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Sample records for adjuvant endocrine treatment

  1. Subjective cognitive complaints one year after ceasing adjuvant endocrine treatment for early-stage breast cancer

    PubMed Central

    Ribi, K; Aldridge, J; Phillips, K-A; Thompson, A; Harvey, V; Thürlimann, B; Cardoso, F; Pagani, O; Coates, A S; Goldhirsch, A; Price, K N; Gelber, R D; Bernhard, J

    2012-01-01

    Background: In the BIG 1-98 trial objective cognitive function improved in postmenopausal women 1 year after cessation of adjuvant endocrine therapy for breast cancer. This report evaluates changes in subjective cognitive function (SCF). Methods: One hundred postmenopausal women, randomised to receive 5 years of adjuvant tamoxifen, letrozole, or a sequence of the two, completed self-reported measures on SCF, psychological distress, fatigue, and quality of life during the fifth year of trial treatment (year 5) and 1 year after treatment completion (year 6). Changes between years 5 and 6 were evaluated using the Wilcoxon signed-rank test. Subjective cognitive function and its correlates were explored. Results: Subjective cognitive function and the other patient-reported outcomes did not change significantly after cessation of endocrine therapy with the exception of improvement for hot flushes (P=0.0005). No difference in changes was found between women taking tamoxifen or letrozole. Subjective cognitive function was the only psychosocial outcome with a substantial correlation between year 5 and 6 (Spearman's R=0.80). Correlations between SCF and the other patient-reported outcomes were generally low. Conclusion: Improved objective cognitive function but not SCF occur following cessation of adjuvant endocrine therapy in the BIG 1-98 trial. The substantial correlation of SCF scores over time may represent a stable attribute. PMID:22531635

  2. Controversies of adjuvant endocrine treatment for breast cancer and recommendations of the 2007 St Gallen conference.

    PubMed

    Rabaglio, Manuela; Aebi, Stefan; Castiglione-Gertsch, Monica

    2007-10-01

    Endocrine treatment for breast cancer was introduced more than a century ago. The discovery of hormone receptors has allowed targeting of endocrine treatment to patients whose primary tumours express these receptors. In the adjuvant setting, different approaches are used in premenopausal or postmenopausal women. In premenopausal patients, suppression of ovarian function and the use of tamoxifen are the most important therapeutic options, even though questions on timing, duration, and combination of these compounds remain unanswered. The use of aromatase inhibitors in combination with ovarian-function suppression is currently under investigation in the premenopausal setting. In postmenopausal patients, aromatase inhibitors given after 2-3 years or 5 years of tamoxifen have shown a significant benefit over tamoxifen alone. However, questions on this treatment also remain unanswered. For example, whether all patients should receive an aromatase inhibitor or whether some subgroups of patients might be optimally treated by tamoxifen alone is yet to be established. In this paper we review the published work on adjuvant endocrine treatment in breast cancer and provide recommendations from the 2007 St Gallen International Conference on Primary Therapy of Early Breast Cancer.

  3. Drug switch because of treatment-related adverse side effects in endocrine adjuvant breast cancer therapy: how often and how often does it work?

    PubMed

    Güth, Uwe; Myrick, Mary Elizabeth; Schötzau, Andreas; Kilic, Nerbil; Schmid, Seraina Margaretha

    2011-10-01

    Therapy-related adverse side effects are a main reason for non-persistence to adjuvant endocrine breast cancer therapy. This study reports frequency of drug-related adverse side effects that were so severe that a modification of the therapy was necessary. We evaluated how many patients discontinued adjuvant endocrine therapy because of these side effects (non-persistence). Last, we analyzed how often a drug switch was undertaken for this reason and how often this measure led to the patient successfully continuing their endocrine therapy. Data concerning all postmenopausal breast cancer patients (≤ 80 years), who initiated endocrine adjuvant therapy between 1998 and 2008 in a Swiss breast center (n = 400), were analyzed. Out of these 400 women, 37 (9.3%) were defined as being non-persistent to the therapy; out of these, 24 (64.9%) because of therapy-related side effects. About 78 patients (19.5%) suffered from severe therapy-related side effects that made a modification of therapy necessary. Out of these 78 cases, 14 patients (17.9%) stopped the therapy without attempting a drug switch (non-persistence). In 64 patients (82.1%; 16% of all women who started endocrine therapy), a drug switch was undertaken. Out of these 64 cases, in 52 cases (81.3%) endocrine therapy was completed after therapy modification. Patients who reported one major adverse effect were more likely to continue the endocrine therapy after a drug switch (P = 0.048) compared with those who suffered from at least two different side effects. In 10 of the 64 cases (15.6%), modification of the therapy was not successful and the patients stopped the treatment prematurely (non-persistence) because of ongoing side effects. In cases when therapy-related side effects occur, a drug switch is a promising step to further improve persistence and, by doing so, the outcome of breast cancer patients.

  4. Exploring the role of physician communication about adjuvant endocrine therapy among breast cancer patients on active treatment: a qualitative analysis

    PubMed Central

    Farias, Albert J.; Ornelas, India J.; Hohl, Sarah D.; Zeliadt, Steven B.; Hansen, Ryan N.; Li, Christopher I.; Thompson, Beti

    2016-01-01

    Purpose To better understand how physicians communicate with breast cancer patients about adjuvant endocrine therapy (AET), we explored, from the breast cancer patient’s perspective, dimensions of the patient-provider communication among women who were on active AET treatment. Methods Qualitative methods using semi-structured in-depth interviews were conducted with breast cancer patients (n = 22) who filled a prescription for AET in the previous 12 months. Interview questions aimed to elicit experiences with AET. We reviewed and coded interview transcripts using qualitative principles of inductive reasoning to identify concepts and themes from interview data. Results We grouped emergent themes into four major functions of physician-patient communication: (1) information exchange, (2) decision-making to take and continue AET, (3) enabling patient self-management and monitoring potential side effects, and (4) emotional support. Physicians exchanged information with patients in a way that they understood and enhanced patient’s health literacy regarding the benefits and knowledge of AET. Physicians empowered patients to make decisions about their care. Patients expressed trust and confidence in their physician which helped them seek care when needed. Patients reported a high degree of self-efficacy to self-manage AET and were continuing treatment despite potential side effects. Conclusions The results from our study suggest that women’s interactions and communication with their physician may be an important factor that contributes to the continued use of AET. Physicians who can communicate information about AET treatment benefits, purpose, and expectations in a way that patients can understand is a critical aspect of care that needs to be further studied. PMID:27557832

  5. Adjuvant Treatment of Melanoma

    PubMed Central

    Moreno Nogueira, J. A.; Valero Arbizu, M.; Pérez Temprano, R.

    2013-01-01

    Melanomas represent 4% of all malignant tumors of the skin, yet account for 80% of deaths from skin cancer.While in the early stages patients can be successfully treated with surgical resection, metastatic melanoma prognosis is dismal. Several oncogenes have been identified in melanoma as BRAF, NRAS, c-Kit, and GNA11 GNAQ, each capable of activating MAPK pathway that increases cell proliferation and promotes angiogenesis, although NRAS and c-Kit also activate PI3 kinase pathway, including being more commonly BRAF activated oncogene. The treatment of choice for localised primary cutaneous melanoma is surgery plus lymphadenectomy if regional lymph nodes are involved. The justification for treatment in addition to surgery is based on the poor prognosis for high risk melanomas with a relapse index of 50–80%. Patients included in the high risk group should be assessed for adjuvant treatment with high doses of Interferon-α2b, as it is the only treatment shown to significantly improve disease free and possibly global survival. In the future we will have to analyze all these therapeutic possibilities on specific targets, probably associated with chemotherapy and/or interferon in the adjuvant treatment, if we want to change the natural history of melanomas. PMID:23476798

  6. Adjuvant Endocrine Therapy in Breast Cancer: A Novel e-Health Approach in Optimizing Treatment for Seniors (OPTIMUM): A Two-Group Controlled Comparison Pilot Study

    PubMed Central

    Tamblyn, Robyn; Meterissian, Sarkis; Law, Susan; Prchal, Jaroslav; Winslade, Nancy; Stern, Donna

    2016-01-01

    Background In women with hormone receptor positive breast cancer, adjuvant endocrine therapy (AET) is associated with a significant survival advantage. Nonadherence is a particular challenge in older women, even though they stand to benefit the most from AET. Therefore, a novel eHealth tool (OPTIMUM) that integrates real-time analysis of health administrative claims data was developed to provide point-of-care decision support for clinicians. Objectives The objectives of the study are to determine the effectiveness of a patient-specific, real-time eHealth alert delivered at point-of-care in reducing rates of AET discontinuation and to understand patient-level factors related to AET discontinuation as well as to assess integration of eHealth alerts regarding deviations from best practices in administration of AET by cancer care teams. Methods A prospective, 2-group controlled comparison pilot study will be conducted at 2 urban, McGill University–affiliated hospitals, the Royal Victoria Hospital and St. Mary’s Hospital. A minimum of 43 patients per study arm will be enrolled through site-level allocation. Follow-up is 1.5 years. Health care professionals at the intervention site will have access to the eHealth tool, which will report to them in real-time medical events with known associations to AET discontinuation, an AET adherence monitor, and a discontinuation alert. Cox proportional hazard ratios with 95% confidence intervals will estimate risks of AET discontinuation. Tests for significance will be 2-sided with a significance level of P<.05. Results This protocol has been approved and funded by the Canadian Institutes of Health Research. The study will evaluate site-level differences between AET discontinuation and AET adherence and assess care team actions at the intervention site. Participant enrollment into this project is expected to start September 2016 with primary data ready to present by June 2018. Conclusion This study will offer an opportunity to

  7. Potential implications of adjuvant endocrine therapy for the oral health of postmenopausal women with breast cancer

    PubMed Central

    Taichman, L. Susan; Havens, Aaron M.

    2012-01-01

    Current adjuvant treatment modalities for breast cancer that express the estrogen receptor or progesterone receptor include adjuvant anti-estrogen therapies, and tamoxifen and aromatase inhibitors. Bone, including the jaw, is an endocrine-sensitive organ, as are other oral structures. This review examines the potential links between adjuvant anti-estrogen treatments in postmenopausal women with hormone receptor positive breast cancer and oral health. A search of PubMed, EMBASE, CENTRAL, and the Web of Knowledge was conducted using combinations of key terms “breast,” “cancer,” “neoplasm,” “Tamoxifen,” “Aromatase Inhibitor,” “chemotherapy,” “hormone therapy,” “alveolar bone loss,” “postmenopausal bone loss,” “estrogen,” “SERM,” “hormone replacement therapy,” and “quality of life.” We selected articles published in peer-reviewed journals in the English. The authors found no studies reporting on periodontal diseases, alveolar bone loss, oral health, or oral health-related quality of life in association with anti-estrogen breast cancer treatments in postmenopausal women. Periodontal diseases, alveolar bone density, tooth loss, and conditions of the soft tissues of the mouth have all been associated with menopausal status supporting the hypothesis that the soft tissues and bone of the oral cavity could be negatively affected by anti-estrogen therapy. As a conclusion, the impact of adjuvant endocrine breast cancer therapy on the oral health of postmenopausal women is undefined. The structures of the oral cavity are influenced by estrogen; therefore, anti-estrogen therapies may carry the risk of oral toxicities. Oral health care for breast cancer patients is an important but understudied aspect of cancer survivorship. PMID:22986813

  8. Start strong or switch? Adjuvant endocrine strategies for postmenopausal women with hormone-sensitive breast cancer.

    PubMed

    Tusquets Trías de Bes, Ignasi; Tormo, Sònia Servitja; Mestres, Joan Albanell

    2009-01-01

    Women are at considerable risk of recurrence in the first few years following initial treatment for early breast cancer. To reduce the risk of recurrence, including distant metastases, those with hormone-sensitive breast cancer receive adjuvant endocrine treatment. Lymph node metastases are a predictor of high risk of early recurrence and distant metastases; however, a significant number of women with node-negative disease will also develop distant metastases. This is of concern, because the development of distant metastases is associated with a high risk of breast cancer death. Studies in postmenopausal women showed that an aromatase inhibitor (AI) as initial, upfront treatment reduces early recurrence, including distant metastases, compared with tamoxifen. The three available AIs (letrozole, anastrozole, and exemestane) are approved for adjuvant use. Upfront letrozole or anastrozole improved time to distant metastasis in patients included in the Breast International Group 1-98 and Arimidex, Tamoxifen, Alone or in Combination trials, respectively. Of note, the beneficial effects of letrozole on distant disease were already observed in the first report at 2 years of follow-up and confirmed in the updated results with 50 months of follow-up. Here, we discuss the available data for all AIs and strategies to be taken into account for patient management, with a special focus on the effects of available options on early recurrences and metastasis risk.

  9. A hard pill to swallow: a qualitative study of women's experiences of adjuvant endocrine therapy for breast cancer

    PubMed Central

    Harrow, Alison; Dryden, Ruth; McCowan, Colin; Radley, Andrew; Parsons, Mark; Thompson, Alastair M; Wells, Mary

    2014-01-01

    Objective To explore women's experiences of taking adjuvant endocrine therapy as a treatment for breast cancer and how their beliefs about the purpose of the medication, side effects experienced and interactions with health professionals might influence adherence. Design Qualitative study using semistructured, one-to-one interviews. Setting 2 hospitals from a single health board in Scotland. Participants 30 women who had been prescribed tamoxifen or aromatase inhibitors (anastrozole or letrozole) and had been taking this medication for 1–5 years. Results Women clearly wished to take their adjuvant endocrine therapy medication as prescribed, believing that it offered them protection against breast cancer recurrence. However, some women missed tablets and did not recognise that this could reduce the efficacy of the treatment. Women did not perceive that healthcare professionals were routinely or systematically monitoring their adherence. Side effects were common and impacted greatly on the women’s quality of life but did not always cause women to stop taking their medication, or to seek advice about reducing the side effects they experienced. Few were offered the opportunity to discuss the impact of side effects or the potential options available. Conclusions Although most women in this study took adjuvant endocrine therapy as prescribed, many endured a range of side effects, often without seeking help. Advice, support and monitoring for adherence are not routinely offered in conventional follow-up settings. Women deserve more opportunity to discuss the pros, cons and impact of long-term adjuvant endocrine therapy. New service models are needed to support adherence, enhance quality of life and ultimately improve survival. These should ideally be community based, in order to promote self-management in the longer term. PMID:24928595

  10. Adjuvant endocrine therapy of premenopausal women with early breast cancer: an overview.

    PubMed

    Hubalek, Michael; Brantner, Christine; Marth, Christian

    2010-04-01

    Tamoxifen is currently the standard of care for premenopausal women with hormone receptor-positive early breast cancers. However, endocrine strategies in premenopausal women include not only estrogen receptor blockade with tamoxifen but also temporary suppression of ovarian estrogen synthesis by luteinizing hormone-releasing hormone (LHRH) agonists, or permanent interruption of ovarian estrogen synthesis with oophorectomy or radiotherapy. Luteinizing hormone-releasing hormone agonists have proven to be as effective as surgical oophorectomy in adjuvant treatment of premenopausal breast cancer. The addition of LHRH agonists compared to no therapy reduces the annual odds of recurrence and death in premenopausal women aged less than 50 years with estrogen receptor-positive tumors. Luteinizing hormone-releasing hormone agonists alone or in combination with tamoxifen have shown disease-free survival rates similar to chemotherapy with CMF (cyclophosphamide/methotrexate/5-fluorouracil) and other second-generation chemotherapies. The role of aromatase inhibitors in combination with ovarian suppression is still not established, especially as a large phase III randomized study (Austrian Breast and Colorectal Cancer Study Group Trial 12) did not show superior efficacy compared with ovarian suppression plus tamoxifen in premenopausal early stage disease. Patients currently continue to receive ovarian suppression and tamoxifen. CYP2D6 status may become an important discriminator for the type of endocrine therapy for the premenopausal patient in the future.

  11. Neoadjuvant endocrine treatment in early breast cancer: An overlooked alternative?

    PubMed

    van Dam, P A; van Dam, V C N; Altintas, S; Papadimitriou, K; Rolfo, C; Trinh, X B

    2016-03-01

    During the last decade neoadjuvant endocrine therapy (NET) has moved from being reserved for elderly and frail non-chemotherapy candidates to a primary systemic modality in selected patients with hormone sensitive breast cancer. Neoadjuvant hormonal treatment in patients with hormone receptor positive, HER-2 negative early breast cancer is proven to be an effective and safe option; it is associated with a higher rate of breast conserving surgery (BCS), may reduce the need for adjuvant chemotherapy and enables a delay of surgery for medical or practical reasons. Clinical responses range from 13% to 100% with at least 3 months of NET. Methods of assessing response should include MRI of the breast, particularly in lobular tumours. In studies comparing tamoxifen with aromatase inhibitors (AI), AI proved to be superior in terms of tumour response and rates of BCS. Change in Ki67 is accepted as a validated endpoint for comparing endocrine neoadjuvant agents. Levels of Ki67 during treatment are more closely related to long-term prognosis than pretreatment Ki67. Neoadjuvant endocrine therapy provides a unique opportunity for studies of endocrine responsiveness and the development of new experimental drugs combined with systemic hormonal treatment.

  12. The use of adjuvant bisphophonates in the treatment of early-stage breast cancer.

    PubMed

    Mathew, Aju; Brufsky, Adam M

    2014-11-01

    Adjuvant treatment of breast cancer has resulted in significant improvement in breast cancer-related outcomes. In addition to chemotherapy and endocrine therapy, the bone-protective agents known as bisphosphonates have been extensively investigated for their putative antitumor effect. Backed by strong preclinical data from in vitro and in vivo models, several randomized clinical trials have evaluated the role of bisphosphonates in an adjuvant setting. The recent NSABP B-34 (National Surgical Adjuvant Breast and Bowel Project protocol B-34) and AZURE (Adjuvant Zoledronic Acid to Reduce Recurrence) studies found no disease-free survival benefit with clodronate and zoledronate, respectively, whereas the ABCSG-12 (Austrian Breast and Colorectal Cancer Study Group trial 12) study found improvement in disease-free survival with zoledronate. Data from these trials suggested a beneficial effect of bisphosphonates in older, postmenopausal women and in premenopausal women treated with ovarian suppression. Given the acceptable toxicity profile of bisphosphonates, these agents could be a useful adjunct to adjuvant chemotherapy or endocrine treatment for early-stage breast cancer in a carefully selected subset of patients. This review aims to critically synthesize the results of clinical trials of adjuvant bisphosphonates in early-stage breast cancer, and to provide guidelines for the use of these agents in early-stage breast cancer.

  13. Positive effect of tamoxifen as part of adjuvant chemo-endocrine therapy for breast cancer. Hokkaido Adjuvant Chemo-Endocrine Therapy for Breast Cancer Study Group.

    PubMed Central

    Uchino, J.; Samejima, N.; Tanabe, T.; Hayasaka, H.; Mito, M.; Hata, Y.; Asaishi, K.

    1994-01-01

    A prospective randomised multicentre clinical study was undertaken for 2 years and 3 months from November 1982, with the aim of examining the significance of using a combination of ftorafur (FT) and tamoxifen (TAM) for post-operative adjuvant therapy of breast cancer. Patients had either stage II or stage IIIa disease, were age 75 or below and had undergone radical mastectomy. Patients were divided into two groups and received one of the following treatment protocols: treatment A, intravenous administration of doxorubicin (DOX), 20 mg on the day of surgery and 10 mg the next day, followed by oral FT 50 mg day-1 for 2 years from the 14th day; treatment B, the same pattern of DOX administration for the first 2 days, followed by a combined therapy of FT and TAM 20 mg day-1 for 2 years. The number of patients was 546 (treatment A 274 and treatment B 272), of whom 34 (6%) were ineligible. The remaining 512 patients (treatment A 254 and treatment B 258) were followed up for 5 years for analysis. Significantly higher 5 year disease-free rate and 5 year survival rates were observed with treatment B compared with treatment A. When seen in terms of background factors, node-positive patients appeared to derive more benefit from tamoxifen than node-negative patients, but the oestrogen receptor-negative and premenopausal subgroups appeared to derive about the same benefit as those who were oestrogen receptor positive and post-menopausal. Indeed, survival in the premenopausal group was significantly better with tamoxifen (P = 0.04). No increase in side-effects was seen by combining TAM with FT. The study results demonstrate that concomitant administration of FT and TAM is better than FT alone for post-operative adjuvant therapy for breast cancer. PMID:8142265

  14. Adjuvant treatment strategies for early colon cancer.

    PubMed

    Waterston, Ashita M; Cassidy, Jim

    2005-01-01

    Colon cancer remains a major cause of death; however, in the last 3 years a number of trials have been published that have led to changes in the treatment of patients with this disease. Initially, the adjuvant treatment of patients following curative resection was based on their Dukes staging; this is now being refined by consideration of other pathological factors, as well as the investigation of newer prognostic markers such as p53, Ki67 and a number of genes on chromosome 18. Tumours generally develop from the progressive accumulation of genetic events, although some develop through mutation or inactivation of DNA mismatch repair proteins leading to microsatellite instability; this is particularly important in Lynch's syndrome. The loss of gene expression can occur by deletion or mutation of genes or by aberrant methylation of CpG islands. In patients with Dukes C colon cancer the standard of care for adjuvant chemotherapy was previously based on bolus fluorouracil (5-fluorouracil) and folinic acid (leucovorin) administered 5 days per month or weekly for 6 months. Recent studies with a combination of infusional fluorouracil, folinic acid and oxaliplatin have been found to be superior. A further study replacing fluorouracil with oral capecitabine has also demonstrated equivalent disease-free survival. Although some debate remains regarding the benefit of adjuvant treatment for patients with Dukes B colon cancer, the emerging consensus is that, for those patients who are younger and have high-risk features, chemotherapy should be discussed. A number of large vaccine trials have also been conducted in the adjuvant setting and, overall, these have been disappointing. This is a rapidly advancing area of therapy and the results of new trials are awaited to determine whether additional benefits can be achieved with biological therapies such as anti-vascular endothelial growth factor and anti-epithelial growth factor receptor monoclonal antibodies, which have already

  15. Adjuvant and neoadjuvant treatment in pancreatic cancer.

    PubMed

    Herreros-Villanueva, Marta; Hijona, Elizabeth; Cosme, Angel; Bujanda, Luis

    2012-04-14

    Pancreatic adenocarcinoma is one of the most aggressive human malignancies, ranking 4th among causes for cancer-related death in the Western world including the United States. Surgical resection offers the only chance of cure, but only 15 to 20 percent of cases are potentially resectable at presentation. Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy. Currently there is no consensus around the world on what constitutes "standard" adjuvant therapy for pancreatic cancer. This controversy derives from several studies, each fraught with its own limitations. Standards of care also vary somewhat with regard to geography and economy, for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe. Regardless of the efforts in adjuvant and neoadjuvant improved therapy, the major goal to combat pancreatic cancer is to find diagnostic markers, identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients. In this review, authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients.

  16. Timing of radiotherapy and outcome in patients receiving adjuvant endocrine therapy

    PubMed Central

    Karlsson, Per; Cole, Bernard F.; Colleoni, Marco; Roncadin, Mario; Chua, Boon; Murray, Elizabeth; Price, Karen N.; Castiglione-Gertsch, Monica; Goldhirsch, Aron; Gruber, Günther

    2010-01-01

    Purpose To evaluate the association between time from breast-conserving surgery (BCS) to radiotherapy and clinical outcome among patients treated with adjuvant endocrine therapy. Methods Patient information was obtained from three International Breast Cancer Study Group trials. Analysis was restricted to 964 patients treated with BCS and adjuvant endocrine therapy. Patients were divided into two groups based on the median number of days between BCS and radiotherapy and into 4 groups based on the quartile of time between BCS and radiotherapy. Endpoints were time to local recurrence (TLR), disease-free survival (DFS) and overall survival (OS). Proportional hazards regression analysis was used to perform comparisons after adjustment for baseline factors. Results The median time between BCS and radiotherapy was 77 days. Radiotherapy timing was significantly associated with age, menopausal status, and estrogen receptor status. After adjustment for these factors no significant effect of radiotherapy delay of up to 20 weeks was found. Adjusted hazard ratios (HRs) (radiotherapy within 77 days vs. after 77 days) were 0.94 (95% CI 0.47–1.87) for TLR, 1.05 (95% CI 0.82–1.34) for DFS and 1.07 (95% CI 0.77–1.49) for OS. For TLR the adjusted HRs for ≤48 days, 49–77 days, and 78–112 days were 0.90 (CI 95% 0.34–2.37), 0.89 (95% CI, 0.33–2.25), and 0.89 (95% CI, 0.33–2.41), respectively relative to ≥ 113 days. Conclusions Radiotherapy delay of up to 20 weeks was significantly associated with baseline factors such as age, menopausal status, and estrogen-receptor status. After adjustment for these factors, timing of radiotherapy was not significantly associated with TLR, DFS, or OS. PMID:20729007

  17. Timing of Radiotherapy and Outcome in Patients Receiving Adjuvant Endocrine Therapy

    SciTech Connect

    Karlsson, Per; Cole, Bernard F.; Colleoni, Marco; Roncadin, Mario; Chua, Boon H.; Murray, Elizabeth; Price, Karen N.; Castiglione-Gertsch, Monica; Goldhirsch, Aron; Gruber, Guenther

    2011-06-01

    Purpose: To evaluate the association between the interval from breast-conserving surgery (BCS) to radiotherapy (RT) and the clinical outcome among patients treated with adjuvant endocrine therapy. Patients and Methods: Patient information was obtained from three International Breast Cancer Study Group trials. The analysis was restricted to 964 patients treated with BCS and adjuvant endocrine therapy. The patients were divided into two groups according to the median number of days between BCS and RT and into four groups according to the quartile of time between BCS and RT. The endpoints were the interval to local recurrence, disease-free survival, and overall survival. Proportional hazards regression analysis was used to perform comparisons after adjustment for baseline factors. Results: The median interval between BCS and RT was 77 days. RT timing was significantly associated with age, menopausal status, and estrogen receptor status. After adjustment for these factors, no significant effect of a RT delay {<=}20 weeks was found. The adjusted hazard ratio for RT within 77 days vs. after 77 days was 0.94 (95% confidence interval [CI], 0.47-1.87) for the interval to local recurrence, 1.05 (95% CI, 0.82-1.34) for disease-free survival, and 1.07 (95% CI, 0.77-1.49) for overall survival. For the interval to local recurrence the adjusted hazard ratio for {<=}48, 49-77, and 78-112 days was 0.90 (95% CI, 0.34-2.37), 0.86 (95% CI, 0.33-2.25), and 0.89 (95% CI, 0.33-2.41), respectively, relative to {>=}113 days. Conclusion: A RT delay of {<=}20 weeks was significantly associated with baseline factors such as age, menopausal status, and estrogen-receptor status. After adjustment for these factors, the timing of RT was not significantly associated with the interval to local recurrence, disease-free survival, or overall survival.

  18. Cognitive function in postmenopausal breast cancer patients one year after completing adjuvant endocrine therapy with letrozole and/or tamoxifen in the BIG 1-98 trial

    PubMed Central

    Phillips, Kelly-Anne; Aldridge, Julie; Ribi, Karin; Sun, Zhuoxin; Thompson, Alastair; Harvey, Vernon; Thürlimann, Beat; Cardoso, Fatima; Pagani, Olivia; Coates, Alan S.; Goldhirsch, Aron; Price, Karen N.; Gelber, Richard D.

    2011-01-01

    Endocrine therapy for breast cancer may affect cognition. The purpose of this study was to examine whether cognitive function improves after cessation of adjuvant endocrine therapy. Change in cognitive function was assessed in 100 postmenopausal breast cancer patients in the BIG 1-98 trial, who were randomized to receive 5 years of adjuvant tamoxifen or letrozole alone or in sequence. Cognitive function was evaluated by computerized tests during the fifth year of trial treatment (Y5) and 1 year after treatment completion (Y6). Cognitive test scores were standardized according to age-specific norms and the change assessed using the Wilcoxon signed-rank test. There was significant improvement in the composite cognitive function score from Y5 to Y6 (median of change = 0.22, effect size = 0.53, P < 0.0001). This improvement was consistent in women taking either tamoxifen or letrozole at Y5 (P = 0.0006 and P = 0.0002, respectively). For postmenopausal patients who received either adjuvant letrozole or tamoxifen alone or in sequence, cognitive function improved after cessation of treatment. PMID:21046229

  19. Adjuvant treatment of GIST: patient selection and treatment strategies.

    PubMed

    Joensuu, Heikki

    2012-04-24

    Tyrosine kinase inhibitors that target the key molecular drivers of gastrointestinal stromal tumour (GIST) are effective treatments of advanced-stage GIST. Yet, most of these patients succumb to the disease. Approximately 60% of patients with GIST are cured by surgery, and these individuals can be identified by risk stratification schemes based on tumour size, mitosis count and site, and assessment of rupture. Two large randomized trials have evaluated imatinib as adjuvant treatment for operable, KIT-positive GIST; adjuvant imatinib substantially improved time to recurrence. One of these trials reported that 3 years of adjuvant imatinib improves overall survival of patients who have a high estimated risk for recurrence of GIST compared with 1 year of imatinib. The optimal adjuvant strategy remains unknown and some patients might benefit from longer than 3 years of imatinib treatment. However, a strategy that involves GIST risk assessment following surgery using a validated scheme, administration of adjuvant imatinib for 3 years, patient monitoring during and after completion of imatinib to detect recurrence early, and reinstitution of imatinib if GIST recurs is a reasonable choice for care of patients with high-risk GIST.

  20. DIAGNOSIS OF ENDOCRINE DISEASE: Endocrine late-effects of childhood cancer and its treatments.

    PubMed

    Chemaitilly, Wassim; Cohen, Laurie E

    2017-04-01

    Endocrine complications are frequently observed in childhood cancer survivors (CCS). One of two CCS will experience at least one endocrine complication during the course of his/her lifespan, most commonly as a late-effect of cancer treatments, especially radiotherapy and alkylating agent chemotherapy. Endocrine late-effects include impairments of the hypothalamus/pituitary, thyroid and gonads, as well as decreased bone mineral density and metabolic derangements leading to obesity and/or diabetes mellitus. A systematic approach where CCS are screened for endocrine late-effects based on their cancer history and treatment exposures may improve health outcomes by allowing the early diagnosis and treatment of these complications.

  1. Effect of a randomized controlled exercise trial on bone outcomes: influence of adjuvant endocrine therapy.

    PubMed

    Knobf, M Tish; Jeon, Sangchoon; Smith, Barbara; Harris, Lyndsay; Kerstetter, Jane; Thompson, A Siobhan; Insogna, Karl

    2016-02-01

    Bone loss is a significant clinical problem for female cancer survivors (FCS) and increases fracture risk. The aim of the Yale Fitness Intervention Trial (Yale FIT) was to determine the effects of a 12-month aerobic-resistance exercise intervention compared to a home-based physical activity group on bone outcomes [bone mineral density (BMD)] and biomarkers bone turnover). Early postmenopausal FCS (N = 154) were randomized to the exercise intervention (3 times/week) or to a home-based physical activity group. Calcium (1200 mg) and Vitamin D (400 IU) supplements were provided to both groups. BMD was measured at baseline and 12 months. No significant difference in BMD was observed for the exercise vs home-based group. However, subjects on Tamoxifen or no endocrine therapy did not significantly lose BMD, with the exception of the femoral neck (FN). In contrast subjects on aromatase inhibitors (AIs) had significant BMD loss at all sites. The majority of subjects had sufficient serum levels of Vitamin D (>20 ng/mL) but there was significantly less bone loss in subjects in the 20-29 ng/mL range at the LS (p = 0.01), hip (p = 0.03), and GT (p = 0.008) compared to lower or higher levels. Exercise stimulates bone remodeling but the intervention was not superior for BMD outcomes at one year. The dose of the osteogenic stimulus in the intervention has been effective in preserving BMD in healthy postmenopausal women but it may be inadequate for survivors with chemotherapy-induced menopause and for those on adjuvant AI therapy.

  2. Successful treatment of accessory breast cancer with endocrine therapy#

    PubMed Central

    Wang, Chun-Xi; Guo, Shu-Li; Han, Li-Na

    2017-01-01

    Accessory breast cancers in males are extremely rare, and only a few cases have been reported in the literature. In this paper, an 87-year-old male patient was diagnosed with an accessory breast cancer by means of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), and immunohistochemistry based on needle biopsy, and has undergone successful resection and postoperative adjuvant endocrine therapy. He was the oldest male patient with an accessory breast cancer reported in the Chinese Hospital Knowledge Database and PubMed literature from 1975 to 2015. PMID:28070998

  3. Genomic predictor of residual risk of recurrence after adjuvant chemotherapy and endocrine therapy in high risk estrogen receptor-positive breast cancers.

    PubMed

    Khan, Sabrina S; Karn, Thomas; Symmans, W Fraser; Rody, Achim; Müller, Volkmar; Holtrich, Uwe; Becker, Sven; Pusztai, Lajos; Hatzis, Christos

    2015-02-01

    A subset of early stage estrogen receptor (ER)-positive breast cancers considered "high risk" for recurrence with endocrine therapy alone by current genomic prognostic predictors, such as Oncotype DX, is no longer high risk after receiving adjuvant chemotherapy. We hypothesized that a recently described gene expression-based outcome predictor adjuvant chemotherapy and endocrine therapy sensitivity (ACES) could re-stratify these patients into high and low risk groups for relapse when treated with both chemo- and endocrine therapies. ACES involves four separate modules (endocrine sensitivity, chemotherapy sensitivity, chemotherapy resistance, and survival prediction) that yield a prediction for good or poor outcome with current standard of care multimodality therapy. ACES was applied to Affymetrix gene expression data from 2 retrospectively collected ER-positive and HER2-negative patient cohorts that were uniformly treated with adjuvant endocrine and chemotherapy (n = 250). Each sample was first risk stratified by a genomic surrogate of Oncotype DX, and the high risk patients (n = 76) were re-stratified by ACES. Recurrence-free survival (RFS) was evaluated with ACES risk categories. The Oncotype DX high risk but ACES good prognosis patients (n = 24, 32%) had an RFS of 95% compared to 76% in the poor prognosis group (n = 52; log-rank p = 0.033) at 5 years. ACES risk category remained an independent predictor in multivariate analysis after adjusting for age, T-stage, and lymph node involvement at diagnosis (hazard ratio 0.15; p = 0.072). Tertiary risk prediction that takes into account chemotherapy and endocrine sensitivity, and baseline prognosis may help identify high risk ER-positive patients who have excellent survival after chemotherapy.

  4. Opinion and evidence for treatments in endocrine disorders.

    PubMed

    2002-01-01

    New treatments and treatment protocols for endocrine disorders are evolving rapidly, and research and development activity in the endocrinology field is high. Optimal therapy remains contentious in some areas. To help you keep up-to-date with the latest advances worldwide on all aspects of drug therapy and management of endocrine disorders, this section of the journal brings you information selected from the rapid drug news alerting service Inpharma Weekly. Each issue contains easy-to-read summaries of the most important research and development news, clinical studies, treatment guidelines, pharmacoeconomic and adverse drug reaction news, and expert opinion pieces published in the world's top endocrinology journals.

  5. Opinion and evidence for treatments in endocrine disorders.

    PubMed

    2003-01-01

    New treatments and treatment protocols for endocrine disorders are evolving rapidly, and research and development activity in the endocrinology field is high. Optimal therapy remains contentious in some areas. To help you keep up-to-date with the latest advances worldwide on all aspects of drug therapy and management of endocrine disorders, this section of the journal brings you information selected from the rapid drug news alerting service Inpharma Weekly. Each issue contains easy-to-read summaries of the most important research and development news, clinical studies, treatment guidelines, pharmacoeconomic and adverse drug reaction news, and expert opinion pieces published in the world's top endocrinology journals.

  6. Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer

    PubMed Central

    Viale, G.; Giobbie-Hurder, A.; Gusterson, B. A.; Maiorano, E.; Mastropasqua, M. G.; Sonzogni, A.; Mallon, E.; Colleoni, M.; Castiglione-Gertsch, M.; Regan, M. M.; Brown, R. W.; Golouh, R.; Crivellari, D.; Karlsson, P.; Öhlschlegel, C.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

    2010-01-01

    Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy. PMID:19633051

  7. WASTEWATER TREATMENT AND ITS MANAGEMENT OF ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Research has shown that wastewater treatment (WWT) can be a significant source of endocrine disrupting chemicals (EDCs) to the environment. WWT can include centralized wastewater treatment plants (WWTPs) or on-site WWT technologies. EDCs found in WWT effluents (aqueous and biosol...

  8. Interaction of green tea catechins with breast cancer endocrine treatment: a systematic review.

    PubMed

    Yiannakopoulou, Eugenia C

    2014-01-01

    Recent data have shown strong chemopreventive and possibly cancer chemotherapeutic effects of green tea polyphenols and EGCG against breast cancer. This systematic review aims to synthesize data on the possible interaction of green tea catechins with breast cancer endocrine treatment. Electronic databases were searched with the appropriate search terms. Experimental trials suggest a synergistic interaction of green tea catechins with tamoxifen or raloxifene in the treatment of estrogen receptor-positive and estrogen receptor-negative breast cancer through estrogen receptor-dependent and -independent mechanisms. No evidence of an interaction of green tea catechins with aromatase inhibitors or fulvestrant has been reported. As green tea catechins are natural compounds with a rather favorable safety profile, the strategy of co-administrating green tea catechins with tamoxifen seems to be a rational approach in chemoprevention, adjuvant and metastatic breast cancer treatment that needs further investigation.

  9. Clinical utility of genetic signatures in selecting adjuvant treatment: Risk stratification for early vs. late recurrences.

    PubMed

    Hayes, Daniel F

    2015-11-01

    Adjuvant endocrine therapy (ET) reduces the odds of distant recurrence and mortality by nearly one-half in women with hormone receptor (HR) positive early stage breast cancer. While the risk of recurrence is lower for HR positive than negative patients during the first 5-7 years, HR positive patients suffer ongoing recurrences between 0.5 and 2% year over subsequent years. Extended adjuvant ET further reduces recurrence during this late phase of follow-up. ET is associated with post-menopausal side effects (hot flashes, sexual dysfunction, mood changes, and weight gain), and occasional major toxicities (thrombosis and endometrial cancer with tamoxifen; bone mineral loss and possibly heart disease with AIs) persist throughout therapy. Accurate and reliable estimates of the risk of recurrence after five years of ET for women with prior HR positive breast cancer would permit appropriate extended ET decisions. The risk of long-term relapse is related to lymph node status and size of tumor, but these are relatively crude. Several groups have investigated whether multi-parameter tumor biomarker tests might identify those patients whose risk of recurrence is so low that extended ET is not justified. These assays include IHC4, the 21-gene "OncotypeDX", the 12-gene "Endopredict," the PAM50, and the 2-gene "Breast Cancer Index (BCI)" assays. The clinical validity of all these tests for this use context have been established, with at least one paper for each that shows a statistically significant difference in risk of distant recurrence during the 5-10 years after the initial five years of adjuvant endocrine therapy. However, the stakes are high, and although each of these represents a "prospective retrospective" study, they require further validation in subsequent datasets before they should be considered to have "clinical utility" and are used to withhold potentially life-saving treatment. Perhaps more importantly, the clinical breast cancer community, and especially the

  10. Effects of 3% trehalose as an adjuvant treatment after LASIK

    PubMed Central

    Mateo Orobia, Antonio J; Casas Pascual, Paula; Cristóbal Bescós, José Á; Perez García, Diana; Peiro Embid, Carlos; del Buey Sayas, M Ángeles; Korobko Kulikova, Valentyna; Lafuente Ojeda, Noelia

    2017-01-01

    Purpose To evaluate the effect of 3% trehalose as an adjuvant in the standard treatment after laser-assisted in situ keratomileusis. Design Interventional prospective comparative single-blind study. Setting Department of Ophthalmology, Hospital Quirón Zaragoza, Spain. Methods A total of 26 eyes (13 patients) were included, of which 12 eyes (group 1) received conventional treatment with lubricant drops of hyaluronic acid (0.15%) and 14 eyes (group 2) received, additionally, an ophthalmic solution of 3% trehalose. Pre- and postoperative quality-of-life tests and vital stains, tear breakup time, and osmolarity measurements were made. Results We obtained statistically significant differences between the groups in the Symptom Assessment in Dry Eye test in all visits with respect to severity, and in the postoperative day 1 visit with respect to frequency, in all cases favoring the trehalose treatment. The values of osmolarity were not significantly different between groups. However, we did find significant differences in the Oxford scale in day 90 for the trehalose treatment (P<0.001), and in the National Eye Institute scale in day 30 (P=0.02). Conclusion The results of this exploratory study indicate that the adjuvant treatment with 3% trehalose could be superior with respect to the standard treatment, with improvements in the objective and subjective parameters of tear quality. PMID:28243058

  11. Early versus delayed initiation of adjuvant treatment for pancreatic cancer

    PubMed Central

    Kim, Hyoung Woo; Lee, Jong-Chan; Lee, Jongchan; Kim, Jin Won; Kim, Jaihwan; Hwang, Jin-Hyeok

    2017-01-01

    Background Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor showing a tendency for early recurrence, even after curative resection. Although adjuvant treatment improves survival, it is unclear whether early adjuvant treatment initiation yields better outcomes in patients with PDAC. Methods We retrospectively enrolled 113 patients who underwent chemotherapy or chemoradiotherapy after curative resection of PDAC: Fifty-six and 57 patients were in the early and delayed groups, respectively based on the median time of treatment initiation (35 days [range, 20–83 days]). Results Patient baseline characteristics were comparable in both groups, except for grade III or IV postoperative complications (5.4% in the early group vs. 22.8% in the delayed group). With a median 20.3-month follow-up, the overall survival (OS) and disease-free survival (DFS) times were 29.5 and 14.7 months, respectively. The early group had significantly prolonged OS (39.1 vs. 21.1 months, p = 0.018) and DFS (18.8 vs. 10.0 months, p = 0.034), compared to the delayed group. Among 71 patients who completed planned adjuvant treatment, patients in the early group tended to have longer, though not statistically significant, OS and DFS times than those in the delayed group. In 67 patients without postoperative complications, patients in the early group had longer OS (42.8 vs. 20.5 months, p = 0.002) and DFS (19.6 vs. 9.1 months, p = 0.005) than those in the delayed group. By multivariate analysis, incompletion of treatment (hazard ratio [HR]: 4.039, 95% confidence interval [CI]: 2.334–6.992), delayed treatment initiation (HR: 1.822, 95% CI: 1.081–3.070), and positive angiolymphatic invasion (HR: 2.116, 95% CI: 1.160–3.862) were significantly associated with shorter OS. Conclusions Adjuvant treatment should be delivered earlier and completed for better outcomes in resected PDAC patients, especially without postoperative complications. PMID:28301556

  12. Endocrine Disorders in Fanconi Anemia: Recommendations for Screening and Treatment

    PubMed Central

    Kanakatti Shankar, Roopa; Giri, Neelam; Hollenberg, Anthony N.; Rutter, Meilan M.; Nathan, Brandon; Lodish, Maya; Alter, Blanche P.; Stratakis, Constantine A.

    2015-01-01

    Context: Endocrine problems are common in patients with Fanconi anemia (FA). About 80% of children and adults with FA have at least one endocrine abnormality, including short stature, GH deficiency, abnormal glucose or insulin metabolism, dyslipidemia, hypothyroidism, pubertal delay, hypogonadism, or impaired fertility. The goal of this report is to provide an overview of endocrine abnormalities and guidelines for routine screening and treatment to allow early diagnosis and timely intervention. Evidence Acquisition: This work is based on a comprehensive literature review, including relevant articles published between 1971 and 2014, and proceedings of a Consensus Conference held by the Fanconi Anemia Research Fund in 2013. Evidence Synthesis: The panel of experts collected published evidence and discussed its relevance to reflect current information about the endocrine care of children and adults with FA before the Consensus Conference and through subsequent deliberations that led to the consensus. Conclusions: Individuals with FA should be routinely screened for endocrine abnormalities, including evaluation of growth; glucose, insulin, and lipid metabolism; thyroid function; puberty; gonadal function; and bone mineral metabolism. Inclusion of an endocrinologist as part of the multidisciplinary patient care team is key to providing comprehensive care for patients with FA. PMID:25575015

  13. [Endocrine consequences in young adult survivors of childhood cancer treatment].

    PubMed

    Leroy, C; Cortet-Rudelli, C; Desailloud, R

    2015-10-01

    Endocrine complications (particularly gonadal, hypothalamic-pituitary and metabolic) of childhood cancer treatments are common in young adults. Gonadal damage may be the result of chemotherapy or radiotherapy. Fertility preservation must be systematically proposed before initiation of gonadotoxic treatment if only the child is eligible. Hypothalamic-pituitary deficiency is common after brain or total-body irradiation, the somatotropic axis is the most sensitive to irradiation. Pituitary deficiency screening must be repeated since this endocrine consequence can occur many years after treatment. Hormone replacement must be prudent particularly in case of treatment with growth hormone or steroids. Metabolic syndrome, diabetes and cardiovascular damage resulting from cancer treatments contribute to the increase of morbidity and mortality in this population and should be screened routinely even if the patient is asymptomatic. The multidisciplinary management of these adults must be organized and the role of the endocrinologist is now well established.

  14. Adjuvant brachytherapy in the treatment of soft-tissue sarcomas.

    PubMed

    Crownover, R L; Marks, K E

    1999-06-01

    For many patients with STS, administering adjuvant radiation treatments in the form of interstitial brachytherapy provides an excellent alternative to a protracted course of EBRT. Ideal patients are those with intermediate- or high-grade tumors amenable to en bloc resection. Attractive features of this approach include an untainted pathologic specimen, expeditious completion of treatment, reduction in wound complications, and improved functional outcome. Brachytherapy can permit definitive reirradiation by tightly localizing the high dose radiation exposure. It is also useful in patients who are known to have or be at high risk of metastatic disease, for whom the rapid completion of local treatment allows systemic therapy to begin quickly. Introduction of HDR techniques has shifted the delivery of brachytherapy from inpatient solitary confinement to an outpatient setting. Early reports using HDR brachytherapy for treatment of adult and pediatric STS are quite encouraging. The clinical equivalence between hyperfractionated HDR schedules and traditional LDR techniques is gaining acceptance.

  15. Interaction of Salicylates and the Other Nonsteroidal Anti-Inflammatory Agents With Breast Cancer Endocrine Treatment: Systematic Review.

    PubMed

    Ch Yiannakopoulou, Eugenia

    2015-12-01

    Despite advances in breast cancer treatment, mortality from breast cancer is still high. Undoubtedly, novel treatment strategies are needed for chemoprevention of high-risk women and for the treatment of receptor-negative breast cancer. An appealing strategy would be the combination of breast endocrine treatment with salicylates and the other nonsteroidal anti-inflammatory agents (NSAIDs). This systematic review aimed to synthesize evidence on the possible synergistic antitumor effect of breast cancer endocrine treatment with salicylates and the other NSAIDs. Electronic databases were searched with the appropriate search terms. Most of the identified studies investigated the possible synergistic effect of exemestane with celecoxib in different clinical settings including metastatic treatment, adjuvant treatment, ductal carcinoma in situ. The possible synergistic effect of tamoxifen with celecoxib was investigated in one experimental study and the possible synergistic effect of exemestane with aspirin was investigated in another experimental study. Synergistic effect was detected in the majority of the studies. In conclusion, existing limited evidence suggests synergistic interaction of salicylates and the other NSAIDs in the treatment of estrogen responsive breast cancer with clinical implications in the reversal of acquired resistance to breast cancer endocrine treatment and in chemoprophylaxis.

  16. Uncaria tomentosa—Adjuvant Treatment for Breast Cancer: Clinical Trial

    PubMed Central

    Santos Araújo, Maria do Carmo; Farias, Iria Luiza; Gutierres, Jessie; Dalmora, Sergio L.; Flores, Nélia; Farias, Julia; de Cruz, Ivana; Chiesa, Juarez; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa

    2012-01-01

    Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma—Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer. PMID:22811748

  17. Endocrine system on chip for a diabetes treatment model.

    PubMed

    Nguyen, Dao Thi Thuy; van Noort, Danny; Jeong, In-Kyung; Park, Sungsu

    2017-02-21

    The endocrine system is a collection of glands producing hormones which, among others, regulates metabolism, growth and development. One important group of endocrine diseases is diabetes, which is caused by a deficiency or diminished effectiveness of endogenous insulin. By using a microfluidic perfused 3D cell-culture chip, we developed an 'endocrine system on chip' to potentially be able to screen drugs for the treatment of diabetes by measuring insulin release over time. Insulin-secreting β-cells are located in the pancreas, while L-cells, located in the small intestines, stimulate insulin secretion. Thus, we constructed a co-culture of intestinal-pancreatic cells to measure the effect of glucose on the production of glucagon-like peptide-1 (GLP-1) from the L-cell line (GLUTag) and insulin from the pancreatic β-cell line (INS-1). After three days of culture, both cell lines formed aggregates, exhibited 3D cell morphology, and showed good viability (>95%). We separately measured the dynamic profile of GLP-1 and insulin release at glucose concentrations of 0.5 and 20 mM, as well as the combined effect of GLP-1 on insulin production at these glucose concentrations. In response to glucose stimuli, GLUTag and INS-1 cells produced higher amounts of GLP-1 and insulin, respectively, compared to a static 2D cell culture. INS-1 combined with GLUTag cells exhibited an even higher insulin production in response to glucose stimulation. At higher glucose concentrations, the diabetes model on chip showed faster saturation of the insulin level. Our results suggest that the endocrine system developed in this study is a useful tool for observing dynamical changes in endocrine hormones (GLP-1 and insulin) in a glucose-dependent environment. Moreover, it can potentially be used to screen GLP-1 analogues and natural insulin and GLP-1 stimulants for diabetes treatment.

  18. Treatment of early uterine sarcomas: disentangling adjuvant modalities

    PubMed Central

    Zagouri, Flora; Dimopoulos, Athanasios-Meletios; Fotiou, Stelios; Kouloulias, Vassilios; Papadimitriou, Christos A

    2009-01-01

    Uterine sarcomas are a rare group of neoplasms with aggressive clinical course and poor prognosis. They are classified into four main histological subtypes in order of decreasing incidence: carcinosarcomas, leiomyosarcomas, endometrial stromal sarcomas and "other" sarcomas. The pathological subtype demands a tailored approach. Surgical resection is regarded as the mainstay of treatment. Total abdominal hysterectomy and bilateral salpingo-oophorectomy represents the standard treatment of uterine sarcomas. Pelvic and para-aortic lymph node dissection in carcinosarcomas is recommended, given their high incidence of lymph node metastases, and may have a role in endometrial stromal sarcomas. Adjuvant radiation therapy has historically been of little survival value, but it appears to improve local control and may delay recurrence. Regarding adjuvant chemotherapy, there is little evidence in the literature supporting its use except for carcinosarcomas. However, more trials are needed to address these issues, especially, their sequential application. Patients with uterine sarcomas should be referred to large academic centers for participation in clinical trials. PMID:19356236

  19. Probiotics as an adjuvant treatment in Helicobacter pylori eradication therapy.

    PubMed

    Zhu, Xinyan; Liu, Fei

    2017-03-10

    Over 80% population with Helicobacter pylori (H. pylori) infection is asymptomatic. H. pylori was considered as a primary reason for various natural gastric physiopathology. Increased antibiotic resistance and less medication compliance lead to the failure of antibiotic eradication therapy. Probiotics have been applied as a supplementary treatment in H. pylori eradication therapy in recent years. They have direct and indirect inhibitory effects on H. pylori in both animal models and clinical trials. Because of the improvement in eradication rates and therapy-related side effects, probiotics have been considered as the useful supplementation to current eradication therapy although the treatment outcomes were controversial due to the heterogeneity of probiotics in species, strains, doses and therapeutic duration. Despite the positive role of probiotics, several factors need to be further considered during the application of probiotics. At last, the adverse effects of probiotics are notable. Further investigation into the safety of adjuvant probiotics to present H. pylori eradication therapy is still needed.

  20. Cachexia in chronic heart failure: endocrine determinants and treatment perspectives.

    PubMed

    Mangner, Norman; Matsuo, Yae; Schuler, Gerhard; Adams, Volker

    2013-04-01

    It is well documented in the current literature that chronic heart failure is often associated with cachexia, defined as involuntary weight loss of 5 % in 12 month or less. Clinical studies unraveled that the presence of cachexia decreases significantly mean survival of the patient. At the molecular level mainly myofibrillar proteins are degraded, although a reduced protein synthesis may also contribute to the loss of muscle mass. Endocrine factors clearly regulate muscle mass and function by influencing the normally precisely controlled balance between protein breakdown and protein synthesis The aim of the present article is to review the knowledge in the field with respect to the role of endocrine factors for the regulation of cachexia in patients with CHF and deduce treatment perspectives.

  1. Growth and endocrine function after treatment for medulloblastoma.

    PubMed

    Brown, I H; Lee, T J; Eden, O B; Bullimore, J A; Savage, D C

    1983-09-01

    Children with medulloblastoma in Bristol are treated surgically and with craniospinal irradiation, and in some cases chemotherapy. Thirteen medium or long term survivors were investigated to determine their growth and endocrine function. Their rate of growth was considerably reduced through the first year of their illness and after spinal irradiation spinal growth was poor. Nine children developed growth hormone deficiency. They were clinically euthyroid but 7 had raised basal thyroid stimulating hormone values. Gonadal function was abnormal in all but the youngest child. The rate of survival is increasing in children with medulloblastoma but this is associated with appreciable endocrine abnormalities. Some of these problems are present shortly after treatment ends but others may develop later and long term surveillance is therefore essential.

  2. Biotherapy in the Adjuvant Treatment of Colorectal Cancer

    PubMed Central

    Tazi, El Mehdi; Essadi, Ismail; Boutayeb, Saber; M’rabti, Hind; Errihani, Hassan

    2011-01-01

    The use of adjuvant chemotherapy has improved survival in early-stage colon cancer. Ongoing adjuvant clinical trials are evaluating the addition of targeted therapies to standard chemotherapy regimen. Preliminary results with bevacizumab were disappointing. Also, cetuximab added to chemotherapy does not seem to be better than chemotherapy alone, even in selected wild-type KRAS populations. A better understanding of mechanisms of action of drugs, tumor biology, and predictive biomarkers are needed to design future adjuvant trials. PMID:27942334

  3. Mitotane effects in a H295R xenograft model of adjuvant treatment of adrenocortical cancer.

    PubMed

    Lindhe, O; Skogseid, B

    2010-09-01

    Adrenocortical cancer is one of the most aggressive endocrine malignancies. Growth through the capsule or accidental release of cancer cells during surgery frequently results in metastatic disease. We investigated the antitumoral effect of 2 adrenocorticolytic compounds, O, P'-DDD and MeSO2-DDE, in the adrenocortical cell line H295R both in vitro and as a xenograft model in vivo. H295R cells were injected s. c. in nude mice. O, P'-DDD, MeSO2-DDE, or oil (control) was administered i. p., either simultaneously with cell injection at day 0 (mimicking adjuvant treatment), or at day 48 (established tumors). Accumulation of PET tracers [ (11)C]methionine (MET), [ (11)C] metomidate (MTO), 2-deoxy-2-[ (18)F]fluoro-d-glucose (FDG), and [ (18)F]-l-tyrosine (FLT) in the aggregates were assessed +/- drug treatment in vitro. Tumor growth was significantly inhibited when O, P'-DDD was given at the same time as injection of tumor cells. No significant growth inhibition was observed after treatment with O, P'-DDD at day 48. A significant reduction in FLT uptake and an increased FDG uptake, compared to control, were observed following treatment with 15 microM O, P'-DDD (p<0.01) in vitro. MeSO2-DDE (15 microM) treatment gave rise to a reduced MET and an increased FLT uptake (p<0.01). Both compounds reduced the uptake of MTO compared to control (p<0.01). Treatment with O, P'-DDD simultaneously to inoculation of H295R cells in mice, imitating release of cells during surgery, gave a markedly better effect than treatment of established H295R tumors. We suggest that FLT may be a potential PET biomarker when assessing adrenocortical cancer treatment with O,P'-DDD. Further studies in humans are needed to investigate this.

  4. Comparable quality attributes of hepatitis E vaccine antigen with and without adjuvant adsorption-dissolution treatment

    PubMed Central

    Zhang, Yue; Li, Min; Yang, Fan; Li, Yufang; Zheng, Zizheng; Zhang, Xiao; Lin, Qingshan; Wang, Ying; Li, Shaowei; Xia, Ningshao; Zhang, Jun; Zhao, Qinjian

    2015-01-01

    Most vaccines require adjuvants for antigen stabilization and immune potentiation. Aluminum-based adjuvants are the most widely used adjuvants for human vaccines. Previous reports demonstrated the preservation of antigen conformation and other antigen characteristics after recovery from adjuvanted Hepatitis B and human papillomavirus vaccines. In this study, we used a combination of various physiochemical and immunochemical methods to analyze hepatitis E vaccine antigen quality attributes after recovery from adjuvants. All biochemical and biophysical methods showed similar characteristics of the p239 protein after recovery from adjuvanted vaccine formulation compared to the antigen in solution which never experienced adsorption/desorption process. Most importantly, we demonstrated full preservation of key antigen epitopes post-recovery from adjuvanted vaccine using a panel of murine monoclonal antibodies as exquisite probes. Antigenicity of p239 was probed with a panel of 9 mAbs using competition/blocking ELISA, surface plasmon resonance and sandwich ELISA methods. These multifaceted analyses demonstrated the preservation of antigen key epitopes and comparable protein thermal stability when adsorbed on adjuvants or of the recovered antigen post-dissolution treatment. A better understanding of the antigen conformation in adjuvanted vaccine will enhanced our knowledge of antigen-adjuvant interactions and facilitate an improved process control and development of stable vaccine formulation. PMID:26018442

  5. Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline

    PubMed Central

    Nieman, Lynnette K.; Biller, Beverly M. K.; Findling, James W.; Murad, M. Hassan; Newell-Price, John; Savage, Martin O.; Tabarin, Antoine

    2015-01-01

    Objective: The objective is to formulate clinical practice guidelines for treating Cushing's syndrome. Participants: Participants include an Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer. The European Society for Endocrinology co-sponsored the guideline. Evidence: The Task Force used the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned three systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus Process: The Task Force achieved consensus through one group meeting, several conference calls, and numerous e-mail communications. Committees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Conclusions: Treatment of Cushing's syndrome is essential to reduce mortality and associated comorbidities. Effective treatment includes the normalization of cortisol levels or action. It also includes the normalization of comorbidities via directly treating the cause of Cushing's syndrome and by adjunctive treatments (eg, antihypertensives). Surgical resection of the causal lesion(s) is generally the first-line approach. The choice of second-line treatments, including medication, bilateral adrenalectomy, and radiation therapy (for corticotrope tumors), must be individualized to each patient. PMID:26222757

  6. Current adjuvant treatment modalities for gastric cancer: From history to the future.

    PubMed

    Kilic, Leyla; Ordu, Cetin; Yildiz, Ibrahim; Sen, Fatma; Keskin, Serkan; Ciftci, Rumeysa; Pilanci, Kezban Nur

    2016-05-15

    The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients.

  7. Current adjuvant treatment modalities for gastric cancer: From history to the future

    PubMed Central

    Kilic, Leyla; Ordu, Cetin; Yildiz, Ibrahim; Sen, Fatma; Keskin, Serkan; Ciftci, Rumeysa; Pilanci, Kezban Nur

    2016-01-01

    The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients. PMID:27190583

  8. Opinion and evidence for treatments in endocrine disorders.

    PubMed

    2006-01-01

    New treatments and treatment protocols for endocrine disorders are evolving rapidly, and research and development activity in the endocrinology field is high. Optimal therapy remains contentious in some areas. To help you keep up to date with the latest advances worldwide on all aspects of drug therapy and management of endocrine disorders, this section of the journal brings you information selected from the rapid drug news alerting service Inpharma WeeklyInpharma Weekly provides rapid alerts to news on drugs and drug therapy. Summarizing information selected from over 1600 biomedical journals, this newsletter is produced by Adis International Limited and is available in a variety of formats. Please contact your nearest Adis office for subscription details. The use of trade names, identified by ['~'] or the use of a registered (((R))) or trademark (trade mark) symbol, is for product identification purposes only and does not imply endorsement.. Each issue contains easy-to-read summaries of the most important research and development news, clinical studies, treatment guidelines, pharmacoeconomic and adverse drug reaction news, and expert opinion pieces published in the world's top endocrinology journals.

  9. Behavior of Selected Endocrine Disrupting Chemicals in Sewage Treatment Plant

    NASA Astrophysics Data System (ADS)

    Wang, Xinze; Lu, Jiaming; Ollivier, Natacha; Saturnino, Anais; Gomez, Elena; Casellas, Claude; Picot, Bernadette

    2010-11-01

    The behavior of endocrine disrupting chemicals in sewage treatment plant affects their final fate in water environment. We selected six endocrine disrupting chemicals: 4 alkylphenols (4-tert-octylphenol, octylphenol, 4-nonylphenol, bisphenol A) and 2 steroids (17α-ethinylestradiol and estriol) as targets, their removal and transformation in wastewater treatment plant were studied. Five mixed liquors were sampled respectively from different stages of Minhang wastewater treatment plant in Shanghai. EDCs concentration were analyzed with GC-MS. The main removal pathways of EDCs include initial adsorption by suspended solids and following biodegradation in biological sludge. The removal efficiency of six targets was more than 86%. The concentration of OP and 4-n-NP in water significantly increased in anoxic stage, the reason may be the releases of EDCs from sludge to water on the condition of low DO. And it was also found that the EDCs could be released to water phase in the secondary clarifier, which may cause potential risk of EDCs entering the environment with discharge.

  10. Concurrent chemoradiotherapy in adjuvant treatment of breast cancer

    PubMed Central

    Ismaili, Nabil; Mellas, Nawfel; Masbah, Ouafae; Elmajjaoui, Sanaa; Arifi, Samia; Bekkouch, Imane; Ahid, Samir; Bazid, Zakaria; Tazi, Mohammed Adnane; Erraki, Abdelouahed; El Mesbahi, Omar; Benjaafar, Noureddine; El Gueddari, Brahim El Khalil; Ismaili, Mohammed; Afqir, Said; Errihani, Hassan

    2009-01-01

    Background The optimal sequencing of chemotherapy and radiotherapy after breast surgery was largely studied but remains controversial. Concurrent chemo-radiotherapy is a valuable method for adjuvant treatment of breast cancer which is under ongoing research program in our hospital. We are evaluating the feasibility of the concomitant use of chemotherapy retrospectively. Methods Two hundred forty four women having breast cancer were investigated in a retrospective study. All patients were either treated by radical surgery or breast conservative surgery. The study compares two adjuvant treatments associating concomitant chemotherapy and radiotherapy. In the first group (group A) the patients were treated by chemotherapy and radiotherapy in concomitant way using anthracycline (n = 110). In the second group (group B) the patients were treated by chemotherapy and radiotherapy in concomitant way using CMF treatment (n = 134). Chemotherapy was administered in six cycles, one each 3 weeks. Radiotherapy delivered a radiation dose of 50 Gy on the whole breast (or on the external wall) and/or on the lymphatic region. The Kaplan-Meier method was used to estimate the rates of disease free survival, loco-regional recurrence-free survival and overall survival. The Pearson Khi2 test was used to analyse the homogeneity between the two groups. The log-rank test was used to evaluate the differences between the two groups A and B. Results After 76.4 months median follow-up (65.3 months mean follow up), only one patient relapsed to loco-regional breast cancer when the treatment was based on anthracycline. However, 8 patients relapsed to loco-regional breast cancer when the treatment was based on CMF. In the anthracycline group, the disease free survival after 5 years, was 80.4% compared to 76.4% in the CMF group (Log-rank test: p = 0.136). The overall survival after 5 years was 82.5% and 81.1% in the anthracycline and CMF groups respectively (Log-rank test: p = 0.428). The loco

  11. Predictive value and clinical utility of centrally assessed ER, PgR, and Ki-67 to select adjuvant endocrine therapy for premenopausal women with hormone receptor-positive, HER2-negative early breast cancer: TEXT and SOFT trials.

    PubMed

    Regan, Meredith M; Pagani, Olivia; Francis, Prudence A; Fleming, Gini F; Walley, Barbara A; Kammler, Roswitha; Dell'Orto, Patrizia; Russo, Leila; Szőke, János; Doimi, Franco; Villani, Laura; Pizzolitto, Stefano; Öhlschlegel, Christian; Sessa, Fausto; Peg Cámara, Vicente; Rodríguez Peralto, José Luis; MacGrogan, Gaëtan; Colleoni, Marco; Goldhirsch, Aron; Price, Karen N; Coates, Alan S; Gelber, Richard D; Viale, Giuseppe

    2015-11-01

    The SOFT and TEXT randomized phase III trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor-positive (HR+) early breast cancer. We investigated the prognostic and predictive value of centrally assessed levels of estrogen receptor (ER), progesterone receptor (PgR), and Ki-67 expression in women with HER2-negative disease. Of 5707 women enrolled, 4115 with HER2-negative (HR+/HER2-) disease had ER, PgR, and Ki-67 centrally assessed by immunohistochemistry. Breast cancer-free interval (BCFI) was defined from randomization to first invasive local, regional, or distant recurrence or contralateral breast cancer. The prognostic and predictive values of ER, PgR and Ki-67 expression levels were assessed using Cox modeling and STEPP methodology. In this HR+/HER2- population, the median ER, PgR, and Ki-67 expressions were 95, 90, and 18 % immunostained cells. As most patients had strongly ER-positive tumors, the predictive value of ER levels could not be investigated. Lower PgR and higher Ki-67 expression were associated with reduced BCFI. There was no consistent evidence of heterogeneity of the relative treatment effects according to PgR or Ki-67 expression levels, though there was a greater 5-year absolute benefit of exemestane + ovarian function suppression (OFS) versus tamoxifen with or without OFS at lower levels of PgR and higher levels of Ki-67. Women with poor prognostic features of low PgR and/or high Ki-67 have greater absolute benefit from exemestane + OFS versus tamoxifen + OFS or tamoxifen alone, but individually PgR and Ki-67 are of limited predictive value for selecting adjuvant endocrine therapy for premenopausal women with HR+/HER2- early breast cancer.

  12. Selective glucocorticoid receptor-activating adjuvant therapy in cancer treatments

    PubMed Central

    Sundahl, Nora; Clarisse, Dorien; Bracke, Marc; Offner, Fritz; Berghe, Wim Vanden; Beck, Ilse M.

    2016-01-01

    Although adverse effects and glucocorticoid resistance cripple their chronic use, glucocorticoids form the mainstay therapy for acute and chronic inflammatory disorders, and play an important role in treatment protocols of both lymphoid malignancies and as adjuvant to stimulate therapy tolerability in various solid tumors. Glucocorticoid binding to their designate glucocorticoid receptor (GR), sets off a plethora of cell-specific events including therapeutically desirable effects, such as cell death, as well as undesirable effects, including chemotherapy resistance, systemic side effects and glucocorticoid resistance. In this context, selective GR agonists and modulators (SEGRAMs) with a more restricted GR activity profile have been developed, holding promise for further clinical development in anti-inflammatory and potentially in cancer therapies. Thus far, the research into the prospective benefits of selective GR modulators in cancer therapy limped behind. Our review discusses how selective GR agonists and modulators could improve the therapy regimens for lymphoid malignancies, prostate or breast cancer. We summarize our current knowledge and look forward to where the field should move to in the future. Altogether, our review clarifies novel therapeutic perspectives in cancer modulation via selective GR targeting. PMID:27713909

  13. Predictors of adjuvant treatment for pancreatic adenocarcinoma at the population level

    PubMed Central

    Kagedan, D.J.; Dixon, M.E.; Raju, R.S.; Li, Q.; Elmi, M.; Shin, E.; Liu, N.; El-Sedfy, A.; Paszat, L.; Kiss, A.; Earle, C.C.; Mittmann, N.; Coburn, N.G.

    2016-01-01

    Background In the present study, we aimed to describe, at the population level, patterns of adjuvant treatment use after curative-intent resection for pancreatic adenocarcinoma (pcc) and to identify independent predictors of adjuvant treatment use. Methods In this observational cohort study, patients undergoing pcc resection in the province of Ontario (population 13 million) during 2005–2010 were identified using the provincial cancer registry and were linked to administrative databases that include all treatments received and outcomes experienced in the province. Patients were defined as having received chemotherapy (ctx), chemoradiation (crt), or observation (obs). Clinicopathologic factors associated with the use of ctx, crt, or obs were identified by chi-square test. Logistic regression analyses were used to identify independent predictors of adjuvant treatment versus obs, and ctx versus crt. Results Of the 397 patients included, 75.3% received adjuvant treatment (27.2% crt, 48.1% ctx) and 24.7% received obs. Within a single-payer health care system with universal coverage of costs for ctx and crt, substantial variation by geographic region was observed. Although the likelihood of receiving adjuvant treatment increased from 2005 to 2010 (p = 0.002), multivariate analysis revealed widespread variation between the treating hospitals (p = 0.001), and even between high-volume hepatopancreatobiliary hospitals (p = 0.0006). Younger age, positive lymph nodes, and positive surgical resection margins predicted an increased likelihood of receiving adjuvant treatment. Among patients receiving adjuvant treatment, positive margins and a low comorbidity burden were associated with crt compared with ctx. Conclusions Interinstitutional medical practice variation contributes significantly to differential patterns in the rate of adjuvant treatment for pcc. Whether such variation is warranted or unwarranted requires further investigation. PMID:27803598

  14. Endocrine therapy for hormone treatment-naïve advanced breast cancer.

    PubMed

    Martin, Miguel; Lopez-Tarruella, Sara; Gilarranz, Yolanda Jerez

    2016-08-01

    A proportion of patients with hormone receptor-positive locally advanced or metastatic breast cancer will not have received prior endocrine therapy. However, there are limited clinical data specifically in these patients. We conducted a review of randomized phase II and III clinical studies of anastrozole, letrozole, exemestane, palbociclib, and fulvestrant to determine the evidence base supporting use of specific endocrine therapies in this patient population. From our findings, there is a paucity of clinical studies in patients with endocrine therapy-naïve disease; however, it appears that first-line treatment effects are consistent between patients who have and have not received prior endocrine treatment.

  15. Effective treatment of rat adjuvant-induced arthritis by celastrol

    PubMed Central

    Cascão, R.; Vidal, B.; Raquel, H.; Neves-Costa, A.; Figueiredo, N.; Gupta, V.; Fonseca, J.E.; Moita, L.F.

    2012-01-01

    We have previously reported an increase in interleukin (IL)-1β and IL-17 levels, and a continuous activation of caspase-1 in early rheumatoid arthritis (RA) patients. These results suggest that drugs targeting IL-1β regulatory pathways, in addition to tumor necrosis factor (TNF), may constitute promising therapeutic agents in early RA. We have recently used a THP-1 macrophage-like cell line to screen 2320 compounds for those that down-regulate both IL-1β and TNF secretion. Celastrol was one of the most promising therapeutic candidates identified in that study. Our main goal in the present work was to investigate whether administration of celastrol is able to attenuate inflammation in a rat model of adjuvant-induced arthritis (AIA). Moreover, since IL-1β is known to play a role in the polarization of Th17 cells, we also investigate whether administration of digoxin, a specific inhibitor of Th17 cells polarization, is able to attenuate inflammation in the same rat model. We found that celastrol administration significantly suppressed joint inflammation. The histological and immunohistochemical evaluation revealed that celastrol-treated rats had a normal joint structure with complete abrogation of the inflammatory infiltrate and cellular proliferation. In contrast, we observed that digoxin administration significantly ameliorated inflammation but only if administrated in the early phase of disease course (after 4 days of disease induction), and it was not efficient at inhibiting the infiltration of immune cells within the joint and in preventing damage. Thus, our results suggest that celastrol has significant anti-inflammatory and anti-proliferative properties and can constitute a potential anti-inflammatory drug with therapeutic efficacy in the treatment of immune-mediated inflammatory diseases such as RA. Furthermore, we find that early inhibition of Th17 cells polarization ameliorates arthritis but it is not as effective as celastrol. PMID:22415021

  16. Design, conduct, and analyses of Breast International Group (BIG) 1-98: A randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer

    PubMed Central

    Giobbie-Hurder, Anita; Price, Karen N; Gelber, Richard D

    2010-01-01

    Background Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. Purpose To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. Methods From 1998–2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. Results The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. Limitations Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. Conclusions BIG 1-98 is an example of an enriched design, involving

  17. REMOVAL OF ENDOCRINE DISRUPTING COMPOUNDS USING DRINKING WATER TREATMENT PROCESSES

    EPA Science Inventory

    A growing body of scientific information has shown that man-made industrial chemicals and pesticides may interfere with the normal functioning of human and wildlife endocrine systems. These agents are referred to collectively as endocrine disrupting compounds (EDCs) and they are ...

  18. Adjuvant Teriparatide Therapy for Surgical Treatment of Femoral Fractures; Does It Work?

    PubMed Central

    Kim, Jung Taek; Jeong, Hyung Jun; Lee, Soong Joon; Kim, Hee Joong

    2016-01-01

    Purpose Atypical femoral fracture (AFF), periprosthetic femoral fracture (PPFF) and femoral nonunion (FNU) are recalcitrant challenges for orthopedic surgeons. Teriparatide (TPTD) had been demonstrated to have anabolic effects on bone in various studies. We postulated that adjuvant TPTD after operation would enhance biologic stimulation for bone formation. We investigated (1) whether the adjuvant TPTD could achieve satisfactory union rate of surgically challenging cases such as displaced AFF, PPFF and FNU; (2) whether the adjuvant TPTD could promote development of abundant callus after surgical fixation; (3) whether the adjuvant TPTD had medically serious adverse effects. Materials and Methods Thirteen patients who agreed to off label use of TPTD in combination of operation were included in this retrospective case series. Median patients' age was 68.7 years, and there were three male and ten female patients. Their diagnoses were nonunion in six patients and acute fracture in seven. Medical records and radiographic images were reviewed. Results Twelve of thirteen fractures were united both clinically and radiologically within a year after adjuvant TPTD. Union completed radiologically median 5.4 months and clinically 5.7 months after the medication, respectively. Callus appeared abundantly showing median 1.4 of fracture healing response postoperatively. There was no serious adverse reaction of medication other than itching, muscle cramp, or nausea. Conclusion Even appropriate surgical treatment is a mainstay of treatment for AFF, PPFF, and FNU, the current report suggested that adjuvant TPTD combined with stable fixation results in satisfactory outcome for the challenging fractures of femur. PMID:27777917

  19. REMOVAL OF ENDOCRINE DISRUPTOR CHEMICALS DURING DRINKING WATER TREATMENT

    EPA Science Inventory

    A group of chemicals, known as endocrine disruptor chemicals (EDCs) have been identified as having the potential to cause adverse health effects in humans and wildlife. Among this group DDT, PCBs, endosulfan, methoxychlor, diethylphthalate, diethylhexylphthalate, and bisphenol A ...

