29%. Grade 3 and 4 adverse effects were infrequent: fatigue (12%, hypertension (12%, thrombocytopenia (7%, neutropenia (5% and hand-foot syndrome (5%. Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. Conclusion: Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS.

  12. 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

    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. Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. 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. 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. Copyright© by the International Brazilian Journal of Urology.

  13. Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe)

    Science.gov (United States)

    Häggström, Christel; Liedberg, Fredrik; Hagberg, Oskar; Aljabery, Firas; Ströck, Viveka; Hosseini, Abolfazl; Gårdmark, Truls; Sherif, Amir; Malmström, Per-Uno; Garmo, Hans; Jahnson, Staffan; Holmberg, Lars

    2017-01-01

    Purpose To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe). Participants The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death. Findings to date Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival. Future plans The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding

  14. CCR7 expressing mesenchymal stem cells potently inhibit graft-versus-host disease by spoiling the fourth supplemental Billingham's tenet.

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    Hong Li

    Full Text Available The clinical acute graft-versus-host disease (GvHD-therapy of mesenchymal stem cells (MSCs is not as satisfactory as expected. Secondary lymphoid organs (SLOs are the major niches serve to initiate immune responses or induce tolerance. Our previous study showed that CCR7 guide murine MSC line C3H10T1/2 migrating to SLOs. In this study, CCR7 gene was engineered into murine MSCs by lentivirus transfection system (MSCs/CCR7. The immunomodulatory mechanism of MSCs/CCR7 was further investigated. Provoked by inflammatory cytokines, MSCs/CCR7 increased the secretion of nitric oxide and calmed down the T cell immune response in vitro. Immunofluorescent staining results showed that transfused MSCs/CCR7 can migrate to and relocate at the appropriate T cell-rich zones within SLOs in vivo. MSCs/CCR7 displayed enhanced effect in prolonging the survival and alleviating the clinical scores of the GvHD mice than normal MSCs. Owing to the critical relocation sites, MSCs/CCR7 co-infusion potently made the T cells in SLOs more naïve like, thus control T cells trafficking from SLOs to the target organs. Through spoiling the fourth supplemental Billingham's tenet, MSCs/CCR7 potently inhibited the development of GvHD. The study here provides a novel therapeutic strategy of MSCs/CCR7 infusion at a low dosage to give potent immunomodulatory effect for clinical immune disease therapy.

  15. Concordance of CCR5 Genotypes that Influence Cell-Mediated Immunity and HIV-1 Disease Progression Rates

    Science.gov (United States)

    Catano, Gabriel; Chykarenko, Zoya A.; Mangano, Andrea; Anaya, J-M; Smith, Alison; Bologna, Rosa; Sen, Luisa; Clark, Robert A.; Lloyd, Andrew; Shostakovich-Koretskaya, Ludmila

    2011-01-01

    We used cutaneous delayed-type hypersensitivity responses, a powerful in vivo measure of cell-mediated immunity, to evaluate the relationships among cell-mediated immunity, AIDS, and polymorphisms in CCR5, the HIV-1 coreceptor. There was high concordance between CCR5 polymorphisms and haplotype pairs that influenced delayed-type hypersensitivity responses in healthy persons and HIV disease progression. In the cohorts examined, CCR5 genotypes containing -2459G/G (HHA/HHA, HHA/HHC, HHC/HHC) or -2459A/A (HHE/HHE) associated with salutary or detrimental delayed-type hypersensitivity and AIDS phenotypes, respectively. Accordingly, the CCR5-Δ32 allele, when paired with non-Δ32-bearing haplotypes that correlate with low (HHA, HHC) versus high (HHE) CCR5 transcriptional activity, associates with disease retardation or acceleration, respectively. Thus, the associations of CCR5-Δ32 heterozygosity partly reflect the effect of the non-▵32 haplotype in a background of CCR5 haploinsufficiency. The correlations of increased delayed-type hypersensitivity with -2459G/G-containing CCR5 genotypes, reduced CCR5 expression, decreased viral replication, and disease retardation suggest that CCR5 may influence HIV infection and AIDS, at least in part, through effects on cell-mediated immunity. PMID:21288827

  16. Haplotypes in CCR5-CCR2, CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort.

    Science.gov (United States)

    Vega, Jorge A; Villegas-Ospina, Simón; Aguilar-Jiménez, Wbeimar; Rugeles, María T; Bedoya, Gabriel; Zapata, Wildeman

    2017-06-01

    Variants in genes encoding for HIV-1 co-receptors and their natural ligands have been individually associated to natural resistance to HIV-1 infection. However, the simultaneous presence of these variants has been poorly studied. To evaluate the association of single and multilocus haplotypes in genes coding for the viral co-receptors CCR5 and CCR2, and their ligands CCL3 and CCL5, with resistance or susceptibility to HIV-1 infection. Nine variants in CCR5-CCR2, two SNPs in CCL3 and two in CCL5 were genotyped by PCR-RFLP in 35 seropositive (cases) and 49 HIV-1-exposed seronegative Colombian individuals (controls). Haplotypes were inferred using the Arlequin software, and their frequency in individual or combined loci was compared between cases and controls by the chi-square test. A p' value ;0.05 after Bonferroni correction was considered significant. Homozygosis of the human haplogroup (HH) E was absent in controls and frequent in cases, showing a tendency to susceptibility. The haplotypes C-C and T-T in CCL3 were associated with susceptibility (p'=0.016) and resistance (p';0.0001) to HIV-1 infection, respectively. Finally, in multilocus analysis, the haplotype combinations formed by HHC in CCR5-CCR2, T-T in CCL3 and G-C in CCL5 were associated with resistance (p'=0.006). Our results suggest that specific combinations of variants in genes from the same signaling pathway can define an HIV-1 resistant phenotype. Despite our small sample size, our statistically significant associations suggest strong effects; however, these results should be further validated in larger cohorts.