  20. EFFECTIVE RISK MANAGEMENT OF ENDOCRINE DISRUPTING CHEMICALS USING DRINKING WATER TREATMENT PROCESSES

    EPA Science Inventory

    The conventional drinking water treamtent processes of coagulation, flocculation, and filtration as well as specialized treatment processes have been examined for their capacity to remove endocrine disrupting chemicals (EDCs). A groupf od EDCs including 4-nonylphenol, diethylphth...

  1. Removal of Selected Endocrine Disrupting Chemicals During On-Site Wastewater Treatment Using A Constructed Wetland

    EPA Science Inventory

    Significant research has shown that domestic and industrial wastewater can be a source of endocrine disrupting chemicals (EDCs) to the environment. Much of this research has focused on municipal and industrial centralized wastewater treatment plants. These plants have been show...

  2. Examples of adjuvant treatment enhancing the antitumor effect of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Cecic, Ivana; Sun, Jinghai; Chaplin, David J.

    1999-07-01

    Strategies for improving the clinical efficacy of photodynamic therapy (PDT) in treatment of solid cancers include applications of different types of adjuvant treatments in addition to this modality that may result in superior therapeutic outcome. Examples of such an approach investigated using mouse tumor models are presented in this report. It is shown that the cures of PDT treated subcutaneous tumors can be substantially improved by adjuvant therapy with: metoclopramide (enhancement of cancer cell apoptosis), combretastatin A-4 (selective destruction of tumor neovasculature), Roussin's Black Salt (light activated tumor localized release of nitric oxide), or dendritic cell-based adoptive immunotherapy (immune rejection of treated tumor).

  3. Long-term endocrine sequelae after treatment of medulloblastoma: prospective study of growth and thyroid function.

    PubMed

    Oberfield, S E; Allen, J C; Pollack, J; New, M I; Levine, L S

    1986-02-01

    Endocrine evaluations were performed prospectively in 22 patients with medulloblastoma (ages 2 1/2 to 23 1/2 years at diagnosis), after craniospinal radiation with or without adjuvant chemotherapy. The mean craniospinal hypothalamic-pituitary). and thyroid radiation doses were 3600 and 2400 rads, respectively. Fourteen (73%) of 19 patients who had not yet completed their growth experienced a decrease in growth velocity. However, only three of 10 of these children, who underwent growth hormone stimulation tests, had evidence of deficient growth hormone responses, suggesting that growth hormone secretory or regulatory dysfunction, rather than absolute growth hormone deficiency, is present in the majority of these children. Elevated thyroid-stimulating hormone levels were noted in 15 of 22 patients; one patient had hypothalamic hypothyroidism. Thus, the late effects of therapy for medulloblastoma include frequent endocrine morbidity involving hypothalamic-pituitary and thyroid dysfunction.

  4. Optimal adjuvant treatment for patients with HER2-positive breast cancer in 2015.

    PubMed

    Zardavas, Dimitrios; Fouad, Tamer M; Piccart, Martine

    2015-11-01

    The introduction of trastuzumab as adjuvant treatment for patients with HER2-positive breast cancer changed the natural course of early-stage disease. Currently, one year of trastuzumab given concurrently with a taxane and following an anthracycline regimen is the preferred standard of care in Europe. The first attempt to escalate this approach, though the implementation of dual HER2 blockade with lapatinib added to trastuzumab, as assessed by the ALTTO trial, failed to improve further clinical outcomes; clinical assessment of the adjuvant trastuzumab/pertuzumab regimen is still ongoing in the APHINITY trial. Negative results were also reported for the addition of bevacizumab to adjuvant trastuzumab treatment within the context of the BETH study. Similarly, efforts to de-escalate through shortening the duration of adjuvant trastuzumab treatment failed (the PHARE trial), whereas others are still ongoing. Of note, evidence supports the use of lighter chemotherapy regimens with one year of adjuvant trastuzumab as backbone, for women with small HER2-positive breast tumors, where the omission of anthracyclines did not compromise the clinical outcome. Despite the successes achieved so far, a proportion of women with early-stage HER2-positive breast cancer, will still experience disease recurrence. The identification of these women is urgently needed, as well as the identification of predictive biomarkers to dictate the optimal treatment strategy. So far, HER2 expression status has been the only validated predictive biomarker for this patient population. Despite the clear association of pCR achieved through neoadjuvant trastuzumab-based chemotherapy with clinical outcome, results from neoadjuvant trials have not been always consistent with what was seen in the adjuvant setting. Similarly, inconsistent results have been reported for the predictive ability of alterations affecting the PI3K signaling pathway or the quantification of tumor infiltrating lymphocytes. In the era

  5. Sequential hormonal therapy for metastatic breast cancer after adjuvant tamoxifen or anastrozole.

    PubMed

    Carlson, Robert W; Henderson, I Craig

    2003-01-01

    The use of adjuvant endocrine therapy in the treatment of hormone receptor-positive, early breast cancer has become important in both pre- and postmenopausal women. Tamoxifen has been the principal adjuvant hormonal therapy in pre- and postmenopausal women with hormone receptor-positive breast cancer for nearly 20 years. Recent data in premenopausal women suggest benefit from ovarian ablation with or without tamoxifen. Early results from the 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial have demonstrated that the third-generation, selective aromatase inhibitor (AI) anastrozole ('Arimidex') is a suitable alternative adjuvant therapy for postmenopausal women with hormone receptor-positive disease. After recurrence or relapse on adjuvant endocrine therapy, responses to the sequential use of additional endocrine agents are common. The increase in the number of options now available for adjuvant therapy will have important implications for the selection of the optimal sequence of endocrine agents in the treatment of recurrent breast cancer. Menopausal status is an important factor in determining the endocrine therapy that a patient receives. For premenopausal women, tamoxifen and/or a luteinizing hormone-releasing hormone agonist such as goserelin ('Zoladex') are both options for adjuvant endocrine treatment. After progression on adjuvant and first-line tamoxifen, ovarian ablation is an appropriate second-line therapy. For premenopausal women who have undergone ovarian ablation, the use of third-line therapy with an AI becomes possible. For postmenopausal women, a wide choice of endocrine treatment options is available and an optimal sequence has yet to be determined. Options for first-line therapy of metastatic disease include an AI for women who have received adjuvant tamoxifen or tamoxifen for patients who have received adjuvant anastrozole. In addition, data suggest that fulvestrant ('Faslodex'), a novel estrogen receptor (ER) antagonist that

  6. A characterization of selected endocrine disruptor compounds in a Portuguese wastewater treatment plant.

    PubMed

    Maurício, R; Diniz, M; Petrovic, M; Amaral, L; Peres, I; Barceló, D; Santana, F

    2006-07-01

    Anthropogenic compounds that are able to disrupt the endocrine system of wildlife species are a major cause for concern and have led to a demand for new screening methods. The identification and quantification of endocrine disruptor compounds at wastewater treatment plant is of major interest to assess the endocrine activity of wastewater treatment plant discharges into the environment. This study consists of a preliminary survey of concentrations of previously selected endocrine disruptor compounds, undertaken to establish environmental concentrations and to support a biological program assay exposing freshwater fish to them. Selected endocrine disrupting chemicals (APEs, bisphenol A and 17 beta-estradiol) were measured in samples from a wastewater treatment plant located in Lisbon (Portugal), using recent commercial enzyme-linked immunosorbent assay kits and also LC-MS/MS. The results show that the wastewater treatment plant treatment process is efficient on the removal of target endocrine disruptor compounds. However, environmentally significant concentrations are still present in the treated effluent. The results also show that enzyme-linked immunosorbent assay kit is suitable for routine analysis of the selected compounds. The results are also useful since the wastewater treatment plant is located in a Mediterranean region, which results in an effluent with its own characteristics.

  7. [What to think of "adjuvant" or "neoadjuvant" thermotherapy in the treatment of uveal melanomas?].

    PubMed

    Grange, J D

    2001-02-01

    Before 810Nm laser thermotherapy has been usd for uveal melanoma, several authors especially in Essen (Germany) were asking themselves about the possibilities of xenon arc or argon laser effects on uveal melanomas. High rates of recurrences due to the non penetration of therapeutic light till the sclera had led to the conception of using adjuvant thermotherapy associated with radiotherapy, through microwaves, ultrasounds or ferromagnetic seeds. In Leyden (Netherlands) was proposed the use of 810Nm laser diode initially as an adjuvant to radiotherapy and later on as primary isolated treatment ("neo adjuvant" TTT), especially for small tumours located in the posterior pole (juxta-papillary tumours). TTT used alone should not be proposed for tumours of inital height of more than 3,5 to 4mm. "Neo adjuvant" thermotherapy finds some other indications like decompensated naevi responsible for macular detachment. Bigger peripheral tumours stabilized by protonbeam therapy but associated with persistent detachment after the 12(th) month could be treated with "adjuvant" TTT. Finally the importance of the quality of the tumour edges treatment should be emphasized.

  8. [Treatment of liver metastasis of endocrine tumors of the pancreas].

    PubMed

    Orozco Zepeda, H

    1997-01-01

    The aim of this review article is to analyze the diagnostic approach, presentation and therapeutic modalities in patients with liver metastasis from endocrine tumors. The paper shows the "state of the art" of therapeutic approaches with emphasis on the roll of different surgery, radio and chemotherapy, arterial embolization and other palliative procedures. The overall results of each of this modalities are also shown.

  9. Radiation Therapy Is Associated With Improved Survival in the Adjuvant and Definitive Treatment of Intrahepatic Cholangiocarcinoma

    SciTech Connect

    Shinohara, Eric T. Mitra, Nandita; Guo Mengye; Metz, James M.

    2008-12-01

    Purpose: Intrahepatic cholangiocarcinomas (IHC) are rare tumors for which large randomized studies regarding the use of radiation are not available. The purpose of this study was to examine the role of adjuvant and definitive radiation therapy in the treatment of IHC in a large group of patients. Methods and Materials: This is a retrospective analysis of 3,839 patients with IHC collected from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was overall survival (OS). Results: Patients received either surgery alone (25%), radiation therapy alone (10%), surgery and adjuvant radiation therapy (7%) or no treatment (58%). The median age of the patient population was 73 years (range, 22-102 years); 52% of patients were male and 81% were Caucasian. Median OS was 11 (95% confidence interval [CI], 9-13), 6 (95% CI, 5-6), 7 (95% CI, 6-8), and 3 months for surgery and adjuvant radiation therapy, sugery alone, radiation therapy alone, and no treatment, respectively. The OS was significantly different between surgery alone and surgery and adjuvant radiation therapy (p = 0.014) and radiation therapy alone and no treatment (p < 0.0001). Use of surgery and adjuvant radiation therapy conferred the greatest benefit on OS (HR = 0.40; 95% CI, 0.34-0.47), followed by surgery alone (hazard ratio [HR], 0.49; 95% CI, 0.44-0.54) and radiation therapy alone (HR, 0.68; 95% CI, 0.59-0.77) compared with no treatment, on multivariate analysis. Propensity score adjusted hazard ratios (controlling for age, race/ethnicity, stage, and year of diagnosis) were also significant (surgery and adjuvant radiation therapy vs. surgery alone (HR, 0.82; 95% CI, 0.70-0.96); radiation therapy alone vs. no treatment (HR, 0.67; 95% CI, 0.58-0.76)). Conclusions: The study results suggest that adjuvant and definitive radiation treatment prolong survival, although cure rates remain low. Future studies should evaluate the addition of chemotherapy and biologics to the treatment of

  10. Contribution of Early Detection and Adjuvant Treatments to Breast Cancer Mortality Reduction in Catalonia, Spain

    PubMed Central

    Vilaprinyo, Ester; Puig, Teresa; Rue, Montserrat

    2012-01-01

    Background Reductions in breast cancer (BC) mortality in Western countries have been attributed to the use of screening mammography and adjuvant treatments. The goal of this work was to analyze the contributions of both interventions to the decrease in BC mortality between 1975 and 2008 in Catalonia. Methodology/Principal Findings A stochastic model was used to quantify the contribution of each intervention. Age standardized BC mortality rates for calendar years 1975–2008 were estimated in four hypothetical scenarios: 1) Only screening, 2) Only adjuvant treatment, 3) Both interventions, and 4) No intervention. For the 30–69 age group, observed Catalan BC mortality rates per 100,000 women-year rose from 29.4 in 1975 to 38.3 in 1993, and afterwards continuously decreased to 23.2 in 2008. If neither of the two interventions had been used, in 2008 the estimated BC mortality would have been 43.5, which, compared to the observed BC mortality rate, indicates a 46.7% reduction. In 2008 the reduction attributable to screening was 20.4%, to adjuvant treatments was 15.8% and to both interventions 34.1%. Conclusions/Significance Screening and adjuvant treatments similarly contributed to reducing BC mortality in Catalonia. Mathematical models have been useful to assess the impact of interventions addressed to reduce BC mortality that occurred over nearly the same periods. PMID:22272292

  11. A Preliminary Evaluation of Fast ForWord-Language as an Adjuvant Treatment in Language Intervention

    ERIC Educational Resources Information Center

    Fey, Marc E.; Finestack, Lizbeth H.; Gajewski, Byron J.; Popescu, Mihai; Lewine, Jeffrey D.

    2010-01-01

    Purpose: Fast ForWord-Language (FFW-L) is designed to enhance children's processing of auditory-verbal signals and, thus, their ability to learn language. As a preliminary evaluation of this claim, we examined the effects of a 5-week course of FFW-L as an adjuvant treatment with a subsequent 5-week conventional narrative-based language…

  12. Adjuvant Stereotactic Radiosurgery and Radiation Therapy for the Treatment of Intracranial Chordomas

    PubMed Central

    Choy, Winward; Terterov, Sergei; Ung, Nolan; Kaprealian, Tania; Trang, Andy; DeSalles, Antonio; Chung, Lawrance K.; Martin, Neil; Selch, Michael; Bergsneider, Marvin; Yong, William; Yang, Isaac

    2015-01-01

    Objective Chordomas are locally aggressive, highly recurrent tumors requiring adjuvant radiotherapy following resection for successful management. We retrospectively reviewed patients treated for intracranial chordomas with adjuvant stereotactic radiosurgery (SRS) and stereotactic radiation therapy (SRT). Methods A total of 57 patients underwent 83 treatments at the UCLA Medical Center between February 1990 and August 2011. Mean follow-up was 57.8 months. Mean tumor diameter was 3.36 cm. Overall, 8 and 34 patients received adjuvant SRS and SRT, and the mean maximal dose of radiation therapy was 1783.3 cGy and 6339 cGy, respectively. Results Overall rate of recurrence was 51.8%, and 1- and 5-year progression-free survival (PFS) was 88.2% and 35.2%, respectively. Gross total resection was achieved in 30.9% of patients. Adjuvant radiotherapy improved outcomes following subtotal resection (5-year PFS 62.5% versus 20.1%; p = 0.036). SRS and SRT produced comparable rates of tumor control (p = 0.28). Higher dose SRT (> 6,000 cGy) (p = 0.013) and younger age (< 45 years) (p = 0.03) was associated with improved rates of tumor control. Conclusion Adjuvant radiotherapy is critical following subtotal resection of intracranial chordomas. Adjuvant SRT and SRS were safe and improved PFS following subtotal resection. Higher total doses of SRT and younger patient age were associated with improved rates of tumor control. PMID:26949587

  13. Duration of adjuvant treatment following radical resection of metastases from gastrointestinal stromal tumours

    PubMed Central

    NANNINI, MARGHERITA; PANTALEO, MARIA ABBONDANZA; MALEDDU, ALESSANDRA; SAPONARA, MARISTELLA; MANDRIOLI, ANNA; LOLLI, CRISTIAN; PALLOTTI, MARIA CATERINA; GATTO, LIDIA; SANTINI, DONATELLA; PATERINI, PAOLA; DI SCIOSCIO, VALERIO; CATENA, FAUSTO; FUSAROLI, PIETRO; PINNA, ANTONIO DANIELE; DEI TOS, ANGELO PAOLO; BIASCO, GUIDO

    2011-01-01

    Large-scale studies have demonstrated that continuative treatment in advanced and adjuvant settings results in a gain-of-survival. However, the discontinuation, and the duration of treatment in disease-free patients who have undergone radical surgical resection of metastases from gastrointestinal stromal tumours (GISTs) have yet to be evaluated. We retrospectively reviewed 40 patients with advanced and recurrent GIST, included in our GIST database, focusing on patients (5 males and 2 females; median age 56 years) who continued medical treatment following radical surgical resection of metastatic lesions. Seven out of 40 patients underwent surgery and continued medical treatment following radical surgical resection of metastatic lesions. The duration of adjuvant therapy was 3, 12, 16, 24, 35, 37 and 52 months, respectively, with a median of 26 months. No patients discontinued therapy and all were disease-free at the final CT-scan evaluation. Considering that the discontinuation of imatinib in responding patients with advanced GIST (even in complete remission) results in a rapid high risk of progression, and a short adjuvant therapy results in a shorter disease-free and overall survival in high-risk GIST patients, it is also likely that treatment should not be discontinued in this setting. However, large-scale studies are required to better assess the optimal duration of treatment, particularly after 5 years, by focusing on the identification of predictive factors for the selection of patients who may benefit from a prolonged or lifelong imatinib treatment. PMID:22740975

  14. Continued value of adjuvant anthracyclines as treatment for early breast cancer.

    PubMed

    Turner, Natalie; Biganzoli, Laura; Di Leo, Angelo

    2015-07-01

    Anthracyclines are frequently used in the adjuvant treatment of early-stage breast cancer. However, with the increasing use of other active drugs--mainly taxanes and trastuzumab in HER2-positive disease--coupled with concerns about anthracycline-associated toxic effects, there is debate about whether anthracyclines are still needed. Three major factors should be taken into consideration with the investigation of the role of anthracyclines in management of early breast cancer; specifically, the proven efficacy of anthracyclines in breast cancer, the absence of superiority of non-anthracycline-based chemotherapy over anthracycline-taxane regimens, and the low risk of toxic effects associated with the cumulative doses of anthracyclines used in contemporary regimens. The risks remain substantially outweighed by the benefits of treatment with anthracyclines, and thus, they maintain an important role in adjuvant treatment of breast cancer, particularly in women with high-risk disease.

  15. [Emergency antibiotherapy and adjuvant treatments for acute bacterial meningitis].

    PubMed

    Mourvillier, B

    2009-01-01

    The management of bacterial meningitis is based on the combination of several components. The objective of this review is to give an overview of the literature concerning both the arguments for urgent antibiotic treatment associated with a particular focus on the place of corticosteroids. Among other treatments, glycerol seems the best rated but symptomatic measures, which may not be achieved by randomized studies, should not be overlooked. Many animal studies explore other treatment options, but none can be translated into clinical practice. The neuroimaging has been little evaluated despite recent technological advances but remains important in monitoring of patients whose evolution is considered unfavorable.

  16. Fish endocrine disruption responses to a major wastewater treatment facility upgrade.

    PubMed

    Barber, Larry B; Vajda, Alan M; Douville, Chris; Norris, David O; Writer, Jeffery H

    2012-02-21

    The urban-water cycle modifies natural stream hydrology, and domestic and commercial activities increase the burden of endocrine-disrupting chemicals, such as steroidal hormones and 4-nonylphenol, that can disrupt endocrine system function in aquatic organisms. This paper presents a series of integrated chemical and biological investigations into the occurrence, fate, and effects of endocrine-disrupting chemicals in the City of Boulder Colorado's WWTF and Boulder Creek, the receiving stream. Results are presented showing the effects of a full-scale upgrade of the WWTF (that treats 0.6 m(3) s(-1) of sewage) from a trickling filter/solids contact process to an activated sludge process on the removal of endocrine-disrupting compounds and other contaminants (including nutrients, boron, bismuth, gadolinium, and ethylenediaminetetraacetic acid) through each major treatment unit. Corresponding impacts of pre- and postupgrade effluent chemistry on fish reproductive end points were evaluated using on-site, continuous-flow experiments, in which male fathead minnows (Pimephales promelas) were exposed for 28 days to upstream Boulder Creek water and WWTF effluent under controlled conditions. The upgrade of the WWTF resulted in improved removal efficiency for many endocrine-disrupting chemicals, particularly 17β-estradiol and estrone, and fish exposed to the postupgrade effluent indicated reduction in endocrine disruption relative to preupgrade conditions.

  17. MANAGING ENDOCRINE DISRUPTING CHEMICALS USING EXISTING AND INNOVATIVE WASTEWATER TREATMENT TECHNOLOGIES

    EPA Science Inventory

    Research has shown that wastewater (WW) can be a significant source of endocrine disrupting chemicals (EDCs) to the environment. WW treatment (WWT) may include centralized wastewater treatment plants (WWTPs) or smaller on-site WWT technologies. EDCs found in WWT effluents (aqueou...

  18. Fate of steroid hormones and endocrine activities in swine manure disposal and treatment facilities.

    PubMed

    Combalbert, Sarah; Bellet, Virginie; Dabert, Patrick; Bernet, Nicolas; Balaguer, Patrick; Hernandez-Raquet, Guillermina

    2012-03-01

    Manure may contain high concern endocrine-disrupting compounds (EDCs) such as steroid hormones, naturally produced by pigs, which are present at μgL(-1) levels. Manure may also contain other EDCs such as nonylphenols (NP), polycyclic aromatic hydrocarbons (PAHs) and dioxins. Thus, once manure is applied to the land as soil fertilizer these compounds may reach aquifers and consequently living organisms, inducing abnormal endocrine responses. In France, manure is generally stored in anaerobic tanks prior spreading on land; when nitrogen removal is requested, manure is treated by aerobic processes before spreading. However, little is known about the fate of hormones and multiple endocrine-disrupting activities in such manure disposal and treatment systems. Here, we determined the fate of hormones and diverse endocrine activities during manure storage and treatment by combining chemical analysis and in vitro quantification of estrogen (ER), aryl hydrocarbon (AhR), androgen (AR), pregnane-X (PXR) and peroxysome proliferator-activated γ (PPARγ) receptor-mediated activities. Our results show that manure contains large quantities of hormones and activates ER and AhR, two of the nuclear receptors studied. Most of these endocrine activities were found in the solid fraction of manure and appeared to be induced mainly by hormones and other unidentified pollutants. Hormones, ER and AhR activities found in manure were poorly removed during manure storage but were efficiently removed by aerobic treatment of manure.

  19. Successful treatment of gallbladder mixed adenoneuroendocrine carcinoma with neo-adjuvant chemotherapy

    PubMed Central

    2012-01-01

    Mixed adenoneuroendocrine carcinoma (MANEC) carcinomas rarely occur in the gallbladder. Here we reported a case of giant gallbladder unresectable mass with local liver invasion and omentum metastasis, which proved to be neuroendocrine carcinoma (NEC) by biopsy, received successful radical operation after neo-adjuvant chemotherapy plus somatostatin treatment. The patient showed good response as the neoplasm diminished dramatically and showed clear margin after 6 courses of treatment. A radical operation including cholecystectomy, hepatic wedge resection of the gallbladder fossa segment and lymph node of group 8a and 8p resection was performed successfully. Postoperative histopathological examination revealed neuroendocrine carcinoma mixed with adenocarcinoma in the gallbladder wall. Followed up showed no evidence of recurrence after 7 months of the operation. We suggest that neo-adjuvant chemotherapy may be beneficial to gallbladder mixed neuroendocrine carcinomas in an advanced stage which could also be advantageous to NEC of other organs. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/2731892837743787 PMID:23186166

  20. Long-term neuro-endocrine sequelae after treatment for childhood medulloblastoma.

    PubMed

    Heikens, J; Michiels, E M; Behrendt, H; Endert, E; Bakker, P J; Fliers, E

    1998-09-01

    The occurrence of neuro-endocrine deficiencies following craniospinal irradiation for medulloblastoma is well known, but data concerning the spectrum and prevalence of endocrine abnormalities in adulthood are scarce. We studied endocrine function in 20 (median age 25 years) adult subjects, 8-25 years (median 16 years) after therapy. The radiation dose to the whole cranium and spinal axis was 35 +/- 2.6 Gray (mean +/- standard deviation) with a boost to the posterior fossa of 18 +/- 3.7 Gray. 13 subjects had received additional chemotherapy. In 15 of 20 (75%) subjects, endocrine abnormalities were observed. In 14 (70%), growth hormone (GH) secretion was impaired; 7 (35%) subjects had an absolute GH deficiency, while 7 (35%) showed subnormal responses to insulin-induced hypoglycaemia. In contrast, only 20% (4) of these subjects showed impairment of the hypothalamus-pituitary-thyroid (HPT) axis, while 15% (3) showed central impairment of hypothalamus-pituitary-gonadal (HPG) function. Central impairment of the HPG axis was associated with impaired GH secretion in all cases. Central adrenal insufficiency was not observed. Basal levels of prolactin were normal in all subjects. Young age at treatment was a determinant of GH deficiency in adulthood (P = 0.014). Neither post-treatment interval, nor the use of chemotherapy were determinants of central endocrine impairment in adulthood. In long-term survivors of medulloblastoma, GH deficiency has a high prevalence. In contrast, impairment of the HPG and HPT axis is less common, while central adrenal insufficiency was not observed.

  1. Vitamin Supplementation as an Adjuvant Treatment for Alzheimer’s Disease

    PubMed Central

    Usman, Muhammad; Ali, Farhan; Satti, Siddique Akbar

    2016-01-01

    Alzheimer’s Disease (AD) is a slowly progressing neurodegenerative disorder representing a major health concern worldwide. This disorder is characterised by progressive dementia and cognitive decline. The pathological hallmarks of AD include the presence of Aβ plaques and tau neurofibrils. Research has shown that oxidative stress represents a major risk factor associated with AD pathology. Accumulation of Aβ plaques and relative lack of antioxidant defence mechanisms, including cellular antioxidant enzymes and dietary antioxidants like vitamins, assist in the exacerbation of oxidative stress. Reactive Oxygen Species (ROS) produced as the result of oxidative stress, that increase structural and functional abnormalities in brain neurons, which then manifests as dementia and decline in cognition. Data from numerous epidemiological studies suggests that nutrition is one of the most important yet modifiable risk factors for AD. Since oxidative stress contributes a great deal in the development and progression of AD, anything that could attenuate oxidative stress would help in decreasing the prevalence and incidence of AD. There is increasing evidence that supports the use of different antioxidant as an adjuvant treatment for AD. Vitamins are one such antioxidant that can be used as an adjuvant in AD treatment. This paper will focus on the evidence, based on current literature, linking the use of vitamin supplementations as an adjuvant treatment for AD. PMID:27656493

  2. Tuberculosis axillary lymph node coexistent breast cancer in adjuvant treatment: case report

    PubMed Central

    Bromberg, Silvio Eduardo; do Amaral, Paulo Gustavo Tenório

    2015-01-01

    Coexistence of breast cancer and tuberculosis is rare. In most cases, involvement by tuberculosis occurs in axillary lymph nodes. We report a case of a 43-years-old patient who had undergone adenomastectomy and left sentinel lymph node biopsy due to a triple negative ductal carcinoma. At the end of adjuvant treatment, the patient had an atypical lymph node in the left axilla. Lymph node was excised, and after laboratory analysis, the diagnosis was ganglion tuberculosis. The patient underwent treatment for primary tuberculosis. The development of these two pathologies can lead to problems in diagnosis and treatment. An accurate diagnosis is important to avoid unnecessary surgical procedures. PMID:26018148

  3. Surgical adjuvant treatment of locally advanced breast cancer.

    PubMed Central

    Townsend, C M; Abston, S; Fish, J C

    1985-01-01

    The reported incidence of local recurrence after mastectomy for locally advanced breast cancer (TNM Stage III and IV) is between 30% and 50%. The purpose of this study was to evaluate the effect of radiation therapy (XRT) followed by total mastectomy on the incidence of local recurrence in patients with locally advanced breast cancer. Fifty-three patients who presented with locally advanced breast cancer, without distant metastases, were treated with XRT (4500-5000 R) to the breast, chest wall, and regional lymph nodes. Five weeks after completion of XRT, total mastectomy was performed. There were no operative deaths. The complications that occurred in 22 patients after surgery were flap necrosis, wound infection, and seroma. Patients have been followed from 3 to 134 months. Twenty-five patients are alive (3-134 months), 12 free of disease; 28 patients have died with distant metastases (6-67 months). Isolated local recurrence occurred in only two patients. Four patients had local and distant recurrence (total local recurrence is 6/53). The remaining patients all developed distant metastases. We have devised a treatment strategy which significantly decreases the incidence of local recurrence in patients with locally advanced breast cancer. However, the rapid appearance of distant metastases emphasizes the need for systemically active therapy in patients with locally advanced breast cancer. PMID:3994434

  4. EVALUATION OF DRINKING WATER TREATMENT TECHNOLOGIES FOR REMOVAL OF ENDOCRINE DISRUPTORS

    EPA Science Inventory

    Evaluation of Drinking Water Treatment Technologies for Removal of Endocrine Disruptors. Schenck, K*, Speth, T, U.S. EPA, Cincinnati, OH, USA, Rosenblum, L, Wendelken, S, Pepich, B, and Krishnan, R, Shaw Environmental, Inc., Cincinnati, OH, USA. Many of the chemicals identified...

  5. Changes of Pain Perception, Autonomic Function, and Endocrine Parameters during Treatment of Anorectic Adolescents

    ERIC Educational Resources Information Center

    Bar, Karl-Jurgen; Boettger, Silke; Wagner, Gerd; Wilsdorf, Christine; Gerhard, Uwe Jens; Boettger, Michael K.; Blanz, Bernhard; Sauer, Heinrich

    2006-01-01

    Objectives: The underlying mechanisms of reduced pain perception in anorexia nervosa (AN) are unknown. To gain more insight into the pathology, the authors investigated pain perception, autonomic function, and endocrine parameters before and during successful treatment of adolescent AN patients. Method: Heat pain perception was assessed in 15…

  6. Removal Of Endocrine Disrupting Chemicals By A Constructed Wetland For On-Site Domestic Wastewater Treatment

    EPA Science Inventory

    Research has shown that domestic and industrial wastewater can be a source of endocrine disrupting chemicals (EDCs) to the environment. Much of this research has focused on municipal and industrial centralized wastewater treatment plants (WWTPs). These WWTPs have been shown to ...

  7. EVALUATION OF DRINKING WATER TREATMENT TECHNOLOGIES FOR REMOVAL OF ENDOCRINE DISRUPTING COMPOUNDS

    EPA Science Inventory

    Many of the chemicals identified as potential endocrine disrupting compounds (EDCs) may be present in surface or ground waters used as drinking water sources due to their introduction from domestic and industrial sewage treatment systems and wet-weather runoff. In order to dec...

  8. Endocrine therapy resistance in breast cancer: current status, possible mechanisms and overcoming strategies.

    PubMed

    Fan, Weimin; Chang, Jinjia; Fu, Peifeng

    2015-08-01

    Endocrine therapy has become one of most effective forms of targeted adjuvant therapy for hormone-sensitive breast cancer and may be given after surgery or radiotherapy, and also prior, or subsequent to chemotherapy. Current commonly used drugs for adjuvant endocrine therapy can be divided into following three classes: selective estrogen receptor modulators, aromatase inhibitors and selective estrogen receptor downregulators. Tumor cells can develop resistance to endocrine therapy, a major obstacle limiting the success of breast cancer treatment. The complicated crosstalk, both genomic and nongenomic, between estrogen receptors and growth factors was considered to be a crucial factor contributing to endocrine resistance. However, resistance to this therapy is thought to be a progressive, step-wise process, and the underlying mechanism remains unclear. In this review, we summarize the possible biological and molecular mechanisms that underlie endocrine resistance, and discuss some novel strategies to overcoming these issues.

  9. Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

    SciTech Connect

    McMillan, Matthew T.; Ojerholm, Eric; Roses, Robert E.; Plastaras, John P.; Metz, James M.; Mamtani, Ronac; Stripp, Diana; Ben-Josef, Edgar; Datta, Jashodeep

    2015-10-01

    Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.

  10. Bisphosphonates in the adjuvant treatment of young women with breast cancer: the estrogen rich is a poor candidate!

    PubMed

    Azim, Hamdy A; Kamal, Nermine S; Malak, Rafaat A

    2013-06-01

    During the last 2 decades the role of bisphosphonates (BPs) to reduce skeletal-related events from bone metastases in breast cancer has been well defined. Several preclinical studies have strongly suggested that BPs may also provide an anti-cancer effect in early breast cancer. Indeed, the use of adjuvant BPs represents a unique approach that attempts at eradicating occult tumor micro-metastases residing in the bone marrow via targeting the bone microenvironment to render it less favorable for cancer cell growth. Although, this concept has been tested clinically for more than 15 years, no final consensus has been reached as for the routine use of BPs in the adjuvant phase of breast cancer, owing to conflicting results of randomized studies. Nevertheless, accumulating evidence from recent trials has indicated a therapeutic benefit of adjuvant BPs-particularly zoledronic acid-in women with established menopause, with no or perhaps detrimental effects in premenopausal women. Indeed, this hypothesis has opened a new chapter on the role of estrogen-poor microenvironment as a potential pre-requisite for the anti-tumor effects of BPs in the adjuvant phase of breast cancer. In this review, we will emphasize the biological rational of using BPs to target bone microenvironment in patients with early breast cancer and we will explore mechanistic differences; related to bisphosphonates effects in premenopausal versus postmenopausal women and how the endocrine environment would influence the anticancer potential of these compounds.

  11. Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients.

    PubMed

    Dienstmann, Rodrigo; Salazar, Ramon; Tabernero, Josep

    2015-06-01

    For more than three decades, postoperative chemotherapy-initially fluoropyrimidines and more recently combinations with oxaliplatin-has reduced the risk of tumor recurrence and improved survival for patients with resected colon cancer. Although universally recommended for patients with stage III disease, there is no consensus about the survival benefit of postoperative chemotherapy in stage II colon cancer. The most recent adjuvant clinical trials have not shown any value for adding targeted agents, namely bevacizumab and cetuximab, to standard chemotherapies in stage III disease, despite improved outcomes in the metastatic setting. However, biomarker analyses of multiple studies strongly support the feasibility of refining risk stratification in colon cancer by factoring in molecular characteristics with pathologic tumor staging. In stage II disease, for example, microsatellite instability supports observation after surgery. Furthermore, the value of BRAF or KRAS mutations as additional risk factors in stage III disease is greater when microsatellite status and tumor location are taken into account. Validated predictive markers of adjuvant chemotherapy benefit for stage II or III colon cancer are lacking, but intensive research is ongoing. Recent advances in understanding the biologic hallmarks and drivers of early-stage disease as well as the micrometastatic environment are expected to translate into therapeutic strategies tailored to select patients. This review focuses on the pathologic, molecular, and gene expression characterizations of early-stage colon cancer; new insights into prognostication; and emerging predictive biomarkers that could ultimately help define the optimal adjuvant treatments for patients in routine clinical practice.

  12. Fulvestrant ('Faslodex')--a new treatment option for patients progressing on prior endocrine therapy.

    PubMed

    Morris, C; Wakeling, A

    2002-12-01

    Since its introduction more than 30 years ago, tamoxifen has been the most widely used endocrine therapy for the treatment of women with advanced breast cancer. More recently, a number of alternative endocrine treatments have been developed, including several selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and, most recently, fulvestrant ('Faslodex'). Fulvestrant is an estrogen receptor (ER) antagonist, which, unlike the SERMs, has no known agonist (estrogenic) effect and downregulates the ER protein. Tamoxifen is effective and well tolerated, although the non-steroidal AIs, anastrozole and letrozole, are more effective treatments for advanced disease than tamoxifen. Fulvestrant has recently gained US Food and Drug Administration approval for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. In two global phase III clinical trials fulvestrant was at least as effective and as equally well tolerated as anastrozole for the treatment of postmenopausal women with advanced and metastatic breast cancer. In a retrospective analysis of the combined data from these trials, mean duration of response was significantly greater for fulvestrant compared with anastrozole. These new hormonal treatments expand the choice of endocrine therapy for women with advanced breast cancer and offer new options for sequencing and combining treatments.

  13. Chinese herbal medicines as adjuvant treatment during chemo- or radio-therapy for cancer.

    PubMed

    Qi, Fanghua; Li, Anyuan; Inagaki, Yoshinori; Gao, Jianjun; Li, Jijun; Kokudo, Norihiro; Li, Xiao-Kang; Tang, Wei

    2010-12-01

    Numerous studies have indicated that in cancer treatment Chinese herbal medicines in combination with chemo- or radio-therapy can be used to enhance the efficacy of and diminish the side effects and complications caused by chemo- and radio-therapy. Therefore, an understanding of Chinese herbal medicines is needed by physicians and other health care providers. This review provides evidence for use of Chinese herbal medicines as adjuvant cancer treatment during chemo- or radio-therapy. First, Chinese herbal medicines (e.g. Astragalus, Turmeric, Ginseng, TJ-41, PHY906, Huachansu injection, and Kanglaite injection) that are commonly used by cancer patients for treating the cancer and/or reducing the toxicity induced by chemo- or radio-therapy are discussed. Preclinical and clinical studies have shown that these Chinese herbal medicines possess great advantages in terms of suppressing tumor progression, increasing the sensitivity of chemo- and radio-therapeutics, improving an organism's immune system function, and lessening the damage caused by chemo- and radio-therapeutics. Second, clinical trials of Chinese herbal medicines as adjuvant cancer treatment are reviewed. By reducing side effects and complications during chemo- and radio-therapy, these Chinese herbal medicines have a significant effect on reducing cancer-related fatigue and pain, improving respiratory tract infections and gastrointestinal side effects including diarrhea, nausea, and vomiting, protecting liver function, and even ameliorating the symptoms of cachexia. This review should contribute to an understanding of Chinese herbal medicines as adjuvant treatment for cancer and provide useful information for the development of more effective anti-cancer drugs.

  14. Salvage treatment for childhood ependymoma after surgery only: Pitfalls of omitting 'at once' adjuvant treatment

    SciTech Connect

    Massimino, Maura . E-mail: maura.massimino@istitutotumori.mi.it; Giangaspero, Felice; Garre, Maria Luisa; Genitori, Lorenzo; Perilongo, Giorgio; Collini, Paola; Riva, Daria; Valentini, Laura; Scarzello, Giovanni; Poggi, Geraldina; Spreafico, Filippo; Peretta, Paola; Mascarin, Maurizio; Modena, Piergiorgio; Sozzi, Gabriella; Bedini, Nice; Biassoni, Veronica; Urgesi, Alessandro; Balestrini, Maria Rosa; Finocchiaro, Gaetano; Sandri, Alessandro; Gandola, Lorenza

    2006-08-01

    Purpose: To discuss the results obtained by giving adjuvant treatment for childhood ependymoma (EPD) at relapse after complete surgery only. Methods and Materials: Between 1993 and 2002, 63 children older than 3 years old entered the first Italian Association for Pediatric Hematology and Oncology protocol for EPD (group A), and another 14 patients were referred after relapsing after more tumor excisions only (group B). Prognostic factors were homogeneously matched in the two groups. We report on the outcome of group B. Results: Mean time to first local progression in group B had been 14 months. Tumors originated in the posterior fossa (PF) in 10 children and were supratentorial (ST) in 4; 11 had first been completely excised (NED) and 3 had residual disease (ED). Diagnoses were classic EPD in 9 patients, anaplastic in 5. Eight children were referred NED and 6 ED after two or more operations, 5 had cranial nerve palsy, 1 had recurrent meningitis, and 2 had persistent hydrocephalus. All received radiotherapy (RT) to tumor bed and 5 also had pre-RT chemotherapy. Six of 14 patients (6/10 with PF tumors) had a further relapse a mean 6 months after the last surgery; 4 of 6 died: progression-free survival and overall survival at 4 years after referral were 54.4% and 77%, respectively. Considering only PF tumors and setting time 0 as at the last surgery for group B, progression-free survival and overall survival were 32% and 50% for group B and 52% (p < 0.20)/70% (p < 0.29) for the 46 patients in group A with PF tumors. Local control was 32% in group B and 70.5% in group A (p = 0.02). Conclusions: Relapsers after surgery only, especially if with PF-EPD, do worse than those treated after first diagnosis; subsequent surgery for tumor relapse has severe neurologic sequelae.

  15. [Clinical and histopathological results after the neo-adjuvant treatment of advanced rectal tumors].

    PubMed

    Varga, László; Baradnay, Gellért; Hohn, József; Simonka, Zsolt; Hideghéthy, Katalin; Maráz, Anikó; Nikolényi, Alíz; Veréb, Blanka; Tiszlavicz, László; Németh, István; Mán, Eszter; Lázár, György

    2010-06-01

    The role of the surgical intervention is decisive in treating colorectal tumors. The neo-adjuvant radio-chemotherapy has improved the efficacy of the treatment of advanced rectum tumors. In order to decrease the size and stage of advanced rectal carcinoma and to increase the rate of resecability, we introduced neoadjuvant radio-chemotherapy. We carried out neo-adjuvant and surgical treatment in case of 67 patients with rectal adenocarcinoma (T 2-4 N 1-2 M 0 ) between June 1, 2005 and July 31, 2008. The average age of the patients was 61.2 years, the division according to sex was 44 males/23 females. Regarding the local stage of the rectal process or the proximity to the sphincter, we applied radio-chemotherapy (radiotherapy 25 times altogether 45 Gy and on the first and last week for 5-5 days they received 350 mg/m 2 /day 5-FU and 20 mg/m 2 /day leucovorin chemotherapy, recently complemented with 3 x 1.8 Gy advanced boost radiation aiming at the macroscopic tumor site with security zone). Patients underwent surgery 8 weeks on average after restaging examinations. Thirty-eight patients underwent anterior rectal resection with double stapler procedure; there were 18 abdominoperineal rectal extirpations, 7 Hartmann operations and 4 per annum excisions. Compared to the preoperative staging, the histological evaluation of the resected specimens showed total remission (pT 0 N 0 ) in 11% and partial remission in 43%. The morbidity necessitating reoperation was 5.9%, without mortality and suture insufficiency. The long-term neo-adjuvant oncological treatment led to down-staging of rectal tumors in most cases and increased the resecability and rate of resection operations.

  16. Adjuvant pegylated liposomal doxorubicin for older women with endocrine nonresponsive breast cancer who are NOT suitable for a “standard chemotherapy regimen”: the CASA randomized trial

    PubMed Central

    Crivellari, Diana; Gray, Kathryn P; Dellapasqua, Silvia; Puglisi, Fabio; Ribi, Karin; Price, Karen N; Láng, István; Gianni, Lorenzo; Spazzapan, Simon; Pinotti, Graziella; Lüthi, Jean-Marc; Gelber, Richard D; Regan, Meredith M; Colleoni, Marco; Castiglione-Gertsch, Monica; Maibach, Rudolf; Rabaglio, Manuela; Coates, Alan S; Goldhirsch, Aron

    2013-01-01

    Summary There is no optimal treatment for breast cancers lacking estrogen (ER) and progesterone (PgR) receptors in elderly women with co-morbidities that prevent use of “standard chemotherapy regimens” such as AC or CMF. The CASA trial studied pegylated liposomal doxorubicin (PLD) and low dose, metronomic cyclophosphamide+ methotrexate (CM) for older (>65), vulnerable women with operable, ER and PgR-negative breast cancer. After two years the trial closed early, due to slow and inadequate accrual, with 77 patients (38:PLD, 36:CM, 3:nil). Sixty-eight percent completed PLD; 83% completed CM (both 16-weeks). Patients on PLD reported worse quality of life, cognitive and physical functioning than non-PLD regimens (primarily CM). At a median follow-up of 42 months, 78% of randomized patients remained free of any breast cancer recurrence. Based on our limited experience, PLD and CM may be reasonable options for further study for elderly vulnerable patients with endocrine non-responsive breast cancer. PMID:23453899

  17. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer.

    PubMed

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim; Millikan, Randall E; Stadler, Walter; De Mulder, Pieter; Sherif, Amir; von der Maase, Hans; Tsukamoto, Taiji; Soloway, Mark S

    2007-01-01

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed, as is chemotherapy for patients with metastatic urothelial cancer. The conference panel consisted of 10 medical oncologists and urologists from 3 continents who are experts in this field and who reviewed the English-language literature through October 2004. Relevant English-language literature was identified with the use of Medline; additional cited works not detected on the initial search regarding neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and chemotherapy for patients with metastatic urothelial cancer were reviewed. Evidence-based recommendations for diagnosis and management of the disease were made with reference to a 4-point scale. Results of the authors' deliberations are presented as a consensus document. Meta-analysis of randomized trials on cisplatin-containing combination neoadjuvant chemotherapy revealed a 5% difference in favor of neoadjuvant chemotherapy. No randomized trials have yet compared survival with transurethral resection of bladder tumor alone versus cystectomy for the management of patients with muscle-invasive disease. Collaborative international adjuvant chemotherapy trials are needed to assist researchers in assessing the true value of adjuvant chemotherapy. Systemic cisplatin-based combination chemotherapy is the only current modality that has been shown in phase 3 trials to improve survival in responsive patients

  18. Pulp and paper mill effluent treatments have differential endocrine-disrupting effects on rainbow trout.

    PubMed

    Orrego, Rodrigo; Guchardi, John; Hernandez, Victor; Krause, Rachelle; Roti, Lucia; Armour, Jeffrey; Ganeshakumar, Mathumai; Holdway, Douglas

    2009-01-01

    Endocrine disruption (ED) effects due to pulp and paper mill effluents extracts involving different industrial procedures and effluent treatments (nontreated, primary, and secondary treated) were evaluated using immature triploid rainbow trout in a pulse-exposure toxicity experiment. The protocol involved the use of intraperitoneal injection of mill extracts (solid-phase extraction [SPE]) corrected for individual fish weight and included several laboratory standards (steroidal hormones and phytosterols). Biological endpoints at two different levels of biological organization were analyzed (molecular and individual organism). Results indicated that nonsignificant changes were observed in the individual physiological indices represented by condition factor, liver somatic index, and gonad somatic index during the experiment. Significant induction of liver ethoxyresorufin-O-deethylase activity was observed between different effluent treatments and experimental controls. Significant endocrine-disrupting effects at the reproductive level were observed in all effluent treatments involving significant increments in plasma vitellogenin (VTG) levels. Fish exposed to untreated effluent extracts had significantly higher VTG levels compared to fish exposed to primary and secondary treatment effluent extracts, indicating a decrease of the estrogenic effect due to the effluent treatment. The present study has shown that for the Chilean pulp and paper mill SPE extracts evaluated, an endocrine disruption effect was induced in immature triploid rainbow, reaffirming the significant estrogenic effects demonstrated previously in laboratory and field experiments.

  19. Endocrine response after prior treatment with fulvestrant in postmenopausal women with advanced breast cancer: experience from a single centre.

    PubMed

    Cheung, K L; Owers, R; Robertson, J F R

    2006-03-01

    The pure anti-oestrogen fulvestrant has now been licensed for use in advanced breast cancer which has progressed on an anti-oestrogen. Optimal sequencing of various endocrine agents becomes very important in the therapeutic strategy. We report our experience of further endocrine response with another endocrine agent after prior fulvestrant treatment. Among all patients with advanced breast cancer who had been entered into five phase II/III trials using fulvestrant as first- to ninth-line endocrine therapy in our Unit since 1993, 54 patients who fulfilled the following criteria were studied for their subsequent endocrine response: (i) oestrogen receptor positive or unknown; (ii) having been on a subsequent endocrine therapy for > or =6 months unless the disease progressed before; and (iii) with disease assessable for response according to International Union Against Cancer criteria. Eleven patients had received an aromatase inhibitor prior to fulvestrant, which resulted in five CBs (clinical benefit = objective remission/stable disease (SD)) for > or =6 months). Twenty-eight patients achieved CB on fulvestrant. They went on subsequent endocrine therapy with two partial responses, 11 SDs and 15 PDs (progressive disease) at 6 months. The median survival from starting fulvestrant and subsequent endocrine therapy was respectively 46.6 and 18.2 months. Among the remaining 26 patients who progressed at 6 months on fulvestrant, there were three SDs and 23 PDs at 6 months on subsequent endocrine therapy. The median survival from starting fulvestrant and subsequent endocrine therapy was respectively 12.5 and 9.3 months. Of all these 54 patients, 30% (n = 16) therefore achieved CB using another (second- to tenth-line) endocrine agent (anastrozole = 26; tamoxifen = 12; megestrol acetate = 11; others = 5). It would thus appear that further endocrine response can be induced in a reasonable proportion of patients after failing fulvestrant.

  20. Obesity and Risk of Recurrence or Death After Adjuvant Endocrine Therapy With Letrozole or Tamoxifen in the Breast International Group 1-98 Trial

    PubMed Central

    Ewertz, Marianne; Gray, Kathryn P.; Regan, Meredith M.; Ejlertsen, Bent; Price, Karen N.; Thürlimann, Beat; Bonnefoi, Hervé; Forbes, John F.; Paridaens, Robert J.; Rabaglio, Manuela; Gelber, Richard D.; Colleoni, Marco; Láng, István; Smith, Ian E.; Coates, Alan S.; Goldhirsch, Aron; Mouridsen, Henning T.

    2012-01-01

    Purpose To examine the association of baseline body mass index (BMI) with the risk of recurrence or death in postmenopausal women with early-stage breast cancer receiving adjuvant tamoxifen or letrozole in the Breast International Group (BIG) 1-98 trial at 8.7 years of median follow-up. Patients and Methods This report analyzes 4,760 patients with breast cancer randomly assigned to 5 years of monotherapy with letrozole or tamoxifen in the BIG 1-98 trial with available information on BMI at randomization. Multivariable Cox modeling assessed the association of BMI with disease-free survival, overall survival (OS), breast cancer–free interval, and distant recurrence-free interval and tested for treatment-by-BMI interaction. Median follow-up was 8.7 years. Results Seventeen percent of patients have died. Obese patients (BMI ≥ 30 kg/m2) had slightly poorer OS (hazard ratio [HR] = 1.19; 95% CI, 0.99 to 1.44) than patients with normal BMI (< 25 kg/m2), whereas no trend in OS was observed in overweight (BMI 25 to < 30 kg/m2) versus normal-weight patients (HR = 1.02; 95% CI, 0.86 to 1.20). Treatment-by-BMI interactions were not statistically significant. The HRs for OS comparing obese versus normal BMI were HR = 1.22 (95% CI, 0.93 to 1.60) and HR = 1.18 (95% CI, 0.91 to 1.52) in the letrozole and tamoxifen groups, respectively. Conclusion There was no evidence that the benefit of letrozole over tamoxifen differed according to patients' BMI. PMID:23045588

  1. Comparison of doxorubicin-cyclophosphamide with doxorubicin-dacarbazine for the adjuvant treatment of canine hemangiosarcoma.

    PubMed

    Finotello, R; Stefanello, D; Zini, E; Marconato, L

    2017-03-01

    Canine hemangiosarcoma (HSA) is a neoplasm of vascular endothelial origin that has an aggressive biological behaviour, with less than 10% of dogs alive at 12-months postdiagnosis. Treatment of choice consists of surgery followed by adjuvant doxorubicin-based chemotherapy. We prospectively compared adjuvant doxorubicin and dacarbazine (ADTIC) to a traditional doxorubicin and cyclophosphamide (AC) treatment, aiming at determining safety and assessing whether this regimen prolongs survival and time to metastasis (TTM). Twenty-seven dogs were enrolled; following staging work-up, 18 were treated with AC and 9 with ADTIC. Median TTM and survival time were longer for dogs treated with ADTIC compared with those receiving AC (>550 versus 112 days, P = 0.021 and >550 versus 142 days, P = 0.011, respectively). Both protocols were well tolerated, without need for dose reduction or increased interval between treatments. A protocol consisting of combined doxorubicin and dacarbazine is safe in dogs with HSA and prolongs TTM and survival time.

  2. Intensified Adjuvant Treatment of Prostate Carcinoma: Feasibility Analysis of a Phase I/II Trial

    PubMed Central

    Mantini, Giovanna; Fersino, Sergio; Frascino, Vincenzo; Massaccesi, Mariangela; Fionda, Bruno; Luzi, Stefano; Balducci, Mario; De Belvis, Antonio; Morganti, Alessio Giuseppe; Valentini, Vincenzo

    2014-01-01

    Purpose. To perform a preliminary feasibility acute and late toxicity evaluation of an intensified and modulated adjuvant treatment in prostate cancer (PCa) patients after radical prostatectomy. Material and Methods. A phase I/II has been designed. Eligible patients were 79 years old or younger, with an ECOG of 0–2, previously untreated, histologically proven prostate adenocarcinoma with no distant metastases, pT2–4 N0-1, and with at least one of the following risk factors: capsular perforation, positive surgical margins, and seminal vesicle invasion. All patients received a minimum dose on tumor bed of 64.8 Gy, or higher dose (70.2 Gy; 85.4%), according to the pathological stage, pelvic lymph nodes irradiation (57.7%), and/or hormonal therapy (69.1%). Results. 123 patients were enrolled and completed the planned treatment, with good tolerance. Median follow-up was 50.6 months. Grade 3 acute toxicity was only 2.4% and 3.3% for genitourinary (GU) and gastrointestinal (GI) tract, respectively. No patient had late grade 3 GI toxicity, and the GU grade 3 toxicity incidence was 5.8% at 5 years. 5-year BDSF was 90.2%. Conclusions. A modulated and intensified adjuvant treatment in PCa was feasible in this trial. A further period of observation can provide a complete assessment of late toxicity and confirm the BDSF positive results. PMID:25093169

  3. Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

    PubMed Central

    Ogedengbe, Oluwatosin O; Jegede, Ayoola I; Onanuga, Ismail O; Offor, Ugochukwu; Naidu, Edwin CS; Peter, Aniekan I; Azu, Onyemaechi O

    2016-01-01

    Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A–D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility (P < 0.05) and count (P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced (P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant (P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof. PMID:27818734

  4. Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs.

    PubMed

    Ogedengbe, Oluwatosin O; Jegede, Ayoola I; Onanuga, Ismail O; Offor, Ugochukwu; Naidu, Edwin Cs; Peter, Aniekan I; Azu, Onyemaechi O

    2016-10-01

    Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A-D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility (P < 0.05) and count (P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced (P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant (P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof.

  5. Treatment of Oral Cavity Squamous Cell Carcinoma With Adjuvant or Definitive Intensity-Modulated Radiation Therapy

    SciTech Connect

    Sher, David J.; Thotakura, Vijaya; Balboni, Tracy A.; Norris, Charles M.; Haddad, Robert I.; Posner, Marshall R.; Lorch, Jochen; Goguen, Laura A.; Annino, Donald J.; Tishler, Roy B.

    2011-11-15

    Purpose: The optimal management of oral cavity squamous cell carcinoma (OCSCC) typically involves surgical resection followed by adjuvant radiotherapy or chemoradiotherapy (CRT) in the setting of adverse pathologic features. Intensity-modulated radiation therapy (IMRT) is frequently used to treat oral cavity cancers, but published IMRT outcomes specific to this disease site are sparse. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for OCSCC. Methods and Materials: Retrospective study of all patients treated at Dana-Farber Cancer Institute for OCSCC with adjuvant or definitive IMRT between August 2004 and December 2009. The American Joint Committee on Cancer disease stage criteria distribution of this cohort included 5 patients (12%) with stage I; 10 patients (24%) with stage II (n = 10, 24%),; 14 patients (33%) with stage III (n = 14, 33%),; and 13 patients (31%) with stage IV. The primary endpoint was overall survival (OS); secondary endpoints were locoregional control (LRC) and acute and chronic toxicity. Results: Forty-two patients with OCSCC were included, 30 of whom were initially treated with surgical resection. Twenty-three (77%) of 30 surgical patients treated with adjuvant IMRT also received concurrent chemotherapy, and 9 of 12 (75%) patients treated definitively without surgery were treated with CRT or induction chemotherapy and CRT. With a median follow-up of 2.1 years (interquartile range, 1.1-3.1 years) for all patients, the 2-year actuarial rates of OS and LRC following adjuvant IMRT were 85% and 91%, respectively, and the comparable results for definitive IMRT were 63% and 64% for OS and LRC, respectively. Only 1 patient developed symptomatic osteoradionecrosis, and among patients without evidence of disease, 35% experienced grade 2 to 3 late dysphagia, with only 1 patient who was continuously gastrostomy-dependent. Conclusions: In this single-institution series, postoperative IMRT was associated with promising LRC

  6. [Adjuvant treatment of breast cancer by concomitant hormonotherapy and radiotherapy: state of the art].

    PubMed

    Azria, D; Lemanski, C; Zouhair, A; Gutowski, M; Belkacémi, Y; Dubois, J B; Romieu, G; Ozsahin, M

    2004-06-01

    Combining radiation and hormone therapy has become common clinical practice in recent years for locally advanced prostate cancer. The use of such concomitant therapy in the treatment of breast disease has been very infrequently reported in the literature, but such an application seems justified given the common hormonal dependence of breast cancer and the potential synergetic effect of these two treatment modalities. As adjuvant therapy, tamoxifen is the key drug in the hormonal treatment arsenal, providing a significant improvement in both local control and global survival rates. Aromatase inhibitors are currently being evaluated in this setting, and initial results are promising. In vitro, tamoxifen does not seem to offer a protective effect against radiation. In clinical use, the few available published studies confirm the superiority of the association of radiation with tamoxifen as opposed to radiation therapy alone in decreasing local recurrences of surgically removed breast tumors. Toxicity associated with such concomitant therapy includes mainly subcutaneous and pulmonary fibroses. However, subcutaneous fibrosis and its cosmetic impact on the treated breast are frequently described side effects of radiation therapy, and their incidence may actually be reduced when tamoxifen is associated. The evidence is less controversial for pulmonary fibrosis, which is more common with the concomitant therapy. The association of radiation and aromatase inhibitors has as of yet rarely been reported. Letrozole (Femara) has a radiosensitizing effect on breast-cancer cell lines transfected with the aromatase gene. Clinical data assessing this effect in vivo are not available. The FEMTABIG study (letrozole vs. tamoxifen vs. sequential treatment) did not specify the sequence of radiation and hormonal therapy. The ATAC study comparing the adjuvant use of anastrozole (Arimidex) and tamoxifen does not provide any information on the number of patients receiving radiation

  7. Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma.

    PubMed

    Finocchiaro, L M E; Glikin, G C

    2008-02-01

    We evaluated the safety, efficacy and anti-tumor effects of a surgery adjuvant treatment on canine patients with malignant melanoma. This approach combined suicide gene therapy with a subcutaneous vaccine composed by formolized tumor cells and irradiated xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. The post-surgical margin of the cavity was infiltrated with lipid-complexed thymidine kinase suicide gene coadministrated with ganciclovir. Toxicity was minimal or absent in all patients. With respect to surgery-treated controls (SC), this combined treatment (CT) significantly increased the fraction of patients local disease-free from 6 to 58% and distant metastases-free from 43 to 78% (Fisher's Exact test). In addition, CT significantly improved both SC overall 78 (23-540) and metastasis-free survival 112 (0-467) days to more than 1312 days (respective ranges: 43-1312 and 0-1312) (Kaplan-Meier analysis). In those patients subjected to partial surgery or presenting local recurrence, the efficacy of CT was verified by a 49% of objective responses that averaged 85% of tumor mass loss, while 22% displayed tumor progression as 94% of SC did. Therefore, surgery adjuvant CT controlled tumor growth, delaying or preventing post-surgical recurrence and distant metastasis, significantly extending survival and recovering the quality of life.

  8. Ozone oxidation of pharmaceuticals, endocrine disruptors and pesticides during drinking water treatment.

    PubMed

    Broséus, R; Vincent, S; Aboulfadl, K; Daneshvar, A; Sauvé, S; Barbeau, B; Prévost, M

    2009-10-01

    This study investigates the oxidation of pharmaceuticals, endocrine disrupting compounds and pesticides during ozonation applied in drinking water treatment. In the first step, second-order rate constants for the reactions of selected compounds with molecular ozone (k(O3)) were determined in bench-scale experiments at pH 8.10: caffeine (650+/-22M(-1)s(-1)), progesterone (601+/-9M(-1)s(-1)), medroxyprogesterone (558+/-9M(-1)s(-1)), norethindrone (2215+/-76M(-1)s(-1)) and levonorgestrel (1427+/-62M(-1)s(-1)). Compared to phenolic estrogens (estrone, 17beta-estradiol, estriol and 17alpha-ethinylestradiol), the selected progestogen endocrine disruptors reacted far slower with ozone. In the second part of the study, bench-scale experiments were conducted with surface waters spiked with 16 target compounds to assess their oxidative removal using ozone and determine if bench-scale results would accurately predict full-scale removal data. Overall, the data provided evidence that ozone is effective for removing trace organic contaminants from water with ozone doses typically applied in drinking water treatment. Ozonation removed over 80% of caffeine, pharmaceuticals and endocrine disruptors within the CT value of about 2 mg min L(-1). As expected, pesticides were found to be the most recalcitrant compounds to oxidize. Caffeine can be used as an indicator compound to gauge the efficacy of ozone treatment.

  9. Review of therapeutic options for adjuvant treatment of focal seizures in epilepsy: focus on lacosamide.

    PubMed

    Becerra, Juan Luis; Ojeda, Joaquín; Corredera, Enrique; Ruiz Giménez, Jesús

    2011-12-05

    Epilepsy is one of the most common serious neurological conditions worldwide, with an age-adjusted incidence of approximately 50 per 100,000 persons per year in developed countries. Antiepileptic therapy can result in long-term remission in 60-70% of patients, but many patients will require combination treatment to achieve optimal seizure control, as monotherapy is ineffective at controlling seizures in 30-53% of patients. Despite the increase in available treatment options, patient outcomes have not improved significantly and there is still a need for more effective therapies. Drugs used in the treatment of focal-onset seizures are a diverse range of compounds, and in most cases their mechanism of action is unknown or poorly defined. This review discusses the efficacy and safety of the newer adjuvant antiepileptic therapies that may improve outcomes in patients unresponsive to monotherapy, including clobazam, vigabatrin, lamotrigine, gabapentin, topiramate, tiagabine, levetiracetam, oxcarbazepine, pregabalin, zonisamide and eslicarbazepine, with focus on lacosamide. Lacosamide has been shown to exert its anticonvulsant effects predominantly by enhancement of the slow inactivation of voltage-gated sodium channels. Lacosamide is indicated for use as adjuvant treatment of focal-onset seizures in patients with epilepsy, and there is some evidence that it may also be of use in patients with status epilepticus and cancer patients with epilepsy. The efficacy of lacosamide has been assessed in three randomized, double-blind, placebo-controlled clinical trials, all of which have shown lacosamide to be effective at reducing seizure frequency and increasing 50% responder rates in patients with focal-onset seizures. Long-term lacosamide treatment is generally well tolerated and is not associated with significant drug interactions; the availability of an intravenous form of the drug also makes it particularly useful for a broad range of patients.

  10. Treatment outcomes after adjuvant radiotherapy following surgery for patients with stage I endometrial cancer

    PubMed Central

    Kim, Jiyoung; Lee, Kyung-Ja; Park, Kyung-Ran; Ha, Boram; Kim, Yi-Jun; Jung, Wonguen; Lee, Rena; Kim, Seung Cheol; Moon, Hye Sung; Ju, Woong; Kim, Yun Hwan; Lee, Jihae

    2016-01-01

    Purpose The purpose of this study is to evaluate the treatment outcomes of adjuvant radiotherapy using vaginal brachytherapy (VB) with a lower dose per fraction and/or external beam radiotherapy (EBRT) following surgery for patients with stage I endometrial carcinoma. Materials and Methods The subjects were 43 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I endometrial cancer who underwent adjuvant radiotherapy following surgery between March 2000 and April 2014. Of these, 25 received postoperative VB alone, while 18 received postoperative EBRT to the whole pelvis; 3 of these were treated with EBRT plus VB. The median EBRT dose was 50.0 Gy (45.0–50.4 Gy) and the VB dose was 24 Gy in 6 fractions. Tumor dose was prescribed at a depth of 5 mm from the cylinder surface and delivered twice per week. Results The median follow-up period for all patients was 57 months (range, 9 to 188 months). Five-year disease-free survival (DFS) and overall survival (OS) for all patients were 92.5% and 95.3%, respectively. Adjuvant radiotherapy was performed according to risk factors and stage IB, grade 3 and lymphovascular invasion were observed more frequently in the EBRT group. Five-year DFS for EBRT and VB alone were 88.1% and 96.0%, respectively (p = 0.42), and 5-year OS for EBRT and VB alone were 94.4% and 96%, respectively (p = 0.38). There was no locoregional recurrence in any patient. Two patients who received EBRT and 1 patient who received VB alone developed distant metastatic disease. Two patients who received EBRT had severe complications, one each of grade 3 gastrointestinal complication and pelvic bone insufficiency fracture. Conclusion Adjuvant radiotherapy achieved high DFS and OS with acceptable toxicity in stage I endometrial cancer. VB (with a lower dose per fraction) may be a viable option for selected patients with early-stage endometrial cancer following surgery. PMID:27703126

  11. Radiation recall dermatitis induced by tamoxifen during adjuvant breast cancer treatment

    PubMed Central

    Rhee, Jiyoung; Kim, Gwi Eon; Lee, Chang Hyun; Kwon, Jung-Mi; Han, Sang-Hoon; Kim, Young Suk

    2014-01-01

    Tamoxifen and radiotherapy are used in breast cancer treatment worldwide. Radiation recall dermatitis (RRD), induced by tamoxifen, has been rarely reported. Herein, we report a RRD case induced by tamoxifen. A 47-year-old woman had a right quadrantectomy and an axillary lymph node dissection due to breast cancer. The tumor was staged pT2N0; it was hormone receptor positive, and human epidermal growth factor receptor 2 negative. The patient received adjuvant chemotherapy followed by tamoxifen and radiotherapy. After 22 months of tamoxifen, the patient developed a localized heating sensation, tenderness, edema, and redness at the irradiated area of the right breast. The symptoms improved within 1 week without treatment. Three weeks later, however, the patient developed similar symptoms in the same area of the breast. She continued tamoxifen before and during dermatitis, and symptoms resolved within 1 week. PMID:25568855

  12. Intraperitoneal insulin infusion: treatment option for type 1 diabetes resulting in beneficial endocrine effects beyond glycaemia.

    PubMed

    van Dijk, P R; Logtenberg, S J J; Gans, R O B; Bilo, H J G; Kleefstra, N

    2014-10-01

    Continuous intraperitoneal insulin infusion (CIPII) is a treatment option for patients with type 1 diabetes mellitus who fail to reach adequate glycaemic control despite intensive subcutaneous (SC) insulin therapy. CIPII has clear advantages over SC insulin administration in terms of pharmacokinetic and pharmacodynamic properties and has been shown to improve glycaemic regulation. Due to the delivery of insulin predominantly in the portal vein, as opposed to systemically, CIPII offers a unique research model to investigate the effects of insulin on endocrine and metabolic parameters in vivo. The aim of the present article is to provide an overview of the literature with respect to the effects of CIPII on glucose management, quality of life, complications and costs, with additional focus on metabolic and endocrine aspects. Finally, future use and research objectives are discussed.

  13. Curative effect of the recent photofrin photodynamic adjuvant treatment on young patients with advanced colorectal cancer

    PubMed Central

    SUN, BO; LI, WEI; LIU, NING

    2016-01-01

    Advanced colorectal cancer has a high mortality rate and conventional treatments have poor therapeutic effects. The aim of the present study was to analyze the recent curative effect and adverse reaction of photofrin photodynamic adjuvant treatment on young patients with advanced colorectal cancer. A total of 23 patients with advanced colorectal cancer who had accepted semiconductor laser photodynamic adjuvant treatment were selected as the observation group. In addition, 30 patients who had accepted concurrent radiotherapy and chemotherapy during the same period served as the control group. The observation group received photofrin (2 mg/kg) intravenously in 100 ml of 5% glucose, followed by the introduction of the endoscopic optical fiber to deliver laser radiation with an intensity of 630 nm wavelength pulse power. After 2 days, necrotic tissues were removed and irradiation of the original or new tumor lesions was performed and necrotic tissues were removed. The total effective rate and survival time was higher and the length of hospital stay was shorter in the observation group in comparison with the control group. The differences were statistically significant (P<0.05). The number of patients in the control and observation groups with symptoms of hematochezia, change in bowel habit, intestinal stimulation and incomplete intestinal obstruction were reduced. Additionally, the reduced ratio of the observation group was significantly increased in comparison with the control group (P<0.05). The adverse reaction rate of the observation group was lower than that of the control group and this difference was also statistically significant (P<0.05). In conclusion, use of photodynamic treatment for young patients with advanced colorectal cancer can effectively improve the clinical symptoms and reduce complications. PMID:26998124

  14. Pros and cons in endocrine practice: pre-surgical treatment with somatostatin analogues in acromegaly.

    PubMed

    Losa, Marco; Bollerslev, Jens

    2016-06-01

    The aim of this commentary is to balance the pros and cons for pre-surgical SSA treatment in a modern perspective ending up with a pragmatic recommendation for treatment based on the current evidence and expertise of the authors. Even though prospective and randomized studies in this particular area are hampered by obvious limitations, the interpretation of the four published trials has in general been in favor of pre-treatment with SSA, showing a better outcome following surgery. However, major drawbacks of these studies, such as non-optimal diagnostic criteria for cure, potential selection bias, and timing of the postoperative evaluation in SSA pre-treated patients, limit their overall interpretation. Three matched-controlled studies showed remarkably similar results with no apparent beneficial effect of SSA pre-treatment on surgical outcome. Both prospective, randomized studies and retrospective studies did not find any significant difference in the rate of endocrine and non-endocrine complications related to surgery, despite the beneficial clinical effects of SSA treatment in most acromegalic patients. The newly diagnosed patient with acromegaly should be carefully evaluated in the trans-disciplinary neuroendocrine team and treatment individualized accordingly. The issue of SSA pre-treatment to improve surgical outcome is yet to be settled and further methodologically sound studies are probably necessary to clarify this point.

  15. Zingiber officinale Roscoe (ginger) as an adjuvant in cancer treatment: a review.

    PubMed

    Pereira, M M; Haniadka, R; Chacko, P P; Palatty, P L; Baliga, M S

    2011-01-01

    Despite acquiring a strong understanding of the molecular basis and advances in treatment, cancer is the second major cause of death in the world. In clinics, the stagedependent treatment strategies may include surgery, radiotherapy and systemic treatments like hormonotherapy and chemotherapy, which are associated with side effects. The use of traditional herbal medicine in cancer patients is on a rise, as it is believed that these medications are non toxic and alleviate the symptoms of cancer, boost the immune system, or may tackle the cancer itself. Since antiquity the rhizome of Zingiber officinale Roscoe commonly known as ginger (family Zingiberaceae) have widely been used as a spice and condiment in different societies. Additionally, ginger also has a long history of medicinal use in various cultures for treating common colds, fever, to aid digestion, treat stomach upset, diarrhoea, nausea, rheumatic disorders, gastrointestinal complications and dizziness. Preclinical studies have also shown that ginger possesses chemopreventive and antineoplastic properties. It is also reported to be effective in ameliorating the side effects of γ-radiation and of doxorubicin and cisplatin; to inhibit the efflux of anticancer drugs by P-glycoprotein (P-gp) and to possess chemosensitizing effects in certain neoplastic cells in vitro and in vivo. The objective of this review is to address observations on the role of ginger as adjuvant to treatment modalities of cancer. Emphasis is also placed on the drawbacks and on future directions for research that will have a consequential effect on cancer treatment and cure.

  16. Radiation Therapy Field Extent for Adjuvant Treatment of Axillary Metastases From Malignant Melanoma

    SciTech Connect

    Beadle, Beth M.; Guadagnolo, B. Ashleigh Ballo, Matthew T.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Cormier, Janice N.; Mansfield, Paul F.; Ross, Merrick I.; Zagars, Gunar K.

    2009-04-01

    Purpose: To compare treatment-related outcomes and toxicity for patients with axillary lymph node metastases from malignant melanoma treated with postoperative radiation therapy (RT) to either the axilla only or both the axilla and supraclavicular fossa (extended field [EF]). Methods and Materials: The medical records of 200 consecutive patients treated with postoperative RT for axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients received postoperative hypofractionated RT for high-risk features; 95 patients (48%) received RT to the axilla only and 105 patients (52%) to the EF. Results: At a median follow-up of 59 months, 111 patients (56%) had sustained relapse, and 99 patients (50%) had died. The 5-year overall survival, disease-free survival, and distant metastasis-free survival rates were 51%, 43%, and 46%, respectively. The 5-year axillary control rate was 88%. There was no difference in axillary control rates on the basis of the treated field (89% for axilla only vs. 86% for EF; p = 0.4). Forty-seven patients (24%) developed treatment-related complications. On both univariate and multivariate analyses, only treatment with EF irradiation was significantly associated with increased treatment-related complications. Conclusions: Adjuvant hypofractionated RT to the axilla only for metastatic malignant melanoma with high-risk features is an effective method to control axillary disease. Limiting the radiation field to the axilla only produced equivalent axillary control rates to EF and resulted in lower treatment-related complication rates.