  17. Internalization of the chemokine receptor CCR4 can be evoked by orthosteric and allosteric receptor antagonists.

    Science.gov (United States)

    Ajram, Laura; Begg, Malcolm; Slack, Robert; Cryan, Jenni; Hall, David; Hodgson, Simon; Ford, Alison; Barnes, Ashley; Swieboda, Dawid; Mousnier, Aurelie; Solari, Roberto

    2014-04-15

    The chemokine receptor CCR4 has at least two natural agonist ligands, MDC (CCL22) and TARC (CCL17) which bind to the same orthosteric site with a similar affinity. Both ligands are known to evoke chemotaxis of CCR4-bearing T cells and also elicit CCR4 receptor internalization. A series of small molecule allosteric antagonists have been described which displace the agonist ligand, and inhibit chemotaxis. The aim of this study was to determine which cellular coupling pathways are involved in internalization, and if antagonists binding to the CCR4 receptor could themselves evoke receptor internalization. CCL22 binding coupled CCR4 efficiently to β-arrestin and stimulated GTPγS binding however CCL17 did not couple to β-arrestin and only partially stimulated GTPγS binding. CCL22 potently induced internalization of almost all cell surface CCR4, while CCL17 showed only weak effects. We describe four small molecule antagonists that were demonstrated to bind to two distinct allosteric sites on the CCR4 receptor, and while both classes inhibited agonist ligand binding and chemotaxis, one of the allosteric sites also evoked receptor internalization. Furthermore, we also characterize an N-terminally truncated version of CCL22 which acts as a competitive antagonist at the orthosteric site, and surprisingly also evokes receptor internalization without demonstrating any agonist activity. Collectively this study demonstrates that orthosteric and allosteric antagonists of the CCR4 receptor are capable of evoking receptor internalization, providing a novel strategy for drug discovery against this class of target. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  18. CCR5 receptor antagonists: discovery and SAR study of guanylhydrazone derivatives.

    Science.gov (United States)

    Wei, Robert G; Arnaiz, Damian O; Chou, Yuo-Ling; Davey, Dave; Dunning, Laura; Lee, Wheeseong; Lu, Shou-Fu; Onuffer, James; Ye, Bin; Phillips, Gary

    2007-01-01

    High throughput screening (HTS) led to the identification of the guanylhydrazone of 2-(4-chlorobenzyloxy)-5-bromobenzaldehyde as a CCR5 receptor antagonist. Initial modifications of the guanylhydrazone series indicated that substitution of the benzyl group at the para-position was well tolerated. Substitution at the 5-position of the central phenyl ring was critical for potency. Replacement of the guanylhydrazone group led to the discovery of a novel series of CCR5 antagonists.

  19. Ccr2 deletion dissociates cavity size and tau pathology after mild traumatic brain injury.

    Science.gov (United States)

    Gyoneva, Stefka; Kim, Daniel; Katsumoto, Atsuko; Kokiko-Cochran, O Nicole; Lamb, Bruce T; Ransohoff, Richard M

    2015-12-03

    Millions of people experience traumatic brain injury (TBI) as a result of falls, car accidents, sports injury, and blast. TBI has been associated with the development of neurodegenerative conditions such as Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). In the initial hours and days, the pathology of TBI comprises neuronal injury, breakdown of the blood-brain barrier, and inflammation. At the cellular level, the inflammatory reaction consists of responses by brain-resident microglia, astrocytes, and vascular elements as well as infiltration of peripheral cells. After TBI, signaling by chemokine (C-C motif) ligand 2 (CCL2) to the chemokine (C-C motif) receptor 2 (CCR2) is a key regulator of brain infiltration by monocytes. We utilized mice with one or both copies of Ccr2 disrupted by red fluorescent protein (RFP, Ccr2 (RFP/+) and Ccr2 (RFP/RFP) ). We subjected these mice to the mild lateral fluid percussion model of TBI and examined several pathological outcomes 3 days later in order to determine the effects of altered monocyte entry into the brain. Ccr2 deletion reduced monocyte infiltration, diminished lesion cavity volume, and lessened axonal damage after mild TBI, but the microglial reaction to the lesion was not affected. We further examined phosphorylation of the microtubule-associated protein tau, which aggregates in brains of people with TBI, AD, and CTE. Surprisingly, Ccr2 deletion was associated with increased tau mislocalization to the cell body in the cortex and hippocampus by tissue staining and increased levels of phosphorylated tau in the hippocampus by Western blot. Disruption of CCR2 enhanced tau pathology and reduced cavity volume in the context of TBI. The data reveal a complex role for CCR2(+) monocytes in TBI, as monitored by cavity volume, axonal damage, and tau phosphorylation.

  20. Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5.