  17. Advanced treatment process for pharmaceuticals, endocrine disruptors, and flame retardants removal.

    PubMed

    Sundaram, Vijay; Emerick, Robert W; Shumaker, Stanley E

    2014-02-01

    The objective of this project was to demonstrate the effectiveness of an advanced treatment process that did not utilize reverse osmosis for the removal of pharmaceuticals, endocrine disruptors and flame retardants (collectively referred as contaminants of emerging concern [CECs]) from municipal effluent. The advanced treatment process consisted of (in the order of use): membrane filtration, ozonation (O3), and biologically active carbon (BAC) filtration. Ozone dosage of 5 mg/L or more was needed for desired CEC removal. Biologically active carbon removed flame retardants, and ozonation byproducts including NDMA and aldehydes. The project successfully demonstrated 1) the removal of a wide range of CECs, 2) reduction of estrogen activity to background levels, and 3) removal of ozonation byproducts. Treatment was achieved at lower costs and power utilization than reverse osmosis and without generating a concentrate stream. Results from this project could make CEC removal feasible, especially in situations where reverse osmosis treatment is infeasible.

  18. Potential pleiotropic beneficial effects of adjuvant melatonergic treatment in posttraumatic stress disorder.

    PubMed

    Agorastos, Agorastos; Linthorst, Astrid C E

    2016-08-01

    Loss of circadian rhythmicity fundamentally affects the neuroendocrine, immune, and autonomic system, similar to chronic stress and may play a central role in the development of stress-related disorders. Recent articles have focused on the role of sleep and circadian disruption in the pathophysiology of posttraumatic stress disorder (PTSD), suggesting that chronodisruption plays a causal role in PTSD development. Direct and indirect human and animal PTSD research suggests circadian system-linked neuroendocrine, immune, metabolic and autonomic dysregulation, linking circadian misalignment to PTSD pathophysiology. Recent experimental findings also support a specific role of the fundamental synchronizing pineal hormone melatonin in mechanisms of sleep, cognition and memory, metabolism, pain, neuroimmunomodulation, stress endocrinology and physiology, circadian gene expression, oxidative stress and epigenetics, all processes affected in PTSD. In the current paper, we review available literature underpinning a potentially beneficiary role of an add-on melatonergic treatment in PTSD pathophysiology and PTSD-related symptoms. The literature is presented as a narrative review, providing an overview on the most important and clinically relevant publications. We conclude that adjuvant melatonergic treatment could provide a potentially promising treatment strategy in the management of PTSD and especially PTSD-related syndromes and comorbidities. Rigorous preclinical and clinical studies are needed to validate this hypothesis.

  19. A Preliminary Evaluation of Fast ForWord-Language as an Adjuvant Treatment in Language Intervention

    PubMed Central

    Fey, Marc E.; Finestack, Lizbeth H.; Gajewski, Byron J.; Popescu, Mihai; Lewine, Jeffrey D.

    2010-01-01

    Purpose Fast ForWord-Language (FFW-L) is designed to enhance children's processing of auditory–verbal signals and, thus, their ability to learn language. As a preliminary evaluation of this claim, we examined the effects of a 5-week course of FFW-L as an adjuvant treatment with a subsequent 5-week conventional narrative-based language intervention (NBLI) that targeted narrative comprehension and production and grammatical output. Method Twenty-three children 6–8 years of age with language impairments were assigned randomly to 1 of 3 intervention sequences: (a) FFW-L/NBLI, (b) NBLI/FFW-L, or (c) wait/NBLI. We predicted that after both treatment periods, the FFW-L/NBLI group would show greater gains on measures of narrative ability, conversational grammar, and nonword repetition than the other groups. Results After the first 5-week study period, the intervention groups, taken together (i.e., FFW-L/NBLI and NBLI/FFW-L), significantly outperformed the no-treatment wait/NBLI group on 2 narrative measures. At the final test period, all 3 groups displayed significant time-related effects on measures of narrative ability, but there were no statistically significant between-groups effects of intervention sequence. Conclusions This preliminary study provides no evidence to support the claim that FFW-L enhances children's response to a conventional language intervention. PMID:19696435

  20. Trastuzumab re-treatment following adjuvant trastuzumab and the importance of distant disease-free interval: the HERA trial experience.

    PubMed

    Metzger-Filho, Otto; de Azambuja, Evandro; Procter, Marion; Krieguer, Magalie; Smith, Ian; Baselga, Jose; Cameron, David; Untch, Michael; Jackisch, Christian; Bell, Richard; Gianni, Luca; Goldhirsch, Aron; Piccart, Martine; Gelber, Richard D

    2016-01-01

    This retrospective analysis conducted using data from patients enrolled onto the Herceptin Adjuvant has two objectives: The first is to evaluate the impact of the time interval between the end of adjuvant trastuzumab and distant recurrence (TDRI) upon overall survival (OS). The second is to describe the duration of trastuzumab-based regimens in the metastatic setting for patients previously treated with adjuvant trastuzumab. The first objective included 187 patients treated with adjuvant trastuzumab and diagnosed with distant recurrence at 4-year median follow-up. The second objective included data from questionnaires sent to investigators retreating patients with trastuzumab upon distant recurrence: 144 of 156 questionnaires were returned (93 %), and 90 patients were selected based on available clinical information and consent for subsequent studies. There was no statistically significant relationship between TDRI following 1 year of adjuvant trastuzumab and OS from distant recurrence: hazard ratio 0.991, p = 0.46. The median OS from distant recurrence was numerically longer among patients with a TDRI of ≥12 months (n = 103) than <12 months (n = 84) but not statistically significant (23.7 vs. 17.8 months, p = 0.47). The median duration of first-line trastuzumab-based regimens for patients previously treated with adjuvant trastuzumab and diagnosed with distant disease recurrence was 8.8 months (n = 88). This retrospective, exploratory study suggests that TDRI did not impact on OS measured from distant recurrence. We argue that prospective collection of treatment information beyond disease progression should be included in future clinical studies.

  1. Adjuvant treatment with the bacterial lysate (OM-85) improves management of atopic dermatitis: A randomized study

    PubMed Central

    Bodemer, Christine; Guillet, Gerard; Cambazard, Frederic; Boralevi, Franck; Ballarini, Stefania; Milliet, Christian; Bertuccio, Paola; La Vecchia, Carlo; Bach, Jean-François; de Prost, Yves

    2017-01-01

    Background Environmental factors play a major role on atopic dermatitis (AD) which shows a constant rise in prevalence in western countries over the last decades. The Hygiene Hypothesis suggesting an inverse relationship between incidence of infections and the increase in atopic diseases in these countries, is one of the working hypothesis proposed to explain this trend. Objective This study tested the efficacy and safety of oral administration of the bacterial lysate OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®, Paxoral®, Vaxoral®), in the treatment of established AD in children. Methods Children aged 6 months to 7 years, with confirmed AD diagnosis, were randomized in a double-blind, placebo-controlled trial to receive, in addition to conventional treatment with emollients and topical corticosteroids, 3.5mg of the bacterial extract OM-85 or placebo daily for 9 months. The primary end-point was the difference between groups in the occurrence of new flares (NF) during the study period, evaluated by Hazard Ratio (HR) derived from conditional Cox proportional hazard regression models accounting for repeated events. Results Among the 179 randomized children, 170 were analysed, 88 in the OM-85 and 82 in the placebo group. As expected most children in both treatment groups experienced at least 1 NF during the study period (75 (85%) patients in the OM-85 group and 72 (88%) in the placebo group). Patients treated with OM-85 as adjuvant therapy had significantly fewer and delayed NFs (HR of repeated flares = 0.80; 95% confidence interval (CI): 0.67–0.96), also when potential confounding factors, as family history of atopy and corticosteroids use, were taken into account (HR = 0.82; 95% CI: 0.69–0.98). No major side effect was reported, with comparable and good tolerability for OM-85 and placebo. Conclusions Results show an adjuvant therapeutic effect of a well standardized bacterial lysate OM-85 on established AD. PMID:28333952

  2. Long-term effects of treatment on endocrine function in children with brain tumors

    SciTech Connect

    Duffner, P.K.; Cohen, M.E.; Anderson, S.W.; Voorhess, M.L.; MacGillivray, M.H.; Panahon, A.; Brecher, M.L.

    1983-11-01

    Fourteen children with brain tumors received endocrine evaluations at least one year following completion of cranial irradiation. Treatment consisted of operation (13 patients), craniospinal irradiation (6), whole brain irradiation (5), posterior fossa irradiation (3), and chemotherapy (10). Endocrine evaluation included bone age roentgenography and measurement of growth hormone (using sequential arginine and insulin stimulation), thyroxine, thyroid-stimulating hormone, plasma cortisol, testosterone, prolactin, and urinary follicle-stimulating hormone and luteinizing hormone. Ten of 12 children (83%) had abnormal responses to both tests of growth hormone stimulation. All growth hormone-deficient patients treated prior to puberty and tested at least 2 years following completion of cranial irradiation had decelerated linear growth. Results of thyroid function tests were abnormal in 4 patients: 2 patients had evidence of primary hypothyroidism, and 2 showed secondary or tertiary hypothyroidism. Two patients had inadequate cortisol responses to insulin hypoglycemia. Urinary follicle-stimulating hormone and luteinizing hormone, serum prolactin, and serum testosterone levels were appropriate for age in all patients.

  3. Long-term effects of treatment on endocrine function in children with brain tumors.

    PubMed

    Duffner, P K; Cohen, M E; Anderson, S W; Voorhess, M L; MacGillivray, M H; Panahon, A; Brecher, M L

    1983-11-01

    Fourteen children with brain tumors received endocrine evaluations at least one year following completion of cranial irradiation. Treatment consisted of operation (13 patients), craniospinal irradiation (6), whole brain irradiation (5), posterior fossa irradiation (3), and chemotherapy (10). Endocrine evaluation included bone age roentgenography and measurement of growth hormone (using sequential arginine and insulin stimulation), thyroxine, thyroid-stimulating hormone, plasma cortisol, testosterone, prolactin, and urinary follicle-stimulating hormone and luteinizing hormone. Ten of 12 children (83%) had abnormal responses to both tests of growth hormone stimulation. All growth hormone-deficient patients treated prior to puberty and tested at least 2 years following completion of cranial irradiation had decelerated linear growth. Results of thyroid function tests were abnormal in 4 patients: 2 patients had evidence of primary hypothyroidism, and 2 showed secondary or tertiary hypothyroidism. Two patients had inadequate cortisol responses to insulin hypoglycemia. Urinary follicle-stimulating hormone and luteinizing hormone, serum prolactin, and serum testosterone levels were appropriate for age in all patients.

  4. Comparison of different wastewater treatments for removal of selected endocrine-disruptors from paper mill wastewaters.

    PubMed

    Balabanič, Damjan; Hermosilla, Daphne; Merayo, Noemí; Klemenčič, Aleksandra Krivograd; Blanco, Angeles

    2012-01-01

    There is increasing concern about chemical pollutants that have the ability to mimic hormones, the so-called endocrine-disrupting compounds (EDCs). One of the main reasons for concern is the possible effect of EDCs on human health. EDCs may be released into the environment in different ways, and one of the most significant sources is industrial wastewater. The main objective of this research was to evaluate the treatment performance of different wastewater treatment procedures (biological treatment, filtration, advanced oxidation processes) for the reduction of chemical oxygen demand and seven selected EDCs (dimethyl phthalate, diethyl phthalate, dibutyl phthalate, benzyl butyl phthalate, bis(2-ethylhexyl) phthalate, bisphenol A and nonylphenol) from wastewaters from a mill producing 100 % recycled paper. Two pilot plants were running in parallel and the following treatments were compared: (i) anaerobic biological treatment followed by aerobic biological treatment, ultrafiltration and reverse osmosis (RO), and (ii) anaerobic biological treatment followed by membrane bioreactor and RO. Moreover, at lab-scale, four different advanced oxidation processes (Fenton reaction, photo-Fenton reaction, photocatalysis with TiO(2), and ozonation) were applied. The results indicated that the concentrations of selected EDCs from paper mill wastewaters were effectively reduced (100 %) by both combinations of pilot plants and photo-Fenton oxidation (98 %), while Fenton process, photocatalysis with TiO(2) and ozonation were less effective (70 % to 90 %, respectively).

  5. High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation as Adjuvant Treatment in High-Risk Breast Cancer: Data from the European Group for Blood and Marrow Transplantation Registry.

    PubMed

    Martino, Massimo; Lanza, Francesco; Pavesi, Lorenzo; Öztürk, Mustafa; Blaise, Didier; Leno Núñez, Rubén; Schouten, Harry C; Bosi, Alberto; De Giorgi, Ugo; Generali, Daniele; Rosti, Giovanni; Necchi, Andrea; Ravelli, Andrea; Bengala, Carmelo; Badoglio, Manuela; Pedrazzoli, Paolo; Bregni, Marco

    2016-03-01

    The aim of this retrospective study was to assess toxicity and efficacy of adjuvant high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (AHSCT) in 583 high-risk breast cancer (BC) patients (>3 positive nodes) who were transplanted between 1995 and 2005 in Europe. All patients received surgery before transplant, and 55 patients (9.5%) received neoadjuvant treatment before surgery. Median age was 47.1 years, 57.3% of patients were premenopausal at treatment, 56.5% had endocrine-responsive tumors, 19.5% had a human epidermal growth factor receptor 2 (HER2)-negative tumor, and 72.4% had ≥10 positive lymph nodes at surgery. Seventy-nine percent received a single HDC procedure. Overall transplant-related mortality was 1.9%, at .9% between 2001 and 2005, whereas secondary tumor-related mortality was .9%. With a median follow-up of 120 months, overall survival and disease-free survival rates at 5 and 10 years in the whole population were 75% and 64% and 58% and 44%, respectively. Subgroup analysis demonstrated that rates of overall survival were significantly better in patients with endocrine-responsive tumors, <10 positive lymph nodes, and smaller tumor size. HER2 status did not affect survival probability. Adjuvant HDC with AHSCT has a low mortality rate and provides impressive long-term survival rates in patients with high-risk BC. Our results suggest that this treatment modality should be considered in selected high-risk BC patients and further investigated in clinical trials.

  6. Autophagy and mitochondrial dysfunction in adjuvant-arthritis rats treatment with resveratrol

    PubMed Central

    Zhang, Junqiang; Song, Xianbin; Cao, Wei; Lu, Jinseng; Wang, Xiaoqing; Wang, Gaoyuan; Wang, Zhicheng; Chen, Xiaoyu

    2016-01-01

    Resveratrol is a polyphenol derivatives which exhibits a pro-apoptotic effect in a variety of human cancers by triggering mitochondria apoptosis pathway and autophagy. However, there are scarcely reports on its apoptosis-promoting effect in abnormal proliferation fibroblast-like synoviocytes (FLSs). In this study, we investigated the underlying mechanism and apoptosis-inducing effects of resveratrol on the abnormal proliferation of FLSs in adjuvant-arthritis (AA) rats. Since using resveratrol for 12 days resulted in a significant decreasing the swelling degree of the paw, reducing malondialdehyde (MDA) content and enhancing superoxide dismutase (SOD) activity, antioxidant capacity, glutathione peroxidase and glutathione reductase ratio in AA rats. Moreover, we found that 5 μMH2O2 could increase cells viability, Beclin1, LC3A/B, MnSOD, SIRT3 protein expression in FLSs. But, resveratrol could reverse these effects by changing mitochondrial membrane potential (Δψm) to promote mitochondrial reactive oxygen species (mtROS) generation in 5 μMH2O2-treatment FLSs. These results suggest that oxidative stress existed in AA rats. Resveratrol could suppress oxidative stress in AA rats and increase mtROS production by reducing autophagy protein Beclin1, LC3A/B and oxidative stress protein MnSOD to promoted the apoptosis of FLSs. Thus, targeting of mtROS may be a crucial mechanism of resveratrol confers patients with rheumatoid arthritis. PMID:27611176

  7. NCCN Task Force Report: Adjuvant Therapy for Breast Cancer.

    PubMed

    Carlson, Robert W; Brown, Elizabeth; Burstein, Harold J; Gradishar, William J; Hudis, Clifford A; Loprinzi, Charles; Mamounas, Eleftherios Paul; Perez, Edith A; Pritchard, Kathleen; Ravdin, Peter; Recht, Abram; Somlo, George; Theriault, Richard L; Winer, Eric P; Wolff, Antonio C

    2006-03-01

    The National Comprehensive Cancer Network (NCCN) first published the NCCN Breast Cancer Treatment Guidelines in 1996. The Guidelines address the treatment of all stages of breast cancer across the spectrum of patient care and have been updated yearly. Adjuvant therapy for breast cancer has undergone an especially rapid evolution over the past few years. Therefore, the NCCN Breast Cancer Guidelines Panel was supplemented by additional experts to form the Adjuvant Therapy Task Force to provide a forum for an extended discussion and expanded input to the adjuvant therapy recommendations for the Breast Cancer Treatment Guidelines. Issues discussed included methods of risk-stratification for recurrence; how biologic markers such as HER2 status, quantitative estrogen receptor, or genetic markers can be incorporated as prognostic or predictive factors; and how age, menopausal status, and estrogen receptor levels impact benefits from chemotherapy and endocrine therapy. Additionally, the task force discussed the strategies for use of aromatase inhibitors in postmenopausal women and the potential incorporation of trastuzumab into adjuvant therapy of women with HER2/neu positive breast cancer. This supplement summarizes the background data and ensuing discussion from the Adjuvant Task Force meeting.

  8. Radiotherapy Is Associated With Improved Survival in Adjuvant and Palliative Treatment of Extrahepatic Cholangiocarcinomas

    SciTech Connect

    Shinohara, Eric T. Mitra, Nandita; Guo Mengye; Metz, James M.

    2009-07-15

    Purpose: Extrahepatic cholangiocarcinomas (EHC) are rare tumors of the biliary tree because of their low incidence, large randomized studies examining radiotherapy (RT) for EHC have not been performed. The purpose of this study was to examine the role of adjuvant and palliative RT in the treatment of EHC in a large patient population. Methods and Materials: This was a retrospective analysis of 4,758 patients with EHC collected from the Surveillance, Epidemiology, and End Results database. The primary endpoint was overall survival. Results: Patients underwent surgery (28.8%), RT (10.0%), surgery and RT (14.7%), or no RT or surgery (46.4%). The median age of the patient population was 73 years (range, 23-104), 52.5% were men, and 80.7% were white. The median overall survival time was 16 months (95% confidence interval [CI] 15-17), 9 months (95% CI 9-11), 9 months (95% CI 9-10), and 4 months (95% CI 3-4) for surgery and RT, surgery, RT, and no RT or surgery, respectively. The overall survival was significantly different between the surgery and surgery and RT groups (p < .0001) and RT and no RT or surgery groups (p < .0001) on the log-rank test. The propensity score-adjusted analyses of surgery and RT vs. surgery (hazard ratio, 0.94; 95% CI, 0.84-1.05) were not significantly different, but that for RT vs. no RT or surgery (hazard ratio, 0.61; 95% CI, 0.54-0.70) was significantly different. Conclusion: These results suggest that palliative RT prolongs survival in patients with EHC. The benefit associated with surgery and RT was significant on univariate analysis but not after controlling for potential confounders using the propensity score. Future studies should evaluate the addition of chemotherapy and biologic agents for the treatment of EHC.

  9. Efficacy of antimicrobial photodynamic therapy as an adjuvant in periodontal treatment in Down syndrome patients.

    PubMed

    Martins, Fabiana; Simões, Alyne; Oliveira, Marcio; Luiz, Ana Claudia; Gallottini, Marina; Pannuti, Claudio

    2016-12-01

    Down syndrome (DS) has characteristics that include mental retardation, a characteristic phenotype, congenital heart defects, immune disorders, and increased risk of periodontal disease (PD). Antimicrobial photodynamic therapy (aPDT) is the combined use of photosensitizers associated with low-level laser (LLL) and oxygen, leading to singlet oxygen formation, which contributes to the antibacterial activity of the phagocytes, killing bacteria. The objective of this study was to evaluate the efficacy of aPDT as an adjuvant to conventional periodontal treatment of PD in DS patients. A double-blinded, controlled, randomized, split-mouth study was conducted. A total of 13 DS subjects who were 18 years or older and who presented at least one tooth in each quadrant of the mouth with probing pocket depth (PPD) equal to or greater than 5 mm were included. The patients were evaluated at three different times: at the baseline, PPD were obtained. After 1 week, conventional scaling and root planing (SRP) was performed, and two randomly selected quadrants also received aPDT. One month after SRP, all the patients were reevaluated. Periodontal conditions were improved among all the participants. The PDT-with-SRP group presented a nonsignificant reduction in PPD (mean = 1.27 mm, median = 1.17 mm) relative to that of the SRP group (mean = 1.00 mm, median = 0.95 mm). Changes over time were compared using the Wilcoxon test. A significant reduction in median PPD was observed in both groups (p = 0.001). Both types of periodontal treatment, with and without PDT, were similarly effective and were associated with good clinical response.

  10. Comparison of the removal efficiency of endocrine disrupting compounds in pilot scale sewage treatment processes.

    PubMed

    Lee, Jiho; Lee, Byoung C; Ra, Jin S; Cho, Jaeweon; Kim, In S; Chang, Nam I; Kim, Hyun K; Kim, Sang D

    2008-04-01

    The removal efficiency of endocrine disrupting compounds from effluents using pilot scale sewage treatment processes, including various treatment technologies, such as membrane bioreactors (MBR), nanofiltration (NF) and reverse osmosis (RO) for the purpose of water reuse, were estimated and compared. The calculated estrogenic activity, expressed in ng-EEQ/l, based on the concentration detected by GC/MS, and relative potencies for each target compound were compared to those measured using the E-screen assay. The removal efficiencies for nonylphenol, was within the range of 55-83% in effluents. High removal efficiencies of approximately >70% based on the detection limits were obtained for bisphenol A, E1, EE2 and genistein with each treatment processes, with the exception of E1 ( approximately 64%) using the MBR process. The measured EEQ values for the effluents from the MBR, NF and RO processes also indicated low estrogenic activities of 0.65, 0.23 and 0.05 ng-EEQ/l, respectively. These were markedly reduced values compared with the value of 1.2 ng-EEQ/l in influent. Consequently, the removals of EDCs in terms of the EEQ value from the biological and chemical determinations were sufficiently achieved by the treatment process applied in this study, especially in the cases of the NF and RO treatments.

  11. Adjuvant treatment with tumor-targeting Salmonella typhimurium A1-R reduces recurrence and increases survival after liver metastasis resection in an orthotopic nude mouse model.

    PubMed

    Murakami, Takashi; Hiroshima, Yukihiko; Zhao, Ming; Zhang, Yong; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2015-12-08

    Colon cancer liver metastasis is often the lethal aspect of this disease. Well-isolated metastases are candidates for surgical resection, but recurrence is common. Better adjuvant treatment is therefore needed to reduce or prevent recurrence. In the present study, HT-29 human colon cancer cells expressing red fluorescent protein (RFP) were used to establish liver metastases in nude mice. Mice with a single liver metastasis were randomized into bright-light surgery (BLS) or the combination of BLS and adjuvant treatment with tumor-targeting S. typhimurium A1-R. Residual tumor fluorescence after BLS was clearly visualized at high magnification by fluorescence imaging. Adjuvant treatment with S. typhimurium A1-R was highly effective to increase survival and disease-free survival after BLS of liver metastasis. The results suggest the future clinical potential of adjuvant S. typhimurium A1-R treatment after liver metastasis resection.

  12. Factors related to endocrine changes and hormone substitution treatment during pre- and post-operation stages in craniopharyngioma

    PubMed Central

    Sun, Fenglei; Sun, Xintang; Du, Xiaolong; Xing, Hongshun; Yang, Bin

    2017-01-01

    Factors related to endocrine changes and hormone substitution treatment during pre- and post-operation periods in craniopharyngioma cases were examined. Twenty patients who underwent tumor resection from January 2012 to January 2015 were included in the study. We monitored factors related to endocrine changes and hormone substitution treatment during pre- and post-operation periods. Blood thyroid-stimulating hormone, triiodothyronine, thyroxine, prolactin, follicle-stimulating hormone, luteinizing hormone and cortisol levels were measured in the patients. Urinary volume and urine specific gravity were also measured before and after the operation. After the operation, we observed diabetes insipidus and a decrease in TSH and gonadal hormone levels more frequently compared to pre-operation. However, incidence of high prolactin was markedly reduced following surgery. The number of hypothyroidism cases before and after surgery had no statistical significance. In conclusion, surgery for craniopharyngioma aggravated endocrine dysfunction. Craniotomy and total tumor resection had considerable effects on the endocrine system. Routine hormone therapy as an alternative treatment was necessary after operation. Alternative treatment of adrenal cortex hormones reduced the incidence on low blood cortisol. PMID:28123549

  13. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline

    PubMed Central

    Bornstein, Stefan R.; Allolio, Bruno; Arlt, Wiebke; Barthel, Andreas; Don-Wauchope, Andrew; Hammer, Gary D.; Husebye, Eystein S.; Merke, Deborah P.; Murad, M. Hassan; Stratakis, Constantine A.; Torpy, David J.

    2016-01-01

    Objective: This clinical practice guideline addresses the diagnosis and treatment of primary adrenal insufficiency. Participants: The Task Force included a chair, selected by The Clinical Guidelines Subcommittee of the Endocrine Society, eight additional clinicians experienced with the disease, a methodologist, and a medical writer. The co-sponsoring associations (European Society of Endocrinology and the American Association for Clinical Chemistry) had participating members. The Task Force received no corporate funding or remuneration in connection with this review. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to determine the strength of recommendations and the quality of evidence. Consensus Process: The evidence used to formulate recommendations was derived from two commissioned systematic reviews as well as other published systematic reviews and studies identified by the Task Force. The guideline was reviewed and approved sequentially by the Endocrine Society's Clinical Guidelines Subcommittee and Clinical Affairs Core Committee, members responding to a web posting, and the Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. Conclusions: We recommend diagnostic tests for the exclusion of primary adrenal insufficiency in all patients with indicative clinical symptoms or signs. In particular, we suggest a low diagnostic (and therapeutic) threshold in acutely ill patients, as well as in patients with predisposing factors. This is also recommended for pregnant women with unexplained persistent nausea, fatigue, and hypotension. We recommend a short corticotropin test (250 μg) as the “gold standard” diagnostic tool to establish the diagnosis. If a short corticotropin test is not possible in the first instance, we recommend an initial screening procedure comprising the measurement of morning plasma ACTH

  14. Splenomegaly and Its Associations with Genetic Polymorphisms and Treatment Outcome in Colorectal Cancer Patients Treated with Adjuvant FOLFOX

    PubMed Central

    Kim, Mi-Jung; Han, Sae-Won; Lee, Dae-Won; Cha, Yongjun; Lee, Kyung-Hun; Kim, Tae-Yong; Oh, Do-Youn; Kim, Se Hyung; Im, Seock-Ah; Bang, Yung-Jue; Kim, Tae-You

    2016-01-01

    Purpose Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients. Materials and Methods Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells. Results Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, –42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly. Conclusion Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly. PMID:26790967

  15. Bone marrow recuperation by AM3 in breast cancer patients submitted to aggressive adjuvant treatment. A preliminary report.

    PubMed

    Millá, A; Sanchiz, F; Sada, G; Villarrubia, V G

    1986-01-01

    The results of a prospective randomized study of 46 patients with breast carcinoma are presented. Twenty six patients were treated with AM3 (biological response modifier) associated with adjuvant radiotherapy and chemotherapy. Bone marrow hypoplasia was observed in 26.9% of the patients treated with AM3 compared with a 65% incidence in the control group (P less than 0.05). All patients showed leukopenia in peripheral blood count; however, the nadir of leukocytes was 4,000 leu/mm3 in the test group, compared with 1,900 leu/mm3 in the control group. None of the patients in the AM3 group showed thrombocytopenia, whereas 55% in the control group did. In none of the AM-3-treated cases was it necessary to modify the therapeutic schedule of adjuvant treatment.

  16. Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial

    PubMed Central

    Holmes, Eileen; Baselga, José; de Azambuja, Evandro; Dueck, Amylou C.; Viale, Giuseppe; Zujewski, Jo Anne; Goldhirsch, Aron; Armour, Alison; Pritchard, Kathleen I.; McCullough, Ann E.; Dolci, Stella; McFadden, Eleanor; Holmes, Andrew P.; Tonghua, Liu; Eidtmann, Holger; Dinh, Phuong; Di Cosimo, Serena; Harbeck, Nadia; Tjulandin, Sergei; Im, Young-Hyuck; Huang, Chiun-Sheng; Diéras, Véronique; Hillman, David W.; Wolff, Antonio C.; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Suter, Thomas; Gelber, Richard D.; Perez, Edith A.

    2016-01-01

    Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2–positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2–positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. PMID:26598744

  17. Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections.

    PubMed

    Draughn, G Logan; Allen, C Leigh; Routh, Patricia A; Stone, Maria R; Kirker, Kelly R; Boegli, Laura; Schuchman, Ryan M; Linder, Keith E; Baynes, Ronald E; James, Garth; Melander, Christian; Pollard, Angela; Cavanagh, John

    2017-01-01

    2-Aminoimidazole (2-AI)-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus, we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound.

  18. Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections

    PubMed Central

    Draughn, G Logan; Allen, C Leigh; Routh, Patricia A; Stone, Maria R; Kirker, Kelly R; Boegli, Laura; Schuchman, Ryan M; Linder, Keith E; Baynes, Ronald E; James, Garth; Melander, Christian; Pollard, Angela; Cavanagh, John

    2017-01-01

    2-Aminoimidazole (2-AI)-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus, we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound. PMID:28138218

  19. Fining treatments of white wines by means of polymeric adjuvants for their stabilization against browning.

    PubMed

    Spagna, G; Barbagallo, R N; Pifferi, P G

    2000-10-01

    Browning and maderization represent important problems for white wine stability. Essentially, this is due to polyphenol oxidation in the wine. The problem has been remedied by adsorption of polyphenol compounds with polymeric adjuvants (chitosans, scleroprotein, and polylactic acid) not used traditionally in wine-making. In particular, some chitosans reduced the polyphenol content and stabilized two Italian white wines (Trebbiano and Albana) to the same extent as did potassium caseinate, an adjuvant normally used in enology. Moreover, chitosans could be reused after a simple regeneration process.

  20. Iodine and doxorubicin, a good combination for mammary cancer treatment: antineoplastic adjuvancy, chemoresistance inhibition, and cardioprotection

    PubMed Central

    2013-01-01

    Background Although mammary cancer (MC) is the most common malignant neoplasia in women, the mortality for this cancer has decreased principally because of early detection and the use of neoadjuvant chemotherapy. Of several preparations that cause MC regression, doxorubicin (DOX) is the most active, first-line monotherapeutic. Nevertheless, its use is limited due to the rapid development of chemoresistance and to the cardiotoxicity caused by free radicals. In previous studies we have shown that supplementation with molecular iodine (I2) has a powerful antineoplastic effect in methylnitrosourea (MNU)-induced experimental models of MC. These studies also showed a consistent antioxidant effect of I2 in normal and tumoral tissues. Methods Here, we analyzed the effect of I2 in combination with DOX treatment in female Sprague Dawley rats with MNU-induced MC. In the first experiment (short) animals were treated with the therapeutic DOX dose (16 mg/kg) or with lower doses (8 and 4 mg/Kg), in each case with and without 0.05% I2 in drinking water. Iodine treatment began on day 0, a single dose of DOX was injected (ip) on day 2, and the analysis was carried out on day 7. In the second experiment (long) animals with and without iodine supplement were treated with one or two injections of 4 mg/kg DOX (on days 0 and 14) and were analyzed on day 56. Results At all DOX doses, the short I2 treatment induced adjuvant antineoplastic effects (decreased tumor size and proliferating cell nuclear antigen level) with significant protection against body weight loss and cardiotoxicity (creatine kinase MB, cardiac lipoperoxidation, and heart damage). With long-term I2, mammary tumor tissue became more sensitive to DOX, since a single injection of the lowest dose of DOX (4 mg/Kg) was enough to stop tumor progression and a second DOX4 injection on day 14 caused a significant and rapid decrease in tumor size, decreased the expression of chemoresistance markers (Bcl2 and survivin), and increased

  1. Oral Zinc Sulfate as Adjuvant Treatment in Children With Nephrolithiasis: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial

    PubMed Central

    Yousefichaijan, Parsa; Cyrus, Ali; Dorreh, Fatemeh; Rafeie, Mohammad; Sharafkhah, Mojtaba; Frohar, Faryar; Safi, Fatemeh

    2015-01-01

    Background: Nephrolithiasis in children is associated with a high rate of complications and recurrence. Objectives: Since some evidences reported that zinc has an important place amongst inhibitors of crystallization and crystal growth, we decided to assess the effectiveness of oral zinc sulfate as adjuvant treatment in children with nephrolithiasis. Patients and Methods: This was a randomized, double-blind, placebo-controlled clinical trial. 102 children in the age range 1 month to 11 years with first nephrolithiasis were recruited. Patients were randomly divided into two equal groups (intervention and control groups). Intervention group received conservative measures for stones and 1 mg/kg/day (maximum 20 mg/day) oral zinc sulfate syrup for 3 months. Control group received placebo in addition to conservative measures, also for 3 months. Patients were followed up by ultrasonography for 9 months, in 5 steps (at the end of 1st, 2nd, 3rd, 6th and 9th month after treatment) assessing size and number of stones in the kidneys. Results: Only at the end of the first month, the average number (intervention: 1.15 ± 3.78, control: 1.3 ± 2.84) (P = 0.001) and size (cm) (intervention: 0.51 ± 1.76, control: 0.62 ± 1.39) (P = 0.001) of stones was significantly lower in the intervention group, and in other points there was no significant therapeutic efficacy in oral zinc adjuvant treatment compared to conservative treatment alone. Also, during the 9-month follow-up, the number and size of stones in both groups decreased significantly (both: P < 0.0001) in a way that the decrease in the intervention group showed no difference with the control group. Conclusions: Adjuvant treatment with zinc is not more effective than consecutive treatment in children with nephrolithiasis. However, further studies are recommended due to the lack of clinical evidence in this field. PMID:26635934

  2. Seasonal variation of endocrine disrupting compounds, pharmaceuticals and personal care products in wastewater treatment plants.

    PubMed

    Yu, Yong; Wu, Laosheng; Chang, Andrew C

    2013-01-01

    The occurrence of 14 endocrine disrupting compounds (EDCs), pharmaceuticals and personal care products (PPCPs) in influents, effluents and sludge from five wastewater treatment plants (WWTPs) in southern California was studied in winter and summer. All 14 compounds were detected in influent samples from the five WWTPs except for estrone. Paracetamol, naproxen and ibuprofen were the dominant compounds, with mean concentrations of 41.7, 35.7 and 22.3 μg/L, respectively. The treatment removal efficiency for most compounds was more than 90% and concentrations in the effluents were relatively low. Seasonal variation of the compounds' concentration in the wastewater was significant: the total concentration of each compound in the wastewater was higher in winter than in summer, which is attributed to more human consumption of pharmaceuticals during winter and faster degradation of the compounds in summer. The highest concentrations of triclosan and octylphenol were detected in sewage sludge, with mean concentrations of 1505 and 1179 ng/g, respectively. Risk quotients (RQs), expressed as the ratios of environmental concentrations and the predicted no-effect concentrations (PNEC), were less than unity for all the compounds except for estrone in the effluents, indicating no immediate ecological risk is expected. However, RQs were higher than unity for 2 EDCs (estrone and octylphenol) and carbamazepine in sludge samples, indicating a significant ecotoxicological risk to human health. Therefore, appropriate treatment of sewage sludge is required before its application.

  3. Analysis and occurrence of typical endocrine-disrupting chemicals in three sewage treatment plants.

    PubMed

    Wang, L Y; Zhang, X H; Tam, N F Y

    2010-01-01

    Seven typical endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA), 4-tert-octylphenol (OP), estrone (E1), estradiol (E2), 17α-estradiol (17α-E2), estriol (E3) and 17α-ethinylestradiol (EE2) in wastewater, were simultaneously determined with gas chromatography-mass spectrometry (GC-MS). Samples, including influents, effluents and wastewater of different unit processes, were taken seasonally from three different sewage treatment plants. The result showed that BPA and EE2 were the two main types of EDCs in all the samples. The average concentration of BPA were in the range of 268.1-2,588.5 ng l⁻¹ in influents and 34.0-3,099.6 ng l⁻¹ in effluents, while EE2 ranging from 133.1 to 403.2 ng l⁻¹ and from 35.3 to 269.1 ng l⁻¹, respectively. Seasonal change of EDCs levels in effluents was obvious between wet season and dry season. Besides, BPA and E3 could be effectively removed by the biological treatment processes (oxidation ditch and A²/O) with the unit removal of 64-91% and 63-100% for each compound, while other five EDCs had moderate or low removal rates. The study also proved that physical treatment processes, including screening, primary sedimentation and pure aeration, had no or little effect on EDCs removal.

  4. Clinical Role of Adjuvant Chemotherapy after Radical Hysterectomy for FIGO Stage IB-IIA Cervical Cancer: Comparison with Adjuvant RT/CCRT Using Inverse-Probability-of-Treatment Weighting

    PubMed Central

    Jung, Phill-Seung; Kim, Dae-Yeon; Lee, Shin-Wha; Park, Jeong-Yeol; Suh, Dae-Shik; Kim, Jong-Hyeok; Kim, Yong-Man; Kim, Young-Tak; Nam, Joo-Hyun

    2015-01-01

    Objective To evaluate the clinical role of adjuvant chemotherapy (AC) in FIGO stage IB-IIA cervical cancer patients. Study Design A cohort of 262 patients with cervical cancer who received radical hysterectomy (RH) and adjuvant therapy at Asan Medical Center between 1992 and 2012 was enrolled. In this cohort, 85 patients received adjuvant chemotherapy (AC), and 177 received adjuvant radiotherapy or concurrent chemoradiation therapy (AR). Oncologic outcomes and adverse events in both treatment arms were compared using weighted Cox proportional hazards regression models with inverse-probability-of-treatment weighting (IPTW) to reduce the impact of treatment selection bias and potential confounding factors. Results During a 46.8-month median follow-up duration, 39 patients (14.9%) had recurrences, and 18 patients (6.9%) died of disease. In multivariate analysis, the hazard ratio (HR) for recurrence and death was not significantly different in patients in either treatment arm (p=0.62 and 0.12, respectively). Also, after IPTW matching, the HR for recurrence did not significantly differ between the arms (HR 1.57, 95% CI 0.68-3.62, p=0.29). Similarly, disease-free survival and overall survival were not significantly different between the arms (p=0.47 and 0.13, respectively). In addition, patients with AC had a much lower prevalence of long-term complications (lymphedema: n=8 (9.4%) vs. 46 (26.0%), p=0.03; ureteral stricture: n=0 vs. 9 (6.2%), p=0.05). Conclusion Patients with FIGO stage IB-IIA cervical cancer can benefit from AC after RH with fewer long-term complications and non-inferior therapeutic effect to AR. Chemotherapy may therefore be an alternative adjuvant treatment option for cervical cancer, particularly in younger patients. PMID:26176626

  5. Analytical approach for monitoring endocrine-disrupting compounds in urban waste water treatment plants.

    PubMed

    Roda, Aldo; Mirasoli, Mara; Michelini, Elisa; Magliulo, Maria; Simoni, Patrizia; Guardigli, Massimo; Curini, Roberta; Sergi, Manuel; Marino, Alessandra

    2006-06-01

    The presence of endocrine-disrupting compounds in influent and effluent water samples from four waste water treatment plants located in Italy was studied. The estrogen-like activity of the water samples was measured using a chemiluminescent recombinant yeast assay which is based on genetically engineered yeast cells that express the human estrogen receptor. This receptor, once activated, elicits the expression of the reporter gene lac-Z and, consequently, the production of beta-galactosidase, which is then measured by chemiluminescence. To control and minimize sample matrix effects, an external control based on a modified yeast strain stably expressing beta-galactosidase was developed and also used in the assay. Rapid and sensitive chemiluminescent enzyme immunoassays were also developed and validated for the quantification of 17beta-estradiol, estrone, and estriol in waste water samples. Results from both methods were compared with a reference high-performance liquid chromatography and electrospray ionization tandem mass spectrometry (HPLC ESI-MS-MS) method developed for the quantification of natural estrogens. The recombinant yeast assay revealed a significant estrogenic activity in the influent samples, ranging from 80 to 400 pmol/L 17beta-estradiol equivalents (EEQ), which was reduced by 70-95% in the effluent samples. The yeast assay also showed a systematic 20-30% overestimation of estrogenic activity relative to the HPLC ESI-MS-MS method, suggesting the presence of other compounds in the samples with estrogenic activity. The chemiluminescent enzyme immunoassays showed the presence of estrogens in the influent samples (mean concentrations: 350-450 pmol/L for estrone, 5-100 pmol/L for 17beta-estradiol, 25-300 pmol/L for estriol), with significantly lower concentrations detected in the respective effluent samples. The waste water treatment was able to reduce natural estrogen concentrations by 40-95%, although a high variability was observed. The enzyme

  6. Treatment results of high dose cabergoline as an adjuvant therapy in six patients with established severe ovarian hyper stimulation syndrome

    PubMed Central

    Saharkhiz, Nasrin; Akbari Sene, Azadeh; Salehpour, Saghar; Tamimi, Maryam; Vasheghani Farahani, Masoumeh; Sheibani, Kourosh

    2014-01-01

    Background: The beneficial role of cabergoline as a prophylactic agent to prevent ovarian hyper stimulation syndrome (OHSS) among high-risk patients has been demonstrated in previous studies. But data for its role as a treatment for established severe OHSS is still limited. We represent the treatment results of high dose oral cabergoline in management of six patients after the syndrome is established. Case: High-dose oral cabergoline (1 mg daily for eight days) was prescribed as an adjuvant to symptomatic treatment for six hospitalized patients with established severe OHSS following infertility treatment cycles. In two cases OHSS resolved rapidly despite the occurrence of ongoing pregnancy. Conclusion: Considering the treatment outcomes of our patients, high dose cabergoline did not eliminate the need for traditional treatments, but it was a relatively effective and safe therapy in management of established severe OHSS, and prevented the increase in its severity following the occurrence of pregnancy. PMID:25469130

  7. Eugenia punicifolia (Kunth) DC. as an adjuvant treatment for type-2 diabetes mellitus: a non-controlled, pilot study.

    PubMed

    Sales, Débora Simone; Carmona, Fabio; de Azevedo, Bruna Cestari; Taleb-Contini, Silvia Helena; Bartolomeu, Ana Carolina Duó; Honorato, Fernando B; Martinez, Edson Z; Pereira, Ana Maria Soares

    2014-12-01

    Type-2 diabetes mellitus (DM) is a highly prevalent disease with significant morbidity and mortality around the world. However, there is no universally effective treatment, because response to different treatment regimens can vary widely among patients. In this study, we aimed to investigate whether the use of the powdered dried leaves of Eugenia punicifolia (Kunth) DC. (Myrtaceae) is effective as an adjuvant to the treatment of patients with type-2 DM. Fifteen patients were enrolled in a pilot, non-controlled study, and received E. punicifolia for 3 months. After treatment, we observed a significant decrease in glycosylated hemoglobin, basal insulin, thyroid-stimulating hormone, C-reactive protein, and both systolic and diastolic blood pressure. There were no changes in fasting and postprandial glycemia. The compounds myricetin-3-O-rhamnoside, quercetin-3-O-galactoside, quercetin-3-O-xyloside, quercetin-3-O-rhamnoside, kaempferol-3-O-rhamnoside, phytol, gallic acid, and trans-caryophyllene present in the powdered dried leaves of E. punicifolia may be responsible for the therapeutic effect. In conclusion, the powdered leaves of E. punicifolia are promising as an adjuvant in the treatment of type-2 DM and deserve further investigation.

  8. Occurrence and removal of phenolic endocrine disrupting chemicals in the water treatment processes

    NASA Astrophysics Data System (ADS)

    Lv, Xuemin; Xiao, Sanhua; Zhang, Gang; Jiang, Pu; Tang, Fei

    2016-03-01

    This paper evaluated the occurrence and removal efficiency of four selected phenolic endocrine disrupting chemicals (bisphenol A (BPA), octylphenol (OP), nonylphenol (NP) and diethylstilbestrol (DES)) in two drinking waterworks in Jiangsu province which take source water from Taihu Lake. The recombined yeast estrogen screen (YES) and liquid chromatography tandem mass spectrometry (LC-MS/MS) were applied to assess the estrogenicity and detect the estrogens in the samples. The estrogen equivalents (EEQs) ranged from nd (not detected) to 2.96 ng/L, and the estrogenic activities decreased along the processes. Among the 32 samples, DES prevailed in all samples, with concentrations ranging 1.46–12.0 ng/L, BPA, OP and NP were partially detected, with concentrations ranging from nd to 17.73 ng/L, nd to 0.49 ng/L and nd to 3.27 ng/L, respectively. DES was found to be the main contributor to the estrogenicity (99.06%), followed by NP (0.62%), OP (0.23%) and BPA (0.09%). From the observation of treatment efficiency, the advanced treatment processes presented much higher removal ratio in reducing DES, the biodegradation played an important role in removing BPA, ozonation and pre-oxidation showed an effective removal on all the four estrogens; while the conventional ones can also reduce all the four estrogens.

  9. Occurrence and removal of phenolic endocrine disrupting chemicals in the water treatment processes

    PubMed Central

    Lv, Xuemin; Xiao, Sanhua; Zhang, Gang; Jiang, Pu; Tang, Fei

    2016-01-01

    This paper evaluated the occurrence and removal efficiency of four selected phenolic endocrine disrupting chemicals (bisphenol A (BPA), octylphenol (OP), nonylphenol (NP) and diethylstilbestrol (DES)) in two drinking waterworks in Jiangsu province which take source water from Taihu Lake. The recombined yeast estrogen screen (YES) and liquid chromatography tandem mass spectrometry (LC-MS/MS) were applied to assess the estrogenicity and detect the estrogens in the samples. The estrogen equivalents (EEQs) ranged from nd (not detected) to 2.96 ng/L, and the estrogenic activities decreased along the processes. Among the 32 samples, DES prevailed in all samples, with concentrations ranging 1.46–12.0 ng/L, BPA, OP and NP were partially detected, with concentrations ranging from nd to 17.73 ng/L, nd to 0.49 ng/L and nd to 3.27 ng/L, respectively. DES was found to be the main contributor to the estrogenicity (99.06%), followed by NP (0.62%), OP (0.23%) and BPA (0.09%). From the observation of treatment efficiency, the advanced treatment processes presented much higher removal ratio in reducing DES, the biodegradation played an important role in removing BPA, ozonation and pre-oxidation showed an effective removal on all the four estrogens; while the conventional ones can also reduce all the four estrogens. PMID:26953121

  10. Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

    SciTech Connect

    Elshaikh, Mohamed A.; Vance, Sean; Suri, Jaipreet S.; Mahan, Meredith; Munkarah, Adnan

    2014-02-01

    Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma

  11. Postsurgical treatment with adjuvant transarterial chemoembolization in patients with hepatitis B-related hepatocellular carcinoma

    PubMed Central

    Hu, Hao; Liu, Rong; Long, Xiao Ran; Han, Xi Kun; Fan, Jia; Yan, Zhi Ping; Wang, Jian Hua

    2016-01-01

    Abstract This study sought to develop a reliable and easy-to-use scoring model to guide the decision to perform postsurgical adjuvant transarterial chemoembolization (PA-TACE) in patients with hepatitis B-related hepatocellular carcinoma (HCC). The study included 235 consecutive patients with hepatitis B-related HCC undergoing PA-TACE at our medical center. Patients were assigned to 2 sets according to the PA-TACE date: initial (2005–2007; n = 130) and internal validation (2008–2009; n = 105) sets. With the aid of a Cox regression model, we developed a risk-scoring model from the independent predictive factors of our initial set designed as a guide for PA-TACE, and the performance of the model was validated with an internal set. External validation was also performed with an independent dataset (n = 84) to assess the discriminatory power of the scoring model. In the multivariate analysis, 4 risk factors (an increase in Child-Pugh score of at least 1 point, hepatitis B virus deoxyribonucleic acid [HBV-DNA] level >104 IU/mL, tumor diameter ≥5 cm, and the presence of vascular invasion) were significantly associated with prognosis. These factors were incorporated into a novel clinicopathological scoring model (assessment for PA-TACE [APT] risk-scoring model) ranging from 0 to 8 that was correlated with prognosis. Different survival outcomes were identified in three groups (0–2 points, 3–6 points, and 7–8 points). The risk-scoring model was further confirmed with 2 independent sets. The novel APT risk-scoring model, merging 4 prognostic factors, may achieve an optimal postsurgical prediction of PA-TACE in HBV-related HCC. The risk for an individual patient with an APT score of ≥7.0 prior to the PA-TACE, who may not profit from further PA-TACE, can be determined, and this may lead to a more appropriate choice of treatment. PMID:28033246

  12. Interpreting breast international group (BIG) 1-98: a randomized, double-blind, phase III trial comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive, early breast cancer

    PubMed Central

    2011-01-01

    The Breast International Group (BIG) 1-98 study is a four-arm trial comparing 5 years of monotherapy with tamoxifen or with letrozole or with sequences of 2 years of one followed by 3 years of the other for postmenopausal women with endocrine-responsive early invasive breast cancer. From 1998 to 2003, BIG -98 enrolled 8,010 women. The enhanced design f the trial enabled two complementary analyses of efficacy and safety. Collection of tumor specimens further enabled treatment comparisons based on tumor biology. Reports of BIG 1-98 should be interpreted in relation to each individual patient as she weighs the costs and benefits of available treatments. Clinicaltrials.gov ID: NCT00004205. PMID:21635709

  13. Occurrence and fate of endocrine disrupting chemicals in ASP based sewage treatment plant in Hardwar.

    PubMed

    Saini, Gita; Pant, Shalini; Alam, Tanveer; Kazmi, A A

    The occurrence of emerging contaminants such as endocrine disrupting chemicals (EDCs) in our water resources is of prime concern. With this context, fate and seasonal variation of six EDCs (testosterone, T; progesterone, P; diethyl phthalate, DEP; dibutyl phthalate, DBP; propyl-paraben, PP and butyl-paraben, BP) were assessed throughout the year, i.e. in rainy, winter, spring and summer seasons in the raw, treated wastewater and activated sludge in an activated sludge process (ASP) based sewage treatment plant (STP) located in Haridwar, India. Qualitative and quantitative measurements were performed by gas chromatography-mass spectrometry (GC-MS) analysis. Results indicate that in summer, the examined STP could effectively remove 82.9% of T, 86.4% of P, 95.5% of DEP, 92.4% of DBP, 91.5% of PP, and 89.9% of BP from the wastewater. Among the EDCs considered, higher removal efficiencies were achieved for phthalates in the summer season. GC-MS analysis showed that a small fraction of EDCs was sorbed on the solid fraction of activated sludge. Scanning electron microscopy, energy dispersive X-ray spectroscopy and Fourier transformation infrared spectroscopy analysis were also performed to investigate the occurrence of EDCs in biomass samples. Results of this study also demonstrated that removal efficiency, assessed in terms of physicochemical and microbiological parameters, was maximum in summer and reached minimum in rainy season.

  14. A systemic approach to cancer treatment: tumor cell reprogramming focused on endocrine-related cancers.

    PubMed

    Biava, P M; Nicolini, A; Ferrari, P; Carpi, A; Sell, S

    2014-01-01

    The term "cancer cell reprogramming" is used to define any kind of intervention aimed at transforming cancer cells into terminally differentiated cells. Using this approach, new technologies have been applied with different methods for a more systemic approach to cancer treatment. This review reports on advances of these technologies, including our personal contributions, mainly carried out on endocrine-related cancers. Some of the interventions, aimed at reverting cancer cells into a normal phenotype, are based on the evidence that tumor development is suppressed by the embryonic microenvironment. On the basis of this rationale, experiments have been conducted using stem cell differentiation stage factors (SCDSFs) taken at different stages of development of Zebrafish embryos, oocyte extracts, or naïve human umbilical cord matrix derived stem cells (UMDSCs). SCDSFs induce significant growth inhibition on different tumor cell lines in vitro, likely because of increases in cell cycle regulatory molecules, such as p53 and pRb. Treatment with these factors activates apoptosis and differentiation related to caspase-3. This is achieved via p73 apoptotic-dependent pathway activation with a concurrent normalization of the E-cadherin and beta-catenin ratio. Extracts from prophase amphibian oocytes could reprogram relevant epigenetic alterations in MCF-7 and HCC1954 breast cancer cell lines, while un-engineered (naïve) human UMDSCs attenuated growth of MDA-231 human breast carcinoma cells. A product prepared for human treatments, containing SCDSFs at very low doses, yielded favorable results in breast cancer and in intermediate-advanced hepatocellular carcinoma. Other reprogramming interventions used in the models of breast, prostate and ovarian cancer cell lines are described. Finally, current and future perspectives of this novel technology are discussed and a new hallmark of cancer is suggested: the loss of differentiation of cancer cells.

  15. Implementation and evaluation of an Asbru-based decision support system for adjuvant treatment in breast cancer.

    PubMed

    Eccher, Claudio; Seyfang, Andreas; Ferro, Antonella

    2014-11-01

    The domain of cancer treatment is a promising field for the implementation and evaluation of a protocol-based clinical decision support system, because of the algorithmic nature of treatment recommendations. However, many factors can limit such systems' potential to support the decision of clinicians: technical challenges related to the interoperability with existing electronic patient records and clinical challenges related to the inherent complexity of the decisions, often collectively taken by panels of different specialists. In this paper, we evaluate the performances of an Asbru-based decision support system implementing treatment protocols for breast cancer, which accesses data from an oncological electronic patient record. Focusing on the decision on the adjuvant pharmaceutical treatment for patients affected by early invasive breast cancer, we evaluate the matching of the system's recommendations with those issued by the multidisciplinary panel held weekly in a hospital.

  16. Ionic imbalance and lack of effect of adjuvant treatment with methylene blue in the hamster model of leptospirosis.

    PubMed

    Santos, Cleiton Silva; Azevedo, Everton Cruz de; Soares, Luciane Marieta; Carvalho, Magda Oliveira Seixas; dos Santos, Andréia Carvalho; das Chagas, Adenizar Delgado; da Silva, Caroline Luane Rabelo; Chagas, Ursula Maira Russo; dos Reis, Mitermayer Galvão; Athanazio, Daniel Abensur

    2013-06-01

    Leptospirosis in humans usually involves hypokalaemia and hypomagnesaemia and the putative mechanism underlying such ionic imbalances may be related to nitric oxide (NO) production. We previously demonstrated the correlation between serum levels of NO and the severity of renal disease in patients with severe leptospirosis. Methylene blue inhibits soluble guanylyl cyclase (downstream of the action of any NO synthase isoforms) and was recently reported to have beneficial effects on clinical and experimental sepsis. We investigated the occurrence of serum ionic changes in experimental leptospirosis at various time points (4, 8, 16 and 28 days) in a hamster model. We also determined the effect of methylene blue treatment when administered as an adjuvant therapy, combined with late initiation of standard antibiotic (ampicillin) treatment. Hypokalaemia was not reproduced in this model: all of the groups developed increased levels of serum potassium (K). Furthermore, hypermagnesaemia, rather than magnesium (Mg) depletion, was observed in this hamster model of acute infection. These findings may be associated with an accelerated progression to acute renal failure. Adjuvant treatment with methylene blue had no effect on survival or serum Mg and K levels during acute-phase leptospirosis in hamsters.

  17. Mixed Lineage Kinases as Novel Targets for the Treatment of Endocrine-Resistant, ER-Positive Breast Cancer

    DTIC Science & Technology

    2016-06-01

    tumors enter exponential growth , but prior to drug treatment. We therefore amended our AUF to allow us to remove the estrogen pellet from animals prior to...administration of the drug to animals. We also established methods for monitoring tumor growth using both cell lines and patient derived xenografts...in immune compromised mice. Experiments are in progress to test the ability of the MLK inhibitor to block the growth of endocrine sensitive and

  18. Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

    SciTech Connect

    Twu, Chih-Wen; Wang, Wen-Yi; Chen, Chien-Chih; Liang, Kai-Li; Jiang, Rong-San; Wu, Ching-Te; Shih, Yi-Ting; Lin, Po-Ju; Liu, Yi-Chun; Lin, Jin-Ching

    2014-05-01

    Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

  19. MiR-4653-3p and its target gene FRS2 are prognostic biomarkers for hormone receptor positive breast cancer patients receiving tamoxifen as adjuvant endocrine therapy

    PubMed Central

    Wang, Zhu; Wang, Yu; Wang, YanPing; Qiu, Yan; Li, Li; Bu, Hong; Li, JiaYuan; Zheng, Hong

    2016-01-01

    Long-term tamoxifen treatment significantly improves the survival of hormone receptor-positive (HR+) breast cancer (BC) patients. However, tamoxifen resistance remains a challenge. We aimed to identify prognostic biomarkers for tamoxifen resistance and reveal the underlying mechanism. From March 2001 to September 2013, 400 HR+ BC women (stage I~III) were treated with adjuvant tamoxifen for 5 years or until relapse in West China Hospital. We included a discovery set of 6 patients who were refractory to tamoxifen, and a validation cohort of 88 patients including 35 cases with relapse. In the discovery set, microRNA microarray showed that miR-4653-3p decreased in recurrent/metastatic lesions compared to the matched primary lesions. In the validation cohort, real-time RT-PCR demonstrated that, following tamoxifen treatment, miR-4653-3p overexpression in the primary tumors decreased the risk of relapse (adjusted hazard ratio [HR] = 0.17, 95% confidence interval [CI] = 0.05~0.57, P = 0.004). Conversely, high expression of FRS2, the key adaptor protein required by FGFR signaling, predicted poor disease-free survival (DFS) (adjusted HR = 2.70, 95% CI = 1.11~6.56, P = 0.03). MiR-4653-3p down regulated FRS2 by binding to its 3′ untranslated region. Either overexpressing miR-4653-3p or attenuating FRS2 expression could restore TAM sensitivity in two tamoxifen-resistant BC cell lines. In conclusion, high miR-4653-3p level was the potential predictor for favorable DFS, while FRS2 overexpression was potential high-risk factor for relapse in HR+ BC patients receiving TAM adjuvant therapy. FGFR/FRS2 signaling might be a promising target for reversing tamoxifen resistance. PMID:27533459

  20. Prognostic and Predictive Value of Centrally Reviewed Ki-67 Labeling Index in Postmenopausal Women With Endocrine-Responsive Breast Cancer: Results From Breast International Group Trial 1-98 Comparing Adjuvant Tamoxifen With Letrozole

    PubMed Central

    Viale, Giuseppe; Giobbie-Hurder, Anita; Regan, Meredith M.; Coates, Alan S.; Mastropasqua, Mauro G.; Dell'Orto, Patrizia; Maiorano, Eugenio; MacGrogan, Gaëtan; Braye, Stephen G.; Öhlschlegel, Christian; Neven, Patrick; Orosz, Zsolt; Olszewski, Wojciech P.; Knox, Fiona; Thürlimann, Beat; Price, Karen N.; Castiglione-Gertsch, Monica; Gelber, Richard D.; Gusterson, Barry A.; Goldhirsch, Aron

    2008-01-01

    Purpose To evaluate the prognostic and predictive value of Ki-67 labeling index (LI) in a trial comparing letrozole (Let) with tamoxifen (Tam) as adjuvant therapy in postmenopausal women with early breast cancer. Patients and Methods Breast International Group (BIG) trial 1-98 randomly assigned 8,010 patients to four treatment arms comparing Let and Tam with sequences of each agent. Of 4,922 patients randomly assigned to receive 5 years of monotherapy with either agent, 2,685 had primary tumor material available for central pathology assessment of Ki-67 LI by immunohistochemistry and had tumors confirmed to express estrogen receptors after central review. The prognostic and predictive value of centrally measured Ki-67 LI on disease-free survival (DFS) were assessed among these patients using proportional hazards modeling, with Ki-67 LI values dichotomized at the median value of 11%. Results Higher values of Ki-67 LI were associated with adverse prognostic factors and with worse DFS (hazard ratio [HR; high:low] = 1.8; 95% CI, 1.4 to 2.3). The magnitude of the treatment benefit for Let versus Tam was greater among patients with high tumor Ki-67 LI (HR [Let:Tam] = 0.53; 95% CI, 0.39 to 0.72) than among patients with low tumor Ki-67 LI (HR [Let:Tam] = 0.81; 95% CI, 0.57 to 1.15; interaction P = .09). Conclusion Ki-67 LI is confirmed as a prognostic factor in this study. High Ki-67 LI levels may identify a patient group that particularly benefits from initial Let adjuvant therapy. PMID:18981464

  1. Changes in endocrine profiles during ovsynch and ovsynch plus norprolac treatment in Murrah buffalo heifers at hot summer season.

    PubMed

    Roy, K S; Prakash, B S

    2009-04-01

    The aim of this study was to compare the changes in hormonal profiles during ovsynch and ovsynch plus norprolac treatment in Murrah buffalo heifers following timed artificial insemination (TAI) at stressful summer months, through intensive endocrine analysis. The norprolac (an anti-prolactin drug) at the dose rate of 10.0 mg/animal /day effectively suppressed the level of prolactin upto 30 hours. The hormones quantified in blood plasma samples collected before, during and after ovsynch and ovsynch plus norprolac treatment were LH, prolactin, progesterone, estradiol-17beta and total estrogens. The plasma prolactin and progesterone concentrations were negatively correlated (r = - 0.24) during summer estrous cycle, which indicated prolactin-induced suppression of progesterone secretion through poor luteal development. The ovsynch treatment reduced the incidence of anestrous from 45% before treatment to only 18% after treatment. The norprolac induced prolactin suppression improved the efficiency of ovsynch treatment upto 100% cyclicity after treatment in comparison to 36% acyclicity before treatment. In both the treatments 45% and 55% of animal became pregnant after TAI, respectively. The high prolactin secretion contributed to poor fertility by lowering gonadal hormones (estradiol-17beta, total estrogens and progesterone) production in summer months. This finding of endocrine changes suggests that ovsynch protocol for estrus synchronization has potential application for improvement of fertility in repeat breeding buffaloes even during extreme summer months through suppression of prolactin secretion.

  2. Effectivity of advanced wastewater treatment: reduction of in vitro endocrine activity and mutagenicity but not of in vivo reproductive toxicity.

    PubMed

    Giebner, Sabrina; Ostermann, Sina; Straskraba, Susanne; Oetken, Matthias; Oehlmann, Jörg; Wagner, Martin

    2016-09-06

    Conventional wastewater treatment plants (WWTPs) have a limited capacity to eliminate micropollutants. One option to improve this is tertiary treatment. Accordingly, the WWTP Eriskirch at the German river Schussen has been upgraded with different combinations of ozonation, sand, and granulated activated carbon filtration. In this study, the removal of endocrine and genotoxic effects in vitro and reproductive toxicity in vivo was assessed in a 2-year long-term monitoring. All experiments were performed with aqueous and solid-phase extracted water samples. Untreated wastewater affected several endocrine endpoints in reporter gene assays. The conventional treatment removed the estrogenic and androgenic activity by 77 and 95 %, respectively. Nevertheless, high anti-estrogenic activities and reproductive toxicity persisted. All advanced treatment technologies further reduced the estrogenic activities by additional 69-86 % compared to conventional treatment, resulting in a complete removal of up to 97 %. In the Ames assay, we detected an ozone-induced mutagenicity, which was removed by subsequent filtration. This demonstrates that a post treatment to ozonation is needed to minimize toxic oxidative transformation products. In the reproduction test with the mudsnail Potamopyrgus antipodarum, a decreased number of embryos was observed for all wastewater samples. This indicates that reproductive toxicants were eliminated by neither the conventional nor the advanced treatment. Furthermore, aqueous samples showed higher anti-estrogenic and reproductive toxicity than extracted samples, indicating that the causative compounds are not extractable or were lost during extraction. This underlines the importance of the adequate handling of wastewater samples. Taken together, this study demonstrates that combinations of multiple advanced technologies reduce endocrine effects in vitro. However, they did not remove in vitro anti-estrogenicity and in vivo reproductive toxicity. This

  3. Endocrine glands

    MedlinePlus Videos and Cool Tools

    ... and nervous systems work very closely together. The brain continuously sends instructions to the endocrine system, and ... master switchboard because it's the part of the brain that controls the endocrine system. The pituitary gland, ...

  4. Toxicity of combined treatment of adjuvant irradiation and interferon alpha2b in high-risk melanoma patients.

    PubMed

    Conill, Carlos; Jorcano, Sandra; Domingo-Domènech, Josep; Marruecos, Jordi; Vilella, Ramón; Malvehy, Josep; Puig, Susana; Sánchez, Marcelo; Gallego, Rosa; Castel, Teresa

    2007-10-01

    Surgically resected stage III melanoma patients commonly receive adjuvant therapy with interferon (IFN) alpha2b. For those patients with high-risk features of draining node recurrence, radiation therapy can also be considered as a treatment option. The purpose of this retrospective study was to assess the efficacy and radiation-related toxicity of this combined therapy. Eighteen patients receiving adjuvant IFNalpha2b therapy during radiation therapy, or within 1 month of its completion, were reviewed retrospectively and analysed for outcome. Radiation was delivered at 600 cGy dose per fraction, in 16 out of 18 patients, twice a week, and at 200 cGy dose per fraction in two patients five times a week. Total radiation dose and number of fractions were as follows: 30 Gy/5 fr (n=8), 36 Gy/6 fr (n=8) and 50 Gy/25 fr (n=2). The percentage of disease-free patients, with no local recurrence, at 3 years was 88%. In 10 patients, IFNalpha2b was administered concurrently with radiotherapy; in three, within 30 days before or after radiation; and in five, more than 30 days after radiation. All the patients experienced acute skin reactions, grade I on the Radiation Therapy Oncology Group (RTOG) scale. Late radiation-related toxicity was seen in one patient with grade III (RTOG) skin reaction and two with grade IV (RTOG) radiation-induced myelitis. Concurrent use of adjuvant radiotherapy and IFNalpha2b might enhance radiation-induced toxicity, and special care should be taken when the spinal cord is included in the radiation field.

  5. Effects of Neonatal Treatment With 6-Hydroxydopamine and Endocrine Disruptors on Motor Activity and Gene Expression in Rats

    PubMed Central

    Masuo, Yoshinori; Ishido, Masami; Morita, Masatoshi; Oka, Syuichi

    2004-01-01

    To investigate the mechanisms underlying motor hyperactivity, we performed intracisternal injection of 6-hydroxydopamine or endocrine disruptors in rats on postnatal day 5. 6-Hydroxydopamine (100 μg, 488 nmol) caused a significant increase in spontaneous motor activities at 4 weeks of age. Gene-expression profiling using a cDNA membrane array revealed alterations in several classes of gene at 8 weeks of age. In the midbrain, gene expression was enhanced in dopamine transporter 1; a platelet-derived growth factor receptor; dopamine receptor D4; galanin receptor 2; arginine vasopressin receptor 2; neuropeptide Y; tachykinin 2; and fibroblast growth factor 10. Expression was also enhanced in the glutamate/aspartate transporter gene in the striatum. Rats received an endocrine disruptor (87 nmol), such as bisphenol A, nonylphenol, p-octylphenol, or diethylhexylphthalate, which also caused motor hyperactivity at 4 weeks. The effects of bisphenol A on motor activity were dose-dependent from 0.87 to 87 nmol. The phenols caused a deficit in dopamine neurons, similarly to the deficit caused by 6-hydroxydopamine. Gene-expression profiles after treatment with endocrine disruptors showed variation and differed from those of 6- hydroxydopamine. The results suggest that neonatal treatment with environmental chemicals can generate an animal model of attention-deficit hyperactivity disorder, in which clinical symptoms are pervasive. PMID:15303306

  6. Effect of wastewater treatment facility closure on endocrine disrupting chemicals in a Coastal Plain stream

    USGS Publications Warehouse

    Bradley, Paul M.; Journey, Celeste; Clark, Jimmy M.

    2016-01-01

    Wastewater treatment facility (WWTF) closures are rare environmental remediation events; offering unique insight into contaminant persistence, long-term wastewater impacts, and ecosystem recovery processes. The U.S. Geological Survey assessed the fate of select endocrine disrupting chemicals (EDC) in surface water and streambed sediment one year before and one year after closure of a long-term WWTF located within the Spirit Creek watershed at Fort Gordon, Georgia. Sample sites included a WWTF-effluent control located upstream from the outfall, three downstream effluent-impacted sites located between the outfall and Spirit Lake, and one downstream from the lake's outfall. Prior to closure, the 2.2-km stream segment downstream from the WWTF outfall was characterized by EDC concentrations significantly higher (α = 0.05) than at the control site; indicating substantial downstream transport and limited in-stream attenuation of EDC, including pharmaceuticals, estrogens, alkylphenol ethoxylate (APE) metabolites, and organophosphate flame retardants (OPFR). Wastewater-derived pharmaceutical, APE metabolites, and OPFR compounds were also detected in the outflow of Spirit Lake, indicating the potential for EDC transport to aquatic ecosystems downstream of Fort Gordon under effluent discharge conditions. After the WWTF closure, no significant differences in concentrations or numbers of detected EDC compounds were observed between control and downstream locations. The results indicated EDC pseudo-persistence under preclosure, continuous supply conditions, with rapid attenuation following WWTF closure. Low concentrations of EDC at the control site throughout the study and comparable concentrations in downstream locations after WWTF closure indicated additional, continuing, upstream contaminant sources within the Spirit Creek watershed. 

  7. Vaginal brachytherapy alone is sufficient adjuvant treatment of surgical stage I endometrial cancer

    SciTech Connect

    Solhjem, Matthew C. . E-mail: petersen.ivy@mayo.edu; Petersen, Ivy A.; Haddock, Michael G.

    2005-08-01

    Purpose To determine the efficacy and complications of adjuvant vaginal high-dose-rate brachytherapy alone for patients with Stage I endometrial cancer in whom complete surgical staging had been performed. Methods and Materials Between April 1998 and March 2004, 100 patients with Stage I endometrial cancer underwent surgical staging (total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic {+-} paraaortic nodal sampling) and postoperative vaginal high-dose-rate brachytherapy at our institution. The total dose was 2100 cGy in three fractions. Results With a median follow-up of 23 months (range 2-62), no pelvic or vaginal recurrences developed. All patients underwent pelvic dissection, and 42% underwent paraaortic nodal dissection. A median of 29.5 pelvic nodes (range 1-67) was removed (84% had >10 pelvic nodes removed). Most patients (73%) had endometrioid (or unspecified) adenocarcinoma, 16% had papillary serous carcinoma, and 11% had other histologic types. The International Federation of Gynecology and Obstetrics stage and grade was Stage IA, grade III in 5; Stage IB, grade I, II, or III in 6, 27, or 20, respectively; and Stage IC, grade I, II, or III in 13, 17, or 10, respectively. The Common Toxicity Criteria (version 2.0) complications were mild (Grade 1-2) and consisted primarily of vaginal mucosal changes, temporary urinary irritation, and temporary diarrhea. Conclusion Adjuvant vaginal high-dose-rate brachytherapy alone may be a safe and effective alternative to pelvic external beam radiotherapy for surgical Stage I endometrial cancer.

  8. Conformal radiotherapy in the adjuvant treatment of gastric cancer: Review of 82 cases

    SciTech Connect

    Kassam, Zahra |; Lockwood, Gina |; O'Brien, Catherine; Brierley, James |; Swallow, Carol ||; Oza, Amit |; Siu, Lillian |; Knox, Jennifer J. |; Wong, Rebecca |; Cummings, Bernard; Kim, John |; Moore, Malcolm |; Ringash, Jolie |. E-mail: jolie.ringash@rmp.uhn.on.cag

    2006-07-01

    Background: The Intergroup 0116 study showed a survival benefit with adjuvant chemoradiotherapy (CRT) for resected gastric cancer. We report our experience using conformal radiotherapy (RT). Methods and Materials: Eighty-two patients with resected gastric or gastroesophageal junction (GEJ) adenocarcinoma, Stage IB to IV (M0), were treated with 45 Gy in 25 fractions using a 5-field conformal technique. Chemotherapy was in accordance with the Intergroup 0116 study, or infusional 5-fluorouracil and cisplatin in a phase I/II trial. Results: Mean age was 56.4 years. Median follow-up was 22.8 months. Grade 3 or greater acute toxicity (National Cancer Institute Common Terminology Criteria of Adverse Events, version 3.0) was noted in 57% of patients (upper gastrointestinal tract 34%, hematologic 33%). One patient died of neutropenic sepsis. Radiation Therapy Oncology Group Grade 3 late toxicity included esophageal strictures (3 patients) and small bowel obstruction (1 patient). Full course CRT was completed by 67% of patients. Of 26 patients who relapsed, 20 died. Site of first relapse was available on 23 patients: 8 locoregional and distant, 4 locoregional alone, 11 distant alone. Overall and relapse-free survival were 69% and 54% at 3 years. Conclusion: Adjuvant CRT for gastric cancer, even with conformal RT, is associated with significant toxicity. Survival was comparable to that reported in the Intergroup 0116 study.

  9. Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis

    PubMed Central

    Coyle, C.; Cafferty, F. H.; Vale, C.; Langley, R. E.

    2016-01-01

    Background Metformin use has been associated with a reduced risk of developing cancer and an improvement in overall cancer survival rates in meta-analyses, but, to date, evidence to support the use of metformin as an adjuvant therapy in individual cancer types has not been presented. Patients and methods We systematically searched research databases, conference abstracts and trial registries for any studies reporting cancer outcomes for individual tumour types in metformin users compared with non-users, and extracted data on patients with early-stage cancer. Studies were assessed for design and quality, and a meta-analysis was conducted to quantify the adjuvant effect of metformin on recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS), to inform future trial design. Results Of 7670 articles screened, 27 eligible studies were identified comprising 24 178 participants, all enrolled in observational studies. In those with early-stage colorectal cancer, metformin use was associated with a significant benefit in all outcomes [RFS hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.47–0.85; OS HR 0.69, CI 0.58–0.83; CSS HR 0.58, CI 0.39–0.86]. For men with early-stage prostate cancer, metformin was associated with significant, or borderline significant, benefits in all outcomes (RFS HR 0.83, CI 0.69–1.00; OS HR 0.82, CI 0.73–0.93; CSS HR 0.58, CI 0.37–0.93); however, there was significant heterogeneity between studies. The data suggest that prostate cancer patients treated with radical radiotherapy may benefit more from metformin (RFS HR 0.45, CI 0.29–0.70). In breast and urothelial cancer, no significant benefits were identified. Sufficient data were not available to conduct analyses on the impact of metformin dose and duration. Conclusions Our findings suggest that metformin could be a useful adjuvant agent, with the greatest benefits seen in colorectal and prostate cancer, particularly in those receiving radical

  10. Assessment of endocrine-disrupting chemicals attenuation in a coastal plain stream prior to wastewater treatment plant closure

    USGS Publications Warehouse

    Bradley, Paul M.; Journey, Celeste

    2014-01-01

    The U.S. Geological Survey is conducting a combined pre/post-closure assessment at a long-term wastewater treatment plant (WWTP) site at Fort Gordon near Augusta, Georgia. Here, we assess select endocrine-active chemicals and benthic macroinvertebrate community structure prior to closure of the WWTP. Substantial downstream transport and limited instream attenuation of endocrine-disrupting chemicals (EDCs) was observed in Spirit Creek over a 2.2-km stream segment downstream of the WWTP outfall. A modest decline (less than 20% in all cases) in surface water detections was observed with increasing distance downstream of the WWTP and attributed to partitioning to the sediment. Estrogens detected in surface water in this study included estrone (E1), 17β-estradiol (E2), and estriol (E3). The 5 ng/l and higher mean estrogen concentrations observed in downstream locations indicated that the potential for endocrine disruption was substantial. Concentrations of alkylphenol ethoxylate (APE) metabolite EDCs also remained statistically elevated above levels observed at the upstream control site. Wastewater-derived pharmaceutical and APE metabolites were detected in the outflow of Spirit Lake, indicating the potential for EDC transport to aquatic ecosystems downstream of Fort Gordon. The results indicate substantial EDC occurrence, downstream transport, and persistence under continuous supply conditions and provide a baseline for a rare evaluation of ecosystem response to WWTP closure.

  11. Growth and endocrine effects of recombinant bovine growth hormone treatment in non-transgenic and growth hormone transgenic coho salmon.

    PubMed

    Raven, P A; Sakhrani, D; Beckman, B; Neregård, L; Sundström, L F; Björnsson, B Th; Devlin, R H

    2012-05-15

    To examine the relative growth, endocrine, and gene expression effects of growth hormone (GH) transgenesis vs. GH protein treatment, wild-type non-transgenic and GH transgenic coho salmon were treated with a sustained-release formulation of recombinant bovine GH (bGH; Posilac). Fish size, specific growth rate (SGR), and condition factor (CF) were monitored for 14 weeks, after which endocrine parameters were measured. Transgenic fish had much higher growth, SGR and CF than non-transgenic fish, and bGH injection significantly increased weight and SGR in non-transgenic but not transgenic fish. Plasma salmon GH concentrations decreased with bGH treatment in non-transgenic but not in transgenic fish where levels were similar to controls. Higher GH mRNA levels were detected in transgenic muscle and liver but no differences were observed in GH receptor (GHR) mRNA levels. In non-transgenic pituitary, GH and GHR mRNA levels per mg pituitary decreased with bGH dose to levels seen in transgenic salmon. Plasma IGF-I was elevated with bGH dose only in non-transgenic fish, while transgenic fish maintained an elevated level of IGF-I with or without bGH treatment. A similar trend was seen for liver IGF-I mRNA levels. Thus, bGH treatment increased fish growth and influenced feedback on endocrine parameters in non-transgenic but not in transgenic fish. A lack of further growth stimulation of GH transgenic fish suggests that these fish are experiencing maximal growth stimulation via GH pathways.

  12. Cytokine-Enhanced Vaccine and Interferon-β plus Suicide Gene Therapy as Surgery Adjuvant Treatments for Spontaneous Canine Melanoma

    PubMed Central

    Fondello, Chiara; Gil-Cardeza, María L.; Rossi, Úrsula A.; Villaverde, Marcela S.; Riveros, María D.; Glikin, Gerardo C.

    2015-01-01

    Abstract We present here a nonviral immunogene therapy trial for canine malignant melanoma, an aggressive disease displaying significant clinical and histopathological overlapping with human melanoma. As a surgery adjuvant approach, it comprised the co-injection of lipoplexes bearing herpes simplex virus thymidine kinase and canine interferon-β genes at the time of surgery, combined with the periodic administration of a subcutaneous genetic vaccine composed of tumor extracts and lipoplexes carrying the genes of human interleukin-2 and human granulocyte-macrophage colony-stimulating factor. Following complete surgery (CS), the combined treatment (CT) significantly raised the portion of local disease-free canine patients from 11% to 83% and distant metastases-free (M0) from 44% to 89%, as compared with surgery-only-treated controls (ST). Even after partial surgery (PS), CT better controlled the systemic disease (M0: 82%) than ST (M0: 48%). Moreover, compared with ST, CT caused a significant 7-fold (CS) and 4-fold (PS) rise of overall survival, and >17-fold (CS) and >13-fold (PS) rise of metastasis-free survival. The dramatic increase of PS metastasis-free survival (>1321 days) and CS recurrence- and metastasis-free survival (both >2251 days) demonstrated that CT was shifting a rapidly lethal disease into a chronic one. In conclusion, this surgery adjuvant CT was able of significantly delaying or preventing postsurgical recurrence and distant metastasis, increasing disease-free and overall survival, and maintaining the quality of life. The high number of canine patients involved in CT (301) and the extensive follow-up (>6 years) with minimal or absent toxicity warrant the long-term safety and efficacy of this treatment. This successful clinical outcome justifies attempting a similar scheme for human melanoma. PMID:25762364

  13. Cytokine-Enhanced Vaccine and Interferon-β plus Suicide Gene Therapy as Surgery Adjuvant Treatments for Spontaneous Canine Melanoma.

    PubMed

    Finocchiaro, Liliana M E; Fondello, Chiara; Gil-Cardeza, María L; Rossi, Úrsula A; Villaverde, Marcela S; Riveros, María D; Glikin, Gerardo C

    2015-06-01

    We present here a nonviral immunogene therapy trial for canine malignant melanoma, an aggressive disease displaying significant clinical and histopathological overlapping with human melanoma. As a surgery adjuvant approach, it comprised the co-injection of lipoplexes bearing herpes simplex virus thymidine kinase and canine interferon-β genes at the time of surgery, combined with the periodic administration of a subcutaneous genetic vaccine composed of tumor extracts and lipoplexes carrying the genes of human interleukin-2 and human granulocyte-macrophage colony-stimulating factor. Following complete surgery (CS), the combined treatment (CT) significantly raised the portion of local disease-free canine patients from 11% to 83% and distant metastases-free (M0) from 44% to 89%, as compared with surgery-only-treated controls (ST). Even after partial surgery (PS), CT better controlled the systemic disease (M0: 82%) than ST (M0: 48%). Moreover, compared with ST, CT caused a significant 7-fold (CS) and 4-fold (PS) rise of overall survival, and >17-fold (CS) and >13-fold (PS) rise of metastasis-free survival. The dramatic increase of PS metastasis-free survival (>1321 days) and CS recurrence- and metastasis-free survival (both >2251 days) demonstrated that CT was shifting a rapidly lethal disease into a chronic one. In conclusion, this surgery adjuvant CT was able of significantly delaying or preventing postsurgical recurrence and distant metastasis, increasing disease-free and overall survival, and maintaining the quality of life. The high number of canine patients involved in CT (301) and the extensive follow-up (>6 years) with minimal or absent toxicity warrant the long-term safety and efficacy of this treatment. This successful clinical outcome justifies attempting a similar scheme for human melanoma.

  14. Loco-regional control after neo-adjuvant chemotherapy and conservative treatment for locally advanced breast cancer patients.

    PubMed

    Levy, Antonin; Borget, Isabelle; Bahri, Manel; Arnedos, Monica; Rivin, Eleonor; Vielh, Philippe; Balleyguier, Corinne; Rimareix, Françoise; Bourgier, Céline

    2014-01-01

    Breast-conserving treatment (BCT) has been validated for breast cancer patients receiving adjuvant chemotherapy. Our objective was to evaluate the difference in loco-regional recurrence (LRR) rates between BCT and mastectomy in patients receiving radiation therapy after neo-adjuvant chemotherapy (NCT). A retrospective data base was used to identify all patients with breast cancer undergoing NCT from 2002 to 2007. Patients with initial metastatic disease were excluded from this analysis. LRR was compared between those undergoing BCT and mastectomy. Individual variables associated with LRR were evaluated. Two hundred eighty-four patients were included, 111 (39%) underwent BCT and 173 (61%) mastectomy. Almost all patients (99%) in both groups received postoperative radiation. Pathologic complete response was seen in 37 patients, of which 28 underwent BCT (p < 0.001). Patients receiving mastectomy had more invasive lobular carcinoma (p = 0.007) and a higher American Joint Committee on Cancer (AJCC) stage (p < 0.001) at diagnosis than those with BCT. At a median follow-up of 6.3 years, the loco-regional control rate was 91% (95% CI: 86-94%). The 10-year LRR rate was similar in the BCT group (9.2% [95% CI: 4.9-16.7%]) and in the mastectomy group (10.7% [95% CI: 5.9-15.2%]; p = 0.8). Ten-year overall survival (OS) rates (63% [95% CI: 46-79%] in the BCT group; 60% [95% CI: 47-73%] in the mastectomy group, p = 0.8) were not statistically different between the two patient populations. Multivariate analysis showed that AJCC stage ≥ III (HR: 2.6; 95% CI: 1.2-5.8; p = 0.02), negative PR (HR: 6; 95% CI: 1.2-30.6, p = 0.03), and number of positive lymph nodes ≥3 (HR: 2.5; 95% CI: 1.1-5.9; p = 0.03) were independent predictors of LRR. Ten-year OS was similar in the BCT and in the mastectomy group (p = 0.1). The rate of LRR was low and did not significantly differ between the BCT and the mastectomy group after NCT. Randomized trials assessing whether mastectomy can be safely

  15. Endocrine Diseases

    MedlinePlus

    ... History Research Resources Research at NIDDK Meetings & Events Technology Advancement & Transfer Health Information Diabetes Digestive Diseases Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition ...

  16. Endocrine therapy of breast cancer

    SciTech Connect

    Cavalli, F.

    1986-01-01

    This book results from a meeting of the ESO (European School of Oncology) Task Force on endocrine aspects of breast cancer. The contributions stem from some of the most outstanding researchers in Europe and highlight mainly methodological issues and new avenues for future research. The chapters on basic research deal primarily with experimental strategies for studying the relationship between steroid hormones, growth factors, and oncongenes. The clinically oriented chapters treat the methodology of clinical trials. Provocative questions are raised, such as: What are the pitfalls in endocrine trials. What does statistical proof mean. How can we consider a quality of life endpoint in the adjuvant setting. Two special reports deal with the controversial issues of chemoprevention in high-risk normal women and the optimization of the hormonal contribution to the adjuvant therapy of breast cancer. Topics considered included oncogenic transformations, radiotherapy, steroid hormones, cell proliferation, tamoxifen, and preventive medicine.

  17. The association between population-based treatment guidelines and adjuvant therapy for node-negative breast cancer. British Columbia/Ontario Working Group.

    PubMed Central

    Sawka, C.; Olivotto, I.; Coldman, A.; Goel, V.; Holowaty, E.; Hislop, T. G.

    1997-01-01

    This study evaluated the impact of province-wide treatment guidelines on consistency of adjuvant therapy for node-negative breast cancer. A retrospective population-based cohort study was conducted in the Canadian provinces of British Columbia, which has province-wide guidelines, and Ontario, which does not. All eligible 1991 incident cases of node-negative breast cancer in British Columbia (n = 942) and a similar number of randomly selected 1991 incident cases in Ontario (n = 938) were reviewed. Consistency of adjuvant therapy received was evaluated by stratifying cases into discrete diagnostic groups using several grouping systems, and by then comparing the distribution of treatments received within each diagnostic group in the two provinces. Recursive partitioning was also performed. We observed that patterns of pathology reporting were consistent with awareness of the factors used in the British Columbia guidelines to define indications for adjuvant therapy. Consistency of care was greater in British Columbia than in Ontario by all diagnostic grouping systems and by recursive partitioning (P < 0.001), and the observed patterns in British Columbia corresponded to the British Columbia guidelines. We conclude that population-based treatment guidelines can play a role in promoting consistent patterns of adjuvant therapy for women with node-negative breast cancer. PMID:9166950

  18. Treatment challenges for community oncologists treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

    PubMed Central

    Gradishar, William J

    2016-01-01

    Community-based oncologists are faced with challenges and opportunities when delivering quality patient care, including high patient volumes and diminished resources; however, there may be the potential to deliver increased patient education and subsequently improve outcomes. This review discusses the treatment of postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2- negative advanced breast cancer in order to illustrate considerations in the provision of pertinent quality education in the treatment of these patients and the management of therapy-related adverse events. An overview of endocrine-resistant breast cancer and subsequent treatment challenges is also provided. Approved treatment options for endocrine-resistant breast cancer include hormonal therapies and mammalian target of rapamycin inhibitors. Compounds under clinical investigation are also discussed. PMID:27468248

  19. Anthracycline and concurrent radiotherapy as adjuvant treatment of operable breast cancer: a retrospective cohort study in a single institution

    PubMed Central

    2010-01-01

    Background Concurrent chemoradiotherapy (CCRT) after breast surgery was investigated by few authors and remains controversial, because of concerns of toxicity with taxanes/anthracyclines and radiation. This treatment is not standard and is more commonly used for locally advanced breast cancer. The aim of our study was to evaluate the efficacy and safety of the concomitant use of anthracycline with radiotherapy (RT). Findings Four hundred women having operable breast cancer, treated by adjuvant chemotherapy (CT) and RT in concomitant way between January 2001 and December 2003, were included in this retrospective cohort study. The study compares 2 adjuvant treatments using CCRT, the first with anthracycline (group A) and the second with CMF (group B). The CT treatment was repeated every 21 days for 6 courses and the total delivered dose of RT was 50 Gy, divided as 2 Gy daily fractions. Locoregional recurrence free (LRFS), event free (EFS), and overall survivals (OS) were estimated by the Kaplan-Meier method. The log-rank test was used to compare survival events. Multivariate Cox-regression was used to evaluate the relationship between patient characteristics, treatment and survival. In the 2 groups (A+B) (n = 400; 249 in group A and 151 in group B), the median follow-up period was 74.5 months. At 5 years, the isolated LRFS was significantly higher in group A compared to group B (98.7% vs 95.3%; hazard ratio [HR] = 0.258; 95% CI, 0.067 to 0.997; log-rank P = .034). In addition, the use of anthracycline regimens was associated with a higher rate of 5 years EFS (80.4% vs 75.1%; HR = 0.665; 95% CI, 0.455 to 1.016; log-rank P = .057). The 5 years OS was 83.2% and 79.2% in the anthracycline and CMF groups, respectively (HR = 0.708; 95% CI, 0.455 to 1.128; log-rank P = .143). Multivariate analysis confirmed the positive effect of anthracycline regimens on LRFS (HR = 0.347; 95% CI, 0.114 to 1.053; log-rank P = .062), EFS (HR = 0.539; 95% CI, 0.344 to 0.846; P = 0.012), and

  20. Combined Paracrine and Endocrine AAV9 mediated Expression of Hepatocyte Growth Factor for the Treatment of Renal Fibrosis

    PubMed Central

    Schievenbusch, Stephanie; Strack, Ingo; Scheffler, Melanie; Nischt, Roswitha; Coutelle, Oliver; Hösel, Marianna; Hallek, Michael; Fries, Jochen WU; Dienes, Hans-Peter; Odenthal, Margarete; Büning, Hildegard

    2010-01-01

    In chronic renal disease, tubulointerstitial fibrosis is a leading cause of renal failure. Here, we made use of one of the most promising gene therapy vector platforms, the adeno-associated viral (AAV) vector system, and the COL4A3-deficient mice, a genetic mouse model of renal tubulointerstitial fibrosis, to develop a novel bidirectional treatment strategy to prevent renal fibrosis. By comparing different AAV serotypes in reporter studies, we identified AAV9 as the most suitable delivery vector to simultaneously target liver parenchyma for endocrine and renal tubular epithelium for paracrine therapeutic expression of the antifibrogenic cytokine human hepatocyte growth factor (hHGF). We used transcriptional targeting to drive hHGF expression from the newly developed CMV-enhancer-Ksp-cadherin-promoter (CMV-Ksp) in renal and hepatic tissue following tail vein injection of rAAV9-CMV-Ksp-hHGF into COL4A3-deficient mice. The therapeutic efficiency of our approach was demonstrated by a remarkable attenuation of tubulointerstitial fibrosis and repression of fibrotic markers such as collagen1α1 (Col1A1), platelet-derived growth factor receptor-β (PDGFR-β), and α-smooth muscle actin (SMA). Taken together, our results show the great potential of rAAV9 as an intravenously applicable vector for the combined paracrine and endocrine expression of antifibrogenic factors in the treatment of renal failure caused by tubulointerstitial fibrosis. PMID:20424598

  1. Endocrine Disruptors

    MedlinePlus

    ... and wildlife. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and plasticizers such as bisphenol A. Endocrine disruptors ...

  2. In vitro characterization of the effectiveness of enhanced sewage treatment processes to eliminate endocrine activity of hospital effluents.

    PubMed

    Maletz, Sibylle; Floehr, Tilman; Beier, Silvio; Klümper, Claudia; Brouwer, Abraham; Behnisch, Peter; Higley, Eric; Giesy, John P; Hecker, Markus; Gebhardt, Wilhelm; Linnemann, Volker; Pinnekamp, Johannes; Hollert, Henner

    2013-03-15

    Occurrence of pharmaceuticals in aquatic ecosystems is related to sewage effluents. Due to the possible adverse effects on wildlife and humans, degradation and removal of pharmaceuticals and their metabolites during wastewater treatment is an increasingly important task. The present study was part of a proof of concept study at a medium sized country hospital in western Germany that investigated efficiency of advanced treatment processes to remove toxic potencies from sewage. Specifically, the efficiency of treatment processes such as a membrane bioreactor (MBR) and ozonation to remove endocrine disruptive potentials was assessed. Estrogenic effects were characterized by use of two receptor-mediated in vitro transactivation assays, the Lyticase Yeast Estrogen Screen (LYES) and the Estrogen Receptor mediated Chemical Activated LUciferase gene eXpression (ER CALUX(®)). In addition, the H295R Steroidogenesis Assay (H295R) was utilized to detect potential disruption of steroidogenesis. Raw sewage contained measurable estrogen receptor (ER)-mediated potency as determined by use of the LYES (28.9 ± 8.6 ng/L, 0.33× concentration), which was reduced after treatment by MBR (2.3 ± 0.3 ng/L) and ozone (1.2 ± 0.4 ng/L). Results were confirmed by use of ER CALUX(®) which measured concentrations of estrogen equivalents (EEQs) of 0.2 ± 0.11 ng/L (MBR) and 0.01 ± 0.02 ng/L (ozonation). In contrast, treatment with ozone resulted in greater production of estradiol and aromatase activity at 3× and greater concentrations in H295R cells. It is hypothesized that this is partly due to formation of active oxidized products during ozonation. Substance-specific analyses demonstrated efficient removal of most of the measured compounds by ozonation. A comparison of the ER-mediated responses measured by use of the LYES and ER CALUX(®) with those from the chemical analysis using a mass-balance approach revealed estrone (E1) to be the main compound that caused the estrogenic effects

  3. Vaccines, adjuvants and autoimmunity.

    PubMed

    Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

    2015-10-01

    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future.

  4. Endocrine System (For Teens)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Endocrine System KidsHealth > For Teens > Endocrine System A A A ... is called the endocrine system . What Is the Endocrine System? Although we rarely think about the endocrine system, ...

  5. Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma

    SciTech Connect

    Shamberger, R.C.; Sherins, R.J.; Ziegler, J.L.; Glatstein, E.; Rosenberg, S.A.

    1981-12-01

    Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD (follicle-stimulating hormone (FSH), 10 +/- 5 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml) and 17 beta-estradiol (E2) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developed persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 108 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and E2 (19 +/- 8 pg/ml). Two additional women (ages 21 and 39 yr) who received radiation (7,000 rad) to the pelvis plus chemotherapy developed prompt cessation of menses and became functional castrates (FSH, 77 and 80 mlU/ml; LH, 40 and 58 mlU/ml; E2, 10 and 19 pg/ml). However, this result would be expected from the radiation dose alone. The data demonstrated that ovarian dysfunction may follow the use of doxorubicin, cyclophosphamide, and high doses of methotrexate and that the injury is age related.

  6. Prognostic and Predictive Biomarkers of Endocrine Responsiveness for Estrogen Receptor Positive Breast Cancer.

    PubMed

    Ma, Cynthia X; Bose, Ron; Ellis, Matthew J

    2016-01-01

    The estrogen-dependent nature of breast cancer is the fundamental basis for endocrine therapy. The presence of estrogen receptor (ER), the therapeutic target of endocrine therapy, is a prerequisite for this therapeutic approach. However, estrogen-independent growth often exists de novo at diagnosis or develops during the course of endocrine therapy. Therefore ER alone is insufficient in predicting endocrine therapy efficacy. Several RNA-based multigene assays are now available in clinical practice to assess distant recurrence risk, with majority of these assays evaluated in patients treated with 5 years of adjuvant endocrine therapy. While MammaPrint and Oncotype Dx are most predictive of recurrence risk within the first 5 years of diagnosis, Prosigna, Breast Cancer Index (BCI), and EndoPredict Clin have also demonstrated utility in predicting late recurrence. In addition, PAM50, or Prosigna, provides further biological insights by classifying breast cancers into intrinsic molecular subtypes. Additional strategies are under investigation in prospective clinical trials to differentiate endocrine sensitive and resistant tumors and include on-treatment Ki-67 and Preoperative Endocrine Prognostic Index (PEPI) score in the setting of neoadjuvant endocrine therapy. These biomarkers have become important tools in clinical practice for the identification of low risk patients for whom chemotherapy could be avoided. However, there is much work ahead toward the development of a molecular classification that informs the biology and novel therapeutic targets in high-risk disease as chemotherapy has only modest benefit in this population. The recognition of somatic mutations and their relationship to endocrine therapy responsiveness opens important opportunities toward this goal.

  7. Endocrine disorders and the neurologic manifestations

    PubMed Central

    2014-01-01

    The nervous system and the endocrine system are closely interrelated and both involved intimately in maintaining homeostasis. Endocrine dysfunctions may lead to various neurologic manifestations such as headache, myopathy, and acute encephalopathy including coma. It is important to recognize the neurologic signs and symptoms caused by the endocrine disorders while managing endocrine disorders. This article provides an overview of the neurologic manifestations found in various endocrine disorders that affect pediatric patients. It is valuable to think about 'endocrine disorder' as a cause of the neurologic manifestations. Early diagnosis and treatment of hormonal imbalance can rapidly relieve the neurologic symptoms. Better understanding of the interaction between the endocrine system and the nervous system, combined with the knowledge about the pathophysiology of the neurologic manifestations presented in the endocrine disorders might allow earlier diagnosis and better treatment of the endocrine disorders. PMID:25654063

  8. Recognizing menopause in women with amenorrhea induced by cytotoxic chemotherapy for endocrine-responsive early breast cancer.

    PubMed

    Torino, Francesco; Barnabei, Agnese; De Vecchis, Liana; Appetecchia, Marialuisa; Strigari, Lidia; Corsello, Salvatore M

    2012-04-01

    Cytotoxic anticancer treatment may induce amenorrhea or menopause to a variable extent. These side effects may not only impair or impede fertility but also cause sexual dysfunction, bone loss, and menopausal symptoms, with a strikingly negative effect on quality of life in many women. Aromatase inhibitors (AIs) are a recommended adjuvant endocrine treatment option in postmenopausal patients affected by early breast cancer (EBC) but are contraindicated in premenopausal women and in those with residual ovarian function. Women over 40 years of age with chemotherapy-induced amenorrhea (CIA) and routine hormonal levels consistent with menopause may receive an AI as adjuvant endocrine treatment. For these women, the tools available to identify menopause do not appear to be completely reliable. This review focused on the pathophysiology of ovarian toxicity induced by cytotoxic agents and on potentially useful methods to diagnose chemotherapy-induced menopause in patients treated with adjuvant chemotherapy for endocrine-responsive EBC. Moreover, practical approaches are proposed to distinguish true menopausal women, who would benefit from AIs, from those with transient or persistent CIA.

  9. Medical comorbidity in bipolar disorder: relationship between illnesses of the endocrine/metabolic system and treatment outcome

    PubMed Central

    Kemp, David E; Gao, Keming; Chan, Philip; Ganocy, Stephen J; Findling, Robert L; Calabrese, Joseph R

    2010-01-01

    Objective The present study examined the relationship between medical burden in bipolar disorder and several indicators of illness severity and outcome. It was hypothesized that illnesses of the endocrine/metabolic system would be associated with greater psychiatric symptom burden and would impact the response to treatment with lithium and valproate. Method Data were analyzed from two studies evaluating lithium and valproate for rapid-cycling presentations of bipolar I and II disorder. General medical comorbidity was assessed by the Cumulative Illness Rating Scale (CIRS). Descriptive statistics and logistic regression analyses were conducted to explore the relationships between medical burden, body mass index (BMI), substance use disorder status, and depressive symptom severity. Results Of 225 patients enrolled, 41.8% had a recent substance use disorder, 50.7% were male, and 69.8% had bipolar I disorder. The mean age of the sample was 36.8 (SD = 10.8) years old. The mean number of comorbid medical disorders per patient was 2.5 (SD = 2.5), and the mean CIRS total score was 4.3 (SD = 3.1). A significant positive correlation was observed between baseline depression severity and the number of organ systems affected by medical illness (p = 0.04). Illnesses of the endocrine/metabolic system were inversely correlated with remission from depressive symptoms (p = 0.02), and obesity was specifically associated with poorer treatment outcome. For every 1-unit increase in BMI, the likelihood of response decreased by 7.5% [odds ratio (OR) = 0.93, 95% confidence interval (CI): 0.87–0.99; p = 0.02] and the likelihood of remission decreased by 7.3% (OR = 0.93, 95% CI: 0.87–0.99; p = 0.03). The effect of comorbid substance use on the likelihood of response differed significantly according to baseline BMI. The presence of a comorbid substance use disorder resulted in a lower odds of response, but only among patients with a BMI ≥ 23 (p = 0.02). Conclusion Among patients with

  10. An assessment of prognostic factors, adjuvant treatment and outcomes of stage IA polyp-limited versus endometrium-limited type II endometrial carcinoma

    PubMed Central

    Liang, Lusha W.; Perez, Alexendar R.; Cangemi, Nicholas A.; Zhou, Qin; Iasonos, Alexia; Abu-Rustum, Nadeem; Alektiar, Kaled M.; Makker, Vicky

    2015-01-01

    Objective To determine clinical outcomes in patients with stage IA polyp-limited versus endometrium-limited high-grade (type II) endometrial carcinoma (EC). Methods We identified all cases of stage IA polyp-limited or endometrium-limited high-grade EC (FIGO Grade 3 endometrioid, Serous, Clear Cell, or Mixed) who underwent simple hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, omental biopsy, and pelvic and paraaortic lymph node dissection and received adjuvant treatment at our institution from 10/1995–11/2012. Progression-free survival (PFS) and overall survival (OS) by histology, adjuvant therapy, and polyp-limited vs endometrium-limited disease status were determined using log-rank test. We analyzed three treatment groups: patients who received chemotherapy with or without Radiation Therapy (RT) (intravaginal or pelvic); patients who received RT (intravaginal RT or pelvic RT) alone; and patients who received no adjuvant treatment. Results In all, 85 women underwent hysterectomy/salpingo-oophorectomy; all were surgically staged with lymph node assessment and had stage IA EC with no lymphovascular or myometrial invasion. Median follow-up for survivors was 46.5 months (range, 1.98–188.8 months). Forty-nine patients (57.6%) had polyp-limited disease and 36 (42.4%) had endometrium-limited disease. There were no significant differences in clinicopathologic characteristics between patients within the three treatment groups with regards to age at diagnosis, mean BMI, ECOG performance status, polyp-limited, endometrium-limited disease, diabetes, or race. The 3-year PFS rate was 94.9% and the 3-year OS rate was 98.8%. Univariate PFS and OS analysis revealed that age was a relevant prognostic factor [(PFS:HR (95%CI):1.13(1.02–1.25); P=0.022 and OS HR (95%CI):1.19(1.02–1.38); P=0.03]. Adjuvant treatment did not impact outcomes. Conclusions Clinical outcomes of surgical stage IA, type II polyp- or endometrium-limited high-grade epithelial EC are

  11. Early versus delayed endocrine therapy for prostate cancer.

    PubMed

    Schröder, Fritz H

    2007-03-01

    Endocrine treatment (ET) has in the past been shown to be beneficial in delaying clinical progression in all stages of prostate cancer, leading to an improvement of progression free survival in virtually all trials ever conducted. The first observations on this issue date back to the studies of the Veterans Administration Cooperative Urological Research Group in the 1960s. The period of time during which ET and the resulting side effects can be avoided is strongly dependent on the clinical stage of the disease. This treatment period is long in men who have minimal disease, such as a rising prostate-specific antigen after potentially curative management; however, it is considerably shorter in men who initially present with metastatic disease. In these situations, the potential benefit in quality of life, and avoidance of adverse events must be matched against the benefit in terms of gaining progression free time for the individual patient. This difficult task is supported by information supplied in this review. Locally advanced and regional (lymph node positive; stage T3N0-1M0Gx) disease is the domain of adjuvant ET. In this field, important progress has recently been made due to trials, which combine aggressive treatment of the primary tumor with adjuvant ET initiated at the same time. Therefore, in locally advanced and regional disease, radiotherapy or surgery combined with adjuvant ET must be considered state-of-the-art.

  12. Clinical evaluation of Rasayana compound as an adjuvant in the management of tuberculosis with anti-Koch's treatment.

    PubMed

    Vyas, Purvi; Chandola, H M; Ghanchi, Firoz; Ranthem, Shivprakash

    2012-01-01

    Tuberculosis (TB) continues to intimidate the human race since time immemorial not only due to its effects as a medical malady, but also by its impact as a social and economic tragedy. At the dawn of the new millennium, we are still mute witnesses to the silent yet efficient march of this sagacious disease, its myriad manifestations and above all its unequalled, vicious power. Through the millennia, TB never ever disappeared from the developing world. In 1991, the World Health Assembly (WHA) resolution recognized TB as a major global public health problem. The DOTS strategy was launched in 1994, and became the global recommended strategy for TB control since then. The present study deals with clinical evaluation of Rasayana drugs considering of Amalaki (Emblica officinalis Gaertn.), Guduchi (Tinospora cordifolia willd.), Ashwagandha (Withania somnifera L.) Dunal, Yastimadhu (Glycyrrhiza glabra Linn.), Pippali (Piper longum Linn.), Sariva (Hemidesmus indicus R.Br.), Kustha (Saussurea lappa Falc.), Haridra (Curcuma longa Linn.) and Kulinjan (Alpinia galangal Linn.) as an adjuvant therapy with anti-Koch's treatment. The results obtained revealed that Rasayana compound was found to decrease cough (83%), fever (93%), dyspnea (71.3%), hemoptysis (87%) and increase body weight (7.7%) with statistically highly significant (P<0.001).

  13. Endocrine Diseases

    MedlinePlus

    ... low, you may have a hormone disorder. Hormone diseases also occur if your body does not respond ... In the United States, the most common endocrine disease is diabetes. There are many others. They are ...

  14. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review

    PubMed Central

    Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc

    2016-01-01

    Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy. PMID:27489751

  15. Riboflavin and ultraviolet-A as adjuvant treatment against Acanthamoeba cysts

    PubMed Central

    Lamy, Ricardo; Chan, Elliot; Good, Samuel D; Cevallos, Vicky; Porco, Travis C; Stewart, Jay M

    2015-01-01

    Background Experimental studies have shown that the standard dose of R or R+UVA as solo treatment are not able to exterminate Acanthamoeba cysts or even trophozoites. The purpose of this study is to determine whether the application of R+UVA can enhance the cysticidal effects of cationic antiseptic agents in vitro. Methods The log of either polyhexamethylene biguanide (PHMB) or chlorhexidine minimal cysticidal concentration (MCC) in solutions containing riboflavin (concentrations 0.1 %; 0.05% and 0.025 %) plus either Acanthamoeba castellanii cysts or Acanthamoeba polyphaga cysts was determined and compared in groups treated with UVA 30 mW/cm2 for 30 min and in control groups (with no exposure to UVA). A permutation test was used to determine the P-value associated with treatment. Results Regardless of the riboflavin concentration and UVA treatment condition, no trophozoites were seen in plates where the cysts were previously exposed to cationic antiseptic agents concentrations ≥ 200 µg/mL for Acanthamoeba castellanii samples and ≥ 100 µg/mL for Acanthamoeba polyphaga samples. There was no statistical evidence that R+UVA treatment was associated with MCC (P = 0.82). Conclusion R+UVA in doses up to 10 times higher than recommended for corneal crosslinking does not enhance the cysticidal effect of either polyhexamethylene biguanide or chlorhexidine in vitro. PMID:26355273

  16. Embolization as an Alternative Treatment of Insulinoma in a Patient with Multiple Endocrine Neoplasia Type 1 Syndrome

    SciTech Connect

    Peppa, Melpomeni; Brountzos, Elias; Economopoulos, Nicolaos; Boutati, Eleni; Pikounis, Vasilios; Patapis, Paul; Economopoulos, Theofanis; Raptis, Sotirios A.; Hadjidakis, Dimitrios

    2009-07-15

    Insulinoma is a rare neuroendocrine tumor, most commonly originating from the pancreas, which is either sporadic or familial as a component of multiple endocrine neoplasia type 1 syndrome (MEN1). It is characterized by increased insulin secretion leading to hypoglycemia. Surgical removal is considered the treatment of choice, with limited side effects and relatively low morbidity and mortality, both being improved by the laparoscopic procedure. We present the case of a 30-year-old patient with MEN1 and recurrent insulinoma with severe hypoglycemic episodes who could not be surgically treated due to the adherence of the tumor to large blood vessels and to prior multiple surgical operations. He was treated by repeated embolization using spherical polyvinyl alcohol particles, resulting in shrinkage of the tumor, improvement of the frequency and severity of the hypoglycemic episodes, and better quality of life.

  17. Occurrence and fate of endocrine disrupting compounds in wastewater treatment plants in Israel and the Palestinian West Bank.

    PubMed

    Dotan, Pniela; Godinger, Tal; Odeh, Wad; Groisman, Ludmila; Al-Khateeb, Nader; Rabbo, Alfred Abed; Tal, Alon; Arnon, Shai

    2016-07-01

    Israel and its Palestinian neighbors constitute a unique venue for evaluating the treatment efficiency and potential environmental risks of endocrine disrupting compounds (EDCs) in wastewater treatment plants (WWTPs), because of their physical proximity yet contrasting societal dynamics. Israel primarily relies on advanced tertiary sewage treatment and recycles over 85% of its treated wastewater, while in the Palestinian Authority (PA), there is only secondary treatment levels at WWTPs and reuse is minimal (<1%). To evaluate the extent of EDC occurrence and treatment efficiency, we conducted four sampling campaigns over two consecutive years, and measured the concentrations of selected EDCs in raw wastewater (WW), treated WW and sludge in six WWTPs in Israel, as well as in two Palestinian plants. Low concentrations of bisphenol A, octylphenol and triclosan measured in the raw WW in the Palestinian WWTPs reflected the relatively modest industrial activity and consumption habits as compared to the westernized consumer patterns in Israel. On the other hand, hormone concentrations in raw WW were higher in the Palestinian WWTPs than those in the Israeli WWTPs, presumably because of a dilution effect associated with a higher water per capita consumption among Israelis. Despite these differences in raw WW concentrations, the removal efficiency in all advanced WWTPs was relatively high when compared to averages reported internationally.

  18. Treatment with CRH-1 antagonist antalarmin reduces behavioral and endocrine responses to social stressors in marmosets (Callithrix kuhlii).

    PubMed

    French, Jeffrey A; Fite, Jeffrey E; Jensen, Heather; Oparowski, Katie; Rukstalis, Michael R; Fix, Holly; Jones, Brenda; Maxwell, Heather; Pacer, Molly; Power, Michael L; Schulkin, Jay

    2007-08-01

    Corticotropin-releasing hormone (CRH) has multiple roles in coordinating the behavioral and endocrine responses to a host of environmental challenges, including social stressors. In the present study we evaluated the role of CRH in mediating responses to a moderate social stressor in Wied's black tufted-eared marmosets (Callithrix kuhlii). Male and female marmosets (n=14) were administered antalarmin (a selective CRH-1 receptor antagonist; 50 microg/kg, p.o.) or vehicle in a blind, counterbalanced, crossover design. One hr after treatment, marmosets were separated from long-term pairmates and then housed alone in a novel enclosure for 7 hr. Behavior was recorded during separation and upon reunion with the partner, and urine samples for cortisol assay collected before, during, and after the intervention. Separation from partners elevated urinary cortisol concentrations over baseline for both conditions, but antalarmin treatment reduced the magnitude of the elevation. Antalarmin also lowered rates of behavioral patterns associated with arousal (alarm and "e-e" vocalizations, object manipulate/chew), but had no effect on contact calls, locomotory activity or alertness. Although most patterns of social behavior upon reunion with the partner were not affected by antalarmin, antalarmin-treated marmosets displayed more sexual behavior (mounts and copulations) upon reunion. These data indicate that antagonism of the CRH-1 receptor acts to reduce the magnitude of both endocrine and behavioral responses to a moderate social stressor without causing any overall reduction in alertness or general activity. This supports the hypothesis that CRH, acting through its type 1 receptor, is involved in coordinating the responses to anxiety-producing events. These results further suggest that the marmoset is a useful model for exploration of the role of CRH in mediating the behavioral and neuroendocrine responses to psychosocial stressors, particularly in the context of heterosexual

  19. A retrospective study on IVF outcome in euthyroid patients with anti-thyroid antibodies: effects of levothyroxine, acetyl-salicylic acid and prednisolone adjuvant treatments

    PubMed Central

    2009-01-01

    Background Anti-thyroid antibodies (ATA), even if not associated with thyroid dysfunction, are suspected to cause poorer outcome of in vitro fertilization (IVF). Methods We retrospectively analyzed: (a) the prevalence of ATA in euthyroid infertile women, (b) IVF outcome in euthyroid, ATA+ patients, and (c) the effect of adjuvant treatments (levothyroxine alone or associated with acetylsalicylic acid and prednisolone) on IVF results in ATA+ patients. One hundred twenty-nine euthyroid, ATA+ women undergoing IVF were compared with 200 matched, ATA-controls. During IVF cycle, 38 ATA+ patients did not take any adjuvant treatment, 55 received levothyroxin (LT), and 38 received LT +acetylsalicylic acid (ASA)+prednisolone (P). Results The prevalence of ATA among euthyroid, infertile patients was 10.5%, similar to the one reported in euthyroid women between 18 and 45 years. ATA+ patients who did not receive any adjuvant treatment showed significantly poorer ovarian responsiveness to stimulation and IVF results than controls. ATA+ patients receiving LT responded better to ovarian stimulation, but had IVF results as poor as untreated ATA+ women. Patients receiving LT+ASA+P had significantly higher pregnancy and implantation rates than untreated ATA+ patients (PR/ET 25.6% and IR 17.7% vs. PR/ET 7.5% and IR 4.7%, respectively), and overall IVF results comparable to patients without ATA (PR/ET 32.8% and IR 19%). Conclusion These observations suggest that euthyroid ATA+ patients undergoing IVF could have better outcome if given LT+ASA+P as adjuvant treatment. This hypothesis must be verified in further randomized, prospective studies. PMID:19941670

  20. Effects of physical exercise during adjuvant breast cancer treatment on physical and psychosocial dimensions of cancer-related fatigue: A meta-analysis.

    PubMed

    van Vulpen, Jonna K; Peeters, Petra H M; Velthuis, Miranda J; van der Wall, Elsken; May, Anne M

    2016-03-01

    Cancer-related fatigue has a multidimensional nature and complaints typically increase during adjuvant treatment for breast cancer. Physical exercise might prevent or reduce cancer-related fatigue. So far, no meta-analysis has investigated the effects of physical exercise on different dimensions of fatigue. The aim of the present meta-analysis was to investigate the effects of physical exercise during adjuvant breast cancer treatment on physical and psychosocial dimensions of fatigue. We performed a systematic literature search in PubMed, Embase and the Cochrane Library in June 2015. Randomised controlled trials reporting the effects of physical exercise during adjuvant breast cancer treatment on different dimensions of fatigue were included. Pooled effects of 6 exercise programmes (including 784 patients) showed significant beneficial exercise effects on general fatigue (ES: -0.22, 95% CI -0.38; -0.05) and physical fatigue (ES: -0.35, 95% CI -0.49; -0.21). Effects on fatigue subscales 'reduced activity' (ES: -0.22, 95% CI -0.38; -0.05) and 'reduced motivation' (ES: -0.18, 95% CI -0.35; -0.01) were also in favour of physical exercise. No effects were found on cognitive and affective fatigue. Including only the supervised exercise programmes (n=4 studies), slightly larger pooled effect estimates were found on general fatigue (ES: -0.25, 95% CI -0.47; -0.04) and physical fatigue (-0.39, 95% CI -0.56; -0.23). In conclusion, physical exercise during adjuvant breast cancer treatment has beneficial effects on general fatigue, physical fatigue, 'reduced activity' and 'reduced motivation', but did not show effects on cognitive and affective fatigue. Largest effect sizes are found for physical fatigue, suggesting that this is the fatigue dimension most sensitive to physical exercise.

  1. Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma

    SciTech Connect

    Shamberger, R.C.; Sherins, R.J.; Ziegler, J.L.; Glatstein, E.; Rosenberg, S.A.

    1981-12-01

    Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD) (follicle-stimulating hormone (FSH), 10 +/- 15 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml) and 17 ..beta..-estradiol (E/sub 2/) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developd persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 109 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and E/sub 2/ (19 +/- 8 pg/ml). Two additional women (ages 21 and 39 yr) who received radiation (7000 rad) to the pelvis plus chemotherapy developed prompt cessation of menses and became functional castrates (FSH, 77 and 80mlU/ml; LH, 40 and 58 mlU/ml; E/sub 2/, 10 and 19 pg/ml). However, this result would be expected from the radiation dose alone. The data demonstrated that ovarian dysfunction may follow the use of doxorubicin, cyclophosphamide, and high doses of methotrexate and that the injury is age related.

  2. Multimodal MRI and cognitive function in patients with breast cancer prior to adjuvant treatment — The role of fatigue

    PubMed Central

    Menning, Sanne; de Ruiter, Michiel B.; Veltman, Dick J.; Koppelmans, V.; Kirschbaum, Clemens; Boogerd, Willem; Reneman, Liesbeth; Schagen, Sanne B.

    2015-01-01

    An increasing body of literature indicates that chemotherapy (ChT) for breast cancer (BC) is associated with adverse effects on the brain. Recent research suggests that cognitive and brain function in patients with BC may already be compromised before the start of chemotherapy. This is the first study combining neuropsychological testing, patient-reported outcomes, and multimodal magnetic resonance imaging (MRI) to examine pretreatment cognition and various aspects of brain function and structure in a large sample. Thirty-two patients with BC scheduled to receive ChT (pre-ChT+), 33 patients with BC not indicated to undergo ChT (pre-ChT−), and 38 no-cancer controls (NCs) were included. The examination consisted of a neuropsychological test battery, self-reported aspects of psychosocial functioning, and multimodal MRI. Patients with BC reported worse scores on several aspects of quality of life, such as higher levels of fatigue and stress. However, cortisol levels were not elevated in the patient groups compared to the control group. Overall cognitive performance was lower in the pre-ChT+ and the pre-ChT− groups compared to NC. Further, patients demonstrated prefrontal hyperactivation with increasing task difficulty on a planning task compared to NC, but not during a memory task. White matter integrity was lower in both patient groups. No differences in regional brain volume and brain metabolites were found. The cognitive and imaging data converged to show that symptoms of fatigue were associated with the observed abnormalities; the observed differences were no longer significant when fatigue was accounted for. This study suggests that cancer-related psychological or biological processes may adversely impact cognitive functioning and associated aspects of brain structure and function before the start of adjuvant treatment. Our findings stress the importance to further explore the processes underlying the expression of fatigue and to study whether it has a

  3. Adjuvant thiamine improved standard treatment in patients with major depressive disorder: results from a randomized, double-blind, and placebo-controlled clinical trial.

    PubMed

    Ghaleiha, Ali; Davari, Hassan; Jahangard, Leila; Haghighi, Mohammad; Ahmadpanah, Mohammad; Seifrabie, Mohammad Ali; Bajoghli, Hafez; Holsboer-Trachsler, Edith; Brand, Serge

    2016-12-01

    Given that antidepressants (ADs) work slowly, there is interest in means to accelerate their therapeutic effect and to reduce side effects. In this regard, thiamine (vitamin B1) is attracting growing interest. Thiamine is an essential nutrient, while thiamine deficiency leads to a broad variety of disorders including irritability and symptoms of depression. Here, we tested the hypothesis that adjuvant thiamine would reduce depression, compared to placebo. A total of 51 inpatients (mean age: 35.2 years; 53 % females) with MDD (Hamilton Depression Rating Scale score (HDRS) at baseline: >24) took part in the study. A standardized treatment with SSRI was introduced and kept at therapeutic levels throughout the study. Patients were randomly assigned either to the thiamine or the placebo condition. Experts rated (HDRS) symptoms of depression at baseline, and after 3, 6, and 12 weeks (end of the study). Between baseline and the end of the study, depression had reduced in both groups. Compared to placebo, adjuvant thiamine improved symptoms of depression after 6 week of treatment, and improvements remained fairly stable until the end of the study, though mean differences at week 12 were not statistically significant anymore. No adverse side effects were reported in either group. Results suggest that among younger patients with MDD adjuvant thiamine alleviated symptoms of depression faster compared to placebo. Importantly, improvements were observed within 6 weeks of initiation of treatment. Thus, thiamine might have the potential to counteract the time lag in the antidepressant effects of ADs.

  4. Use of an In Vitro, Nuclear Receptor Assay Panel to Characterize the Endocrine-Disrupting Activity Load of Wastewater Treatment Plant Effluent Extracts

    EPA Science Inventory

    Use of an In Vitro, Nuclear Receptor Assay Panel to Characterize the Endocrine-Disrupting Activity Load of Wastewater Treatment Plant Effluent Extracts Katie B. Paul 1.2, Ruth Marfil-Vega 1 Marc A. Mills3, Steve 0. Simmons2, Vickie S. Wilson4, Kevin M. Crofton2 10ak Rid...

  5. Clinical Outcome of Adjuvant Treatment of Endometrial Cancer Using Aperture-Based Intensity-Modulated Radiotherapy

    SciTech Connect

    Bouchard, Myriam; Nadeau, Sylvain M.Sc.; Gingras, Luc; Raymond, Paul-Emile; Beaulieu, Frederic; Beaulieu, Luc; Fortin, Andre; Germain, Isabelle

    2008-08-01

    Purpose: To assess disease control and acute and chronic toxicity with aperture-based intensity-modulated radiotherapy (AB-IMRT) for postoperative pelvic irradiation of endometrial cancer. Methods and Materials: Between January and July 2005, after hysterectomy for endometrial cancer, 15 patients received 45 Gy to the pelvis using AB-IMRT. The AB-IMRT plans were generated by an in-house treatment planning system (Ballista). The AB-IMRT plans were used for treatment and were dosimetrically compared with three other approaches: conventional four-field, enlarged four-field, and beamlet-based IMRT (BB-IMRT). Disease control and toxicity were prospectively recorded and compared with retrospective data from 30 patients treated with a conventional four-field technique. Results: At a median follow-up of 27 months (range, 23-30), no relapse was noted among the AB-IMRT group compared with five relapses in the control group (p = 0.1). The characteristics of each group were similar, except for the mean body mass index, timing of brachytherapy, and applicator type used. Patients treated with AB-IMRT experienced more frequent Grade 2 or greater gastrointestinal acute toxicity (87% vs. 53%, p 0.02). No statistically significant difference was noted between the two groups regarding the incidence or severity of chronic toxicities. AB-IMRT plans significantly improved target coverage (93% vs. 76% of planning target volume receiving 45 Gy for AB-IMRT vs. conventional four-field technique, respectively). The sparing of organs at risk was similar to that of BB-IMRT. Conclusion: The results of our study have shown that AB-IMRT provides excellent disease control with equivalent late toxicity compared with the conventional four-field technique. AB-IMRT provided treatment delivery and quality assurance advantages compared with BB-IMRT and could reduce the risk of second malignancy compared with BB-IMRT.

  6. Determination of a broad spectrum of pharmaceuticals and endocrine disruptors in biofilm from a waste water treatment plant-impacted river.

    PubMed

    Huerta, B; Rodriguez-Mozaz, S; Nannou, C; Nakis, L; Ruhí, A; Acuña, V; Sabater, S; Barcelo, D

    2016-01-01

    Wastewater treatment plants (WWTPs) are one of the main sources of pharmaceuticals and endocrine disrupting compounds in freshwater ecosystems, and several studies have reported bioaccumulation of these compounds in different organisms in those ecosystems. River biofilms are exceptional indicators of pollution, but very few studies have focused on the accumulation of these emerging contaminants. The objectives of this study were first to develop an efficient analytical methodology for the simultaneous analysis of 44 pharmaceuticals and 13 endocrine disrupting compounds in biofilm, and second, to assess persistence, distribution, and bioaccumulation of these contaminants in natural biofilms inhabiting a WWTP-impacted river. The method is based on pressurized liquid extraction, purification by solid-phase extraction, and analysis by ultra performance liquid chromatography coupled to a mass spectrometer (UPLC-MS/MS) in tandem. Recoveries for pharmaceuticals were 31-137%, and for endocrine disruptors 32-93%. Method detection limits for endocrine disruptors were in the range of 0.2-2.4 ng g(-1), and for pharmaceuticals, 0.07-6.7 ng g(-1). A total of five endocrine disruptors and seven pharmaceuticals were detected in field samples at concentrations up to 100 ng g(-1).

  7. Micro and Macro Element Composition of Kalanchoe integra Leaves: An Adjuvant Treatment for Hypertension in Ghana

    PubMed Central

    Frimpong-Manso, S.; Asiedu-Gyekye, I. J.; Naadu, J. P.; Magnus-Aryitey, G. T.; Nyarko, A. K.; Boamah, D.; Awan, M.

    2015-01-01

    Two samples, water extract and blended whole leaves, of fresh Kalanchoe integra leaves (Crassulaceae), a traditional antihypertensive medicine used in Ghana, were analyzed with Energy Dispersive X-Ray Fluorescence spectroscopy (EDXRF). Analysis revealed 12 macro and 26 micro elements in both extracts. Further quantitative assessment of the results for amounts of elements that are pharmacologically significant revealed that the amounts of calcium, potassium, and magnesium present in the extracts could be correlated to its traditional usage in managing hypertension and arrhythmias. However, heavy metals (lead and inorganic arsenic) detected in the extracts may pose a threat at doses normally used traditionally for the treatment of hypertension. PMID:26495138

  8. Aromatherapy as an adjuvant treatment in cancer care--a descriptive systematic review.

    PubMed

    Boehm, Katja; Büssing, Arndt; Ostermann, Thomas

    2012-01-01

    Claims of benefits of aromatherapy for cancer patients include reduced anxiety levels and relief of emotional stress, pain, muscular tension and fatigue. The objective of this paper is to provide an updated descriptive, systematic review of evidence from pre-clinical and clinical trials assessing the benefits and safety of aromatherapy for cancer patients. Literature databases such as Medline (via Ovid), the Cochrane database of systematic reviews, Cochrane Central were searched from their inception until October 2010. Only studies on cancer cells or cancer patients were included. There is no long lasting effect of aromatherapy massage, while short term improvements were reported for general well being, anxiety and depression up to 8 weeks after treatment. The reviewed studies indicate short-term effects of aromatherapy on depression, anxiety and overall wellbeing. Specifically, some clinical trials found an increase in patient-identified symptom relief, psychological wellbeing and improved sleep. Furthermore, some found a short-term improvement (up to 2 weeks after treatment) in anxiety and depression scores and better pain control. Although essential oils have generally shown minimal adverse effects, potential risks include ingesting large amounts (intentional misuse); local skin irritation, especially with prolonged skin contact; allergic contact dermatitis; and phototoxicity from reaction to sunlight (some oils). Repeated topical administration of lavender and tea tree oil was associated with reversible prepubertal gynecomastia.

  9. Pharmaceutical chemicals and endocrine disrupters in municipal wastewater in Tokyo and their removal during activated sludge treatment.

    PubMed

    Nakada, Norihide; Tanishima, Toshikatsu; Shinohara, Hiroyuki; Kiri, Kentaro; Takada, Hideshige

    2006-10-01

    We measured six acidic analgesics or anti-inflammatories (aspirin, ibuprofen, naproxen, ketoprofen, fenoprofen, mefenamic acid), two phenolic antiseptics (thymol, triclosan), four amide pharmaceuticals (propyphenazone, crotamiton, carbamazepine, diethyltoluamide), three phenolic endocrine disrupting chemicals (nonylphenol, octylphenol, bisphenol A), and three natural estrogens (17beta-estradiol, estrone, estriol) in 24-h composite samples of influents and secondary effluents collected seasonally from five municipal sewage treatment plants in Tokyo. Aspirin was most abundant in the influent, with an average concentration of 7300 ng/L (n = 16), followed by crotamiton (921 ng/L), ibuprofen (669 ng/L), triclosan (511 ng/L), and diethyltoluamide (503 ng/L). These concentrations were 1 order of magnitude lower than those reported in the USA and Europe. This can be ascribed to lower consumption of the pharmaceuticals in Japan. Aspirin, ibuprofen, and thymol were removed efficiently during primary + secondary treatment (> 90% efficiency). On the other hand, amide-type pharmaceuticals, ketoprofen, and naproxen showed poor removal (< 50% efficiency), which is probably due to their lower hydrophobicity (logKow < 3). Because of the persistence of crotamiton during secondary treatment, crotamiton was most abundant among the target pharmaceuticals in the effluent. This is the first paper to report ubiquitous occurrence of crotamiton, a scabicide, in sewage. Because crotamiton is used worldwide and it is persistent during secondary treatment, it is a promising molecular marker of sewage and secondary effluent.

  10. Adjuvant quercetin therapy for combined treatment of epilepsy and comorbid depression.

    PubMed

    Singh, Tanveer; Kaur, Taranjot; Goel, Rajesh Kumar

    2017-03-01

    Epilepsy is one of the major neurological disorders frequently associated with psychiatric disorders such as depression. The predisposition of tryptophan metabolism towards kynurenine pathway has been reported as one of the plausible reasons for association of depression in epilepsy. Hence, this study was envisaged to evaluate the dose dependent inhibition of indoleamine 2,3-dioxygenase (IDO) enzyme employing quercetin (screened employing in vitro method) with levetiracetam for combined management of epilepsy and comorbid depression. Kindling was induced in male swiss albino mice by administration of pentylenetetrazole subconvulsive doses (35 mg/kg, i.p.) at an interval of 48 ± 2 h. Kindled animals were treated with vehicle, levetiracetam (40 mg/kg/day i.p.) levetiracetam in combination with different doses of quercetin (10 mg/kg; 20 mg/kg; 40 mg/kg)/day/p.o. for 15 days. Except naïve, all the groups were challenged with pentylenetetrazole (35 mg/kg i.p.) on day 5, 10, and 15 to evaluate the seizure severity score. Depression was evaluated in all experimental groups using the tail suspension and sucrose preference test on days 1, 5, 10 and 15, 2 h after pentylenetetrazole challenge. Results suggested that vehicle treated kindled animals were significantly associated with depression. Chronic levetiracetam treatment significantly reduced seizure severity score, but further worsened the associated depression. Quercetin supplementation with levetiracetam dose dependently ameliorated depression associated with epilepsy. Neurochemical and biochemical findings also supported the behavioural findings of the study. Thus, our results suggested that supplementation of quercetin with levetiracetam could be explored further for combined treatment of epilepsy and comorbid depression.

  11. What is the optimal neo-adjuvant treatment for liver metastasis?

    PubMed Central

    Haraldsdottir, Sigurdis; Wu, Christina; Bloomston, Mark

    2013-01-01

    Colorectal cancer is the third most common cancer in the Western population and has a 5-year overall survival of 5–10% when metastatic. Approximately 30% of the patients with metastatic colorectal cancer have limited disease apparently isolated to the liver and, if this can be resected, the 5-year overall survival is improved to 30–60%. Therefore, it is important to identify patients who have both resectable disease and those with initially unresectable tumors who can potentially be downsized with chemotherapy to allow resection. First-line doublet chemotherapy regimens lead to response rates of 50–60%, triplet chemotherapy regimens may result in a response rate of up to 70%, and biological agents may add to responses or induce morphologic changes that facilitate disease resection. Surgical advances in recent years have also increased resectability rates and have challenged prior rules of resectability. Local therapies including ablation and radiation, often performed in conjunction with resection, may further aid in control of disease. The aim of this article is to focus on the role of neoadjuvant therapy in the treatment of colorectal liver metastases. PMID:23858331

  12. Estrogen Receptor Alpha Is Expressed in Mesenteric Mesothelial Cells and Is Internalized in Caveolae upon Freund's Adjuvant Treatment

    PubMed Central

    Balogh, Petra; Szabó, Arnold; Katz, Sándor; Likó, István; Patócs, Attila; L.Kiss, Anna

    2013-01-01

    Transformation of epithelial cells into connective tissue cells (epithelial-mesenchymal transition, EMT) is a complex mechanism involved in tumor metastasis, and in normal embryogenesis, while type II EMT is mainly associated with inflammatory events and tissue regenaration. In this study we examined type II EMT at the ultrastructural and molecular level during the inflammatory process induced by Freund's adjuvant treatment in rat mesenteric mesothelial cells. We found that upon the inflammatory stimulus mesothelial cells lost contact with the basal lamina and with each other, and were transformed into spindle-shaped cells. These morphological changes were accompanied by release of interleukins IL-1alpha, -1beta and IL-6 and by secretion of transforming growth factor beta (TGF-β) into the peritoneal cavity. Mesothelial cells also expressed estrogen receptor alpha (ER-α) as shown by immunolabeling at the light and electron microscopical levels, as well as by quantitative RT-PCR. The mRNA level of ER-α showed an inverse correlation with the secretion of TGF-β. At the cellular and subcellular levels ER-α was colocalized with the coat protein caveolin-1 and was found in the plasma membrane of mesothelial cells, in caveolae close to multivesicular bodies (MVBs) or in the membrane of these organelles, suggesting that ER-α is internalized via caveola-mediated endocytosis during inflammation. We found asymmetric, thickened, electron dense areas on the limiting membrane of MVBs (MVB plaques) indicating that these sites may serve as platforms for collecting and organizing regulatory proteins. Our morphological observations and biochemical data can contribute to form a potential model whereby ER-α and its caveola-mediated endocytosis might play role in TGF-β induced type II EMT in vivo. PMID:24244516

  13. Fibrin glue as adjuvant treatment for gastrocutaneous fistula after gastrostomy tube removal.

    PubMed

    González-Ojeda, A; Avalos-González, J; Muciño-Hernández, M I; López-Ortega, A; Fuentes-Orozco, C; Sánchez-Hochoa, M; Anaya-Prado, R; Arenas-Márquez, H

    2004-04-01

    Gastrocutaneous fistulas are infrequent after gastrostomy tube removal. However, if the fistulous tract remains permeable, even low-volume output can produce significant cutaneous burns. The use of biodegradable adhesives has been described, where fibrin glue is applied directly over the fistulous tract or under the guidance of procedures such as upper or lower gastrointestinal endoscopy or fistuloscopy. We studied the use of fibrin glue in five consecutive adult patients with gastrocutaneous fistulas after gastrostomy tube removal, with no complications that might impede spontaneous closure. A comparison group included seven patients treated during the preceding 2 years with conservative medical management, who were not treated with fibrin glue. There was no difference between the two groups with regard to age and gender, nor with regard to type of gastrostomy (surgical or endoscopic). The mean output volume from the fistulas was 151.4 +/- 146.1 ml/24 h in the study group and 115.0 +/- 42.7 ml/24 h in the control group, which was not significantly different ( P = 0.80). The duration of previous conservative treatment was 93.8 +/- 85.1 days for the study group and 95.8 +/- 80.7 days for the control group and this also did not differ significantly ( P = 0.93). The time to achieve total fistula closure was 7.0 +/- 3.1 days in the study group and 32.7 +/- 15.7 days in the control group. This difference was statistically significant ( P < 0.004). The time required before oral feeding could be recommenced after spontaneous or induced closure was similar in the two groups, at 2.8 +/- 1.3 days and 4.71 +/- 2.36 days, respectively. Endoscopic guidance allows direct instillation of fibrin glue via the external opening through the whole fistulous tract. This procedure reduces the time required for the closure of gastrocutaneous fistulas.

  14. The Efficacy of Adjuvant Intratympanic Steroid Treatment for Otitis Media with Effusion in Children

    PubMed Central

    Amer, Hazem Saeed; El-Anwar, Mohammad Waheed; Elfeky, Alaa Eldin

    2015-01-01

    Introduction  Otitis media with effusion (OME) is a leading cause of hearing impairment in children. Therefore, early and proper management is essential. Objectives  The objective of this research is to assess the efficacy of intratympanic (IT) steroids injection for management of otitis media with effusion (OME). Methods  This study involved 42 children (84 ears) with bilateral OME. We used tympanometry to confirm the childreńs middle ear effusion and pure tone audiometry to determine hearing threshold. We performed myringotomy and inserted ventilation tubes (VTs) bilaterally, followed by a steroid injection of 0.4–0.6 mL methylprednisolone (40 mg/mL) into one randomly selected middle ear. This procedure was followed by once-weekly administration of steroids (0.5 mL methylprednisolone at a concentration of 40 mg/mL) into the middle ear for three consecutive weeks. Results  We found recurrent OME after VT alone in nine (21.4%) ears; whereas, after VT combined with steroid administration, we found two (4.76%), with statistically significant difference. We noted tympanosclerosis postoperatively in six (12.9%) ears and in one of the injected ears (2.3%) (p = 0.0484). Otorrhea occurred in eight (19%) ears with VT alone and in three (7.1%) injected ears, with non-significant difference. The duration between VT insertion and its extrusion was 6.6 = 1.1 months for ears with VT alone and 6.95 =1.12 months in injected ears (p = 0.1541 NS). Conclusion  IT Steroids injection for treatment of OME is a safe and simple intervention with lower incidence of symptoms recurrence and postoperative complications. Thus, its use in management of OME is recommended. PMID:27413407

  15. Estrogen content and relative performance of Japanese and British sewage treatment plants and their potential impact on endocrine disruption.

    PubMed

    Johnson, Andrew; Tanaka, Hiroaki; Okayasu, Yuji; Suzuki, Yutaka

    2007-01-01

    Both the UK and Japan are densely populated islands with relatively short rivers. Therefore, both countries are likely to be highly exposed to contaminants emanating from their human populations. This review considered how effective the different sewage treatment facilities of the two countries are at removing steroid estrogens from the effluent. The methods of estrogen analysis in sewage effluent, the number and importance of different sewage treatment types, and their apparent effectiveness at removing estrogens were all considered. In both countries, the activated sludge treatment was dominant in terms of people served and water discharged. The analytical techniques used by those studying estrogen concentrations in effluents in both countries were broadly similar. Activated sludge plant (ASP) effluent in the UK typically contained around 2 ng/L estradiol (E2) and 8 ng/L estrone (E1), while Japanese ASPs typically reported E2 as below detection, and 10 ng/L E1 in their effluents. When estrogenic bioassays were used in Japan, they typically record an estrogenic potency of 10 ng/L E2 equivalents. Even taking into account ethinylestradiol (EE2) (not found in Japanese effluents), the overall estrogenicity of British sewage effluents would appear to be the same as that of Japanese sewage effluents (around 10 ng/L E2 equivalents). This suggests that the ASPs serving the large urban communities in Japan and the UK would have effluent of similar estrogenic potencies. Less information is available about the more numerous biological (trickling) filter plants (BFP) in the UK and oxygen ditches (OD) in Japan which tend to serve smaller, more rural communities. The available data would suggest that the BFPs are significantly less efficient than the ODs at removing E1. This would suggest that in similar circumstances, British headwaters (where this sewage treatment plant (STP) type is often found) might be more at risk from endocrine disruption than their Japanese counterparts

  16. Ventricular-Arterial Coupling in Breast Cancer Patients After Treatment With Anthracycline-Containing Adjuvant Chemotherapy

    PubMed Central

    Koelwyn, Graeme J.; Lewis, Nia C.; Ellard, Susan L.; Jones, Lee W.; Gelinas, Jinelle C.; Rolf, J. Douglass; Melzer, Bernie; Thomas, Samantha M.; Douglas, Pamela S.; Khouri, Michel G.

    2016-01-01

    Background. Anthracycline-containing chemotherapy (Anth-C) is associated with long-term cardiovascular mortality. Although cardiovascular risk assessment has traditionally focused on the heart, evidence has demonstrated that vascular dysfunction also occurs during and up to 1 year following Anth-C. Whether vascular dysfunction persists long-term or negatively influences cardiac function remains unknown. Hence, the present study evaluated ventricular-arterial coupling, in concert with measures of vascular structure and function, in the years following Anth-C. Methods. Arterial elastance (Ea), end-systolic elastance (Ees), and ventricular-arterial coupling (Ea/Ees) were measured during rest and exercise using echocardiography. Resting vascular function (flow-mediated dilation) and structure (carotid intima-media thickness, arterial stiffness) were also measured. Results. Thirty breast cancer survivors (6.5 ± 3.6 years after Anth-C) with normal left ventricular ejection fraction (LVEF) (60% ± 6%) and 30 matched controls were studied. At rest, no differences were found in Ea, Ees, Ea/Ees, or LVEF between groups. The normal exercise-induced increase in Ees was attenuated in survivors at 50% and 75% of maximal workload (p < .01). Ea/Ees was also higher at all workloads in the survivors compared with the controls (p < .01). No differences in vascular structure and function were observed between the two groups (p > .05). Conclusion. In the years after Anth-C, ventricular-arterial coupling was significantly attenuated during exercise, primarily owing to decreased LV contractility (indicated by a reduced Ees). This subclinical dysfunction appears to be isolated to the heart, as no differences in Ea were observed. The previously reported adverse effects of Anth-C on the vasculature appear to not persist in the years after treatment, as vascular structure and function were comparable to controls. Implications for Practice: Anthracycline-induced cardiotoxicity results in

  17. Olfactory dysfunction in acute rhinosinusitis: intranasal sodium hyaluronate as adjuvant treatment.

    PubMed

    Ciofalo, Andrea; de Vincentiis, Marco; Zambetti, Giampietro; Altissimi, Giancarlo; Fusconi, Massimo; Greco, Antonio; Ottaviano, Giancarlo; Magliulo, Giuseppe

    2017-02-01

    Acute rhinosinusitis (ARS) is defined as an inflammation of the mucosa of the nose and paranasal sinuses and affects 1-5 % of general population in Europe. Sinonasal diseases represent the main cause of smell alterations in adult patients and lead to mucosal congestion, increased quantity and density of secretions and altered mucociliary transport. For this reason the odorous molecules contained in the inspired air, cannot interact with the olfactory epithelium. Medical therapy of ARS has to reduce the severity and duration of symptoms and prevent complications. Recent studies have shown that Sodium hyaluronate modulate inflammation and has a reparative effect on the nasal mucosa. 48 patients affected by acute rhinosinusitis proven by CT scan, were enrolled. They were submitted to nasal endoscopy, olfactometric and mucociliary transport evaluation (MCTt), Visual Analogue Scale Questionnaire (VAS) at T0, after 14-18 days (T1) and after 30-35 days (T2). The patients were randomized into two treatment groups, A and B, and were treated for 30 days; each group was composed of 24 subjects. All patients received Levofloxacin (500 mg for 10 days) and Prednisone (50 mg for 8 days, 25 mg for 4 days and 12, 5 mg for 4 days). Moreover, Group A received twice a day for 30 days high molecular weight Sodium Hyaluronate (3 %) plus saline solution (3 mL sodium chloride-NaCl-0.9 %) using a nebulizer ampoule for nasal douche. Group B received twice a day for 30 days saline solution (6 mL sodium chloride-NaCl-0.9 %) using a nebulizer ampoule for nasal douche. At T1 Group A shown lower values in MCTt and threshold score was significantly higher than in Group B. VAS showed statistically significant differences between the two groups, in particular for smell, nasal obstruction and for nasal discharge. At T2 Group A MCTt was significantly lower than in Group B; odour threshold improved in both groups but in Group A was still significantly higher than in Group B. No

  18. Endocrine System (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Endocrine System KidsHealth > For Parents > Endocrine System A A A ... to help the body function properly. About the Endocrine System The foundations of the endocrine system are the ...

  19. [Dengzhan Xixin injection as an adjuvant treatment for angina pectoris: a systematic review and Meta-analysis of randomized controlled trials].

    PubMed

    Wang, Feng-jiao; Xie, Yan-ming; Liao, Xing; Jia, Min

    2015-08-01

    The paper is to systematically evaluate the efficacy and safety of Deng Zhan Xi Xin injection ( DZXXI) as an adjuvant treatment for patients with angina pectoris. The Cochrane Library, Medline, EMbase, CBM, CNKI, VIP, and Wan fang Data base were searched. Randomized controlled trials (RCTs) of DZXXI combined with western medicine routine treatment versus western medicine routine treatment alone for angina pectoris patients were all included. All trials were assessed according to the Cochrane Reviewer' s Handbook 5.1 for Systematic Reviews of Intervention and Meta analyses were performed by RevMan 5. 2 Software. A total of 30RCTs (3 086 patients including 1 572 patients of treatment group and 1 514 patients of control group) were included. Meta-analysis of treatment group compared with control group showed superior effect over reducing cardiovascular events ( OR = 0.33; 95% CI: [0.16, 0.67], P = 0.002, improving effective rate of DZXXI as adjuvant treatment for angina pectoris patients (OR = 3.97; 95% CI: [3.15, 5.02]; P < 0.000 010 and electrocardiogram curative effect (OR = 2.21; 95% CI; [1.83, 2.68]; P < 0.000 010. Funnel figure seemed that there was publication bias. The current limited evidence showed that when compared with the control group, treatment group was superior in improving patients with angina pectoris. But based on the limitations of the study, rigorous design with long follow up clinical trials are necessary for further evidence.

  20. The treatment outcomes and the use of adjuvant therapies in breast cancer patients with severe co-morbidities

    PubMed Central

    Han, Jaihong; Lee, Han-Byoel; Lee, Eun-Shin; Kang, Young Joon; Kim, Yumi; Choi, Jihye; Rhu, Jiyoung; Shin, Hee-Chul; Han, Wonshik; Noh, Dong-Young

    2017-01-01

    Purpose Studies have suggested a potential role of patient’s co-morbidity in determining the survival outcomes of breast cancer. In this study, we examined the long-term oncologic outcomes in breast cancer patients who underwent curative surgery according to their pre-existing comorbid conditions and analyzed the association between the co-morbidity and the use of adjuvant therapies. Methods The medical records of 2,501 patients who underwent surgery for primary breast cancer from June 2006 to June 2010 were reviewed retrospectively. The patients were classified into three groups according to preoperative ASA status determined by the anesthesiologists. Clinico-pathologic characteristics and survival outcomes of the patients were compared among the different co-morbidity groups. Results There were 1,792 (71.6%), 665 (26.6%), and 44 (1.8%) patients in ASA I, II, and III, respectively. Total 95 (3.8%) deaths and 269 (10.8%) recurrences (loco-regional and distant) occurred during the median follow-up period of 71 months. Patients with high comorbidity showed significantly higher rate of deaths (51 (2.8%), 38 (5.7%) and 6 (13.6%) deaths in ASA I, II and III group, respectively, p<0.001). The ASA 3 patients also showed significantly higher rate of breast cancer recurrence when compared to other groups (180 (10.0%), 80 (12.0%) and 9 (20.5%) in ASA I, II, and III, respectively, p = 0.041). Significantly fewer patients in the high co-morbidity group received adjuvant therapies (77 (4.3%), 44 (6.6%) and 8 (18.2%) in ASA I, II, and III, respectively, p<0.001). The increased recurrence of breast cancer in the high morbidity group was mostly seen in patients who did not receive adjuvant therapies. The incidence of serious adverse effect during the adjuvant therapy did not differ according to the co-morbidity conditions. Conclusions In this study, high comorbidity was related to increased risk of death and recurrence in breast cancer. The increased risk of recurrence in high

  1. Adjuvant chemotherapy plus radiotherapy is superior to chemotherapy following surgical treatment of stage IIIA N2 non-small-cell lung cancer

    PubMed Central

    Lei, Tao; Xu, Xiao-Ling; Chen, Wei; Xu, Ya-Ping; Mao, Wei-Min

    2016-01-01

    The use of additional radiotherapy for resected stage IIIA N2 non-small-cell lung cancer in the setting of standard adjuvant chemotherapy remains controversial. A comprehensive search (last search updated in March 2015) for relevant studies comparing patients with stage IIIA N2 non-small-cell lung cancer undergoing resection after treatment with adjuvant postoperative chemotherapy alone or adjuvant postoperative chemoradiotherapy (POCRT) was conducted. Hazard ratios (HRs) were extracted from these studies to give pooled estimates of the effects of POCRT on overall survival (OS) and disease-free survival (DFS). Six studies were included. The meta-analysis demonstrated that POCRT had a greater OS benefit than postoperative chemotherapy (HR =0.87, 95% confidence interval [CI]: 0.79–0.96, P=0.006). Unfortunately, there was no significant difference in DFS between the two groups: the combined HR for DFS was 0.91 (95% CI: 0.57–1.46, P=0.706). In a subgroup analysis of two randomized controlled trials (n=172 patients), adding radiation was of no benefit to either OS (HR =0.72, 95% CI: 0.49–1.06, P=0.094) or DFS (HR =1.45, 95% CI: 1.00–2.09, P=0.047). In summary, compared with postoperative chemotherapy, POCRT was beneficial to OS but not DFS in patients with stage IIIA N2 non-small-cell lung cancer. PMID:26966380

  2. Treatment of Endocrine-Resistant Breast Cancer with a Small Molecule C-MYC Inhibitor

    DTIC Science & Technology

    2014-06-01

    women. Tamoxifen has been a front-line treatment for estrogen receptor alpha (ERα)-positive breast tumors in premenopausal women. However resistance to... tamoxifen occurs in many patients. ERα still plays a critical role in the growth of breast cancer cells with acquired tamoxifen resistance...suggesting that ERα remains a valid target for treatment of tamoxifen - resistant breast cancer. In an effort to identify novel regulators of ERα signaling

  3. MANAGEMENT OF ENDOCRINE DISEASE: Long-term outcomes of the treatment of central precocious puberty.

    PubMed

    Guaraldi, Federica; Beccuti, Guglielmo; Gori, Davide; Ghizzoni, Lucia

    2016-03-01

    GnRH analogues (GnRHa) are the treatment of choice for central precocious puberty (CPP), with the main objective to recover the height potential compromised by the premature fusion of growth cartilages. The aim of this review was to analyze long-term effects of GnRHa on height, body weight, reproductive function, and bone mineral density (BMD) in patients with CPP, as well as the potential predictors of outcome. Because randomized controlled trials on the effectiveness and long-term outcomes of treatment are not available, only qualified conclusions about the efficacy of interventions can be drawn. GnRHa treatment appears to improve adult height in girls with CPP, especially if diagnosed before the age of 6, whereas a real benefit in terms of adult height is still controversial in patients with the onset of puberty between 6 and 8 years of age. No height benefit was shown in patients treated after 8 years. Gonadal function is promptly restored in girls after cessation of treatment, and reproductive potential appears normal in young adulthood. Data are conflicting on the long-term risk of polycystic ovarian syndrome in both treated and untreated women. Fat mass is increased at the start of treatment but normalizes thereafter, and GnRHa itself does not seem to have any long-term effect on BMI. Similarly, analogue treatment does not appear to have a negative impact on BMD. Owing to the paucity of data available, no conclusions can be drawn on the repercussions of CPP and/or its treatment on the timing of menopause and on the health of the offspring.