    Science.gov (United States)

    Berg, Christian; Spiess, Katja; Lüttichau, Hans R; Rosenkilde, Mette M

    2016-12-01

    Since the discovery of HIV's use of CCR5 as the primary coreceptor in fusion, the focus on developing small-molecule receptor antagonists for inhibition hereof has only resulted in one single drug, Maraviroc. We therefore investigated the possibility of using small-molecule CCR5 agonists as HIV-1 fusion inhibitors. A virus-free cell-based fusion reporter assay, based on mixing "effector cells" (expressing HIV Env and luciferase activator) with "target cells" (expressing CD4, CCR5 wild type or a selection of well-described mutations, and luciferase reporter), was used as fusion readout. Receptor expression was evaluated by ELISA and fluorescence microscopy. On CCR5 WT, Maraviroc and Aplaviroc inhibited fusion with high potencies (EC 50 values of 91 and 501 nM, respectively), whereas removal of key residues for both antagonists (Glu283Ala) or Maraviroc alone (Tyr251Ala) prevented fusion inhibition, establishing this assay as suitable for screening of HIV entry inhibitors. Both ligands inhibited HIV fusion on signaling-deficient CCR5 mutations (Tyr244Ala and Trp248Ala). Moreover, the steric hindrance CCR5 mutation (Gly286Phe) impaired fusion, presumably by a direct hindrance of gp120 interaction. Finally, the efficacy switch mutation (Leu203Phe) - converting small-molecule antagonists/inverse agonists to full agonists biased toward G-protein activation - uncovered that also small-molecule agonists can function as direct HIV-1 cell entry inhibitors. Importantly, no agonist-induced receptor internalization was observed for this mutation. Our studies of the pharmacodynamic requirements for HIV-1 fusion inhibitors highlight the possibility of future development of biased ligands with selective targeting of the HIV-CCR5 interaction without interfering with the normal functionality of CCR5.

  1. VEGF-production by CCR2-dependent macrophages contributes to laser-induced choroidal neovascularization.

    Directory of Open Access Journals (Sweden)

    Torsten A Krause

    Full Text Available Age-related macular degeneration (AMD is the most prevalent cause of blindness in the elderly, and its exsudative subtype critically depends on local production of vascular endothelial growth factor A (VEGF. Mononuclear phagocytes, such as macrophages and microglia cells, can produce VEGF. Their precursors, for example monocytes, can be recruited to sites of inflammation by the chemokine receptor CCR2, and this has been proposed to be important in AMD. To investigate the role of macrophages and CCR2 in AMD, we studied intracellular VEGF content in a laser-induced murine model of choroidal neovascularisation. To this end, we established a technique to quantify the VEGF content in cell subsets from the laser-treated retina and choroid separately. 3 days after laser, macrophage numbers and their VEGF content were substantially elevated in the choroid. Macrophage accumulation was CCR2-dependent, indicating recruitment from the circulation. In the retina, microglia cells were the main VEGF+ phagocyte type. A greater proportion of microglia cells contained VEGF after laser, and this was CCR2-independent. On day 6, VEGF-expressing macrophage numbers had already declined, whereas numbers of VEGF+ microglia cells remained increased. Other sources of VEGF detectable by flow cytometry included in dendritic cells and endothelial cells in both retina and choroid, and Müller cells/astrocytes in the retina. However, their VEGF content was not increased after laser. When we analyzed flatmounts of laser-treated eyes, CCR2-deficient mice showed reduced neovascular areas after 2 weeks, but this difference was not evident 3 weeks after laser. In summary, CCR2-dependent influx of macrophages causes a transient VEGF increase in the choroid. However, macrophages augmented choroidal neovascularization only initially, presumably because VEGF production by CCR2-independent eye cells prevailed at later time points. These findings identify macrophages as a relevant source

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

    Science.gov (United States)

    ... Services National Institutes of Health National Cancer Institute What if the tools you need to quit smoking were as easy to find as a cigarette? NCI QuitPal is a free, interactive app for iPhone or iPad that uses proven quit ...

  3. Prevalence of Precancerous Conditions and Gastric Cancer Based upon the National Cancer Screening Program in Korea for 7 Years, Single Center Experience

    Directory of Open Access Journals (Sweden)

    Ji Hyuk Kang

    2015-01-01

    Full Text Available Aims. Gastric cancer is the second most prevalent cancer and the third leading cause of cancer-related deaths in Korea. The National Cancer Screening Program (NCSP has implemented esophagogastroduodenoscopy (EGD biennially for all Koreans starting in their 40s. This study was conducted to estimate the clinical relevance of NCSP through identifying the prevalence of gastric disease, including cancer. Materials and Methods. Data from 40,821 subjects who received the screening EGD in the single center for 7 years were retrospectively investigated. Results. The overall prevalence of nonatrophic/atrophic/metaplastic gastritis, peptic ulcer, adenoma, early gastric cancer (EGC, and advanced gastric cancer (AGC was 44.28%, 27.97%, 14.95%, 0.59%, 0.43%, 0.21%, and 0.09%, respectively. The prevalence of metaplastic gastritis, peptic ulcer, adenoma, EGC, and AGC was significantly higher in men than in women. The prevalence of preneoplastic/neoplastic disease significantly increased with age. Judged from the ratio of EGC to AGC, the proportion of EGC made up to 70% of all cancers. Conclusions. Screening endoscopy starting for people in their 40s should be strongly recommended for the elderly. Through the NCSP, the early detection of gastric cancer might contribute to the decreased mortality rate due to gastric cancer in Korea.