  4. A new strategy of CyberKnife treatment system based radiosurgery followed by early use of adjuvant bevacizumab treatment for brain metastasis with extensive cerebral edema.

    PubMed

    Wang, Yang; Wang, Enmin; Pan, Li; Dai, Jiazhong; Zhang, Nan; Wang, Xin; Liu, Xiaoxia; Mei, Guanghai; Sheng, Xiaofang

    2014-09-01

    Bevacizumab blocks the effects of vascular endothelial growth factor in leakage-prone capillaries and has been suggested as a new treatment for cerebral radiation edema and necrosis. CyberKnife is a new, frameless stereotactic radiosurgery system. This work investigated the safety and efficacy of CyberKnife followed by early bevacizumab treatment for brain metastasis with extensive cerebral edema. The eligibility criteria of the patients selected for radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1) brain tumors from metastasis with one solitary brain lesion and symptomatic extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery due to the physical conditions and the risk of surgery; (4) no contraindications for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a maximum of 6 injections with a 2-week interval between treatments, beginning within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS) ≥30. Tumor size and edema were monitored by magnetic resonance imaging (MRI). Dexamethasone dosage, KPS, adverse event occurrence and associated clinical outcomes were also recorded. Eight patients were accrued for this new treatment. Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the 61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2-week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and 63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological improvements. Dexamethasone was reduced in all patients, with five successfully discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation. Hypertension, a bevacizumab-related adverse event, occurred in one patient. After 3-8 months, all patients studied were alive and primary brain metastases were under control, 2 developed new brain

  5. Ecological risk assessment associated to the removal of endocrine-disrupting parabens and benzophenone-4 in wastewater treatment.

    PubMed

    Molins-Delgado, Daniel; Díaz-Cruz, M Silvia; Barceló, Damià

    2016-06-05

    The occurrence of four widely used and endocrine disrupting parabens (PBs) (methylparaben, propylparaben, butylparaben and benzylparaben) and a polar UV filter (benzophenone-4) were determined in influent and effluent wastewater from the 19 major wastewater treatment plants (WWTPs) of Catalonia, Spain. For their analysis an on-line solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS) method was developed and validated. Laboratory analysis revealed high levels for both PBs and BP4, with maximum concentrations of 5700ngL(-1) and 1806ngL(-1), respectively, in influent samples, and 137ngL(-1) and 1080ngL(-1), respectively in effluent wastewaters. Removal rates (RE%) for the target compounds in each WWTPs were calculated. RE% for parabens were almost 100%, whereas for BP4 values where in the range 5-91%. The half-life time (t1/2), hydraulic retention time (HRT), and annual mass load (ML) for each facility was estimated. Results indicated that there was no clear influence of HRT on the RE% of BP4. MLs for BP4 were in the range 0.9-110.1kgy(-1), with the highest values in the most populated areas. Finally, a risk assessment, estimated in terms of hazard quotients (HQs), was carried out for aquatic biota. HQs for the target compounds in effluent wastewaters indicated a negligible effect, whereas for some influent wastewaters' HQs pointed out that some species are at risk.

  6. Simultaneously photocatalytic treatment of hexavalent chromium (Cr(VI)) and endocrine disrupting compounds (EDCs) using rotating reactor under solar irradiation.

    PubMed

    Kim, Youngji; Joo, Hyunku; Her, Namguk; Yoon, Yeomin; Sohn, Jinsik; Kim, Sungpyo; Yoon, Jaekyung

    2015-05-15

    In this study, simultaneous treatments, reduction of hexavalent chromium (Cr(VI)) and oxidation of endocrine disrupting compounds (EDCs), such as bisphenol A (BPA), 17α-ethinyl estradiol (EE2) and 17β-estradiol (E2), were investigated with a rotating photocatalytic reactor including TiO₂ nanotubes formed on titanium mesh substrates under solar UV irradiation. In the laboratory tests with a rotating type I reactor, synergy effects of the simultaneous photocatalytic reduction and oxidation of inorganic (Cr(VI)) and organic (BPA) pollutants were achieved. Particularly, the concurrent photocatalytic reduction of Cr(VI) and oxidation of BPA was higher under acidic conditions. The enhanced reaction efficiency of both pollutants was attributed to a stronger charge interaction between TiO₂ nanotubes (positive charge) and the anionic form of Cr(VI) (negative charge), which are prevented recombination (electron-hole pair) by the hole scavenging effect of BPA. In the extended outdoor tests with a rotating type II reactor under solar irradiation, the experiment was extended to examine the simultaneous reduction of Cr(VI) in the presence of additional EDCs, such as EE2 and E2 as well as BPA. The findings showed that synergic effect of both photocatalytic reduction and oxidation was confirmed with single-component (Cr(VI) only), two-components (Cr(VI)/BPA, Cr(VI)/EE2, and Cr(VI)/E2), and four-components (Cr(VI)/BPA/EE2/E2) under various solar irradiation conditions.

  7. [Multiple endocrine neoplasia type 1 (MEN 1): clinical, biochemical and molecular diagnosis and treatment of the associated disturbances].

    PubMed

    Hoff, Ana Oliveira; Hauache, Omar Magid

    2005-10-01

    Multiple endocrine neoplasia (MEN) syndromes include types 1 (MEN 1) and 2 (MEN 2), von Hippel-Lindau syndrome, neurofibromatosis type 1 and Carney complex. These are complex genetic syndromes caused by activation or inactivation of different types of genes known to be involved in the regulation of cell proliferation. In this review we will discuss the clinical manifestations and management of the MEN 1 syndrome as well as the genetic screening of potential MEN 1 gene carriers. MEN 1 is a hereditary syndrome, transmitted in an autosomic dominant fashion and caused by an inactivating mutation of the MEN 1 gene, characterized by the development of primary hyperparathyroidism, islet cell tumors and pituitary adenomas. In addition, these patients can present with cutaneous manifestations such as angiofibromas and collagenomas, and can develop other neoplastic manifestations including carcinoids, thyroid tumors, adrenal adenomas, lipomas, pheochromocytomas and meningiomas. The MEN 1 gene encodes a peptide which is a tumor suppressor gene called menin. Several studies have demonstrated its importance in regulation of cell proliferation and have confirmed its role in the pathogenesis of the MEN 1 syndrome. The discovery of the MEN 1 gene and the genetic analysis of MEN 1 patients have resulted in earlier diagnosis and treatment of asymptomatic carriers which can potentially result in a longer survival of these patients. Further investigation of the function and signaling pathways of the menin protein will hopefully offer therapeutic alternatives to patients with malignant progression of MEN 1-related tumors and also result in improved survival.

  8. Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone agonist.

    PubMed

    Dittrich, R; Binder, H; Cupisti, S; Hoffmann, I; Beckmann, M W; Mueller, A

    2005-12-01

    In transsexual people, cross-sex hormone therapy is an important component of medical treatment. In male-to-female transsexuals, feminizing effects should be achieved before irreversible sex reassignment surgery (SRS) is considered. The most common treatment regimen in male-to-female transsexuals is a combination of ethinyl oestradiol and cyproterone acetate, with the exception of transdermal oestradiol-17beta in individuals over the age of 40. The mortality and morbidity rates with this treatment regimen have been reported in more than 800 patients. Typical side effects include venous thrombosis, elevated liver enzymes, symptomatic gallstones, hyperprolactinaemia and depression. Sixty male-to-female transsexuals were treated with monthly injections of gonadotropin-releasing hormone agonist (GnRHa) and oral oestradiol-17beta valerate for 2 years to achieve feminisation until SRS. There was a significant decline in gonadotropins, total testosterone and calculated free testosterone. In general, the treatment regimen was well accepted. An equal increase in breast size was achieved compared to common hormone therapy. Two side effects were documented. One, venous thrombosis, occurred in a patient with a homozygous MTHFR mutation. One patient was found to be suffering from symptomatic preexisting gallstones. No other complications were documented. Liver enzymes, lipids, and prolactin levels were unchanged. Significantly increased oestradiol and SHBG serum levels were detectable. In addition, an increase in bone mass density, in the femoral neck and lumbar spine, was recorded. We conclude that cross-sex hormone treatment of male-to-female transsexuals using GnRHa and oestradiol-17beta valerate is effective, and side effects and complication rates can be reduced using the treatment regimen presented here.

  9. Novel adjuvant therapies for pancreatic adenocarcinoma

    PubMed Central

    Oyasiji, Tolutope

    2015-01-01

    Contemporary adjuvant therapy for pancreatic cancer patients following surgical resection includes chemotherapy and chemoradiotherapy. However, the median survival remains approximately 20 months despite multi-modality treatment using gemcitabine or fluoropyrimidine systemic chemotherapy. Adjuvant randomized trials are currently underway to evaluate cytotoxic combinations found to be active in advanced disease including FOLFIRINOX, gemcitabine/nab-paclitaxel and gemcitabine/capecitabine. Immunotherapy using genetically engineered cell-based vaccines had shown promise in resected pancreatic cancer patients during early phase trials, and algenpantucel-L vaccine is currently being evaluated in adjuvant setting in a randomized trial. This review focuses on novel adjuvant therapies currently in clinical evaluation. PMID:26261729

  10. A retrospective study on IVF/ICSI outcome in patients with anti-nuclear antibodies: the effects of prednisone plus low-dose aspirin adjuvant treatment

    PubMed Central

    2013-01-01

    Background Anti-nuclear antibodies (ANA) are suspected of having relevance to adverse reproductive events. Methods This study aims to investigate the potential effect of ANA on IVF/ICSI outcome and the therapeutic role of prednisone plus low-dose aspirin (P + A) adjuvant treatment in ANA + patients. The first IVF/ICSI cycles without P + A of sixty-six ANA + women were enrolled as the ANA + group, and the 233 first IVF/ICSI cycles of matched ANA- women served as the ANA- group. The ANA + group was divided into the Titre < =1:320 subgroup and the Titre > 1:320 subgroup. Twenty-one ANA + women with adverse outcomes in their first cycles (ANA + cycles without P + A) received P + A adjuvant treatment for three months before the second IVF/ICSI cycle (ANA + cycles with P + A). The clinical characteristics and the IVF/ICSI outcomes were compared, respectively, between 1) the ANA + group and the ANA- group, 2) the Titre < =1:320 subgroup and the Titre > 1:320 subgroup, and 3) the ANA + cycles without P + A and the ANA + cycles with P + A. Results No significant differences were observed between each of the two-group pairs in the clinical characteristics. The ANA + group exhibited significantly lower MII oocytes rate, normal fertilisation, pregnancy and implantation rates, as well as remarkably higher abnormal fertilisation and early miscarriage rates. The Titre < =1:320 subgroup’s IVF/ICSI outcomes were as poor as those of the Titre > 1:320 subgroup. After the P + A adjuvant treatment, the number of two pro-nuclei, perfect embryos and available embryos, and the implantation rate increased significantly. Conclusions These observations suggest that ANA could exert a detrimental effect on IVF/ICSI outcome that might not be titre-dependent, and P + A adjuvant treatment could be useful for ANA + patients. This hypothesis should be verified in further prospective randomised studies. PMID:24093222

  11. Triple-negative breast cancer: the impact of guideline-adherent adjuvant treatment on survival--a retrospective multi-centre cohort study.

    PubMed

    Schwentner, L; Wolters, R; Koretz, K; Wischnewsky, M B; Kreienberg, R; Rottscholl, R; Wöckel, A

    2012-04-01

    Triple-negative breast cancer (TNBC) (ER-/PGR-/erb-2-) constitutes an aggressive subtype in breast cancer because it is accompanied by a significant decrease in overall survival (OAS) and recurrence-free survival (RFS) compared with hormone receptor positive breast cancers. This retrospective cohort study investigates the following issues: (1) Is there an impact of guideline-adherent treatment on RFS and OAS in TNBC? (2) Which adjuvant treatment has the most important impact on RFS and OAS in TNBC? This German retrospective multi-centre cohort study included 3,658 patients with primary breast cancer recruited from 2000 to 2005. The definition of guideline adherence was based on the German national S3 guideline for diagnosis and treatment of breast cancer (2004). A total of 371 patients (10.1%) had TNBC. Compared with HR+/erb-2- breast cancer (P = 0.001; HR = 1.75; 95% CI: 1.27-2.40), the recurrence rate of TNBC was significantly higher (P < 0.001; HR = 2.86; 95% CI: 2.17-3.76). Furthermore, the 5-year RFS and OAS was significantly lower in TNBC (RFS: 74.8% [95% CI: 68.8-80.8%] vs. 86.5% [95% CI: 84.6-88.4%] [log-rank P = 0.0001]) (OAS: 75.8% [95% CI: 69.9-81.8%] vs. 86.0% [95% CI: 84.1-87.9%] [log-rank P = 0.0001]). The most important parameters predicting RFS and OAS in TNBC after receiving guideline-conform chemotherapy are guideline-adherent surgery, radiotherapy, nodal status and grading. Overall, 66.8% TNBC were found with one or more (18%) guideline violations, which subsequently impaired OAS and RFS. The most important impact on OAS and RFS in TNBC patients was because of guideline violations (GV) concerning adjuvant radiotherapy and GV concerning adjuvant chemotherapy. Patients with TNBC primarily have a worse prognosis in terms of RFS and OAS than patients of a primarily non-TNBC phenotype. There is a strong association between guideline-adherent adjuvant treatment and improved survival outcome in TNBC. The outcome significantly decreases with the number

  12. Retrospective analysis of drug utilization, health care resource use, and costs associated with IFN therapy for adjuvant treatment of malignant melanoma

    PubMed Central

    Zhang, Ying; Le, Trong Kim; Shaw, James W; Kotapati, Srividya

    2015-01-01

    Background This study examines real-world drug utilization patterns, health care resource use, and costs among patients receiving adjuvant treatment with IFN versus patients receiving no treatment (“observation”) for malignant melanoma following surgery. Methods A retrospective cohort study was conducted using administrative claims from Truven Health Analytics (MarketScan®) to identify all adjuvant melanoma patients (aged ≥18 years) diagnosed between June 2007 and June 2011 who had a lymph node dissection (ie, index surgery) and were treated with IFN or subsequently observed. Health care resource use and costs of services were converted to 2012 US dollars and were evaluated and compared using multivariable regression. Results Of 1,999 eligible subjects with melanoma surgery claims, 179 (9.0%) were treated with IFN and 1,820 (91.0%) were observed. The median duration (days) and number of doses of IFN therapy were 73 and 36, respectively. Among IFN-treated patients, only 10.6% completed ≥80% of maintenance therapy. The total average cost for patients treated with IFN was US$60,755±$3,972 (n=179); significantly higher than for patients undergoing observation ($31,641±$2,471; P<0.0001). Similar trends were observed when evaluating total cost components, including melanoma-related and non-melanoma–related medical costs. Among the melanoma-related medical costs, outpatient services, including office visits and laboratory testing, represented between 33% and 53% of total costs and demonstrated the largest difference between IFN-treated and observation patients. Outpatient service costs for IFN-treated patients were $32,414±$2,498, over three times greater than those for observation patients ($10,556±$1,128; P<0.0001). Conclusion The majority of adjuvant melanoma patients in this study was treated with observation versus IFN treatment. Among those who attempted IFN treatment, most could not complete the recommended course of therapy. Health care costs were

  13. Adjuvant aqueous ozone in the treatment of bisphosphonate induced necrosis of the jaws: report of two cases and long-term follow-up.

    PubMed

    Brozoski, M A; Lemos, C A; Da Graça Naclério-Homem, M; Deboni, M C Z

    2014-01-01

    Bisphosphonate induced necrosis of the jaws (BONJ) does not have a unique protocol of treatment and many therapeutic approaches have been arising in oral medicine with debatable results. A male and a female attended the University Oral Surgery Clinic presenting oral bone lesions induced by intravenous and oral bisphosphonates respectively as complications of dental extraction. Treatment included daily mouthwashes and weekly intra oral irrigations with 4 mg/L of aqueous-ozone, antibiotic therapy and sequential superficial debridment for sequestrectomies. Long-standing follow-ups showed complete mucosa covering of exposed bone area and resolution of purulent secretion. Antibacterial and antifungal properties of aqueous ozone may have played important roles in the treatment. The outcome measured intra oral examination and panoramic radiographs of the affected bone. The application of aqueous ozone daily mouthwashes and weekly professional irrigation were safe; free from adverse effects, easily of handling and worked as an important adjuvant therapeutic strategy for the treatment of BONJ.

  14. Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes.

    PubMed

    Rafacho, Alex; Ortsäter, Henrik; Nadal, Angel; Quesada, Ivan

    2014-12-01

    Glucocorticoids (GCs) are broadly prescribed for numerous pathological conditions because of their anti-inflammatory, antiallergic and immunosuppressive effects, among other actions. Nevertheless, GCs can produce undesired diabetogenic side effects through interactions with the regulation of glucose homeostasis. Under conditions of excess and/or long-term treatment, GCs can induce peripheral insulin resistance (IR) by impairing insulin signalling, which results in reduced glucose disposal and augmented endogenous glucose production. In addition, GCs can promote abdominal obesity, elevate plasma fatty acids and triglycerides, and suppress osteocalcin synthesis in bone tissue. In response to GC-induced peripheral IR and in an attempt to maintain normoglycaemia, pancreatic β-cells undergo several morphofunctional adaptations that result in hyperinsulinaemia. Failure of β-cells to compensate for this situation favours glucose homeostasis disruption, which can result in hyperglycaemia, particularly in susceptible individuals. GC treatment does not only alter pancreatic β-cell function but also affect them by their actions that can lead to hyperglucagonaemia, further contributing to glucose homeostasis imbalance and hyperglycaemia. In addition, the release of other islet hormones, such as somatostatin, amylin and ghrelin, is also affected by GC administration. These undesired GC actions merit further consideration for the design of improved GC therapies without diabetogenic effects. In summary, in this review, we consider the implication of GC treatment on peripheral IR, islet function and glucose homeostasis.

  15. Therapy in endocrine disease: treatment of hirsutism in the polycystic ovary syndrome.

    PubMed

    Pasquali, Renato; Gambineri, Alessandra

    2014-02-01

    Hirsutism is a common medical complaint among women of reproductive age, and it affects the majority of women with the polycystic ovary syndrome (PCOS). Increased rate of androgen production and its availability in tissue represent the main pathophysiological mechanisms responsible for hirsutism. In addition, androgens may be generated de novo in the hair follicle; therefore, circulating androgen levels do not quantify the real exposure of the hair follicle to androgens, as a quota is locally generated. Hirsutism is a clinical sign and not a disease in itself; its presence does not therefore necessarily require treatment, particularly in mild-to-moderate forms, and when an affected woman does not worry about it. Physicians should decide whether hirsutism is to be treated or not by evaluating not only the severity of the phenomenon but also the subjective perception of the patient, which does not necessarily correspond to the true extent of hair growth. In any case, a physician should manage a woman with hirsutism only on the basis of a diagnosis of the underlying cause, and after a clear explanation of the efficacy of each therapeutic choice. Cosmetic procedures and pharmacological intervention are commonly used in the treatment of hirsutism and are discussed in this paper. Importantly, there are different phenotypes of women with hirsutism and PCOS that may require specific attention in the choice of treatment. In particular, when obesity is present, lifestyle intervention should be always considered, and if necessary combined with pharmacotherapy.

  16. The impact of ERBB-family germline single nucleotide polymorphisms on survival response to adjuvant trastuzumab treatment in HER2-positive breast cancer

    PubMed Central

    Furney, Simon J.; Fan, Yue; McCormack, Mark; Stapleton, Carragh; Cremona, Mattia; Cavalleri, Gianpiero L.; Milewska, Malgorzata; Elster, Naomi; Carr, Aoife; Fay, Joanna; Kay, Elaine W.; Kennedy, Susan; Crown, John; Gallagher, William M.; Hennessy, Bryan T.; Eustace, Alex J.

    2016-01-01

    Background Trastuzumab treatment for women with HER2-positive breast cancer (BC) resulted in the significant improvement of both relapse free survival (RFS) and overall survival (OS). However, many women who are classified as HER2-positive do not respond. Many studies have focused on the role of somatic mutations rather than germline polymorphisms in trastuzumab resistance. Results We completed an Agena MassArray screen of 10 ERBB-family single nucleotide polymorphisms (SNPs) in 194 adjuvant trastuzumab treated HER2-positive BC patients. SNPs in EGFR genes have a significant association with RFS and OS. Patients with the minor allele of EGFR N158N had significantly worse OS (hazard ratio (HR) = 4.01, (confidence interval (CI) = 1.53– 10.69), p = 0.05) relative to those with either the heterozygous or wild-type (WT) allele. Patients with the minor allele of EGFR T903T (HR = 3.52, (CI = 1.38– 8.97), p = 0.05) had worse RFS relative to those with either the heterozygous or WT allele. Patients and methods Using next generation sequencing (NGS) we identified ERBB-family (EGFR, HER2, HER3 and HER4) single nucleotide polymorphisms (SNPs) that occurred in 2 or more patients of a 32 HER2-positive BC patient cohort. Agena MassArray analysis confirmed the frequency of these SNPs in 194 women with HER2-positive BC who received trastuzumab in the adjuvant setting. Using Kaplan-Meier estimates and Cox regression analysis we correlated the presence of ERBB-family SNPs with both RFS and OS. Conclusions The presence of germline ERBB-family SNPs may play an important role in how a patient responds to adjuvant trastuzumab, and clinical assessment of these SNPs by targeted genetic screening of patients' blood may be important to stratify patients for treatment. PMID:27776352

  17. Impact of intratumoral expression levels of fluoropyrimidine-metabolizing enzymes on treatment outcomes of adjuvant S-1 therapy in gastric cancer.

    PubMed

    Kim, Ji-Yeon; Shin, Eun; Kim, Jin Won; Lee, Hye Seung; Lee, Dae-Won; Kim, Se-Hyun; Lee, Jeong-Ok; Kim, Yu Jung; Kim, Jee Hyun; Bang, Soo-Mee; Ahn, Sang-Hoon; Park, Do Joong; Lee, Jong Seok; Lee, Ju-Seog; Kim, Hyung-Ho; Lee, Keun-Wook

    2015-01-01

    We analyzed the expression levels of fluoropyrimidine-metabolizing enzymes (thymidylate synthase [TS], dihydropyrimidine dehydrogenase [DPD], thymidine phosphorylase [TP] and orotate phosphoribosyltransferase [OPRT]) to identify potential biomarkers related to treatment outcomes in gastric cancer (GC) patients receiving adjuvant S-1 chemotherapy. In this study, 184 patients who received curative gastrectomy (D2 lymph node dissection) and adjuvant S-1 were included. Immunohistochemistry and quantitative reverse transcription polymerase chain reaction were performed to measure the protein and mRNA levels of TS, DPD, TP, and OPRT in tumor tissue. In univariate analysis, low intratumoral DPD protein expression was related to poorer 5-year disease-free survival (DFS; 78% vs. 88%; P = 0.068). Low intratumoral DPD mRNA expression (1st [lowest] quartile) was also related to poorer DFS (69% vs. 90%; P < 0.001) compared to high intratumoral DPD expression (2nd to 4th quartiles). In multivariate analyses, low intratumoral DPD protein or mRNA expression was related to worse DFS (P < 0.05), irrespective of other clinical variables. TS, TP, and OPRT expression levels were not related to treatment outcomes. Severe non-hematologic toxicities (grade ≥ 3) had a trend towards more frequent development in patients with low intratumoral DPD mRNA expression (29% vs. 16%; P = 0.068). In conclusion, GC patients with high intratumoral DPD expression did not have inferior outcome following adjuvant S-1 therapy compared with those with low DPD expression. Instead, low intratumoral DPD expression was related to poor DFS.

  18. Adjuvant treatment may benefit patients with high-risk upper rectal cancer: A nomogram and recursive partitioning analysis of 547 patients

    PubMed Central

    Wang, Xin; Jin, Jing; Yang, Yong; Liu, Wen-Yang; Ren, Hua; Feng, Yan-Ru; Xiao, Qin; Li, Ning; Deng, Lei; Fang, Hui; Jing, Hao; Lu, Ning-Ning; Tang, Yu; Wang, Jian-Yang; Wang, Shu-Lian; Wang, Wei-Hu; Song, Yong-Wen; Liu, Yue-Ping; Li, Ye-Xiong

    2016-01-01

    Purpose The role of adjuvant chemoradiotherapy (ACRT) or adjuvant chemotherapy (ACT) in treating patients with locally advanced upper rectal cancer (URC) after total mesorectal excision (TME) surgery remains unclear. We developed a clinical nomogram and a recursive partitioning analysis (RPA)-based risk stratification system for predicting 5-year cancer-specific survival (CSS) to determine whether these individuals require ACRT or ACT. Materials and Methods This retrospective analysis included 547 patients with primary URC. A nomogram was developed based on the Cox regression model. The performance of the model was assessed by concordance index (C-index) and calibration curve in internal validation with bootstrapping. RPA stratified patients into risk groups based on their tumor characteristics. Results Five independent prognostic factors (age, preoperative increased carcinoembryonic antigen and carcinoma antigen 19-9, positive lymph node [PLN] number, tumor deposit [TD], pathological T classification) were identified and entered into the predictive nomogram. The bootstrap-corrected C-index was 0.757. RPA stratification of the three prognostic groups showed obviously different prognosis. Only the high-risk group (patients with PLN ≤ 6 and TD, or PLN > 6) benefited from ACRT plus ACT when compared with surgery followed by ACRT or ACT, and surgery alone (5-year CSS: 70.8% vs. 57.8% vs. 15.6%, P < 0.001). Conclusions Our nomogram predicts 5-year CSS after TME surgery for locally advanced rectal cancer and RPA-based stratification indicates that ACRT plus ACT post-surgery may be an important treatment plan with potentially significant survival advantages in high-risk URC. This may help to select candidates of adjuvant treatment in prospective studies. PMID:27449095

  19. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study

    SciTech Connect

    Schaake-Koning, C.; van der Linden, E.H.; Hart, G.; Engelsman, E.

    1985-10-01

    Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together. LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results. In conclusion: adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer.

  20. [Adolescents with gender identity disorder: reconsideration of the age limits for endocrine treatment and surgery].

    PubMed

    Nakatsuka, Mikiya

    2012-01-01

    The third versions of the guideline for treatment of people with gender identity disorder (GID) of the Japanese Society of Psychiatry and Neurology does not include puberty-delaying hormone therapy. It is recommended that feminizing/masculinizing hormone therapy and genital surgery should not be carried out until 18 year old and 20 year old, respectively. On the other hand, the sixth (2001) and the seventh (2011) versions of the standards of care for the health of transsexual, transgender, and gender nonconforming people of World Professional Association for Transgender Health (WPATH) recommend that transsexual adolescents (Tanner stage 2, [mainly 12-13 years of age]) are treated by the endocrinologists to suppress puberty with gonadotropin-releasing hormone (GnRH) agonists until age 16 years old, after which cross-sex hormones may be given. A questionnairing on 181 people with GID diagnosed in the Okayama University Hospital (Japan) showed that female to male (FTM) transsexuals hoped to begin masculinizing hormone therapy at age of 15.6 +/- 4.0 (mean +/- S.D.) whereas male to female (MTF) transsexuals hoped to begin feminizing hormone therapy as early as age 12.5 +/- 4.0, before presenting secondary sex characters. After confirmation of strong and persistent cross-gender identification, adolescents with GID should be treated with cross-gender hormone or puberty-delaying hormone to prevent developing undesired sex characters. These treatments may prevent transsexual adolescents from attempting suicide, being depressive, and refusing to attend school. Subsequent early breast and genital surgery may help being employed in desired sexuality.

  1. Subclinical Myocardial Impairment Occurred in Septal and Anterior LV Wall Segments After Anthracycline-Embedded Chemotherapy and did not Worsen During Adjuvant Trastuzumab Treatment in Breast Cancer Patients.

    PubMed

    Lange, Stefan Andreas; Jung, Jens; Jaeck, Almut; Hitschold, Thomas; Ebner, Bernd

    2016-04-01

    In a previous study of breast cancer patients, we found changes in cardiac function and size during the early stages of adjuvant trastuzumab (Herceptin(®)) therapy. Here we present a subgroup analysis of this patient cohort. This subgroup received a anthracycline-embedded chemotherapy followed by at least 3 months up to 6 months of adjuvant Herceptin(®) therapy. Twenty-seven female breast cancer patients with Her-2/-neu overexpression were studied using conventional echocardiography and 2D speckle tracking. These methods were done before anthracycline-embedded chemotherapy, before adjuvant trastuzumab therapy, and both 3 and 6 months after the start of the therapy (T3, T6). The LV-EF (Simpson biplane) decreased significantly from before the chemotherapy to after the chemotherapy and further decreased after 3 months of trastuzumab therapy (66.2 ± 1.5 vs. 58.7 ± 1.2 vs. 55.6 ± 1.3 vs. 55.9 ± 1.5 %; p < 0.05). The stroke volume index remained constant after chemotherapy (22.0 ± 0.8 vs. 22.6 ± 1.3 ml/m(2); p = 0.9), but increased significantly during trastuzumab therapy (26.7 ± 1.1 and 27.3 ± 1.0 ml/m(2); p < 0.01). Global longitudinal strain exclusively decreased during chemotherapy (-21.0 ± 0.5 vs. -18.9 ± 0.5 %, p < 0.001). Regional longitudinal strain decreased significantly after chemotherapy in septal, anteroseptal, anterolateral, and apex segments. Mitral valve regurgitation increased during the whole treatment, but especially during trastuzumab. Right ventricular function decreased exclusively during chemotherapy. Anthracycline-embedded chemotherapy in patients with breast cancer led to a decrease in LV function, especially of the septal and anterior segments, and did not worsen during adjuvant trastuzumab treatment.

  2. Differences in Supratentorial Damage of White Matter in Pediatric Survivors of Posterior Fossa Tumors With and Without Adjuvant Treatment as Detected by Magnetic Resonance Diffusion Tensor Imaging

    SciTech Connect

    Rueckriegel, Stefan Mark; Driever, Pablo Hernaiz; Blankenburg, Friederike; Luedemann, Lutz; Henze, Guenter; Bruhn, Harald

    2010-03-01

    Purpose: To elucidate morphologic correlates of brain dysfunction in pediatric survivors of posterior fossa tumors by using magnetic resonance diffusion tensor imaging (DTI) to examine neuroaxonal integrity in white matter. Patients and Methods: Seventeen medulloblastoma (MB) patients who had received surgery and adjuvant treatment, 13 pilocytic astrocytoma (PA) patients who had been treated only with surgery, and age-matched healthy control subjects underwent magnetic resonance imaging on a 3-Tesla system. High-resolution conventional T1- and T2-weighted magnetic resonance imaging and DTI data sets were obtained. Fractional anisotropy (FA) maps were analyzed using tract-based spatial statistics, a part of the Functional MRI of the Brain Software Library. Results: Compared with control subjects, FA values of MB patients were significantly decreased in the cerebellar midline structures, in the frontal lobes, and in the callosal body. Fractional anisotropy values of the PA patients were not only decreased in cerebellar hemispheric structures as expected, but also in supratentorial parts of the brain, with a distribution similar to that in MB patients. However, the amount of significantly decreased FA was greater in MB than in PA patients, underscoring the aggravating neurotoxic effect of the adjuvant treatment. Conclusions: Neurotoxic mechanisms that are present in PA patients (e.g., internal hydrocephalus and damaged cerebellar structures affecting neuronal circuits) contribute significantly to the alteration of supratentorial white matter in pediatric posterior fossa tumor patients.

  3. Detection of sentinel lymph node in breast cancer recurrence may change adjuvant treatment decision in patients with breast cancer recurrence and previous axillary surgery.

    PubMed

    Cordoba, Octavi; Perez-Ceresuela, Francesc; Espinosa-Bravo, Martin; Cortadellas, Tomas; Esgueva, Antonio; Rodriguez-Revuelto, Robert; Peg, Vicente; Reyes, Victoria; Xercavins, Jordi; Rubio, Isabel T

    2014-08-01

    Use of sentinel lymph node dissection in patients with ipsilateral breast cancer recurrence is still controversial. The objective of this study is to evaluate the feasibility of the sentinel lymph node in breast cancer recurrence (SLNBR) and whether the positivity had impact in the adjuvant treatment. Between 2008 and 2012 we performed SLNBR in patients with ipsilateral breast tumor recurrence. We included 53 patients in a prospective study. Forty-three patients (81%) had a previous axillary lymph node dissection (ALND) and ten (19%) had a previous sentinel lymph node biopsy (SLNB). Identification rate after SLNB was 50% and after ALND was 60.5% (p = 0.4). Nine patients (26%) had a positive SLNBR. Adjuvant systemic treatment was given to all the patients with a positive SLNBR and to 23 (85%) with a negative SLNBR (p = 0.29). Six patients (66%) with positive SLNBR and 4 patients (14%) with negative SLNBR underwent radiation therapy (p < 0.01). As conclusions of our study we conclude that sentinel lymph node biopsy in breast tumor recurrence is feasible and significant differences were found in the use of radiation therapy in patients with a positive SLNBR.

  4. Long-term quality of life after intensified multi-modality treatment of oral cancer including intra-arterial induction chemotherapy and adjuvant chemoradiation

    PubMed Central

    Kovács, Adorján F.; Stefenelli, Ulrich; Thorn, Gerrit

    2015-01-01

    Background: Quality of life (QoL) studies are well established when accompanying trials in head and neck cancer, but studies on long-term survivors are rare. Aims: The aim was to evaluate long-term follow-up patients treated with an intensified multi-modality therapy. Setting and Design: Cross-sectional study, tertiary care center. Patients and Methods: A total of 135 oral/oropharyngeal cancer survivors having been treated with an effective four modality treatment (intra-arterial induction chemotherapy, radical surgery, adjuvant radiation, concurrent systemic chemotherapy) filled European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and HN35 questionnaires. Mean distance to treatment was 6.1 (1.3–16.6) years. Results were compared with a reference patient population (EORTC reference manual). In-study group comparison was also carried out. Statistical Analysis: One-sample t-test, Mann–Whitney-test, Kruskal–Wallis analysis. Results: QoL scores of both populations were well comparable. Global health status, cognitive and social functioning, fatigue, social eating, status of teeth, mouth opening and dryness, and sticky saliva were significantly worse in the study population; pain and need for pain killers, cough, need for nutritional support, problems with weight loss and gain were judged to be significantly less. Patients 1-year posttreatment had generally worse scores as compared to patients with two or more years distance to treatment. Complex reconstructive measures and adjuvant (chemo) radiation were main reasons for significant impairment of QoL. Conclusion Subjective disease status of patients following a maximized multi-modality treatment showed an expectable high degree of limitations, but was generally comparable to a reference group treated less intensively, suggesting that the administration of an intensified multi-modality treatment is feasible in terms of QoL/effectivity ratio. PMID:26389030

  5. Utility of PET/CT Imaging Performed Early After Surgical Resection in the Adjuvant Treatment Planning for Head and Neck Cancer

    SciTech Connect

    Shintani, Stephanie A.; Foote, Robert L. Lowe, Val J.; Brown, Paul D.; Garces, Yolanda I.; Kasperbauer, Jan L.

    2008-02-01

    Purpose: To evaluate the utility of positron emission tomography (PET)/computed tomography (CT) early after surgical resection and before postoperative adjuvant radiation therapy. Methods and Materials: We studied a prospective cohort of 91 consecutive patients referred for postoperative adjuvant radiation therapy after complete surgical resection. Tumor histologies included 62 squamous cell and 29 non-squamous cell cancers. Median time between surgery and postoperative PET/CT was 28 days (range, 13-75 days). Findings suspicious for persistent/recurrent cancer or distant metastasis were biopsied. Correlation was made with changes in patient care. Results: Based on PET/CT findings, 24 patients (26.4%) underwent biopsy of suspicious sites. Three patients with suspicious findings did not undergo biopsy because the abnormalities were not easily accessible. Eleven (45.8%) biopsies were positive for cancer. Treatment was changed for 14 (15.4%) patients (11 positive biopsy and 3 nonbiopsied patients) as a result. Treatment changes included abandonment of radiation therapy and switching to palliative chemotherapy or hospice care (4), increasing the radiation therapy dose (6), extending the radiation therapy treatment volume and increasing the dose (1), additional surgery (2), and adding palliative chemotherapy to palliative radiation therapy (1). Treatment for recurrent cancer and primary skin cancer were significant predictors of having a biopsy-proven, treatment-changing positive PET/CT (p < 0.03). Conclusions: Even with an expectedly high rate of false positive PET/CT scans in this early postoperative period, PET/CT changed patient management in a relatively large proportion of patients. PET/CT can be recommended in the postoperative, preradiation therapy setting with the understanding that treatment-altering PET/CT findings should be biopsied for confirmation.

  6. Laparoscopic ovarian treatment in infertile patients with polycystic ovarian syndrome (PCOS): endocrine changes and clinical outcome.

    PubMed

    Liguori, G; Tolino, A; Moccia, G; Scognamiglio, G; Nappi, C

    1996-08-01

    During the years 1991-1994, 97 anovulatory infertile women with polycystic ovarian syndrome (PCOS) were treated with laparoscopic electrocautery of the ovarian surface after they had failed to ovulate under ovarian stimulation. To assess the endocrinological and clinical outcome and in an attempt to determine the mechanism of action, the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), androstenedione, testosterone and dehydroepiandrosterone sulfate (DHEAS) were determined before and after laparoscopic ovarian cautery. Fifty regularly cycling women undergoing laparoscopy for investigation of infertility or tubal ligation served as controls. In patients with PCOS but not in controls, the reduction of androgen levels and normalization of cycle length were highly significant. In contrast, LH and FSH levels rose during the first 2 days after the operation. These results resemble those reported after ovarian wedge resection. Ovulation was obtained in 90% (81 of 90) and pregnancy in 81.1% (73 of 90) of the patients; that increased to 84.4%, including the non-responders (nine patients) treated with clomiphene citrate (CC), after electrocautery. The response to ovarian electrocautery was influenced by body weight, with an ovulation rate of 95-96% in the slim and moderately obese women, decreasing to 81-82% in the really obese ones. When ovulation was established, the pregnancy rate was independent of body weight. However, a striking relationship was detected between smoking habits and pregnancy rate subsequent to ovarian electrocautery, ranging from 24% in smokers to 92% in non-smoking couples. In 30 second-look operations, de novo adhesions were found in 23.3% of the patients (7 of 30). Therefore, ovarian electrocautery is an effective procedure to improve the intraovarian mechanism of selecting a dominant follicle for patients with PCOS in whom initial medical management fails, and it appears to be one of the possible treatments for this

  7. Mastectomy With Immediate Expander-Implant Reconstruction, Adjuvant Chemotherapy, and Radiation for Stage II-III Breast Cancer: Treatment Intervals and Clinical Outcomes

    SciTech Connect

    Wright, Jean L.; Cordeiro, Peter G.; Ben-Porat, Leah; Van Zee, Kimberly J.; Hudis, Clifford; Beal, Kathryn; McCormick, Beryl

    2008-01-01

    Purpose: To determine intervals between surgery and adjuvant chemotherapy and radiation in patients treated with mastectomy with immediate expander-implant reconstruction, and to evaluate locoregional and distant control and overall survival in these patients. Methods and Materials: Between May 1996 and March 2004, 104 patients with Stage II-III breast cancer were routinely treated at our institution under the following algorithm: (1) definitive mastectomy with axillary lymph node dissection and immediate tissue expander placement, (2) tissue expansion during chemotherapy, (3) exchange of tissue expander for permanent implant, (4) radiation. Patient, disease, and treatment characteristics and clinical outcomes were retrospectively evaluated. Results: Median age was 45 years. Twenty-six percent of patients were Stage II and 74% Stage III. All received adjuvant chemotherapy. Estrogen receptor staining was positive in 77%, and 78% received hormone therapy. Radiation was delivered to the chest wall with daily 0.5-cm bolus and to the supraclavicular fossa. Median dose was 5040 cGy. Median interval from surgery to chemotherapy was 5 weeks, from completion of chemotherapy to exchange 4 weeks, and from exchange to radiation 4 weeks. Median interval from completion of chemotherapy to start of radiation was 8 weeks. Median follow-up was 64 months from date of mastectomy. The 5-year rate for locoregional disease control was 100%, for distant metastasis-free survival 90%, and for overall survival 96%. Conclusions: Mastectomy with immediate expander-implant reconstruction, adjuvant chemotherapy, and radiation results in a median interval of 8 weeks from completion of chemotherapy to initiation of radiation and seems to be associated with acceptable 5-year locoregional control, distant metastasis-free survival, and overall survival.

  8. Adjuvant-induced Human Monocyte Secretome Profiles Reveal Adjuvant- and Age-specific Protein Signatures*

    PubMed Central

    Oh, Djin-Ye; Dowling, David J.; Ahmed, Saima; Choi, Hyungwon; Brightman, Spencer; Bergelson, Ilana; Berger, Sebastian T.; Sauld, John F.; Pettengill, Matthew; Kho, Alvin T.; Pollack, Henry J.; Steen, Hanno; Levy, Ofer

    2016-01-01

    Adjuvants boost vaccine responses, enhancing protective immunity against infections that are most common among the very young. Many adjuvants activate innate immunity, some via Toll-Like Receptors (TLRs), whose activities varies with age. Accordingly, characterization of age-specific adjuvant-induced immune responses may inform rational adjuvant design targeting vulnerable populations. In this study, we employed proteomics to characterize the adjuvant-induced changes of secretomes from human newborn and adult monocytes in response to Alum, the most commonly used adjuvant in licensed vaccines; Monophosphoryl Lipid A (MPLA), a TLR4-activating adjuvant component of a licensed Human Papilloma Virus vaccine; and R848 an imidazoquinoline TLR7/8 agonist that is a candidate adjuvant for early life vaccines. Monocytes were incubated in vitro for 24 h with vehicle, Alum, MPLA, or R848 and supernatants collected for proteomic analysis employing liquid chromatography-mass spectrometry (LC-MS) (data available via ProteomeXchange, ID PXD003534). 1894 non-redundant proteins were identified, of which ∼30 - 40% were common to all treatment conditions and ∼5% were treatment-specific. Adjuvant-stimulated secretome profiles, as identified by cluster analyses of over-represented proteins, varied with age and adjuvant type. Adjuvants, especially Alum, activated multiple innate immune pathways as assessed by functional enrichment analyses. Release of lactoferrin, pentraxin 3, and matrix metalloproteinase-9 was confirmed in newborn and adult whole blood and blood monocytes stimulated with adjuvants alone or adjuvanted licensed vaccines with distinct clinical reactogenicity profiles. MPLA-induced adult monocyte secretome profiles correlated in silico with transcriptome profiles induced in adults immunized with the MPLA-adjuvanted RTS,S malaria vaccine (Mosquirix™). Overall, adjuvants such as Alum, MPLA and R848 give rise to distinct and age-specific monocyte secretome profiles

  9. A2A Adenosine Receptors Are Differentially Modulated by Pharmacological Treatments in Rheumatoid Arthritis Patients and Their Stimulation Ameliorates Adjuvant-Induced Arthritis in Rats

    PubMed Central

    Vincenzi, Fabrizio; Padovan, Melissa; Targa, Martina; Corciulo, Carmen; Giacuzzo, Sarah; Merighi, Stefania; Gessi, Stefania; Govoni, Marcello; Borea, Pier Andrea; Varani, Katia

    2013-01-01

    A2A adenosine receptors (ARs) play a key role in the inhibition of the inflammatory process. The purpose of this study was to evaluate the modulation of A2AARs in rheumatoid arthritis (RA) patients after different pharmacological treatments and to investigate the effect of A2AAR stimulation in a rat model of arthritis. We investigated A2AAR density and functionality in RA progression by using a longitudinal study in RA patients before and after methotrexate (MTX), anti-TNFα agents or rituximab treatments. A2AARs were analyzed by saturation binding assays in lymphocytes from RA patients throughout the 24-month study timeframe. In an adjuvant-induced arthritis model in rats we showed the efficacy of the A2AAR agonist, CGS 21680 in comparison with standard therapies by means of paw volume assessment, radiographic and ultrasonographic imaging. Arthritic-associated pain was investigated in mechanical allodynia and thermal hyperalgesia tests. IL-10 release following A2AAR stimulation in lymphocytes from RA patients and in serum from arthritic rats was measured. In lymphocytes obtained from RA patients, the A2AAR up-regulation was gradually reduced in function of the treatment time and the stimulation of these receptors mediated a significant increase of IL-10 production. In the same cells, CGS 21680 did not affected cell viability and did not produced cytotoxic effects. The A2AAR agonist CGS 21680 was highly effective, as suggested by the marked reduction of clinical signs, in rat adjuvant-induced arthritis and associated pain. This study highlighted that A2AAR agonists represent a physiological-like therapeutic alternative for RA treatment as suggested by the anti-inflammatory role of A2AARs in lymphocytes from RA patients. The effectiveness of A2AAR stimulation in a rat model of arthritis supported the role of A2AAR agonists as potential pharmacological treatment for RA. PMID:23326596

  10. Additional treatment of wastewater reduces endocrine disruption in wild fish--a comparative study of tertiary and advanced treatments.

    PubMed

    Baynes, Alice; Green, Christopher; Nicol, Elizabeth; Beresford, Nicola; Kanda, Rakesh; Henshaw, Alan; Churchley, John; Jobling, Susan

    2012-05-15

    Steroid estrogens are thought to be the major cause of feminization (intersex) in wild fish. Widely used wastewater treatment technologies are not effective at removing these contaminants to concentrations thought to be required to protect aquatic wildlife. A number of advanced treatment processes have been proposed to reduce the concentrations of estrogens entering the environment. Before investment is made in such processes, it is imperative that we compare their efficacy in terms of removal of steroid estrogens and their feminizing effects with other treatment options. This study assessed both steroid removal and intersex induction in adult and early life stage fish (roach, Rutilus rutilus). Roach were exposed directly to either secondary (activated sludge process (ASP)), tertiary (sand filtrated (SF)), or advanced (chlorine dioxide (ClO(2)), granular activated charcoal (GAC)) treated effluents for six months. Surprisingly, both the advanced GAC and tertiary SF treatments (but not the ClO(2) treatment) significantly removed the intersex induction associated with the ASP effluent; this was not predicted by the steroid estrogen measurements, which were higher in the tertiary SF than either the GAC or the ClO(2). Therefore our study highlights the importance of using both biological and chemical analysis when assessing new treatment technologies.

  11. First report of a permanent breast {sup 103}Pd seed implant as adjuvant radiation treatment for early-stage breast cancer

    SciTech Connect

    Pignol, Jean-Philippe . E-mail: Jean-Philippe.Pignol@sw.ca; Keller, Brian; Rakovitch, Eileen; Sankreacha, Raxa; Easton, Harry; Que, William

    2006-01-01

    Purpose: A new technique of adjuvant partial breast irradiation using {sup 103}Pd permanent breast seed implants (PBSI) is presented. The procedure is performed in a single 1-hour session under local anesthesia. Methods and Materials: Patients referred to a single institution for adjuvant radiotherapy after lumpectomy for an infiltrating ductal carcinoma {<=}3 cm in diameter, surgical margin {>=}2 mm, no extensive in situ carcinoma, no lymphovascular invasion, and minimal or negative lymph node involvement were offered a PBSI. Results: Between May and December 2004, 31 eligible patients underwent CT scan and ultrasound simulations assessing PBSI feasibility. Fifteen were excluded because of feasibility issues, and 16 received PBSI. A minimal peripheral dose of 90 Gy was prescribed to the planning target volume corresponding to the clinical target volume identified on the CT scan plus a margin of 1 cm. The procedure was well tolerated; 56% of the patients reported no pain during the procedure, and 46% of the patients developed National Cancer Institute Common Toxicity Criteria Grade 1 acute reaction. None experienced toxicity Grade 2 or 3. Conclusions: Permanent breast seed implantation seems feasible and well tolerated on these preliminary clinical data and represents an ultimate step in the reduction of treatment fraction for partial breast irradiation.

  12. The relationship between nuclear factor (NF)-κB family gene expression and prognosis in triple-negative breast cancer (TNBC) patients receiving adjuvant doxorubicin treatment.

    PubMed

    Kim, Ji-Yeon; Jung, Hae Hyun; Ahn, Soomin; Bae, SooYoun; Lee, Se Kyung; Kim, Seok Won; Lee, Jeong Eon; Nam, Seok Jin; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

    2016-08-22

    We investigated gene expression profiles of the NF-κB pathway in patients with triple-negative breast cancer (TNBC) receiving adjuvant chemotherapy to determine the prognostic value of NF-κB pathway genes according to chemotherapeutic regimen. We used the nCounter expression assay to measure expression of 11 genes (NFKB1, NFKB2, RELA, RELB, REL, TP53, FOXC1, TBP, SP1, STAT3 and IRF1 genes) belonging to the NF-κB pathway using mRNA extracted from paraffin-embedded tumor tissues from 203 patients diagnosed with TNBC. Of the 203 patients, 116 were treated with a chemotherapeutic regimen containing doxorubicin. As revealed by the expression profiles of the 11 genes, increased expression of SP1 was associated with poor prognosis in TNBC patients treated with adjuvant doxorubicin chemotherapy (5-year distant recurrence-free survival [5Y DRFS], low vs. high expression [cut-off: median]: 92.3% vs. 71.6%, P = 0.001). In a multivariate Cox regression model, SP1 expression was a useful marker for predicting long-term prognosis in TNBC patients receiving doxorubicin treatment, and we thus suggest that SP1 expression could serve as a prognostic marker in these patients.

  13. Endocrine active chemicals and endocrine disruption in Minnesota streams and lakes: implications for aquatic resources, 1994-2008

    USGS Publications Warehouse

    Lee, Kathy E.; Schoenfuss, Heiko L.; Barber, Larry B.; Writer, Jeff H.; Blazer, Vicki; Keisling, Richard L.; Ferrey, Mark L.

    2010-01-01

    Although these studies indicate that wastewater-treatment plant effluent is a conduit for endocrine active chemicals to surface waters, endocrine active chemicals also were present in surface waters with no obvious wastewater-treatment plant effluent sources. Endocrine active chemicals were detected and indicators of endocrine disruption in fish were measured at numerous sites upstream from discharge of wastewater-treatment plant effluent. These observations indicate that other unidentified sources of endocrine active chemicals exist, such as runoff from land surfaces, atmospheric deposition, inputs from onsite septic systems, or other groundwater sources. Alternatively, some endocrine active chemicals may not yet have been identified or measured. The presence of biological indicators of endocrine disruption in male fish indicates that the fish are exposed to endocrine active chemicals. However indicators of endocrine disruption in male fish does not indicate an effect on fish reproduction or changes in fish populations.

  14. Endocrine oncology in pregnancy.

    PubMed

    Lansdown, A; Rees, D A

    2011-12-01

    Endocrine tumours occur rarely in pregnant women but present clinicians with unique challenges. A high index of suspicion is often required to make a diagnosis since the symptoms and signs associated with many of these tumours, including insulinoma, adrenocortical carcinoma and phaeochromocytoma, mimic those of normal pregnancy or its complications, such as pre-eclampsia. The evidence base which informs management is very limited hence decisions on investigation and therapy must be individualised and undertaken jointly by the multidisciplinary medical team and the patient. The optimal strategy will depend on the nature and stage of the endocrine tumour, gestational stage, treatments available and patient wishes. Thus, surgical intervention, appropriately timed, may be considered in pregnancy for resectable adrenocortical carcinoma or phaeochromocytoma, but delayed until the postpartum period for well-differentiated thyroid cancer. Medical therapy may be required to reduce the drive to tumour growth, control symptoms of hormone excess and to minimise the risks of surgery, anaesthesia or labour.

  15. Bromocriptine and endocrine disorders.

    PubMed

    Spark, R F; Dickstein, G

    1979-06-01

    Bromocriptine, a dopaminergic agonist, has been used to treat many endocrine disorders. In hyperprolactinemia associated with galactorrhea, amenorrhea, oligospermia, and impotence, bromocriptine reduces prolactin levels to normal and allows for satisfactory return of sexual and reproductive function in 90% of patients. In acromegaly, bromocriptine brings about subjective improvement in 75% of patients with reduction in growth-hormone levels to normal in 22% of patients. Bromocriptine has been used in premenstrual tension, functional infertility, Nelson's syndrome, and Cushing's disease with variable benefit. In low doses, side-effects are minimal. In higher doses, digital vasospasm and gastrointestinal bleeding have occurred. Although bromocriptine has been used in a wide variety of endocrine disorders, it appears to be most useful in treatment of male and female infertility associated with hyperprolactinemia.

  16. [Adjuvant hormonal treatment for estrogen receptor-positive breast cancer-a questionnaire survey conducted by Japanese breast cancer society-authorized facilities in Hokkaido].

    PubMed

    Takahashi, Masato; Ohmura, Tousei; Kitada, Masahiro; Kutomi, Goro; Hosoda, Mitsuchika; Masuoka, Hideji; Watanabe, Kenichi; Watanabe, Yoshiki; Yamashita, Hiroko; Hirata, Koichi

    2015-05-01

    According to the Japanese Breast Cancer Society national breast cancer registration, 71.8%of breast cancer cases reported in 2004 and 79.8% of cases reported in 2010 were estrogen receptor(ER)positive. The frequency of ER-positive breast cancer is increasing annually in Japan. Many clinical trials have proven that adjuvant hormonal treatment affects both progression- free survival and overall survival in ER-positive breast cancer cases. However, some clinical questions remain, including those regarding the definition of preoperative hormonal treatment, appropriate dosage period, and therapeutic drug choice. In January 2013, we conducted a questionnaire survey of 53 medical doctors engaged in breast cancer treatment at 15 Japanese Breast Cancer Society-authorized facilities in Hokkaido. This survey included 6 clinical questions about preoperative hormonal treatment, 5 clinical questions about postoperative hormonal treatment for premenopausal breast cancer, and 4 clinical questions about postoperative hormonal treatment for postmenopausal breast cancer. We obtained replies from 35 medical doctors at 27 facilities. The response rate was 66%. We accumulated and analyzed these data. The discussion of questionnaire results in the medical administration field facilitates the sharing of information regarding differences in the approaches of different facilities to breast cancer patients. As a result, standardization of the breast cancer medical treatment system in this area has been accomplished.

  17. Tracking multiple modes of endocrine activity in Australia's largest inland sewage treatment plant and effluent- receiving environment using a panel of in vitro bioassays.

    PubMed

    Roberts, Jenna; Bain, Peter A; Kumar, Anupama; Hepplewhite, Christopher; Ellis, David J; Christy, Andrew G; Beavis, Sara G

    2015-10-01

    Estrogenicity of sewage effluents, and related ecotoxicological effects in effluent-receiving environments, have been widely reported over the last 2 decades. However, relatively little attention has been given to other endocrine pathways that may be similarly disrupted by a growing list of contaminants of concern. Furthermore, the Australian evidence base is limited compared with those of Europe and North America. During a low dilution period in summer, the authors investigated multiple endocrine potencies in Australia's largest inland sewage treatment plant (STP) and the Lower Molonglo/Upper Murrumbidgee effluent-receiving environment. This STP receives 900 L/s of mostly domestic wastewater from a population of 350 000, and contributes a high proportion of total flow in the lower catchment during dry periods. A panel of in vitro receptor-driven transactivation assays were used to detect (anti)estrogenic, (anti) androgenic, (anti)progestagenic, glucocorticoid, and peroxisome-proliferator activity at various stages of the sewage treatment process. Total estrogenic and (anti)androgenic potency was removed after primary and/or secondary treatment; however, total removal efficiency for glucocorticoid potency was poorer (53-66%), and progestagenic potency was found to increase along the treatment train. Estrogenicity was detected in surface waters and bed sediments upstream and downstream of the effluent outfall, at maximum levels 10 times lower than low-hazard thresholds. Glucocorticoid and progestagenic activity were found to persist to 4 km downstream of the effluent outfall, suggesting that future research is needed on these endocrine-disrupting chemical categories in effluent-receiving systems.

  18. Treatment with novel AP-1 and NF-κB inhibitors restores the colonic endocrine cells to normal levels in rats with DSS-induced colitis

    PubMed Central

    EL-SALHY, MAGDY; UMEZAWA, KAZUO

    2016-01-01

    The aim of this study was to determine the effects of two anti-inflammatory agents on the abnormalities in colonic endocrine cells in dextran sodium sulfate (DSS)-induced colitis. Colitis was induced in male Wistar rats (n=45) using DSS; a further 15 rats without colitis were included in a healthy control group. The animals with DSS-induced colitis were randomly divided into 3 treatment groups as follows: i) DSS group, rats were treated with 0.5 ml of 0.5% carboxymethyl cellulose (CMC); ii) DSS-G group, rats were treated with 3-[(dodecyl thiocarbonyl)-methyl]-glutarimide (DTCM-G), a novel activator protein 1 (AP-1) inhibitor, 20 mg/kg in CMC; and iii) DSS-Q group, rats were treated with dehydroxymethylepoxyquinomicin, a nuclear factor κB (NF-κB) inhibitor, 15 mg/kg in CMC. The treatments were administered intraperitoneally, twice daily for 5 days, after which the animals were sacrificed and tissue samples from the colon were immunostained for chromogranin A (CgA), serotonin, peptide YY (PYY), enteroglucagon, pancreatic polypeptide (PP), somatostatin, leukocytes, B/T lymphocytes, B lymphocytes, T lymphocytes, macrophages/monocytes and mast cells. The densities of these endocrine and immune cells were quantified by computer-aided image analysis. The densities of CgA-, serotonin-, PYY- and enteroglucagon-producing cells were significantly higher, and those of PP- and somatostatin-producing cells were significantly lower in the DSS-G, DSS-Q and control groups than in the DSS group. The densities of all the immune cells were lower in the DSS-G, DSS-Q and control groups than in the DSS group. The densities of all endocrine cell types and immune cells in both the DSS groups treated with anti-inflammatory agents were restored to control levels. In conclusion, our data demonstrate that there is an interaction between endocrine and immune cells during inflammation. This interaction with subsequent changes in endocrine cells is responsible for the clinical manifestation of

  19. Treatment with novel AP-1 and NF-κB inhibitors restores the colonic endocrine cells to normal levels in rats with DSS-induced colitis.

    PubMed

    El-Salhy, Magdy; Umezawa, Kazuo

    2016-03-01

    The aim of this study was to determine the effects of two anti-inflammatory agents on the abnormalities in colonic endocrine cells in dextran sodium sulfate (DSS)-induced colitis. Colitis was induced in male Wistar rats (n=45) using DSS; a further 15 rats without colitis were included in a healthy control group. The animals with DSS-induced colitis were randomly divided into 3 treatment groups as follows: i) DSS group, rats were treated with 0.5 ml of 0.5% carboxymethyl cellulose (CMC); ii) DSS‑G group, rats were treated with 3-[(dodecylthiocarbonyl)‑methyl]‑glutarimide (DTCM‑G), a novel activator protein 1 (AP-1) inhibitor, 20 mg/kg in CMC; and iii) DSS‑Q group, rats were treated with dehydroxymethylepoxyquinomicin, a nuclear factor κB (NF-κB) inhibitor, 15 mg/kg in CMC. The treatments were administered intraperitoneally, twice daily for 5 days, after which the animals were sacrificed and tissue samples from the colon were immunostained for chromogranin A (CgA), serotonin, peptide YY (PYY), enteroglucagon, pancreatic polypeptide (PP), somatostatin, leukocytes, B/T lymphocytes, B lymphocytes, T lymphocytes, macrophages/monocytes and mast cells. The densities of these endocrine and immune cells were quantified by computer‑aided image analysis. The densities of CgA-, serotonin-, PYY- and enteroglucagon-producing cells were significantly higher, and those of PP- and somatostatin-producing cells were significantly lower in the DSS‑G, DSS‑Q and control groups than in the DSS group. The densities of all the immune cells were lower in the DSS‑G, DSS‑Q and control groups than in the DSS group. The densities of all endocrine cell types and immune cells in both the DSS groups treated with anti‑inflammatory agents were restored to control levels. In conclusion, our data demonstrate that there is an interaction between endocrine and immune cells during inflammation. This interaction with subsequent changes in endocrine cells is responsible for the

  20. The use of Ginkgo biloba for the prevention of chemotherapy-related cognitive dysfunction in women receiving adjuvant treatment for breast cancer, N00C9

    PubMed Central

    Burger, Kelli; Novotny, Paul J.; Fitch, Tom R.; Kohli, Sadhna; Soori, Gamini; Wilwerding, Mary Beth; Sloan, Jeff A.; Kottschade, Lisa A.; Rowland, Kendrith M.; Dakhil, Shaker R.; Nikcevich, Daniel A.; Loprinzi, Charles L.

    2012-01-01

    Purpose Patients undergoing treatment for cancer often report problems with their cognitive function, which is an essential component of health-related quality of life. Pursuant to this, a two-arm randomized, placebo-controlled, double-blind, phase III clinical trial was conducted to evaluate Ginkgo biloba (EGB 761) for the prevention of chemotherapy-related cognitive dysfunction in patients with breast cancer. Methods Previously chemotherapy naïve women about to receive adjuvant chemotherapy for breast cancer were randomized to receive 60 mg of EGB 761 or a matching placebo twice daily. The study agent was to begin before their second cycle of chemotherapy and to be taken throughout chemotherapy and 1 month beyond completion. The primary measure for cognitive function was the High Sensitivity Cognitive Screen (HSCS), with a secondary measure being the Trail Making Tests (TMT) A and B. Subjective assessment of cognitive function was evaluated by the cognitive subscale of the Perceived Health Scale (PHS) and the Profile of Mood States (POMS). Data were collected at baseline and at intervals throughout and after chemotherapy, up to 24 months after completion of adjuvant treatment. The primary statistical analysis included normalized area under the curve (AUC) comparisons of the HSCS, between the arms. Secondary analyses included evaluation of the other measures of cognition as well as correlational analyses between self-report and cognitive testing. Results One hundred and sixty-six women provided evaluable data. There were no significant differences in AUC up to 12 months on the HSCS between arms at the end of chemotherapy or at any other time point after adjuvant treatment. There were also no significant differences in TMT A or B at any data point. Perceived cognitive functions, as measured by the PHS and confusion/bewilderment subscale of the POMS, were not different between arms at the end of chemotherapy. There was also little correlation between self

  1. Adjuvant analgesics in cancer pain: a review.

    PubMed

    Mitra, Raj; Jones, Stephanie

    2012-02-01

    Adjuvant analgesics (co-analgesics) are medications whose primary indication is the management of a medical condition with secondary effects of analgesia. Cancer pain is multifactorial and often involves inflammatory, nociceptive, and neuropathic pain subtypes. Adjuvant analgesics used in conjunction with opioids have been found to be beneficial in the management of many cancer pain syndromes; however, they are currently underutilized. Antidepressants, anticonvulsants, local anesthetics, topical agents, steroids, bisphosphonates, and calcitonin are all adjuvants which have been shown to be effective in the management of cancer pain syndromes. When utilizing analgesic adjuvants in the treatment of cancer pain, providers must take into account the particular side effect profile of the medication. Ideally, adjuvant analgesics will be initiated at lower dosages and escalated as tolerated until efficacy or adverse effects are encountered.

  2. Breast-Conserving Treatment in the Elderly: Long-Term Results of Adjuvant Hypofractionated and Normofractionated Radiotherapy

    SciTech Connect

    Kirova, Youlia M. Campana, Francois; Savignoni, Alexia; Laki, Fatima; Muresan, Marius; Dendale, Remi; Bollet, Marc A.; Salmon, Remy J.; Fourquet, Alain

    2009-09-01

    Purpose: To evaluate the long-term cause-specific survival (CSS), locoregional recurrence-free survival (LRFS), and metastases-free survival (MFS) in elderly breast cancer patients receiving adjuvant normofractionated (NF) or hypofractionated (HF) radiotherapy (RT). Methods and Materials: Between 1995 and 1999, 367 women aged {>=}70 years with nonmetastatic Stage T1 or T2 tumors were treated by breast-conserving surgery and adjuvant RT at the Institut Curie. They underwent wide tumor excision with or without lymph node dissection followed by RT. They received either a NF-RT schedule, which delivered a total dose of 50 Gy (25 fractions, 5 fractions weekly) to the whole breast, followed by a boost to the tumor bed when indicated, or a HF-RT schedule, which delivered a total dose of 32.5 Gy (five fractions of 6.5 Gy, once weekly) with no subsequent boost. The HF-RT schedule was indicated for the more elderly patients. Results: A total of 317 patients were in the NF-RT group, with 50 in the HF-RT group. The median follow-up was 93 months (range, 9-140). The 5- and 7-year CSS, LRFS, and MFS rates were similar in both groups. The 5-year NF-RT and HF-RT rate was 96% and 95% for CSS, 95% and 94% for LRFS, and 94% and 95% for MFS, respectively. The 7-year NF-RT and HF-RT rate was 93% and 87% for CSS, 93% and 91% for LRFS, and 92% and 93% for MFS, respectively. Conclusion: According to the findings from this retrospective study, the HF-RT schedule is an acceptable alternative to NF-RT for elderly patients. However, large-scale prospective randomized trials are needed to confirm these results.

  3. Non-Specific Immunotherapies and Adjuvants

    MedlinePlus

    ... and Side Effects Treatment Types Immunotherapy Non-specific cancer immunotherapies and adjuvants Non-specific immunotherapies don’t target ... This makes BCG useful as a form of cancer immunotherapy. BCG was one of the earliest immunotherapies used ...

  4. A retrospective study on IVF outcome in patients with anticardiolipin antibody: effects of methylprednisolone plus low-dose aspirin adjuvant treatment.

    PubMed

    Ying, Ying; Zhong, Yi-ping; Zhou, Can-quan; Xu, Yan-wen; Wang, Qiong; Li, Jie; Wu, Hai-tao; Shen, Xiao-ting

    2012-06-01

    Patients undergoing in vitro fertilization-embryo transfer have a high prevalence of anticardiolipin antibody (ACA). However, the relationship between ACA and IVF outcome is still controversial. The aim of the present study was to evaluate the potential effect of anticardiolipin antibody on IVF outcome and determine the role of adjuvant treatment in these ACA positive patients. The study included a total of 116 infertile women (116 IVF-ET cycles) positive for ACA, including 56 women pretreated with methylprednisolone plus low-dose aspirin before IVF (treated ACA+ group) and 60 patients without treatment (untreated ACA+ group). In addition, 518 infertile women (518 IVF-ET cycles) negative for ACA were enroled as controls (ACA- group). The results show that ACA+ patients who did not receive any adjuvant treatment showed a significantly lower fertilization rate, less high-quality embryos, as well as a markedly lower pregnancy rate and implantation rate than controls. Moreover, ACA+ patients who received methylprednisolone plus aspirin achieved significantly higher fertilization, pregnancy and implantation rates than untreated ACA+ patients (FR 69.0%, PR 46.4% and IR 25.4% vs. FR 60.0%, PR 33.3% and IR 17.9%, respectively). The overall IVF results in the treated ACA+ group were comparable to patients negative for ACA (PR 53.9% and IR 32.3%). Thus, while the presence of ACA exerts a detrimental effect on IVF outcome, ACA+ patients have a better outcome if given methylprednisolone for immunosuppression and low-dose aspirin as an anti-thrombotic agent.

  5. Usefulness of hexamethylenetetramine as an adjuvant to radiation and cisplatin in the treatment of solid tumors: its independency of p53 status.

    PubMed

    Masunaga, Shin-ichiro; Tano, Keizo; Nakamura, Jun; Watanabe, Masami; Kashino, Genro; Takahashi, Akihisa; Tanaka, Hiroki; Suzuki, Minoru; Ohnishi, Ken; Kinashi, Yuko; Liu, Yong; Ohnishi, Takeo; Ono, Koji

    2010-01-01

    The usefulness of hexamethylenetetramine as an adjuvant to radiation and cisplatin in the treatment of solid tumors and its dependency on the p53 status of tumor cells were examined. Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53), or with neo vector as a control (SAS/neo), were inoculated subcutaneously into both the hind legs of Balb/cA nude mice. The tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all proliferating (P) cells in the tumors. Then, they received hexamethylenetetramine (HMTA), intraperitoneally or continuously, combined with or without gamma-ray irradiation or cisplatin treatment. Immediately after treatment following HMTA, the response of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The response of the total (= P + Q) tumor cells was determined from the BrdU non-treated tumors. A higher toxicity of HMTA to Q cells than total cells, especially in SAS/neo, was made less clear by continuous administration. There was no apparent difference in the radio- and cisplatin-sensitivity enhancing effects by HMTA combination between SAS/neo and SAS/mp53 tumors, with a slightly greater effect in SAS/mp53. In both SAS/neo and SAS/mp53 tumors, continuous HMTA administration produced higher radio- and cisplatin-sensitivity enhancing effects than intraperitoneal single administration. Therefore, the use of HMTA as an adjuvant to radiation or cisplatin might be promising in curing solid tumors with large fraction of hypoxic cells and also with frequent loss-of-function in p53.

  6. Classical Cyclophosphamide, Methotrexate, and Fluorouracil Chemotherapy Is More Effective in Triple-Negative, Node-Negative Breast Cancer: Results From Two Randomized Trials of Adjuvant Chemoendocrine Therapy for Node-Negative Breast Cancer

    PubMed Central

    Colleoni, Marco; Cole, Bernard F.; Viale, Giuseppe; Regan, Meredith M.; Price, Karen N.; Maiorano, Eugenio; Mastropasqua, Mauro G.; Crivellari, Diana; Gelber, Richard D.; Goldhirsch, Aron; Coates, Alan S.; Gusterson, Barry A.

    2010-01-01

    Purpose Retrospective studies suggest that primary breast cancers lacking estrogen receptor (ER) and progesterone receptor (PR) and not overexpressing human epidermal growth factor receptor 2 (HER2; triple-negative tumors) are particularly sensitive to DNA-damaging chemotherapy with alkylating agents. Patients and Methods Patients enrolled in International Breast Cancer Study Group Trials VIII and IX with node-negative, operable breast cancer and centrally assessed ER, PR, and HER2 were included (n = 2,257). The trials compared three or six courses of adjuvant classical cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without endocrine therapy versus endocrine therapy alone. We explored patterns of recurrence by treatment according to three immunohistochemically defined tumor subtypes: triple negative, HER2 positive and endocrine receptor absent, and endocrine receptor present. Results Patients with triple-negative tumors (303 patients; 13%) were significantly more likely to have tumors > 2 cm and grade 3 compared with those in the HER2-positive, endocrine receptor–absent, and endocrine receptor–present subtypes. No clear chemotherapy benefit was observed in endocrine receptor–present disease (hazard ratio [HR], 0.90; 95% CI, 0.74 to 1.11). A statistically significantly greater benefit for chemotherapy versus no chemotherapy was observed in triple-negative breast cancer (HR, 0.46; 95% CI, 0.29 to 0.73; interaction P = .009 v endocrine receptor–present disease). The magnitude of the chemotherapy effect was lower in HER2-positive endocrine receptor–absent disease (HR, 0.58; 95% CI, 0.29 to 1.17; interaction P = .24 v endocrine receptor–present disease). Conclusion The magnitude of benefit of CMF chemotherapy is largest in patients with triple-negative, node-negative breast cancer. PMID:20458051

  7. Endocrine disrupting alkylphenolic chemicals and other contaminants in wastewater treatment plant effluents, urban streams, and fish in the Great Lakes and Upper Mississippi River Regions

    USGS Publications Warehouse

    Barber, Larry B.; Loyo-Rosales, Jorge E.; Rice, Clifford P.; Minarik, Thomas A.; Oskouie, Ali K.