  4. Difference of stage at cancer diagnosis by socioeconomic status for four target cancers of the National Cancer Screening Program in Korea: Results from the Gwangju and Jeonnam cancer registries.

    Science.gov (United States)

    Kweon, Sun-Seog; Kim, Min-Gyeong; Kang, Mi-Ran; Shin, Min-Ho; Choi, Jin-Su

    2017-07-01

    The aim of this study was to evaluate whether stage at cancer diagnosis differed according to patient economic status. A total of 10,528 patients with cancer of the stomach, colorectum, breast, or cervix, which are target organs of the Korean National Cancer Screening Program (NCSP; fully implemented in 2005) were extracted from population-based cancer registries. The patients were classified into four groups based on socioeconomic status (SES), as determined using their National Health Insurance (NHI) monthly premium at the time of cancer diagnosis. Cancer stage at diagnosis was defined as early (in situ/local) or late stage (regional/distant) based on the Surveillance, Epidemiology, and End Results (SEER) summary stage. Multivariable logistic regression analysis was performed to estimate the risk of non-local stage using age, residential area, and community deprivation index as covariates. The lowest SES subjects showed significantly higher risks of being diagnosed at a later stage for stomach, colorectal, and female breast cancer, but not for cervical cancer, compared with the highest SES subjects. The estimated ORs were 1.28 (95% CI, 1.10-1.49), 1.29 (95% CI, 1.03-1.61), and 1.35 (95% CI, 1.02-1.81) in the lowest SES subjects with stomach, colorectal, and breast cancer, respectively. In conclusion, later stage diagnoses of stomach, colon, and female breast cancer are still associated with SES in Korea in the era of the NCSP for the lower SES population. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  5. [The human and economic burden of cancer in France in 2014, based on the Sniiram national database].

    Science.gov (United States)

    Tuppin, Philippe; Pestel, Laurence; Samson, Solène; Cuerq, Anne; Rivière, Sébastien; Tala, Stéphane; Denis, Pierre; Drouin, Jérôme; Gissot, Claude; Gastaldi-Ménager, Christelle; Fagot-Campagna, Anne

    2017-06-01

    The national health insurance information system (Sniiram) can be used to estimate the national medical and economic burden of cancer. This study reports the annual rates, characteristics and expenditure of people reimbursed for cancer. Among 57 million general health scheme beneficiaries (86% of the French population), people managed for cancer were identified using algorithms based on hospital diagnoses and full refund for long-term cancer. The reimbursed costs (euros) related to the cancer, paid off by the health insurance, were estimated. In 2014, 2.491 million people (4.4%) covered by the general health scheme had a cancer managed (men 1.1 million, 5.1%; women 1.3 million, 4.9%). The annual (2012-2014) average growth rate of patients was 0.8%. The spending related to the cancer was 13.5 billion: 5 billion for primary health care (drugs 2.3 billion), 7.5 billion for the hospital (drugs 1.3 billions) and 900 million for sick leave and invalidity pensions. Spending annual average growth rate (2012-2014) was 4% (drugs 2%). The rates of patients and the relative spending were 1.8% and 2.5 billion for the breast cancer (women), 1.5% and 1.0 billion for prostate cancer, 0.9% and 1.5 billion for the colon cancer, and 0.19% and 1.3 billion for lung cancer. Cancers establish one of the first groups of chronic diseases pathologies in terms of patients and spending. If the numbers of patients remain stables, the spending increases, mainly for medicines. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  6. Burden of cancer attributable to tobacco smoking in member countries of the Association of Southeast Asian Nations (ASEAN), 2012.

    Science.gov (United States)

    Kristina, Susi Ari; Endarti, Dwi; Thavorncharoensap, Montarat

    2016-10-01

    Cancer is an increasing problem in ASEAN (Association of Southeast Asian Nations). Tobacco use is a well-established risk factor for many types of cancers. Evidence on burden of cancer attributable to tobacco is essential to raise public and political awareness of the negative effects of tobacco on cancer and to be used to stimulate political action aims at reducing smoking prevalence in ASEAN member countries. The objective of this study was to estimate burden of cancer attributable to tobacco smoking in ASEAN, 2012. In this study, smoking prevalence was combined with Relative Risks (RRs) of cancer to obtain Smoking Attributable Fractions (SAFs). Cancer incidence and mortality data among individuals aged 15 years and older were derived from GLOBOCAN 2012. Fourteen types of cancer were included in the analysis. Sensitivity analyses were conducted to examine the impact of the use of alternative RRs and the use of alternative prevalence of smoking in some countries. The findings showed that tobacco smoking was responsible for 131,502 cancer incidence and 105,830 cancer mortality in ASEAN countries in 2012. In other words, tobacco smoking was accounted for 28.4% (43.3% in male and 8.5% in female) of cancer incidence and 30.5% (44.2% in male and 9.4% in female) of cancer mortality in ASEAN. When looking at the types of cancer, lung cancer showed the strongest association with tobacco smoking. Incidence of cancer and cancer mortality attributable to tobacco smoking varied by countries due to the differences in size of population, background risk of cancer, and prevalence of smoking in each country. According to the sensitivity analyses, RRs of lung cancer, pharynx cancer, and larynx cancer used in the estimates have significant impact on the estimates. As about one-third of cancer incidence and mortality in ASEAN are attributable to tobacco smoking ASEAN member countries are strongly encouraged to put in place stronger tobacco control policies and to strengthen the