    2015-01-01

    Urban streams are an integral part of the municipal water cycle and provide a point of discharge for wastewater treatment plant (WWTP) effluents, allowing additional attenuation through dilution and transformation processes, as well as a conduit for transporting contaminants to downstream water supplies. Domestic and commercial activities dispose of wastes down-the-drain, resulting in wastewater containing complex chemical mixtures that are only partially removed during treatment. A key issue associated with WWTP effluent discharge into streams is the potential to cause endocrine disruption in fish. This study provides a long-term (1999-2009) evaluation of the occurrence of alkylphenolic endocrine disrupting chemicals (EDCs) and other contaminants discharged from WWTPs into streams in the Great Lakes and Upper Mississippi River Regions (Indiana, Illinois, Michigan, Minnesota, and Ohio). The Greater Metropolitan Chicago Area Waterways, Illinois, were evaluated to determine contaminant concentrations in the major WWTP effluents and receiving streams, and assess the behavior of EDCs from their sources within the sewer collection system, through the major treatment unit processes at a WWTP, to their persistence and transport in the receiving stream. Water samples were analyzed for alkylphenolic EDCs and other contaminants, including 4-nonylphenol (NP), 4-nonylphenolpolyethoxylates (NPEO), 4-nonylphenolethoxycarboxylic acids (NPEC), 4-tert-octylphenol (OP), 4-tert-octylphenolpolyethoxylates (OPEO), bisphenol A, triclosan, ethylenediaminetetraacetic acid (EDTA), and trace elements. All of the compounds were detected in all of the WWTP effluents, with EDTA and NPEC having the greatest concentrations. The compounds also were detected in the WWTP effluent dominated rivers. Multiple fish species were collected from river and lake sites and analyzed for NP, NPEO, NPEC, OP, and OPEO. Whole-body fish tissue analysis indicated widespread occurrence of alkylphenolic compounds

  8. Endocrine disrupting alkylphenolic chemicals and other contaminants in wastewater treatment plant effluents, urban streams, and fish in the Great Lakes and Upper Mississippi River Regions.

    PubMed

    Barber, Larry B; Loyo-Rosales, Jorge E; Rice, Clifford P; Minarik, Thomas A; Oskouie, Ali K

    2015-06-01

    Urban streams are an integral part of the municipal water cycle and provide a point of discharge for wastewater treatment plant (WWTP) effluents, allowing additional attenuation through dilution and transformation processes, as well as a conduit for transporting contaminants to downstream water supplies. Domestic and commercial activities dispose of wastes down-the-drain, resulting in wastewater containing complex chemical mixtures that are only partially removed during treatment. A key issue associated with WWTP effluent discharge into streams is the potential to cause endocrine disruption in fish. This study provides a long-term (1999-2009) evaluation of the occurrence of alkylphenolic endocrine disrupting chemicals (EDCs) and other contaminants discharged from WWTPs into streams in the Great Lakes and Upper Mississippi River Regions (Indiana, Illinois, Michigan, Minnesota, and Ohio). The Greater Metropolitan Chicago Area Waterways, Illinois, were evaluated to determine contaminant concentrations in the major WWTP effluents and receiving streams, and assess the behavior of EDCs from their sources within the sewer collection system, through the major treatment unit processes at a WWTP, to their persistence and transport in the receiving stream. Water samples were analyzed for alkylphenolic EDCs and other contaminants, including 4-nonylphenol (NP), 4-nonylphenolpolyethoxylates (NPEO), 4-nonylphenolethoxycarboxylic acids (NPEC), 4-tert-octylphenol (OP), 4-tert-octylphenolpolyethoxylates (OPEO), bisphenol A, triclosan, ethylenediaminetetraacetic acid (EDTA), and trace elements. All of the compounds were detected in all of the WWTP effluents, with EDTA and NPEC having the greatest concentrations. The compounds also were detected in the WWTP effluent dominated rivers. Multiple fish species were collected from river and lake sites and analyzed for NP, NPEO, NPEC, OP, and OPEO. Whole-body fish tissue analysis indicated widespread occurrence of alkylphenolic compounds

  9. Histologic evaluation of the depth of necrosis produced by argon beam coagulation: implications for use as adjuvant treatment of bone tumors.

    PubMed

    Heck, Robert K; Pope, Wood D; Ahn, Jae I; Smith, Richard A; Webber, Bruce L

    2009-01-01

    Argon beam coagulation (ABC) has been advocated as adjuvant treatment after curettage of aggressive benign bone tumors. This study was done to evaluate the depth of necrosis in cancellous bone treated with ABC. A 6-month-old pig was sacrificed and 20 1.5-cm cortical windows were created in the metaphyseal areas of the humeri, femora, and tibiae, exposing the underlying cancellous bone. The defects were randomly assigned to four groups: A, control; B, ABC at 50 W; C, 100 W; and D, 150 W. Histologic evaluation determined the depth of necrosis at each setting: A, 0.1 +/- 0.1 mm; B, 1.0 +/- 0.5 mm; C, 2.9 +/- 1.0 mm; and D, 4.2 +/- 0.7 mm. There were statistically significant differences between each of the experimental groups and the control (p < .0001), between groups B and C (p < .0001), and groups C and D (p = .0002).

  10. Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up.

    PubMed

    Finocchiaro, L M E; Glikin, G C

    2012-12-01

    We present here the updated results after 9 years of the beginning of a trial on canine patients with malignant melanoma. This surgery adjuvant approach combined local suicide gene therapy with a subcutaneous vaccine composed by tumor cells extracts and xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. Toxicity was absent or minimal in all patients (0≤VCOG-CTCAE grade≤1). With respect to surgery-treated controls (ST), the complete surgery (CS) arm of this combined treatment (CT) significantly increased the fraction of local disease-free patients from 13 to 81% and distant metastases free from 32 to 84%. Even though less effective than the CS arm, the partial surgery (PS) arm of this CT was significantly better controlling the disease than only surgery (14% while PS-ST: 0%, P<0.01 and CS-ST: 5%, P<0.05). In addition, CT produced a significant sevenfold (CS) and threefold (PS) increase in overall survival. The CS-CT arm significantly improved both CS-ST metastasis-free- and melanoma overall survival from 99 days (respective ranges: 11-563 and 10-568) to >2848 days (81-2848 and 35-2848). Thus, more of 50% of our CT patients died of melanoma unrelated causes, transforming a lethal disease into a chronic one. Finally, surgery adjuvant CT delayed or prevented post-surgical recurrence and distant metastasis, significantly improved disease-free and overall survival maintaining the quality of life. Long-term safety and efficacy of this treatment are supported by the high number of CT patients (283) and extensive follow-up (>9 years). The successful clinical outcome encourages the further translation of similar approaches to human gene therapy trials.

  11. Endocrine Disruptors

    PubMed Central

    2015-01-01

    Law and science combine in the estimation of risks from endocrine disruptors (EDs) and actions for their regulation. For both, dose–response models are the causal link between exposure and probability (or percentage change) of adverse response. The evidence that leads to either regulations or judicial decrees is affected by uncertainty and limited knowledge, raising difficult policy issues that we enumerate and discuss. In the United States, some courts have dealt with EDs, but causation based on animal studies has been a stumbling block for plaintiffs seeking compensation, principally because those courts opt for epidemiological evidence. The European Union (EU) has several regulatory tools and ongoing research on the risks associated with bisphenol A, under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulation and other regulations or directives. The integration of a vast (in kind and in scope) number of research papers into a statement of causation for either policy or to satisfy legal requirements, in both the United States and the EU, relies on experts. We outline the discursive dilemma and issues that may affect consensus-based results and a Bayesian causal approach that accounts for the evolution of information, yielding both value of information and flexibility associated with public choices. PMID:26740809

  12. Altered mental status and endocrine diseases.

    PubMed

    Park, Elizabeth; Abraham, Michael K

    2014-05-01

    Although the altered mental status is a common presentation in the emergency department, altered mental status caused by endocrine emergencies is rare. The altered patient could have an endocrine cause that can quickly improve with appropriate diagnosis and interventions. When dealing with limited information and an obtunded patient, it is important to have a broad differential diagnosis, pick up on the physical examination findings, and evaluate laboratory abnormalities that could suggest an underlying endocrine emergency. This article outlines the findings and provides a description of altered patients with endocrine emergencies to facilitate the diagnosis and treatment in the emergency department.

  13. A(2A) adenosine receptors are differentially modulated by pharmacological treatments in rheumatoid arthritis patients and their stimulation ameliorates adjuvant-induced arthritis in rats.

    PubMed

    Vincenzi, Fabrizio; Padovan, Melissa; Targa, Martina; Corciulo, Carmen; Giacuzzo, Sarah; Merighi, Stefania; Gessi, Stefania; Govoni, Marcello; Borea, Pier Andrea; Varani, Katia

    2013-01-01

    A(2A) adenosine receptors (ARs) play a key role in the inhibition of the inflammatory process. The purpose of this study was to evaluate the modulation of A(2A)ARs in rheumatoid arthritis (RA) patients after different pharmacological treatments and to investigate the effect of A(2A)AR stimulation in a rat model of arthritis. We investigated A(2A)AR density and functionality in RA progression by using a longitudinal study in RA patients before and after methotrexate (MTX), anti-TNFα agents or rituximab treatments. A(2A)ARs were analyzed by saturation binding assays in lymphocytes from RA patients throughout the 24-month study timeframe. In an adjuvant-induced arthritis model in rats we showed the efficacy of the A(2A)AR agonist, CGS 21680 in comparison with standard therapies by means of paw volume assessment, radiographic and ultrasonographic imaging. Arthritic-associated pain was investigated in mechanical allodynia and thermal hyperalgesia tests. IL-10 release following A(2A)AR stimulation in lymphocytes from RA patients and in serum from arthritic rats was measured. In lymphocytes obtained from RA patients, the A(2A)AR up-regulation was gradually reduced in function of the treatment time and the stimulation of these receptors mediated a significant increase of IL-10 production. In the same cells, CGS 21680 did not affected cell viability and did not produced cytotoxic effects. The A(2A)AR agonist CGS 21680 was highly effective, as suggested by the marked reduction of clinical signs, in rat adjuvant-induced arthritis and associated pain. This study highlighted that A(2A)AR agonists represent a physiological-like therapeutic alternative for RA treatment as suggested by the anti-inflammatory role of A(2A)ARs in lymphocytes from RA patients. The effectiveness of A(2A)AR stimulation in a rat model of arthritis supported the role of A(2A)AR agonists as potential pharmacological treatment for RA.

  14. Three-Dimensional Non-Coplanar Conformal Radiotherapy Yields Better Results Than Traditional Beam Arrangements for Adjuvant Treatment of Gastric Cancer

    SciTech Connect

    Soyfer, Viacheslav Corn, Benjamin W.; Melamud, Alex B.S.; Alani, Shlomi; Tempelhof, Haim; Agai, Reuben; Shmueli, Anat; Figer, Arie; Kovner, Felix

    2007-10-01

    Purpose: The current standard of adjuvant treatment for gastric cancer after curative resection is concurrent administration of radiotherapy and 5-fluorouracil-based chemotherapy. The radiation fields are often arranged as anterioposterior-posteroanterior opposed parallel fields with general recommendations for sparing at least two-thirds of one kidney. We investigated whether a better radiation distribution would be achievable with three-dimensional conformal approaches compared with the classic anterioposterior-posteroanterior fields. Methods and Materials: A total of 19 patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a non-coplanar four-field arrangement. In each case, parallel planning using an anterioposterior-posteroanterior arrangement and a four-field 'box' was performed, and the generated plans were subsequently compared for coverage of target volumes and doses to irradiated organs next to the tumor bed. A separate analysis was performed for kidneys exposed to greater and lower doses in each patient. The mean radiation dose and percentage of kidney volume receiving a dose >20 Gy were registered. Statistical analysis was performed using the two-tailed t test. Results: The clinical target volume was adequately covered in all three plans. In the greater-dose kidney group, all the differences were statistically significant with a benefit for the three-dimensional plan. In the lower-dose kidney group, the differences in the mean radiation dose did not reach the level of statistical significance, and the differences in the kidney volume receiving a dose >20 Gy showed a statistically significant benefit for the three-dimensional plan. Conclusion: Non-coplanar three-dimensional-based conformal planning for postoperative radiotherapy for gastric cancer provided the best results regarding kidney and spinal cord exposure with adequate clinical target volume coverage. This technique was readily implemented in clinical

  15. Genomic Analysis Reveals That Immune Function Genes Are Strongly Linked to Clinical Outcome in the North Central Cancer Treatment Group N9831 Adjuvant Trastuzumab Trial

    PubMed Central

    Perez, Edith A.; Thompson, E. Aubrey; Ballman, Karla V.; Anderson, S. Keith; Asmann, Yan W.; Kalari, Krishna R.; Eckel-Passow, Jeanette E.; Dueck, Amylou C.; Tenner, Kathleen S.; Jen, Jin; Fan, Jian-Bing; Geiger, Xochiquetzal J.; McCullough, Ann E.; Chen, Beiyun; Jenkins, Robert B.; Sledge, George W.; Winer, Eric P.; Gralow, Julie R.; Reinholz, Monica M.

    2015-01-01

    Purpose To develop a genomic signature that predicts benefit from trastuzumab in human epidermal growth factor receptor 2–positive breast cancer. Patients and Methods DASL technology was used to quantify mRNA in samples from 1,282 patients enrolled onto the Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer (North Central Cancer Treatment Group N9831 [NCCTG-N9831]) adjuvant trastuzumab trial. Cox proportional hazard ratios (HRs), adjusted for significant clinicopathologic risk factors, were used to determine the association of each gene with relapse-free survival (RFS) for 433 patients who received chemotherapy alone (arm A) and 849 patients who received chemotherapy plus trastuzumab (arms B and C). Network and pathway analyses were used to identify key biologic processes linked to RFS. The signature was built by using a voting scheme. Results Network and functional ontology analyses suggested that increased RFS was linked to a subset of immune function genes. A voting scheme model was used to define immune gene enrichment based on the expression of any nine or more of 14 immune function genes at or above the 0.40 quantile for the population. This model was used to identify immune gene–enriched tumors in arm A and arms B and C. Immune gene enrichment was linked to increased RFS in arms B and C (HR, 0.35; 95% CI, 0.22 to 0.55; P < .001), whereas arm B and C patients who did not exhibit immune gene enrichment did not benefit from trastuzumab (HR, 0.89; 95% CI, 0.62 to 1.28; P = .53). Enriched immune function gene expression as defined by our predictive signature was not associated with increased RFS in arm A (HR, 0.90; 95% CI, 0.60 to 1.37; P = .64). Conclusion Increased expression of a subset of immune function genes may provide a means of predicting benefit from adjuvant trastuzumab. PMID:25605861

  16. HER2 amplification level is not a prognostic factor for HER2-positive breast cancer with trastuzumab-based adjuvant treatment: a systematic review and meta-analysis

    PubMed Central

    Xu, Qian-Qian; Pan, Bo; Wang, Chang-Jun; Zhou, Yi-Dong; Mao, Feng; Lin, Yan; Guan, Jing-Hong; Shen, Song-Jie; Zhang, Xiao-Hui; Xu, Ya-Li; Zhong, Ying; Wang, Xue-Jing; Zhang, Yan-Na; Sun, Qiang

    2016-01-01

    Background Trastuzumab-based therapy is a standard, targeted treatment for HER2-positive breast cancer in the adjuvant setting. However, patients do not benefit equally from it and the association between HER2 amplification level and patients' survival remains controversial. A systematic review and meta-analysis was conducted by incorporating all available evidence to evaluate the association between disease free survival (DFS) and HER2 amplification level. Results Three cohort studies involving 1360 HER2-positive breast cancer patients stratified by HER2 amplification magnitude were eligible for meta-analysis. The combined HRs for DFS were 1.05 (95% CI: 0.80−1.36, p = 0.74) and 0.97 (95% CI: 0.73−1.29, p = 0.83) for HER2 gene copy number (GCN) and HER2/CEP 17 ratio. No evidence of heterogeneity or public bias was found. Methods Databases including PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL), were searched for eligible literature. HER2 amplification level was evaluated by fluorescence in situ hybridization (FISH) in terms of gene copy number (GCN) and HER2/CEP17 ratio. Hazard ratios (HRs) for DFS with 95% confidence interval (CI) according to the amplification level of HER2 were extracted. The outcomes were synthesized based on a fixed-effects model. Conclusions HER2 amplification level is not a prognostic factor for HER2-positive breast cancer with trastuzumab-based targeted therapy in the clinical adjuvant setting. PMID:27566580

  17. Regulation of the CCN genes by vitamin D: A possible adjuvant therapy in the treatment of cancer and fibrosis.

    PubMed

    Piszczatowski, Richard T; Lents, Nathan H

    2016-10-01

    The CCN family is composed of six cysteine-rich, modular, and conserved proteins whose functions span a variety of tissues and include cell proliferation, adhesion, angiogenesis, and wound healing. Roles for the CCN proteins throughout the entire body including the skin, kidney, brain, blood vessels, hematopoietic compartment and others, are continuously being elucidated. Likewise, an understanding of the regulation of this important gene family is constantly becoming clearer, through identification of transcription factors that directly activate, repress, or respond to upstream cell signaling pathways, as well as other forms of gene expression control. Vitamin D (1,25-dihydroxyvitamin D3 or calcitriol), a vitamin essential for numerous biological processes, acts as a potent gene expression modulator. The regulation of the CCN gene family members by calcitriol has been described in many contexts. Here, we provide a concise and thorough overview of what is known about calcitriol and its regulation of the CCN genes, and argue that its regulation is of physiological importance in a wide breadth of tissues in which CCN genes function. In addition, we highlight the effects of vitamin D on CCN gene expression in the setting of two common pathologic conditions, fibrosis and cancer, and propose that the therapeutic effects of vitamin D3 described in these disease states may in part be attributable to CCN gene modulation. As vitamin D is perfectly safe in a wide range of doses and already showing promise as an adjuvant therapeutic agent, a deeper understanding of its control of CCN gene expression may have profound implications in clinical management of disease.

  18. Isolated Lung Perfusion as an Adjuvant Treatment of Colorectal Cancer Lung Metastases: A Preclinical Study in a Pig Model

    PubMed Central

    Pagès, Pierre-Benoit; Facy, Olivier; Mordant, Pierre; Ladoire, Sylvain; Magnin, Guy; Lokiec, Francois; Ghiringhelli, Francois; Bernard, Alain

    2013-01-01

    Background The lung is a frequent site of colorectal cancer (CRC) metastases. After surgical resection, lung metastases recurrences have been related to the presence of micrometastases, potentially accessible to a high dose chemotherapy administered via adjuvant isolated lung perfusion (ILP). We sought to determine in vitro the most efficient drug when administered to CRC cell lines during a short exposure and in vivo its immediate and delayed tolerance when administered via ILP. Methods First, efficacy of various cytotoxic molecules against a panel of human CRC cell lines was tested in vitro using cytotoxic assay after a 30-minute exposure. Then, early (operative) and delayed (1 month) tolerance of two concentrations of the molecule administered via ILP was tested on 19 adult pigs using hemodynamic, biological and histological criteria. Results In vitro, gemcitabine (GEM) was the most efficient drug against selected CRC cell lines. In vivo, GEM was administered via ILP at regular (20 µg/ml) or high (100 µg/ml) concentrations. GEM administration was associated with transient and dose-dependant pulmonary vasoconstriction, leading to a voluntary decrease in pump inflow in order to maintain a stable pulmonary artery pressure. After this modulation, ILP using GEM was not associated with any systemic leak, systemic damage, and acute or delayed histological pulmonary toxicity. Pharmacokinetics studies revealed dose-dependant uptake associated with heterogenous distribution of the molecule into the lung parenchyma, and persistent cytotoxicity of venous effluent. Conclusions GEM is effective against CRC cells even after a short exposure. ILP with GEM is a safe and reproducible technique. PMID:23527205

  19. Genetic Predictors of Taxane-induced Neurotoxicity in a SWOG Phase III Intergroup Adjuvant Breast Cancer Treatment Trial (S0221)

    PubMed Central

    Sucheston, Lara E.; Zhao, Hua; Yao, Song; Zirpoli, Gary; Liu, Song; Barlow, William E.; Budd, G. Thomas; Hershman, Dawn L.; Davis, Warren; Ciupak, Gregory L.; Stewart, James A.; Isaacs, Claudine; Hobday, Timothy J.; Salim, Muhammad; Hortobagyi, Gabriel N.; Gralow, Julie R.; Livingston, Robert B.; Albain, Kathy S.; Hayes, Daniel F.; Ambrosone, Christine B.

    2012-01-01

    Purpose We assessed SNPS in the Fanconi Anemia (FA)/BRCA pathway in women being was taxanes for breast cancer in an effort to find a prognostic biomarker for neurological toxicities, which while improve survival remain a debilitating outcome. Patients and Methods We used data and samples (n=888) from SWOG0221, a phase III adjuvant trial of 4 dose/schedules of cyclophosphamide (C), doxorubicin (A) and paclitaxel (T) for high risk breast cancer. The relationship of SNPs in the (FA)/BRCA pathway with risk grade 3/4 neurotoxicities. In a separate cohort we measured the correlation of significant SNPs in this pathway with corresponding gene expression. Results No associations between SNPs in BRCA1 and taxane-induced neuropathy was found. For FANCD2, significant associations between 4 (out of 20) SNPs and neurological toxicities, with risk estimates approaching 2. Two FANCD2 haplotypes were also found to be significantly associated with neurological toxicity, increasing the odds in the overall population 1.8 (95% confidence interval (CI) 1.3–2.5) and 1.7 (95% CI, 1.2–2.4) fold. Although numbers were small, there appeared to be a specific African-American haplotype that was associated with an almost 3-fold increase in risk of neurological toxicity. Expression analyses revealed that significant FANCD2 SNPs were associated with FANCD2 expression levels (p=0.03) Conclusion SNPs in FANCD2, were associated with a 70 to 80% increase in the odds of grade 3/4 neurological toxicities and increased expression of the gene. If replicated, women with these genotypes should be closely monitored for toxicities, and could be targeted for preventive measures or alternative therapeutic approaches. PMID:21766209

  20. Oral Curcumin (Meriva) Is Effective as an Adjuvant Treatment and Is Able to Reduce IL-22 Serum Levels in Patients with Psoriasis Vulgaris

    PubMed Central

    Bonciolini, Veronica; Volpi, Walter; Del Bianco, Elena; Caproni, Marzia

    2015-01-01

    Curcumin is a complementary therapy that may be helpful for the treatment of psoriasis due to its anti-inflammatory, antiangiogenic, antioxidant, and antiproliferative effects. In the present study we performed a randomized, double-blind, placebo-controlled clinical trial to assess the effectiveness of a bioavailable oral curcumin in the treatment of psoriasis. Sixty-three patients with mild-to-moderate psoriasis vulgaris (PASI < 10) were randomly divided into two groups treated with topical steroids and Meriva, a commercially available lecithin based delivery system of curcumin, at 2 g per day (arm 1), or with topical steroids alone (arm 2), both for 12 weeks. At the beginning (T0) and at the end of the therapy (T12), clinical assessment and immunoenzymatic analysis of the serum levels of IL-17 and IL-22 were performed. At T12, both groups achieved a significant reduction of PASI values that, however, was higher in patients treated with both topical steroids and oral curcumin than in patients treated only with topical steroids. Moreover, IL-22 serum levels were significantly reduced in patients treated with oral curcumin. In conclusion, curcumin was demonstrated to be effective as an adjuvant therapy for the treatment of psoriasis vulgaris and to significantly reduce serum levels of IL-22. PMID:26090395

  1. Adjuvant Hormonal Therapy in Women with Early-stage Breast Cancer.

    PubMed

    Lumachi, Franco; Santeufemia, Davide A; Fadda, Giovanni M; Tozzoli, Renato; Chiara, Giordano B; Basso, Stefano M M

    2016-01-01

    For decades, adjuvant hormonal therapy has become the standard treatment of patients with estrogen receptor-positive breast cancer. Currently, the drugs available are GnRH agonists, selective estrogen receptor modulators, and aromatase inhibitors. The use of GnRH agonists represents a potentially reversible treatment that can restore ovarian function after chemotherapy. In premenopausal women, systemic therapy based on selective estrogen receptor modulators administration (e.g., tamoxifen) usually represents the standard adjuvant treatment. There are not sufficient data to recommend the routine addition of GnRH agonists to other endocrine therapies. In postmenopausal women, the disease-free survival was significantly prolonged in patients treated with aromatase inhibitor compared with those treated with tamoxifen, but the survival benefit was modest. Better results were obtained when the two drugs were administered sequentially. According to the ASCO guidelines, after 5 years of tamoxifen treatment, either tamoxifen or aromatase inhibitors therapy should be suggested for an additional 5 years. Unfortunately, most adverse events are consistent with estrogen deprivation and are common to all therapies, and the cumulative toxicity causes discontinuation and nonadherence to therapy in up to 50% of patients. Switching tamoxifen to an aromatase inhibitor may reduce adverse event incidence. Molecular-targeted therapy is useful in patients with advanced, relapsed or hormonal therapy-resistant tumors, usually as second- or third-line treatment. These drugs are usually added to aromatase inhibitors; however, currently, they have not yet been used in patients with early breast cancer.

  2. Trends in the Utilization of Adjuvant Vaginal Cuff Brachytherapy and/or External Beam Radiation Treatment in Stage I and II Endometrial Cancer: A Surveillance, Epidemiology, and End-Results Study

    SciTech Connect

    Patel, Mehul K.; Cote, Michele L.; Ali-Fehmi, Rouba; Buekers, Thomas; Munkarah, Adnan R.; Elshaikh, Mohamed A.

    2012-05-01

    Purpose: The optimal adjuvant radiation treatment for endometrial carcinoma (EC) remains controversial. Adjuvant vaginal cuff brachytherapy (VB) has emerged as an increasingly common treatment modality. However, the time trends for using VB, external beam radiation therapy (EBRT), or combined therapy (VB+EBRT) have not been well characterized. We therefore examined the utilization trends of VB, EBRT, and VB+EBRT for adjuvant RT in International Federation of Gynecologic Oncology (FIGO) stage I and II EC over time. Methods and Materials: We evaluated treatment patterns for 48,122 patients with EC diagnosed between January 1995 and December 2005, using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) public use database. Chi-squared tests were used to assess differences by radiation type (VB, EBRT, and VB+EBRT) and various demographic and clinical variables. Results: Analyses were limited to 9,815 patients (20.4%) with EC who met the inclusion criteria. Among women who received adjuvant RT, the proportion receiving VB increased yearly (12.9% in 1995 compared to 32.8% in 2005 (p < 0.0001). The increasing use of VB was proportional to the decreasing use of EBRT (56.1% in 1995 to 45.8% in 2005; p < 0.0001) and VB+EBRT (31.0% in 1995 to 21.4% in 2005; p < 0.001). Conclusions: This population-based report demonstrates an increasing trend in the use of VB in the adjuvant setting after hysterectomy for treatment of women with FIGO stage I-II EC. VB alone appears to be replacing pelvic EBRT and VB+EBRT therapy in the management of stage I-II EC.

  3. Luminal breast cancer: from biology to treatment.

    PubMed

    Ignatiadis, Michail; Sotiriou, Christos

    2013-09-01

    Oestrogen receptor (ER)-positive--or luminal--tumours represent around two-thirds of all breast cancers. Luminal breast cancer is a highly heterogeneous disease comprising different histologies, gene-expression profiles and mutational patterns, with very varied clinical courses and responses to systemic treatment. Despite adjuvant endocrine therapy and chemotherapy treatment for patients at high risk of relapse, both early and late relapses still occur, a fact that highlights the unmet medical needs of these patients. Ongoing research aims to identify those patients who can be spared adjuvant chemotherapy and who will benefit from extended adjuvant hormone therapy. This research also aims to explore the role of adjuvant bisphosphonates, to interrogate new agents for targeting minimal residual disease, and to address endocrine resistance. Data from next-generation sequencing studies have given us new insight into the biology of luminal breast cancer and, together with advances in preclinical models and the availability of newer targeted agents, have led to the testing of rationally chosen combination treatments in clinical trials. However, a major challenge will be to make sense of the large amount of patient genomic data that is becoming increasingly available. This analysis will be critical to our understanding how intertumour and intratumour heterogeneity can influence treatment response and resistance.

  4. Second non-breast primary cancer following adjuvant therapy for early breast cancer: A report from the International Breast Cancer Study Group

    PubMed Central

    Gianni, Lorenzo; Gelber, Shari; Ravaioli, Alberto; Price, Karen N.; Panzini, Ilaria; Fantini, Manuela; Castiglione-Gertsch, Monica; Pagani, Olivia; Simoncini, Edda; Gelber, Richard D.; Coates, Alan S.; Goldhirsch, Aron

    2009-01-01

    The incidence of second non-breast primary cancer following adjuvant treatment was evaluated using data from patients enrolled from 1978 to 1999 in four International Breast Cancer Study Group (IBCSG) trials. The occurrence of these tumours as sites of first failure was assessed separately for two treatment comparisons: toremifene versus tamoxifen for five years in 1035 patients in IBCSG Trials 12-93 and 14-93 with a median follow-up of eight years and endocrine therapy (toremifene or tamoxifen) versus chemoendocrine therapy (CMF or AC plus toremifene or tamoxifen) in 1731 patients from IBCSG Trials III, VII and 12-93, with a combined median follow-up of 14 years. No significant differences in second non-breast primary tumours were observed in either comparison. In particular the incidences of second primary uterine tumours with toremifene and tamoxifen were similar and no significant increase of secondary leukaemias was observed with chemoendocrine therapy compared with endocrine therapy. PMID:19062268

  5. Camel milk as an adjuvant therapy for the treatment of type 1 diabetes: verification of a traditional ethnomedical practice.

    PubMed

    Mohamad, Ragaa Hosny; Zekry, Zekry Khalid; Al-Mehdar, Hussain A; Salama, Omar; El-Shaieb, Siad Ebrahim; El-Basmy, Amany A; Al-said, Mohamad Gamil Abdel Monem; Sharawy, Sabry Mohamed

    2009-04-01

    There is a traditional belief in the Middle East that regular consumption of camel milk may aid in prevention and control of diabetes. The aim of this work was to evaluate the efficacy of camel milk as an adjuvant therapy in young type 1 diabetics. This 16-week randomized study enrolled 54 type 1 diabetic patients (average age 20 years) selected from those attending the outpatient diabetes clinic of the Menofia University Hospital, affiliated with Egypt's National Cancer Institute. Subjects were randomly divided into two groups of 27 patients: one received usual management (diet, exercise, and insulin), whereas the other received 500 mL of camel milk daily in addition to standard management. A control group of 10 healthy subjects was also assessed. The following parameters were evaluated at baseline and at 4 and 16 weeks: hemoglobin A1c (HbA1c), human C-peptide, lipid profile, serum insulin, anti-insulin antibodies, creatinine clearance, albumin in 24-hour urine, body mass index, and Diabetes Quality of Life score. The following parameters were significantly different between the usual-management group versus the camel milk group after 16 weeks: fasting blood sugar (227.2 +/- 17.7 vs. 98.9 +/- 16.2 mg/dL), HbA1c (9.59 +/- 2.05[%] vs. 7.16 +/- 1.84[%]), serum anti-insulin antibodies (26.20 +/- 7.69 vs. 20.92 +/- 5.45 microU/mL), urinary albumin excretion (25.17 +/- 5.43 vs. 14.54 +/- 5.62 mg/dL/24 hours), daily insulin dose (48.1 +/- 6.95 vs. 23 +/- 4.05 units), and body mass index (18.43 +/- 3.59 vs. 24.3 +/- 2.95 kg/m(2)). Most notably, C-peptide levels were markedly higher in the camel milk group (0.28 +/- 0.6 vs. 2.30 +/- 0.51 pmol/mL). These results suggest that, as an adjunct to standard management, daily ingestion of camel milk can aid metabolic control in young type 1 diabetics, at least in part by boosting endogenous insulin secretion.

  6. Evaluation of the Presence of Endocrine-Disrupting Compounds in Dissolved and Solid Wastewater Treatment Plant Samples of Gran Canaria Island (Spain)

    PubMed Central

    Vega-Morales, T.; Sosa-Ferrera, Z.; Santana-Rodríguez, J. J.

    2013-01-01

    Liquid and solid samples from two wastewater treatment plants (WWTPs) on Gran Canaria Island (Spain) have been tested for the presence of compounds with endocrine-disrupting properties. The selected degradation stages were sampled bimonthly from each WWTP over the 12-month period from July 2010 to July 2011. The analytical methods used for the determination of the endocrine-disrupting compounds (EDCs) were based on on-line solid phase extraction, microwave-assisted extraction (MAE), and ultrasonic-assisted extraction (UAE) coupled to UHPLC-MS/MS. All of the hyphenated methodologies employed in this work showed good recoveries (72–104%) and sensitivities, with LODs lower than 7.0 ng L−1 and 6.3 ng g−1 for the dissolved and solid fractions, respectively. We have also evaluated the estrogenicity of the samples in terms of their estradiol equivalent concentrations (EEQs). The chemical analysis of the selected EDCs revealed fairly low concentrations for both natural and synthetic oestrogens, alkylphenolic compounds, and bisphenol-A in each of the dissolved, particulate, and sludge samples (ng L−1 or ng g−1). However, the estimated estrogenic activity indicated that the majority of samples could represent an important environmental risk, clearly surpassing the threshold to exert deleterious consequences on living beings. PMID:24163820

  7. A controlled randomised trial of t-UDCA as adjuvant to interferon for treatment of chronic hepatitis C: an interferon sparing effect of t-UDCA.

    PubMed

    Gracielle, Pigozzi; Roberta, Sorbara; Ornella, Baisini; Luciana, Di; Alessandro, Reggiani; Daniela, Quattrocchi; Gianpaolo, Lorini; Grazia, De; Lamberto, Bettini; Anna, Cominotti; Maurizio, Favret; Alberto, Lanzini

    2002-08-01

    BACKGROUND: Combination of the cytoprotective effect of tauro-ursodeoxycholic acid (t-UDCA) with the antiviral effect of interferon may be more effective than interferon alone for treatment of chronic hepatitis C. METHODS: We randomised 106 patients with chronic hepatitis C to interferon 3 MU/m(2)/3 times per week given alone (regimen A, n=51) or in combination with t-UDCA 10 mg/kg/day (regimen B, n=55) for 6 months followed by IFN dose tapering for further 6 months. Control liver biopsies were obtained 6 months after stopping treatment. RESULTS: At the end of the trial a similar proportion of patients had normal serum alanine aminotransferase activity (ALT) levels (41 and 44%) and negative viremia (42 and 43%) with regimens A and B, respectively. The effect on liver histology was also similar, and the Knodell score decreased by 2.9+/-0.4 points with both regimens. During the dose tapering phase, the cumulative interferon dose to maintain ALT activity within the normal range was significantly lower for regimen B (142+/-4 million units, MU) than for regimen A (180+/-12 MU, P<0.005). CONCLUSIONS: Adjuvant t-UDCA exerts an 'interferon sparing effect' that may be of value for patients intolerant to high dose interferon.

  8. Endocrine system and obesity.

    PubMed

    Ashburn, Doyle D; Reed, Mary Jane

    2010-10-01

    Obesity is associated with significant alterations in endocrine function. An association with type 2 diabetes mellitus and dyslipidemia has been well documented. This article highlights the complexities of treating endocrine system disorders in obese patients.

  9. Chronobiology in the endocrine system.

    PubMed

    Haus, Erhard

    2007-08-31

    Biological signaling occurs in a complex web with participation and interaction of the central nervous system, the autonomous nervous system, the endocrine glands, peripheral endocrine tissues including the intestinal tract and adipose tissue, and the immune system. All of these show an intricate time structure with rhythms and pulsatile variations in multiple frequencies. Circadian (about 24-hour) and circannual (about 1-year) rhythms are kept in step with the cyclic environmental surrounding by the timing and length of the daily light span. Rhythmicity of many endocrine variables is essential for their efficacy and, even in some instances, for the qualitative nature of their effects. Indeed, the continuous administration of certain hormones and their synthetic analogues may show substantially different effects than expected. In the design of drug-delivery systems and treatment schedules involving directly or indirectly the endocrine system, consideration of the human time organization is essential. A large amount of information on the endocrine time structure has accumulated, some of which is discussed in this review.

  10. Introduction to the Endocrine System

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... in Balance › Hormones and Health › Journey Through the Endocrine System Journey Through the Endocrine System Endocrine-related Organs ...

  11. Adjuvant therapy after surgical stone management.

    PubMed

    Ferrandino, Michael N; Monga, Manoj; Preminger, Glenn M

    2009-01-01

    The aim of this article was to review the most widely researched adjuvant medical therapies for the surgical management of urolithiasis. Articles were identified and reviewed from PubMed and Medline databases with MeSH headings focusing on the various surgical treatments of urolithiasis and adjuvant therapy. Additional articles were retrieved from references and conference proceedings. Surgical treatments reviewed included shockwave lithotripsy, ureteroscopy, and percutaneous nephrolithotomy. Adjuvant therapy was considered medical or complementary therapy as an adjunct to these surgical interventions. Adjuvant therapy for the surgical management of urolithiasis has been documented to increase stone-free rates, reduce stone remission rates, prevent renal damage, and decrease postoperative morbidity. A variety of agents have been studied, ranging from antioxidants to alpha-blockers and to alkalinizing agents. Additionally, there is increasing interest in complementary adjuvant therapy (ie, acupuncture). Adjuvant therapy is a fertile area for research in the surgical management of urolithiasis. The optimal agents have yet to be determined and therefore further investigation is warranted and necessary.

  12. Exocrine and endocrine testicular function during the treatment of experimental orchitis and nonspecific orchoepididymitis by low-energy laser radiation

    NASA Astrophysics Data System (ADS)

    Reznikov, Leonid L.; Pupkova, Ludmila S.; Bell, H.; Murzin, Alexander G.

    1995-05-01

    Investigations into the biological effects of low-energy laser radiation (LLR) are characterized by a score of challenges, which are due primarily to a cascade of laser-induced and sometimes antagonistic processes. To investigate these processes on various biologic levels, we analyzed local and general effects of LLR on the exocrine and endocrine functions of the accessory sex glands in experimentally induced orchitis and orchoepididymitis in rabbits, and in clinical studies on male patients. The results indicate that LLR may alter the inflammatory response, including the exudative reaction, macrophage migration, and fibroblast activity. Furthermore, LLR may result in changes in serum concentrations of LH, FSH, and ACTH, prolactin, testosterone, cortisol and aldosterone. Some of these changes may be at least partially responsible for the well-known anti-inflammatory effects of LLR.

  13. Is Adjuvant Cellular Immunotherapy Essential after TACE-Predominant Minimally-Invasive Treatment for Hepatocellular Carcinoma? A Systematic Meta-Analysis of Studies Including 1774 Patients

    PubMed Central

    Chi, Jiachang; Wang, Tao; Tang, Xiaoyin; Cui, Dan; Qian, Qijun; Zhai, Bo

    2016-01-01

    Purpose Cellular immunotherapy has appeared to be a promising modality for the treatment of malignant tumor. The objective of this study was to evaluate the efficacy of cellular immunotherapy combined with minimally invasive therapy. Methods We searched PubMed, Web of Science and The Cochrane Library through March 2016 for relevant studies. Short-term efficacy (the disease control rate, the control rate of quality life and the AFP descent rate) and long-term efficacy (overall survival (OS) and progression-free survival (PFS) rate) were compared as the major outcome measures. The meta-analysis was performed using Review Manager 5.3. Results A total of 1174 references in 3 databases were found of which 19 individual studies with 1774 HCC patients enrolled in this meta-analysis. Meta-analysis results showed that cellular immunotherapy combined with minimally-invasive treatment significantly improved the measures of short-term response (the disease control rate (OR = 5.91, P = 0.007), the control rate of quality lift (OR = 3.38, P = 0.003) and the AFP descent rate (OR = 4.48, P = 0.02)). Also higher 6-month PFS (OR = 2.78, P = 0.05), ≥12-month PFS (OR = 3.56, P<0.00001) rate and 6-month OS (OR = 2.81, P = 0.0009), 12-month OS (OR = 3.05, P<0.00001) and 24-month OS (OR = 3.52, P<0.0001) rate were observed in patients undergoing cellular immunotherapy. Conclusions This meta-analysis suggested that cellular immunotherapy is a feasible adjuvant treatment that could be beneficial for the improvement of the clinical outcomes for hepatocellular carcinoma (HCC) patients after minimally invasive treatment, including short-term response and long-term survival. PMID:28006010

  14. Developments in the rat adjuvant arthritis model and its use in therapeutic evaluation of novel non-invasive treatment by SOD in Transfersomes.

    PubMed

    Simões, S I; Delgado, T C; Lopes, R M; Jesus, S; Ferreira, A A; Morais, J A; Cruz, M E M; Corvo, M L; Martins, M B F

    2005-03-21

    The aim of this study was firstly to refine a rat model of arthritis, the adjuvant arthritis (AA) model, by studying the time course of the disease, introducing new evaluation methods such as haematological and biochemical parameters in order to identify the main stages of the disease. An optimisation of treatment schedule and evaluation criteria was developed. This refinement provided novel non-invasive anti-inflammatory treatment of the AA with SOD by using mixed lipid vesicles specially developed for transdermal delivery, Transfersomes (Tfs), this being the second major aim. The time course of AA includes a first stage: 1 day after the disease induction, the induced paw volume more than doubled and the paw circumference increased by approx. 50%. Two weeks later, another stage occurred where the disease shifted from the local arthritis form towards polyarthritis: an additional increase of volume and circumference of the induced and non-induced paws, occurred. The animals also started to loose weight around day 14 after the disease induction. Radiographic observable lesions increased correspondingly. Treatment of animals, started at day 1 after induction, by epicutaneous application of SOD-Tfs showed that 1 mg SOD/kg body weight is more efficient than 0.66 mg SOD /kg body weight. As a positive control, SOD liposomes intravenously injected were used for comparison and confirmed the biological efficiency of epicutaneously applied SOD in Tfs. SOD solution and empty Tfs epicutaneously applied exerted no effect. In addition, epicutaneous application of SOD-Tfs used prophylactically was able to suppress the induced rat paw oedema. Radiographic images showed less joint lesions in SOD-Tfs treated animals in comparison with control and placebo treated rats. It was shown for the first time that SOD incorporated into Tfs and applied onto a skin area not necessarily close to the inflamed tissue is able to promote non-invasive treatment of induced arthritis.

  15. The efficacy of nicotinamide gel 4% as an adjuvant therapy in the treatment of cutaneous erosions of pemphigus vulgaris.

    PubMed

    Iraji, Fariba; Banan, Laleh

    2010-01-01

    The high rate of morbidity and mortality resulting from long-term use of corticosteroids in pemphigus vulgaris (PV) warrants discovery of a new treatment strategy. Based on the pathophysiology of PV, nicotinamide can block the process of blister formation through its anti-inflammatory properties. This study was conducted to evaluate the clinical effectiveness of nicotinamide gel in the treatment of skin lesions of PV. In a double-blind, placebo-controlled study, eight PV patients with a total of 60 skin lesions were treated by either nicotinamide or placebo gel. After 30 days of treatment, epithelialization index of the two groups was compared. The mean of the epithelialization index in skin lesions that received nicotinamide was significantly higher than that of the placebo group (26 vs. -5.8, p < 0.001). Our results were suggestive that nicotinamide gel can effectively be used as an adjunctive treatment for PV lesions.

  16. Occurrence of endocrine-disrupting and other wastewater compunds during water treatment with case studies from Lincoln, Nebraska and Berlin, Germany

    USGS Publications Warehouse

    Verstraeten, Ingrid M.; Heberer, T.; Vogel, J.R.; Speth, T.; Zuehlke, S.; Duennbier, U.

    2003-01-01

    Research on the fate and transport of endocrine-disrupting compounds and other organic wastewater compounds released into the environment and their potential presence in drinking water is in its infancy. Studies conducted during the last decade in Lincoln, Nebraska, and Berlin, Germany, indicate that removal of less polar compounds probably can be obtained through bank filtration, ground-water enrichment, and additional drinking-water and wastewater treatment processes. Polar compounds, such as atrazine and some metabolites, occur in drinking water obtained from contaminated surface water or ground water, but at concentrations generally lower than those occurring in wastewater and surface water. The results of the studies also suggest that concentrations of nonpolar estrogenic compounds decrease during drinking-water pretreatment processes such as bank filtration and ground-water enrichment.

  17. The molecular classification of hereditary endocrine diseases.

    PubMed

    Ye, Lei; Ning, Guang

    2015-12-01

    Hereditary endocrine diseases are an important group of diseases with great heterogeneity. The current classification for hereditary endocrine disease is mostly based upon anatomy, which is helpful for pathophysiological interpretation, but does not address the pathogenic variability associated with different underlying genetic causes. Identification of an endocrinopathy-associated genetic alteration provides evidence for differential diagnosis, discovery of non-classical disease, and the potential for earlier diagnosis and targeted therapy. Molecular diagnosis should be routinely applied when managing patients with suspicion of hereditary disease. To enhance the accurate diagnosis and treatment of patients with hereditary endocrine diseases, we propose categorization of endocrine diseases into three groups based upon the function of the mutant gene: cell differentiation, hormone synthesis and action, and tumorigenesis. Each category was further grouped according to the specific gene function. We believe that this format would facilitate practice of precision medicine in the field of hereditary endocrine diseases.

  18. Semi-individualised Chinese medicine treatment as an adjuvant management for diabetic nephropathy: a pilot add-on, randomised, controlled, multicentre, open-label pragmatic clinical trial

    PubMed Central

    Chan, Kam Wa; Ip, Tai Pang; Kwong, Alfred Siu Kei; Lui, Sing Leung; Chan, Gary Chi Wang; Cowling, Benjamin John; Yiu, Wai Han; Wong, Dickson Wai Leong; Liu, Yang; Feng, Yibin; Tan, Kathryn Choon Beng; Chan, Loretta Yuk Yee; Leung, Joseph Chi Kam; Lai, Kar Neng; Tang, Sydney Chi Wai

    2016-01-01

    Introduction Diabetes mellitus and diabetic nephropathy (DN) are prevalent and costly to manage. DN is the leading cause of end-stage kidney disease. Conventional therapy blocking the renin–angiotensin system has only achieved limited effect in preserving renal function. Recent observational data show that the use of Chinese medicine (CM), a major form of traditional medicine used extensively in Asia, could reduce the risk of end-stage kidney disease. However, existing clinical practice guidelines are weakly evidence-based and the effect of CM remains unclear. This trial explores the effect of an existing integrative Chinese–Western medicine protocol for the management of DN. Objective To optimise parameters and assess the feasibility for a subsequent phase III randomised controlled trial through preliminary evaluation on the effect of an adjuvant semi-individualised CM treatment protocol on patients with type 2 diabetes with stages 2–3 chronic kidney disease and macroalbuminuria. Methods and analysis This is an assessor-blind, add-on, randomised, controlled, parallel, multicentre, open-label pilot pragmatic clinical trial. 148 patients diagnosed with DN will be recruited and randomised 1:1 to a 48-week additional semi-individualised CM treatment programme or standard medical care. Primary end points are the changes in estimated glomerular filtration rate and spot urine albumin-to-creatinine ratio between baseline and treatment end point. Secondary end points include fasting blood glucose, glycated haemoglobin, brain natriuretic peptide, fasting insulin, C peptide, fibroblast growth factor 23, urinary monocyte chemotactic protein-1, cystatin C, nephrin, transforming growth factor-β1 and vascular endothelial growth factor. Adverse events are monitored through self-completed questionnaire and clinical visits. Outcomes will be analysed by regression models. Enrolment started in July 2015. Ethics and registration This protocol is approved by the Institutional

  19. Intraoperative radiation therapy as adjuvant treatment in locally advanced stage tumours involving the middle ear: a hypothesis-generating retrospective study.

    PubMed

    Cristalli, G; Mercante, G; Marucci, L; Soriani, A; Telera, S; Spriano, G

    2016-04-01

    The objective of this study was to evaluate the safety, effectiveness and functional outcomes of intraoperative radiotherapy (IORT) followed by intensity-modulated radiation therapy (IMRT) in locally advanced stage tumours involving the middle ear. Data on 13 consecutive patients treated for malignant tumor of external auditory canal involving the middle ear were retrospectively reviewed. Median follow-up was 33 months (range 6-133). Five (38%) patients were stage III and 8 (62%) were Stage IV according to the University of Pittsburgh staging system. Lateral temporal bone resection (LTBR) was performed in all cases. LTBR was associated with parotidectomy in 5 (38%) cases, and with neck dissection and parotidectomy in 6 (46%) cases. No patients had gross residual tumour. Surgical treatment was followed by IORT (12 Gy) and IMRT (50 Gy). Adjuvant chemotherapy was used in 4 (30%) cases. Preoperative and postoperative audiometric tests were performed to assess hearing loss. 5-year local-control (LC), 5-year distant-metastasis (DM), 5-year disease-free-survival (DFS) and 5-year overall-survival (OS) were calculated with Kaplan-Meyer method. Significant changes in bone conduction were reported after treatment. Partial flap necrosis was the only early complication observed in three (23%) cases, while meningeal fistula was seen in one (7.6%) case as a late complication. The 5-year LC-rate was 68%. The 5-year DM-rate was 90%. The 5-year DFS-rate was 61%. The 5-year OS-rate was 69%. IORT followed by IMRT for the treatment of advanced external auditory canal and middle ear tumours seems to be safe. No intraoperative death was reported. IORT may reduce the postoperative irradiation of remnant tissue obtaining the same full dose on the tumour bed. No complications of the residual external ear were observed. Detriment of neurosensory hearing may be expected. Future studies are required to confirm the benefit of this procedure in the ear.

  20. A comparative study of occurrence and fate of endocrine disruptors: diethyl phthalate and dibutyl phthalate in ASP- and SBR-based wastewater treatment plants.

    PubMed

    Saini, Gita; Pant, Shalini; Singh, Shri Om; Kazmi, A A; Alam, Tanveer

    2016-11-01

    Phthalates are endocrine-disrupting chemicals which affect endocrine system by bio-accumulation in aquatic organisms and produce adverse health effects in aquatic organisms as well as human beings, when come in contact. Present study focuses on occurrence and removal of two phthalates: diethylphthalate (DEP) and dibutylphthalate (DBP) in two full-scale wastewater treatment plants (WWTPs) i.e. sewage treatment plants (STPs) based on well-adopted technologies, activated sludge process (ASP) and sequencing batch reactor (SBR).Gas chromatography-mass spectrometry (GC-MS) analysis was performed for both wastewater and sludge sample for determination and identification of the concentration of these compounds in both STPs by monitoring the STPs for 9 months. It was observed that the concentration of DEP was less than DBP in the influent of ASP and SBR. Average concentrations of DEP and DBP in sludge sample of ASP were found to be 2.15 and 2.08 ng/g, whereas in SBR plant, these values were observed as 1.71 and 2.01 ng/g, respectively. Concerning the removal efficiency of DEP, SBR and ASP plants were found effective with removal efficiency of 91.51 and 91.03 %, respectively. However, in the case of DBP, SBR showed lower removal efficiency (85.42 %) as compared to ASP (92.67 %). Comparative study of both plants proposed that in ASP plant, DBP reduction was higher than the SBR. Fourier transformation infrared (FTIR) analysis also confirmed the same result of sludge analysis for both STPs. Sludge disposal studied with scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and thermo-gravimetric analysis (TGA) techniques confirmed that sludge of both STPs have high calorific value and can be used as fuel to make fuel-briquettes and bottom ash to make firebricks.

  1. Overview on cardiac, pulmonary and cutaneous toxicity in patients treated with adjuvant radiotherapy for breast cancer.

    PubMed

    Meattini, Icro; Guenzi, Marina; Fozza, Alessandra; Vidali, Cristiana; Rovea, Paolo; Meacci, Fiammetta; Livi, Lorenzo

    2017-01-01

    Conservative management of breast cancer represents the standard treatment for early disease. Breast conserving surgery associated with radiotherapy for stage I-II has been proven to be as equally effective as mastectomy in term of local control, distant disease, and overall survival. The growing minimal invasive surgical approach on the axillary region, and the new breast reconstructive techniques, will probably lead to a significant decrease of the rate of side-effects related to mastectomy. Therefore, the adverse events caused by adjuvant radiation still remain a challenge. Cutaneous, pulmonary and cardiac toxicity represent the main toxicities of adjuvant radiotherapy for breast cancer. Safety profile of radiation is strongly dependent on the multidisciplinary management of the single case (systemic treatment, endocrine therapy, surgery), individual characteristics (i.e., co-morbidities, age, habits), and radiation-related aspects. Radiation techniques development, and facilities implementation concerning organs-at-risk sparing systems (i.e., image-guided radiotherapy, tracking systems, respiratory gating), represent brand new tools for the clinical oncologist, that would certainly minimize toxicity profile in the next future. However, data reported from published literature will greatly help physicians, to give to the patients appropriate counseling regarding the efficacy and potential adverse events of treatments, thus optimizing the informed decision-making process.

  2. Multiple endocrine neoplasia type 1

    PubMed Central

    Marini, Francesca; Falchetti, Alberto; Monte, Francesca Del; Sala, Silvia Carbonell; Gozzini, Alessia; Luzi, Ettore; Brandi, Maria Luisa

    2006-01-01

    Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary, and characterised by a very high penetrance and an equal sex distribution. It occurs in approximately one in 30,000 individuals. Two different forms, sporadic and familial, have been described. The sporadic form presents with two of the three principal MEN1-related endocrine tumours (parathyroid adenomas, entero-pancreatic tumours and pituitary tumours) within a single patient, while the familial form consists of a MEN1 case with at least one first degree relative showing one of the endocrine characterising tumours. Other endocrine and non-endocrine lesions, such as adrenal cortical tumours, carcinoids of the bronchi, gastrointestinal tract and thymus, lipomas, angiofibromas, collagenomas have been described. The responsible gene, MEN1, maps on chromosome 11q13 and encodes a 610 aminoacid nuclear protein, menin, with no sequence homology to other known human proteins. MEN1 syndrome is caused by inactivating mutations of the MEN1 tumour suppressor gene. This gene is probably involved in the regulation of several cell functions such as DNA replication and repair and transcriptional machinery. The combination of clinical and genetic investigations, together with the improving of molecular genetics knowledge of the syndrome, helps in the clinical management of patients. Treatment consists of surgery and/or drug therapy, often in association with radiotherapy or chemotherapy. Currently, DNA testing allows the early identification of germline mutations in asymptomatic gene carriers, to whom routine surveillance (regular biochemical and/or radiological screenings to detect the development of MEN1-associated tumours and lesions) is recommended. PMID:17014705

  3. Innate immunity and adjuvants

    PubMed Central

    Akira, Shizuo

    2011-01-01

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  4. The Use of Amielle Vaginal Trainers as Adjuvant in the Treatment of Vestibulodynia: An Observational Multicentric Study

    PubMed Central

    Murina, Filippo; Bernorio, Roberto; Palmiotto, Rosanna

    2008-01-01

    Objective To assess the effectiveness of a specific set of vaginal dilators (Amielle Comfort) as a part of vestibulodynia therapy. Study design Fifteen women referred for vestibulodynia, localized vulvodynia, were advised to use vaginal dilators (Amielle Comfort) accompanied by standardized instructions, after previously receiving 1 or more therapies for the vestibulodynia. Results The post-treatment Marinoff scale for dyspareunia significantly improved in patients after vaginal dilator treatment compared with baseline values (2.2 ± 0.4 vs 1.1 ± 0.9; P < .01), and the Female Sexual Function Index scores were significantly improved compared with the prestudy values (16.3 ± 5.5 vs 25.3 ± 7.5; P < .01). Conclusion Among women with previous therapy for vestibulodynia, vaginal dilator use was associated with improvement in symptoms. Vaginal dilators can play an important role in overcoming pelvic floor muscular responses that remain and sometimes increase after pain perception has decreased. PMID:18324333

  5. Endocrine disorders.

    PubMed

    Hordon, L D; Wright, V

    1992-02-01

    The effect of thyroxine replacement therapy on bone mass continues to attract attention. Although the advice of the American Thyroid Association to normalize serum thyroxine and thyroid-stimulating hormone concentrations is recommended, even physiologic doses of thyroxine may have an adverse effect on bone mass. The diagnosis and treatment of osteomyelitis in the diabetic foot is aided by magnetic resonance imaging, and long-term review of cases of diabetic femoral neuropathy emphasizes the good prognosis. Adrenal insufficiency as a complication of antiphospholipid syndrome is reviewed, and a useful physical sign, the acromegalic rosary, rediscovered. The association of sex steroids, oral contraception, and parity with rheumatoid arthritis is discussed. The outcome of pregnancy in women with juvenile rheumatoid arthritis is good, and quiescent disease does not appear to be permanently reactivated. Calcium deficiency, rather than vitamin D deficiency, is a cause of rickets in some Nigerian children.

  6. Adjuvant chemotherapy for early-stage cervical cancer

    PubMed Central

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-01-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  7. Characterization and treatment monitoring of inflammatory arthritis by photoacoustic imaging: a study on adjuvant-induced arthritis rat model

    NASA Astrophysics Data System (ADS)

    Wang, Xueding; Rajian, Justin; Shao, Xia; Chamberland, David L.; Girish, Gandikota

    2014-03-01

    Neovascularity also known as angiogenesis is an early feature of inflammatory arthritis disease. Therefore, identifying the development of neovascularity is one way to potentially detect and characterize arthritis. Laser-based photoacoustic imaging (PAI) is an emerging biomedical imaging modality which may aid in detection of both early and continued development of neovascularity. In this work, we investigated the feasibility of PAI to measure angiogenesis, for the purpose of evaluating and monitoring inflammatory arthritis after treatment. The imaging results on an arthritis rat model demonstrate that 1) there is noticeable enhancement in image intensity in the arthritic ankle joints when compared to the normal joints, and 2) there is noticeable decrease in image intensity in the arthritic ankle joints after treatment when compared to the untreated arthritic joints. In order to validate the findings from PAI, we performed positron emission tomography (PET) and histology on the same joints. The diameters of the ankle joints, as a clinical score of the arthritis, were also measured at each time point.

  8. Cerebrolysin adjuvant treatment in Broca's aphasics following first acute ischemic stroke of the left middle cerebral artery

    PubMed Central

    Muresanu, DF; Bajenaru, O; Popescu, BO; Deme, SM; Moessler, H; Meinzingen, SZ; Petrica, L; Serpe, M; Ursoniu, S

    2010-01-01

    Background: The aim of our study was to assess the efficacy of Cerebrolysin administration in Broca's aphasics with acute ischemic stroke. Methods: We registered 2,212 consecutive Broca's aphasics following an acute ischemic stroke admitted in four departments of neurology in Romania, between September 2005 and September 2009. Language was evaluated with the Romanian version of the Western Aphasia Battery (WAB). The following inclusion criteria were used for this study: age 20%75 years, admission in the hospital within 12 hours from the onset of the symptoms, diagnosis of first acute left middle cerebral artery (MCA) ischemic stroke, presence of large artery disease (LAD) stroke, a NIHSS score of 5%22 points, and a therapeutic time window within 72 h. Fifty two patients were treated with Cerebrolysin (Cerebrolysin group) as an adjunctive treatment. A placebo group, which received saline infusions (n=104 patients) were matched to the NIHSS and WAB scores, gender and age of the Cerebrolysin group at baseline. We assessed spontaneous speech (SS), comprehension (C), repetition (R), naming (N), and Aphasia Quotient (AQ) scores of the two groups in an open label design, over 90 days, the mRS scores and mortality. Results: The Cerebrolysin and the placebo groups had similar age (66+/%8 versus 65+/%8 years) and sex ratio (14/38 versus 30/74). The mean AQ scores and the mean subscores for 3 subtests of WAB (SS, R, N) were similar at baseline and improved in the Cerebrolysin group significantly (p<0.05) over placebo group at all study time points. The mRS score at 90 days was also lower in the Cerebrolysin group than in the placebo group. Cerebrolysin and placebo were both tolerated and safe, and no difference in the mortality rate was seen (3.8% in each group). Conclusion: Cerebrolysin is effective for the treatment of Broca's aphasics with a first acute ischemic stroke of the left MCA territory. PMID:20945821

  9. Oncology providers’ perspectives on endocrine therapy prescribing and management

    PubMed Central

    Wheeler, Stephanie B; Roberts, Megan C; Bloom, Diane; Reeder-Hayes, Katherine E; Espada, Maya; Peppercorn, Jeffrey; Golin, Carol E; Earp, Jo Anne

    2016-01-01

    Purpose Adjuvant endocrine therapy (ET) can reduce the risk of recurrence among females with hormone receptor-positive breast cancer. Overall, initiation and adherence to ET are suboptimal, though reasons are not well described. The study’s objective was to better understand ET decision making, prescribing, and patient management from oncology providers’ perspectives. Methods Using purposive sampling, we recruited oncology providers who saw five or more breast cancer patients per week (n=20). We conducted 30–45-minute telephone interviews, using a semistructured guide to elicit perspectives on ET use. We used thematic content analysis to systematically identify categories of meaning and double-coded transcripts using Atlas.ti. Results Providers recommend ET to all eligible patients except those with contraindications or other risk factors. Providers base their ET prescribing decisions on the patient’s menopausal status, side effects, and comorbidities. ET is typically discussed multiple times: at the onset of breast cancer treatment and in more detail after other treatment completion. Providers felt that the associated recurrence risk reduction is the most compelling argument for patients during ET decision making. While providers rarely perceived noninitiation as a problem, nonadherence was prevalent, often due to unresolvable side effects. Conclusion From the clinicians’ perspectives, side effects from ET are the dominant factor in nonadherence. Efforts to improve adherence should focus on strategies to minimize side effects and ensure clinicians and patients are well informed regarding optimal side effect management. This finding has important implications for novel endocrine regimens that offer improved outcomes through longer duration or more intensive therapy. PMID:27757021

  10. Health from the Hive: Propolis as an Adjuvant in the Treatment of Chronic Periodontitis - A Clinicomicrobiologic Study

    PubMed Central

    Sanghani, Nehal N; S, Savita

    2014-01-01

    Objectives: This study was aimed at the clinical and microbiological evaluation of the efficacy of subgingivally delivered Indian propolis extract as an adjunct to scaling and root planing (SRP) in the treatment of periodontitis. Materials and Methods: Twenty patients diagnosed with chronic periodontitis presenting a minimum of two pockets (probing depth ≥5 mm) were selected. Sites were assigned randomly into control sites (n=20) which received SRP alone or test sites (n=20) which received SRP and locally delivered propolis. At selected sites, the clinical parameters were assessed and subgingival plaque samples were collected at baseline, 15 days and one month. The samples were cultured anerobically for periodontal pathogens. Results: The results indicated that there was a significant improvement in both clinical and microbiological parameters (p<0.01) in the test sites compared to the control sites at the end of the study. Conclusion: Subgingival delivery of propolis showed promising results as an adjunct to SRP in patients with chronic periodontitis when assessed by clinical and microbiological parameters. PMID:25386520

  11. Oxidative removal of selected endocrine-disruptors and pharmaceuticals in drinking water treatment systems, and identification of degradation products of triclosan.

    PubMed

    Wu, Qihua; Shi, Honglan; Adams, Craig D; Timmons, Terry; Ma, Yinfa

    2012-11-15

    The potential occurrences of endocrine-disrupting compounds (EDCs), as well as pharmaceuticals, are considered to be emerging environmental problems due to their persistence and continuous input into the aquatic ecosystem, even at only trace concentrations. This study systematically investigated the oxidative removal of eight specially selected ECDs and pharmaceuticals by comparing their relative reactivity as a function of different oxidative treatment processes (i.e., free chlorine, ozone, monochloramine, and permanganate) under various pH conditions. For the oxidative removal study, EDC and pharmaceutical standards were spiked into both deionized water and natural water, followed by treatment using common oxidants at typical water treatment concentrations. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for identification and quantification. The removal efficiency of the EDCs and pharmaceuticals varied significantly between oxidation processes. Free chlorine, permanganate, and ozone treatments were all highly effective at the elimination of triclosan and estrone, while they were not effective for removing ibuprofen, iopromide, and clofibric acid. Monochloramine (at a dose of 3mg/L) was mostly ineffective in eliminating any of the selected EDCs and pharmaceuticals under the tested conditions. pH also played an important role in the removal efficiency of the EDCs and pharmaceuticals during free chlorine, permanganate, and ozone treatments. Additionally, the study identified the oxidation products of triclosan by permanganate, and 2,4-dichlorophenol was identified as the major oxidation product of triclosan by permanganate in drinking water system treatment. Furthermore, 2,4-dichlorophenol was further degradated to 4,5-dichloro-2-(2,4-dichlorophenoxy)phenol and/or 5,6-dichloro-2-(2,4-dichlorophenoxy)phenol. The kinetics for this reaction indicated that the reaction was first order in the drinking water system.

  12. Adjuvant chemotherapy in early breast cancer.

    PubMed

    Ejlertsen, Bent

    2016-05-01

    these CMF regimens has not been compared within the context of a randomised trial. Shifting from the 77B's classic CMF regimen to the 82B four-weekly IV regimen or the 89B three-weekly IV regimen was associated with a 30% increased risk of a DFS event in a multivariate analysis of a population-based cohort study. Furthermore, the four-weekly regimen used in 82B was associated with a 40% increase in mortality. The strengths of the design include identical selection criteria, uniform and prospective registration of treatment, tumour and patient characteristics. Caution is still required due to the non-experimental design of the comparison. Another finding was a substantial difference in the risk of amenorrhoea; and while 15% of patients aged 40 or younger in 77B had regular menses throughout chemotherapy, the corresponding percentage was 37 in 82B and 47 in 89B. The DBCG in collaboration with a Swedish and a Dutch centre participating in the DBCG trial 89B compared CMF with ovarian ablation in premenopausal high-risk breast cancer patients with ER-positive tumours. No significant differences were found in DFS or OS in the preplanned analysis, suggesting that the benefits of CMF may, at least in part, be explained by ovarian suppression in premenopausal patients with ER-positive tumours. However, these results are not clinically useful by themselves as other chemotherapy regimens have been more efficacious, and knowledge is still lacking regarding the benefits from adding ovarian suppression to chemotherapy plus tamoxifen. The results from the DBCG 77B and 82C are in accordance with other large adjuvant trials and the EBCTCG meta-analyses. The benefits obtained with any individual anticancer drug are largely determined by the cancer (somatic) genome; and by being a molecular target of anthracyclines, TOP2A aberrations could obviously be associated with cancer drug benefits. In the DBCG 89D, a significant heterogeneity was observed between a beneficial effect on DFS and OS

  13. (Neo)adjuvant systemic therapy for melanoma.

    PubMed

    van Zeijl, M C T; van den Eertwegh, A J; Haanen, J B; Wouters, M W J M

    2017-03-01

    Surgery still is the cornerstone of treatment for patients with stage II and III melanoma, but despite great efforts to gain or preserve locoregional control with excision of the primary tumour, satellites, intransits, sentinel node biopsy and lymphadenectomy, surgery alone does not seem to improve survival any further. Prognosis for patients with high risk melanoma remains poor with 5-year survival rates of 40 to 80%. Only interferon-2b has been approved as adjuvant therapy since 1995, but clinical integration is low considering the high risk-benefit ratio. In recent years systemic targeted- and immunotherapy have proven to be beneficial in advanced melanoma and could be a promising strategy for (neo)adjuvant treatment of patients with resectable high risk melanomas as well. Randomised, placebo- controlled phase III trials on adjuvant systemic targeted- and immunotherapy are currently being performed using new agents like ipilimumab, pembrolizumab, nivolumab, vemurafenib and dabrafenib plus trametinib. In this article we review the literature on currently known adjuvant therapies and currently ongoing trials of (neo)adjuvant therapies in high risk melanomas.

  14. Is the toxicity of adjuvant aromatase inhibitor therapy underestimated? Complementary information from patient-reported outcomes (PROs).

    PubMed

    Oberguggenberger, Anne; Hubalek, Michael; Sztankay, Monika; Meraner, Verena; Beer, Beate; Oberacher, Herbert; Giesinger, Johannes; Kemmler, Georg; Egle, Daniel; Gamper, Eva-Maria; Sperner-Unterweger, Barbara; Holzner, Bernhard

    2011-07-01

    Adjuvant endocrine treatment-related adverse effects have a strong impact on patients' quality of life and thereby limit therapy's risk benefit ratio resulting in morbidity and treatment discontinuation. Still, many AI adverse effects remain untreated given that they are unrecognized by conservative methods (e.g., proxy ratings). The ability of complementary patient-reported outcomes (PROs) to provide a more comprehensive assessment of side-effects is to be explored. A cross-sectional study sample of 280 postmenopausal, early stage breast cancer patients was subjected to a comprehensive PRO assessment (FACT-B/+ES) at their after-care appointment. Prevalence and severity of patient-reported physical side-effects and psychosocial burden related to adjuvant AI therapy were compared with prevalences derived from pivotal phase IV trials (ATAC 2005, BIG1-98 2005). Across all symptom categories, highest prevalence rates were found for joint pain (59.6%), hot flushes (52%), lost interest in sexual intercourse (51.4%), and lack of energy (40.3%). Overall, PROs resulted in significantly higher prevalence rates as compared to physician ratings for all symptoms published in pivotal clinical trials except vaginal bleeding and nausea. The treatment duration exerted no significant impact on symptom frequency (P > 0.05). Established prevalence rates of endocrine treatment-related toxicity seem to be underestimated. The incorporation of PRO data should be mandatory or at least highly recommended in clinical treatment planning to arrive at a more accurate assessment of a patient's actual symptom burden enabling improved individualized management of side-effects and mediating the preservation of treatment adherence.

  15. Endocrine system: part 1.

    PubMed

    Johnstone, Carolyn; Hendry, Charles; Farley, Alistair; McLafferty, Ella

    2014-05-27

    This article, which forms part of the life sciences series and is the first of two articles on the endocrine system, examines the structure and function of the organs of the endocrine system. It is important that nurses understand how the endocrine system works and its role in maintaining health. The role of the endocrine system and the types, actions and control of hormones are explored. The gross structure of the pituitary and thyroid glands are described along with relevant physiology. Several disorders of the thyroid gland are outlined. The second article examines growth hormone, the pancreas and adrenal glands.

  16. Endocrine glands (image)

    MedlinePlus

    Endocrine glands release hormones (chemical messengers) into the bloodstream to be transported to various organs and tissues throughout the body. For instance, the pancreas secretes insulin, which ...

  17. [Postpartum endocrine syndrome].

    PubMed

    Ducarme, G; Châtel, P; Luton, D

    2008-05-01

    Postpartum endocrine syndromes occur in the year after delivery. They are due to immunologic and vascular modifications during pregnancy. The Sheehan syndrome is the first described postpartum endocrine syndrome and consists on a hypophyse necrosis in relation with a hypovolemic shock during delivery. The immunologic consequences of the pregnancy are the most frequent, sometimes discrete and transitory. The physiological evolution of the endocrine glands during pregnancy and the most frequent post-partum endocrine syndromes are discussed: postpartum lymphocytic hypophysitis, thyroiditis and Sheehan' syndrome.

  18. Occurrence, fate and environmental risk assessment of endocrine disrupting compounds at the wastewater treatment works in Pietermaritzburg (South Africa).

    PubMed

    Manickum, T; John, W

    2014-01-15

    Steroid hormone Endocrine Disrupting Compounds (EDCs) (natural estrogens (17-β-estradiol (E2), estrone (E1), estriol (E3), synthetic estrogen (17-α-ethinylestradiol (EE2)), natural androgen (testosterone) (tes) and natural progestogen (progesterone) (pro)) at an activated sludge wastewater works (WWW), were quantitated using Enzyme-linked immunosorbent assay (ELISA). The steroid hormone profile in the adjacent surface water was also determined. Pro was the most abundant (41%, 408 ng/L) in the influent, followed by tes (35%, 343 ng/L) and E2 (12%, 119 ng/L). E1 was the most abundant (35%, 23 ng/L) in effluent, followed by E2 (30%, 20 ng/L) and tes (17%, 11 ng/L). Chemical removal efficiencies of the steroid hormones by the WWW averaged 92%. High removal efficiency was observed for pro (98% ± 2) and tes (96% ± 1), compared to natural (72-100%) and synthetic estrogen (90% ± 3), with biodegradation being the major removal route for pro and tes. The lowest removal for E2 is in spring (65%), and maximum removal is in winter (95%). Natural (E2, E1) and synthetic estrogen (EE2) were major contributors to influent (E2 = 69%) and effluent (E2 = 73%) estrogenic potency. The estrogenic potency removal averaged 85% (range: 73-100). Risk assessment of the steroid hormones present in wastewater effluent, and surface water, indicated that EE2 and E2 pose the highest risk to human health and fish. EE2 was found to be much more resistant to biodegradation, compared to E2, in surface water. Estrone, as the breakdown product of E2 and EE2 in wastewater, appears to be suitable as an indicator of EDCs. The study suggests that a battery of tests: quantitative chemical assay, bioassay for estrogenic activity and risk assessment methods, collectively, are preferred in order to make meaningful, accurate conclusions regarding potential adverse effects of EDCs present in treated wastewater effluent or surface water, to the aquatic environment, human health, and wildlife systems.

  19. Glucuronidation and sulfonation, in vitro, of the major endocrine-active metabolites of methoxychlor in the channel catfish, Ictalurus punctatus, and induction following treatment with 3-methylcholanthrene

    PubMed Central

    James, Margaret O.; Stuchal, Leah D.; Nyagode, Beatrice A.

    2008-01-01

    The organochlorine pesticide, methoxychlor (MXC), is metabolized in animals to phenolic mono- and bis-demethylated metabolites (OH-MXC and HPTE respectively) that interact with estrogen receptors and may be endocrine disruptors. The phase II detoxication of these compounds will influence the duration of action of the estrogenic metabolites, but has not been investigated extensively. In this study, the glucuronidation and sulfonation of OH-MXC and HPTE were investigated in subcellular fractions of liver and intestine from untreated, MXC-treated and 3-methylcholanthrene (3-MC)-treated channel catfish, Ictalurus punctatus. MXC-treated fish were given i.p. injections of 2 mg MXC/kg daily for 6 days and sacrificed 24 hr after the last dose. The 3-MC treatment was a single 10 mg/kg i.p. dose 5 days prior to sacrifice. In hepatic microsomes from control fish, the Vmax value (mean ± S.D., n=4) for glucuronidation of OH-MXC was 270 ± 50 pmol/min/mg protein, higher than found for HPTE (110 ± 20 pmol/min/mg protein). For each substrate, the Vmax values observed in intestinal microsomes were approximately twice those found in the liver. The Km values for OH-MXC and HPTE glucuronidation in control liver were not significantly different and were 0.32 ± 0.04 mM for OH-MXC and 0.26 ± 0.06 mM for HPTE. The Km for the co-substrate, UDPGA, was higher in liver (0.28 ± 0.09 mM) than intestine (0.04 ± 0.02 mM). Treatment with 3-MC but not MXC increased the Vmax for glucuronidation in liver and intestine. Glucuronidation was a more efficient pathway than sulfonation for both substrates, in both tissues. The Vmax values for sulfonation of OH-MXC and HPTE respectively in liver cytosol were 7 ± 3 and 17 ± 4 pmol/min/mg protein and in intestinal cytosol were 13 ± 3 and 30 ± 5 pmol/min/mg protein. Treatment with 3-MC but not MXC increased rates of sulfonation of OH-MXC and HPTE and the model substrate, 3-hydroxy-benzo(a)pyrene in both intestine and liver. Comparison of the kinetics

  20. Removal of selected pharmaceuticals and personal care products (PPCPs) and endocrine-disrupting chemicals (EDCs) during sand filtration and ozonation at a municipal sewage treatment plant.

    PubMed

    Nakada, Norihide; Shinohara, Hiroyuki; Murata, Ayako; Kiri, Kentaro; Managaki, Satoshi; Sato, Nobuyuki; Takada, Hideshige

    2007-11-01

    We investigated the efficiencies of removal of 24 pharmaceutically active compounds (PhACs) during sand filtration and ozonation in an operating municipal sewage treatment plant (STP). The target compounds were 2 phenolic antiseptics (thymol, triclosan), 5 acidic analgesics or anti-inflammatories (ibuprofen, naproxen, ketoprofen, fenoprofen, mefenamic acid), 4 amide pharmaceuticals (propyphenazone, crotamiton, carbamazepine, diethyltoluamide), 7 antibiotics (sulfapyridine, sulfamethoxazole, trimethoprim, azithromycin, erythromycin anhydride, clarithromycin, roxithromycin), 3 phenolic endocrine-disrupting chemicals (EDCs) (nonylphenol:NP, octylphenol:OP, bisphenol A:BPA) and 3 natural estrogens (17 beta-estradiol:E2, estrone:E1, estriol:E3). Ozonation removed approximately 80% or more of the phenolic antiseptics, crotamiton, sulfonamide and macrolide antibiotics, and 17 beta-estradiol. Their removal is discussed in terms of chemical structure. The study ascertained the validity of ozonation mechanisms proposed by previous studies in an actually running STP. Compounds with a CC double bond or an aromatic structure with electron donors (e.g., phenol, alkyl, methoxy, or non-protonated amine) were susceptible to ozonation. Compounds with amide structures were resistant. Removal of the PhACs during sand filtration was generally inefficient, probably because of their low hydrophobicities. The combination of ozonation and sand filtration with activated sludge treatment gave efficient removal (>80%) of all the target compounds except carbamazepine and diethyltoluamide. Among all the steps in the plant, ozonation contributed substantially to overall removal of naproxen, ketoprofen, triclosan, crotamiton, sulfapyridine, macrolide antibiotics, and estrone.

  1. Endocrine Therapy of Breast Cancer

    DTIC Science & Technology

    2005-06-01

    breast cancers is whether an aromatase inhibitor, e.g., letrozole (LET) or TAM should be given as first line endocrine therapy . Unfortunately...response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies , e.g., -40% of tumors...effective treatment for hormone receptor positive invasive breast cancer. Such therapy includes antiestrogens (tamoxifen, fulvestrant ) and aromatase

  2. Endocrine Therapy of Breast Cancer

    DTIC Science & Technology

    2006-06-01

    or TAM should be given as first line endocrine therapy . Unfortunately, response rates are lower, and response durations are shorter, on crossover than...when these agents are given as first line therapies , e.g., ~40% of tumors show cross resistance to TAM or an aromatase inhibitor on crossover. Only...effective treatment for hormone receptor positive invasive breast cancer. Such therapy includes antiestrogens (tamoxifen, fulvestrant ) and aromatase

  3. Sleep and the endocrine system.

    PubMed

    Morgan, Dionne; Tsai, Sheila C

    2015-07-01

    In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed.

  4. Sleep and the Endocrine System.

    PubMed

    Morgan, Dionne; Tsai, Sheila C

    2016-03-01

    In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed.

  5. ENDOCRINE DISRUPTORS IN THE ENVIRONMENT

    EPA Science Inventory

    The endocrine system produces hormones which are powerful natural chemicals that regulate important life processes. Endocrine disruptors are human-made chemicals distributed globally which have the potential to interfere with the endocrine system and produce serious biological e...

  6. Adjuvant Embolization with N-butyl Cyanoacrylate in the Treatment of Cerebral Arteriovenous Malformations: Outcomes, Complications, and Predictors of Neurologic Deficits

    PubMed Central

    Starke, Robert M.; Komotar, Ricardo J.; Otten, Marc L.; Hahn, David K.; Fischer, Laura E.; Hwang, Brian Y.; Garrett, Matthew C.; Sciacca, Robert R.; Sisti, Michael B.; Solomon, Robert A.; Lavine, Sean D.; Connolly, E. Sander; Meyers, Philip M.

    2009-01-01

    Background and Purpose To assess the frequency, severity, and predictors of neurologic deficits following adjuvant embolization for cerebral arteriovenous malformations (AVMs). Methods From 1997-2006, 202 of 275 AVM patients received embolization prior to microsurgery (n=176) or radiosurgery (n=26). Patients were examined before and after endovascular embolization, and at clinical follow-up (mean 43.4±34.6 months). Outcome was classified according to the modified Rankin Scale (mRS). New neurological deficits after embolization were defined as minimal (no change in overall mRS), moderate (mRS≤2), or significant (mRS>2). Results 202 patients were treated in 377 embolization procedures. There were a total of 29 new clinical deficits after embolization (8% of procedures; 14% of patients), of which 19 were moderate or significant. Post-embolization deficits resolved in a significant number of patients over time (p<0.0001). Five patients suffered persistent neurological deficits due to embolization (1.3% of procedures; 2.5% of patients). In multivariate analysis, the following variables significantly predicted new neurological deficit following embolization: complex AVM with treatment plan specifying more than one embolization procedure (OR=2.7; 95% CI, 1.4-8.6), diameter <3cm (OR=3.2; 95%, CI 1.2-9.1), diameter >6cm (OR=6.2; 95% CI, 1.0-57.0), deep venous drainage (OR=2.7; 95% CI, 1.1-6.9) or eloquent location (OR=2.4; 95% CI, 1.0-5.7). These variables were weighted and used to compute an AVM Embolization Prognostic Risk Score for each patient. A score of 0 predicted no new deficits, a score of 1 predicted a new deficit rate of 6%, a score of 2 predicted a new deficit rate of 15%, a score of 3 predicted a new deficit rate of 21%, and a score of 4 predicted a new deficit rate of 50% (p<0.0001). Conclusions Small and large size, eloquent location, deep venous drainage, and complex vascular anatomy requiring multiple embolization procedures are risk factors for the

  7. Outcomes of re-treatment with first-line trastuzumab plus a taxane in HER2 positive metastatic breast cancer patients after (neo)adjuvant trastuzumab: A prospective multicenter study

    PubMed Central

    Xu, Binghe; Hu, Xichun; Zheng, Hong; Wang, Xiaojia; Zhang, Qingyuan; Cui, Shude; Liu, Donggeng; Liao, Ning; Luo, Rongcheng; Sun, Qiang; Yu, Shiying

    2016-01-01

    Trastuzumab is the backbone of HER2-positive early breast cancer (eBC) and metastatic breast cancer (mBC) treatment, but limited data exist as to re-treatment in relapsed patients. In this prospective, single arm, multicenter trial, we assessed efficacy and safety of trastuzumab and taxane combination in Chinese patients with HER2-positive mBC relapsed after prior (neo)adjuvant trastuzumab. Patients with previous (neo)adjuvant trastuzumab treatment for≥9 weeks and a relapse-free interval ≥6 months were assigned to trastuzumab treatment with paclitaxel or docetaxel. The primary endpoint was progression free survival (PFS). Secondary endpoints included overall response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), time to progression (TTP), overall survival (OS) and safety profile. Thirty-two patients were enrolled and treated for a median duration of 33.5 weeks. The median PFS was 9.9 months (95% CI, 6.28 - 13.63 months). The ORR was 81.3% (95% CI, 63.6% - 92.8%) and CBR (CR+PR+SD≥6months) was 81.3% (95% CI, 63.6% - 92.8%). The median DOR was 9.8 months (95% CI, 5.82 - 11.60 months) and median TTP was 9.9 months (95% CI, 6.28-13.63 months). OS median follow-up time was 20.1 months and 25% OS time was 25.5 months. The safety profile was acceptable with common adverse events including leukopenia (59.4%), neutropenia (56.3%), hypoaesthesia (34.4%) and granulocytopenia (31.3%). In conclusion, re-treatment with trastuzumab plus a taxane as first-line therapy is an effective regimen for patients with HER2-positive mBC relapsed after (neo)adjuvant trastuzumab. The safety profile was good and the adverse reactions were tolerable and manageable. PMID:27276706

  8. The endocrine quiz.

    PubMed

    Kalra, Sanjay; Baruah, Manash P; Nagesh, V Sri

    2014-05-01

    With the recent explosion in endocrine conferences, audience fatigue has set in and conference planners are now looking at newer pedagogic methods to revive the interest of audiences in these conferences. The endocrine quiz has finally come of vogue and is increasingly becoming one of the most popular attractions of any ranking endocrine conference. The endocrine quiz has a large and varied palette and draws questions from religious scriptures, history, literature, current affairs, sports, movies and basic and paramedical sciences. The more we delve into the quizzable aspects of endocrinology, the more we realize that endocrinology is ubiquitous and there is no sphere in human life untouched by endocrine disorders. Be it epic characters like Kumbhakarna and Bheema, fiction characters like Tintin or Orphan Annie, sportspersons like Gail Devers or heads of state like George Bush Sr and Boris Yeltsin, all have contributed to the melting pot of endocrine quizzing. Adding further grist to the endocrine mill are the Nobel prizes, with their attendant anecdotes and controversies. Step into this world of endocrine quizzing to have an up close and personal look at the diverse facets of this subject.

  9. The endocrine quiz

    PubMed Central

    Kalra, Sanjay; Baruah, Manash P.; Nagesh, V. Sri

    2014-01-01

    With the recent explosion in endocrine conferences, audience fatigue has set in and conference planners are now looking at newer pedagogic methods to revive the interest of audiences in these conferences. The endocrine quiz has finally come of vogue and is increasingly becoming one of the most popular attractions of any ranking endocrine conference. The endocrine quiz has a large and varied palette and draws questions from religious scriptures, history, literature, current affairs, sports, movies and basic and paramedical sciences. The more we delve into the quizzable aspects of endocrinology, the more we realize that endocrinology is ubiquitous and there is no sphere in human life untouched by endocrine disorders. Be it epic characters like Kumbhakarna and Bheema, fiction characters like Tintin or Orphan Annie, sportspersons like Gail Devers or heads of state like George Bush Sr and Boris Yeltsin, all have contributed to the melting pot of endocrine quizzing. Adding further grist to the endocrine mill are the Nobel prizes, with their attendant anecdotes and controversies. Step into this world of endocrine quizzing to have an up close and personal look at the diverse facets of this subject. PMID:24944922

  10. Microbiota Influences Vaccine and Mucosal Adjuvant Efficacy

    PubMed Central

    2017-01-01

    A symbiotic relationship between humans and the microbiota is critical for the maintenance of our health, including development of the immune system, enhancement of the epithelial barrier, and acquisition of nutrients. Recent research has shown that the microbiota impacts immune cell development and differentiation. These findings suggest that the microbiota may also influence adjuvant and vaccine efficacy. Indeed, several factors such as malnutrition and poor sanitation, which affect gut microbiota composition, impair the efficacy of vaccines. Although there is little evidence that microbiota alters vaccine efficacy, further understanding of human immune system-microbiota interactions may lead to the effective development of adjuvants and vaccines for the treatment of diseases. PMID:28261017

  11. Microbiota Influences Vaccine and Mucosal Adjuvant Efficacy.

    PubMed

    Kim, Yun-Gi

    2017-02-01

    A symbiotic relationship between humans and the microbiota is critical for the maintenance of our health, including development of the immune system, enhancement of the epithelial barrier, and acquisition of nutrients. Recent research has shown that the microbiota impacts immune cell development and differentiation. These findings suggest that the microbiota may also influence adjuvant and vaccine efficacy. Indeed, several factors such as malnutrition and poor sanitation, which affect gut microbiota composition, impair the efficacy of vaccines. Although there is little evidence that microbiota alters vaccine efficacy, further understanding of human immune system-microbiota interactions may lead to the effective development of adjuvants and vaccines for the treatment of diseases.

  12. Adjuvants and vector systems for allergy vaccines.

    PubMed

    Moingeon, Philippe; Lombardi, Vincent; Saint-Lu, Nathalie; Tourdot, Sophie; Bodo, Véronique; Mascarell, Laurent

    2011-05-01

    Allergen-specific immunotherapy represents a curative treatment of type I allergies. Subcutaneous immunotherapy is conducted with allergens adsorbed on aluminum hydroxide or calcium phosphate particles, whereas sublingual immunotherapy relies on high doses of soluble allergen without any immunopotentiator. There is a potential benefit of adjuvants enhancing regulatory and Th1 CD4+T cell responses during specific immunotherapy. Molecules affecting dendritic cells favor the induction of T regulatory cell and Th1 responses and represent valid candidate adjuvants for allergy vaccines. Furthermore, the interest in viruslike particles and mucoadhesive particulate vector systems, which may better address the allergen(s) to tolerogenic antigen-presenting cells, is documented.

  13. Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

    NASA Astrophysics Data System (ADS)

    Payne, Richard; McDonald, David; Byrne, Scott

    2015-10-01

    Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

  14. Adjuvant and Definitive Radiotherapy for Adrenocortical Carcinoma

    SciTech Connect

    Sabolch, Aaron; Feng, Mary; Griffith, Kent; Hammer, Gary; Doherty, Gerard; Ben-Josef, Edgar

    2011-08-01

    Purpose: To evaluate the impact of both adjuvant and definitive radiotherapy on local control of adrenocortical carcinoma. Methods and Materials: Outcomes were analyzed from 58 patients with 64 instances of treatment for adrenocortical carcinoma at the University of Michigan's Multidisciplinary Adrenal Cancer Clinic. Thirty-seven of these instances were for primary disease, whereas the remaining 27 were for recurrent disease. Thirty-eight of the treatment regimens involved surgery alone, 10 surgery plus adjuvant radiotherapy, and 16 definitive radiotherapy for unresectable disease. The effects of patient, tumor, and treatment factors were modeled simultaneously using multiple variable Cox proportional hazards regression for associations with local recurrence, distant recurrence, and overall survival. Results: Local failure occurred in 16 of the 38 instances that involved surgery alone, in 2 of the 10 that consisted of surgery plus adjuvant radiotherapy, and in 1 instance of definitive radiotherapy. Lack of radiotherapy use was associated with 4.7 times the risk of local failure compared with treatment regimens that involved radiotherapy (95% confidence interval, 1.2-19.0; p = 0.030). Conclusions: Radiotherapy seems to significantly lower the risk of local recurrence/progression in patients with adrenocortical carcinoma. Adjuvant radiotherapy should be strongly considered after surgical resection.

  15. Cognitive function in postmenopausal women receiving adjuvant letrozole or tamoxifen for breast cancer in the BIG 1-98 randomized trial

    PubMed Central

    Phillips, Kelly Anne; Ribi, Karin; Sun, Zhuoxin; Stephens, Alisa; Thompson, Alastair; Harvey, Vernon; Thürlimann, Beat; Cardoso, Fatima; Pagani, Olivia; Coates, Alan S.; Goldhirsch, Aron; Price, Karen N.; Gelber, Richard D.; Bernhard, Jürg

    2010-01-01

    Summary Cognitive function in postmenopausal women receiving letrozole or tamoxifen as adjuvant endocrine treatment was compared during the fifth year of treatment in a substudy of the BIG 1-98 trial. In BIG 1-98 patients were randomized to receive adjuvant A) 5-years tamoxifen, B) 5-years letrozole, C) 2-years tamoxifen followed by 3-years letrozole, or D) 2-years letrozole followed by 3-years tamoxifen. The primary comparison was the difference in composite score for patients taking letrozole (B+C; N=65) versus tamoxifen (A+D; N=55). The patients taking letrozole had better overall cognitive function than those taking tamoxifen (difference in mean composite z-scores =0.28, p=0.04, 95% CI:0.02, 0.54, Cohen's D = 0.40 indicating small to moderate effect). In this substudy, breast cancer patients taking adjuvant letrozole during the fifth year of treatment had better cognitive function than those taking tamoxifen, suggesting aromatase inhibitors do not adversely impact cognition compared with tamoxifen. PMID:20385495

  16. Occurrence of Endocrine-Disrupting and Other Wastewater Compounds during Water Treatment with Case Studies from Lincoln, Nebraska and Berlin, Germany

    EPA Science Inventory

    Except for herbicides, research on the fate and transport of endocrine disrupting compounds and other organic wastewater compounds released into the environment and their potential presence in drinking water is in its infancy. Analytical methods still are being developed, evalua...

  17. Circadian clock control of endocrine factors.

    PubMed

    Gamble, Karen L; Berry, Ryan; Frank, Stuart J; Young, Martin E

    2014-08-01

    Organisms experience dramatic fluctuations in demands and stresses over the course of the day. In order to maintain biological processes within physiological boundaries, mechanisms have evolved for anticipation of, and adaptation to, these daily fluctuations. Endocrine factors have an integral role in homeostasis. Not only do circulating levels of various endocrine factors oscillate over the 24 h period, but so too does responsiveness of target tissues to these signals or stimuli. Emerging evidence suggests that these daily endocrine oscillations do not occur solely in response to behavioural fluctuations associated with sleep-wake and feeding-fasting cycles, but are orchestrated by an intrinsic timekeeping mechanism known as the circadian clock. Disruption of circadian clocks by genetic and/or environmental factors seems to precipitate numerous common disorders, including the metabolic syndrome and cancer. Collectively, these observations suggest that strategies designed to realign normal circadian rhythmicities hold potential for the treatment of various endocrine-related disorders.

  18. The skeleton as an endocrine organ.

    PubMed

    DiGirolamo, Douglas J; Clemens, Thomas L; Kousteni, Stavroula

    2012-11-01

    Surprising new discoveries in the field of skeletal biology show that bone cells produce endocrine hormones that regulate phosphate and glucose homeostasis. In this Review, we examine the features of these new endocrine pathways and discuss their physiological importance in the context of our current understanding of energy metabolism and mineral homeostasis. Consideration of evolutionary and comparative biology provides clues that a key driving force for the emergence of these hormonal pathways was the development of a large, energy-expensive musculoskeletal system. Specialized bone cells also evolved and produced endocrine hormones to integrate the skeleton in global mineral and nutrient homeostasis. The recognition of bone as a true endocrine organ represents a fertile area for further research and should improve the diagnosis and treatment of metabolic diseases such as osteoporosis and diabetes mellitus.

  19. Gliadel wafer implantation combined with standard radiotherapy and concurrent followed by adjuvant temozolomide for treatment of newly diagnosed high-grade glioma: a systematic literature review.

    PubMed

    Ashby, Lynn S; Smith, Kris A; Stea, Baldassarre

    2016-08-24

    Since 2003, only two chemotherapeutic agents, evaluated in phase III trials, have been approved by the US Food and Drug Administration for treatment of newly diagnosed high-grade glioma (HGG): Gliadel wafers (intracranially implanted local chemotherapy) and temozolomide (TMZ) (systemic chemotherapy). Neither agent is curative, but each has been shown to improve median overall survival (OS) compared to radiotherapy (RT) alone. To date, no phase III trial has tested these agents when used in sequential combination; however, a number of smaller trials have reported favorable results. We performed a systematic literature review to evaluate the combination of Gliadel wafers with standard RT (60 Gy) plus concurrent and adjuvant TMZ (RT/TMZ) for newly diagnosed HGG. A literature search was conducted for the period of January 1995 to September 2015. Data were extracted and categorized, and means and ranges were determined. A total of 11 publications met criteria, three prospective trials and eight retrospective studies, representing 411 patients who received Gliadel plus standard RT/TMZ. Patients were similar in age, gender, and performance status. The weighted mean of median OS was 18.2 months (ten trials, n = 379, range 12.7 to 21.3 months), and the weighted mean of median progression-free survival was 9.7 months (seven trials, n = 287, range 7 to 12.9 months). The most commonly reported grade 3 and 4 adverse events were myelosuppression (10.22 %), neurologic deficit (7.8 %), and healing abnormalities (4.3 %). Adverse events reflected the distinct independent safety profiles of Gliadel wafers and RT/TMZ, with little evidence of enhanced toxicity from their use in sequential combination. In the 11 identified trials, an increased benefit from sequentially combining Gliadel wafers with RT/TMZ was strongly suggested. Median OS tended to be improved by 3 to 4 months beyond that observed for Gliadel wafers or TMZ when used alone in the respective phase III

  20. Endocrine disorders & female infertility.

    PubMed

    Unuane, David; Tournaye, Herman; Velkeniers, Brigitte; Poppe, Kris

    2011-12-01

    Female infertility occurs in about 37% of all infertile couples and ovulatory disorders account for more than half of these. The ovaries are in continuous interaction with the other endocrine organs. The interplay may account for infertility occurring at different levels and may render the diagnosis of infertility a difficult exercise for the involved physician. A hypothalamic cause of female infertility should be considered in an appropriate clinical context, with tests pointing to a hypogonadotropic hypogonadism. It can be functional, physiological or related to organic causes. Hyperprolactinemia has well characterized effects on the normal gonadal function and treatment is well established. Acromegaly and Cushing's disease may impair fertility at different levels, mechanisms involved however remain ill defined. Thyroid disorders, both hyperthyroidism and hypothyroidism, can interact with the ovaries, through a direct effect on ovarian function, but autoimmunity may be involved, as well as alterations of the sex hormone binding protein levels. Primary ovarian disorders, such as the polycystic ovary syndrome and primary ovarian insufficiency are frequent diseases, for which novel treatments are currently being developed and discussed. We will propose an algorithm for the diagnosis and approach of the female patient presenting with infertility on the basis of the available evidence in literature.

  1. Adjuvant chemotherapy in elderly patients with pancreatic cancer

    PubMed Central

    Nagrial, A M; Chang, D K; Nguyen, N Q; Johns, A L; Chantrill, L A; Humphris, J L; Chin, V T; Samra, J S; Gill, A J; Pajic, M; Pinese, M; Colvin, E K; Scarlett, C J; Chou, A; Kench, J G; Sutherland, R L; Horvath, L G; Biankin, A V

    2014-01-01

    Background: Adjuvant chemotherapy improves survival for patients with resected pancreatic cancer. Elderly patients are under-represented in Phase III clinical trials, and as a consequence the efficacy of adjuvant therapy in older patients with pancreatic cancer is not clear. We aimed to assess the use and efficacy of adjuvant chemotherapy in older patients with pancreatic cancer. Methods: We assessed a community cohort of 439 patients with a diagnosis of pancreatic ductal adenocarcinoma who underwent operative resection in centres associated with the Australian Pancreatic Cancer Genome Initiative. Results: The median age of the cohort was 67 years. Overall only 47% of all patients received adjuvant therapy. Patients who received adjuvant chemotherapy were predominantly younger, had later stage disease, more lymph node involvement and more evidence of perineural invasion than the group that did not receive adjuvant treatment. Overall, adjuvant chemotherapy was associated with prolonged survival (median 22.1 vs 15.8 months; P<0.0001). Older patients (aged ⩾70) were less likely to receive adjuvant chemotherapy (51.5% vs 29.8% P<0.0001). Older patients had a particularly poor outcome when adjuvant therapy was not delivered (median survival=13.1 months; HR 1.89, 95% CI: 1.27–2.78, P=0.002). Conclusion: Patients aged ⩾70 are less likely to receive adjuvant therapy although it is associated with improved outcome. Increased use of adjuvant therapy in older individuals is encouraged as they constitute a large proportion of patients with pancreatic cancer. PMID:24263063

  2. Cushing's syndrome presenting as treatment-resistant bipolar affective disorder: A step in understanding endocrine etiology of mood disorders

    PubMed Central

    Ummar, I. Syed; Rajaraman, Venkateswaran; Loganathan, N.

    2015-01-01

    Cushing's syndrome (CS) is the multisystem disorder which is due to cortisol excess. It is very difficult to diagnose in early stages, especially when psychiatric manifestations are the predominant complaints. It could result in significant morbidity and mortality. We report a case of resistant bipolar affective disorder secondary to CS. Early diagnosis and treatment will lead to better functional outcome and prevention of neurocognitive side-effects of excessive cortisol. PMID:26124528

  3. Androgenic endocrine disruptors in wastewater treatment plant effluents in India: Their influence on reproductive processes and systemic toxicity in male rats

    SciTech Connect

    Kumar, Vikas; Chakraborty, Ajanta; Viswanath, Gunda; Roy, Partha

    2008-01-01

    Endocrine-disrupting chemicals (EDC) are linked to human health and diseases as they mimic or block the normal functioning of endogenous hormones. The present work dealt with a comparative study of the androgenic potential of wastewater treatment plant (WWTP) influents and effluents in Northern region of India, well known for its polluted water. Water samples were screened for their androgenic potential using the Hershberger assay and when they were found positive for androgenicity, we studied their mode of action in intact rats. The data showed a significant change in the weight and structure of sex accessory tissues (SATs) of castrated and intact rats. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis demonstrated a significant change in the expression patterns of the major steroidogenic enzymes in adrenal and testis: cytochrome P450{sub SCC}, cytochrome P450{sub C17}, 3{beta}-hydroxysteroid dehydrogenase, 17{beta}-hydroxysteroid dehydrogenase. This was further supported by increased enzymatic activities measured in vitro spectrophotometrically. Serum hormone profile showed a decreased level of gonadotrophic hormones and increased testosterone level. Further, increase in the serum level of alkaline phosphatase, SGPT and SGOT and histopathological changes in kidney and liver of treated animals, confirmed the toxic effects of contaminating chemicals. Analysis of water samples using HPLC and GC-MS showed the presence of various compounds and from them, four prominent aromatic compounds viz. nonylphenol, hexachlorobenzene and two testosterone equivalents, were identified. Our data suggest that despite rigorous treatment, the final treated effluent from WWTP still has enough androgenic and toxic compounds to affect general health.

  4. Adjuvant therapy for colon cancer in the new millenium.

    PubMed

    Rao, S; Cunningham, D

    2003-01-01

    A significant proportion of patients with colon cancer who undergo curative surgical resection develop metastatic disease. Over the last 20 years large prospective randomised studies have demonstrated a clear survival benefit for patients with stage III colon cancer who are treated with adjuvant 5FU based chemotherapy. At the present time 6 months of 5FU and leucovorin is generally considered the standard adjuvant therapy. For stage II disease the routine use of adjuvant treatment remains controversial. Newer drugs such as oxaliplatin, irinotecan, and the oral fluoropyrimidines have proven active in advanced colorectal cancer and are currently being evaluated in the adjuvant setting. Molecular markers for this disease are being identified and may help define those patients who would benefit from therapy. The integration of adjuvant immunotherapy with conventional chemotherapy offers the potential to improve the long-term outcome for surgically resected colon cancer.

  5. The endocrine system in diabetes mellitus.

    PubMed

    Alrefai, Hisham; Allababidi, Hisham; Levy, Shiri; Levy, Joseph

    2002-07-01

    The pathophysiology of diabetes mellitus is complex and not fully understood. However, it emerges as an abnormal metabolic condition associated with a systemic damage to the vascular bed. Cumulative evidence also reveals that the endocrine system is not intact in patients with diabetes mellitus. It is not clear whether the changes observed in the endocrine system represent a primary defect or reflect the effects of the impaired insulin action and abnormal carbohydrate and lipid metabolism on the hormonal milieu. Review of the literature reveals that the function of the entire endocrine system including the functions of hormones from the hypothalamus, pituitary, adrenal, thyroid, parathyroid, the vitamin D system, the gonads, and the endocrine function of the adipose tissue, is impaired. Good metabolic control and insulin treatment may reverse some of these abnormalities. It remains unanswered as to what extent these changes in the endocrine system contribute to the vascular pathologies observed in individuals affected by diabetes mellitus and whether part of the abnormalities observed in the endocrine system reflect a basic cellular defect in the diabetic syndrome.

  6. Criteria for malignancy in gastrointestinal endocrine tumors.

    PubMed

    Bordi, Cesare; D'Adda, Tiziana; Azzoni, Cinzia; Pizzi, Silvia; Bottarelli, Lorena; Mormandi, Francesca; Antonetti, Tommaso; Luong, Tu Vinh; Rindi, Guido

    2006-01-01

    In contrast with the large amount of data generated from endocrine tumors of the pancreas, sparse and mostly unconfirmed data are available on the criteria for the assessment of malignancy risk and patient outcome in endocrine tumors of the gastrointestinal tract. In these conditions the 2000 WHO classification with its standardized scheme of pathologic report constitutes a framework facilitating the assessment of tumor malignancy and has been regarded as useful for clinical purposes, providing the basis for proper management of the patients and for the design of treatment protocols. The classification is based on a combination of pathological and clinical features with parameters specific for each organ in which the endocrine tumors originate. Three main categories, one further subdivided into two subgroups, are considered: (1) well-differentiated endocrine tumors, further subdivided into tumors with benign and with uncertain behavior; (2) well-differentiated endocrine carcinomas, low grade; and (3) poorly differentiated endocrine carcinomas, high grade. In this review the differential tumor characteristics between the different categories are summarized. Moreover, the relevance of additional features with respect to tumor prognostication, chiefly the Ki-67 proliferation index and malignancy-associated genetic changes, is discussed with emphasis on the discrepancies emerging between tumors of foregut and of midgut origin.

  7. Clinical and endocrine responses to pituitary radiotherapy in pediatric Cushing's disease: an effective second-line treatment.

    PubMed

    Storr, Helen L; Plowman, P Nicholas; Carroll, Paul V; François, Inge; Krassas, Gerasimos E; Afshar, Farhad; Besser, G Michael; Grossman, Ashley B; Savage, Martin O

    2003-01-01

    Transsphenoidal surgery (TSS) is considered first-line treatment for Cushing's disease (CD). Options for treatment of postoperative persisting hypercortisolemia are pituitary radiotherapy (RT), repeat TSS, or bilateral adrenalectomy. From 1983 to 2001, we treated 18 pediatric patients (age, 6.4-17.8 yr) with CD. All underwent TSS, and 11 were cured (postoperative serum cortisol, <50 nM). Seven (39%) had 0900-h serum cortisol of 269-900 nM during the immediate postoperative period (2-20 d), indicating lack of cure. These patients (6 males and 1 female; mean age, 12.8 yr; range, 6.4-17.8 yr; 4 prepubertal; 3 pubertal) received external beam RT to the pituitary gland, using a 6-MV linear accelerator, with a dose of 45 Gy in 25 fractions over 35 d. Until the RT became effective, hypercortisolemia was controlled with ketoconazole (dose, 200-600 mg/d) (n = 4) and metyrapone (750 mg-3 g/d) +/- aminoglutethimide (1 g/d) or o'p'DDD (mitotane, 3 mg/d) (n = 3). All patients were cured after pituitary RT. The mean interval from RT to cure (mean serum cortisol on 5-point day curve, <150 nM) was 0.94 yr (0.25-2.86 yr). Recovery of pituitary-adrenal function (mean cortisol, 150-300 nM) occurred at mean 1.16 yr (0.40-2.86 yr) post RT. At 2 yr post RT, puberty occurred early in one male patient (age, 9.8 yr) but was normal in the others. GH secretion was assessed at 0.6-2.5 yr post RT in all patients: six had GH deficiency (peak on glucagon/insulin provocation, <1.0-17.9 mU/liter) and received human GH replacement. Follow-up of pituitary function 7.6 and 9.5 yr post RT in two patients showed normal gonadotropin secretion and recovery of GH peak to 29.7 and 19.2 mU/liter. The seven patients were followed for mean 6.9 yr (1.4-12.0 yr), with no evidence of recurrence of CD. In conclusion, pituitary RT is an effective and relatively rapid-onset treatment for pediatric CD after failure of TSS. GH deficiency occurred in 86% patients. Long-term follow-up suggests some recovery of GH

  8. Research on Endocrine Disruptors

    EPA Pesticide Factsheets

    EPA researchers are developing innovative approaches, tools, models and data to improve the understanding of potential risks to human health and wildlife from chemicals that could disrupt the endocrine system.

  9. Multiple Endocrine Neoplasia Syndromes

    MedlinePlus

    ... Endocrine Neoplasia Syndromes By Patricia A. Daly, MD, University of Virginia;Front Royal Internal Medicine, VA ; Lewis Landsberg, MD, Northwestern University NOTE: This is the Consumer Version. DOCTORS: Click ...

  10. Endocrine Drugs in Aircrew

    DTIC Science & Technology

    2001-06-01

    stresses. common endocrine diseases are diabetes mellitus, thyrotoxicosis, hypothyroidism, nodular goiter , The human adrenal consists of an outer cortex...about 40% goiter or thyroid carcinoma. of patients with primary hypothyroidism. Insulin requirements in diabetics are frequently increased in

  11. Endocrine Disrupting Chemicals (EDCs)

    MedlinePlus

    ... your body handles stress and responds to the environment. Results of animal and human scientific studies support a link between EDCs and ... to cause endocrine, reproductive, or neurological problems in humans. ... environmental contamination. For example, in 1976 an industrial accident ...

  12. Adjuvant therapy use among Appalachian breast cancer survivors.

    PubMed

    Tan, Xi; Marshall, Vincent D; Anderson, Roger T; Donohoe, Joseph; Camacho, Fabian; Balkrishnan, Rajesh

    2015-07-01

    There is a paucity of literature systemically examining the effects of access to cancer care resources on adjuvant endocrine therapy (AET) use behaviors, especially in underserved regions such as the Appalachian region in the United States, where gaps in healthcare access are well documented. The objectives of this study were to explore AET adherence and persistence in Appalachia, delineate the effects of access to care cancer on adherence/persistence, and evaluate the influences of adherence and persistence on overall survival.A retrospective cohort study from 2006 to 2008 was conducted among female breast cancer survivors living in the Appalachian counties of 4 states (PA, OH, KY, and NC). We linked cancer registries to Medicare claims data and included patients with invasive, nonmetastatic, hormone-receptor-positive breast cancer who received guideline-recommended AET. Medication adherence was defined as corresponding to a Medication Possession Ratio (MPR) ≥0.8 and logistic regression was utilized to assess predictors of adherence. Medication nonpersistence was defined as the discontinuation of drugs after exceeding a 60-day medication gap, and multivariate adjusted estimates of nonpersistence were obtained using the Cox proportional hazards (PH) model.About 31% of the total 428 patients were not adherent to AET, and 30% were not persistent over an average follow-up period of 421 days. Tamoxifen, relative to aromatase inhibitors, was associated with higher odds of adherence (odds ratio = 2.82, P < 0.001) and a lower risk of nonpersistence (hazard ratio = 0.40, P < 0.001). Drug-related side effects like pain may be an important factor leading to nonadherence and early discontinuation. In addition, aromatase inhibitor (AI) adherence and persistence were significantly influenced by out-of-pocket drug costs, dual eligibility status, and coverage gaps. Nonadherence to and nonpersistence with AET were associated with higher risks of all-cause mortality.Our findings

  13. Endocrine system: part 2.

    PubMed

    Hendry, Charles; Farley, Alistair; McLafferty, Ella; Johnstone, Carolyn

    2014-06-03

    This article, the last in the life sciences series, is the second of two articles on the endocrine system. It discusses human growth hormone, the pancreas and adrenal glands. The relationships between hormones and their unique functions are also explored. It is important that nurses understand how the endocrine system works and its role in maintaining health to provide effective care to patients. Several disorders caused by human growth hormone or that affect the pancreas and adrenal glands are examined.

  14. Year-long evaluation on the occurrence and fate of pharmaceuticals, personal care products, and endocrine disrupting chemicals in an urban drinking water treatment plant.

    PubMed

    Padhye, Lokesh P; Yao, Hong; Kung'u, Francis T; Huang, Ching-Hua

    2014-03-15

    The occurrence and removal of thirty representative pharmaceutical and personal care products (PPCPs) and endocrine disrupting chemicals (EDCs) in an urban drinking water treatment plant (DWTP) were investigated for a period of one year to evaluate current system's treatment efficacy and assess occurrence of PPCPs and EDCs in finished drinking water. Results showed that the average total PPCPs and EDCs concentration in the surface water source was around 360 ng/L (median concentration = 340 ng/L) with 57% coefficient of variation (CV). The median concentrations of most of the individual PPCPs and EDCs in the surface water were below 15 ng/L except for N,N-diethyltoluamide (DEET) and nonylphenol, which were at 122 and 83 ng/L, respectively. The compounds DEET, nonylphenol, ibuprofen, triclosan, atrazine, tris(2-chloroethyl)-phosphate (TCEP), bisphenol-A, and caffeine (in the order of decreasing median concentration) were among twenty compounds detected at least once in the surface water, while all of the above detected compounds, except two, were also detected in the finished drinking water. The average total PPCPs and EDCs concentration in the finished drinking water was around 98 ng/L (median concentration = 96 ng/L) with 66% CV. The median concentrations of most detected PPCPs and EDCs in drinking water were below 5 ng/L except for DEET and nonylphenol, which were at 12 and 20 ng/L, respectively. There was a strong correlation (r = 0.97) between PPCPs and EDCs' concentrations in the source water and in the drinking water over the one-year study period when data points from two sampling events with unusual removals were excluded. Individual water treatment unit processes showed greater temporal variations of PPCPs and EDCs removal efficiencies than the overall treatment processes. The removal efficiencies also varied greatly among different PPCPs and EDCs. The average removal for total PPCPs and EDCs was 76 ± 18% at the DWTP, with ozonation

  15. Activity of glycated chitosan and other adjuvants to PDT vaccines

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

    2015-03-01

    Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

  16. Endometrial adenocarcinoma, adjuvant radiotherapy tailored to prognostic factors.

    PubMed

    Meerwaldt, J H; Hoekstra, C J; van Putten, W L; Tjokrowardojo, A J; Koper, P C

    1990-02-01

    The optimal adjuvant radiotherapy for surgically treated endometrial cancer has not yet been defined. We report on 389 patients treated between 1970 and 1985 with adjuvant radiotherapy. The treatment was tailored to the known prognostic factors: myometrial invasion and grade of differentiation of the tumor. Ten-year overall survival was 67%, 10-year relapse-free survival 77%; 23% relapse, of which 21% distant and 6% locoregional relapse. In a multivariate analysis, stage (pT), grade, and myometrial invasion were prognostic factors. The number of locoregional failures was very small (n = 23). This small number, the fact that radiation treatment was tailored to prognostic factors, and the absence of a nontreated control group precluded an analysis of the effect of the adjuvant irradiation. Large randomized studies with a control (no treatment) arm should be performed to determine the value of adjuvant radiotherapy.

  17. Pancreatic endocrine neoplasms: Epidemiology and prognosis of pancreatic endocrine tumors

    PubMed Central

    Halfdanarson, Thorvardur R.; Rubin, Joseph; Farnell, Michael B.; Grant, Clive S.; Petersen, Gloria M.

    2009-01-01

    Pancreatic endocrine neoplasms (PETs) are uncommon tumors with an annual incidence less than 1 per 100,000 persons per year in the general population. PETs that produce hormones resulting in symptoms are designated as functional. The majority of PETs are nonfunctional. Of the functional tumors, insulinomas are the most common, followed by gastrinomas. The clinical course of patients with PETs is variable and depends on the extent of the disease and the treatment rendered. Patients with completely resected tumors generally have a good prognosis, and aggressive surgical therapy in patients with advanced disease may also prolong survival. The epidemiology, prognosis and established and novel prognostic markers of PETs are reviewed. PMID:18508996

  18. Performance characteristics of a conformal ultra-wideband multilayer applicator (CUMLA) for hyperthermia in veterinary patients: a pilot evaluation of its use in the adjuvant treatment of non-resectable tumours.

    PubMed

    Smrkovski, O A; Koo, Y; Kazemi, R; Lembcke, L M; Fathy, A; Liu, Q; Phillips, J C

    2013-03-01

    Performance and clinical characteristics of a novel hyperthermia antenna operating at 434 MHz were evaluated for the adjuvant treatment of locally advanced superficial tumours in cats, dogs and horses. Electromagnetic simulations were performed to determine electric field characteristics and compared to simulations for a flat microwave antenna with similar dimensions. Simulation results show a reduced skin surface and backfield irradiation and improved directional irradiation (at broadside) compared to a flat antenna. Radiated power and penetration is notably increased with a penetration depth of 4.59 cm compared to 2.74 cm for the flat antenna. Clinical use of the antenna was then evaluated in six animals with locoregionally advanced solid tumours receiving adjuvant chemotherapy. During clinical applications, therapeutic temperatures were achieved at depths ≥4 cm. Objective responses were seen in all patients; tissue toxicity in one case limited further therapy. This antenna provides compact, efficient, focused and deep-penetrating clinical hyperthermia for the treatment of solid tumours in veterinary patients.

  19. Prognostic impact of progesterone receptor status combined with body mass index in breast cancer patients treated with adjuvant aromatase inhibitor.

    PubMed

    Ohara, Masahiro; Akimoto, Etsushi; Noma, Midori; Matsuura, Kazuo; Doi, Mihoko; Kagawa, Naoki; Itamoto, Toshiyuki

    2015-11-01

    Aromatase inhibitors have played a central role in endocrine therapy for the treatment of estrogen receptor (ER)-positive breast cancer in postmenopausal patients. However, prognostic factors for recurrence following such treatment have not been identified. The current study aimed to validate the prognostic value of endocrine-related progesterone receptor (PgR) status combined with body mass index (BMI). Among 659 consecutive patients with primary breast cancer who underwent curative surgery between 2002 and 2012, 184 postmenopausal patients with ER-positive (ER+) and human epidermal growth factor receptor type 2-negative (HER2-) breast cancer who were treated with adjuvant aromatase inhibitor therapy were assessed. The patients were assigned to groups based on BMI, according to the WHO cut-off value: ≥25 kg/m(2) (high, H) or <25 kg/m(2) (low, L). Positive nodal status, negative PgR status, BMI-H and a high Ki-67 labeling index (≥20%) were found to be significantly associated with a short recurrence-free interval (RFI) upon univariate analysis (P=0.048, 0.007, 0.027, and 0.012, respectively). The patients were further grouped based on their combined PgR/BMI status. The RFI was significantly shorter in the PgR- and/or BMI-H group compared with that of the PgR+/BMI-L group (P=0.012). Multivariate analysis revealed PgR- tumors and/or BMI-H and positive nodal status to be independent prognostic factors (P=0.012 and 0.020, respectively). The present findings indicate that PgR/BMI status may serve as a practical tool in the management of ER+ and HER2- breast cancer in patients treated with adjuvant aromatase inhibitors.

  20. [Neoadjuvant, inductive or adjuvant chemotherapy of bladder cancer].

    PubMed

    Ohlmann, C-H; De Santis, M

    2013-11-01

    Perioperative chemotherapy is a standard treatment for patients with muscle-invasive bladder carcinoma undergoing radical cystectomy; however, direct comparisons of neoadjuvant and adjuvant chemotherapy are lacking. Evidence-based data and implementation into daily clinical practice favor neoadjuvant chemotherapy; nevertheless, neoadjuvant chemotherapy is still underused in daily practice compared to adjuvant chemotherapy. If neoadjuvant chemotherapy has not been used and patients are fit enough to receive cisplatin, adjuvant chemotherapy should be considered in patients with pT3-pT4 and/or lymph node metastases.

  1. Endocrine Disease in Aged Horses.

    PubMed

    Durham, Andy E

    2016-08-01

    Aging horses may be at particular risk of endocrine disease. Two major equine endocrinopathies, pituitary pars intermedia dysfunction and equine metabolic syndrome, are commonly encountered in an aging population and may present with several recognizable signs, including laminitis. Investigation, treatment, and management of these diseases are discussed. Additionally, aging may be associated with development of rarer endocrinopathic problems, often associated with neoplasia, including diabetes mellitus and other confounders of glucose homeostasis, as well as thyroid, parathyroid, and adrenal diseases. Brief details of the recognition and management of these conditions are presented.

  2. Inhibition of focal adhesion kinase suppresses the adverse phenotype of endocrine-resistant breast cancer cells and improves endocrine response in endocrine-sensitive cells.

    PubMed

    Hiscox, Stephen; Barnfather, Peter; Hayes, Edd; Bramble, Pamela; Christensen, James; Nicholson, Robert I; Barrett-Lee, Peter

    2011-02-01

    Acquired resistance to endocrine therapy in breast cancer is a major clinical problem. Previous reports have demonstrated that cell models of acquired endocrine resistance have altered cell-matrix adhesion and a highly migratory phenotype, features which may impact on tumour spread in vivo. Focal adhesion kinase (FAK) is an intracellular kinase that regulates signalling pathways central to cell adhesion, migration and survival and its expression is frequently deregulated in breast cancer. In this study, we have used the novel FAK inhibitor PF573228 to address the role of FAK in the development of endocrine resistance. Whilst total-FAK expression was similar between endocrine-sensitive and endocrine-resistant MCF7 cells, FAK phosphorylation status (Y397 or Y861) was altered in resistance. PF573228 promoted a dose-dependent inhibition of FAK phosphorylation at Y397 but did not affect other FAK activation sites (pY407, pY576 and pY861). Endocrine-resistant cells were more sensitive to these inhibitory effects versus MCF7 (mean IC(50) for FAK pY397 inhibition: 0.43 μM, 0.05 μM and 0.13 μM for MCF7, TamR and FasR cells, respectively). Inhibition of FAK pY397 was associated with a reduction in TamR and FasR adhesion to, and migration over, matrix components. PF573228 as a single agent (0-1 μM) did not affect the growth of MCF7 cells or their endocrine-resistant counterparts. However, treatment of endocrine-sensitive cells with PF573228 and tamoxifen combined resulted in greater suppression of proliferation versus single agent treatment. Together these data suggest the importance of FAK in the process of endocrine resistance, particularly in the development of an aggressive, migratory cell phenotype and demonstrate the potential to improve endocrine response through combination treatment.

  3. Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study

    PubMed Central

    Marston, Louise; Walters, Kate; Geddes, John R.; King, Michael; Osborn, David P. J.

    2016-01-01

    0.73; p = 0.013) were also reduced relative to lithium. However, rates of greater than 15% weight gain on valproate, olanzapine, and quetiapine were higher (valproate HR 1.62; 95% CI 1.31–2.01; p < 0.001, olanzapine HR 1.84; 95% CI 1.47–2.30; p < 0.001, quetiapine HR 1.67; 95% CI 1.24–2.20; p < 0.001) than in individuals prescribed lithium, as were rates of hypertension in the olanzapine treated group (HR 1.41, 95% CI 1.06–1.87; p = 0.017). We found no significant difference in rates of chronic kidney disease stage 4 or more severe, type 2 diabetes mellitus, cardiovascular disease, or hepatotoxicity. Despite estimates being robust following sensitivity analyses, limitations include the potential for residual confounding and ascertainment bias and an inability to examine dosage effects. Conclusions Lithium use is associated with more renal and endocrine adverse events but less weight gain than commonly used alternative mood stabilizers. Risks need to be offset with the effectiveness and anti-suicidal benefits of lithium and the potential metabolic side effects of alternative treatment options. PMID:27483368

  4. Anthropogenic tracers, endocrine disrupting chemicals, and endocrine disruption in Minnesota lakes

    USGS Publications Warehouse

    Writer, J.H.; Barber, L.B.; Brown, G.K.; Taylor, H.E.; Kiesling, R.L.; Ferrey, M.L.; Jahns, N.D.; Bartell, S.E.; Schoenfuss, H.L.

    2010-01-01

    Concentrations of endocrine disrupting chemicals and endocrine disruption in fish were determined in 11 lakes across Minnesota that represent a range of trophic conditions and land uses (urban, agricultural, residential, and forested) and in which wastewater treatment plant discharges were absent. Water, sediment, and passive polar organic integrative samplers (POCIS) were analyzed for steroidal hormones, alkylphenols, bisphenol A, and other organic and inorganic molecular tracers to evaluate potential non-point source inputs into the lakes. Resident fish from the lakes were collected, and caged male fathead minnows were deployed to evaluate endocrine disruption, as indicated by the biological endpoints of plasma vitellogenin and gonadal histology. Endocrine disrupting chemicals, including bisphenol A, 17??-estradiol, estrone, and 4-nonylphenol were detected in 90% of the lakes at part per trillion concentrations. Endocrine disruption was observed in caged fathead minnows and resident fish in 90% of the lakes. The widespread but variable occurrence of anthropogenic chemicals in the lakes and endocrine disruption in fish indicates that potential sources are diverse, not limited to wastewater treatment plant discharges, and not entirely predictable based on trophic status and land use. ?? 2010.

  5. Anthropogenic tracers, endocrine disrupting chemicals, and endocrine disruption in Minnesota lakes.

    PubMed

    Writer, Jeffrey H; Barber, Larry B; Brown, Greg K; Taylor, Howard E; Kiesling, Richard L; Ferrey, Mark L; Jahns, Nathan D; Bartell, Steve E; Schoenfuss, Heiko L

    2010-12-01

    Concentrations of endocrine disrupting chemicals and endocrine disruption in fish were determined in 11 lakes across Minnesota that represent a range of trophic conditions and land uses (urban, agricultural, residential, and forested) and in which wastewater treatment plant discharges were absent. Water, sediment, and passive polar organic integrative samplers (POCIS) were analyzed for steroidal hormones, alkylphenols, bisphenol A, and other organic and inorganic molecular tracers to evaluate potential non-point source inputs into the lakes. Resident fish from the lakes were collected, and caged male fathead minnows were deployed to evaluate endocrine disruption, as indicated by the biological endpoints of plasma vitellogenin and gonadal histology. Endocrine disrupting chemicals, including bisphenol A, 17β-estradiol, estrone, and 4-nonylphenol were detected in 90% of the lakes at part per trillion concentrations. Endocrine disruption was observed in caged fathead minnows and resident fish in 90% of the lakes. The widespread but variable occurrence of anthropogenic chemicals in the lakes and endocrine disruption in fish indicates that potential sources are diverse, not limited to wastewater treatment plant discharges, and not entirely predictable based on trophic status and land use.

  6. Ductal Carcinoma In Situ: Treatment Update and Current Trends.

    PubMed

    Mitchell, Katrina B; Kuerer, Henry

    2015-11-01

    Ductal carcinoma in situ (DCIS) traditionally has been managed through various combinations of surgery, radiation, and endocrine therapy. However, concern for under- or over-treatment of DCIS has led many surgeons to question historically standardized approaches and instead begin to tailor treatment based on individual prognostic indicators. Recent and ongoing clinical trials have investigated the potential for active surveillance in DCIS, the possibility of eliminating radiation therapy (RT), and ways in which adjuvant systemic therapy may be refined. This review will summarize the current trends in the treatment of DCIS, as well as highlight the most pertinent clinical trials that are shaping management today.

  7. Prospective evaluation of mitotane toxicity in adrenocortical cancer patients treated adjuvantly.

    PubMed

    Daffara, Fulvia; De Francia, Silvia; Reimondo, Giuseppe; Zaggia, Barbara; Aroasio, Emiliano; Porpiglia, Francesco; Volante, Marco; Termine, Angela; Di Carlo, Francesco; Dogliotti, Luigi; Angeli, Alberto; Berruti, Alfredo; Terzolo, Massimo

    2008-12-01

    Toxicity of adjuvant mitotane treatment is poorly known; thus, our aim was to assess prospectively the unwanted effects of adjuvant mitotane treatment and correlate the findings with mitotane concentrations. Seventeen consecutive patients who were treated with mitotane after radical resection of adrenocortical cancer (ACC) from 1999 to 2005 underwent physical examination, routine laboratory evaluation, monitoring of mitotane concentrations, and a hormonal work-up at baseline and every 3 months till ACC relapse or study end (December 2007). Mitotane toxicity was graded using NCI CTCAE criteria. All biochemical measurements were performed at our center and plasma mitotane was measured by an in-house HPLC assay. All the patients reached mitotane concentrations >14 mg/l and none of them discontinued definitively mitotane for toxicity; 14 patients maintained consistently elevated mitotane concentrations despite tapering of the drug. Side effects occurred in all patients but were manageable with palliative treatment and adjustment of hormone replacement therapy. Mitotane affected adrenal steroidogenesis with a more remarkable inhibition of cortisol and DHEAS than aldosterone. Mitotane induced either perturbation of thyroid function mimicking central hypothyroidism or, in male patients, inhibition of testosterone secretion. The discrepancy between salivary and serum cortisol, as well as between total and free testosterone, is due to the mitotane-induced increase in hormone-binding proteins which complicates interpretation of hormone measurements. A low-dose monitored regimen of mitotane is tolerable and able to maintain elevated drug concentrations in the long term. Mitotane exerts a complex effect on the endocrine system that may require multiple hormone replacement therapy.

  8. Management of adjuvant mitotane therapy following resection of adrenal cancer.

    PubMed

    Terzolo, M; Ardito, A; Zaggia, B; Laino, F; Germano, A; De Francia, S; Daffara, F; Berruti, A

    2012-12-01

    Whenever adrenal cancer (ACC) is completely removed we should face the dilemma to treat by means of adjuvant therapy or not. In our opinion, adjuvant mitotane is the preferable approach in most cases because the majority of patients following radical removal of an ACC have an elevated risk of recurrence. A better understanding of factors that influence prognosis and response to treatment will help in stratifying patients according to their probability of benefiting from adjuvant mitotane, with the aim of sparing unnecessary toxicity to patients who are likely unresponsive. However, until significant advancements take place, we have to deal with uncertainty using our best clinical judgement and personal experience in the clinical decision process. In the present paper, we present the current evidence on adjuvant mitotane treatment and describe the management strategies of patients with ACC after complete surgical resection. We acknowledge the limit that most recommendations are based on personal experience rather than solid evidence.

  9. Endocrine Treatment of Transsexual Persons

    MedlinePlus

    ... Before puberty, the major visible body differences between boys and girls are their external genitals—the male penis and ... enlargement will disappear and menstruation will stop in girls. In boys, development of a masculine body appearance will stop ...

  10. Treatment patterns of adjuvant interferon-α2b for high-risk melanoma: a retrospective study of the Grupo Español Multidisciplinar de Melanoma - Prima study.

    PubMed

    Espinosa, Enrique; Soriano, Virtudes; Malvehy, Josep; Berrocal, Alfonso; Martínez de Prado, Purificación; Quindós, María; Soria, Ainara; Márquez-Rodas, Iván; Palacio, Isabel; Cerezuela, Pablo; López-Vivanco, Guillermo; Alonso, Lorenzo; Samaniego, Elia; Ballesteros, Ana; Puértolas, Teresa; Díaz-Beveridge, Rodrigo; de la Cruz-Merino, Luis; López Castro, Rafael; López López, Rafael; Stevinson, Kendall; Del Barrio, Patricia; Tornamira, Maria V; Guillém, Vicente; Martín-Algarra, Salvador

    2016-06-01

    Adjuvant interferon-α2b (IFN-α2b) has been studied extensively in clinical trials, but there have been few studies of real-world use. The aim of this study is to describe the IFN-α2b real-world patterns in patients with high-risk melanoma in Spain. This was a retrospective and multicentre chart review study of an unselected cohort of patients with melanoma at high risk for relapse (stage IIB/IIC/III) treated with IFN-α2b. Patterns were assessed in terms of dose and compliance to planned treatment. A survival analysis was carried out for the full population and according to Kirkwood scheme compliance and the presence of ulceration. Of 327 patients treated with IFN-α2b, 318 received a high-dose regimen following the standard Kirkwood scheme; thus, patterns are described for this regimen. A total of 121 (38%) and 88 (28%) patients had at least one dose reduction during the induction and maintenance phases, respectively. Dose delay was required in fewer than 10% of patients. A total of 78, 40 and 38% of the patients completed the induction phase, maintenance phase and completed treatment, respectively. The median progression-free and overall survival for the full population were 3.2 and 10.5 years, respectively. There were no differences in progression-free survival and overall survival according to Kirkwood scheme compliance and the presence of ulceration. The most frequent adverse events were neutropenia (31%) and fatigue (30%). High-dose IFN-α2b is the most frequently used regimen in Spain as an adjuvant systemic treatment for high-risk melanoma. Despite poor compliance, in this retrospective study, IFN-α2b treatment provided a benefit consistent with that described previously.

  11. Treatment patterns of adjuvant interferon-α2b for high-risk melanoma: a retrospective study of the Grupo Español Multidisciplinar de Melanoma – Prima study

    PubMed Central

    Soriano, Virtudes; Malvehy, Josep; Berrocal, Alfonso; Martínez de Prado, Purificación; Quindós, María; Soria, Ainara; Márquez-Rodas, Iván; Palacio, Isabel; Cerezuela, Pablo; López-Vivanco, Guillermo; Alonso, Lorenzo; Samaniego, Elia; Ballesteros, Ana; Puértolas, Teresa; Díaz-Beveridge, Rodrigo; de la Cruz-Merino, Luis; López Castro, Rafael; López López, Rafael; Stevinson, Kendall; del Barrio, Patricia; Tornamira, Maria V.; Guillém, Vicente; Martín-Algarra, Salvador

    2016-01-01

    Adjuvant interferon-α2b (IFN-α2b) has been studied extensively in clinical trials, but there have been few studies of real-world use. The aim of this study is to describe the IFN-α2b real-world patterns in patients with high-risk melanoma in Spain. This was a retrospective and multicentre chart review study of an unselected cohort of patients with melanoma at high risk for relapse (stage IIB/IIC/III) treated with IFN-α2b. Patterns were assessed in terms of dose and compliance to planned treatment. A survival analysis was carried out for the full population and according to Kirkwood scheme compliance and the presence of ulceration. Of 327 patients treated with IFN-α2b, 318 received a high-dose regimen following the standard Kirkwood scheme; thus, patterns are described for this regimen. A total of 121 (38%) and 88 (28%) patients had at least one dose reduction during the induction and maintenance phases, respectively. Dose delay was required in fewer than 10% of patients. A total of 78, 40 and 38% of the patients completed the induction phase, maintenance phase and completed treatment, respectively. The median progression-free and overall survival for the full population were 3.2 and 10.5 years, respectively. There were no differences in progression-free survival and overall survival according to Kirkwood scheme compliance and the presence of ulceration. The most frequent adverse events were neutropenia (31%) and fatigue (30%). High-dose IFN-α2b is the most frequently used regimen in Spain as an adjuvant systemic treatment for high-risk melanoma. Despite poor compliance, in this retrospective study, IFN-α2b treatment provided a benefit consistent with that described previously. PMID:26958991

  12. Genetics Home Reference: multiple endocrine neoplasia

    MedlinePlus

    ... Multiple endocrine neoplasia, type 4 Genomics Education Programme (UK): Multiple Endocrine Neoplasia type 1 Genomics Education Programme (UK): Multiple Endocrine Neoplasia type 2A MalaCards: multiple endocrine ...

  13. Multiple Endocrine Neoplasia Syndromes

    PubMed Central

    Pont, Allan

    1980-01-01

    The multiple endocrine neoplasia (MEN) syndromes consist of three distinct disease entities. They have in common adenomatous, carcinomatous or hyperplastic involvement of a variety of endocrine glands, and an autosomal dominant inheritance. MEN I includes hyperparathyroidism, islet cell and pituitary tumors. The components of MEN IIa are hyperparathyroidism, medullary thyroid carcinoma and pheochromocytoma. MEN IIb includes multiple neuromas, medullary thyroid carcinoma and pheochromocytoma. Effective tests are available for the early detection of components of the syndromes in potentially affected patients. Screening can lead to therapeutic intervention before clinical sequelae ensue. PMID:6247851

  14. Phase 1 testing of detoxified LPS/group B meningococcal outer membrane protein vaccine with and without synthetic CPG 7909 adjuvant for the prevention and treatment of sepsis

    PubMed Central

    Cross, Alan S.; Greenberg, Nancy; Billington, Melissa; Zhang, Lei; DeFilippi, Christopher; May, Ryan C.; Bajwa, Kanwaldeep K.

    2015-01-01

    Background Gram-negative bacteria (GNB) are a leading cause of nosocomial infection and sepsis. Increasing multi-antibiotic resistance has left clinicians with fewer therapeutic options. Antibodies to GNB lipopolysaccharide (LPS, or endotoxin) have reduced morbidity and mortality as a result of infection and are not subject to the resistance mechanisms deployed by bacteria against antibiotics. In this phase 1 study, we administered a vaccine that elicits antibodies against a highly conserved portion of LPS with and without a CpG oligodeoxynucleotide (ODN) TLR9 agonist as adjuvant. Methods A vaccine composed of the detoxified LPS (dLPS) from E. coli O111:B4 (J5 mutant) non-covalently complexed to group B meningococcal outer membrane protein (OMP). Twenty healthy adult subjects received three doses at 0, 29 and 59 days of antigen (10 μg dLPS) with or without CPG 7909 (250 or 500 μg). Subjects were evaluated for local and systemic adverse effects and laboratory findings. Anti-J5 LPS IgG and IgM antibody levels were measured by electrochemiluminesence. Due to premature study termination, not all subjects received all three doses. Results All vaccine formulations were well-tolerated with no local or systemic events of greater than moderate severity. The vaccine alone group achieved a ≥4-fold “responder” response in IgG and IgM antibody in only one of 6 subjects. In contrast, the vaccine plus CPG 7909 groups appeared to have earlier and more sustained (to 180 days) responses, greater mean-fold increases, and a higher proportion of “responders” achieving ≥4-fold increases over baseline. Conclusions Although the study was halted before all enrolled subjects received all three doses, the J5dLPS/OMP vaccine, with or without CpG adjuvant, was safe and well-tolerated. The inclusion of CpG increased the number of subjects with a ≥4-fold antibody response, evident even after the second of three planned doses. A vaccine comprising J5dLPS/OMP antigen with Cp

  15. Your Endocrine System (For Kids)

    MedlinePlus

    ... Dictionary of Medical Words En Español What Other Kids Are Reading Taking Care of Your Ears Taking ... an X-ray Your Endocrine System KidsHealth > For Kids > Your Endocrine System Print A A A en ...

  16. Design of a randomised controlled trial of adapted physical activity during adjuvant treatment for localised breast cancer: the PASAPAS feasibility study

    PubMed Central

    Touillaud, M; Foucaut, A-M; Berthouze, S E; Reynes, E; Kempf-Lépine, A-S; Carretier, J; Pérol, D; Guillemaut, S; Chabaud, S; Bourne-Branchu, V; Perrier, L; Trédan, O; Fervers, B; Bachmann, P

    2013-01-01

    Introduction After a diagnosis of localised breast cancer, overweight, obesity and weight gain are negatively associated with prognosis. In contrast, maintaining an optimal weight through a balanced diet combined with regular physical activity appears to be effective protective behaviour against comorbidity or mortality after a breast cancer diagnosis. The primary aim of the Programme pour une Alimentation Saine et une Activité Physique Adaptée pour les patientes atteintes d'un cancer du Sein (PASAPAS) randomised controlled trial is to evaluate the feasibility of implementing an intervention of adapted physical activity (APA) for 6 months concomitant with the prescription of a first line of adjuvant chemotherapy. Secondary aims include assessing the acceptability of the intervention, compliance to the programme, process implementation, patients’ satisfaction, evolution of biological parameters and the medicoeconomic impact of the intervention. Methods and analysis The study population consists of 60 women eligible for adjuvant chemotherapy after a diagnosis of localised invasive breast cancer. They will be recruited during a 2-year inclusion period and randomly allocated between an APA intervention arm and a control arm following a 2:1 ratio. All participants should benefit from personalised dietetic counselling and patients allocated to the intervention arm will be offered an APA programme of two to three weekly sessions of Nordic walking and aerobic fitness. During the 6-month intervention and 6-month follow-up, four assessments will be performed including blood draw, anthropometrics and body composition measurements, and questionnaires about physical activity level, diet, lifestyle factors, psychological criteria, satisfaction with the intervention and medical data. Ethics and dissemination The study was approved by the French Ethics Committee (Comité de Protection des Personnes Sud-Est IV) and the national agencies for biomedical studies and for privacy

  17. Long-Term Treatment by Vitamin B1 and Reduction of Serum Proinflammatory Cytokines, Hyperalgesia, and Paw Edema in Adjuvant-Induced Arthritis

    PubMed Central

    Zaringhalam, Jalal; Akbari, Akhtar; Zali, Alireza; Manaheji, Homa; Nazemian, Vida; Shadnoush, Mahdi; Ezzatpanah, Somayeh

    2016-01-01

    Introduction: Immune system is involved in the etiology and pathophysiology of inflammation and vitamins are important sources of substances inducing nonspecific immunomodulatory effects. Given the proinflammatory role of cytokines in the inflammation and pain induction, this study aimed to assess the effects of long-term administration of vitamin B1 on the proinflammatory cytokines, edema, and hyperalgesia during the acute and chronic phases of adjuvant-induced arthritis. Methods: On the first day of study, inflammation was induced by intraplantar injection of complete Freund's adjuvant (CFA) in the hindpaws of rats. Vitamin B1 at doses of 100, 150, and 200 mg/kg was administrated intraperitoneally during 21 days of the study. Antinociceptive and anti-inflammatory effects of vitamin B1 were also compared to indomethacin (5 mg/kg). Inflammatory symptoms such as thermal hyperalgesia and paw edema were measured by radiant heat and plethysmometer, respectively. Serum TNF-α and IL-1β levels were checked by rat standard enzyme-linked immune sorbent assay (ELISA) specific kits. Results: The results indicated that vitamin B1(150 and 200 mg/kg) attenuated the paw edema, thermal hyperalgesia, and serum levels of TNF-α and IL-1β during both phases of CFA-induced inflammation in a dose-dependent manner. Effective dose of vitamin B1(150 mg/kg) reduced inflammatory symptoms and serum levels of TNF-α and IL-1β compare to indomethacin during the chronic phase of inflammation. Conclusion: Anti-inflammatory and antihyperalgesic effects of vitamin B1 during CFA-induced arthritis, more specifically after chronic vitamin B1 administration, suggest its therapeutic property for inflammation. PMID:27872694

  18. Your Endocrine System (For Kids)

    MedlinePlus

    ... Room? What Happens in the Operating Room? Your Endocrine System KidsHealth > For Kids > Your Endocrine System A A A en español Tu sistema endocrino ... a pea, is the "master gland" of the endocrine system. It makes and releases a bunch of hormones ...

  19. Proteomics as a Guide for Personalized Adjuvant Chemotherapy in Patients with Early Breast Cancer.

    PubMed

    Lumachi, Franco; Chiara, Giordano B; Foltran, Luisa; Basso, Stefano M M

    2015-01-01

    Proteomics allows for better understanding of the function and regulation of cancer cells mediated by intra- and extracellular signaling networks. Integrating such information with clinicopathological characteristics of the tumor may lead to either detection of disease biomarkers useful to differentiate high-from low-risk patients, or to identification of new drug targets. Adjuvant chemotherapy is currently a personalized treatment strategy, especially for breast cancer (BC) patients, and the risk assessment of each patient influences its use because the benefit strictly correlates with the level of risk. Luminal A BCs are endocrine therapy (ET)-sensitive but exhibit low sensitivity to chemotherapy, while luminal B cancers, according to the Ki-67 proliferation rate may require for chemotherapy in addition to ET, and HER2-positive tumors derive benefit from adjuvant chemotherapy containing an anthracycline, a taxane and trastuzumab for one year. Triple-negative BCs have a high degree of genomic instability exhibiting a more aggressive clinical course with respect to other types of BC, and the anthracycline-taxane regimen constitutes the standard approach. Studies considering the use of targeted approaches (drugs), including poly (ADP-ribose) polymerase (PARP-1), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) inhibitors, or EFGR and HER2 blockers, are still under evaluation. In the genomic era, promising new targeted-therapies are worthy of further investigation, and mTOR inhibitors have been used for patients with high-risk ER-positive and HER2-negative tumors. In the near future, genetic and molecular profiling of BC will help to better-categorize patients, determine the choice of chemotherapy in low-risk, or intensify the treatment in high-risk cancer patients, eventually revealing new targeted agents.

  20. The Endocrine Machinery.

    ERIC Educational Resources Information Center

    Fillman, David

    1987-01-01

    Promotes a reductionist approach to teaching about the endocrine system in high school biology and anatomy courses. Encourages the study of how hormones travel to the cells and affect them. Provides suggestions for activities and discussion questions, along with sample diagrams and flow charts. (TW)

  1. ENDOCRINE DISRUPTORS: LESSONS LEARNED

    EPA Science Inventory

    For more than ten years, major international efforts have been aimed at understanding the mechanism and extent of endocrine disruption in experimental models, wildlife, and people; its occurrence in the real world; and in developing tools for screening and prediction of risk. Mu...

  2. Therapeutic usefulness of postoperative adjuvant chemotherapy with Tegafur-Uracil (UFT) in patients with breast cancer: focus on the results of clinical studies in Japan.

    PubMed

    Nakayama, Takahiro; Noguchi, Shinzaburo

    2010-01-01

    In Japan, the history of postoperative chemotherapy for breast cancer started with 5-fluorouracil (5-FU), launched in the 1980s. Currently, oral fluoropyrimidine-based regimens indicated for the treatment of breast cancer in Japan include tegafur plus uracil (UFT); tegafur, gimeracil, and oteracil (TS-1); doxifluridine; and capecitabine. In particular, UFT represents an important option for long-term treatment because of minimal adverse events and the potential for long-term maintenance of effective plasma concentrations of 5-FU to inhibit micrometastasis after surgery. Therefore, various clinical studies of postoperative adjuvant chemotherapy with UFT have been conducted in patients with completely resected tumors. Recent studies have shown that UFT prolongs survival after tumor resection in patients with gastric cancer, colorectal cancer, and lung cancer. In patients with breast cancer, large clinical trials of UFT-based postoperative chemotherapy conducted in Japan have shown that UFT is useful for the treatment of intermediate-risk patients with no lymph node metastasis. This paper reviews the results of clinical studies of UFT conducted in Japan to assess the therapeutic usefulness of this oral 5-FU. The types of patients most likely to benefit from UFT are discussed on the basis of currently available evidence and a global consensus of treatment recommendations. The optimal timing of endocrine therapy and strategies for postoperative adjuvant chemotherapy with UFT in patients with breast cancer are also discussed.

  3. Deregulation of IGF-binding proteins -2 and -5 contributes to the development of endocrine resistant breast cancer in vitro.

    PubMed

    Hawsawi, Yousef; Humphries, Matthew P; Wright, Alexander; Berwick, Angelene; Shires, Mike; Al-Kharobi, Hanaa; El-Gendy, Reem; Jove, Maria; Twelves, Chris; Speirs, Valerie; Beattie, James

    2016-05-31

    Tamoxifen (TAM) remains the adjuvant therapy of choice for pre-menopausal women with ERα-positive breast cancer. Resistance and recurrence remain, however, a major challenge with many women relapsing and subsequently dying. The insulin-like growth factor (IGF) axis is involved in breast cancer pathogenesis and progression to endocrine resistant disease, but there is very little data on the expression and potential role of IGF-binding proteins (IGFBP) during acquisition of the resistant phenotype. The aim of this study was to determine the expression and functional role of IGFBP-2 and -5 in the development of TAM resistance (TamR) in vitro and to test retrospectively whether they were predictive of resistance in a tissue microarray of 77 women with primary breast cancers who relapsed on/after endocrine therapy and 193 who did not with long term follow up. Reciprocal expression of IGFBP-2 and IGFBP-5 was observed at both mRNA and protein level in TamR cells. IGFBP-2 expression was increased by 10-fold while IGFBP-5 was decreased by 100-fold, compared to TAM-sensitive control cells. shRNA-mediated silencing of IGFBP-2 in TamR cells restored TAM sensitivity suggesting a causal role for this gene in TamR. While silencing of IGFBP-5 in control cells had no effect on TAM sensitivity, it significantly increased the migratory capacity of these cells. Quantitative image analysis of immunohistochemical data failed, however, to demonstrate an effect of IGFBP2 expression in endocrine-relapsed patients. Likewise, IGFBP-2 and IGFBP-5 expression failed to show any significant associations with survival either in patients relapsing or those not relapsing on/after endocrine therapy. By contrast, in silico mining of a separate published dataset showed that in patients who received endocrine treatment, loss of expression of IGBP-5 was significantly associated with worse survival. Overall these data suggest that co-ordinated and reciprocal alteration in IGFBP-2 and -5 expression may

  4. [Adjuvant therapy of breast cancer with trastuzumab].

    PubMed

    Beneder, Christine; Marth, Christian

    2008-01-01

    With the approval of trastuzumab (Herceptin) in 1998, a new era of breast cancer treatment has been heralded. This antibody is directed at the intracellular domain of a member of the epidermal growth factor receptor family, the so-called HER2 receptor. About 25-30% of all breast cancers overexpress this factor, which is associated with a more unfavorable prognosis. Trastuzumab is indicated for patients whose tumor overexpresses HER2. All previous studies on the adjuvant therapy with trastuzumab show very consistent results and provide evidence that the risk of recurrence can be reduced by half by the antibody. Nevertheless, there are still numerous open and controversially discussed questions concerning the use of trastuzumab in adjuvant therapy.

  5. [Neoadjuvant or Adjuvant Chemotherapy for Bladder Cancer?].

    PubMed

    Hupe, M C; Kramer, M W; Kuczyk, M A; Merseburger, A S

    2015-05-01

    Advanced urothelial carcinoma of the bladder is associated with a high metastatic potential. Life expectancy for metastatic patients is poor and rarely exceeds more than one year without further therapy. Neoadjuvant chemotherapy can decrease the tumour burden while reducing the risk of death. Adjuvant chemotherapy has been discussed controversially. Patients with lymph node-positive metastases seem to benefit the most from adjuvant chemotherapy. In selected patients, metastasectomy can prolong survival. In metastastic patients, the combination of gemcitabine and cisplatin has become the new standard regimen due to a lower toxicity in comparison to the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). For second-line treatment, vinflunine is the only approved therapeutic agent.