  7. Increasing time to treatment initiation for head and neck cancer: an analysis of the National Cancer Database.

    Science.gov (United States)

    Murphy, Colin T; Galloway, Thomas J; Handorf, Elizabeth A; Wang, Lora; Mehra, Ranee; Flieder, Douglas B; Ridge, John A

    2015-04-15

    The objective of this study was to identify trends and predictors of the time to treatment initiation (TTI) for patients with head and neck squamous cell carcinoma (HNSCC). The National Cancer Database (NCDB) was reviewed for the following head and neck cancer sites: oral tongue, oropharynx, larynx, and hypopharynx. TTI was defined as the number of days from diagnosis to the initiation of definitive treatment and was measured according to covariates. Significant differences in the median TTI across each covariate were measured using the Kruskal-Wallis test, and the Spearman test was used to measure trends within covariates. For multivariate analysis, a zero-inflated, negative, binomial regression model was used to estimate the expected TTI, which was expressed in the predicted number of days; and the Vuong test was used to identify the predictors of TTI. In total, 274,630 patients were included. Between 1998 and 2011, the median TTI for all patients was 26 days, and it increased from 19 days to 30 days (P < .0001). Treatment with chemoradiation (CRT) (P < .0001), treatment at academic facilities (P < .0001), and stage IV disease (P < .0001) were associated with increased TTI. TTI significantly increased for each disease stage (P < .0001), treatment modality (P < .0001), and facility type (P < .0001) over time. In addition, patients became more likely to transition care between facilities after diagnosis for treatment initiation (P < .0001) over time. On multivariate analysis, treatment at academic facilities (33 days), transitioning care (37 days), and receipt of CRT (39 days) predicted for a longer TTI. TTI is rising for patients with HNSCC. Those who have advanced-stage disease, receive treatment with CRT, are treated at academic facilities, and who have a transition in care realized the greatest increases in TTI. © 2014 American Cancer Society.

  8. National Trends and Predictors of Androgen Deprivation Therapy Use in Low-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, David D. [Harvard Medical School, Boston, Massachusetts (United States); Muralidhar, Vinayak [Department of Medicine, Harvard Medical School, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Mahal, Brandon A. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Labe, Shelby A.; Nezolosky, Michelle D.; Vastola, Marie E.; King, Martin T.; Martin, Neil E.; Orio, Peter F. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Choueiri, Toni K. [Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Trinh, Quoc-Dien [Division of Urological Surgery, Harvard Medical School, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Spratt, Daniel E. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); University of Michigan, Ann Arbor, Michigan (United States); Hoffman, Karen E. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Feng, Felix Y. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); Departments of Urology & Medicine and Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California (United States); and others

    2017-06-01

    Purpose: Androgen deprivation therapy (ADT) is not recommended for low-risk prostate cancer because of its lack of benefit and potential for harm. We evaluated the incidence and predictors of ADT use in low-risk disease. Methods and Materials: Using the National Cancer Database, we identified 197,957 patients with low-risk prostate cancer (Gleason score of 3 + 3 = 6, prostate-specific antigen level <10 ng/mL, and cT1-T2a) diagnosed from 2004 to 2012 with complete demographic and treatment information. We used multiple logistic regression to evaluate predictors of ADT use and Cox regression to examine its association with all-cause mortality. Results: Overall ADT use decreased from 17.6% in 2004 to 3.5% in 2012. In 2012, 11.5% of low-risk brachytherapy patients and 7.6% of external beam radiation therapy patients received ADT. Among 82,352 irradiation-managed patients, predictors of ADT use included treatment in a community versus academic cancer program (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.50-1.71; P<.001; incidence, 14.0% vs 6.0% in 2012); treatment in the South (AOR, 1.51), Midwest (AOR, 1.81), or Northeast (AOR, 1.90) versus West (P<.001); and brachytherapy use versus external beam radiation therapy (AOR, 1.32; 95% CI, 1.27-1.37; P<.001). Among 25,196 patients who did not receive local therapy, predictors of primary ADT use included a Charlson-Deyo comorbidity score of ≥2 versus 0 (AOR, 1.42; 95% CI, 1.06-1.91; P=.018); treatment in a community versus academic cancer program (AOR, 1.61; 95% CI, 1.37-1.90; P<.001); and treatment in the South (AOR, 1.26), Midwest (AOR, 1.52), or Northeast (AOR, 1.28) versus West (P≤.008). Primary ADT use was associated with increased all-cause mortality in patients who did not receive local therapy (adjusted hazard ratio, 1.28; 95% CI, 1.14-1.43; P<.001) after adjustment for age and comorbidity. Conclusions: ADT use in low-risk prostate cancer has declined nationally but may remain an issue

  9. Functional characterization of CCR in birch (Betula platyphylla × Betula pendula) through overexpression and suppression analysis.

    Science.gov (United States)

    Zhang, Wenbo; Wei, Rui; Chen, Su; Jiang, Jing; Li, Huiyu; Huang, Haijiao; Yang, Guang; Wang, Shuo; Wei, Hairong; Liu, Guifeng

    2015-06-01

    We cloned a Cinnamoyl-CoA Reductase gene (BpCCR1) from an apical meristem and first internode of Betula platyphylla and characterized its functions in lignin biosynthesis, wood formation and tree growth through transgenic approaches. We generated overexpression and suppression transgenic lines and analyzed them in comparison with the wild-type in terms of lignin content, anatomical characteristics, height and biomass. We found that BpCCR1 overexpression could increase lignin content up to 14.6%, and its underexpression decreased lignin content by 6.3%. Surprisingly, modification of BpCCR1 expression led to conspicuous changes in wood characteristics, including xylem vessel number and arrangement, and secondary wall thickness. The growth of transgenic trees in terms of height was also significantly influenced by the modification of BpCCR1 genes. We discuss the functions of BpCCR1 in the context of a phylogenetic tree built with CCR genes from multiple species. © 2014 Scandinavian Plant Physiology Society.

  10. 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.

  11. 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.

  12. Non-small cell lung cancer in young adults: presentation and survival in the English National Lung Cancer Audit.

    Science.gov (United States)

    Rich, A L; Khakwani, A; Free, C M; Tata, L J; Stanley, R A; Peake, M D; Hubbard, R B; Baldwin, D R

    2015-11-01

    Non-small cell lung cancer (NSCLC) in young adults is a rare but devastating illness with significant socioeconomic implications, and studies of this patient subgroup are limited. This study employed the National Lung Cancer Audit to compare the clinical features and survival of young adults with NSCLC with the older age groups. A retrospective cohort review using a validated national audit dataset. Data were analysed for the period between 1 January 2004 and 31 December 2011. Young adults were defined as between 18 and 39 years, and all others were divided into decade age groups, up to the 80 years and above group. We performed logistic and Cox regression analyses to assess clinical outcomes. Of a total of 1 46 422 patients, 651 (0.5%) were young adults, of whom a higher proportion had adenocarcinoma (48%) than in any other age group. Stage distribution of NSCLC was similar across the age groups and 71% of young patients had stage IIIb/IV. Performance status (PS) was 0-1 for 85%. Young adults were more likely to have surgery and chemotherapy compared with the older age groups and had better overall and post-operative survival. The proportion with adenocarcinoma, better PS and that receiving surgery or chemotherapy diminished progressively with advancing decade age groups. In our cohort of young adults with NSCLC, the majority had good PS despite the same late-stage disease as older patients. They were more likely to have treatment and survive longer than older patients. © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. National estimates and correlates of secondhand smoke exposure in US cancer survivors.

    Science.gov (United States)

    Asfar, Taghrid; Arheart, Kristopher L; Koru-Sengul, Tulay; Byrne, Margaret M; Dietz, Noella A; Chen, Charles Jeng; Lee, David J

    2017-08-01

    Cancer survivors comprise a vulnerable population for exposure to secondhand smoke (SHS). This study examined and compared the prevalence, time trends, and predictors of SHS exposure between nonsmoking adult cancer survivors and nonsmoking adults without cancer history (control group). Data were obtained from the 2001-2012 National Health and Nutrition Examination Survey (survivors: n = 2168; controls: n = 19,436). All adults ≥20 years of age who reported not smoking and had a serum cotinine level of 0.015-10 ng/mL were included in the study. Prevalence and 95% confidence intervals, weighted linear regression of prevalence on year for trend analysis, and logistic regression analysis were performed with adjustments made for the complex survey design. Survivors were significantly less likely to be exposed to SHS (65.4 vs. 70.6%, respectively). Exposure over time decreased by 16% (from 67.1% in 2001 to 53.3% in 2012) among survivors and by 24% (from 72% in 2001 to 56% in 2012) among controls. Exposed survivors were more likely to be young (OR = 0.98 [95% CI = 0.97-0.99]), non-Hispanic Black (2.51 [1.49-4.26]), with some college education (2.47 [1.56-3.93]), a high school education (2.72 [1.76-4.19]), less than a high school education (2.49 [1.58-3.91]), and poor (1.80 [1.10-2.96]). Considerable numbers of US cancer survivors are exposed to SHS and exposure disparities persist. More efforts are needed to develop and test population policies and clinical-based interventions targeting cancer survivors.

  14. Results of the FIT-based National Colorectal Cancer Screening Program in Slovenia.

    Science.gov (United States)

    Tepeš, Bojan; Bracko, Matej; Novak Mlakar, Dominika; Stefanovic, Milan; Stabuc, Borut; Frkovic Grazio, Snjezana; Maucec Zakotnik, Jozica

    2017-07-01

    Colorectal cancer (CRC) is one of the most common malignancies in the western world. We aimed to assess the first round of fecal immunochemical test (FIT)-based National CRC screening program (NCSP). In the NCSP conducted in Slovenia, a FIT and colonoscopy for those tested positive was used. The NCSP central unit sent 536,709 invitations to Slovenian residents age 50 to 69 years old between 2009 and 2011. The adherence rate was 56.9% (303,343 participants). FIT was positive in 6.2% (15,310) of the participants (men, 7.8%; women, 5.0%; P<0.01). A total of 13,919 unsedated colonoscopies were performed with the cecal intubation rate of 97.8%. The overall adenoma detection rate was 51.3% [95% confidence interval (CI), 50.5%-52.1%] of which 61.0% (95% CI, 59.9%-62.1%) was in men, and 39.1% (95% CI, 37.8%-40.3%) in women (P<0.01). The mean number of adenoma per positive colonoscopy was 1.94 (95% CI, 1.90-1.97). Adenoma, advanced adenoma, or cancer were found in 7732 (55.5%) colonoscopies. A total of 862 (6.2%) CRC cases were found. Only 161 (18.7%) carcinomas were situated in the right colon. A total of 597 (70.2%) patients with cancer were in the early clinical stages (N, negative; 194 22.8%) of all cancers were cured with only endoscopic resection. In the NCSP, CRC was found in 6.2% of those participants attending colonoscopy, with 81.3% of carcinomas found in the left colon. A localized clinical stage was found in 70.2% participants. In 22.8% of CRC patients, cancer was cured with endoscopic resection only.

  15. 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.

  16. Exploring Knowledge, Attitudes, and Practices Related to Breast and Cervical Cancers in Mongolia: A National Population-Based Survey.

    Science.gov (United States)

    Yerramilli, Pooja; Dugee, Otgonduya; Enkhtuya, Palam; Knaul, Felicia M; Demaio, Alessandro R

    2015-11-01

    Mongolia bears the second-highest cancer burden in the world (5,214 disability-adjusted life years per 100,000 people, age standardized). To determine drivers of the growing burden of noncommunicable diseases, including breast and cervical cancers, a national knowledge, attitudes, and practices (KAP) survey was implemented in 2010. This paper analyzed the results of the 2010 KAP survey, which sampled 3,450 households nationally. Reflecting Mongolian screening policies, women aged 30 and older were included in analyses of questions regarding breast and cervical cancer (n = 1,193). Univariate and multivariate odds ratios (MORs) were derived through logistic regression to determine associations between demographic covariables (residence, age, education, employment) and survey responses. This study found that 25.7% (95% confidence interval [CI]: 23.3-28.3) and 22.1% (95% CI: 19.8-24.5) of female participants aged 30 years or older self-rated their knowledge of breast and cervical cancers, respectively, as "none." Employment and education were associated with greater awareness of both cancers and participation in screening examinations (p migration. Finally, although there is awareness that early detection improves outcomes, a significant proportion of women do not engage in screening. These trends warrant further research on barriers and solutions. The rising burden of breast and cervical cancers, particularly in low- and middle-income countries, necessitates the development of effective strategies for cancer control. This paper examines barriers to health service use in Mongolia, a country with a high cancer burden. The 2010 national knowledge, attitude and practices survey data indicate that cancer control efforts should focus on improving health education among lower-educated, rural, and unemployed populations, who display the least knowledge of breast and cervical cancers. Moreover, the findings support the need to emphasize individual risk for disease in cancer

  17. Five National Cancer Institute-designated cancer centers' data collection on racial/ethnic minority participation in therapeutic trials: a current view and opportunities for improvement.

    Science.gov (United States)

    Hawk, Ernest T; Habermann, Elizabeth B; Ford, Jean G; Wenzel, Jennifer A; Brahmer, Julie R; Chen, Moon S; Jones, Lovell A; Hurd, Thelma C; Rogers, Lisa M; Nguyen, Lynne H; Ahluwalia, Jasjit S; Fouad, Mona; Vickers, Selwyn M

    2014-04-01

    To ensure that National Institutes of Health-funded research is relevant to the population's needs, specific emphasis on proportional representation of minority/sex groups into National Cancer Institute (NCI) cancer centers' clinical research programs is reported to the NCI. EMPaCT investigators at 5 regionally diverse comprehensive cancer centers compared data reported to the NCI for their most recent Cancer Center Support Grant competitive renewal to assess and compare the centers' catchment area designations, data definitions, data elements, collection processes, reporting, and performance regarding proportional representation of race/ethnicity and sex subsets. Cancer centers' catchment area definitions differed widely in terms of their cancer patient versus general population specificity, levels of specificity, and geographic coverage. Racial/ethnic categories were similar, yet were defined differently, across institutions. Patients' socioeconomic status and insurance status were inconsistently captured across the 5 centers. Catchment area definitions and the collection of patient-level demographic factors varied widely across the 5 comprehensive cancer centers. This challenged the assessment of success by cancer centers in accruing representative populations into the cancer research enterprise. Accrual of minorities was less than desired for at least 1 racial/ethnic subcategory at 4 of the 5 centers. Institutions should clearly and consistently declare their primary catchment area and the rationale and should report how race/ethnicity and sex are defined, determined, collected, and reported. More standardized, frequent, consistent collection, reporting, and review of these data are recommended, as is a commitment to collecting socioeconomic data, given that socioeconomic status is a primary driver of cancer disparities in the United States. © 2014 American Cancer Society.

  18. Qualification of National Cancer Institute-Designated Cancer Centers for Quantitative PET/CT Imaging in Clinical Trials.

    Science.gov (United States)

    Scheuermann, Joshua S; Reddin, Janet S; Opanowski, Adam; Kinahan, Paul E; Siegel, Barry A; Shankar, Lalitha K; Karp, Joel S

    2017-07-01

    The National Cancer Institute developed the Centers for Quantitative Imaging Excellence (CQIE) initiative in 2010 to prequalify imaging facilities at all of the National Cancer Institute-designated comprehensive and clinical cancer centers for oncology trials using advanced imaging techniques, including PET. Here we review the CQIE PET/CT scanner qualification process and results in detail. Methods: Over a period of approximately 5 y, sites were requested to submit a variety of phantoms, including uniform and American College of Radiology-approved phantoms, PET/CT images, and examples of clinical images. Submissions were divided into 3 distinct time periods: initial submission (T0) and 2 requalification submissions (T1 and T2). Images were analyzed using standardized procedures, and scanners received a pass or fail designation. Sites had the opportunity to submit new data for scanners that failed. Quantitative results were compared across scanners within a given time period and across time periods for a given scanner. Results: Data from 65 unique PET/CT scanners across 56 sites were submitted for CQIE T0 qualification; 64 scanners passed the qualification. Data from 44 (68%) of those 65 scanners were submitted for T2. From T0 to T2, the percentage of scanners passing the CQIE qualification on the first attempt rose from 38% for T1 to 67% for T2. The most common reasons for failure were SUV outside specifications, incomplete submission, and uniformity issues. Uniform phantom and American College of Radiology-approved phantom results between scanner manufacturers were similar. Conclusion: The results of the CQIE process showed that periodic requalification may decrease the frequency of deficient data submissions. The CQIE project also highlighted the concern within imaging facilities about the burden of maintaining different qualifications and accreditations. Finally, for quantitative imaging-based trials, further evaluation of the relationships between the level of

  19. National Performance Benchmarks for Modern Screening Digital Mammography: Update from the Breast Cancer Surveillance Consortium.

    Science.gov (United States)

    Lehman, Constance D; Arao, Robert F; Sprague, Brian L; Lee, Janie M; Buist, Diana S M; Kerlikowske, Karla; Henderson, Louise M; Onega, Tracy; Tosteson, Anna N A; Rauscher, Garth H; Miglioretti, Diana L

    2017-04-01

    Purpose To establish performance benchmarks for modern screening digital mammography and assess performance trends over time in U.S. community practice. Materials and Methods This HIPAA-compliant, institutional review board-approved study measured the performance of digital screening mammography interpreted by 359 radiologists across 95 facilities in six Breast Cancer Surveillance Consortium (BCSC) registries. The study included 1 682 504 digital screening mammograms performed between 2007 and 2013 in 792 808 women. Performance measures were calculated according to the American College of Radiology Breast Imaging Reporting and Data System, 5th edition, and were compared with published benchmarks by the BCSC, the National Mammography Database, and performance recommendations by expert opinion. Benchmarks were derived from the distribution of performance metrics across radiologists and were presented as 50th (median), 10th, 25th, 75th, and 90th percentiles, with graphic presentations using smoothed curves. Results Mean screening performance measures were as follows: abnormal interpretation rate (AIR), 11.6 (95% confidence interval [CI]: 11.5, 11.6); cancers detected per 1000 screens, or cancer detection rate (CDR), 5.1 (95% CI: 5.0, 5.2); sensitivity, 86.9% (95% CI: 86.3%, 87.6%); specificity, 88.9% (95% CI: 88.8%, 88.9%); false-negative rate per 1000 screens, 0.8 (95% CI: 0.7, 0.8); positive predictive value (PPV) 1, 4.4% (95% CI: 4.3%, 4.5%); PPV2, 25.6% (95% CI: 25.1%, 26.1%); PPV3, 28.6% (95% CI: 28.0%, 29.3%); cancers stage 0 or 1, 76.9%; minimal cancers, 57.7%; and node-negative invasive cancers, 79.4%. Recommended CDRs were achieved by 92.1% of radiologists in community practice, and 97.1% achieved recommended ranges for sensitivity. Only 59.0% of radiologists achieved recommended AIRs, and only 63.0% achieved recommended levels of specificity. Conclusion The majority of radiologists in the BCSC surpass cancer detection recommendations for screening

  20. Cancer risk and all-cause mortality among Norwegian military United Nations peacekeepers deployed to Kosovo between 1999 and 2011.

    Science.gov (United States)

    Strand, Leif Aage; Martinsen, Jan Ivar; Borud, Einar Kristian

    2014-08-01

    Media reports of leukaemia and other cancers among European United Nations (UN) peacekeepers who served in the Balkans, and a scientific finding of excess Hodgkin lymphoma among Italian UN peacekeepers who served in Bosnia, suggested a link between cancer incidence and depleted uranium (DU) exposure. This spurred several studies on cancer risk among UN peacekeepers who served in the Balkans. Although these studies turned out to be negative, the debate about possible cancers and other health risks caused by DU exposure continues. The aim of the present study was to investigate cancer incidence and all-cause mortality in a cohort of 6076 (4.4% women) Norwegian military UN peacekeepers deployed to Kosovo between 1999 and 2011. The cohort was followed for cancer incidence and mortality from 1999 to 2011. Standardised incidence ratios for cancer (SIR) and mortality ratios (SMR) were calculated from national rates. Sixty-nine cancer cases and 38 deaths were observed during follow-up. Cancer incidence in the cohort was similar to that in the general Norwegian population. No cancers in the overall cohort significantly exceeded incidence rates in the general Norwegian population, but there was an elevated SIR for melanoma of skin in men of 1.90 (95% confidence interval [CI] 0.95-3.40). A fivefold increased incidence of bladder cancer was observed among men who served in Kosovo for ≥ 1 year, based on 2 excess cases (SIR=5.27; 95% CI 1.09-15.4). All-cause mortality was half the expected rate (SMR=0.49; 95% CI 0.35-0.67). Our study did not support the suggestion that UN peacekeeping service in Kosovo is associated with increased cancer risk. Copyright © 2014 Elsevier Ltd. All rights reserved.