  6. Molecular signatures of vaccine adjuvants.

    PubMed

    Olafsdottir, Thorunn; Lindqvist, Madelene; Harandi, Ali M

    2015-09-29

    Mass vaccination has saved millions of human lives and improved the quality of life in both developing and developed countries. The emergence of new pathogens and inadequate protection conferred by some of the existing vaccines such as vaccines for tuberculosis, influenza and pertussis especially in certain age groups have resulted in a move from empirically developed vaccines toward more pathogen tailored and rationally engineered vaccines. A deeper understanding of the interaction of innate and adaptive immunity at molecular level enables the development of vaccines that selectively target certain type of immune responses without excessive reactogenicity. Adjuvants constitute an imperative element of modern vaccines. Although a variety of candidate adjuvants have been evaluated in the past few decades, only a limited number of vaccine adjuvants are currently available for human use. A better understanding of the mode of action of adjuvants is pivotal to harness the potential of existing and new adjuvants in shaping a desired immune response. Recent advancement in systems biology powered by the emerging cutting edge omics technology has led to the identification of molecular signatures rapidly induced after vaccination in the blood that correlate and predict a later protective immune response or vaccine safety. This can pave ways to prospectively determine the potency and safety of vaccines and adjuvants. This review is intended to highlight the importance of big data analysis in advancing our understanding of the mechanisms of actions of adjuvants to inform rational development of future human vaccines.

  7. Single-arc volumetric-modulated arc therapy (sVMAT) as adjuvant treatment for gastric cancer: Dosimetric comparisons with three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT)

    SciTech Connect

    Wang, Xin; Li, Guangjun; Zhang, Yingjie; Bai, Sen; Xu, Feng; Wei, Yuquan; Gong, Youling

    2013-01-01

    To compare the dosimetric differences between the single-arc volumetric-modulated arc therapy (sVMAT), 3-dimensional conformal radiotherapy (3D-CRT), and intensity-modulated radiotherapy (IMRT) techniques in treatment planning for gastric cancer as adjuvant radiotherapy. Twelve patients were retrospectively analyzed. In each patient's case, the parameters were compared based on the dose-volume histogram (DVH) of the sVMAT, 3D-CRT, and IMRT plans, respectively. Three techniques showed similar target dose coverage. The maximum and mean doses of the target were significantly higher in the sVMAT plans than that in 3D-CRT plans and in the 3D-CRT/IMRT plans, respectively, but these differences were clinically acceptable. The IMRT and sVMAT plans successfully achieved better target dose conformity, reduced the V{sub 20/30}, and mean dose of the left kidney, as well as the V{sub 20/30} of the liver, compared with the 3D-CRT plans. And the sVMAT technique reduced the V{sub 20} of the liver much significantly. Although the maximum dose of the spinal cord were much higher in the IMRT and sVMAT plans, respectively (mean 36.4 vs 39.5 and 40.6 Gy), these data were still under the constraints. Not much difference was found in the analysis of the parameters of the right kidney, intestine, and heart. The IMRT and sVMAT plans achieved similar dose distribution to the target, but superior to the 3D-CRT plans, in adjuvant radiotherapy for gastric cancer. The sVMAT technique improved the dose sparings of the left kidney and liver, compared with the 3D-CRT technique, but showed few dosimetric advantages over the IMRT technique. Studies are warranted to evaluate the clinical benefits of the VMAT treatment for patients with gastric cancer after surgery in the future.

  8. Endocrine disrupting pesticides: a leading cause of cancer among rural people in Pakistan.

    PubMed

    Ejaz, Sohail; Akram, Waseem; Lim, Chae Woong; Lee, Jong Jin; Hussain, Imtiaz

    2004-06-01

    Evidence on the relationship between cancer and occupational exposure to pesticides and endocrine disrupting chemicals is reviewed. In animal studies it has been proved that majority of endocrine disrupting pesticides are carcinogenic. In humans, pesticides have been classified as carcinogens by the International Agency for Research on Cancer. Farmers may therefore be at higher risk for acute and chronic health effects associated with pesticides. Human data, however, are limited by the small number of studies that evaluate individual endocrine disrupting pesticide. Cancer of the breast, ovary, prostate, testis, and thyroid are hormone-dependent, which fostered research on the potential risk associated with occupational and environmental exposure to the so-called endocrine-disrupting pesticides. Professional as well as public exposure to pesticides raises cancer risk. Interaction with adjuvant and with other toxicants increases the actual risk. On the other hand, organochlorine pesticides and triazine herbicides require further investigation for a possible etiologic role in some hormone-dependent cancers.

  9. Multiple endocrine neoplasia type I.

    PubMed

    Beukes, E; Dent, D M; De Villiers, J C; Miller, J L

    1985-08-17

    During the 13-year period 1970-1983 only 7 cases of multiple endocrine neoplasia type I (MEN I) were seen at Groote Schuur Hospital, suggesting that the associated gene is rare in this area. Only 1 of these patients was black. Endocrine associations were as follows: hyperparathyroidism--6 cases, pituitary hypersecretion--6 cases (3 each involving growth hormone and prolactin), and pancreatic hypersecretion--3 cases (2 of gastrinoma and 1 of insulinoma). The presenting features were predictably diverse and depended on the component which manifested first. There was little difficulty in reaching a diagnosis on routine investigation. All patients with hyperparathyroidism underwent a 3 1/2-gland parathyroidectomy as the first treatment procedure, normocalcaemia being achieved in 5 cases, but persistent hypercalcaemia in the 6th suggested a supernumerary gland. A pituitary adenoma was removed in 4 cases, but persistent prolactinaemia necessitated bromocriptine therapy in 3. Successful distal pancreatectomy was undertaken in a patient with insulinoma and a patient with gastrinoma, and a further patient with gastrinoma awaits surgery. The overall prognosis in cases of MEN I appears to depend on the most aggressive component, often the pancreatic lesion; our patients have run a surprisingly benign course with only 1 late death, from hypertensive heart disease.

  10. Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3.

    PubMed

    Van Cutsem, Eric; Labianca, Roberto; Bodoky, György; Barone, Carlo; Aranda, Enrique; Nordlinger, Bernard; Topham, Claire; Tabernero, Josep; André, Thierry; Sobrero, Alberto F; Mini, Enrico; Greil, Richard; Di Costanzo, Francesco; Collette, Laurence; Cisar, Laura; Zhang, Xiaoxi; Khayat, David; Bokemeyer, Carsten; Roth, Arnaud D; Cunningham, David

    2009-07-01

    PURPOSE The primary objective of this randomized, multicenter, phase III trial was to investigate whether the addition of irinotecan to the de Gramont infusional fluorouracil (FU)/leucovorin (LV) adjuvant regimen (LV5FU2) would improve disease-free survival (DFS) in patients with stage III colon cancer. PATIENTS AND METHODS After curatively intentioned surgery, patients with stage II and III colon cancer were randomly allocated surgery to receive LV5FU2 (LV 200 mg/m(2) as a 2-hour infusion, followed by FU; as a 400 mg/m(2) bolus and then a 600 mg/m(2) continuous infusion over 22 hours, days 1 and 2, every 2 weeks for 12 cycles: de Gramont regimen) with or without irinotecan (180 mg/m(2) as a 30- to 90-minute infusion, day 1, every 2 weeks). In total, 260 (7.9%) of 3,278 patients received an alternative high-dose infusional FU/LV regimen (Arbeitsgemeinschaft Internische Onkologie regimen) with or without irinotecan. Results The principal efficacy analysis was based on 2,094 treated patients with stage III disease, randomly allocated in the LV5FU2 strata. After a median follow-up of 66.3 months, the 5-year DFS rate was 56.7% with irinotecan/LV5FU2 and 54.3% with LV5FU2 alone (primary end point: log-rank P = .106). Combining irinotecan with LV5FU2 did not significantly improve overall survival in this patient group compared with LV5FU2 alone (5-year rate 73.6% v 71.3%, respectively; log-rank P = .094). The addition of irinotecan to LV5FU2 was associated with an increased incidence of grade 3 to 4 GI events and neutropenia. CONCLUSION Irinotecan added to LV5FU2 as adjuvant therapy did not confer a statistically significant improvement in DFS or overall survival in patients with stage III colon cancer compared with LV5FU2 alone.

  11. The changing role of ER in endocrine resistance.

    PubMed

    Nardone, Agostina; De Angelis, Carmine; Trivedi, Meghana V; Osborne, C Kent; Schiff, Rachel

    2015-11-01

    Estrogen receptor (ER) is expressed in approximately 70% of newly diagnosed breast tumors. Although endocrine therapy targeting ER is highly effective, intrinsic or acquired resistance is common, significantly jeopardizing treatment outcomes and minimizing overall survival. Even in the presence of endocrine resistance, a continued role of ER signaling is suggested by several lines of clinical and preclinical evidence. Indeed, inhibition or down-regulation of ER reduces tumor growth in preclinical models of acquired endocrine resistance, and many patients with recurrent ER+ breast tumors progressing on one type of ER-targeted treatment still benefit from sequential endocrine treatments that target ER by a different mechanism. New insights into the nature and biology of ER have revealed several mechanisms sustaining altered ER signaling in endocrine-resistant tumors, including deregulated growth factor receptor signaling that results in ligand-independent ER activation, unbalanced ER co-regulator activity, and genomic alterations involving the ER gene ESR1. Therefore, biopsies of recurrent lesions are needed to assess the changes in epi/genomics and signaling landscape of ER and associated pathways in order to tailor therapies to effectively overcome endocrine resistance. In addition, more completely abolishing the levels and activity of ER and its co-activators, in combination with selected signal transduction inhibitors or agents blocking the upstream or downstream targets of the ER pathway, may provide a better therapeutic strategy in combating endocrine resistance.

  12. Endocrine causes of nonalcoholic fatty liver disease

    PubMed Central

    Marino, Laura; Jornayvaz, François R

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed. PMID:26494962

  13. Adjuvant therapy of resectable rectal cancer.

    PubMed

    Minsky, Bruce D

    2002-08-01

    The two conventional treatments for clinically resectable rectal cancer are surgery followed by postoperative combined modality therapy and preoperative combined modality therapy followed by surgery and postoperative chemotherapy. Preoperative therapy (most commonly combined modality therapy) has gained acceptance as a standard adjuvant therapy. The potential advantages of the preoperative approach include decreased tumor seeding, less acute toxicity, increased radiosensitivity due to more oxygenated cells, and enhanced sphincter preservation. There are a number of new chemotherapeutic agents that have been developed for the treatment of patients with colorectal cancer. Phase I/II trials examining the use of new chemotherapeutic agents in combination with pelvic radiation therapy are in progress.

  14. Cationic liposomes as vaccine adjuvants.

    PubMed

    Christensen, Dennis; Korsholm, Karen Smith; Andersen, Peter; Agger, Else Marie

    2011-04-01

    The application of cationic liposomes as vaccine delivery systems and adjuvants has been investigated extensively over the last few decades. However, cationic liposomes are, in general, not sufficiently immunostimulatory, which is why the combination of liposomes with immunostimulating ligands has arisen as a strategy in the development of novel adjuvant systems. Within the last 5 years, two novel adjuvant systems based on cationic liposomes incorporating Toll-like receptor or non-Toll-like receptor immunostimulating ligands have progressed from preclinical testing in smaller animal species to clinical testing in humans. The immune responses that these clinical candidates induce are primarily of the Th1 type for which there is a profound unmet need. Furthermore, a number of new cationic liposome-forming surfactants with notable immunostimulatory properties have been discovered. In this article we review the recent progress on the application of cationic liposomes as vaccine delivery systems/adjuvants.

  15. [Endocrine disease symptoms].

    PubMed

    Reincke, M

    2013-10-01

    Diseases of the endocrine system can be classified according to the prevalence into two categories: very frequent endocrinopathies, which affect a population of several millions in Germany and include diabetes mellitus, endemic goiter, osteoporosis and obesity. On the other hand there are a large number of rare endocrine diseases which share the paradox of other rare diseases: they are also often falsely suspected in patients who are not affected but at the same time there are sometimes long delays in diagnosis in those who do have the disease. In cases of adrenal insufficiency, absolute glucocorticoid deficiency can progress to an adrenal crisis which is fatal if not treated. Patients with de Quervain thyroiditis often suffer from prolonged episodes of fever with tender, diffuse goiter and neck pain. Pheochromocytomas should be recognized early in the course of disease because of life-threatening cardiovascular complications. This article highlights the essential characteristics in order to increase awareness.

  16. Endocrine disrupters as obesogens

    PubMed Central

    Grün, Felix; Blumberg, Bruce

    2009-01-01

    The recent dramatic rise in obesity rates is an alarming global health trend that consumes an ever increasing portion of health care budgets in Western countries. The root cause of obesity is thought to be a prolonged positive energy balance. Hence, the major focus of preventative programs for obesity has been to target overeating and inadequate physical exercise. Recent research implicates environmental risk factors, including nutrient quality, stress, fetal environment and pharmaceutical or chemical exposure as relevant contributing influences. Evidence points to endocrine disrupting chemicals that interfere with the body's adipose tissue biology, endocrine hormone systems or central hypothalamic-pituitary-adrenal axis as suspects in derailing the homeostatic mechanisms important to weight control. This review highlights recent advances in our understanding of the molecular targets and mechanisms of action for these compounds and areas of future research needed to evaluate the significance of their contribution to obesity. PMID:19433244

  17. Opioids and endocrine dysfunction

    PubMed Central

    Hester, Joan

    2012-01-01

    The endocrine effects of opioids used for the management of persistent pain are poorly understood by clinicians and patients, and hormone levels are rarely measured. It is recognized that opioids exert this effect via the hypothalamic-pituitary-gonadal axis. Additional effects on adrenal hormones, weight, blood pressure and bone density may also occur. Symptoms and signs of sex hormone deficiency occur in both men and women but are under-reported and are often clinically unrecognized. The potential effects of long term opioid therapy on the endocrine system should be explained to patients before opioid therapy is commenced. Monitoring of sex hormones is recommended; if there are deficiencies opioids should be tapered and withdrawn, if this is clinically acceptable. If opioid therapy has to continue, hormone replacement therapy should be initiated and monitored by an endocrinologist. PMID:26516462

  18. [Xenoestrogens: endocrine disrupting compounds].

    PubMed

    Wozniak, Milena; Murias, Marek

    2008-11-01

    In recent years much attention has been paid to the issues of chemicals that disrupt the normal function of endocrine system, namely xenoestrogens. These chemicals can mimic the activity of endogenous estrogens, antagonize their interaction with estrogen receptors or disrupt the synthesis, metabolism and functions of endogenous female hormones. Due to the fact that they act thanks to many different mechanisms, it is very difficult to estimate their estrogenic activity by means of a simple tests. The important issue remains the fact that xenoestrogens may have a positive or negative influence on the function of the endocrine system. It seems to be very important that there are many sources of xenoestrogens, that is not only vegetables and fruit (phytoestrogens), but also metals (Co, Cu, Ni, Cr, Pb), dental appliances (alkilphenols), food containers or blood containers (PVC--polyvinyl chloride, DEHP--di-(2-ethylhexyl) phthalate), cosmetics (parabens) and pesticides (DDT--dichlor-diphenyl-trichlorethylane, endosulfane).

  19. Endorectal MRI assessment of local relapse after surgery for prostate cancer: A model to define treatment field guidelines for adjuvant radiotherapy in patients at high risk for local failure

    SciTech Connect

    Miralbell, Raymond . E-mail: Raymond.Miralbell@hcuge.ch; Vees, Hansjoerg; Lozano, Joan; Khan, Haleem; Molla, Meritxell; Hidalgo, Alberto; Linero, Dolors; Rouzaud, Michel

    2007-02-01

    Purpose: To assess the role of endorectal magnetic resonance imaging (MRI) in defining local relapse after radical prostatectomy for prostate cancer to help to reassess the clinical target volume (CTV) for adjuvant postprostatectomy radiotherapy. Methods and Materials: Sixty patients undergoing an endorectal MRI before salvage radiotherapy were selected. Spatial coordinates of the relapses were assessed using two reference points: the inferior border of the pubic symphysis (point 1) and the urethro-vesical anastomosis (point 2). Every lesion on MRI was delineated on the planning computed tomography and center of mass coordinates were plotted in two separate diagrams (along the x, y, and z axes) with the urethro-vesical anastomosis as the coordinate origin. An 'ideal' CTV was constructed, centered at a point defined by the mathematical means of each of the three coordinates with dimensions defined as twice 2 standard deviations in each of the three axes. The dosimetric impact of the new CTV definition was evaluated in six adjuvantly treated patients. Results: The ideal CTV center of mass was located at coordinates 0 (x), -5 (y), and -3 (z) mm with SDs of 6 (x), 6 (y), and 9 (z) mm, respectively. The CTV size was 24 (x) x 24 (y) x 36 (z) mm. Significant rectal sparing was observed with the new CTV. Conclusions: A CTV with an approximately cylindrical shape ({approx}4 x 3 cm) centered 5 mm posterior and 3 mm inferior to the urethro-vesical anastomosis was defined. Such CTV may reduce the irradiation of normal nontarget tissue in the pelvis potentially improving treatment tolerance.

  20. Adjuvant Therapy for Gallbladder Carcinoma: The Mayo Clinic Experience

    SciTech Connect

    Gold, Douglas G.; Miller, Robert C. Haddock, Michael G.; Gunderson, Leonard L.; Quevedo, Fernando; Donohue, John H.; Bhatia, Sumita; Nagorney, David M.

    2009-09-01

    Purpose: To analyze the effect of adjuvant chemoradiotherapy on gallbladder carcinoma. Methods and Materials: We retrospectively reviewed the records from consecutive patients who underwent R0 resection of gallbladder carcinoma between January 1, 1985, and December 31, 2004. Patients had either Stage I (T1-T2N0M0) or Stage II (T3N0M0 or T1-T3N1M0) disease. Patients undergoing adjuvant therapy received 5-fluorouracil chemotherapy concurrently with radiotherapy (median dosage, 50.4 Gy in 28 fractions). Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) were evaluated. Results: A total of 73 patients were included in the analysis; of these, 25 received adjuvant chemoradiotherapy. On univariate analysis, no adverse prognostic factors for OS reached statistical significance, but trends were noted for Stage N1 vs. N0 (p = .06), Nx vs. N0 (p = .09), Stage T3 vs. T1-T2 (p = .06), and histologic findings other than adenocarcinoma (p = .13). The median OS for patients receiving adjuvant chemoradiotherapy vs. surgery alone was 4.8 years and 4.2 years, respectively (log-rank test, p = .56). However, a significantly greater percentage of patients receiving adjuvant chemoradiotherapy had Stage II disease (p <.001). In the multivariate Cox model, increasing T and N category and histologic findings other than adenocarcinoma were significant predictors of decreased OS. Additionally, adjuvant chemoradiotherapy was a significant predictor of improved OS after adjusting for these prognostic factors (hazard ratio for death, 0.3; 95% confidence interval, 0.13-0.69; p = .004). Conclusion: After adjusting for the stage parameters and histologic findings, our data suggest that adjuvant chemoradiotherapy might improve OS for patients with gallbladder cancer.

  1. Capecitabine and Oxaliplatin in the Preoperative Multimodality Treatment of Rectal Cancer: Surgical End Points From National Surgical Adjuvant Breast and Bowel Project Trial R-04

    PubMed Central

    O'Connell, Michael J.; Colangelo, Linda H.; Beart, Robert W.; Petrelli, Nicholas J.; Allegra, Carmen J.; Sharif, Saima; Pitot, Henry C.; Shields, Anthony F.; Landry, Jerome C.; Ryan, David P.; Parda, David S.; Mohiuddin, Mohammed; Arora, Amit; Evans, Lisa S.; Bahary, Nathan; Soori, Gamini S.; Eakle, Janice; Robertson, John M.; Moore, Dennis F.; Mullane, Michael R.; Marchello, Benjamin T.; Ward, Patrick J.; Wozniak, Timothy F.; Roh, Mark S.; Yothers, Greg; Wolmark, Norman

    2014-01-01

    Purpose The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT. Patients and Methods Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m2, 5 days per week), with or without intravenous oxaliplatin (50 mg/m2 once per week for 5 weeks) or oral capecitabine (825 mg/m2 twice per day, 5 days per week), with or without oxaliplatin (50 mg/m2 once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery). Results From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001). Conclusion Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred. PMID:24799484

  2. Which is the best IVF/ICSI protocol to be used in poor responders receiving growth hormone as an adjuvant treatment? A prospective randomized trial.

    PubMed

    Dakhly, Dina M R; Bayoumi, Yomna A; Gad Allah, Sherine H

    2016-01-01

    This open label randomized study aims to define the best protocol to be used with growth hormone in poor responders, with comparison performed to delineate which protocol offers the best cycle outcomes. Two-hundred eighty-seven poor responders were included. The patients were randomly allocated into four groups receiving growth hormone (GH) as an adjuvant therapy added to either long or short agonist protocol, miniflare or antagonist protocols. The short/GH gave significantly lower mean number of oocytes when compared with the long/GH, antagonist/GH and miniflare/GH (4 ± 1.69 versus 5.06 ± 1.83, 4.95 + / = 1.90 and4.98 ± 2.51, respectively p = 0.005). Considering the number of fertilized oocytes, the long/GH showed significantly higher levels than short/GH and antagonist/GH (3.73 ± 1.47 versus 3.02 ± 1.52 and 2.89 ± 1.14, respectively). The main drawback is that it required significantly higher HMG dose and longer duration of stimulation. The long/GH was superior when compared with the three protocols regarding the number of oocytes retrieved and fertilized. But, when considering the clinical pregnancy rates, there was a difference in favor of the long/GH but not reaching a statistically significant value (ClinicalTrials.gov Identifier: NCT01897324).

  3. Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer.

    PubMed

    Coleman, R; Woodward, E; Brown, J; Cameron, D; Bell, R; Dodwell, D; Keane, M; Gil, M; Davies, C; Burkinshaw, R; Houston, S J; Grieve, R J; Barrett-Lee, P J; Thorpe, H

    2011-06-01

    The AZURE trial is an ongoing phase III, academic, multi-centre, randomised trial designed to evaluate the role of zoledronic acid (ZOL) in the adjuvant therapy of women with stage II/III breast cancer. Here, we report the safety and tolerability profile of ZOL in this setting. Eligible patients received (neo)adjuvant chemotherapy and/or endocrine therapy and were randomised to receive neither additional treatment nor intravenous ZOL 4 mg. ZOL was administered after each chemotherapy cycle to exploit potential sequence-dependent synergy. ZOL was continued for 60 months post-randomisation (six doses in the first 6 months, eight doses in the following 24 months and five doses in the final 30 months). Serious (SAE) and non-serious adverse event (AE) data generated during the first 36 months on study were analysed for the safety population. 3,360 patients were recruited to the AZURE trial. The safety population comprised 3,340 patients (ZOL 1,665; control 1,675). The addition of ZOL to standard treatment did not significantly impact on chemotherapy delivery. SAE were similar in both treatment arms. No significant safety differences were seen apart from the occurrence of osteonecrosis of the jaw (ONJ) in the ZOL group (11 confirmed cases; 0.7%; 95% confidence interval 0.3-1.1%). ZOL in the adjuvant setting is well tolerated, and can be safely administered in addition to adjuvant therapy including chemotherapy. The adverse events were consistent with the known safety profile of ZOL, with a low incidence of ONJ.

  4. [Hypotension from endocrine origin].

    PubMed

    Vantyghem, Marie-Christine; Douillard, Claire; Balavoine, Anne-Sophie

    2012-11-01

    Hypotension is defined by a low blood pressure either permanently or only in upright posture (orthostatic hypotension). In contrast to hypertension, there is no threshold defining hypotension. The occurrence of symptoms for systolic and diastolic measurements respectively below 90 and 60 mm Hg establishes the diagnosis. Every acute hypotensive event should suggest shock, adrenal failure or an iatrogenic cause. Chronic hypotension from endocrine origin may be linked to adrenal failure from adrenal or central origin, isolated hypoaldosteronism, pseudohypoaldosteronism, pheochromocytoma, neuro-endocrine tumors (carcinoïd syndrome) or diabetic dysautonomia. Hypotension related to hypoaldosteronism associates low blood sodium and above all high blood potassium levels. They are generally classified according to their primary (hyperreninism) or secondary (hyporeninism) adrenal origin. Isolated primary hypoaldosteronisms are rare in adults (intensive care unit, selective injury of the glomerulosa area) and in children (aldosterone synthase deficiency). Isolated secondary hypoaldosteronism is related to mellitus diabetes complicated with dysautonomia, kidney failure, age, iatrogenic factors, and HIV infections. In both cases, they can be associated to glucocorticoid insufficiency from primary adrenal origin (adrenal failure of various origins with hyperreninism, among which congenital 21 hydroxylase deficiency with salt loss) or from central origin (hypopituitarism with hypo-reninism). Pseudohypoaldosteronisms are linked to congenital (type 1 pseudohypoaldosteronism) or acquired states of resistance to aldosterone. Acquired salt losses from enteric (total colectomy with ileostomy) or renal (interstitial nephropathy, Bartter and Gitelman syndromes…) origin might be responsible for hypotension and are associated with hyperreninism-hyperaldosteronism. Hypotension is a rare manifestation of pheochromocytomas, especially during surgical removal when the patient has not been

  5. How to define green adjuvants.

    PubMed

    Beck, Bert; Steurbaut, Walter; Spanoghe, Pieter

    2012-08-01

    The concept 'green adjuvants' is difficult to define. This paper formulates an answer based on two approaches. Starting from the Organisation for Economic Cooperation and Development (OECD) definition for green chemistry, production-based and environmental-impact-based definitions for green adjuvants are proposed. According to the production-based approach, adjuvants are defined as green if they are manufactured using renewable raw materials as much as possible while making efficient use of energy, preferably renewable energy. According to the environmental impact approach, adjuvants are defined as green (1) if they have a low human and environmental impact, (2) if they do not increase active ingredient environmental mobility and/or toxicity to humans and non-target organisms, (3) if they do not increase the exposure to these active substances and (4) if they lower the impact of formulated pesticides by enhancing the performance of active ingredients, thus potentially lowering the required dosage of active ingredients. Based on both approaches, a tentative definition for 'green adjuvants' is given, and future research and legislation directions are set out.

  6. Classification of Laser Vaccine Adjuvants

    PubMed Central

    Kashiwagi, Satoshi; Brauns, Timothy; Poznansky, Mark C

    2016-01-01

    An immunologic adjuvant, which enhances the magnitude and quality of immune responses to vaccine antigens, has become an essential part of modern vaccine practice. Chemicals and biologicals have been typically used for this purpose, but there are an increasing number of studies that are being conducted on the vaccine adjuvant effect of laser light on the skin. Currently, four different types or classes of laser devices have been shown to systemically enhance immune responses to intradermal vaccination: ultra-short pulsed lasers, non-pulsed lasers, non-ablative fractional lasers and ablative fractional lasers. Aside from involving the application of laser light to the skin in a manner that minimizes discomfort and damage, each type of laser vaccine adjuvant involves emission parameters, modes of action and immunologic adjuvant effects that are quite distinct from each other. This review provides a summary of the four major classes of “laser vaccine adjuvant” and clarifies and resolves their characteristics as immunologic adjuvants. These aspects of each adjuvant’s properties will ultimately help define which laser would be most efficacious in delivering a specific clinical benefit with a specific vaccine. PMID:27104047

  7. [Postoperative adjuvant chemotherapy using NCS (neocarzinostatin) and 5-FU in the treatment of gastric cancer. First report--A comparison with the 5-year survival rate of patients undergoing combined therapy with MMC and 5-FU].

    PubMed

    Yokomori, T; Taniguchi, T; Iesato, H; Sakata, Y; Watanabe, T; Kawabe, K

    1987-11-01

    As a postoperative adjuvant chemotherapy for gastric cancer, we have administered a combination of NCS (Neocarzinostatin) and 5-FU (NF treatment method) and in this paper we have compiled the results obtained in patients who were treated for 5 years in an attempt to compare the 5-year survival rate with that of patients administered a combination of MMC and 5-FU (MF treatment group) and a control group administered no anticancer agents. As the selection of either NF or MF treatment was conducted on an annual basis, this study can be considered an historical controlled study. The results obtained are summarized as follows. On comparing the survival rate of the NF treatment group and the control group, the 5-year survival rate for all patients who underwent curative resection and all patients with histological stage III cancers and the curative resection PS (+) group, as well as the survival period of the non-resected patients, showed a statistically significant difference, indicating that the survival rate was higher in the NF group. On comparing the NF group and the MF group, although no statistically significant difference was observed between then based on a stratified analysis of all resected cases, histological stage differences and n.ps factors, etc., certain values tended to indicate a higher survival rate for the NF group. Moreover, the survival rate of the non-resected patients was more favorable in the NF group. These results confirm that NCS is useful for the treatment of stomach cancer and compares favorably with MMC. The appearance of side-effects was significantly lower in the NF group in comparison with the MF group and the number of patients who had to discontinue therapy was extremely low.

  8. Toxicity Assessment of a Phase III Study Evaluating FEC-Doc and FEC-Doc Combined with Gemcitabine as an Adjuvant Treatment for High-Risk Early Breast Cancer: the SUCCESS-A Trial

    PubMed Central

    Schröder, L.; Rack, B.; Sommer, H.; Koch, J. G.; Weissenbacher, T.; Janni, W.; Schneeweiss, A.; Rezai, M.; Lorenz, R.; Jäger, B.; Schramm, A.; Häberle, L.; Fasching, P. A.; Friedl, T. W. P.; Beckmann, M. W.; Scholz, C.

    2016-01-01

    Introduction: This paper aims to evaluate the toxicity profile of additive gemcitabine to adjuvant taxane-based chemotherapy in breast cancer patients. Methods: Patients enrolled in this open-label randomized controlled Phase III study were treated with 3 cycles of epirubicin-fluorouracil-cyclophosphamide (FEC) chemotherapy followed by 3 cycles of docetaxel with those receiving 3 cycles of FEC followed by 3 cycles of gemcitabine-docetaxel (FEC-DG). 3690 patients were evaluated according to National Cancer Institute (NCI) toxicity criteria (CTCAE). The study medications were assessed by the occurrence of grade 3–4 adverse events, dose reductions, postponements of treatment cycles and granulocyte colony-stimulating factor (G-CSF) support. Results: No differences in neutropenia or febrile neutropenia were demonstrated. However, thrombocytopenia was significantly increased with FEC-DG treatment (2.0 vs. 0.5 %, p < 0.001), as was leukopenia (64.1 vs. 58.5 %, p < 0.001). With FEC-DG significantly more G-CSF support in cycles 4 to 6 (FEC-DG: 57.8 %, FEC-D: 36.3 %, p < 0.001) was provided. Transaminase elevation was significantly more common with FEC-DG (SGPT: 6.3 %, SGOT: 2 %), whereas neuropathy (1.2 %), arthralgia (1.6 %) and bone pain (2.6 %) were more common using FEC-D. Dose reductions > 20 % (4 vs. 2.4 %) and postponement of treatment cycles (0.9 vs. 0.4 %) were significantly more frequent in the FEC-DG arm. Eight deaths occurred during treatment in the FEC-DG arm and four in the FEC-D arm. Conclusion: The addition of gemcitabine increased hematological toxicity and was associated with more dose reductions and postponements of treatment cycles. PMID:27239063

  9. Fluosol and oxygen breathing as an adjuvant to radiation therapy in the treatment of locally advanced non-small cell carcinoma of the lung: Results of a phase I/II study

    SciTech Connect

    Lustig, R.; Lowe, N.; Prosnitz, L.; Spaulding, M.; Cohen, M.; Stitt, J.; Brannon, R. )

    1990-07-01

    Fluosol, a perflourcarbon emulsion, has the ability to carry oxygen in solution. In conjunction with oxygen breathing and radiation, fluosol has been shown in animal models to enhance local tumor control. In September 1985, a Phase I/II Study was instituted to evaluate the effect of this adjuvant therapy with radiation in non-small cell carcinomas of the lung. Of the 49 patients administered Fluosol, 34 mild moderate adverse reactions were noted in 22 patients to either the test dose/infusion or post infusion. Flushing, dyspnea and hypertension and chills and/or fever were the typical symptoms. Transient elevation of blood chemistries were noted in some patients. Six patients had transient depression of WBC counts and two patients had transient depression of platelets. None of these altered treatment. Forty-five patients received Fluosol of which 34 completed the planned therapy. Six patients were diagnosed with metastatic disease during therapy and three patients died of their disease during treatment. Radiation therapy was administered at a daily fraction of 165 to 200 cGy per fraction to a total dose of 5940 to 6800 cGy.

  10. Clinical use of adjuvants in allergen-immunotherapy.

    PubMed

    Klimek, L; Schmidt-Weber, C B; Kramer, M F; Skinner, M A; Heath, M D

    2017-02-04

    Introduction Allergen-specific Immunotherapy (AIT) is the only available treatment aimed to tackle the underlying causes of allergy. The active components of subcutaneous vaccines traditionally consist of natural or modified allergen extracts which can be combined with adjuvant platforms. In recent years new targets have been further developed in an attempt to raise the safety and efficacy profile of AIT. Areas Covered In this review, we discuss the desirable attributes of adjuvants and delivery systems from empiricism to rational design, for current and future clinical applications in AIT. Expert Summary The introduction of novel adjuvants, in combination with active targets, has been demonstrated to reduce side-effects of AIT, increase clinical efficacy of allergy treatment and reduce the number of doses. The evolution of vaccine development for AIT is entering a phase of scientific progress that challenges dogmas. Over the past century the traditional concept of immunotherapy, entailing long-course administration of native extract preparations and first generation adjuvants has seen evolution in the past decade from proof-of-concept to clinical development pipelines encompassing the advent of second generation adjuvants and delivery systems that form essential components of modern AIT development.

  11. Endocrine Disruptor Screening Program Reports to Congress

    EPA Pesticide Factsheets

    This page includes EPA reports to congress on pesticide licensing and endocrine disruptor screening activities, Endocrine Disruptor Methods Validation Subcomittee (EDMVS) progress, and Endocrine Disruptor Screening Program (EDSP) implementation progress.

  12. Successful Shortening of Tuberculosis Treatment Using Adjuvant Host-Directed Therapy with FDA-Approved Phosphodiesterase Inhibitors in the Mouse Model

    PubMed Central

    Ammerman, Nicole C.; Gupta, Radhika; Guo, Haidan; Maiga, Marama C.; Lun, Shichun; Bishai, William R.

    2012-01-01

    Global control of tuberculosis (TB), an infectious disease that claims nearly 2 million lives annually, is hindered by the long duration of chemotherapy required for curative treatment. Lack of adherence to this intense treatment regimen leads to poor patient outcomes, development of new or additional drug resistance, and continued spread of M.tb. within communities. Hence, shortening the duration of TB therapy could increase drug adherence and cure in TB patients. Here, we report that addition of the United Stated Food and Drug Administration-approved phosphodiesterase inhibitors (PDE-Is) cilostazol and sildenafil to the standard TB treatment regimen reduces tissue pathology, leads to faster bacterial clearance and shortens the time to lung sterilization by one month, compared to standard treatment alone, in a murine model of TB. Our data suggest that these PDE-Is could be repurposed for use as adjunctive drugs to shorten TB treatment in humans. PMID:22319585

  13. The ultrastructure of tomatine adjuvant.

    PubMed

    Yang, Ya-Wun; Sheikh, Nadeem A; Morrow, W J W

    2002-12-01

    The tomatine adjuvant, consisting of tomatine, n-octyl-beta-D-glucopyranoside, phosphatidylethanolamine, cholesterol, and ovalbumin, has recently been shown to potentiate the immunogenicity of protein antigen and elicit cytotoxic T-lymphocyte responses in immunized animals. The physicochemical properties of tomatine adjuvant have not been characterized. The aim of this study was to examine the microstructure of this complex formulation, as directly related to its physicochemical properties. To elucidate the micromorphology of this system, the tomatine adjuvant was separated by isopycnic ultracentrifugation, followed by freeze fracturing and examination by transmission and scanning electron microscopy. The adjuvant mixture was shown to be composed of several micro- and nano-structures. The major fraction obtained from isopycnic separation was shown to consist of flaky needle-like microcrystals, approximately 80-160 nm in width and 2-4 microm in length. The tomatine crystals alone in 0.9% NaCl, on the other hand, were shown to be elongated hollow tubular crystals of hundreds of nanometers up to a few microns in length, along which n-octyl-beta-glucopyranoside was speculated to serve as a seeding microtemplate for gel crystallization of protein complexes. Indented marks within the gel phase were observed in the freeze fractured replicas of the adjuvant, suggesting that protein complexes may have been crystallized or precipitated within the gels. Several other forms of micro- and nano-structures were also observed, showing multiple-dispersion features with gel characteristics. The presence of gel crystalline and multiple-dispersed phases is postulated to contribute to the sustained immunopotentiation effect of tomatine adjuvant.

  14. The occurrence and ecological risks of endocrine disrupting chemicals in sewage effluents from three different sewage treatment plants, and in natural seawater from a marine reserve of Hong Kong.

    PubMed

    Xu, Elvis G B; Liu, Shan; Ying, Guang-Guo; Zheng, Gene J S; Lee, Joseph H W; Leung, Kenneth M Y

    2014-08-30

    We determined the concentrations of 12 endocrine disrupting chemicals (EDCs) in sewage effluents collected from three different sewage treatment plants (STPs) in Hong Kong, and found 4-nonylphenol (NP) and bisphenol A (BPA) were the most abundant EDCs. Effluent concentrations of NP and BPA were higher in dry season than in wet season, but opposite seasonal changes of NP were observed in receiving waters, probably due to the surface runoff. The two secondary STPs showed higher removal efficiency for these compounds than the preliminary STP, while having higher removal efficiency in wet season. Therefore, it is necessary to upgrade the preliminary STP and improve the EDC removal efficiency in dry season. Seawaters from the Cape D' Aguilar Marine Reserve adjacent to these STPs also exhibited elevated NP levels with a hazard quotient >1. Furthermore, diluted effluents from the STPs elicited significant transcriptional responses of EDC-related genes in the marine medaka fish.

  15. Trauma and the endocrine system.

    PubMed

    Mesquita, Joana; Varela, Ana; Medina, José Luís

    2010-12-01

    The endocrine system may be the target of different types of trauma with varied consequences. The present article discusses trauma of the hypothalamic-pituitary axes, adrenal glands, gonads, and pancreas. In addition to changes in circulating hormone levels due to direct injury to these structures, there may be an endocrine response in the context of the stress caused by the trauma.

  16. Adjuvant therapy in pancreatic cancer.

    PubMed

    Jones, Owain Peris; Melling, James Daniel; Ghaneh, Paula

    2014-10-28

    Pancreatic cancer remains one of the leading causes of cancer related death worldwide with an overall five-year survival of less than 5%. Potentially curative surgery, which alone can improve 5-year survival to 10%, is an option for only 10%-20% of patients at presentation owing to local invasion of the tumour or metastatic disease. Adjuvant chemotherapy has been shown to improve 5-year survival to 20%-25% but conflicting evidence remains with regards to chemoradiation. In this article we review the current evidence available from published randomised trials and discuss ongoing phase III trials in relation to adjuvant therapy in pancreatic cancer.

  17. [Current status of adjuvant chemotherapy for resected lung cancer at our institute--focus on clinical trial enrollment].

    PubMed

    Sawada, Shigeki; Yamashita, Motohiro; Komori, Eisaku; Suehiro, Hiroshi; Ogino, Atsuko; Nogami, Hiroyuki; Segawa, Yoshihiko; Shinkai, Tetsu

    2010-03-01

    Adjuvant chemotherapy after complete resection in Stage I B-III A non-small cell lung cancer is recommended. Several clinical trials of adjuvant chemotherapy are now underway in Japan. Our institute also participates in adjuvant clinical trials, but slow patient recruitment is a problem. In this paper, we reported the current status of adjuvant chemotherapy and recruitment for clinical trials at our institute. Between August 2001 and December 2008, candidates for adjuvant chemotherapy were 315 patients. Among them 186 who received adjuvant chemotherapy were younger and had less co-morbidity than those who did not receive adjuvant chemotherapy. Twenty-five of the 186 patients participated in the clinical trials. The major reason of refusal of a clinical trial was that patients preferred to choose their own treatment and disliked randomized trials.

  18. Clinical utility of exemestane in the treatment of breast cancer

    PubMed Central

    Zucchini, Giorgia; Geuna, Elena; Milani, Andrea; Aversa, Caterina; Martinello, Rossella; Montemurro, Filippo

    2015-01-01

    Breast cancer is the most prevalent cancer in women, causing a significant mortality worldwide. Different endocrine strategies are available for the treatment of hormone-sensitive breast cancer, including antiestrogen tamoxifen and fulvestrant, as well as third-generation aromatase inhibitors (AIs), such as letrozole, anastrozole, and exemestane. In this review, we will focus on exemestane, its clinical use, and its side effects. Exemestane is a steroidal third-generation AI now used in all treatment settings for breast cancer. In the metastatic disease, it has been extensively investigated as the first-, second-, and further-line treatment and it is now registered for the treatment of postmenopausal women with advanced estrogen-receptor-positive breast cancer whose disease has progressed following antiestrogen therapy. A potential lack of cross-resistance with nonsteroidal AIs has been described, giving additional therapeutic opportunities in sequences of endocrine agents. Exemestane is also approved for the adjuvant treatment of postmenopausal early breast cancer, either as upfront monotherapy for 5 years, as a switch following 2–3 years of tamoxifen, or as extended therapy beyond 5 years of adjuvant treatment. New promising data also showed a beneficial effect in young premenopausal early breast cancer patients, when administered together with ovarian suppression. Interesting results have also emerged when exemestane has been investigated as neodjuvant treatment as well as preventive agent in healthy women at high risk for breast cancer. Exemestane is generally well tolerated, with a side effect profile similar to that of other AIs, including menopausal symptoms, arthralgia, and bone loss. In conclusion, exemestane can be considered an effective and well-tolerated endocrine treatment option for all stages of breast cancer. PMID:26064072

  19. Clinical utility of exemestane in the treatment of breast cancer.

    PubMed

    Zucchini, Giorgia; Geuna, Elena; Milani, Andrea; Aversa, Caterina; Martinello, Rossella; Montemurro, Filippo

    2015-01-01

    Breast cancer is the most prevalent cancer in women, causing a significant mortality worldwide. Different endocrine strategies are available for the treatment of hormone-sensitive breast cancer, including antiestrogen tamoxifen and fulvestrant, as well as third-generation aromatase inhibitors (AIs), such as letrozole, anastrozole, and exemestane. In this review, we will focus on exemestane, its clinical use, and its side effects. Exemestane is a steroidal third-generation AI now used in all treatment settings for breast cancer. In the metastatic disease, it has been extensively investigated as the first-, second-, and further-line treatment and it is now registered for the treatment of postmenopausal women with advanced estrogen-receptor-positive breast cancer whose disease has progressed following antiestrogen therapy. A potential lack of cross-resistance with nonsteroidal AIs has been described, giving additional therapeutic opportunities in sequences of endocrine agents. Exemestane is also approved for the adjuvant treatment of postmenopausal early breast cancer, either as upfront monotherapy for 5 years, as a switch following 2-3 years of tamoxifen, or as extended therapy beyond 5 years of adjuvant treatment. New promising data also showed a beneficial effect in young premenopausal early breast cancer patients, when administered together with ovarian suppression. Interesting results have also emerged when exemestane has been investigated as neodjuvant treatment as well as preventive agent in healthy women at high risk for breast cancer. Exemestane is generally well tolerated, with a side effect profile similar to that of other AIs, including menopausal symptoms, arthralgia, and bone loss. In conclusion, exemestane can be considered an effective and well-tolerated endocrine treatment option for all stages of breast cancer.

  20. Glucocorticosteroids enhance replication of respiratory viruses: effect of adjuvant interferon

    PubMed Central

    Thomas, Belinda J.; Porritt, Rebecca A.; Hertzog, Paul J.; Bardin, Philip G.; Tate, Michelle D.

    2014-01-01

    Glucocorticosteroids (GCS) are used on a daily basis to reduce airway inflammation in asthma and chronic obstructive pulmonary disease (COPD). This treatment is usually escalated during acute disease exacerbations, events often associated with virus infections. We examined the impact of GCS on anti-viral defences and virus replication and assessed supplementary interferon (IFN) treatment. Here, we report that treatment of primary human airway cells in vitro with GCS prior to rhinovirus (RV) or influenza A virus (IAV) infection significantly reduces the expression of innate anti-viral genes and increases viral replication. Mice given intranasal treatment with GCS prior to IAV infection developed more severe disease associated with amplified virus replication and elevated inflammation in the airways. Adjuvant IFN treatment markedly reduced GCS-amplified infections in human airway cells and in mouse lung. This study demonstrates that GCS cause an extrinsic compromise in anti-viral defences, enhancing respiratory virus infections and provides a rationale for adjuvant IFN treatment. PMID:25417801

  1. A Novel Non-Invasive Adjuvant Biomechanical Treatment for Patients with Altered Rehabilitation after Total Knee Arthroplasty: Results of a Pilot Investigation

    PubMed Central

    Kosashvili, Yona; Segal, Ganit; Shemesh, Shai; Velkes, Steven; Mor, Amit; Debi, Ronen; Bernfeld, Benjamin; Elbaz, Avi

    2015-01-01

    Background Many factors contribute to suboptimal results after total knee arthroplasty (TKA) but little is known regarding the value of postsurgical rehabilitation after TKA. We examined the effects of an enhanced closed kinematic chain exercises program (AposTherapy) on gait patterns and clinical outcomes among patients with a lack of progress in their postsurgical rehabilitation. Methods Twenty-two patients were prospectively followed during the study. Gait spatiotemporal parameters were measured at the initial evaluation, after 15 minutes of therapy, and after 3 months of therapy. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the short form (SF) 36 health survey were completed by patients before treatment and after 3 months of treatment. Results The WOMAC and SF-36 scores improved significantly after 3 months of treatment. Gait velocity, single limb support, and step length of the operated leg improved significantly even after a single 15 minutes treatment. Normal gait velocity was observed in 36% of patients after 3 months of treatment. Conclusions A physiotherapy program that included enhanced closed kinematic chain biomechanical therapy was beneficial for patients who experienced a suboptimal rehabilitation course after TKA. PMID:26217465

  2. Adrenocortical endocrine disruption.

    PubMed

    Harvey, Philip W

    2016-01-01

    The adrenal has been neglected in endocrine disruption regulatory testing strategy. The adrenal is a vital organ, adrenocortical insufficiency is recognised in life threatening "adrenal crises" and Addison's disease, and the consequences of off-target toxicological inhibition of adrenocortical steroidogenesis is well recognised in clinical medicine, where drugs such as aminoglutethimide and etomidate killed patients via unrecognised inhibition of adrenocortical steroidogenic enzymes (e.g. CYP11B1) along the cortisol and aldosterone pathways. The consequences of adrenocortical dysfunction during early development are also recognised in the congenital salt wasting and adrenogenital syndromes presenting neonatally, yet despite a remit to focus on developmental and reproductive toxicity mechanisms of endocrine disruption by many regulatory agencies (USEPA EDSTAC; REACH) the assessment of adrenocortical function has largely been ignored. Further, every step in the adrenocortical steroidogenic pathway (ACTH receptor, StAR, CYP's 11A1, 17, 21, 11B1, 11B2, and 3-hydroxysteroid dehydrogenase Δ4,5 isomerase) is known to be a potential target with multiple examples of chemicals inhibiting these targets. Many of these chemicals have been detected in human and wildlife tissues. This raises the question of whether exposure to low level environmental chemicals may be affecting adrenocortical function. This review examines the omission of adrenocortical testing in the current regulatory frameworks; the characteristics that make the adrenal cortex particularly vulnerable to toxic insult; chemicals and their toxicological targets within the adrenocortical steroidogenic pathways; the typical manifestations of adrenocortical toxicity (e.g. human iatrogenically induced pharmacotoxicological adrenal insufficiency, manifestations in typical mammalian regulatory general toxicology studies, manifestations in wildlife) and models of adrenocortical functional assessment. The utility of the

  3. Radiation plus chemotherapy as adjuvant therapy for rectal cancer.

    PubMed

    Minsky, Bruce D

    2002-04-01

    The most common neo-adjuvant therapy for rectal cancer is chemotherapy and concurrent radiation therapy. In general, it is delivered pre-operatively for patients with clinical evidence of T(3-4) disease or post-operatively in patients who have undergone surgery and have T(3) and/or N(1-2) disease. This chapter reviews the rationale and results for neo-adjuvant therapy, the selection process for pre-operative versus post-operative treatment, and new approaches and controversies.

  4. Aluminum adjuvants elicit fibrin-dependent extracellular traps in vivo

    PubMed Central

    Munks, Michael W.; McKee, Amy S.; MacLeod, Megan K.; Powell, Roger L.; Degen, Jay L.; Reisdorph, Nichole A.; Kappler, John W.

    2010-01-01

    It has been recognized for nearly 80 years that insoluble aluminum salts are good immunologic adjuvants and that they form long-lived nodules in vivo. Nodule formation has long been presumed to be central for adjuvant activity by providing an antigen depot, but the composition and function of these nodules is poorly understood. We show here that aluminum salt nodules formed within hours of injection and contained the clotting protein fibrinogen. Fibrinogen was critical for nodule formation and required processing to insoluble fibrin by thrombin. DNase treatment partially disrupted the nodules, and the nodules contained histone H3 and citrullinated H3, features consistent with extracellular traps. Although neutrophils were not essential for nodule formation, CD11b+ cells were implicated. Vaccination of fibrinogen-deficient mice resulted in normal CD4 T-cell and antibody responses and enhanced CD8 T-cell responses, indicating that nodules are not required for aluminum's adjuvant effect. Moreover, the ability of aluminum salts to retain antigen in the body, the well-known depot effect, was unaffected by the absence of nodules. We conclude that aluminum adjuvants form fibrin-dependent nodules in vivo, that these nodules have properties of extracellular traps, and the nodules are not required for aluminum salts to act as adjuvants. PMID:20876456

  5. [The potential dangers of endocrinal disorders].

    PubMed

    Kaufman, E; Garfunkel, A; Findler, M; Malamed, S F; Zusman, S P; Elad, S; Galili, D

    2002-01-01

    The symptoms of most endocrine system diseases are usually clearly recognizable and most of the times are accompanied by a rich medical history. Many general practitioners are reluctant to treat such cases and prefer to refer these patients to specialists who are trained in management of the medically compromised thus increasing the chances of dental treatment without complications. However, sometimes endocrinal diseases develop slowly and their clinical manifestations are hidden or subclinical in nature. In these cases, neither the patient nor the dentist are aware of the condition and there is the potential of life threatening, emergency situations in what at first seem as simple, straightforward dental procedures. Therefore, the dentist must be able to recognize the clinical problem, differentiate between the different symptoms and initiate the proper management protocol. The most unstable endocrinal disorders that should be treated with great care are diabetes mellitus, mainly hypoglycemia, hyperthyroidism and adrenal insufficiency. The general practitioner dentist can treat patients suffering from these disorders providing the disease is well controlled and balanced and that the dental treatment is not very traumatic.

  6. QS-21: a potent vaccine adjuvant

    Technology Transfer Automated Retrieval System (TEKTRAN)

    QS-21 is an potent adjuvant derived from the bark of a Chilean tree, Quillaja saponaria. One of the advantages of this adjuvant is that it promotes a balanced humoral and cell-mediaed immune response and can be widely applicable to a variety of vaccines. This adjuvant has used for some veterinary va...

  7. Drift reduction with drift control adjuvants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Five new drift control adjuvants were sele...

  8. Drift reduction with drift control adjuvants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Four new drift control adjuvants were sele...

  9. Next Generation Sequencing in Endocrine Practice

    PubMed Central

    Forlenza, Gregory P.; Calhoun, Amy; Beckman, Kenneth B.; Halvorsen, Tanya; Hamdoun, Elwaseila; Zierhut, Heather; Sarafoglou, Kyriakie; Polgreen, Lynda E.; Miller, Bradley S.; Nathan, Brandon; Petryk, Anna

    2016-01-01

    With the completion of the Human Genome Project and advances in genomic sequencing technologies, the use of clinical molecular diagnostics has grown tremendously over the last decade. Next-generation sequencing (NGS) has overcome many of the practical roadblocks that had slowed the adoption of molecular testing for routine clinical diagnosis. In endocrinology, targeted NGS now complements biochemical testing and imaging studies. The goal of this review is to provide clinicians with a guide to the application of NGS to genetic testing for endocrine conditions, by compiling a list of established gene mutations detectable by NGS, and highlighting key phenotypic features of these disorders. As we outline in this review, the clinical utility of NGS-based molecular testing for endocrine disorders is very high. Identifying an exact genetic etiology improves understanding of the disease, provides clear explanation to families about the cause, and guides decisions about screening, prevention and/or treatment. PMID:25958132

  10. Adrenomedullin and endocrine disorders.

    PubMed

    Letizia, C; Rossi, G; Cerci, S

    2003-12-01

    Adrenomedullin (AM) is a recently discovered potent vasodilatory peptide, originally isolated in extracts of human pheochromocytoma, with activities including maintenance of cardiovascular and renal homeostasis through vasodilatation, diuresis and natriuresis. Human AM consists of 52 amino acids with a 6-member ring structure linked by a disulfide bond and amidated COOH terminal, which belongs to calcitonin gene-related peptide (CGRP) and amylin. The main sites of AM production are the lungs, vascular tissues (both endothelial and smooth muscle cells), heart, kidney, adrenal glands, pancreatic islets, placenta, anterior pituitary gland and gastrointestinal neuroendocrine system. Intravenous injection of AM increases blood flow predominantly in the tissues with the highest AM expression, suggesting that AM functions primarily as a paracrine/autocrine hormone, but it is also important as circulating hormone. The objective of this review is to analyze the evidence that AM may play a role in some endocrine disorders.

  11. [Acne vulgaris: endocrine aspects].

    PubMed

    Dekkers, O M; Thio, B H; Romijn, J A; Smit, J W A

    2006-06-10

    Androgens play an important part in the development of acne vulgaris. Androgen levels in patients with acne are higher than those in controls and people with the androgen insensitivity syndrome do not develop acne. Local factors other than androgen plasma levels, also play a part in the development of acne. The skin contains enzymes that convert precursor hormones to the more potent androgens such as testosterone and dihydrotestosterone. Androgen synthesis can therefore be regulated locally. The effects of androgens on the skin are the result of circulating androgens and enzyme activity in local tissues and androgen receptors. Acne is a clinical manifestation of some endocrine diseases. The polycystic ovary syndrome has the highest prevalence. In women with acne that persists after puberty, in 10-200% of cases polycystic ovary syndrome is later diagnosed. The mechanism of hormonal anti-acne therapy may work by blocking the androgen-production (oestrogens) or by blocking the androgen receptor (cyproterone, spironolactone).

  12. Enhancement removal of endocrine-disrupting pesticides and nitrogen removal in a biofilm reactor coupling of biodegradable Phragmites communis and elastic filler for polluted source water treatment.

    PubMed

    Feng, Lijuan; Yang, Guangfeng; Zhu, Liang; Xu, Xiangyang; Gao, Feng; Mu, Jun; Xu, Yanmei

    2015-01-01

    The coupling of conventional elastic filler and solid carbon source of Phragmites communis (P. communis) as the biofilm support was applied in a biofilm system for treating polluted source water containing nitrogen and trace endocrine-disrupting pesticides (cypermethrin and chlorpyrifos). Results showed that removal efficiencies of TN and EDPs were improved with addition of 3.6kg P. communis/m(3) in the biofilm system. Meanwhile, the uniform distribution of P. communis favored simultaneously nitrogen and organics removal but not to trace EDPs compared with non-uniform distribution of P. communis. The biofilm on elastic filler was mainly responsible for the nitrification with NH4(+)-N oxidation efficiency of 82.9±1.5%. Poor nitrification with NH4(+)-N oxidation efficiency of 36.3±6.1% but effective denitrification with a TN removal efficiency of 56.5±2.0% were obtained by the biofilm on P. communis. Cypermethrin was mainly removed via adsorption and microbial degradation, and chlorpyrifos removal mostly depended on the microbial degradation in biofilm system.

  13. Use of gentamicin sulfate-impregnated sponges as adjuvant therapy for the treatment of chronic foreign body associated sternal osteomyelitis in a dog

    PubMed Central

    Wainberg, Shannon H.; Brisson, Brigitte A.; Hayes, Galina M.; Mackenzie, Shawn

    2015-01-01

    A 2-year-old Labrador retriever dog was referred for evaluation of parasternal chronic draining sinus tracts associated with sternal osteomyelitis secondary to the presence of a residual wooden foreign body. The use of gentamicin-impregnated collagen sponges as adjunctive therapy to osteomyelitis treatment is reported herein. PMID:26538672

  14. Management of Pediatric Myxopapillary Ependymoma: The Role of Adjuvant Radiation

    SciTech Connect

    Agbahiwe, Harold C.; Wharam, Moody; Batra, Sachin; Cohen, Kenneth; Terezakis, Stephanie A.

    2013-02-01

    Introduction: Myxopapillary ependymoma (MPE) is a rare tumor in children. The primary treatment is gross total resection (GTR), with no clearly defined role for adjuvant radiation therapy (RT). Published reports, however, suggest that children with MPE present with a more aggressive disease course. The goal of this study was to assess the role of adjuvant RT in pediatric patients with MPE. Methods: Sixteen patients with MPE seen at Johns Hopkins Hospital (JHH) between November 1984 and December 2010 were retrospectively reviewed. Fifteen of the patients were evaluable with a mean age of 16.8 years (range, 12-21 years). Kaplan-Meier curves and descriptive statistics were used for analysis. Results: All patients received surgery as the initial treatment modality. Surgery consisted of either a GTR or a subtotal resection (STR). The median dose of adjuvant RT was 50.4 Gy (range, 45-54 Gy). All patients receiving RT were treated at the involved site. After a median follow-up of 7.2 years (range, 0.75-26.4 years), all patients were alive with stable disease. Local control at 5 and 10 years was 62.5% and 30%, respectively, for surgery alone versus 100% at both time points for surgery and adjuvant RT. Fifty percent of the patients receiving surgery alone had local failure. All patients receiving STR alone had local failure compared to 33% of patients receiving GTR alone. One patient in the surgery and adjuvant RT group developed a distant site of recurrence 1 year from diagnosis. No late toxicity was reported at last follow-up, and neurologic symptoms either improved or remained stable following surgery with or without RT. Conclusions: Adjuvant RT improved local control compared to surgery alone and should be considered after surgical resection in pediatric patients with MPE.

  15. A Canadian Critical Care Trials Group project in collaboration with the international forum for acute care trialists - Collaborative H1N1 Adjuvant Treatment pilot trial (CHAT): study protocol and design of a randomized controlled trial

    PubMed Central

    2011-01-01

    Background Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes. Methods/Design A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to medication administration

  16. Xuan Bai Cheng Qi formula as an adjuvant treatment of acute exacerbation of chronic obstructive pulmonary disease of the syndrome type phlegm-heat obstructing the lungs: a multicenter, randomized, double-blind, placebo-controlled clinical trial

    PubMed Central

    2014-01-01

    Background Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause of morbidity and mortality. Traditional Chinese medicine (TCM) is used to treat AECOPD as adjunctive therapy. This study aimed to evaluate the efficacy and safety of the TCM formula Xuan Bai Cheng Qi as an adjuvant therapy for AECOPD patients with the syndrome type of phlegm-heat obstructing the lungs. Methods A multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 244 patients were divided into the intervention group (n = 122, treated with conventional medicine and Xuan Bai Cheng Qi) and the control group (n = 122, treated with conventional medicine and placebo). Total symptom scores (cough, phlegm, wheezing, chest congestion) before treatment and at 3, 5, 7, 10 days post-treatment were recorded. Lung function, arterial blood gas, serum inflammatory cytokines, oxidation/anti-oxidation index were observed before treatment and at the end of the 10-day treatment. Results A total of 242 patients completed the study. The full analysis set (FAS) population was 244 and the per-protocol analysis set (PPS) population was 229. After the 10-day treatment, symptom scores of the Xuan Bai Cheng Qi group were significantly lower over time compared with the control group (FAS: mean difference -1.84, 95% CI -2.66 to -1.03, P < .001; PPS: mean difference -1.87, 95% CI -2.71 to -1.03, P < .001). FEV1, FVC, and FEV1%pred were significantly higher over time in the Xuan Bai Cheng Qi group compared with those in the control group (day 10, FAS and PPS: P < .05). PaO2 and PaCO2 were significantly improved in the Xuan Bai Cheng Qi group (day 10, FAS and PPS: P < .05). Xuan Bai Cheng Qi was also found to ameliorate cytokine levels and oxidation/antioxidant index compared with placebo. There were no differences in safety variables and adverse events between the two groups. Conclusions Xuan Bai Cheng Qi formula appears to be a

  17. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    PubMed Central

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  18. Endocrine Effects of Circadian Disruption.

    PubMed

    Bedrosian, Tracy A; Fonken, Laura K; Nelson, Randy J

    2016-01-01

    Disruption of circadian rhythms, provoked by artificial lighting at night, inconsistent sleep-wake schedules, and transmeridian air travel, is increasingly prevalent in modern society. Desynchrony of biological rhythms from environmental light cycles has dramatic consequences for human health. In particular, disrupting homeostatic oscillations in endocrine tissues and the hormones that these tissues regulate can have cascading effects on physiology and behavior. Accumulating evidence suggests that chronic disruption of circadian organization of endocrine function may lead to metabolic, reproductive, sleep, and mood disorders. This review discusses circadian control of endocrine systems and the consequences of distorting rhythmicity of these systems.

  19. Key roles of adjuvants in modern vaccines.

    PubMed

    Reed, Steven G; Orr, Mark T; Fox, Christopher B

    2013-12-01

    Vaccines containing novel adjuvant formulations are increasingly reaching advanced development and licensing stages, providing new tools to fill previously unmet clinical needs. However, many adjuvants fail during product development owing to factors such as manufacturability, stability, lack of effectiveness, unacceptable levels of tolerability or safety concerns. This Review outlines the potential benefits of adjuvants in current and future vaccines and describes the importance of formulation and mechanisms of action of adjuvants. Moreover, we emphasize safety considerations and other crucial aspects in the clinical development of effective adjuvants that will help facilitate effective next-generation vaccines against devastating infectious diseases.

  20. Environmental impact of adjuvants in crop protection.

    PubMed

    Ryckaert, B; Spanoghe, P; Steurbaut, W; Heremans, B; Haesaert, G; de Coen, W

    2005-01-01

    The overall performance of chemical and biological plant protection products is enhanced by the use of adjuvants in the formulation (formulation adjuvants) or in the spray tank (spray adjuvants). Both types of adjuvants aim to stabilize the formulation, to improve the efficiency of the active ingredients and to reduce application and environmental risks. As an important part of the formulation, both quantitatively and qualitatively, the environmental impact and toxicology of adjuvants can not always be considered as inert. However, little is known of their impact as part of plant protection products compared with the active substances. Therefore an experimental framework is needed as a tool for a consistent environmental legislation.

  1. Adjuvant Iodine131 Lipiodol after Resection of Hepatocellular Carcinoma

    PubMed Central

    Furtado, Ruelan V.; Ha, Leo; Clarke, Stephen; Sandroussi, Charbel

    2015-01-01

    Background. Survival after liver resection for HCC is compromised by a high rate of intrahepatic recurrence. Adjuvant treatment with a single, postoperative dose of intra-arterial I131 lipiodol has shown promise, as a means of prolonging disease-free survival (DFS). Methodology. DFS and overall survival (OS) after a single dose of postoperative I131 lipiodol were compared to liver resection alone, for treatment of hepatocellular carcinoma (HCC). Data were collected retrospectively for patients who had a curative resection for HCC between December 1993 and September 2011. Seventy-two patients were given I131 lipiodol after surgery and 70 patients had surgery alone. Results. The DFS at 1, 3, and 5 years was 72%, 43%, and 26% in the surgery group and 70%, 39%, and 29% in the adjuvant I131 lipiodol group (p = 0.75). The 1-, 3-, and 5-year OS was 83%, 64%, and 52% in the surgery group and 96%, 72%, and 61% in the adjuvant I131 lipiodol group (p = 0.16). Conclusion. This retrospective study has found no significant benefit to survival, after adjuvant treatment with I131 lipiodol. PMID:26713092

  2. Pathogenetic difference between collagen arthritis and adjuvant arthritis

    PubMed Central

    1984-01-01

    Daily treatment with cyclosporin at a dose of 25 mg/kg for 14 d gave complete suppression of the development of collagen arthritis and adjuvant arthritis in Sprague-Dawley rats during an observation period of 45 d. To study whether the immunologic unresponsiveness produced by cyclosporin is antigen specific, we rechallenged the cyclosporin- protected rats with either type II collagen or complete Freund's adjuvant (CFA) after discontinuation of cyclosporin treatment. Type II collagen-immunized, cyclosporin-protected rats did not develop arthritis in response to reimmunization with type II collagen, but, they did develop arthritis in response to a subsequent injection of CFA. Similarly, CFA-injected, cyclosporin-protected rats showed a suppressed arthritogenic reaction in response to reinjection of CFA, whereas their response to a subsequent immunization with type II collagen was unaffected. On the other hand, the rats that were treated with cyclosporin without any prior antigenic challenge could develop arthritis in response to a subsequent injection of CFA or type II collagen after cessation of cyclosporin treatment. These results indicate that specific immunologic unresponsiveness can be induced by cyclosporin in the two experimental models of polyarthritis, collagen arthritis and adjuvant arthritis, and that there is no cross-reactivity between type II collagen and the mycobacterial cell wall components. The results further indicate that immunity to type II collagen plays a critical role in the pathogenesis of collagen arthritis but that its pathogenetic role in adjuvant arthritis is insignificant. PMID:6201583

  3. Combination of External Beam Radiotherapy (EBRT) With Intratumoral Injection of Dendritic Cells as Neo-Adjuvant Treatment of High-Risk Soft Tissue Sarcoma Patients

    SciTech Connect

    Finkelstein, Steven E.; Iclozan, Cristina; Bui, Marilyn M.; Cotter, Matthew J.; Ramakrishnan, Rupal; Ahmed, Jamil; Noyes, David R.; Cheong, David; Gonzalez, Ricardo J.; Heysek, Randy V.; Berman, Claudia; Lenox, Brianna C.; Janssen, William; Zager, Jonathan S.; Sondak, Vernon K.; Letson, G. Douglas; Antonia, Scott J.; Gabrilovich, Dmitry I.

    2012-02-01

    Purpose: The goal of this study was to determine the effect of combination of intratumoral administration of dendritic cells (DC) and fractionated external beam radiation (EBRT) on tumor-specific immune responses in patients with soft-tissue sarcoma (STS). Methods and Material: Seventeen patients with large (>5 cm) high-grade STS were enrolled in the study. They were treated in the neoadjuvant setting with 5,040 cGy of EBRT, split into 28 fractions and delivered 5 days per week, combined with intratumoral injection of 10{sup 7} DCs followed by complete resection. DCs were injected on the second, third, and fourth Friday of the treatment cycle. Clinical evaluation and immunological assessments were performed. Results: The treatment was well tolerated. No patient had tumor-specific immune responses before combined EBRT/DC therapy; 9 patients (52.9%) developed tumor-specific immune responses, which lasted from 11 to 42 weeks. Twelve of 17 patients (70.6%) were progression free after 1 year. Treatment caused a dramatic accumulation of T cells in the tumor. The presence of CD4{sup +} T cells in the tumor positively correlated with tumor-specific immune responses that developed following combined therapy. Accumulation of myeloid-derived suppressor cells but not regulatory T cells negatively correlated with the development of tumor-specific immune responses. Experiments with {sup 111}In labeled DCs demonstrated that these antigen presenting cells need at least 48 h to start migrating from tumor site. Conclusions: Combination of intratumoral DC administration with EBRT was safe and resulted in induction of antitumor immune responses. This suggests that this therapy is promising and needs further testing in clinical trials design to assess clinical efficacy.

  4. Calculation methods to perform mass balance of endocrine disrupting compounds in a submerged membrane bioreactor: fate and distribution of estrogens during the biological treatment.

    PubMed

    Estrada-Arriaga, E B; Mijaylova, P

    2011-01-01

    The purpose of this paper is to report the study of the fate and distribution of three endocrine disrupting compounds (estrogens); Estrone (E1), 17β-estradiol (E2), and 17α-ethinylestradiol (EE2) in a laboratory scale submerged membrane bioreactor (SMBR). For this matter, both aqueous and solids phases were analyzed for the presence of E1, E2 and EE2. The outcome of this study was that three SMBRs showed enhanced elimination of estrogens in different operational conditions; the estrogen removal was close to 100% in SMBR. Additionally, E1, E2 and EE2 were detected in SMBR sludge at concentrations of up to 41.2, 37.3 and 36.9 ng g(-1) dry weight, respectively. The estrogen removal in the SMBRs was directly influenced by a combination of simultaneous biodegradation-adsorption processes, indicating that the main removal mechanism of the estrogens in the SMBRs is the biodegradation process. The E1, E2 and EE2 were biologically degraded in the SMBR (87-100%). The sorption of estrogens onto activated sludge was from 2%. Therefore, a high potential for estrogen removal by biodegradation in the SMBR was observed, allowing less estrogen concentration in the dissolved phase available for the adsorption of these compounds onto biological flocs. Two different methods were carried out for mass balance calculations of estrogens in SMBR. For the first method, the measured data was used in both liquid and solid phases, whereas for the second one, it was in aqueous phase and solid-water distribution coefficients (K(d)) value of E1, E2 and EE2. The purpose of these methodologies is to make easier the identification of the main mechanisms involved in the removal of E1, E2 and EE2 in a SMBR. Both methods can be applied in order to determine the mechanism, fate and distribution of estrogens in a SMBR.

  5. Vaccine adjuvants as potential cancer immunotherapeutics

    PubMed Central

    Temizoz, Burcu; Kuroda, Etsushi

    2016-01-01

    Accumulated evidence obtained from various clinical trials and animal studies suggested that cancer vaccines need better adjuvants than those that are currently licensed, which include the most commonly used alum and incomplete Freund’s adjuvant, because of either a lack of potent anti-tumor immunity or the induction of undesired immunity. Several clinical trials using immunostimulatory adjuvants, particularly agonistic as well as non-agonistic ligands for TLRs, C-type lectin receptors, retinoic acid-inducible gene I-like receptors and stimulator of interferon genes, have revealed their therapeutic potential not only as vaccine adjuvants but also as anti-tumor agents. Recently, combinations of such immunostimulatory or immunomodulatory adjuvants have shown superior efficacy over their singular use, suggesting that seeking optimal combinations of the currently available or well-characterized adjuvants may provide a better chance for the development of novel adjuvants for cancer immunotherapy. PMID:27006304

  6. Weight control, endocrine hormones and cancer prevention.

    PubMed

    King, Brenee; Jiang, Yu; Su, Xiaoyu; Xu, Jianteng; Xie, Linglin; Standard, Joseph; Wang, Weiqun

    2013-05-01

    The prevalence of obesity is increasing which becomes worrisome due to its association with several diseases and certain types of cancers. While weight control through dietary caloric restriction and/or physical activity protects against cancer in animal models, the underlying mechanisms are not fully defined. Weight loss due to negative energy balance is associated with alterations of multiple growth factors and endocrine hormones. The altered hormones and hormone-related functions appear to be responsible for anti-cancer mechanisms. In this review, we summarize the recent studies related to weight loss and the altered endocrine hormones, focusing on the reduced levels of the mitogenic insulin-like growth factor 1 (IGF-1) and adipokine leptin as well as the raised levels of adiponectin and glucocorticoids. The potential molecular targets of these hormone-dependent signalling pathways are also discussed. Considering the increasing trends of obesity throughout the world, a better understanding of the underlying mechanisms between body weight, endocrine hormones and cancer risk may lead to novel approaches to cancer prevention and treatment.

  7. International network on endocrine complications in thalassaemia (I-CET): an opportunity to grow.

    PubMed

    De Sanctis, V; Soliman, A T; Angastiniotis, M; Eleftheriou, A; Kattamis, Ch; Karimi, M; El Kholy, M; Elsedfy, H; Yassin, Mohd Abdel Daem Mohd; El Awwa, A; Stoeva, I; Skordis, N; Raiola, G; Fiscina, B

    2012-04-01

    Most of the endocrine complications in thalassaemia are attributable to iron overload which may be the result of economic circumstances (expense of the chelation therapy), late onset of chelation therapy or poor compliance with the iron chelation therapy. The major difficulties reported by hematologists or pediatric endocrinologists experienced in thalassaemias or thalassaemia syndromes in following growth disorders and endocrine complications were: lack of familiarity with medical treatment of endocrine complications (40%), interpretation of endocrine tests (30%), costs (65%), absence of paediatric endocrinologist for consultation on growth disorders and endocrine complications (27%), facilities (27%), other (e.g. lack of collaboration and on-time consultation between thalassaemic Centers supervised by hematologists and endocrinologists) (17%). Because any progress we make in research into growth disorders and endocrine complications in thalassaemia should be passed on to all those suffering from it, guaranteeing them the same therapeutic benefits and the same quality of life, on the 8th of May, 2009 in Ferrara (Italy), the International Network on Endocrine Complications in Thalassemia (I-CET) was founded. The I-CET group is planning to conduct, in Ferrara in May 2012, a workshop, "MRI and Endocrine Complications in Thalassaemia", and in Doha (Qatar) in September 2012, a 3-day intensive course entitled, "Growth disorders and Endocrine Complications in Thalassaemia", to provide interested pediatricians, physicians and hematologists from all over the world with an in-depth approach to the diagnosis and management of growth and endocrine disorders in thalassaemic patients.

  8. Adjuvant Whole Brain Radiotherapy: Strong Emotions Decide But Rational Studies Are Needed

    SciTech Connect

    Brown, Paul D. Asher, Anthony L.; Farace, Elana

    2008-04-01

    Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival.