Science.gov

Sample records for adjuvant hormone therapy

  1. Menopausal status and adjuvant hormonal therapy for breast cancer patients: a practical guideline.

    PubMed

    De Vos, F Y F L; van Laarhoven, H W M; Laven, J S E; Themmen, A P N; Beex, L V A M; Sweep, C G J; Seynaeve, C; Jager, A

    2012-11-01

    Breast cancer is the most common malignancy amongst women in the developed world. For patients with hormone-sensitive breast cancer eligible for adjuvant hormonal therapy, it is important to know if the ovaries are (still) functional or not. Indeed, the choice for a specific adjuvant hormonal treatment depends on the menopausal status of an individual woman. The currently available measures to determine the menopausal status are conflicting. Until better measures become available, we propose a practical guideline enabling an optimal choice of adjuvant hormonal therapy for women with a hormone receptor positive breast cancer taking into account uncertainties about their menopausal status.

  2. 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

  3. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review.

    PubMed

    Murphy, Caitlin C; Bartholomew, L Kay; Carpentier, Melissa Y; Bluethmann, Shirley M; Vernon, Sally W

    2012-07-01

    Adjuvant hormonal therapy significantly improves long-term survival of breast cancer patients with hormone receptor-positive disease. Despite the proven clinical efficacy of tamoxifen and aromatase inhibitors, many breast cancer survivors either fail to take the correct dosage at the prescribed frequency (adherence) or discontinue therapy (persistence). This systematic review aims to: (1) determine the prevalence of adherence and persistence to adjuvant hormonal therapy among breast cancer survivors in clinical practice, and (2) identify correlates of adherence and persistence. We searched Medline, PubMed, PsycINFO, and CINAHL for studies that measured rates and/or correlates of adherence and/or persistence to adjuvant hormonal therapy. Studies were reviewed in a multi-step process: (1) the lead author screened titles and abstracts of all potentially eligible studies; (2) each coauthor reviewed a random 5 % sample of abstracts; and (3) two sets of coauthors each reviewed half of all "maybe" abstracts. Any disagreements were discussed until consensus was reached. Twenty-nine studies met inclusion criteria. Prevalence of adherence ranged from 41 to 72 % and discontinuation (i.e., nonpersistence) ranged from 31 to 73 %, measured at the end of 5 years of treatment. Extremes of age (older or younger), increasing out-of-pocket costs, follow-up care with a general practitioner (vs. oncologist), higher CYP2D6 activity, switching from one form of therapy to another, and treatment side effects were negatively associated with adherence and/or persistence. Taking more medications at baseline, referral to an oncologist, and earlier year at diagnosis were positively associated with adherence and/or persistence. Adherence and persistence to adjuvant hormonal therapy among breast cancer survivors is suboptimal. Many of the correlates of adherence and persistence studied to date are not modifiable. Our review reveals a critical need for further research on modifiable factors

  4. Racial/ethnic differences in initiation of adjuvant hormonal therapy among women with hormone receptor-positive breast cancer.

    PubMed

    Livaudais, Jennifer C; Hershman, Dawn L; Habel, Laurel; Kushi, Lawrence; Gomez, Scarlett Lin; Li, Christopher I; Neugut, Alfred I; Fehrenbacher, Louis; Thompson, Beti; Coronado, Gloria D

    2012-01-01

    Mortality after breast cancer diagnosis is known to vary by race/ethnicity even after adjustment for differences in tumor characteristics. As adjuvant hormonal therapy decreases risk of recurrence and increases overall survival among women with hormone receptor-positive tumors, treatment disparities may play a role. We explored racial/ethnic differences in initiation of adjuvant hormonal therapy, defined as two or more prescriptions for tamoxifen or aromatase inhibitor filled within the first year after diagnosis of hormone receptor-positive localized or regional-stage breast cancer. The sample included women diagnosed with breast cancer enrolled in Kaiser Permanente Northern California (KPNC). Odds ratios [OR] and 95% confidence intervals [CI] compared initiation by race/ethnicity (Hispanic, African American, Chinese, Japanese, Filipino, and South Asian vs. non-Hispanic White [NHW]) using logistic regression. Covariates included age and year of diagnosis, area-level socioeconomic status, co-morbidities, tumor stage, histology, grade, breast cancer surgery, radiation and chemotherapy use. Our sample included 13,753 women aged 20-79 years, diagnosed between 1996 and 2007, and 70% initiated adjuvant hormonal therapy. In multivariable analysis, Hispanic and Chinese women were less likely than NHW women to initiate adjuvant hormonal therapy ([OR] = 0.82; [CI] 0.71-0.96 and [OR] = 0.78; [CI] 0.63-0.98, respectively). Within an equal access, insured population, lower levels of initiation of adjuvant hormonal therapy were found for Hispanic and Chinese women. Findings need to be confirmed in other insured populations and the reasons for under-initiation among these groups need to be explored.

  5. Adjuvant hormonal therapy for breast cancer and risk of hormone receptor-specific subtypes of contralateral breast cancer.

    PubMed

    Li, Christopher I; Daling, Janet R; Porter, Peggy L; Tang, Mei-Tzu C; Malone, Kathleen E

    2009-09-01

    Compared with the breast cancer risk women in the general population have, breast cancer survivors have a substantially higher risk of developing a second primary contralateral breast cancer. Adjuvant hormonal therapy reduces this risk, but preliminary data indicate that it may also increase risk of hormone receptor-negative contralateral tumors. We conducted a population-based nested case-control study including 367 women diagnosed with both first primary estrogen receptor (ER)-positive invasive breast cancer and second primary contralateral breast cancer and 728 matched control women diagnosed only with a first breast cancer. Data on adjuvant hormonal therapy, other treatments, and breast cancer risk factors were ascertained through telephone interviews and medical record abstractions. Two-sided statistical tests using conditional logistic regression were conducted to quantify associations between adjuvant hormonal therapy and risk of hormone receptor-specific subtypes of contralateral breast cancer (n = 303 ER+ and n = 52 ER- cases). Compared with women not treated with hormonal therapy, users of adjuvant tamoxifen for >or=5 years had a reduced risk of ER+ contralateral breast cancer [odds ratio, 0.4; 95% confidence interval (CI), 0.3-0.7], but a 4.4-fold (95% CI, 1.03-19.0) increased risk of ER- contralateral breast cancer. Tamoxifen use for <5 years was not associated with ER- contralateral breast cancer risk. Although adjuvant hormonal therapy has clear benefits, risk of the relatively uncommon outcome of ER- contralateral breast cancer may now need to be tallied among its risks. This is of clinical concern given the poorer prognosis of ER- compared with ER+ tumors.

  6. Understanding Breast Cancer Survivors' Beliefs and Concerns About Adjuvant Hormonal Therapy: Promoting Adherence.

    PubMed

    Hurtado-de-Mendoza, Alejandra; Jensen, Roxanne E; Jennings, Yvonne; Sheppard, Vanessa B

    2017-02-15

    Adjuvant hormonal therapy is recommended for women with hormone receptor (HR)-positive breast cancer. Though critical, many patients are non-adherent to this therapy. Few scales have been developed to specifically address beliefs about adjuvant hormonal therapy. This study explores the clarity and relevance of the Beliefs about Medicine Questionnaire (BMQ) in the context of adherence behaviors to hormonal therapy in Black and White breast cancer survivors. We recruited women diagnosed with HR-positive cancer from the Washington, DC, area. An interviewer administered a standardized survey and conducted a cognitive interview. Participants rated the BMQ across three areas: relevance, difficulty, and clarity. We coded whether the comments identified item level issues: limited applicability, unclear reference, unclear perspective, or wording or tone. In-depth interviews were conducted with women who prematurely discontinued hormone therapy. The sample (n = 30) was equally split between Black and White survivors. On average, women were 57.9 years old (SD = 9.0). Overall 77% rated scale as relevant. Cognitive interviews revealed areas of perceived limited acceptability such as the notion of becoming too dependent or the notion of becoming worse if not taking the medication. Women who discontinued hormonal therapy (n = 2) felt ambivalent towards hormonal therapy as they reported having both positive and negative beliefs about the medication. Our study findings suggest new areas for further research and instrument development to accurately measure self-reported beliefs about hormonal therapy by HR-positive breast cancer survivors.

  7. 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.

  8. 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.

  9. Frailty and Adherence to Adjuvant Hormonal Therapy in Older Women With Breast Cancer: CALGB Protocol 369901

    PubMed Central

    Sheppard, Vanessa B.; Faul, Leigh Anne; Luta, George; Clapp, Jonathan D.; Yung, Rachel L.; Wang, Judy Huei-yu; Kimmick, Gretchen; Isaacs, Claudine; Tallarico, Michelle; Barry, William T.; Pitcher, Brandelyn N.; Hudis, Clifford; Winer, Eric P.; Cohen, Harvey J.; Muss, Hyman B.; Hurria, Arti; Mandelblatt, Jeanne S.

    2014-01-01

    Purpose Most patients with breast cancer age ≥ 65 years (ie, older patients) are eligible for adjuvant hormonal therapy, but use is not universal. We examined the influence of frailty on hormonal therapy noninitiation and discontinuation. Patients and Methods A prospective cohort of 1,288 older women diagnosed with invasive, nonmetastatic breast cancer recruited from 78 sites from 2004 to 2011 were included (1,062 had estrogen receptor–positive tumors). Interviews were conducted at baseline, 6 months, and annually for up to 7 years to collect sociodemographic, health care, and psychosocial data. Hormonal initiation was defined from records and discontinuation from self-report. Baseline frailty was measured using a previously validated 35-item scale and grouped as prefrail or frail versus robust. Logistic regression and proportional hazards models were used to assess factors associated with noninitiation and discontinuation, respectively. Results Most women (76.4%) were robust. Noninitiation of hormonal therapy was low (14%), but in prefrail or frail (v robust) women the odds of noninitiation were 1.63 times as high (95% CI, 1.11 to 2.40; P = .013) after covariate adjustment. Nonwhites (v whites) had higher odds of noninitiation (odds ratio, 1.71; 95% CI, 1.04 to 2.80; P = .033) after covariate adjustment. Among initiators, the 5-year continuation probability was 48.5%. After adjustment, the risk of discontinuation was higher with increasing age (P = .005) and lower for stage ≥ IIB (v stage I) disease (P = .003). Conclusion Frailty is associated with noninitiation of hormonal therapy, but it does not seem to be a major predictor of early discontinuation in older patients. PMID:24934786

  10. Non-initiation of adjuvant hormonal therapy in women with hormone receptor-positive breast cancer: The Breast Cancer Quality of Care Study (BQUAL).

    PubMed

    Neugut, Alfred I; Hillyer, Grace Clarke; Kushi, Lawrence H; Lamerato, Lois; Leoce, Nicole; Nathanson, S David; Ambrosone, Christine B; Bovbjerg, Dana H; Mandelblatt, Jeanne S; Magai, Carol; Tsai, Wei-Yann; Jacobson, Judith S; Hershman, Dawn L

    2012-07-01

    Adjuvant hormonal therapy for non-metastatic hormone receptor (HR)-positive breast cancer decreases risk of breast cancer recurrence and increases survival. However, some women do not initiate this life-saving treatment. We used a prospective cohort design to investigate factors related to non-initiation of hormonal therapy among women with newly diagnosed, non-metastatic HR-positive breast cancer recruited from three U.S. sites. Serial interviews were conducted at baseline and during treatment to examine sociodemographic factors, tumor characteristics, and treatment decision-making factors. Multivariate modeling assessed associations between variables of interest and hormonal therapy initiation. Of 1,050 breast cancer patients recruited, 725 (69%) had HR-positive breast cancer, of whom 87 (12.0%) based on self-report and 122 (16.8%) based on medical record/pharmacy fill rates did not initiate hormonal therapy. In a multivariable analysis, non-initiation of hormonal therapy, defined by medical record/pharmacy, was associated with having greater negative beliefs about efficacy of treatment (OR 1.42, 95% CI 1.18-1.70). Non-initiation was less likely in those who found the quality of patient/physician communication to be higher (OR 0.96, 95% CI 0.93-0.99), the hormonal therapy treatment decision an easy one to make (OR 0.45, 95% CI 0.23-0.90) or neither easy nor difficult (OR 0.34, 95% CI 0.20-0.58); and had more positive beliefs about hormonal therapy efficacy (OR 0.40, 95% CI 0.34-0.62). Factors influencing non-initiation of adjuvant hormonal therapy are complex and influenced by patient beliefs regarding treatment efficacy and side effects. Educational interventions to women about the benefits of hormonal therapy may decrease negative beliefs and increase hormone therapy initiation.

  11. Cutaneous adverse effects of hormonal adjuvant therapy for breast cancer: a case of localised urticarial vasculitis following anastrozole therapy and a review of the literature.

    PubMed

    Bock, Vanessa L; Friedlander, Michael; Waring, Dale; Kossard, Steven; Wood, Glenda K

    2014-11-01

    Hormonal therapy with either tamoxifen or aromatase inhibitors is commonly used to treat women with breast cancer in both the adjuvant and recurrent disease setting. Cutaneous adverse reactions to these drugs have been rarely reported in the literature. We report an unusual case of urticarial vasculitis following the aromatase inhibitor anastrozole that localised to the unilateral trunk and mastectomy scar, and review the literature on the cutaneous adverse effects of hormonal therapy for breast cancer.

  12. Evolution of Long-Term Adjuvant Anti-hormone Therapy: Consequences and Opportunities. The St. Gallen Prize Lecture

    PubMed Central

    Jordan, V. Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R.; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

    2012-01-01

    The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5-years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of “longer is better” for adjuvant therapy in pre-menopausal patients. One-year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five-years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten-years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective nor-epinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical

  13. The St. Gallen Prize Lecture 2011: evolution of long-term adjuvant anti-hormone therapy: consequences and opportunities.

    PubMed

    Jordan, V Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

    2011-10-01

    The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5 years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of "longer is better" for adjuvant therapy in pre-menopausal patients. One year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective norepinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical experience

  14. Racial differences in receipt of adjuvant hormonal therapy among Medicaid enrollees in South Carolina diagnosed with breast cancer.

    PubMed

    Felder, Tisha M; Do, D Phuong; Lu, Z Kevin; Lal, Lincy S; Heiney, Sue P; Bennett, Charles L

    2016-05-01

    Several factors contribute to the pervasive Black-White disparity in breast cancer mortality in the U.S., such as tumor biology, access to care, and treatments received including adjuvant hormonal therapy (AHT), which significantly improves survival for hormone receptor-positive breast cancers (HR+). We analyzed South Carolina Central Cancer Registry-Medicaid linked data to determine if, in an equal access health care system, racial differences in the receipt of AHT exist. We evaluated 494 study-eligible, Black (n = 255) and White women (n = 269) who were under 65 years old and diagnosed with stages I-III, HR+ breast cancers between 2004 and 2007. Bivariate and multivariate analyses were conducted to assess receipt of ≥1 AHT prescriptions at any point in time following (ever-use) or within 12 months of (early-use) breast cancer diagnosis. Seventy-two percent of the participants were ever-users (70 % Black, 74 % White) and 68 % were early-users (65 % Black, 71 % White) of AHT. Neither ever-use (adjusted OR (AOR) = 0.75, 95 % CI 0.48-1.17) nor early-use (AOR = 0.70, 95 % CI 0.46-1.06) of AHT differed by race. However, receipt of other breast cancer-specific treatments was independently associated with ever-use and early-use of AHT [ever-use: receipt of surgery (AOR = 2.15, 95 % CI 1.35-3.44); chemotherapy (AOR = 1.97, 95 % CI 1.22-3.20); radiation (AOR = 2.33, 95 % CI 1.50-3.63); early-use: receipt of surgery (AOR = 2.03, 95 % CI 1.30-3.17); chemotherapy (AOR = 1.90, 95 % CI 1.20-3.03); radiation (AOR = 1.73, 95 % CI 1.14-2.63)]. No racial variations in use of AHT among women with HR+ breast cancers insured by Medicaid in South Carolina were identified, but overall rates of AHT use by these women is low. Strategies to improve overall use of AHT should include targeting breast cancer patients who do not receive adjuvant chemotherapy and/or radiation.

  15. Oncologist-patient discussion of adjuvant hormonal therapy in breast cancer: results of a linguistic study focusing on adherence and persistence to therapy.

    PubMed

    Davidson, Brad; Vogel, Victor; Wickerham, Lawrence

    2007-03-01

    Although studies have proven the benefit of 5+ years of adjuvant hormonal therapy (AHT) for breast cancer, data show adherence and persistence with therapy are suboptimal. This observational linguistic study analyzed communication between breast cancer patients and their oncologists to determine how adherence was addressed and to identify areas where communication could be improved. Community-based oncologists were recruited by letter to participate. Researchers visited oncologists (n = 14) to record patient-oncologist interactions and conduct separate post-visit interviews. Comprehensive linguistic analyses of visits between 28 postmenopausal, early-stage breast cancer patients on or initiating hormonal therapy and their oncologists were conducted to determine the nature of discussions of adherence and persistence to therapy. Oncologist-patient discussions about AHT were generally good but did not address potential difficulties of remaining adherent with long-term therapy. Discussions of persistence were usually monologues addressing the current state of "study data" and were not linked to the patient, the importance of persistence, or how the study data related to her situation. Because the patient's cancer was framed as being "in the past," discussions resembled those of chronic management in preventive medicine. This more ad-hoc approach to adherence and persistence is a potential stumbling block for motivating patients to stay on hormonal therapy. Additionally, the oncologists participating in this study recognized that adherence to therapy is a problem but did not feel "their patients" fell into this pattern. In this office-based evaluation, minimal nurse interactions were observed, which increases the importance of oncologist-patient communication. The authors recommend that oncologists leverage the existing good communication with their patients by increasing the amount and quality of discussions around the importance of adherence and persistence to AHT.

  16. Comparison of two adjuvant hormone therapy regimens in patients with high-risk localized prostate cancer after radical prostatectomy: primary results of study CU1005.

    PubMed

    Chang, Kun; Qin, Xiao-Jian; Zhang, Hai-Liang; Dai, Bo; Zhu, Yao; Shi, Guo-Hai; Shen, Yi-Jun; Zhu, Yi-Ying; Ye, Ding-Wei

    2016-01-01

    The role of adjuvant hormonal therapy and optimized regimens for high-risk localized prostate cancer after radical prostatectomy remains controversial. Herein, the clinical trial CU1005 prospectively evaluated two regimens of maximum androgen blockage  or bicalutamide 150 mg daily as immediate adjuvant therapy for high-risk localized prostate cancer. Overall, 209 consecutive patients were recruited in this study, 107 of whom received 9 months of adjuvant maximum androgen blockage, whereas 102 received 9 months of adjuvant bicalutamide 150 mg. The median postoperative follow-up time was 27.0 months. The primary endpoint was biochemical recurrence. Of the 209 patients, 59 patients developed biochemical recurrence. There was no difference between the two groups with respect to clinical characteristics, including age, pretreatment prostate-specific antigen, Gleason score, surgical margin status, or pathological stages. The maximum androgen blockage group experienced longer biochemical recurrence-free survival (P = 0.004) compared with the bicalutamide 150 mg group. Side-effects in the two groups were similar and could be moderately tolerated in all patients. In conclusion, immediate, 9-month maximum androgen blockage should be considered as an alternative to bicalutamide 150 mg as adjuvant treatment for high-risk localized prostate cancer patients after radical prostatectomy.

  17. Deciding about hormone therapy

    MedlinePlus

    HRT - deciding; Estrogen replacement therapy - deciding; ERT- deciding; Hormone replacement therapy - deciding; Menopause - deciding; HT - deciding; Menopausal hormone therapy - deciding; MHT - deciding

  18. Barriers and facilitators of adjuvant hormone therapy adherence and persistence in women with breast cancer: a systematic review

    PubMed Central

    Moon, Zoe; Moss-Morris, Rona; Hunter, Myra S; Carlisle, Sophie; Hughes, Lyndsay D

    2017-01-01

    Purpose Nonadherence to hormone therapy in breast cancer survivors is common and associated with increased risk of mortality. Consistent predictors of nonadherence and nonpersistence are yet to be identified, and little research has examined psychosocial factors that may be amenable to change through intervention. This review aimed to identify predictors of nonadherence and nonpersistence to hormone therapy in breast cancer survivors in order to inform development of an intervention to increase adherence rates. Methods Studies published up to April 2016 were identified through MEDLINE, Embase, Web of Science, PsycINFO, CINAHL and gray literature. Studies published in English measuring associations between adherence or persistence and any predictor variables were included. Eligible studies were assessed for methodological quality, data were extracted and a narrative synthesis was conducted. Results Sixty-one eligible articles were identified. Most studies focused on clinical and demographic factors with inconsistent results. Some evidence suggested that receiving specialist care and social support were related to increased persistence, younger age and increased number of hospitalizations were associated with nonadherence, and good patient–physician relationship and self-efficacy for taking medication were associated with better adherence. A small amount of evidence suggested that medication beliefs were associated with adherence, but more high-quality research is needed to confirm this. Conclusion Some psychosocial variables were associated with better adherence and persistence, but the results are currently tentative. Future high-quality research should be carried out to identify psychosocial determinants of nonadherence or nonpersistence that are modifiable through intervention. PMID:28260867

  19. Hormone Therapy

    MedlinePlus

    ... estrogen , a hormone that helps control the menstrual cycle . Changing estrogen levels can bring on symptoms such ... two hormones—estrogen and progesterone —control your menstrual cycle. These hormones are made by the ovaries . Estrogen ...

  20. 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.

  1. Hormone therapy in acne.

    PubMed

    Lakshmi, Chembolli

    2013-01-01

    Underlying hormone imbalances may render acne unresponsive to conventional therapy. Relevant investigations followed by initiation of hormonal therapy in combination with regular anti-acne therapy may be necessary if signs of hyperandrogenism are present. In addition to other factors, androgen-stimulated sebum production plays an important role in the pathophysiology of acne in women. Sebum production is also regulated by other hormones, including estrogens, growth hormone, insulin, insulin-like growth factor-1, glucocorticoids, adrenocorticotropic hormone, and melanocortins. Hormonal therapy may also be beneficial in female acne patients with normal serum androgen levels. An understanding of the sebaceous gland and the hormonal influences in the pathogenesis of acne would be essential for optimizing hormonal therapy. Sebocytes form the sebaceous gland. Human sebocytes express a multitude of receptors, including receptors for peptide hormones, neurotransmitters and the receptors for steroid and thyroid hormones. Various hormones and mediators acting through the sebocyte receptors play a role in the orchestration of pathogenetic lesions of acne. Thus, the goal of hormonal treatment is a reduction in sebum production. This review shall focus on hormonal influences in the elicitation of acne via the sebocyte receptors, pathways of cutaneous androgen metabolism, various clinical scenarios and syndromes associated with acne, and the available therapeutic armamentarium of hormones and drugs having hormone-like actions in the treatment of acne.

  2. [Adjuvant dermato-cosmetic acne therapy].

    PubMed

    Bayerl, Christiane; Degitz, Klaus; Meigel, Eva; Kerscher, Martina

    2010-03-01

    Adjuvant dermato-cosmetic therapy in acne is an essential part of the concept of treating acne after initiation and during maintenance therapy. Those are mechanical peeling, chemical peeling and its combination. It needs supervision by an experienced dermatologist.

  3. 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

  4. 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.

  5. Extended Adjuvant Therapy for Breast Cancer

    Cancer.gov

    An NCI Cancer Currents blog on findings from a recent clinical trial which showed that extending adjuvant therapy with an aromatase inhibitor can have important benefits for some women with early-stage cancer.

  6. Postoperative adjuvant therapy of breast cancer. Oncology Overview

    SciTech Connect

    Not Available

    1984-12-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Postoperative chemotherapy; Postoperative radiotherapy; Postoperative hormone therapy; Postoperative immunotherapy and chemoimmunotherapy; Postoperative multimodal therapy; Prognostic factors in postoperative adjuvant therapy.

  7. 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.

  8. (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.

  9. [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.

  10. 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.

  11. 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

  12. Hormone replacement therapy and longevity.

    PubMed

    Comhaire, F

    2016-02-01

    To assess whether hormone replacement therapy influences longevity, an analysis was made of published life tables allowing for the calculation of the relative benefit of hormone replacement therapy on longevity in men with late onset hypogonadism and in post-menopausal women. It was found that testosterone replacement therapy of men suffering from late onset hypogonadism increased survival rate by 9-10% in 5 years, similar to that of eugonadal, non-LOH men with normal endogenous testosterone secretion. Oestrogen replacement therapy resulted in increased survival by 2.6% in 5 years. It is concluded that hormone replacement therapy increases longevity.

  13. Overview of adjuvant systemic therapy in early stage breast cancer.

    PubMed

    Newman, Lisa A; Singletary, S Eva

    2007-04-01

    The benefits of adjuvant systemic therapy in reducing risk of distant relapse from breast cancer have been recognized for several decades. The intent of adjuvant therapy is to eliminate the occult micrometastatic breast cancer burden before it progresses into clinically apparent disease. Successful delivery of effective adjuvant systemic therapy as a complement to surgical management of breast cancer has contributed to the steady declines in breast cancer mortality observed internationally over the past 2 decades. Ongoing clinical and translational research in breast cancer seeks to improve the efficacy of systemic agents for use in the conventional postoperative (adjuvant) setting.

  14. Hormone therapy for transgender patients

    PubMed Central

    2016-01-01

    Many transgender men and women seek hormone therapy as part of the transition process. Exogenous testosterone is used in transgender men to induce virilization and suppress feminizing characteristics. In transgender women, exogenous estrogen is used to help feminize patients, and anti-androgens are used as adjuncts to help suppress masculinizing features. Guidelines exist to help providers choose appropriate candidates for hormone therapy, and act as a framework for choosing treatment regimens and managing surveillance in these patients. Cross-sex hormone therapy has been shown to have positive physical and psychological effects on the transitioning individual and is considered a mainstay treatment for many patients. Bone and cardiovascular health are important considerations in transgender patients on long-term hormones, and care should be taken to monitor certain metabolic indices while patients are on cross-sex hormone therapy. PMID:28078219

  15. Hormone therapy for breast cancer

    MedlinePlus

    ... Mood swings Depression Loss of interest in sex Drug Side Effects The side effects of hormone therapy depend on the drug. Common side effects include hot flashes, night sweats, and vaginal dryness . ...

  16. Side Effects of Hormone Therapy

    MedlinePlus

    ... FAQs Why Give to PCF? Featured Blue Jacket Fashion Show Featured Donate Contact Us Menu Close Donate ... Featured Why Give to PCF? Featured Blue Jacket Fashion Show Contact Us Side Effects of Hormone Therapy ...

  17. Types of Cancer Treatment: Hormone Therapy

    Cancer.gov

    Describes how hormone therapy slows or stops the growth of breast and prostate cancers that use hormones to grow. Includes information about the types of hormone therapy and side effects that may happen.

  18. 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.

  19. The Promher Study: An Observational Italian Study on Adjuvant Therapy for HER2-Positive, pT1a-b pN0 Breast Cancer

    PubMed Central

    Gori, Stefania; Inno, Alessandro; Fiorio, Elena; Foglietta, Jennifer; Ferro, Antonella; Gulisano, Marcella; Pinotti, Graziella; Gubiotti, Marta; Cavazzini, Maria Giovanna; Turazza, Monica; Duranti, Simona; De Simone, Valeria; Iezzi, Laura; Bisagni, Giancarlo; Spazzapan, Simon; Cavanna, Luigi; Saggia, Chiara; Bria, Emilio; Cretella, Elisabetta; Vici, Patrizia; Santini, Daniele; Fabi, Alessandra; Garrone, Ornella; Frassoldati, Antonio; Amaducci, Laura; Saracchini, Silvana; Evangelisti, Lucia; Barni, Sandro; Gamucci, Teresa; Mentuccia, Lucia; Laudadio, Lucio; Zoboli, Alessandra; Marchetti, Fabiana; Bogina, Giuseppe; Lunardi, Gianluigi; Boni, Luca

    2015-01-01

    Background The management of pT1a-b pN0 HER2-positive breast cancer is controversial and no data about the efficacy of trastuzumab in this setting are available from randomized clinical trials. The aims of this retrospective study were to assess how patients are managed in clinical practice in Italy, which clinical or biological characteristics influenced the choice of adjuvant systemic therapy and the outcome of patients. Methods Data of consecutive patients who underwent surgery from January 2007 to December 2012 for HER2-positive, pT1a-b pN0 M0 breast cancer were retrospectively collected from 28 Italian centres. Analysis of contingency tables and multivariate generalized logit models were used to investigate the association between the baseline clinical and biological features and the treatment strategy adopted. Results Among 303 enrolled patients, 204 received adjuvant systemic therapy with trastuzumab, 65 adjuvant systemic therapy without trastuzumab and 34 did not receive adjuvant systemic therapy. At the multivariate analysis age, tumor size, proliferation index and hormone receptor status were significantly associated with the treatment choice. Five-year disease-free survival (DFS) probability was 95%, 94.3% and 69.6% for patients treated with adjuvant systemic therapy and trastuzumab, with adjuvant systemic therapy without trastuzumab and for patients who did not receive adjuvant systemic therapy, respectively (p<0.001). Conclusions The majority of patients (66%) with pT1a-b pN0 HER2-positive breast cancer enrolled in this retrospective study received adjuvant systemic therapy with trastuzumab, whereas only 11% patients did not receive any adjuvant systemic therapy. The choice of treatment type seems to be mainly influenced by tumor size, proliferation index, hormone receptor status and age. The 5-year DFS probability was significantly higher for patients receiving adjuvant systemic therapy with trastuzumab compared with patients not receiving adjuvant

  20. 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

  1. 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.

  2. 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.

  3. Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience

    SciTech Connect

    Bhatia, Sumita; Miller, Robert C. . E-mail: miller.robert@mayo.edu; Haddock, Michael G.; Donohue, John H.; Krishnan, Sunil

    2006-10-01

    Purpose: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. Methods and Materials: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. Results: Adverse prognostic factors for decreased OS by univariate analysis included lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p = 0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p = 0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. Conclusions: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed.

  4. 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.

  5. Progestogens in menopausal hormone therapy

    PubMed Central

    Woroń, Jarosław

    2015-01-01

    Progestogens share one common effect: the ability to convert proliferative endometrium to its secretory form. In contrast, their biological activity is varied, depending on the chemical structure, pharmacokinetics, receptor affinity and different potency of action. Progestogens are widely used in the treatment of menstrual cycle disturbances, various gynaecological conditions, contraception and menopausal hormone therapy. The administration of progestogen in menopausal hormone therapy is essential in women with an intact uterus to protect against endometrial hyperplasia and cancer. Progestogen selection should be based on the characteristics available for each progestogen type, relying on the assessment of relative potency of action in experimental models and animal models, and on the indirect knowledge brought by studies of the clinical use of different progestogen formulations. The choice of progestogen should involve the conscious use of knowledge of its benefits, with a focus on minimizing potential side effects. Unfortunately, there are no direct clinical studies comparing the metabolic effects of different progestogens. PMID:26327902

  6. Hormone therapy and cognitive function

    PubMed Central

    Maki, Pauline M.; Sundermann, Erin

    2009-01-01

    BACKGROUND Clinical trials yield discrepant information about the impact of hormone therapy on verbal memory and executive function. This issue is clinically relevant because declines in verbal memory are the earliest predictor of Alzheimer's disease and declines in executive function are central to some theories of normal, age-related changes in cognition. METHODS We conducted a systematic review of randomized clinical trials of hormone therapy (i.e. oral, transdermal, i.m.) and verbal memory, distinguishing studies in younger (i.e. ≤65 years of age; n = 9) versus older (i.e. >65 years; n = 7) women and studies involving estrogen alone versus estrogen plus progestogen. Out of 32 placebo-controlled trials, 17 were included (13 had no verbal memory measures and 2 involved cholinergic manipulations). We also provide a narrative review of 25 studies of executive function (two trials), since there are insufficient clinical trial data for systematic review. RESULTS There is some evidence for a beneficial effect of estrogen alone on verbal memory in younger naturally post-menopausal women and more consistent evidence from small-n studies of surgically post-menopausal women. There is stronger evidence of a detrimental effect of conjugated equine estrogen plus medroxyprogesterone acetate on verbal memory in younger and older post-menopausal women. Observational studies and pharmacological models of menopause provide initial evidence of improvements in executive function with hormone therapy. CONCLUSIONS Future studies should include measures of executive function and should address pressing clinical questions; including what formulation of combination hormone therapy is cognitively neutral/beneficial, yet effective in treating hot flashes in the early post-menopause. PMID:19468050

  7. 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.

  8. 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.

  9. [Hormonal therapy for prostatic cancer--state of the art].

    PubMed

    Miyakita, Hideshi

    2005-02-01

    Following the studies of Huggins and colleagues in 1941, the hormonal treatment of prostatic cancer has been aimed at neutralizing the influence of testicular androgens through surgical castration or the administration of high dose estrogen. Labrie et al introduced combined use of a LHRH agonist and an androgen antagonist for prostatic cancer. Various reports demonstrated a beneficial effect for combined androgen blockade using nonsteroidal antiandrogens for advanced prostatic cancer through meta-analysis of published randomized control trials. In Japanese status, a combined androgen blockade is popular for advanced prostatic cancer as well as local cancer by J-Cap survey. There is a lot of controversy about adjuvant hormonal therapy for prostatic cancer including intermittent hormonal therapy, but the results are not gotten yet.

  10. 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

  11. Postoperative hormonal therapy prevents recovery of neurological damage after surgery in patients with breast cancer

    PubMed Central

    Sekiguchi, Atsushi; Sato, Chiho; Matsudaira, Izumi; Kotozaki, Yuka; Nouchi, Rui; Takeuchi, Hikaru; Kawai, Masaaki; Tada, Hiroshi; Ishida, Takanori; Taki, Yasuyuki; Ohuchi, Noriaki; Kawashima, Ryuta

    2016-01-01

    Cancer survivors are exposed to several risk factors for cognitive dysfunction, such as general anesthesia, surgical trauma, and adjuvant therapies. In our recent study we showed that thalamic volume reduction and attentional dysfunction occurred shortly after surgery. Here, we examined the 6-month prognosis of the 20 patients with breast cancer who underwent surgery. Seven patients did not receive any adjuvant therapy after the surgery and 13 patients received a hormonal therapy after the surgery. We assessed their attentional functions, and thalamic volumes shortly after and 6 months after surgery. We found a significant group x time interaction in the attentional functions (p = 0.033) and the right thalamus (p <  0.05, small volume correction), suggesting the thalamic volume reduction and attentional dysfunction recovered in patients without adjuvant therapy. Our findings provide a better understanding of the potential role of hormonal therapy in relation to the cognitive dysfunction of cancer survivors. PMID:27708377

  12. Management of sexual dysfunction in postmenopausal breast cancer patients taking adjuvant aromatase inhibitor therapy

    PubMed Central

    Derzko, C.; Elliott, S.; Lam, W.

    2007-01-01

    Treatment with aromatase inhibitors for postmenopausal women with breast cancer has been shown to reduce or obviate invasive procedures such as hysteroscopy or curettage associated with tamoxifen-induced endometrial abnormalities. The side effect of upfront aromatase inhibitors, diminished estrogen synthesis, is similar to that seen with the natural events of aging. The consequences often include vasomotor symptoms (hot flushes) and vaginal dryness and atrophy, which in turn may result in cystitis and vaginitis. Not surprisingly, painful intercourse (dyspareunia) and loss of sexual interest (decreased libido) frequently occur as well. Various interventions, both non-hormonal and hormonal, are currently available to manage these problems. The purpose of the present review is to provide the practitioner with a wide array of management options to assist in treating the sexual consequences of aromatase inhibitors. The suggestions in this review are based on recent literature and on the recommendations set forth both by the North American Menopause Association and in the clinical practice guidelines of the Society of Gynaecologists and Obstetricians of Canada. The complexity of female sexual dysfunction necessitates a biopsychosocial approach to assessment and management alike, with interventions ranging from education and lifestyle changes to sexual counselling, pelvic floor therapies, sexual aids, medications, and dietary supplements—all of which have been reported to have a variable, but often successful, effect on symptom amelioration. Although the use of specific hormone replacement—most commonly local estrogen, and less commonly, systemic estrogen with or without an androgen, progesterone, or the additional of an androgen in an estrogenized woman (or a combination)—may be highly effective, the concern remains that in patients with estrogen-dependent breast cancer, including those receiving anti-estrogenic adjuvant therapies, the use of these hormones may be

  13. Management of sexual dysfunction in postmenopausal breast cancer patients taking adjuvant aromatase inhibitor therapy.

    PubMed

    Derzko, C; Elliott, S; Lam, W

    2007-12-01

    Treatment with aromatase inhibitors for postmenopausal women with breast cancer has been shown to reduce or obviate invasive procedures such as hysteroscopy or curettage associated with tamoxifen-induced endometrial abnormalities. The side effect of upfront aromatase inhibitors, diminished estrogen synthesis, is similar to that seen with the natural events of aging. The consequences often include vasomotor symptoms (hot flushes) and vaginal dryness and atrophy, which in turn may result in cystitis and vaginitis. Not surprisingly, painful intercourse (dyspareunia) and loss of sexual interest (decreased libido) frequently occur as well. Various interventions, both non-hormonal and hormonal, are currently available to manage these problems. The purpose of the present review is to provide the practitioner with a wide array of management options to assist in treating the sexual consequences of aromatase inhibitors. The suggestions in this review are based on recent literature and on the recommendations set forth both by the North American Menopause Association and in the clinical practice guidelines of the Society of Gynaecologists and Obstetricians of Canada. The complexity of female sexual dysfunction necessitates a biopsychosocial approach to assessment and management alike, with interventions ranging from education and lifestyle changes to sexual counselling, pelvic floor therapies, sexual aids, medications, and dietary supplements-all of which have been reported to have a variable, but often successful, effect on symptom amelioration. Although the use of specific hormone replacement-most commonly local estrogen, and less commonly, systemic estrogen with or without an androgen, progesterone, or the additional of an androgen in an estrogenized woman (or a combination)-may be highly effective, the concern remains that in patients with estrogen-dependent breast cancer, including those receiving anti-estrogenic adjuvant therapies, the use of these hormones may be

  14. Adjuvant Therapy for Renal Cell Carcinoma: Past, Present, and Future

    PubMed Central

    Pal, Sumanta K.

    2014-01-01

    At the present time, the standard of care for patients who have received nephrectomy for localized renal cell carcinoma (RCC) is radiographic surveillance. With a number of novel targeted agents showing activity in the setting of metastatic RCC, there has been great interest in exploring the potential of the same agents in the adjuvant setting. Herein, we discuss the evolution of adjuvant trials in RCC, spanning from the immunotherapy era to the targeted therapy era. Pitfalls of current studies are addressed to provide a context for interpreting forthcoming results. Finally, we outline avenues to incorporate promising investigational agents, such as PD-1 (programmed death-1) inhibitors and MNNG transforming gene inhibitors, in future adjuvant trials. PMID:24969163

  15. [Hormonal therapy in breast cancer].

    PubMed

    Espinós, J; Reyna, C; de la Cruz, S; Oiler, C; Hernández, A; Fernández Hidalgo, O; Santisteban, M; García Foncillas, J

    2008-01-01

    Hormonal therapy has been the first systemic treatment against breast cancer. Up to now Tamoxifen and ovarian supression/ablation were the best optionts we had to treat early breast cancer as advancer disease. The advent of aromatase inhibitors, new SERMS and antistrogen Fulvestrant have supoused a great advance in the treatment of this disease and at the same time have complicated the election of the optimal drug for each patient. This article tries to review the aviable treatment options insiting on its indications.

  16. Hormonal therapy of prostate cancer.

    PubMed

    Labrie, Fernand

    2010-01-01

    Of all cancers, prostate cancer is the most sensitive to hormones: it is thus very important to take advantage of this unique property and to always use optimal androgen blockade when hormone therapy is the appropriate treatment. A fundamental observation is that the serum testosterone concentration only reflects the amount of testosterone of testicular origin which is released in the blood from which it reaches all tissues. Recent data show, however, that an approximately equal amount of testosterone is made from dehydroepiandrosterone (DHEA) directly in the peripheral tissues, including the prostate, and does not appear in the blood. Consequently, after castration, the 95-97% fall in serum testosterone does not reflect the 40-50% testosterone (testo) and dihydrotestosterone (DHT) made locally in the prostate from DHEA of adrenal origin. In fact, while elimination of testicular androgens by castration alone has never been shown to prolong life in metastatic prostate cancer, combination of castration (surgical or medical with a gonadotropin-releasing hormone (GnRH) agonist) with a pure anti-androgen has been the first treatment shown to prolong life. Most importantly, when applied at the localized stage, the same combined androgen blockade (CAB) can provide long-term control or cure of the disease in more than 90% of cases. Obviously, since prostate cancer usually grows and metastasizes without signs or symptoms, screening with prostate-specific antigen (PSA) is absolutely needed to diagnose prostate cancer at an 'early' stage before metastasis occurs and the cancer becomes non-curable. While the role of androgens was believed to have become non-significant in cancer progressing under any form of androgen blockade, recent data have shown increased expression of the androgen receptor (AR) in treatment-resistant disease with a benefit of further androgen blockade. Since the available anti-androgens have low affinity for AR and cannot block androgen action completely

  17. 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.

  18. Postmenopausal hormone therapy and cognition.

    PubMed

    McCarrey, Anna C; Resnick, Susan M

    2015-08-01

    This article is part of a Special Issue "Estradiol and cognition". Prior to the publication of findings from the Women's Health Initiative (WHI) in 2002, estrogen-containing hormone therapy (HT) was used to prevent age-related disease, especially cardiovascular disease, and to treat menopausal symptoms such as hot flushes and sleep disruptions. Some observational studies of HT in midlife and aging women suggested that HT might also benefit cognitive function, but randomized clinical trials have produced mixed findings in terms of health and cognitive outcomes. This review focuses on hormone effects on cognition and risk for dementia in naturally menopausal women as well as surgically induced menopause, and highlights findings from the large-scale WHI Memory Study (WHIMS) which, contrary to expectation, showed increased dementia risk and poorer cognitive outcomes in older postmenopausal women randomized to HT versus placebo. We consider the 'critical window hypothesis', which suggests that a window of opportunity may exist shortly after menopause during which estrogen treatments are most effective. In addition, we highlight emerging evidence that potential adverse effects of HT on cognition are most pronounced in women who have other health risks, such as lower global cognition or diabetes. Lastly, we point towards implications for future research and clinical treatments.

  19. History of growth hormone therapy.

    PubMed

    Blizzard, Robert M

    2012-01-01

    The first human to receive GH therapy was in 1956; it was of bovine origin and was given for 3 wk for metabolic balance studies revealing no effects. By 1958, three separate laboratories utilizing different extraction methods retrieved hGH from human pituitaries, purified it and used for clinical investigation. By 1959 presumed GHD patients were being given native hGH collected and extracted by various methods. Since 1 mg of hGH was needed to treat one patient per day, >360 human pituitaries were needed per patient per year. Thus, the availability of hGH was limited and was awarded on the basis of clinical research protocols approved by the National Pituitary Agency (NPA) established in 1961. hGH was dispensed and injected on a milligram weight basis with varied concentrations between batches from 0.5 units/mg to 2.0 units/mg of hGH. By 1977 a centralized laboratory was established to extract all human pituitaries in the US, this markedly improved the yield of hGH obtained and most remarkably, hGH of this laboratory was never associated with Creutzfeld-Jacob disease (CJD) resulting from the injection of apparently prior- contaminated hGH produced years earlier. However, widespread rhGH use was not possible even if a pituitary from each autopsy performed in the US was collected, this would only permit therapy for about 4,000 patients. Thus, the mass production of rhGH required the identification of the gene structure of the hormone, methodology that began in 1976 to make insulin by recombinant technology. Serendipity was manifest in 1985 when patients who had received hGH years previously were reported to have died of CJD. This led to the discontinuation of the distribution and use of hGH, at a time when a synthetic rhGH became available for clinical use. The creation of a synthetic rhGH was accompanied by unlimited supplies of hGH for investigation and therapy. However, the appropriate use and the potential abuse of this hormone are to be dealt with. The

  20. Cognitive Deficits in Breast Cancer Survivors After Chemotherapy and Hormonal Therapy.

    PubMed

    Frank, Jennifer Sandson; Vance, David E; Triebel, Kristen L; Meneses, Karen M

    2015-12-01

    Adjuvant treatments, specifically chemotherapy and hormonal therapy, have dramatically increased breast cancer survival, resulting in increased attention to the residual effects of treatment. Breast cancer survivors (BCS) frequently report that cognitive deficits are a particular source of distress, interfering with many aspects of quality of life. The literature on neuropsychological performance measures in BCS supports the reality of subtle cognitive deficits after both chemotherapy and hormonal therapy. This premise is supported by recent imaging studies, which reveal anatomical changes after chemotherapy as well as changes in patterns of neural activation while performing cognitive tasks. This review suggests that, even when performance on neuropsychological performance measures is within normal limits, BCS may be using increased cognitive resources in the face of reduced cognitive reserve. Potential interventions for cognitive deficits after adjuvant therapy include prescriptions for healthy living, pharmacotherapy, complementary therapy, and cognitive remediation therapy directed toward specific cognitive deficits or a combination of several strategies.

  1. Adjuvant radiation therapy, local recurrence, and the need for salvage therapy in atypical meningioma

    PubMed Central

    Aizer, Ayal A.; Arvold, Nils D.; Catalano, Paul; Claus, Elizabeth B.; Golby, Alexandra J.; Johnson, Mark D.; Al-Mefty, Ossama; Wen, Patrick Y.; Reardon, David A.; Lee, Eudocia Q.; Nayak, Lakshmi; Rinne, Mikael L.; Beroukhim, Rameen; Weiss, Stephanie E.; Ramkissoon, Shakti H.; Abedalthagafi, Malak; Santagata, Sandro; Dunn, Ian F.; Alexander, Brian M.

    2014-01-01

    Background The impact of adjuvant radiation in patients with atypical meningioma remains poorly defined. We sought to determine the impact of adjuvant radiation therapy in this population. Methods We identified 91 patients with World Health Organization grade II (atypical) meningioma managed at Dana-Farber/Brigham and Women's Cancer Center between 1997 and 2011. A propensity score model incorporating age at diagnosis, gender, Karnofsky performance status, tumor location, tumor size, reason for diagnosis, and era of treatment was constructed using logistic regression for the outcome of receipt versus nonreceipt of radiation therapy. Propensity scores were then used as continuous covariates in a Cox proportional hazards model to determine the adjusted impact of adjuvant radiation therapy on both local recurrence and the combined endpoint of use of salvage therapy and death due to progressive meningioma. Results The median follow-up in patients without recurrent disease was 4.9 years. After adjustment for pertinent confounding variables, radiation therapy was associated with decreased local recurrence in those undergoing gross total resection (hazard ratio, 0.25; 95% CI, 0.07–0.96; P = .04). No differences in overall survival were seen in patients who did and did not receive radiation therapy. Conclusion Patients who have had a gross total resection of an atypical meningioma should be considered for adjuvant radiation therapy given the improvement in local control. Multicenter, prospective trials are required to definitively evaluate the potential impact of radiation therapy on survival in patients with atypical meningioma. PMID:24891451

  2. Physical and hormonal evaluation of transsexual patients during hormonal therapy.

    PubMed

    Meyer, W J; Finkelstein, J W; Stuart, C A; Webb, A; Smith, E R; Payer, A F; Walker, P A

    1981-08-01

    The optimal hormonal therapy for transsexual patients is not known. The physical and hormonal characteristics of 38 noncastrate male-to-female transsexuals and 14 noncastrate female-to-male transsexuals have been measured before and/or during therapy with various forms and dosages of hormonal therapy. All patients were hormonally and physically normal prior to therapy. Ethinyl estradiol was superior to conjugated estrogen in suppression of testosterone and gonadotropins but equal in effecting breast growth. The changes in physical and hormonal characteristics were the same for 0.1 mg/d and 0.5 mg/d of ethinyl estradiol. The female-to-male transsexuals were well managed with a dose of intramuscular testosterone cypionate of 400 mg/month, usually given 200 mg every two weeks. The maximal clitoral length reached was usually 4 cm. Higher doses of testosterone did not further increase clitoral length or suppression of gonadotropins; lower doses did not suppress the gonadotropins. Based on the information found in this study, we recommend 0.1 mg/d of ethinyl estradiol for the noncastrate male-to-female transsexual and 200 mg of intramuscular testosterone cypionate every two weeks for the noncastrate female-to-male transsexual.

  3. Exercise as an Adjuvant Therapy for Hematopoietic Stem Cell Mobilization

    PubMed Central

    Emmons, Russell; Niemiro, Grace M.; De Lisio, Michael

    2016-01-01

    Hematopoietic stem cell transplant (HSCT) using mobilized peripheral blood hematopoietic stem cells (HSPCs) is the only curative strategy for many patients suffering from hematological malignancies. HSPC collection protocols rely on pharmacological agents to mobilize HSPCs to peripheral blood. Limitations including variable donor responses and long dosing protocols merit further investigations into adjuvant therapies to enhance the efficiency of HSPCs collection. Exercise, a safe and feasible intervention in patients undergoing HSCT, has been previously shown to robustly stimulate HSPC mobilization from the bone marrow. Exercise-induced HSPC mobilization is transient limiting its current clinical potential. Thus, a deeper investigation of the mechanisms responsible for exercise-induced HSPC mobilization and the factors responsible for removal of HSPCs from circulation following exercise is warranted. The present review will describe current research on exercise and HSPC mobilization, outline the potential mechanisms responsible for exercise-induced HSPC mobilization, and highlight potential sites for HSPC homing following exercise. We also outline current barriers to the implementation of exercise as an adjuvant therapy for HSPC mobilization and suggest potential strategies to overcome these barriers. PMID:27123008

  4. Perspectives in hormone replacement therapy.

    PubMed

    Kenemans, P; van Unnik, G A; Mijatovic, V; van der Mooren, M J

    2001-06-15

    Estrogens have been convincingly shown to be highly effective in preventing and reversing menopause-related conditions, such as hot flushes, urogenital complaints, and postmenopausal bone loss. Observational studies report that long-term, estrogen-containing, postmenopausal hormone replacement therapy (HRT) leads to a substantial reduction in hip fractures, myocardial infarction, and possibly colonic cancer, with important consequences for health and quality of life. Estrogen replacement may postpone the onset of Alzheimer's disease and extend life. While many of these effects are biologically plausible, with a variety of cellular mechanisms being involved, only ongoing and future large-scale randomized clinical trials can and should define the effects of HRT more precisely. Long-term compliance is a key issue for long-term benefits, and offering women a choice of administration routes and regimens can only be beneficial in this respect. Pills, patches, gels, and implants are all widely prescribed. Intravaginal or intranasal forms of administration, which are very easy to use and adaptable on an individual level, are among the new options which could improve long-term continuation of HRT use. Fear of breast cancer and recurrence of vaginal bleeding are real concerns for many women considering HRT. This has led to research into lower-dose, estrogen-containing regimens, into continuous combined regimens, and into the potential of estrogen receptor alpha or beta binding molecules that may help to prevent such problems from arising. The prospects for safe and effective postmenopausal HRT with either estrogens or estrogen-like drugs are very promising when these drugs are used in a patient-tailored, risk profile-based manner.

  5. The role of targeted agents in adjuvant therapy for non-small cell lung cancer.

    PubMed

    Kelly, Karen

    2005-07-01

    The recent survival benefit of adjuvant chemotherapy in early stage non-small cell lung cancer provides optimism for the future success of targeted therapy in this setting. It is important that we begin to explore molecularly targeted agents in the adjuvant arena, but how best to accomplish this in the face of these new findings presents a challenge. Criteria for selecting promising targeted therapies and optimal trial designs to evaluate them expeditiously in the adjuvant setting are clearly needed.

  6. 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

  7. Adjuvant Radiation Therapy and Survival for Pure Tubular Breast Carcinoma-Experience From the SEER Database

    SciTech Connect

    Li Baoqing; Chen, Margaret; Nori, Dattatreyudu; Chao, K.S. Clifford; Chen, Allen M.; Chen, Steven L.

    2012-09-01

    Purpose: Pure tubular carcinoma of the breast (PTCB) represents a distinct subtype of invasive ductal carcinoma (IDC) that is generally thought to be associated with better prognosis than even low-grade IDC. There has been controversy as to the role of adjuvant radiation therapy (RT) in this population. We hypothesized that adjuvant RT would demonstrate a survival improvement. Methods and Materials: We queried the Surveillance, Epidemiology and End Results database for the years 1992-2007 to identify patients with pure tubular carcinomas of the breast. Patient demographics, tumor characteristics, and surgical and RT treatments were collected. Survival analysis was performed using the Kaplan-Meier method for univariate comparisons and Cox proportional hazards modeling for multivariate comparisons, stratifying on the basis of age with a cutoff age of 65. Results: A total of 6465 patients were identified: 3624 (56.1%) patients underwent lumpectomy with RT (LUMP+RT), 1525 (23.6%) patients underwent lumpectomy alone (LUMP), 1266 (19.6%) patients received mastectomy alone (MAST), and 50 (0.8%) patients underwent mastectomy with RT (MAST+RT). When we compared the LUMP+RT and LUMP groups directly, those receiving adjuvant RT tended to be younger and were less likely to be hormone receptor-positive. Overall survival was 95% for LUMP+RT and 90% for LUMP patients at 5 years. For those 65 or younger, the absolute overall survival benefit of LUMP+RT over LUMP was 1% at 5 years and 3% at 10 years. On stratified multivariate analysis, adjuvant RT remained a significant predictor in both age groups (P=.003 in age {<=}65 and P=.04 in age >65 patients). Other significant unfavorable factors were older age and higher T stage (age >65 only). Conclusions: Since sufficiently powered large scale clinical trials are unlikely, we would recommend that adjuvant radiation be considered in PTCB patients age 65 or younger, although consideration of the small absolute survival benefit is

  8. Natural zeolite clinoptilolite: new adjuvant in anticancer therapy.

    PubMed

    Pavelić, K; Hadzija, M; Bedrica, L; Pavelić, J; Dikić, I; Katić, M; Kralj, M; Bosnar, M H; Kapitanović, S; Poljak-Blazi, M; Krizanac, S; Stojković, R; Jurin, M; Subotić, B; Colić, M

    2001-01-01

    Natural silicate materials, including zeolite clinoptilolite, have been shown to exhibit diverse biological activities and have been used successfully as a vaccine adjuvant and for the treatment of diarrhea. We report a novel use of finely ground clinoptilolite as a potential adjuvant in anticancer therapy. Clinoptilolite treatment of mice and dogs suffering from a variety of tumor types led to improvement in the overall health status, prolongation of life-span, and decrease in tumors size. Local application of clinoptilolite to skin cancers of dogs effectively reduced tumor formation and growth. In addition, toxicology studies on mice and rats demonstrated that the treatment does not have negative effects. In vitro tissue culture studies showed that finely ground clinoptilolite inhibits protein kinase B (c-Akt), induces expression of p21WAF1/CIP1 and p27KIP1 tumor suppressor proteins, and blocks cell growth in several cancer cell lines. These data indicate that clinoptilolite treatment might affect cancer growth by attenuating survival signals and inducing tumor suppressor genes in treated cells.

  9. Hormonal component of tumor photodynamic therapy response

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Merchant, Soroush

    2008-02-01

    The involvement of adrenal glucocorticoid hormones in the response of the treatment of solid tumors by photodynamic therapy (PDT) comes from the induction of acute phase response by this modality. This adrenal gland activity is orchestrated through the engagement of the hypothalamic-pituitary-adrenal hormonal axis incited by stress signals emanating from the PDT-treated tumor. Glucocorticoid hormone activity engendered within the context of PDT-induced acute phase response performs multiple important functions; among other involvements they beget acute phase reactant production, systemic neutrophil mobilization, and control the production of inflammation-modulating and immunoregulatory proteins.

  10. Adjuvant photodynamic therapy in surgical management of cerebral tumors

    NASA Astrophysics Data System (ADS)

    Chen, Zong-Qian; Wu, Si-En; Zhu, Shu-Gan

    1993-03-01

    We have performed high dose photoradiation therapy in patients with cerebral tumors. Twenty-seven patients had gliomas, two had metastatic cancer of the brain, one had malignant meningioma. Hematoporphyrin derivative was administered intravenously. All patients underwent a craniotomy with a radical or partial excision of the tumor. There was no evidence of increased cerebral edema and other toxicity from the therapy, and all patients were discharged from the hospital within 15 days after surgery. On the basis of animal experiments our institute started using photodynamic therapy (PDT) as an adjuvant measure to the operative therapy in 30 cases of cerebral tumors. Ten of these patients were excluded from this group because of the short postoperative following time. Here, the details of our experiences are presented as follows: 106 of C6 type glioma cell strain were implanted into the frontal lobe of a Chinese hamster. Fourteen days later intracranial gliomas developed, which were larger than 4 mm in diameter, HpD in a dosage of 4 mg/kg was injected into the tail vein of the animals. The fluorescence was seen 5 minutes later. The diagnostic laser used was He-Ca (Hc-type 15A, made at Shanghai Laser Institute) with a wavelength of 441.6 nm, power of 30 mw. The fluorescence reached its peak point 24 hours later, and the normal tissue can be identified by the lack of fluorescence. Then, the tumor tissue was further radiated with an Ar laser (made in Nanjing Electronic Factory, type 360), pumped dye-laser (made in Changchun Optic Machinery Institute, type 901) with a wavelength of 630 nm, and an energy density of more than 200 Joules/cm2, which might get the tumor cells destroyed selectively. The effect of photoradiation may reach as deep as 4 - 7 mm into the brain tissue without cerebral edema or necrosis.

  11. [How to stop hormone replacement therapy?].

    PubMed

    Polo, Päivi

    2015-01-01

    Hormone replacement therapy is indicated for the treatment of menopausal and urogenital symptoms. The therapy is recommended to be started at the lowest effective dose for a minimum period of time. Discontinuation of the therapy or at least reduction of the dose should be considered yearly. The treatment can be stopped immediately or gradually. The risk of recurrence of menopausal symptoms is equal for both techniques of cessation. Furthermore, the number of those having restarted the therapy does not differ between cessation techniques. A woman is thus able to choose her own cessation technique. Immediate cessation is often successful, whereby complicated instructions for drug reduction are avoided.

  12. Growth hormone replacement therapy in Costello syndrome.

    PubMed

    Triantafyllou, Panagiota; Christoforidis, Athanasios; Vargiami, Euthymia; Zafeiriou, Dimitrios I

    2014-12-01

    Costello syndrome (CS) is considered an overgrowth disorder given the macrosomia that is present at birth .However, shortly after birth the weight drops dramatically and the patients are usually referred for failure to thrive. Subsequently, affected patients develop the distinctive coarse facial appearance and are at risk for cardiac anomalies and solid tumor malignancies. Various endocrine disorders, although not very often, have been reported in patients with CS, including growth hormone deficiency, hypoglycemia, ACTH deficiency, cryptorchidism and hypothyroidism. We report a case of Costello syndrome with hypothyroidism, cryptorchidism and growth hormone deficiency and we evaluate the long-term safety and efficacy of growth hormone replacement therapy. The index patient is a paradigm of successful and safe treatment with growth hormone for almost 7 years. Since patients with CS are at increased risk for cardiac myopathy and tumor development they deserve close monitoring during treatment.

  13. Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

    SciTech Connect

    Ohri, Nitin; Garg, Madhur K.; Aparo, Santiago; Kaubisch, Andreas; Tome, Wolfgang; Kennedy, Timothy J.; Kalnicki, Shalom; Guha, Chandan

    2013-06-01

    Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy.

  14. [Hormone replacement therapy--growth hormone, melatonin, DHEA and sex hormones].

    PubMed

    Fukai, Shiho; Akishita, Masahiro

    2009-07-01

    The ability to maintain active and independent living as long as possible is crucial for the healthy longevity. Hormones responsible for some of the manifestations associated with aging are growth hormone, insulin-like growth factor-1 (IGF-1), melatonin, dehydroepiandrosterone (DHEA), sex hormones and thyroid hormones. These hormonal changes are associated with changes in body composition, visceral obesity, muscle weakness, osteoporosis, urinary incontinence, loss of cognitive functioning, reduction in well being, depression, as well as sexual dysfunction. With the prolongation of life expectancy, both men and women today live the latter third life with endocrine deficiencies. Hormone replacement therapy may alleviate the debilitating conditions of secondary partial endocrine deficiencies by preventing or delaying some aspects of aging.

  15. Utilization and impact of adjuvant therapy in anaplastic oligodendroglioma: an analysis on 1692 patients.

    PubMed

    Shin, Jacob Y; Diaz, Aidnag Z

    2016-09-01

    The aim of this study was to determine the utilization rates and impact of adjuvant therapy on overall survival (OS) for anaplastic oligodendroglioma (AO). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 1692 patients with AO who underwent surgery were identified. 945 (55.9 %) received adjuvant radiotherapy with concomitant chemotherapy (chemoRT), 102 (6.0 %) adjuvant radiotherapy (RT) sequentially followed by chemotherapy, 244 (14.4 %) adjuvant RT alone, and 401 (23.7 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 vs. 2004-2008 (p < 0.001), had Karnofsky Performance Status >70 vs. <70 (p = 0.018), had private insurance vs. Medicaid vs. no insurance (p < 0.001), or had median income ≥$63,000 vs. <$63,000 (p = 0.014). Those who received adjuvant chemoRT (concomitant or sequential) had significantly better 5-year OS than those who received adjuvant RT alone or no adjuvant therapy (59.8 % vs. 65.0 % vs. 44.9 % vs. 45.6 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age. There was no difference in OS when comparing concomitant chemoRT to sequential RT and chemotherapy (p = 0.481). On multivariate analysis, receipt of adjuvant chemoRT (concomitant or sequential) remained an independent prognostic factor for improved OS. Adjuvant chemoRT (concomitant or sequential) is an independent prognostic factor for improved OS in anaplastic oligodendroglioma and should be considered for all clinically suitable patients who have undergone surgery for the disease.

  16. Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy

    NASA Astrophysics Data System (ADS)

    Petryk, Alicia Ailie

    Magnetic nanoparticle hyperthermia (mNPH) is an emerging cancer therapy which has shown to be most effective when applied in the adjuvant setting with chemotherapy, radiation or surgery. Although mNPH employs heat as a primary therapeutic modality, conventional heat may not be the only cytotoxic effect. As such, my studies have focused on the mechanism and use of mNPH alone and in conjunction with cisplatinum chemotherapy in murine breast cancer cells and a related in vivo model. MNPH was compared to conventional microwave tumor heating, with results suggesting that mNPH (mNP directly injected into the tumor and immediately activated) and 915 MHz microwave hyperthermia, at the same thermal dose, result in similar tumor regrowth delay kinetics. However, mNPH shows significantly less peri-tumor normal tissue damage. MNPH combined with cisplatinum also demonstrated significant improvements in regrowth delay over either modality applied as a monotherapy. Additional studies demonstrated that a relatively short tumor incubation time prior to AMF exposure (less than 10 minutes) as compared to a 4-hour incubation time, resulted in faster heating rates, but similar regrowth delays when treated to the same thermal dose. The reduction of heating rate correlated well with the observed reduction in mNP concentration in the tumor observed with 4 hour incubation. The ability to effectively deliver cytotoxic mNPs to metastatic tumors is the hope and goal of systemic mNP therapy. However, delivering relevant levels of mNP is proving to be a formidable challenge. To address this issue, I assessed the ability of cisplatinum to simultaneously treat a tumor and improve the uptake of systemically delivered mNPs. Following a cisplatinum pretreatment, systemic mNPs uptake was increased by 3.1 X, in implanted murine breast tumors. Additional in vitro studies showed the necessity of a specific mNP/ Fe architecture and spatial relation for heat-based cytotoxicity in cultured cells.

  17. [The role of Lactobacillus acidophilus in the prevention and adjuvant therapy of certain infectious diseases].

    PubMed

    Halmy, C; Halmy, L

    1998-09-27

    Authors call attention to the role of lactic acid bacteria in the prevention and adjuvant therapy of certain infective diseases. It has special importance in the prevention and adjuvant therapy of new-born and childhood enteritis, different urogenital inflammations and antibiotic associated diarrhoea. Administration of lactic acid bacteria create eubiosis between the human organism and the world of bacteria, that is, eubacteriosis is developed instead of a pathogen flora, assuring normal physiologic functions for the well-being of the organism.

  18. 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.

  19. Hormone Replacement Therapy, Iron, and Breast Cancer

    DTIC Science & Technology

    2005-10-01

    culture models with different status of estrogen and progesterone receptors as well as an iron loaded transgenic mouse model. Our results have shown that...Hormone replacement therapy, iron, estrogen, cell proliferation, progesterone , breast cancer 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...release an egg every month. Estrogen and progesterone together help regulate this event. As a woman matures, the ovaries have fewer eggs to stimulate

  20. Concurrent or Sequential Hormonal and Radiation Therapy in Breast Cancer: A Literature Review

    PubMed Central

    Yu, Edward; Potvin, Kylea; D'souza, David; Lock, Michael

    2015-01-01

    Background and objectives: Adjuvant hormonal therapy is frequently used in the treatment of women with estrogen receptor (ER)/progesterone receptor (PR) positive breast cancer. When radiotherapy is given, hormone therapy may be delivered in a concurrent or sequential manner. Hormonal blockade with tamoxifen or aromatase inhibitors is thought to arrest hormonally dependent cancer cells in the early G1 phase of the cell cycle. This has been theorized to reduce the efficacy of radiation, which is known to be more effective in cells that are actively dividing. Therefore, there has been a reluctance by many to treat with concurrent hormonal and radiation therapy. Methods: We performed a search of the Medline database that led to the identification of 39 studies. Abstract and full-text review of these studies led to the identification of seven English non-review studies in peer-reviewed literature between 1995 and 2015 that addressed the question of timing of radiation and hormonal therapy. Outcome measures were captured from each of the studies. Results: No difference in survival or local-regional recurrence was identified between concurrent versus sequential treatment. Furthermore, no difference in cosmetic outcome or adverse effects was noted for either approach. However, when comparing radiation alone or radiation and hormonal therapy, there was an increased risk of breast and lung fibrosis with combined treatment. Conclusions: Hormone therapy, concurrent or sequential, with radiation results in comparable disease-related outcomes, including survival and recurrence. However, given the theoretical reduction in efficacy and increased rates of fibrosis with concurrent use, it is reasonable to support the use of sequential therapy. PMID:26623219

  1. Do Patients with Luminal A Breast Cancer Profit from Adjuvant Systemic Therapy? A Retrospective Multicenter Study

    PubMed Central

    Blettner, Maria; Häusler, Sebastian; Janni, Wolfgang; Kreienberg, Rolf; Stein, Roland; Stüber, Tanja; Schwentner, Lukas; Bartmann, Catharina; Wöckel, Achim

    2016-01-01

    Background Luminal A breast cancers respond well to anti-hormonal therapy (HT), are associated with a generally favorable prognosis and constitute the majority of breast cancer subtypes. HT is the mainstay of treatment of these patients, accompanied by an acceptable profile of side effects, whereas the added benefit of chemotherapy (CHT), including anthracycline and taxane-based programs, is less clear-cut and has undergone a process of critical revision. Methods In the framework of the BRENDA collective, we analyzed the benefits of CHT compared to HT in 4570 luminal A patients (pts) with primary diagnosis between 2001 and 2008. The results were adjusted by nodal status, age, tumor size and grading. Results There has been a progressive reduction in the use of CHT in luminal A patients during the last decade. Neither univariate nor multivariate analyses showed any statistically significant differences in relapse free survival (RFS) with the addition of CHT to adjuvant HT, independent of the nodal status, age, tumor size or grading. Even for patients with more than 3 affected lymph nodes, there was no significant difference (univariate: p = 0.865; HR 0.94; 95% CI: 0.46–1.93; multivariate: p = 0.812; HR 0.92; 95% CI: 0.45–1.88). Conclusions The addition of CHT to HT provides minimal or no clinical benefit at all to patients with luminal A breast cancer, independent of the RFS-risk. Consequently, risk estimation cannot be the initial step in the decisional process. These findings–that are in line with several publications–should encourage the critical evaluation of applying adjuvant CHT to patients with luminal A breast cancer. PMID:27992550

  2. Adjuvant therapy for intrahepatic cholangiocarcinoma: the debate continues.

    PubMed

    Zhu, Andrew X; Knox, Jennifer J

    2012-01-01

    lymph nodes were obtained, all of which were negative, consistent with a stage T2, N0, MX intrahepatic cholangiocarcinoma. The tumor was positive for CK7, CK19, and CA19-9 and negative for CK20, CDX2, CA125, ER, PR, GCDFP-15, synaptophysin, and chromogranin (Table 1). The uninvolved liver was unremarkable and a trichrome stain showed no fibrosis. Following an uneventful postoperative recovery, she was referred for consideration of adjuvant therapy.

  3. Cytokines, fatigue, and cutaneous erythema in early stage breast cancer patients receiving adjuvant radiation therapy.

    PubMed

    De Sanctis, Vitaliana; Agolli, Linda; Visco, Vincenzo; Monaco, Flavia; Muni, Roberta; Spagnoli, Alessandra; Campanella, Barbara; Valeriani, Maurizio; Minniti, Giuseppe; Osti, Mattia F; Amanti, Claudio; Pellegrini, Patrizia; Brunetti, Serena; Costantini, Anna; Alfò, Marco; Torrisi, Maria Rosaria; Marchetti, Paolo; Enrici, Riccardo Maurizi

    2014-01-01

    We investigated the hypothesis that patients developing high-grade erythema of the breast skin during radiation treatment could be more likely to present increased levels of proinflammatory cytokines which may lead, in turn, to associated fatigue. Forty women with early stage breast cancer who received adjuvant radiotherapy were enrolled from 2007 to 2010. Fatigue symptoms, erythema, and cytokine levels (IL-1β, IL-2, IL6, IL-8, TNF-α, and MCP-1) were registered at baseline, during treatment, and after radiotherapy completion. Seven (17.5%) patients presented fatigue without associated depression/anxiety. Grade ≥2 erythema was observed in 5 of these 7 patients. IL-1β, IL-2, IL-6, and TNF-α were statistically increased 4 weeks after radiotherapy (P < 0.05). After the Heckman two-step analysis, a statistically significant influence of skin erythema on proinflammatory markers increase (P = 0.00001) was recorded; in the second step, these blood markers showed a significant impact on fatigue (P = 0.026). A seeming increase of fatigue, erythema, and proinflammatory markers was observed between the fourth and the fifth week of treatment followed by a decrease after RT. There were no significant effects of hormone therapy, breast volume, and anemia on fatigue. Our study seems to suggest that fatigue is related to high-grade breast skin erythema during radiotherapy through the increase of cytokines levels.

  4. Postmenopausal Hormone Therapy and Risk of Stroke

    PubMed Central

    Carcaillon, Laure; Plu-Bureau, Geneviève; Oger, Emmanuel; Singh-Manoux, Archana; Tubert-Bitter, Pascale; Elbaz, Alexis; Scarabin, Pierre-Yves

    2016-01-01

    Background and Purpose— The benefit/risk analysis of hormone therapy in postmenopausal women is not straightforward and depends on cardiovascular disease. Evidence supports the safety of transdermal estrogens and the importance of progestogens for thrombotic risk. However, the differential association of oral and transdermal estrogens with stroke remains poorly investigated. Furthermore, there are no data regarding the impact of progestogens. Methods— We set up a nested case–control study of ischemic stroke (IS) within all French women aged 51 to 62 years between 2009 and 2011 without personal history of cardiovascular disease or contraindication to hormone therapy. Participants were identified using the French National Health Insurance database, which includes complete drug claims for the past 3 years and French National hospital data. We identified 3144 hospitalized IS cases who were matched for age and zip code to 12 158 controls. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Results— Compared with nonusers, the adjusted ORs of IS were1.58 (95% CI, 1.01–2.49) in oral estrogen users and 0.83 (0.56–1.24) in transdermal estrogens users (P<0.01). There was no association of IS with use of progesterone (OR, 0.78; 95% CI, 0.49–1.26), pregnanes (OR, 1.00; 95% CI, 0.60–1.67), and nortestosterones (OR, 1.26; 95% CI, 0.62–2.58), whereas norpregnanes increased IS risk (OR, 2.25; 95% CI, 1.05–4.81). Conclusions— Both route of estrogen administration and progestogens were important determinants of IS. Our findings suggest that transdermal estrogens might be the safest option for short-term hormone therapy use. PMID:27256671

  5. Alterations in Hormone Levels After Adjuvant Chemoradiation in Male Rectal Cancer Patients

    SciTech Connect

    Yoon, Frederick H.; Perera, Francisco Fisher, Barbara; Stitt, Larry

    2009-07-15

    Purpose: To evaluate follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels after postoperative chemoradiation in men with rectal cancer. Methods and Materials: Forty-three men with rectal cancer had baseline and postchemoradiation FSH, LH, and testosterone measured. Adjuvant chemoradiation consisted of two 5-day cycles of bolus 5-fluorouracil (5-FU) every 4 weeks at a dose of 500 mg/m{sup 2}/d followed by concurrent chemoradiation followed by two additional 5-day cycles of 5-FU at a dose of 450 mg/m{sup 2}/d. Continuous-infusion 5-FU at 225 mg/m{sup 2}/d was given during radiation. Pelvic radiation consisted of a three- or four-field technique with a median dose of 54.0 Gy in 30 fractions. Results: Median follow-up was 6.1 years. Mean baseline FSH levels increased from 5.3 to a peak of 23.9 IU/L (p < 0.001) 13-24 months after chemoradiation. Mean baseline LH levels increased from 4.3 to a peak of 8.5 IU/L (p < 0.001) within 6 months after chemoradiation. Mean testosterone levels decreased from 15.4 nmol/L at baseline to 8.0 nmol/L more than 4 years after chemoradiation. Mean testosterone to mean LH ratio decreased from 4.4 at baseline to 1.1 after 48 months posttreatment, suggesting a continued decrease in Leydig cell function with time. Testicular dose was measured in 5 patients. Median dose was 4 Gy (range, 1.5-8.9 Gy). Conclusions: Chemoradiation in men with rectal cancer causes persistent increases in FSH and LH levels and decreases in testosterone levels.

  6. Glioblastoma multiforme in conus medullaris with intracranial metastasis after postoperative adjuvant therapy

    PubMed Central

    Yan, Chengrui; Kong, Xiangyi; Yin, Hua; Wang, Yu; He, Huayu; Zhang, Hui; Gao, Jun; Li, Yongning; Ma, Wenbin

    2017-01-01

    Abstract Spinal glioblastoma multiforme is not common among spinal cord tumors. According to our literature review, only 27 cases originating from the conus medullaris were reported. We herein reported a case of a 10-year-old child diagnosed with glioblastoma multiforme. The patient received adjuvant radiotherapy and standard temozolomide chemotherapy after total excision. Intracranial lesions were found 1 month after postoperative adjuvant therapy. We described the clinical characteristics and postoperative therapy of the patient, and reviewed all of the published cases of conus medullaris glioblastoma. Location, age, leptomeningeal spread, and secondary hydrocephalus may be predictive factors. Immunohistochemical factors such as p53 and Ki-67 are also important. Combined treatment of surgery and postoperative adjuvant therapy is commonly used, but is controversial. PMID:28353599

  7. Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

    SciTech Connect

    Horowitz, David P.; Hsu, Charles C.; Wang Jingya; Makary, Martin A.; Winter, Jordan M.; Robinson, Ray; Schulick, Richard D.; Cameron, John L.; Pawlik, Timothy M.; Herman, Joseph M.

    2011-08-01

    Purpose: To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients {>=}75 years of age. Methods: The study group of 655 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma at the Johns Hopkins Hospital over a 12-year period (8/30/1993 to 2/28/2005). Demographic characteristics, comorbidities, intraoperative data, pathology data, and patient outcomes were collected and analyzed by adjuvant treatment status and age {>=}75 years. Cox proportional hazards analysis determined clinical predictors of mortality and morbidity. Results: We identified 166 of 655 (25.3%) patients were {>=}75 years of age and 489 of 655 patients (74.7%) were <75 years of age. Forty-nine patients in the elderly group (29.5%) received adjuvant CRT. For elderly patients, node-positive metastases (p = 0.008), poor/anaplastic differentiation (p = 0.012), and undergoing a total pancreatectomy (p = 0.010) predicted poor survival. The 2-year survival for elderly patients receiving adjuvant therapy was improved compared with surgery alone (49.0% vs. 31.6%, p = 0.013); however, 5-year survival was similar (11.7% vs. 19.8%, respectively, p = 0.310). After adjusting for major confounders, adjuvant therapy in elderly patients had a protective effect with respect to 2-year survival (relative risk [RR] 0.58, p = 0.044), but not 5-year survival (RR 0.80, p = 0.258). Among the nonelderly, CRT was significantly associated with 2-year survival (RR 0.60, p < 0.001) and 5-year survival (RR 0.69, p < 0.001), after adjusting for confounders. Conclusions: Adjuvant therapy after PD is significantly associated with increased 2-year but not 5-year survival in elderly patients. Additional studies are needed to select which elderly patients are likely to benefit from adjuvant CRT.

  8. Hand osteoarthritis, menopause and menopausal hormone therapy.

    PubMed

    Watt, Fiona E

    2016-01-01

    Hand osteoarthritis (OA) is one of the commonest musculoskeletal conditions, primarily affecting women over the age of 50, typically around the age of the menopause. Symptomatic disease can give rise to substantial pain, impairment of hand function and quality of life, leading to significant socioeconomic cost. There is currently no disease-modifying therapy, representing a huge unmet clinical need. The evidence for a relationship between hand OA and the menopause is summarised. Whether there is evidence for an effect of menopausal hormonal therapy on the incidence, prevalence or severity of symptomatic hand OA is critically reviewed, and gaps in our knowledge identified. Lastly, the potential mechanisms by which estrogen, or newer agents such as SERMs, might act to interfere with disease pathogenesis are overviewed. The need for specifically designed, controlled trials of agents in cohorts with symptomatic hand OA, refractory to standard symptomatic management is highlighted.

  9. Enzyme and combination therapy with cyclosporin A in the rat developing adjuvant arthritis.

    PubMed

    Rovenská, E; Svík, K; Stancíková, M; Rovenský, J

    1999-01-01

    Recent knowledge of the pathophysiology of rheumatoid arthritis and the mechanism of drug effects have enabled the use of new drugs and drug combinations in rheumatoid arthritis therapy. This study investigates the efficacy of both enzyme therapy and combined therapy with cyclosporin in rats with adjuvant arthritis. Rats with adjuvant-induced arthritis were administered either cyclosporin A (2.5 or 5.0 mg/kg/day per os), a mixture of enzymes (Phlogenzym (PHL); 45 mg/kg twice daily intrarectally), or a combination of 2.5 mg cyclosporin A and 90 mg PHL for a period of 40 days from the adjuvant application. Levels of serum albumin, changes in hind paw swelling and bone erosions were measured in rats as variables of inflammation and arthritis-associated destructive changes. Treatment with 5 mg of cyclosporin A, as well as with the combination therapy with cyclosporin A plus PHL, significantly inhibited both the inflammation and destructive arthritis-associated changes. However, 2.5 mg of cyclosporin A and PHL alone inhibited these disease markers, although to a lesser extent and at a later stage of arthritis development. The results show the inhibitory effect of enzyme therapy on rat adjuvant arthritis, as well as the efficacy of a low dose of cyclosporin A given in combination with enzyme therapy, which may be useful in the treatment of rheumatoid arthritis.

  10. 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

  11. Adjuvant Therapy: Treatment to Keep Cancer from Returning

    MedlinePlus

    ... or neoadjuvant therapy doesn't come without a price — the side effects can be more than minor ... chemotherapy. Radiation therapy. Radiation therapy uses high-powered energy beams, such as X-rays, to kill cancer ...

  12. 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).

  13. Successful management of chronic multifocal Q fever Osteomyelitis with adjuvant interferon-gamma therapy.

    PubMed

    Neth, Olaf Werner; Falcon, Dolores; Peromingo, Estrella; Soledad Camacho, Maria; Rodríguez-Gallego, Carlos; Obando, Ignacio

    2011-09-01

    We present a 3-year-old girl who had chronic recurrent multifocal osteomyelitis caused by Coxiella burnetii despite long-term dual antibiotic therapy. Excellent clinical response was achieved and sustained when immunomodulatory therapy with interferon-γ was initiated. This is the case of a first child who was successfully treated with interferon-γ as adjuvant therapy for chronic multifocal Q fever osteomyelitis.

  14. Hormone therapy and radiotherapy for early prostate cancer: A utility-adjusted number needed to treat (NNT) analysis

    SciTech Connect

    Jani, Ashesh B.; Kao, Johnny; Heimann, Ruth; Hellman, Samuel . E-mail: s-hellman@uchicago.edu

    2005-03-01

    Purpose: To quantify, using the number needed to treat (NNT) methodology, the benefit of short-term ({<=}6 months) hormone therapy adjuvant to radiotherapy in the group of patients with early (clinical stage T1-T2c) prostate cancer. Methods and materials: The absolute biochemical control benefit for the use of hormones adjuvant to radiotherapy in early-stage disease was determined by literature review. A model was developed to estimate the utility-adjusted survival detriment due to the side effects of hormone therapy. The NNTs before and after the incorporation of hormone sequelae were computed; the sign and magnitude of the NNTs were used to gauge the effect of the hormones. Results: The absolute NNT analysis, based on summarizing the results of 8 reports including a total of 3652 patients, demonstrated an advantage to the addition of hormones for the general early-stage prostate cancer population as well as for all prognostic groups. After adjustment for hormone-induced functional loss, the advantage of hormones remained considerable in the high- and intermediate-risk groups, with the utility-adjusted NNT becoming weakened in the low-risk group when the utility compromise from complications of hormones was assumed to be considerable. Conclusions: Short-term hormone therapy seems to be beneficial for selected early-stage prostate cancer patients. The advantage seems to be greatest in the intermediate- and high-risk groups; with current follow-up, the side effects of hormones may outweigh their benefit in certain clinical situations in the favorable group. The present investigation demonstrates the significant role of the NNT technique for oncologic and radiotherapeutic management decisions when treatment complications need to be considered and balanced with the beneficial effects of the treatment.

  15. 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.

  16. Adding hormonal therapy to chemotherapy and trastuzumab improves prognosis in patients with hormone receptor-positive and human epidermal growth factor receptor 2-positive primary breast cancer.

    PubMed

    Hayashi, Naoki; Niikura, Naoki; Yamauchi, Hideko; Nakamura, Seigo; Ueno, Naoto T

    2013-01-01

    Adjuvant hormonal therapy for hormone receptor (HR)-positive primary breast cancer patients and a human epidermal growth factor receptor 2 (HER2)-targeted agent for HER2-positive primary breast cancer patients are standard treatment. However, it is not well known whether adding hormonal therapy to the combination of preoperative or postoperative chemotherapy and HER2-targeted agent contributes any additional clinical benefit in patients with HR-positive/HER2-positive primary breast cancer regardless of cross-talk between HR and HER2. We retrospectively reviewed records from 897 patients with HR-positive/HER2-positive primary breast cancer with clinical stage I-III disease who underwent surgery between 1988 and 2009. We determined the overall survival (OS) and disease-free survival (DFS) rates according to whether they received hormonal therapy or not and according to the type of hormonal therapy, tamoxifen and aromatase inhibitor, they received. The median followup time was 52.8 months (range 1-294.6 months). Patients who received hormonal therapy with chemotherapy and trastuzumab (n = 128) had significantly higher OS and DFS rates than did those who received only chemotherapy and trastuzumab (n = 46) in log-rank analysis (OS 96.1 vs. 87.0 %, p = 0.023, DFS 86.7 vs. 78.3 %, p = 0.029). There was no statistical difference in OS or DFS between those given an aromatase inhibitor and those given tamoxifen. In multivariate analysis, receiving hormonal therapy in addition to the combination of chemotherapy and trastuzumab was the sole independent prognostic factor for DFS (hazard ratio 0.446; 95 % CI 0.200-0.992; p = 0.048), and there was a similar trend in OS. Our study supported that hormonal therapy, whether in the form of an aromatase inhibitor or tamoxifen, confers a survival benefit when added to chemotherapy and trastuzumab in patients with HR-positive/HER2-positive primary breast cancer. Adjuvant treatment without hormonal therapy is inferior for this patient

  17. Adjuvant Therapy for a Microscopically Incomplete Resection Margin after an Esophagectomy for Esophageal Squamous Cell Carcinoma

    PubMed Central

    Qiu, Bo; Li, JiaXiang; Wang, Bin; Wang, ZhiQiang; Liang, Ying; Cai, Peiqiang; Chen, ZhaoLin; Liu, MengZhong; Fu, JianHua; Yang, Hong; Liu, Hui

    2017-01-01

    Purpose: To investigate the prognosis of esophageal squamous cell carcinoma with a microscopically incomplete (R1) resection margin following an esophagectomy, as well as the impact of adjuvant treatment on survival. Methods: Data obtained from 124 patients with R1-resected ESCC were reviewed. The impact of clinicopathological factors and adjuvant treatment on the overall survival, locoregional recurrence, and distant recurrence were explored. Results: For a median follow-up time of 16.8 months, the median overall survival of 124 patients was 25.6 months. The 1, 3, and 5-year overall survival rates were 75.6%±4.0%, 35.9%±5.1%, and 23.2%±5.0%, respectively. Adjuvant therapy was administered in 78 patients. In the univariate analyses, patients with a pN0 stage (log rank, p=0.028) and adjuvant chemotherapy (log rank, p=0.032) exhibited more favorable overall survival. In the multivariate analyses, the pN stage (HR=2.192, p=0.004) and adjuvant chemotherapy (HR=0.032, p=0.004) were independent prognostic factors for overall survival. Locoregional recurrence was the main failure pattern after R1 resection. The pN stage (HR=2.567, p=0.009) and adjuvant radiotherapy (HR=0.278, p=0.000) were independent prognostic factors for locoregional recurrence. Conclusion: In R1-resected esophageal squamous cell carcinoma, adjuvant radiotherapy reduced locoregional recurrence; however, it did not improve overall survival. Adjuvant chemotherapy demonstrated benefits for overall survival. The pN stage was an independent prognostic factor for locoregional recurrence and overall survival. PMID:28243329

  18. 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

  19. High-Dose Adjuvant Radiotherapy After Radical Prostatectomy With or Without Androgen Deprivation Therapy

    SciTech Connect

    Ost, Piet; Cozzarini, Cesare; De Meerleer, Gert; Fiorino, Claudio; De Potter, Bruno; Briganti, Alberto; Nagler, Evi V.T.; Montorsi, Francesco; Fonteyne, Valerie; Di Muzio, Nadia

    2012-07-01

    Purpose: To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Methods and Materials: Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was left at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification. Results: After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT. Conclusions: This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.

  20. Hormone therapy for inmates: a metonym for transgender rights.

    PubMed

    Maruri, Silpa

    2011-01-01

    The issue of hormone therapy for transgender inmates, while seemingly limited in importance, is one that involves issues of greater importance for the transgender community. The greatest issue at the heart of the matter is the legal argument that is traditionally used to gain access to hormone therapy: the Eighth Amendment. The Eighth Amendment prohibits deliberate indifference to the medical needs of inmates. Traditionally, transgender inmates have gained access to hormone therapy by appealing to the DSM-IV's classification of Gender Identity Disorder (GID) as a mental illness, and by establishing that prison officials' failure to provide hormone therapy constitutes deliberate indifference to a serious medical need. However, appeal to GID is a double-edged sword: while it allows access to hormone therapy, it does so by describing transgender individuals as somehow sick or infirm. This description is at odds with the transgender community's conceptualization of itself. This Note seeks to square the legal arguments for provision of hormone therapy to transgender inmates with the philosophical backdrop that shapes the transgender rights movement by using Plyler v. Doe as a model. This Note argues that access to hormone therapy by transgender inmates involves the intersection of a quasi-fundamental right with a quasi-suspect class. By utilizing such an argument, the transgender community is not bound by the negative expressive effect that the law may have in describing it as infirm or deficient.

  1. Profiling and Hormonal Therapy for Acne in Women

    PubMed Central

    Ghosh, Sangita; Chaudhuri, Soumik; Jain, Vijay Kumar; Aggarwal, Kamal

    2014-01-01

    Acne vulgaris is the most common condition treated by physicians worldwide. Though most acne patients remit spontaneously, for the ones that do not or are unresponsive to conventional therapy or have obvious cutaneous signs of hyperandrogenism, hormonal therapy is the next option in the therapeutic ladder. It is not strictly indicated for only those patients who have cutaneous or biochemical evidence of hyperandrogenism, but can be used even without any evidence of hyperandrogenism, for therapy-resistant acne. It can be prescribed as monotherapy, but when used in combination with other conventional therapies, it may prove to be more beneficial. Hormonal evaluation is a prerequisite for hormonal therapy, to identify the cause behind hyperandrogenism, which may be ovarian or adrenal. This article reviews guidelines for patient selection and the various available hormonal therapeutic options, their side-effect profile, indications and contraindications, and various other practical aspects, to encourage dermatologists to become comfortable prescribing them. PMID:24700926

  2. Dose-dense and sequential strategies in adjuvant breast cancer therapy.

    PubMed

    Untch, M; Von Koch, F; Crohns, C; Sobotta, K; Kahlert, S; Konecny, G; Hepp, H

    2001-05-01

    Several attempts have been made to improve the survival rates of breast cancer patients. The benefit of adjuvant chemotherapy was clearly shown, but the absolute difference of 2% to 11% in overall survival, depending on the patient group, is disappointingly small. In particular, high-risk patients, such as those with > or = 10 involved lymph nodes, extracapsular spread, or vascular invasion, still have an excessive risk of recurrence even after standard adjuvant chemotherapy. To increase the survival rates after adjuvant therapy, new chemotherapeutic agents and new strategies of application are currently being evaluated in clinical trials. Chemotherapy with cyclophosphamide (Cytoxan, Neosar), methotrexate, and fluorouracil (CMF) seems to be safe and effective in patients with breast cancer. In addition, in metastatic patients, dose-intensified chemotherapy is being investigated. The introduction of epirubicin (Ellence), an agent less cardiotoxic and equally active compared to doxorubicin, enabled the escalation of anthracyclines in adjuvant therapy without serious cardiotoxic effects. The combination of dose-intensified chemotherapy and sequential application in the treatment of breast cancer is reviewed.

  3. Postmenopausal hormone therapy and Alzheimer disease

    PubMed Central

    Tuppurainen, Marjo; Rikkonen, Toni; Kivipelto, Miia; Soininen, Hilkka; Kröger, Heikki; Tolppanen, Anna-Maija

    2017-01-01

    Objective: To explore the association between postmenopausal hormone therapy (HT) and Alzheimer disease (AD). Methods: Twenty-year follow-up data from the Kuopio Osteoporosis Risk Factor and Prevention study cohort were used. Self-administered questionnaires were sent to all women aged 47–56 years, residing in Kuopio Province starting in 1989 until 2009, every 5th year. Register-based information on HT prescriptions was available since 1995. Probable AD cases, based on DSM-IV and National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria, were identified from the special reimbursement register (1999–2009). The study population included 8,195 women (227 cases of incident AD). Results: Postmenopausal estrogen use was not associated with AD risk in register-based or self-reported data (hazard ratio/95% confidence interval 0.92/0.68–1.2, 0.99/0.75–1.3, respectively). Long-term self-reported postmenopausal HT was associated with reduced AD risk (0.53/0.31–0.91). Similar results were obtained with any dementia diagnosis in the hospital discharge register as an outcome. Conclusions: Our results do not provide strong evidence for a protective association between postmenopausal HT use and AD or dementia, although we observed a reduced AD risk among those with long-term self-reported HT use. PMID:28202700

  4. Adjuvant chemotherapy and HER-2-directed therapy for early-stage breast cancer in the elderly

    PubMed Central

    Sun, J; Chia, S

    2017-01-01

    There is a lack of sufficient evidence-based data defining the optimal adjuvant systemic therapies in older women. Recommendations are mainly based on retrospective studies, subgroup analyses within larger randomised trials and expert opinion. Treatment decisions should consider the functional fitness of the patient, co-morbidities, in addition to chronological age with the aim to balance risks and potential benefits from treatment(s). In this review, we discuss assessment tools to aid clinicians to select elderly patients who are ‘fit' for chemotherapy, and review the literature on the use of chemotherapy and of the anti-HER 2 antibody trastuzumab in this population. We will also review two commonly used prediction models to assess their accuracy in predicting survival outcomes in elderly patients. Ongoing clinical trials specifically focusing on older patients may help to clarify the absolute benefits and risks of adjuvant systemic therapy in this age group. PMID:27875517

  5. Starting Hormone Therapy at Menopause Increases Breast Cancer Risk

    Cancer.gov

    According to a January 28, 2011 article in the Journal of the National Cancer Institute, women who start taking menopausal hormone therapy around the time of menopause have a higher risk of breast cancer than women who begin taking hormones a few years later.

  6. Menopausal Hormone Therapy for the Primary Prevention of Chronic Conditions

    MedlinePlus

    ... recommendations summarize what the Task Force learned: The harms of hormone therapy, when used to prevent chronic ... Primary Prevention of Chronic Conditions Potential Benefits and Harms The Task Force found that taking both estrogen ...

  7. Hormone Replacement Therapy: Can It Cause Vaginal Bleeding?

    MedlinePlus

    Diseases and Conditions Menopause I'm taking hormone therapy for menopause symptoms, and my monthly menstrual periods have returned. Is this normal? Answers from Shannon K. Laughlin-Tommaso, M.D. Some forms ...

  8. Cell membrane modulation as adjuvant in cancer therapy.

    PubMed

    Zalba, Sara; Ten Hagen, Timo L M

    2017-01-01

    Cancer is a complex disease involving numerous biological processes, which can exist in parallel, can be complementary, or are engaged when needed and as such can replace each other. This redundancy in possibilities cancer cells have, are fundamental to failure of therapy. However, intrinsic features of tumor cells and tumors as a whole provide also opportunities for therapy. Here we discuss the unique and specific makeup and arrangement of cell membranes of tumor cells and how these may help treatment. Interestingly, knowledge on cell membranes and associated structures is present already for decades, while application of membrane modification and manipulation as part of cancer therapy is lagging. Recent developments of scientific tools concerning lipids and lipid metabolism, opened new and previously unknown aspects of tumor cells and indicate possible differences in lipid composition and membrane function of tumor cells compared to healthy cells. This field, coined Lipidomics, demonstrates the importance of lipid components in cell membrane in several illnesses. Important alterations in cancer, and specially in resistant cancer cells compared to normal cells, opened the door to new therapeutic strategies. Moreover, the ability to modulate membrane components and/or properties has become a reality. Here, developments in cancer-related Lipidomics and strategies to interfere specifically with cancer cell membranes and how these affect cancer treatment are discussed. We hypothesize that combination of lipid or membrane targeted strategies with available care to improve chemotherapy, radiotherapy and immunotherapy will bring the much needed change in treatment in the years to come.

  9. Locoregional Failure in Early-Stage Breast Cancer Patients Treated With Radical Mastectomy and Adjuvant Systemic Therapy: Which Patients Benefit From Postmastectomy Irradiation?

    SciTech Connect

    Trovo, Marco; Durofil, Elena; Polesel, Jerry; Roncadin, Mario; Perin, Tiziana; Mileto, Mario; Piccoli, Erica; Quitadamo, Daniela; Massarut, Samuele; Carbone, Antonino; Trovo, Mauro G.

    2012-06-01

    Purpose: To assess the locoregional failure in patients with Stage I-II breast cancer treated with radical mastectomy and to evaluate whether a subset of these patients might be at sufficiently high risk of locoregional recurrence (LRR) to benefit from postmastectomy irradiation (PMRT). Methods and Materials: Stage I-II breast cancer patients (n = 150) treated with radical mastectomy without adjuvant irradiation between 1999 and 2005 were analyzed. The pattern of LRR was reported. Kaplan-Meier analysis was used to calculate rates of LRR, and Cox proportional hazards methods were used to evaluate potential risk factors. Results: Median follow-up was 75 months. Mean patient age was 56 years. One-hundred forty-three (95%) patients received adjuvant systemic therapy: 85 (57%) hormonal therapy alone, 14 (9%) chemotherapy alone, and 44 (29%) both chemotherapy and hormonal therapy. Statistically significant factors associated with increased risk of LRR were premenopausal status (p = 0.004), estrogen receptor negative cancer (p = 0.02), pathologic grade 3 (p = 0.02), and lymphovascular invasion (p = 0.001). T and N stage were not associated with increased risk of regional recurrence. The 5-year LRR rate for patients with zero or one, two, three, and four risk factors was 1%, 10.3%, 24.2%, and 75%, respectively. Conclusions: A subset of patients with early-stage breast cancer is at high risk of LRR, and therefore PMRT might be beneficial.

  10. Preoperative adjuvant transarterial chemoembolization cannot improve the long term outcome of radical therapies for hepatocellular carcinoma.

    PubMed

    Jianyong, Lei; Jinjing, Zhong; Lunan, Yan; Jingqiang, Zhu; Wentao, Wang; Yong, Zeng; Bo, Li; Tianfu, Wen; Jiaying, Yang

    2017-02-03

    Combinations of transarterial chemoembolization (TACE) and radical therapies (pretransplantation, resection and radiofrequency ablation) for hepatocellular carcinoma (HCC) have been reported as controversial issues in recent years. A consecutive sample of 1560 patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B HCC who underwent solitary Radiofrequency ablation (RFA), resection or liver transplantation (LT) or adjuvant pre-operative TACE were included. The 1-, 3- and 5-year overall survival rates and tumor-free survival rates were comparable between the solitary radical therapy group and TACE combined group in the whole group and in each of the subgroups (RFA, resection and LT) (P > 0.05). In the subgroup analysis, according to BCLC stage A or B, the advantages of adjuvant TACE were also not observed (P > 0.05). A Neutrophil-lymphocyte ratio (NLR) more than 4, multiple tumor targets, BCLC stage B, and poor histological grade were significant contributors to the overall and tumor-free survival rates. In conclusions, our results indicated that preoperative adjuvant TACE did not prolong long-term overall or tumor-free survival, but LT should nevertheless be considered the first choice for BCLC stage A or B HCC patients. Radical therapies should be performed very carefully in BCLC stage B HCC patients.

  11. Preoperative adjuvant transarterial chemoembolization cannot improve the long term outcome of radical therapies for hepatocellular carcinoma

    PubMed Central

    Jianyong, Lei; Jinjing, Zhong; Lunan, Yan; Jingqiang, Zhu; Wentao, Wang; Yong, Zeng; Bo, Li; Tianfu, Wen; Jiaying, Yang

    2017-01-01

    Combinations of transarterial chemoembolization (TACE) and radical therapies (pretransplantation, resection and radiofrequency ablation) for hepatocellular carcinoma (HCC) have been reported as controversial issues in recent years. A consecutive sample of 1560 patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B HCC who underwent solitary Radiofrequency ablation (RFA), resection or liver transplantation (LT) or adjuvant pre-operative TACE were included. The 1-, 3- and 5-year overall survival rates and tumor-free survival rates were comparable between the solitary radical therapy group and TACE combined group in the whole group and in each of the subgroups (RFA, resection and LT) (P > 0.05). In the subgroup analysis, according to BCLC stage A or B, the advantages of adjuvant TACE were also not observed (P > 0.05). A Neutrophil-lymphocyte ratio (NLR) more than 4, multiple tumor targets, BCLC stage B, and poor histological grade were significant contributors to the overall and tumor-free survival rates. In conclusions, our results indicated that preoperative adjuvant TACE did not prolong long-term overall or tumor-free survival, but LT should nevertheless be considered the first choice for BCLC stage A or B HCC patients. Radical therapies should be performed very carefully in BCLC stage B HCC patients. PMID:28155861

  12. Prognostic values of DLK1 for surgery and imatinib mesylate adjuvant therapy in gastrointestinal stromal tumors

    PubMed Central

    Xu, Jia; Wang, Ming; Zhang, Zizhen; Zhao, Wenyi; Wang, Chaojie; Tu, Lin; Zhang, Yeqian; Cao, Hui

    2016-01-01

    The Delta-like 1 homolog (DLK1) gene is a paternal imprinting gene located on human chromosome 14q32, a site associated with frequent chromosomal mutations in GIST. The expression level of DLK1 is closely associated with the outcome of tumours. However, no study has reported the DLK1 expression in GIST. Here, we demonstrated that DLK1 showed low expression in GIST patients with low risk according to the modified National Institute of Health (NIH) criteria. With increasing tumour risk level, DLK1 gene and protein expression levels gradually increased. In the test cohort, tissue microarray data showed that DLK1 protein expression was significantly associated with tumour size, mitotic figure count, NIH risk level, and Ki67 expression. In terms of either disease-free survival (DFS) or overall survival (OS), the long-term outcome was significantly better in DLK1-negative patients than in DLK1-positive patients. Univariate and multivariate analyses suggested that DLK1 expression was an independent risk factor influencing tumour DFS. Additionally, for intermediate/high-risk GIST patients received postoperative IM adjuvant therapy, Kaplan-Meier analysis showed that IM adjuvant therapy was associated with a better outcome in DLK1-negative patients than in DLK1-positive patients. All of the above results were verified in the validation cohort. Taken together, DLK1 is a promising prognostic biomarker for GISTs that may help to predict surgical outcomes and guide adjuvant IM therapy. PMID:27904782

  13. Increased survival in men with metastatic prostate cancer receiving chemo and hormone therapy

    Cancer.gov

    Men with hormone-sensitive metastatic prostate cancer who received the chemotherapy drug docetaxel given at the start of standard hormone therapy lived longer than patients who received hormone therapy alone, according to early results from a NIH-supporte

  14. Estrogen Receptor Polymorphisms and the Vascular Effects of Hormone Therapy

    PubMed Central

    Rossouw, Jacques; Bray, Paul; Liu, Jingmin; Kooperberg, Charles; Hsia, Judith; Lewis, Cora; Cushman, Mary; Bonds, Denise; Hendrix, Susan; Papanicolaou, George; Howard, Tim; Herrington, David

    2010-01-01

    Objective To test whether estrogen receptor polymorphisms modify the effects of postmenopausal hormone therapy on biomarkers and on risk of coronary heart disease events, stroke, or venous thrombo-embolism. Methods and Results The design was a nested case-control study in the Women’s Health Initiative trials of postmenopausal hormone therapy. The study included all cases in the first 4 years: coronary heart disease, 359; stroke, 248; venous thrombo-embolism, 217). Six estrogen receptor-αand one estrogen receptor-β polymorphisms were genotyped; 8 biomarkers known to be affected by hormone therapy were measured at baseline and one year after randomization. The polymorphisms were not associated with risk of vascular events, and did not modify the increased risks of coronary heart disease, stroke, or venous thrombo-embolism due to hormone therapy. However, a reduced response of plasmin-antiplasmin (PAP) to hormone therapy was noted for ESR1 IVS1-354 (interaction P<0.0001, corrected for multiple comparisons P=0.014) and ESR1 IVS1-1415 (interaction P<0.0001, corrected P= 0.014). Conclusions Estrogen receptor polymorphisms reduce the effect of postmenopausal hormone therapy on PAP, a marker of coagulation and fibrinolysis. However screening for ER polymorphisms to identify women at less risk of adverse cardiovascular outcomes is not likely to be useful for making HT treatment decisions. PMID:21106950

  15. Effects of hormone therapy on brain structure

    PubMed Central

    Tosakulwong, Nirubol; Lesnick, Timothy G.; Zuk, Samantha M.; Gunter, Jeffrey L.; Gleason, Carey E.; Wharton, Whitney; Dowling, N. Maritza; Vemuri, Prashanthi; Senjem, Matthew L.; Shuster, Lynne T.; Bailey, Kent R.; Rocca, Walter A.; Jack, Clifford R.; Asthana, Sanjay; Miller, Virginia M.

    2016-01-01

    Objective: To investigate the effects of hormone therapy on brain structure in a randomized, double-blinded, placebo-controlled trial in recently postmenopausal women. Methods: Participants (aged 42–56 years, within 5–36 months past menopause) in the Kronos Early Estrogen Prevention Study were randomized to (1) 0.45 mg/d oral conjugated equine estrogens (CEE), (2) 50 μg/d transdermal 17β-estradiol, or (3) placebo pills and patch for 48 months. Oral progesterone (200 mg/d) was given to active treatment groups for 12 days each month. MRI and cognitive testing were performed in a subset of participants at baseline, and at 18, 36, and 48 months of randomization (n = 95). Changes in whole brain, ventricular, and white matter hyperintensity volumes, and in global cognitive function, were measured. Results: Higher rates of ventricular expansion were observed in both the CEE and the 17β-estradiol groups compared to placebo; however, the difference was significant only in the CEE group (p = 0.01). Rates of ventricular expansion correlated with rates of decrease in brain volume (r = −0.58; p ≤ 0.001) and with rates of increase in white matter hyperintensity volume (r = 0.27; p = 0.01) after adjusting for age. The changes were not different between the CEE and 17β-estradiol groups for any of the MRI measures. The change in global cognitive function was not different across the groups. Conclusions: Ventricular volumes increased to a greater extent in recently menopausal women who received CEE compared to placebo but without changes in cognitive performance. Because the sample size was small and the follow-up limited to 4 years, the findings should be interpreted with caution and need confirmation. Classification of evidence: This study provides Class I evidence that brain ventricular volume increased to a greater extent in recently menopausal women who received oral CEE compared to placebo. PMID:27473135

  16. Adjuvant combined ozone therapy for extensive wound over tibia.

    PubMed

    Shah, Prasham; Shyam, Ashok K; Shah, Sambhav

    2011-07-01

    Disinfectant and antibacterial properties of ozone are utilized in the treatment of nonhealing or ischemic wounds. We present here a case of 59 years old woman with compartment syndrome following surgical treatment of stress fracture of proximal tibia with extensively infected wound and exposed tibia to about 4/5 of its extent. The knee joint was also infected with active pus draining from a medial wound. At presentation the patient had already taken treatment for 15 days in the form of repeated wound debridements and parenteral antibiotics, which failed to heal the wound and she was advised amputation. Topical ozone therapy twice daily and ozone autohemotherapy once daily were given to the patient along with daily dressings and parenteral antibiotics. Within 5 days, the wound was healthy enough for spilt thickness skin graft to provide biological dressing to the exposed tibia bone. Topical ozone therapy was continued for further 5 days till the knee wound healed. On the 15(th) day, implant removal, intramedullary nailing, and latissimus dorsi pedicle flap were performed. Both the bone and the soft tissue healed without further complications and at 20 months follow-up, the patient was walking independently with minimal disability.

  17. Adjuvant combined ozone therapy for extensive wound over tibia

    PubMed Central

    Shah, Prasham; Shyam, Ashok K; Shah, Sambhav

    2011-01-01

    Disinfectant and antibacterial properties of ozone are utilized in the treatment of nonhealing or ischemic wounds. We present here a case of 59 years old woman with compartment syndrome following surgical treatment of stress fracture of proximal tibia with extensively infected wound and exposed tibia to about 4/5 of its extent. The knee joint was also infected with active pus draining from a medial wound. At presentation the patient had already taken treatment for 15 days in the form of repeated wound debridements and parenteral antibiotics, which failed to heal the wound and she was advised amputation. Topical ozone therapy twice daily and ozone autohemotherapy once daily were given to the patient along with daily dressings and parenteral antibiotics. Within 5 days, the wound was healthy enough for spilt thickness skin graft to provide biological dressing to the exposed tibia bone. Topical ozone therapy was continued for further 5 days till the knee wound healed. On the 15th day, implant removal, intramedullary nailing, and latissimus dorsi pedicle flap were performed. Both the bone and the soft tissue healed without further complications and at 20 months follow-up, the patient was walking independently with minimal disability. PMID:21772635

  18. 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

  19. Management of stage II colon cancer - the use of molecular biomarkers for adjuvant therapy decision

    PubMed Central

    2013-01-01

    Background There is uncertainty on the benefit of adjuvant chemotherapy in patients with stage II colorectal cancers. The aim of this study is to investigate the combined role of clinical, pathological and molecular parameters to identify those stage II patients who better benefit from adjuvant therapy. Methods We examined 120 stage II colon cancer patients. Of these, 60 patients received adjuvant 5-FU chemotherapy after surgery and the other 60 did not receive therapy. Immunohistochemical (IHC) analyses were performed to evaluate the expressions of Thymidylate synthetase (TYMS), TP53 (p53), β-catenin (CTNNB1) and CD8. For TYMS, its mRNA expression levels were also investigated by real time qRT-PCR. The entire case study was characterized by the presence of a defect in the MMR (mismatch repair) system, the presence of the CpG island methylator phenotype (CIMP or CIMP-High) and for the V600E mutation in the BRAF gene. At the histo-pathological level, the depth of tumour invasion, lymphovascular invasion, invasion of large veins, host lymphocytic response and tumour border configuration were recorded. Results The presence of the V600E mutation in the BRAF gene was a poor prognostic factor for disease free and overall survival (DFS; hazard ratio [HR], 2.57; 95% CI: 1.03 -6.37; p = 0.04 and OS; HR, 3.68; 95% CI: 1.43-9.47; p < 0.01 respectively), independently of 5-FU treatment. Adjuvant therapy significantly improved survival in patients with high TYMS levels (p = 0.04), while patients with low TYMS had a better outcome if treated by surgery alone (DFS; HR, 6.07; 95% CI, 0.82 to 44.89; p = 0.04). In patients with a defect in the MMR system (dMMR), 5-FU therapy was associated to reduced survival (DFS; HR, 37.98; 95% CI, 1.04 to 1381.31; p = 0.04), while it was beneficial for CIMP-High associated tumours (DFS; HR, 0.17; 95% CI, 0.02 to 1.13; p = 0.05). Conclusions Patients’ characterization according to MMR status, CIMP phenotype and TYMS m

  20. Adjuvant therapy with tamoxifen compared to aromatase inhibitors for 257 male breast cancer patients.

    PubMed

    Eggemann, Holm; Ignatov, Atanas; Smith, Bobbie J; Altmann, Udo; von Minckwitz, Gunter; Röhl, Freidrich W; Jahn, Mark; Costa, Serban-Dan

    2013-01-01

    To determine the impact of adjuvant treatment with tamoxifen and aromatase inhibitors (AI) on the survival of men with breast cancer. We analyzed 257 male patients with hormone-receptor-positive breast cancer from numerous German population-based cancer registries treated with tamoxifen (N = 207) or aromatase inhibitors (N = 50). The median follow-up was 42.2 (range 2-115) months. Median age at diagnosis was 68 (range 36-91) years. Thirty-seven (17.9 %) patients treated with tamoxifen and 16 (32.0 %) patients treated with AI died (log rank p = 0.007). After the adjustment for the patient's age, tumor size, node status, and tumor grading, the AI treatment was linked to a 1.5-fold increase in risk of mortality compared to tamoxifen (HR 1.55; 95 % CI: 1.13-2.13; p = 0.007). The overall survival in male breast cancer was significantly better after adjuvant treatment with tamoxifen compared to an aromatase inhibitor. Tamoxifen should be considered as the treatment of choice for hormone-receptor-positive male breast cancer.

  1. Current status of hormone therapy in patients with hormone receptor positive (HR+) advanced breast cancer.

    PubMed

    Dalmau, Elsa; Armengol-Alonso, Alejandra; Muñoz, Montserrat; Seguí-Palmer, Miguel Ángel

    2014-12-01

    The natural history of HR+ breast cancer tends to be different from hormone receptor-negative disease in terms of time to recurrence, site of recurrence and overall aggressiveness of the disease. The developmental strategies of hormone therapy for the treatment of breast cancer have led to the classes of selective estrogen receptor modulators, selective estrogen receptor downregulators, and aromatase inhibitors. These therapeutic options have improved breast cancer outcomes in the metastatic setting, thereby delaying the need for chemotherapy. However, a subset of hormone receptor-positive breast cancers do not benefit from endocrine therapy (intrinsic resistance), and all HR+ metastatic breast cancers ultimately develop resistance to hormonal therapies (acquired resistance). Considering the multiple pathways involved in the HR network, targeting other components of pathologically activated intracellular signaling in breast cancer may prove to be a new direction in clinical research. This review focuses on current and emerging treatments for HR+ metastatic breast cancer.

  2. Stage III Melanoma in the Axilla: Patterns of Regional Recurrence After Surgery With and Without Adjuvant Radiation Therapy

    SciTech Connect

    Pinkham, Mark B.; Foote, Matthew C.; Burmeister, Elizabeth; Thomas, Janine; Meakin, Janelle; Smithers, B. Mark; Burmeister, Bryan H.

    2013-07-15

    Purpose: To describe the anatomic distribution of regionally recurrent disease in patients with stage III melanoma in the axilla after curative-intent surgery with and without adjuvant radiation therapy. Methods and Materials: A single-institution, retrospective analysis of a prospective database of 277 patients undergoing curative-intent treatment for stage III melanoma in the axilla between 1992 and 2012 was completed. For patients who received radiation therapy and those who did not, patterns of regional recurrence were analyzed, and univariate analyses were performed to assess for potential factors associated with location of recurrence. Results: There were 121 patients who received adjuvant radiation therapy because their clinicopathologic features conferred a greater risk of regional recurrence. There were 156 patients who received no radiation therapy. The overall axillary control rate was 87%. There were 37 patients with regional recurrence; 17 patients had received adjuvant radiation therapy (14%), and 20 patients (13%) had not. The likelihood of in-field nodal recurrence was significantly less in the adjuvant radiation therapy group (P=.01) and significantly greater in sites adjacent to the axilla (P=.02). Patients with high-risk clinicopathologic features who did not receive adjuvant radiation therapy also tended to experience in-field failure rather than adjacent-field failure. Conclusions: Patients who received adjuvant radiation therapy were more likely to experience recurrence in the adjacent-field regions rather than in the in-field regions. This may not simply reflect higher-risk pathology. Using this data, it may be possible to improve outcomes by reducing the number of adjacent-field recurrences after adjuvant radiation therapy.

  3. Emerging Adjuvant Therapy for Cancer: Propolis and its Constituents.

    PubMed

    Patel, Seema

    2016-01-01

    Propolis is a bee-metabolized resinous substance (bee glue) from plant sap and gums. It has been in usage as a healing agent since antiquity, yet has not garnered global popularity as a health promoter. Its biological effects, which range from antimicrobial, antioxidant, anti-inflammatory, antidiabetic, dermatoprotective, anti-allergic, laxative and immunomodulatory to anticancer, have been validated. Propolis has shown efficacy against brain, head and neck, skin, breast, liver, pancreas, kidney, bladder, prostate, colon and blood cancers. The inhibition of matrix metalloproteinases, anti-angiogenesis, prevention of metastasis, cell-cycle arrest, induction of apoptosis and moderation of the chemotherapy-induced deleterious side effects have been deduced as the key mechanisms of cancer manipulation. The components conferring antitumor potentials have been identified as caffeic acid phenethyl ester, chrysin, artepillin C, nemorosone, galangin, cardanol, etc. These compounds target various genetic and biochemical pathways of cancer progression. Depending on the botanical sources and the geographical origin, biological activities of propolis vary. Despite phenomenal development in cancer research, conventional therapy falls short in complete malignancy management. The findings obtained so far build hope that propolis as a complementary medicine may address the lacunae. This review documents the recent advances and scope of amendement in cancer remediation with adequate emphasis on the mechanistic aspect of propolis.

  4. 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.

  5. Vascular Effects of Estrogenic Menopausal Hormone Therapy

    PubMed Central

    Reslan, Ossama M.; Khalil, Raouf A.

    2011-01-01

    Cardiovascular disease (CVD) is more common in men and postmenopausal women (Post-MW) than premenopausal women (Pre-MW). Despite recent advances in preventive measures, the incidence of CVD in women has shown a rise that matched the increase in the Post-MW population. The increased incidence of CVD in Post-MW has been related to the decline in estrogen levels, and hence suggested vascular benefits of endogenous estrogen. Experimental studies have identified estrogen receptor ERα, ERβ and a novel estrogen binding membrane protein GPR30 (GPER) in blood vessels of humans and experimental animals. The interaction of estrogen with vascular ERs mediates both genomic and non-genomic effects. Estrogen promotes endothelium-dependent relaxation by increasing nitric oxide, prostacyclin, and hyperpolarizing factor. Estrogen also inhibits the mechanisms of vascular smooth muscle (VSM) contraction including [Ca2+]i, protein kinase C and Rho-kinase. Additional effects of estrogen on the vascular cytoskeleton, extracellular matrix, lipid profile and the vascular inflammatory response have been reported. In addition to the experimental evidence in animal models and vascular cells, initial observational studies in women using menopausal hormonal therapy (MHT) have suggested that estrogen may protect against CVD. However, randomized clinical trials (RCTs) such as the Heart and Estrogen/progestin Replacement Study (HERS) and the Women’s Health Initiative (WHI), which examined the effects of conjugated equine estrogens (CEE) in older women with established CVD (HERS) or without overt CVD (WHI), failed to demonstrate protective vascular effects of estrogen treatment. Despite the initial set-back from the results of MHT RCTs, growing evidence now supports the ‘timing hypothesis’, which suggests that MHT could increase the risk of CVD if started late after menopause, but may produce beneficial cardiovascular effects in younger women during the perimenopausal period. The choice of

  6. Endometrial bleeding in postmenopausal women: with and without hormone therapy.

    PubMed

    Archer, David F

    2011-04-01

    The aim of this study was to present a review of the potential mechanisms involved in the occurrence of endometrial bleeding in postmenopausal women using hormone therapy. Selected literature on the incidence of bleeding in postmenopausal women using estrogen progestogen therapy was reviewed. The incidence of spotting and bleeding in women using continuous-combined hormone therapy was presented. Relevant articles related to the role of angiogenic factors and vasculogenesis in the endometrium, endometrial leukocytes, and endometrial metalloproteinases were used for the review. The cause or etiology of endometrial bleeding with hormone therapy is unknown. Several options are known to alter angiogenesis or be involved in tissue remodeling during normal menstruation. Vascular endothelial growth factor and thrombospondin-1 are proangiogenic and antiangiogenic factors that could cause dysfunction in vasculogenesis that could result in blood vessel fragility and bleeding. The role of pericytes in maintaining vessel morphology and integrity is discussed. Endometrial leukocytes and metalloproteinases are involved in normal menstruation, but their role in postmenopausal bleeding is not clear suggesting involvement of mechanisms in the bleeding. There is limited information on clinical investigation into the etiology of postmenopausal bleeding associated with hormone therapy. The major cause of hormone therapy-related bleeding is unknown. Alterations in angiogenic factors that could result in vascular dysfunction and vessel breakdown provide a working hypothesis as to the potential cause of vessel breakdown.

  7. Capecitabine with radiation is an effective adjuvant therapy in gastric cancers

    PubMed Central

    Tham, Chee Kian; Choo, Su Pin; Poon, Donald Yew Hee; Toh, Han Chong; Ong, Simon Yew Kuang; Tan, Sze Huey; Wang, Michael Lian Chek; Foo, Kian Fong

    2010-01-01

    AIM: To analyze the outcome of patients who received concurrent capecitabine (Xeloda) and radiation (XRT) compared to the established concurrent 5-fluorouracil (5-FU) with radiation (5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers. METHODS: All patients with gastric cancers who received adjuvant treatment at the National Cancer Centre Singapore between 1996 and 2006 were reviewed. Treatment outcomes of patients who received XRT were compared with those who had 5FU-RT or chemotherapy alone as adjuvant therapy for gastric cancers. RESULTS: A total of 108 patients were reviewed. Median age at diagnosis was 60. The majority of the patients (64.8%) had advanced stage III and IV disease (with no distant metastasis). All except 4 patients had D2 gastrectomy. Twenty one patients (19.4%) had positive surgical resection margins. Thirty three patients received XRT compared with 52 who had 5FU-RT and 23 who received chemotherapy alone. For the patients in the chemotherapy-only group, all had fluoropyrimidine-based therapy, with added cisplatin in 7 patients and epirubicin in 2 patients. Median recurrence-free survival was longer for the XRT group (52 mo) compared to the 5FU-RT (35 mo) and chemotherapy-only groups (25 mo) (P = 0.48). The patients in the XRT group achieved similar median overall survival (53 mo) as the 5FU-RT (54 mo) and the chemotherapy-only groups (44 mo) (P = 0.5). CONCLUSION: Capecitabine with concurrent radiation was as effective as concurrent 5FU with radiation or fluoropyrimidine-based chemotherapy alone when used as adjuvant treatment in patients with gastric cancers. PMID:20677345

  8. Venous thromboembolism associated with pregnancy and hormonal therapy.

    PubMed

    Jacobsen, Anne Flem; Sandset, Per Morten

    2012-09-01

    Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality during or early after pregnancy and in women taking hormonal therapy for contraception or for replacement therapy. Post-thrombotic syndrome, including leg oedema and leg pain, is an unrecognized burden after pregnancy-related VTE, which will affect more than two of five women. Women with a prior VTE, a family history of VTE, certain clinical risk factors and thrombophilia are at considerably increased risk both for pregnancy-related VTE and for VTE on hormonal therapy. This review critically assesses the epidemiology and risk factors for pregnancy-related VTE and current guidelines for prophylaxis and treatment. We also provide information on the risk of VTE related to hormonal contraception and replacement therapy.

  9. Pattern Alopecia during Hormonal Anticancer Therapy in Patients with Breast Cancer.

    PubMed

    Park, Jin; Kim, Ju-Ik; Yun, Seok-Kweon; Kim, Han-Uk; Ihm, Chull-Wan

    2014-12-01

    We report five cases of pattern alopecia in female patients who are undergoing hormonal anticancer therapy for the prevention of recurrence of breast cancer after surgery. Three patients demonstrated male pattern alopecia with receding frontal hairlines, and two patients demonstrated female pattern alopecia without receding hairlines. The detailed clinical history showed that the pattern alopecia of the patients developed after the full recovery of global hair loss of the entire scalp due to previous cytotoxic chemotherapy. All of the adjuvant hormonal anticancer drugs that were used in the patients are antiestrogenic agents, either aromatase inhibitors or selective estrogen receptor modulators. Considering androgen effect on the hair follicles of the fronto-parietal scalp, the androgen-estrogen imbalance caused by the drugs was thought to be the reason for the onset of pattern alopecia in the patients. In general, alopecia that develops during cytotoxic chemotherapy is well known to both physicians and patients; however, the diagnosis of pattern alopecia during hormonal anticancer therapy in breast cancer patients seems to be overlooked.

  10. Clinical and immunological assessment in breast cancer patients receiving anticancer therapy and bovine dialyzable leukocyte extract as an adjuvant.

    PubMed

    Lara, Humberto H; Turrent, Liliana Ixtepan; Garza-Treviño, Elsa N; Tamez-Guerra, Reyes; Rodriguez-Padilla, Cristina

    2010-05-01

    Dialyzable leukocyte extract (DLE) is one of the immunological agents used as an adjuvant in cancer therapy; it has been associated with improved quality of life during cancer chemotherapy. Based on these previous findings and on the observed clinical benefits attributed to DLE in other types of cancer, we investigated its clinical and immunological effects as a therapy adjuvant on breast cancer patients who received only chemotherapy, as compared to patients administered bovine DLE (bDLE) as an adjuvant. This study included 43 breast cancer patients who were about to begin chemotherapy. This group was divided as follows: 25 received chemotherapy and bDLE as an adjuvant therapy, and 18 received only chemotherapy without the adjuvant. All patient clinical and immunological responses were monitored. Among patients in the group that received bDLE as adjuvant, 60% showed a complete response, 32% showed a partial response and 8% did not respond. By contrast, in the group without the adjuvant, 39% showed a complete response, 50% displayed a partial response and 11% were non-responders. In addition, bDLE treatment in combination with chemotherapy resulted in the enhancement of the Karnofsky performance scale during chemotherapy. Even though patients underwent several cycles of chemotherapy without bDLE, the lymphocyte population dropped to below the reference value. On the other hand, in patients with bDLE as adjuvant, the CD4(+) and CD8(+) lymphocytes and the B lymphocytes were maintained within the median range of the reference value. The number of natural killer cells also increased after chemotherapy treatment with bDLE as an adjuvant. In conclusion, bDLE treatment contributes to significant immunological recovery in patients that have undergone heavy chemotherapy, increasing the clinical response and quality of life during chemotherapy.

  11. The association of adjuvant therapy with survival at the population level following pancreatic adenocarcinoma resection

    PubMed Central

    Kagedan, Daniel J.; Raju, Ravish S.; Dixon, Matthew E.; Shin, Elizabeth; Li, Qing; Liu, Ning; Elmi, Maryam; El-Sedfy, Abraham; Paszat, Lawrence; Kiss, Alexander; Earle, Craig C.; Mittmann, Nicole; Coburn, Natalie G.

    2016-01-01

    Background Using a retrospective observational cohort approach, the overall survival (OS) following curative-intent resection of pancreatic adenocarcinoma (PC) was defined at the population level according to adjuvant treatment, and predictors of OS were identified. Methods Patients undergoing resection of PC in the province of Ontario between 2005 and 2010 were identified using the provincial cancer registry, and linked to databases that include all treatments received and outcomes experienced in the province. Pathology reports were abstracted for staging and margin status. Patients were identified as having received chemotherapy (CT), chemoradiation therapy (CRT), or no adjuvant treatment (NAT). Kaplan–Meier survival analysis of patients surviving ≥6 months was performed, and predictors of OS identified by log-rank test. Cox multivariable analysis was used to define independent predictors of OS. Results Among the 473 patients undergoing PC resection, the median survival was 17.8 months; for the 397 who survived ≥6 months following surgery, the 5-year OS for the CT, CRT, and NAT groups was 21%, 16%, and 17%, respectively (p = 0.584). Lymph node-negative patients demonstrated improved OS associated with chemotherapy on multivariable analysis (HR = 2.20, 95% CI = 1.25–3.83 for NAT vs. CT). Conclusions Following PC resection, only patients with negative lymph nodes demonstrated improved OS associated with adjuvant chemotherapy. PMID:27037203

  12. Tailoring Adjuvant Radiation Therapy by Intraoperative Imaging to Detect Residual Cancer

    PubMed Central

    Whitley, Melodi J.; Weissleder, Ralph; Kirsch, David G.

    2015-01-01

    For many solid cancers, radiation therapy is offered as an adjuvant to surgical resection in order to lower rates of local recurrence and improve survival. However, a subset of patients treated with surgery alone will not have a local recurrence. Currently, there is no way to accurately determine which patients have microscopic residual disease in the tumor bed after surgery and therefore are most likely to benefit from adjuvant radiation therapy. To address this problem, a number of technologies have been developed to try to improve margin assessment of resected tissue and to detect residual cancer in the tumor bed. Moreover, some of these approaches have been translated from the preclinical arena into clinical trials. Here, we review different types of intraoperative molecular imaging systems for cancer. Optical imaging techniques like epi-illumination, fluorescence molecular tomography and optoacoustic imaging can be coupled with exogenous fluorescent imaging probes that accumulate in tumors passively via the enhanced permeability and retention effect or are targeted to tumor tissues based on affinity or enzyme activity. In these approaches, detection of fluorescence in the tumor bed may indicate residual disease. Protease activated probes have generated great interest because of their potential for leading to high tumor to normal contrast. Recently, the first Phase I clinical trial to assess the safety and activation of a protease activated probe was conducted. Spectroscopic methods like radiofrequency spectroscopy and Raman spectroscopy, which are based on energy absorption and scattering respectively, have also been tested in humans and are able to distinguish between normal and tumors tissues intraoperatively. Most recently, multi-modal contrast agents have been developed that target tumors and contain both fluorescent dyes and MRI contrast agents, allowing for preoperative planning and intraoperative margin assessment with a single contrast agent. Further

  13. Clinical Characteristics, Surgical Management and Adjuvant Therapy of Patients with Uterine Carcinosarcoma: A Retrospective Case Series

    PubMed Central

    Wallwiener, C.; Hartkopf, A.; Kommoss, S.; Joachim, C.; Wallwiener, M.; Taran, F. A.; Brucker, S.

    2016-01-01

    Purpose: To review a single-center experience over a 27-year period of managing uterine carcinosarcoma (UCS), focusing on surgical practice, adjuvant therapy and clinical outcome. Material and Methods: This was a retrospective study of women with histologically proven UCS treated at the Department of Obstetrics and Gynecology, University of Tübingen, Germany, between 1983 and 2010. Inpatient and outpatient records were reviewed; follow-up and survival data were ascertained. Results: The study population comprised 18 patients with UCS. Primary surgical treatment consisted of total abdominal hysterectomy in 12 patients (67 %) and laparoscopic total hysterectomy in 4 patients (22 %). Bilateral salpingo-oophorectomy was performed in 94 % of patients (17/18). Lymph nodes were evaluated in 15 patients (83 %). Positive pelvic lymph nodes were present in 2 patients (11 %). A total of 17 patients (94 %) received adjuvant therapy. Disease recurred in 7 (39 %) patients of our study group, with no recurrence noted in the 4 patients who underwent laparoscopic surgical staging. Median disease-free survival (DFS) was 48.7 months (95 % CI: 0.0–157.3) and median overall survival (OS) was 49.9 months (95 % CI: 0.0–108.2). The 5-year survival rate was 40 %. Conclusion: UCS is a rare and aggressive uterine neoplasm with high recurrence rates and metastatic potential. Surgical staging consisting of total hysterectomy with bilateral salpingo-oophorectomy and systematic lymphadenectomy is the most important treatment for patients with UCS. Adjuvant radiation therapy appears to decrease pelvic recurrence, but there is a high incidence of distant recurrence, indicating the need for additional systemic treatment. PMID:26941453

  14. Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer.

    PubMed Central

    Korbelik, M.; Naraparaju, V. R.; Yamamoto, N.

    1997-01-01

    The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII tumour model (squamous cell carcinoma). The results show that DBPMAF can markedly enhance the curative effect of PDT. The most effective DBPMAF therapy consisted of a combination of intraperitoneal and peritumoral injections (50 and 0.5 ng kg-1 respectively) administered on days 0, 4, 8 and 12 after PDT. Used with a PDT treatment curative to 25% of the treated tumours, this DBPMAF regimen boosted the cures to 100%. The DBPMAF therapy alone showed no notable effect on the growth of SCCVII tumour. The PDT-induced immunosuppression, assessed by the evaluation of delayed-type contact hypersensitivity response in treated mice, was greatly reduced with the combined DBPMAF treatment. These observations suggest that the activation of macrophages in PDT-treated mice by adjuvant immunotherapy has a synergistic effect on tumour cures. As PDT not only reduces tumour burden but also induces inflammation, it is proposed that recruitment of the activated macrophages to the inflamed tumour lesions is the major factor for the complete eradication of tumours. PMID:9010027

  15. Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer.

    PubMed

    Korbelik, M; Naraparaju, V R; Yamamoto, N

    1997-01-01

    The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII tumour model (squamous cell carcinoma). The results show that DBPMAF can markedly enhance the curative effect of PDT. The most effective DBPMAF therapy consisted of a combination of intraperitoneal and peritumoral injections (50 and 0.5 ng kg-1 respectively) administered on days 0, 4, 8 and 12 after PDT. Used with a PDT treatment curative to 25% of the treated tumours, this DBPMAF regimen boosted the cures to 100%. The DBPMAF therapy alone showed no notable effect on the growth of SCCVII tumour. The PDT-induced immunosuppression, assessed by the evaluation of delayed-type contact hypersensitivity response in treated mice, was greatly reduced with the combined DBPMAF treatment. These observations suggest that the activation of macrophages in PDT-treated mice by adjuvant immunotherapy has a synergistic effect on tumour cures. As PDT not only reduces tumour burden but also induces inflammation, it is proposed that recruitment of the activated macrophages to the inflamed tumour lesions is the major factor for the complete eradication of tumours.

  16. Endometrial carcinoma--relative effectiveness of adjuvant irradiation vs therapy reserved for relapse.

    PubMed

    Ackerman, I; Malone, S; Thomas, G; Franssen, E; Balogh, J; Dembo, A

    1996-02-01

    Fifty-four patients with recurrent endometrial carcinoma were identified from a retrospective review of charts of 304 endometrial cancer patients seen between 1983 and 1989 at our center. A review was undertaken to identify the patterns of relapse, to determine the outcome of salvage treatment, to examine the factors predictive of effective salvage, and, if salvage is effective, to assess an alternative strategy to routine adjuvant postoperative pelvic radiotherapy. Forty percent of the entire recurrent population are long-term survivors. Of the 54 relapsing patients, primary therapy had been surgery alone in 32 and surgery and adjuvant radiotherapy (rt) in 22. Isolated pelvic recurrence was the predominate relapse site in those who had not received adjuvant pelvic RT as primary therapy (23 of 32 or 72%). Distant relapse predominated in those who received adjuvant RT (17 or 22 or 77%). Twenty-eight (54%) failed in the pelvis alone, and 26 (46%) had a component of distant failure. Of the 28 with isolated pelvic relapse, 16 had vaginal mucosal disease involvement only and 12 had disease in the parametrium and/or the pelvic sidewall. With a minimum follow-up for the survivors of 5 years, 21 of the 28 with isolated pelvic relapse received radical radiotherapy and 14 or 67% had maintained pelvic control until death or last follow-up. Eleven of 14 (79%) with disease confined to the mucosa had pelvic control, whereas only 3 of 7 (43%) with extramucosal disease were controlled. No patient experienced major treatment-related toxicity. Tumor size, anatomic extent of pelvic recurrence, RT dose, and disease-free interval were examined for prognostic significance for pelvic control and survival by univariate analysis. Only anatomic extent of pelvic recurrence showed a nonstatistically significant trend as a predictor for control with P = 0.08. In conclusion, a significant proportion of patients with disease recurrence confined to the pelvis can be rendered disease-free long

  17. Positive esophageal proximal resection margin: an important prognostic factor for esophageal cancer that warrants adjuvant therapy

    PubMed Central

    Wang, Yun-Cang; Deng, Han-Yu; Wang, Wen-Ping; He, Du; Ni, Peng-Zhi; Hu, Wei-Peng; Wang, Zhi-Qiang

    2016-01-01

    Background Positive esophageal proximal resection margin (ERM+) following esophagectomy was considered as incomplete or R1 resection. The clinicopathological data and long-term prognosis of esophageal cancer (EC) patients with ERM+ after esophagectomy were still unknown. Therefore, the aim of this study was to assess the clinical significance of ERM+ and its therapeutic option. Methods From November 2008 to December 2014, 3,594 patients with histologically confirmed EC underwent radical resection in our department. Among them there were 37 patients (1.03%) who had ERM+. ERM+ was defined as carcinoma or atypical hyperplasia (severe or moderate) at the residual esophageal margin in our study. For comparison, another 74 patients with negative esophageal proximal resection margin (ERM−) were propensity-matched at a ratio of 1:2 as control group according to sex, age, tumor location and TNM staging. The relevant prognostic factors were investigated by univariate and multivariate regression analysis. Results In this large cohort of patients, the rate of ERM+ was 1.03%. The median survival time was 35.000 months in patients with ERM+, significantly worse than 68.000 months in those with ERM− (Chi-square =4.064, P=0.044). Survival in patients with esophageal residual atypical hyperplasia (severe or moderate) was similar to those with esophageal residual carcinoma. Survival rate in stage I–II was higher than that in stage III–IV (Chi-square =27.598, P=0.000) in ERM−; But there was no difference between the two subgroups of patients in ERM+. Furthermore, in those patients with ERM+, survival was better in those who having adjuvant therapy, compared to those without adjuvant therapy (Chi-square =5.480, P=0.019). And the average survival time which was improved to a well situation for ERM+ patients who have adjuvant therapy was 68.556 months which is comparable to average survival time (65.815 months) of ERM− for those patients who are at earlier stages

  18. Toxicity associated with adjuvant postoperative therapy for adenocarcinoma of the rectum

    SciTech Connect

    Thomas, P.R.; Lindblad, A.S.; Stablein, D.M.; Knowlton, A.H.; Bruckner, H.W.; Childs, D.S.; Mittelman, A.

    1986-03-15

    An adjuvant rectal carcinoma study compared four postoperative treatment regimens: (1) control (no adjuvant therapy); (2) chemotherapy alone consisting of pulses of 5-fluorouracil and methyl CCNU for 18 months; (3) pelvic and perineal radiotherapy using parallel opposed fields with 4000 rad in 4.5 to 5 weeks or 4800 rad in 5 to 5.5 weeks; and (4) a combination of both modalities. The results of this study are published elsewhere and show a significantly reduced recurrence rate and prolonged disease-free survival time for the combined modality arm compared with the no therapy arm. Severe toxicity in the combined therapy arm was significantly worse (P less than 0.001) than in either single modality arm. Most of the differences in toxicity experienced between the three regimens involved diarrhea, thrombocytopenia, and leukopenia. Analysis of all parameters of radiotherapy quality assurance data was not significantly associated with toxicity. Radiation enteritis was noted in 5 patients of 96 (5.2%) in the two arms containing irradiation. All five required laparotomy. The two enteritis fatalities occurred late at 605 and 1000 days after start of combined modality treatment, respectively. One other patient on the chemotherapy arm died of acute nonlymphocytic leukemia. The authors conclude that combined radiotherapy and chemotherapy, although significantly more effective in reducing recurrence than no therapy, is significantly more toxic than single-modality therapy in many parameters, although most of the toxicity is transient and therefore not limiting. Late complications, which are less reversible and therefore much more important than early reactions, and radiation enteritis in this study were relatively uncommon. This schedule of combined modality therapy is not only effective but appears to have tolerable toxicity, because of the relative lack of late effects.

  19. Hormone replacement therapy: the need for reconsideration.

    PubMed

    Rosenberg, L

    1993-12-01

    Millions of menopausal women are taking hormone supplements. Observational studies suggest that unopposed estrogens reduce the risk of cardiovascular disease and fractures and increase the risk of endometrial cancer and, possibly, breast cancer. In the absence of information from randomized trials, how much of the apparent beneficial effect on heart disease is due to the tendency of healthier women to use these drugs is unknown. The effect on the cardiovascular system of estrogen taken with a progestin is unknown, and this regimen may increase the risk of breast cancer. An approach to health and illness that focuses on a single cause or preventive and on single organ systems is severely limited. Alternative ways to improve cardiovascular and skeletal health that do not increase the risk of cancer are available. A reconsideration of the appropriate use of hormone supplements is needed.

  20. Hormonal therapies for individuals with intersex conditions: protocol for use.

    PubMed

    Warne, Garry L; Grover, Sonia; Zajac, Jeffrey D

    2005-01-01

    Hormonal therapy forms part of the treatment of every intersex condition. For some conditions, such as salt-wasting congenital adrenal hyperplasia, hormonal replacement therapy is life saving because hormones necessary for survival (cortisol and aldosterone) are replaced. In contrast, other hormones such as androgens or mineralocorticoids are secreted in excessive amounts in congenital adrenal hyperplasia due to an enzyme imbalance, and the role of hormonal therapy is to suppress the unwanted hormone excess by exerting negative feedback. For patients with one of the many causes of hypogonadism, sex hormone replacement therapy may be prescribed to stimulate sexual development: growth of a hypoplastic penis in a young boy, pubertal changes (male or female), psychosexual development, and adult sexual behavior. It has equally important and highly beneficial effects on bone mineral density. Hormonal therapy is also used to treat the unborn child. For the last 20 years, prenatal dexamethasone treatment administered to the pregnant woman has been used to prevent the development of ambiguous genitalia in females with 21-hydroxylase deficiency. Outcome studies show this treatment to be well tolerated and, in general, efficacious. Intersex conditions are, however, difficult to treat because they may intrinsically perturb complex aspects of the person's gender identity, gender-role behavior, sexual orientation, sexual functioning, and psychologic adjustment. Furthermore, decisions made about the sex of an infant by doctors and parents do not always turn out to be correct; the person may grow up feeling uncertain about his or her gender identity, or worse still, harbor a sense of outrage about their life and treatment experiences. Such a person will have definite views about hormonal therapy when the time comes and skillful counseling will be needed. A vigorous debate about ethical aspects of current medical practices relating to intersex conditions has been waged for the last

  1. Does adjuvant radiation therapy benefit women with small mammography-detected breast cancers?

    PubMed Central

    Jerzak, K.; Dudalski, N.; Pritchard, K.; Sun, P.; Narod, S.A.

    2017-01-01

    Background Women with small nonpalpable breast tumours have an excellent prognosis. The benefit of radiotherapy in this group of low-risk women is unknown. Methods A cohort of 1595 women with stages i–iii invasive breast cancer treated with breast-conserving surgery were followed for local recurrence. Using t-tests, baseline demographic data and tumour characteristics were compared for the women who had palpable (n = 1023) and mammography-detected (n = 572) breast cancers. The 15-year actuarial risk of local recurrence was estimated using a Kaplan–Meier method, stratified for adjuvant radiation therapy (yes or no), tumour palpability (palpable or not), and tumour size (≤1 cm or >1 cm). Hazard ratios (hrs) and 95% confidence intervals (95% cis) were calculated using a multivariate Cox regression model. Results were considered statistically significant if 2-tailed p values were less than 0.05. Results Among women with a nonpalpable tumour, the 15-year actuarial rates of local recurrence were, respectively, 13.9% and 18.3% for those treated and not treated with adjuvant radiation therapy (hr: 0.65; 95%ci: 0.40 to 1.06; p = 0.08). Among women with small nonpalpable breast cancers (≤1.0 cm), the rates were 14.6% and 13.4% respectively (p = 0.67). The absolute reduction in 15-year local recurrence was 11.0% for women with palpable tumours. Conclusions Our results suggest that women with small (<1 cm) screen-detected nonpalpable breast cancers likely derive little benefit from adjuvant radiotherapy; however, an adequately powered randomized trial would be required to make definitive conclusions. PMID:28270722

  2. [Effect of adjuvant therapy with Dingguier umbilical paste on intestinal flora of diarrhea infants and its action characteristics].

    PubMed

    Sun, Hai-Feng; Gao, Yan-Yun; An, Cui-Hong; Li, Yu-Lan; Duan, Li-Jun; Yu, Yu-Hong; Ren, Wu-Xian

    2014-07-01

    The applicator therapy is a unique method to treat infant diarrhea in traditional Chinese medicines and widely applied in clinical practice. Currently, many researchers have proved the rationality of the therapy based on the traditional Chinese medicine mechanism and on the data from clinical practice, but its action mechanism is uncertain at present. In this study, with the assistance of pediatric practitioners, the automated ribosomal intergenic-spacer analysis (ARISA) was adopted to study the effect of the adjuvant therapy with Dingguier umbilical paste on intestinal flora of diarrhea infants, in which Dingguier umbilical paste served as the adjuvant therapy in oral traditional Chinese medicines and fecal samples of infants with different diarrhea symptoms were collected and used as the study materials. The results showed that the adjuvant therapy had a significant effect on the shift of intestinal flora, which was associated with the decrease in the similarity difference to the normal control group and the increase in the number of operational taxonomic units (OTUs) shared with the normal control group. Additionally, adjuvant therapy with Dingguier umbilical paste also showed long action duration and increased OTUs number. These results indicated that Dingguier umbilical paste has the effect in restoring the micro-ecosystem of unbalanced intestinal bacteria. Intestinal flora may be one of major targets for the applicator therapy for the infant diarrhea, but not for the single oral traditional Chinese medicine for infant diarrhea.

  3. Exogenous Hormone Use: Oral Contraceptives, Postmenopausal Hormone Therapy, and Health Outcomes in the Nurses’ Health Study

    PubMed Central

    Grodstein, Francine; Stampfer, Meir J.; Willett, Walter C.; Hu, Frank B.; Manson, JoAnn E.

    2016-01-01

    Objectives. To review the contribution of the Nurses’ Health Study (NHS) to our understanding of the complex relationship between exogenous hormones and health outcomes in women. Methods. We performed a narrative review of the publications of the NHS and NHS II from 1976 to 2016. Results. Oral contraceptive and postmenopausal hormone use were studied in relation to major health outcomes, including cardiovascular disease and cancer. Current or recent oral contraceptive use is associated with a higher risk of cardiovascular disease (mainly among smokers), melanoma, and breast cancer, and a lower risk of colorectal and ovarian cancer. Although hormone therapy is not indicated primarily for chronic disease prevention, findings from the NHS and a recent analysis of the Women’s Health Initiative indicate that younger women who are closer to menopause onset have a more favorable risk–benefit profile than do older women from use of hormone therapy for relief of vasomotor symptoms. Conclusions. With updated information on hormone use, lifestyle factors, and other variables, the NHS and NHS II continue to contribute to our understanding of the complex relationship between exogenous hormones and health outcomes in women. PMID:27459451

  4. [Effects of growth hormone replacement therapy on bone metabolism].

    PubMed

    Yamamoto, Masahiro; Sugimoto, Toshitsugu

    2014-06-01

    Growth hormone (GH) as well as insulin like growth factor-1 (IGF-1) are essential hormones to maintain homeostasis of bone turnover by activating osteoblastogenesis and osteoclastogenesis. Results from GH replacement therapy for primary osteoporosis and adult-onset GH deficiency (AGHD) suggest that one year or more treatment period by this agent is required to gain bone mineral density (BMD) over the basal level after compensating BMD loss caused by dominant increase in bone resorption which was observed at early phase of GH treatment. A recent meta-analysis demonstrates the efficacy of GH replacement therapy on increases in BMD in male patients with AGHD. Additional analyses are needed to draw firm conclusions in female patients with AGHD, because insufficient amounts of GH might be administrated to them without considerations of influence of estrogen replacement therapy on IGF-1 production. Further observational studies are needed to clarify whether GH replacement therapy prevent fracture risk in these patients.

  5. [Value of adjuvant basic therapy in chronic recurrent skin diseases. Neurodermatitis atopica/psoriasis vulgaris].

    PubMed

    Schöpf, E; Mueller, J M; Ostermann, T

    1995-07-01

    Atopic dermatitis and psoriasis vulgaris belong to the most common diseases in dermatology. Since these chronical diseases progress over years and decades, they may lead to restrictions in private and professional life as well as to psychological stress of concerned patients. Therefore, a lasting, stabilising, stage-adjusted topical treatment is necessary. Main component of this treatment in a complete therapeutical concept consists in an adjuvant basic therapy with oil baths and with emollients containing urea or no drug additives at all. Thus the vehicle itself is therapeutically effective. Altered structure and function of the skin measured by increased transepidermal water loss, dysfunction of skin lipid barrier, augmented skin permeability and skin roughness can be improved. Due to this treatment clinical symptoms can be diminished and relapses can be avoided. Corticosteroids and other specific medications can be reduced by using basic therapeutics with little side effects. This means economical benefit as well. So far adjuvant basic treatment is an essential part in the therapy of chronic inflammatory skin diseases.

  6. Tamoxifen as the First Targeted Long Term Adjuvant Therapy for Breast Cancer

    PubMed Central

    Jordan, V. Craig

    2014-01-01

    Tamoxifen is an unlikely pioneering medicine in medical oncology. Nevertheless, the medicine has continued to surprise us, perform and save lives for the past 40 years. Unlike any other medicine in oncology, it is used to treat all stages of breast cancer, ductal carcinoma in situ, male breast cancer, pioneered the use of chemoprevention by reducing the incidence of breast cancer in women at high risk and induces ovulation in subfertile women! The impact of tamoxifen is ubiquitous. However, the power to save lives from this unlikely success story came from the first laboratory studies which defined that “longer was going to be better” when tamoxifen was being considered as an adjuvant therapy (Jordan 1978 Use of the DMBA-induced rat mammary carcinoma system for the evaluation of tamoxifen as a potential adjuvant therapy Reviews in Endocrine Related Cancer. October Supplement: 49–55.). This is that success story, with a focus on the interdependent components of: excellence in drug discovery, investment in self-selecting young investigators, a conversation with Nature, a conversation between the laboratory and the clinic, and the creation of the Oxford Overview Analysis. Each of these factors was essential to propel the progress of tamoxifen to evolve as an essential part of the fabric of society. “Science is adventure, discovery, new horizons, insight into our world, a means of predicting the future and enormous power to help others”(Hoagland 1990).- Mahlon Hoagland, MD. Director, Worcester Foundation for Experimental Biology (1970–85) PMID:24659478

  7. 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).

  8. [Recurrent micro-satellite stable colonic cancer: prolonged survival of 16 years without adjuvant therapy].

    PubMed

    Grothe, D; Kasperk, R

    2004-10-01

    Long-term survival in malignant disease is often linked to intensified therapeutic interventions. We report the case of a colonic cancer in a 78 years old female patient, who underwent her first operation in 1987 for a symptomatic T4 carcinoma. Since then, the patient has always denied any form of follow-up examination and adjuvant therapy. Recently, she has undergone her fourth operation, which for the first time demonstrated peritoneal carcinosis, and is still in very good health.Clinical experience shows that in some cases standard therapies may unexpectedly produce extremely long survival times. This has to be kept in mind when the value of prognostic markers is discussed and limits the validity of survival data in the context of small scale studies dealing with especially extended therapeutic protocols.

  9. Plasmapheresis as adjuvant therapy in Stevens-Johnson syndrome and hepatic encephalopathy.

    PubMed

    Hung, Po-Cheng; Wang, Huei-Shyong; Hsia, Shao-Hsuan; Wong, Alex M-C

    2014-04-01

    Stevens-Johnson syndrome (SJS) is a severe idiosyncratic reaction, most commonly triggered by medications, which is characterized by fever and mucocutaneous lesions, leading to necrosis and sloughing of the epidermis. Aside from skin and mucosal manifestations, SJS may also compromise heart, liver, kidney, lung, and gastrointestinal tract. Although cholestatic liver disease has been reported to occur in SJS, hepatic encephalopathy (HE) as a delayed complication has never been reported. We report a 4-year-old female child with anticonvulsant-induced SJS complicated by HE who was completely cured with a combination of systemic corticosteroid, intravenous immunoglobulin (IVIG), and plasmapheresis therapy. We suggested that plasmapheresis may be used as an adjuvant therapy for SJS with HE.

  10. Insulin sensitivity and counter-regulatory hormones in hypothyroidism and during thyroid hormone replacement therapy.

    PubMed

    Stanická, Sona; Vondra, Karel; Pelikánová, Terezie; Vlcek, Petr; Hill, Martin; Zamrazil, Václav

    2005-01-01

    We examined insulin sensitivity and secretion, together with the levels of selected glucoregulatory hormones, in 15 female patients with severe hypothyroidism (H) and during subsequent thyroid hormone replacement therapy (HRT) using the euglycaemic hyperinsulinaemic clamp technique. Insulin action, as evaluated by glucose disposal, the insulin sensitivity index, and fasting post-hepatic insulin delivery rate were established. The basal levels of insulin, C-peptide and counter-regulatory hormones were measured in basal condition. In H, glucose disposal (p<0.01), the insulin sensitivity index (p<0.01) and post-hepatic insulin delivery rate (p<0.05) were significantly lower than during HRT. No significant changes in the levels of fasting insulin and C-peptide were observed. The levels of counter-regulatory hormones in patients with H were significantly higher than during HRT (glucagon, p<0.05; epinephrine, p<0.01; cortisol, p<0.05; growth hormone, p<0.05). In H, an inverse correlation between insulin sensitivity and insulin secretion was observed (p<0.05). Cortisol was the most important factor affecting the variability of insulin sensitivity values, regardless of thyroid function (p=0.0012). In conclusion, H altered both insulin sensitivity and the levels of selected counter-regulatory hormones. The situation was restored by HRT, as manifested not only by normalisation of insulin sensitivity, secretion and levels of glucoregulatory hormones, but also by improvement of their relationships.

  11. Concomitant therapies (glucocorticoids and sex hormones) in adult patients with growth hormone deficiency.

    PubMed

    Scaroni, C; Ceccato, F; Rizzati, S; Mantero, F

    2008-09-01

    Adult-onset GH deficiency (GHD), mostly due to organic lesions of the pituitary-hypothalamic region, is frequently associated with multiple anterior pituitary deficiencies that need long-term substitutive treatment. The GH-IGF-I axis may play an important role in modulating peripheral metabolism of hormones (adrenal, thyroid, and sex hormones) and these interactions may have clinically significant implications on the phenotypes of adult GHD patients and on the effects of the combined replacement hormonal treatment of this condition. By accelerating the peripheral metabolism of cortisol, GH therapy may precipitate adrenal insufficiency in susceptible hypopituitary patients; estrogen replacement blunts the response to GH in women whereas in men with androgen substitution the responsivity increases over time. Endocrinologists should be mindful of these phenomena when starting patients with hypopituitarism on GH replacement therapy.

  12. Effect of oxandrolone therapy on adult height in Turner syndrome patients treated with growth hormone: a meta-analysis.

    PubMed

    Sheanon, Nicole M; Backeljauw, Philippe F

    2015-01-01

    Turner syndrome is a chromosomal abnormality in which there is complete or partial absence of the X chromosome. Turner syndrome effects 1 in every 2000 live births. Short stature is a cardinal feature of Turner Syndrome and the standard treatment is recombinant human growth hormone. When growth hormone is started at an early age a normal adult height can be achieved. With delayed diagnosis young women with Turner Syndrome may not reach a normal height. Adjuvant therapy with oxandrolone is used but there is no consensus on the optimal timing of treatment, the duration of treatment and the long term adverse effects of treatment. The objective of this review and meta-analysis is to examine the effect of oxandrolone on adult height in growth hormone treated Turner syndrome patients. Eligible trials were identified by a literature search using the terms: Turner syndrome, oxandrolone. The search was limited to English language randomized-controlled trials after 1980. Twenty-six articles were reviewed and four were included in the meta-analysis. A random effects model was used to calculate an effect size and confidence interval. The pooled effect size of 2.0759 (95 % CI 0.0988 to 4.0529) indicates that oxandrolone has a positive effect on adult height in Turner syndrome when combined with growth hormone therapy. In conclusion, the addition of oxandrolone to growth hormone therapy for treatment of short stature in Turner syndrome improves adult height. Further studies are warranted to investigate if there is a subset of Turner syndrome patients that would benefit most from growth hormone plus oxandrolone therapy, and to determine the optimal timing and duration of such therapy.

  13. Adjuvant therapy after primary surgery for stage I-IIA carcinoma of the cervix.

    PubMed

    Thomas, G M

    1996-01-01

    Radical hysterectomy and bilateral pelvic lymph node dissection is commonly used as a primary management option for treatment of stage IB/IIA carcinoma of the cervix. Overall cure rates approach 85%. However, a spectrum of relapse risk exists, depending on the presence or absence of primary tumor and nodal-related prognostic factors. Known factors include number and location of lymph nodes; size of primary, deep invasion in the cervix; capillary lymphatic space involvement; occult parametrial involvement; and positive or close surgical margins. Biologic determinants have yet to be identified. No systematic analysis has examined various combinations of prognostic factors to precisely define associated levels of risk and to predict the sites of relapse. Decreased local control and survival rates in some high-risk subgroups, usually those with nodal positivity, has led to the exploration of adjuvant therapies. Compiled data from retrospective series have defined the overall patterns of failure. Seventy-two percent of those relapsing have a component of pelvic failure, while 42% experience relapse in the pelvis alone. Fifty-eight percent have a component of distant failure but only 28% have distant disease alone. Adjuvant treatment options include pelvic radiotherapy, extended-field radiotherapy, chemoradiotherapy, and chemotherapy. Trials of adjuvant chemotherapy are too few to evaluate the use of available agents. Pelvic radiotherapy has been shown to reduce the relapse risk when surgical margins are close or positive. It also reduces the risk of pelvic relapse and improves the relapse-free interval but has no apparent impact on overall survival in the groups that have been selected for treatment. The apparent lack of benefit may relate to the choice of patients with nodal involvement who, despite high risk of pelvic failure, most likely have a predominant pattern of distant failure. Maximization of the survival benefit of pelvic radiotherapy requires the

  14. 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

  15. What You Should Know about Hormone Therapy Health Risks and Benefits

    MedlinePlus

    ... HAT Y OU S HOULD K NOW A BOUT Hormone Therapy Health Risks and Benefits V aginal dryness and ... for- women/ menopauseflashes/ news- you- can- use- about- hormone- therapy. Menopause and The North American Menopause Society grant ...

  16. Neoadjuvant or adjuvant therapy for resectable gastric cancer? A practice guideline

    PubMed Central

    Earle, Craig C.; Maroun, Jean; Zuraw, Lisa

    2002-01-01

    Objective To make recommendations on the use of neoadjuvant or adjuvant therapy in addition to surgery in patients with resectable gastric cancer (T1–4, N1–2, M0). Options Neoadjuvant or adjuvant treatments compared with “curative” surgery alone. Outcomes Overall survival, disease-free survival, and adverse effects. Evidence The MEDLINE, CANCERLIT and Cochrane Library databases and relevant conference proceedings were searched to identify randomized trials. Values Evidence was selected and reviewed by one member of the Cancer Care Ontario Practice Guidelines Initiative (CCOPGI) Gastrointestinal Cancer Disease Site Group and methodologists. A systematic review of the published literature was combined with a consensus process around the interpretation of the evidence in the context of conventional practice, to develop an evidence-based practice guideline. This report has been reviewed and approved by the Gastrointestinal Cancer Disease Site Group, comprising medical oncologists, radiation oncologists, surgeons, a pathologist and 2 community representatives. Benefits, harms and costs When compared with surgery alone, at 3 years adjuvant chemoradiotherapy has been shown to increase overall survival by 9% (50% v. 41%, p = 0.005) and to improve relapse-free survival from 31% to 48% (p = 0.001). At 5 years, it has been shown to increase overall survival by 11.6% (40% v. 28.4%) and to improve relapse-free survival from 25% to 38% (p < 0.001). Treatment has been associated with toxic deaths in 1% of patients. The most frequent adverse effects (> grade 3 [Southwest Oncology Group toxicity scale] are hematologic (54%), gastrointestinal (33%), influenza-like (9%), infectious (6%) and neurologic (4%). The radiation fields used can possibly damage the left kidney, resulting in hypertension and other renal problems. Furthermore, this therapy could increase the demand on radiation resources. Physicians and patients should understand the tradeoffs between survival benefit

  17. Adjuvant and Salvage Radiation Therapy After Prostatectomy: American Society for Radiation Oncology/American Urological Association Guidelines

    SciTech Connect

    Valicenti, Richard K.; Thompson, Ian; Albertsen, Peter; Davis, Brian J.; Goldenberg, S. Larry; Wolf, J. Stuart; Sartor, Oliver; Klein, Eric; Hahn, Carol; Michalski, Jeff; Roach, Mack; Faraday, Martha M.

    2013-08-01

    Purpose: The purpose of this guideline was to provide a clinical framework for the use of radiation therapy after radical prostatectomy as adjuvant or salvage therapy. Methods and Materials: A systematic literature review using PubMed, Embase, and Cochrane database was conducted to identify peer-reviewed publications relevant to the use of radiation therapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. Results: Guideline statements are provided for patient counseling, use of radiation therapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a restaging evaluation. Conclusions: Physicians should offer adjuvant radiation therapy to patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invastion, positive surgical margins, extraprostatic extension) and salvage radiation therapy to patients with prostate-specific antigen (PSA) or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiation therapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiation therapy as well as the potential benefits of preventing recurrence. The decision to administer radiation therapy should be made by the patient and the multidisciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. The American Society for Radiation Oncology and American Urological Association websites show this guideline in its entirety, including the full literature review.

  18. Adjuvant diet to improve hormonal and metabolic factors affecting breast cancer prognosis.

    PubMed

    Berrino, Franco; Villarini, Anna; De Petris, Michela; Raimondi, Milena; Pasanisi, Patrizia

    2006-11-01

    Western lifestyle, characterized by reduced physical activity and a diet rich in fat, refined carbohydrates, and animal protein is associated with high prevalence of overweight, metabolic syndrome, insulin resistance, and high plasma levels of several growth factors and sex hormones. Most of these factors are associated with breast cancer risk and, in breast cancer patients, with increased risk of recurrences. Recent trials have proven that such a metabolic and endocrine imbalance can be favorably modified through comprehensive dietary modification, shifting from Western to Mediterranean and macrobiotic diet.

  19. Anaplastic astrocytoma: prognostic factors and survival in 4807 patients with emphasis on receipt and impact of adjuvant therapy.

    PubMed

    Shin, Jacob Y; Diaz, Aidnag Z

    2016-09-01

    To determine the receipt and impact of adjuvant therapy on overall survival (OS) for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4807 patients with AA diagnosed from 2004 to 2013 who underwent surgery were identified. 3243 (67.5 %) received adjuvant chemoRT, 525 (10.9 %) adjuvant radiotherapy (RT) alone, 176 (3.7 %) adjuvant chemotherapy alone and 863 (18.0 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 (p = 0.022), were ≤ 50 years (p < 0.001), were male (p = 0.043), were Asian or White race (p < 0.001), had private insurance (p < 0.001), had income ≥$38,000 (p < 0.001), or underwent total resection (p < 0.003). Those who received adjuvant chemoRT had significantly better 5-year OS than the other adjuvant treatment types (41.8 % vs. 31.2 % vs. 29.8 % vs. 27.4 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age at diagnosis. Of those undergoing adjuvant chemoRT, those receiving ≥59.4 Gy had significantly better 5-year OS than those receiving <59.4 Gy (44.4 % vs. 25.9 %, p < 0.001). There was no significant difference in OS when comparing 59.4 Gy to higher RT doses. On multivariate analysis, receipt of adjuvant chemoRT, age at diagnosis, extent of disease, and insurance status were independent prognostic factors for OS. Adjuvant chemoRT is an independent prognostic factor for improved OS in AA and concomitant chemoRT should be considered for all clinically suitable patients who have undergone surgery for the disease.

  20. Hormone therapy for younger patients with endometrial cancer.

    PubMed

    Lee, Wen-Ling; Lee, Fa-Kung; Su, Wen-Hsiang; Tsui, Kuan-Hao; Kuo, Cheng-Deng; Hsieh, Shie-Liang Edmond; Wang, Peng-Hui

    2012-12-01

    The relationship between hormones and endometrial cancer is well known because disease states, such as chronic anovulation and endogenous estrogen production from hormone-secreting tumors (for example, granulosa cell tumor of the ovary), are related to excess estrogen, and unopposed estrogen use might lead to endometrial overgrowth, hyperplasia, and subsequent development of endometrial carcinoma. Therefore, the possibility of using antihormone therapy in endometrial carcinoma and/or its precancer lesions, such as simple hyperplasia with and without atypia and complex hyperplasia with and without atypia, is always supposed, as in the management of breast cancer. In addition, if women in whom endometrial cancer is diagnosed are very young, some critical issues should be considered, including the possibility of ovary preservation-partial preservation of fertility and the possibility of both ovary and uterus preservation-complete preservation of fertility. Other factors are also important to consider and include oncologic risk, appropriateness of candidates for treatment, type of hormone use, response rate of hormonal therapy, appropriate surveillance, and additional counseling for issues such as anxiety about relapse and metastasis, distress about side effects, advice of the family, advice of the medical staff, and economic burden. This review will be focused on updated information and recent knowledge of the use of hormones in the management of younger women with endometrial cancer who want fertility preservation.

  1. [Hormone therapy in menopause: when not to use].

    PubMed

    Spritzer, Poli Mara; Wender, Maria Celeste Osório

    2007-10-01

    Menopause is defined as the permanent cessation of menses, as a result of the loss of ovarian follicular function or of surgical removal of ovaries. The mean age for occurrence of natural menopause is around 50 years. Estrogen deficiency has been associated with vasomotor symptoms, urogenital atrophy, and cognitive impairment, as well as increased risk of chronic degenerative diseases such as osteoporosis and Alzheimer's disease. Estrogen therapy remains the most effective treatment for the management of vasomotor symptoms and urogenital atrophy. Progesterone or progestins should be added to estrogen treatment in women with uterus, in order to antagonize the estrogen-induced endometrial proliferation. In turn, in specific clinical conditions hormone therapy is not recommended. In the present article, the authors critically focus these clinical conditions in which hormone therapy should not be used.

  2. Revisiting the Cutaneous Impact of Oral Hormone Replacement Therapy

    PubMed Central

    Piérard, Gérald E.; Humbert, Philippe; Berardesca, Enzo; Gaspard, Ulysse; Hermanns-Lê, Trinh; Piérard-Franchimont, Claudine

    2013-01-01

    Menopause is a key point moment in the specific aging process of women. It represents a universal evolution in life. Its initiation is defined by a 12-month amenorrhea following the ultimate menstrual period. It encompasses a series of different biologic and physiologic characteristics. This period of life appears to spot a decline in a series of skin functional performances initiating tissue atrophy, withering, and slackness. Any part of the skin is possibly altered, including the epidermis, dermis, hypodermis, and hair follicles. Hormone replacement therapy (oral and nonoral) and transdermal estrogen therapy represent possible specific managements for women engaged in the climacteric phase. All the current reports indicate that chronologic aging, climacteric estrogen deficiency, and adequate hormone therapy exert profound effects on various parts of the skin. PMID:24455744

  3. A Prospective Cohort Study on Cardiotoxicity of Adjuvant Trastuzumab Therapy in Breast Cancer Patients

    PubMed Central

    Matos, Erika; Jug, Borut; Blagus, Rok; Zakotnik, Branko

    2016-01-01

    Background Cardiotoxicity is an important side effect of trastuzumab therapy and cardiac surveillance is recommended. Objectives The aim of our study was to prospectively assess baseline patients' characteristics, level of N-terminal pro-brain natriuretic peptide (NT-proBNP) and echocardiographic parameters as possible predictors of trastuzumab-related cardiac dysfunction. Methods In a prospective cohort study, clinical, echocardiographic and neurohumoral assessment was performed at baseline, after 4, 8 and 12 months in breast cancer patients undergoing post-anthracycline (3-4 cycles) adjuvant therapy with trastuzumab. Trastuzumab-related cardiac dysfunction was defined as a decline of ≥ 10% in left ventricular ejection fraction (LVEF). Results 92 patients (mean age, 53.6 ± 9.0 years) were included. Patients who developed trastuzumab-related LVEF decline ≥ 10% (20.6%) during treatment had significantly higher baseline LVEF (70.7 ± 4.4%) than those without (64.8 ± 5.5%) (p = 0.0035). All other measured baseline parameters (age, body mass index, arterial hypertension, level of NT-proBNP and other echocardiographic parameters) were not identified as significant. Conclusions Our findings suggest that baseline patient' characteristics, level of NT-proBNP and echocardiographic parameters, as long as they are within normal range, are not a reliable tool to predict early trastuzumab-related cardiac dysfunction in patients undergoing post-low dose anthracycline adjuvant trastuzumab therapy. A LVEF decline in patients with high-normal baseline level although statistically significant is not clinically relevant. PMID:27305108

  4. [Hormone-based classification and therapy concepts in psychiatry].

    PubMed

    Himmerich, H; Steinberg, H

    2011-07-01

    This study retells key aspects of the history of the idea of hormone-based classification and therapy concepts in psychiatry. Different contributions to the history are not only represented from a historical, but also from a current medico-scientific perspective. One of the oldest, yet ethically most problematic, indications concerning hormonal methods to modify undesirable behaviour and sexuality was castration, which was widely used in the 20th century to "cure" homosexuality. Felix Platter, whose concept was humoral-pathological in nature, documented the first postpartum psychosis in the German-speaking countries, the pathogenesis of which according to present-day expertise is brought about by changes in female hormones. The concept of an "endocrine psychiatry" was developed at the beginning of the 20th century. Some protagonists for neuroendocrinology are highlighted, such as Paul Julius Möbius around 1900 or, in the 1950s, Manfred Bleuler, the nestor of this new discipline. Only the discovery of the hormones as such and the development of technologies like radioimmunassay to measure and quantify these hormone changes in mental illnesses allowed investigating these conditions properly. Ever since hormone-based therapeutic and classification concepts have played an important role, above all, in sexual, affective and eating disorders as well as alcohol dependence.

  5. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy

    NASA Astrophysics Data System (ADS)

    Chen, Qian; Xu, Ligeng; Liang, Chao; Wang, Chao; Peng, Rui; Liu, Zhuang

    2016-10-01

    A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours.

  6. 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.

  7. Herbal Medicine and Acupuncture for Breast Cancer Palliative Care and Adjuvant Therapy

    PubMed Central

    Liao, Guo-Shiou; Shyur, Lie-Fen

    2013-01-01

    Breast cancer is a life-threatening disease among women worldwide with annual rates of reported incidence and death increasing alarmingly. Chemotherapy is a recommended and effective treatment option for breast cancer; however, the narrow therapeutic indices and varied side effects of currently approved drugs present major hurdles in increasing its effectiveness. An increasing number of literature evidence indicate that complementary and alternative medicine (CAM) used in treatment-related symptom control and alleviation of side effects plays an important role in increasing survival rate and quality of life in breast cancer patients. This review focuses on the use of herbal medicines and acupuncture in palliative care and as adjuvants in the treatment of breast cancer. Herbal medicinal treatments, the correlation of clinical use with demonstrated in vitro and in vivo mechanisms of action, and the use of certain acupoints in acupuncture are summarized. The aim of this review is to facilitate an understanding of the current practice and usefulness of herbal medicine and acupuncture as adjuvants in breast cancer therapy. PMID:23840256

  8. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy

    PubMed Central

    Chen, Qian; Xu, Ligeng; Liang, Chao; Wang, Chao; Peng, Rui; Liu, Zhuang

    2016-01-01

    A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours. PMID:27767031

  9. Cyclophosphamide and tamoxifen as adjuvant therapies in the management of breast cancer. CRC Adjuvant Breast Trial Working Party.

    PubMed Central

    1988-01-01

    In 1980 the Cancer Research Campaign launched a multi-centre breast cancer trial; aimed at repeating the Scandinavian Chemotherapy Study Group's cyclophosphamide trial, and the NATO tamoxifen study; thereby further evaluating the role of these two adjuvant regimens in patients with early breast cancer. Two thousand two hundred and thirty women were randomized into this trial between 1980 and 1985 and preliminary analyses demonstrate a significant improvement in event-free survival for both regimens. Results from this study closely parallel the two trials it set out to repeat. PMID:2900646

  10. 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

  11. Mechanisms of hormonal therapy resistance in breast cancer.

    PubMed

    Hayashi, Shin-ichi; Kimura, Mariko

    2015-04-01

    Whilst estrogen receptor (ER)-positive breast cancers are preferentially treated with hormone therapy, approximately one-third of them relapse. The mechanisms of refractoriness have been investigated by numerous studies but have not been fully clarified. Hormonal therapy resistance, particularly aromatase inhibitor (AI) resistance, may be related to the acquisition of alternative intracellular ER signaling. We have been investing the mechanisms using cancer specimens and cell lines by monitoring the transcription activity of ERs. AI refractory specimens showed diverse ER activity in the adenovirus estrogen receptor element-green fluorescent protein (ERE-GFP) assay and varied sensitivity to anti-estrogens, indicating the existence of multiple resistant mechanisms. We established six different types of cell lines mimicking AI resistance from ERE-GFP-introduced ER-positive cell lines. They revealed that multiple and alternative ER activating pathways were involved in the resistance, such as phosphorylation-dependent or androgen metabolite-dependent mechanisms. The response to fulvestrant and mammalian target of rapamycin inhibitor also varied among individual resistant cell lines. These results indicate that further subclassification of ER-positive breast cancer is extremely important to decide the therapeutic management of not only hormonal therapy but also new molecular target therapy.

  12. Use of Adjuvant 5-Fluorouracil and Radiation Therapy After Gastric Cancer Resection Among the Elderly and Impact on Survival

    SciTech Connect

    Strauss, Joshua; Hershman, Dawn L.; Buono, Donna; McBride, Russell; Clark-Garvey, Sean; Woodhouse, Shermian A.; Abrams, Julian A.

    2010-04-15

    Purpose: In randomized trials patients with resected nonmetastatic gastric cancer who received adjuvant chemotherapy and radiotherapy (chemoRT) had better survival than those who did not. We investigated the effectiveness of adjuvant chemoRT after gastric cancer resection in an elderly general population and its effects by stage. Methods and Materials: We identified individuals in the Surveillance, Epidemiology, and End Results-Medicare database aged 65 years or older with Stage IB through Stage IV (M0) gastric cancer, from 1991 to 2002, who underwent gastric resection, using multivariate modeling to analyze predictors of chemoRT use and survival. Results: Among 1,993 patients who received combined chemoRT or no adjuvant therapy after resection, having a later year of diagnosis, having a more advanced stage, being younger, being white, being married, and having fewer comorbidities were associated with combined treatment. Among 1,476 patients aged less than 85 years who survived more than 4 months, the 313 who received combined treatment had a lower mortality rate (hazard ratio, 0.83; 95% confidence interval, 0.71-0.98) than the 1,163 who received surgery alone. Adjuvant therapy significantly reduced the mortality rate for Stages III and IV (M0), trended toward improved survival for Stage II, and showed no benefit for Stage IB. We observed trends toward improved survival in all age categories except 80 to 85 years. Conclusions: The association of combined adjuvant chemoRT with improved survival in an overall analysis of Stage IB through Stage IV (M0) resected gastric cancer is consistent with clinical trial results and suggests that, in an elderly population, adjuvant chemoradiotherapy is effective. However, our observational data suggest that adjuvant treatment may not be effective for Stage IB cancer, is possibly appropriate for Stage II, and shows significant survival benefits for Stages III and IV (M0) for those aged less than 80 years.

  13. Hormonal therapy for acne: why not as first line therapy? facts and controversies.

    PubMed

    Katsambas, Andreas D; Dessinioti, Clio

    2010-01-01

    Standard systemic therapeutic agents used in acne include oral antimicrobials, isotretinoin, and hormonal agents. Appropriate patient selection is the key to decide when to use hormonal agents as first-line therapy as well as to achieve optimal results. Indications of hormonal therapy in acne in girls and women include proven ovarian or adrenal hyperandrogenism, recalcitrant acne, acne not responding to repeated courses of oral isotretinoin, acne tarda, polycystic ovary syndrome, or the presence of clinical signs of hyperandrogenism such as androgenic alopecia or the presence of the seborrhea, acne, hirsutism, alopecia syndrome. We describe the hormonal agents currently available for acne treatment, discuss their indications and contraindications, and address the question of whether they may be used as a first-line therapy in acne.

  14. Vascular dysfunction as a target for adjuvant therapy in cerebral malaria

    PubMed Central

    Carvalho, Leonardo José de Moura; Moreira, Aline da Silva; Daniel-Ribeiro, Cláudio Tadeu; Martins, Yuri Chaves

    2014-01-01

    Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum malaria that continues to be a major global health problem. Brain vascular dysfunction is a main factor underlying the pathogenesis of CM and can be a target for the development of adjuvant therapies for the disease. Vascular occlusion by parasitised red blood cells and vasoconstriction/vascular dysfunction results in impaired cerebral blood flow, ischaemia, hypoxia, acidosis and death. In this review, we discuss the mechanisms of vascular dysfunction in CM and the roles of low nitric oxide bioavailability, high levels of endothelin-1 and dysfunction of the angiopoietin-Tie2 axis. We also discuss the usefulness and relevance of the murine experimental model of CM by Plasmodium berghei ANKA to identify mechanisms of disease and to screen potential therapeutic interventions. PMID:25185000

  15. Doxorubicin and deracoxib adjuvant therapy for canine splenic hemangiosarcoma: a pilot study.

    PubMed

    Kahn, S Anthony; Mullin, Christine M; de Lorimier, Louis-Philippe; Burgess, Kristine E; Risbon, Rebecca E; Fred, Rogers M; Drobatz, Kenneth; Clifford, Craig A

    2013-03-01

    Canine hemangiosarcoma (HSA) is a highly malignant tumor for which standard chemotherapy has done little to substantially improve survival. Cyclooxygenase-2 (Cox-2) plays a role in the formation, growth, and metastasis of tumors and inhibitors have demonstrated therapeutic benefit with certain canine cancers. In this prospective study, 21 dogs received adjuvant therapy combining the selective Cox-2 inhibitor deracoxib with doxorubicin, following splenectomy for HSA. The combination was well-tolerated with only low-grade gastrointestinal and hematologic toxicities noted. An overall median survival of 150 days (range; 21 to 1506 days) was noted. Although there was no significant difference in survival based upon stage of disease, dogs with stage III HSA (n = 11) had a median survival of 149 days, which appears to be longer than previously reported. Further studies are warranted to evaluate the potential benefit of Cox-2 inhibitors in the treatment of canine HSA.

  16. Selective Thrombolysis in Acute Deep Vein Thrombosis: Evaluation of Adjuvant Therapy In Vivo

    SciTech Connect

    Roy, Sumit; Brosstad, Frank; Sakariassen, Kjell S.

    1999-09-15

    Purpose: To evaluate in a porcine model of acute deep vein thrombosis (DVT) the efficacy of dalteparin and antithrombin with respect to heparin for local adjuvant therapy during selective thrombolysis, and the utility of nitroglycerin and iloprost as heparin supplements. Methods: DVT was induced in both hind limbs using a previously described technique (n = 20). Thirty minutes later, the animal was heparinized (2500 IU IV), and bilateral sequestrated thrombolysis was performed using 8 mg alteplase: both external iliac veins were endoluminally occluded with Swan-Ganz catheters, and a multi-sideport infusion wire coaxially introduced through each catheter and advanced into the ipsilateral popliteal vein. In the control limbs, tissue plasminogen activator (tPA) 8 mg was injected as 0.8-ml boluses at 3-min intervals for 2 hr as a 0.25-mg/ml solution containing heparin 50 IU/ml (n 20). On the contralateral side, heparin was substituted with either dalteparin 50 IU/ml (n = 5) or antithrombin 12.5 IU/ml (n = 5), or supplemented with either nitroglycerin 0.075 mg/ml (n = 5) or iloprost (150 ng/ml) (n = 5). Blood samples were taken at predetermined intervals to measure the activated partial thromboplastin time (aPTT), prothrombin time (PT), and fibrinogen concentration. At autopsy, the thrombus mass in the iliofemoral veins was measured, and the extent of residual thrombosis in the venous tributaries graded at four sites. Results: Bilateral thrombolysis was successfully completed in all animals. The median thrombus mass in the iliofemoral veins after thrombolysis was 0.48 g (range 0.06-1.58 g), 0.95 g (0.59-1.29 g), 0.74 g (0.52-0.96 g), and 0.29 g (0.0-0.77 g) for dalteparin, antithrombin, iloprost, and nitroglycerin respectively, as compared with 0.53 g (0.18-0.88 g) (p = 0.69), 0.97 g (0.46-1.15 g) (p = 0.69), 0.53 g (0.48-1.10 g) (p = 0.69), and 0.18 g (0.13-1.04 g) (p = 0.5) for the respective controls. Likewise, the severity of residual thrombosis in the venous

  17. Herpes virus infection and uterine cervix carcinoma. General considerations, personal experimental data and suggestions for a specific antiherpes adjuvant therapy.

    PubMed

    Nastac, E; Hozoc, M; Stoian, M

    1982-01-01

    The authors review some data of the literature and results of personal investigations that point out a relationship between human herpes simplex virus infection and the etiopathogeny of uterine cervix carcinoma. On the ground of these data the authors suggest a "specific antiherpes" adjuvant therapy in this form of human cancer.

  18. Hormone Therapy and Other Treatments for Symptoms of Menopause.

    PubMed

    Hill, D Ashley; Crider, Mark; Hill, Susan R

    2016-12-01

    The results of large clinical trials have led physicians and patients to question the safety of hormone therapy for menopause. In the past, physicians prescribed hormone therapy to improve overall health and prevent cardiac disease, as well as for symptoms of menopause. Combined estrogen/progestogen therapy, but not estrogen alone, increases the risk of breast cancer when used for more than three to five years. Therefore, in women with a uterus, it is recommended that physicians prescribe combination therapy only to treat menopausal symptoms such as vasomotor symptoms (hot flashes) and vaginal atrophy, using the smallest effective dosage for the shortest possible duration. Although estrogen is the most effective treatment for hot flashes, nonhormonal alternatives such as low-dose paroxetine, venlafaxine, and gabapentin are effective alternatives. Women with a uterus who are using estrogen should also take a progestogen to reduce the risk of endometrial cancer. Women who cannot tolerate adverse effects of progestogens may benefit from a combined formulation of estrogen and the selective estrogen receptor modulator bazedoxifene. There is no highquality, consistent evidence that yoga, paced respiration, acupuncture, exercise, stress reduction, relaxation therapy, and alternative therapies such as black cohosh, botanical products, omega-3 fatty acid supplements, and dietary Chinese herbs benefit patients more than placebo. One systematic review suggests modest improvement in hot flashes and vaginal dryness with soy products, and small studies suggest that clinical hypnosis significantly reduces hot flashes. Patients with genitourinary syndrome of menopause may benefit from vaginal estrogen, nonhormonal vaginal moisturizers, or ospemifene (the only nonhormonal treatment approved by the U.S. Food and Drug Administration for dyspareunia due to menopausal atrophy). The decision to use hormone therapy depends on clinical presentation, a thorough evaluation of the risks and

  19. Prognosis of invasive breast cancer after adjuvant therapy evaluated with VEGF microvessel density and microvascular imaging.

    PubMed

    Li, Ying; Wei, Xi; Zhang, Sheng; Zhang, Jin

    2015-11-01

    The aim of this study was to investigate the role of ultrasonographic microvascular imaging in the evaluation of prognosis of patients with invasive breast cancer treated by adjuvant therapies. A total of 121 patients with invasive breast cancer underwent ultrasonographic contrast-enhanced imaging, vascular endothelial growth factor (VEGF) staining, and microvessel density (MVD) counts. The parameters of microvascular imaging and the expression of VEGF and MVD in primary breast cancer were calculated. The correlation between these factors and the overall and progression-free survival rate were analyzed using the Kaplan-Meier method. Among 121 cases, the positive VEGF cases were 75 and negative ones were 46. The cut point of 52.3 was calculated by the regressive curve for MVD counts. The data showed the mean intensity (MI) was positively associated with both the MVD counts (r = .51, p < .001) and VEGF expression (r = .35, p < .001). For the prognosis of patients, high VEGF expression and MVD counts were associated with reduced progressive and survival times (PFS, p = .032 and p = .034; OS, p = .041 and p = .038, respectively). The correlation between parameters of microvascular imaging, VEGF expressive status, and the MVD counts were established. The cut point of mean intensity (MI = 40) was used to investigate as an independent predictor for PFS (p = .021) and OS (p = .025), respectively, due to a strong correlation between MVD counts and VEGF expression in patients with invasive breast cancer. The microvascular imaging could be a visual and helpful tool to predict the prognosis of patients with invasive breast cancer treated by adjuvant therapies.

  20. 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

  1. 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.

  2. 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

  3. Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: first results from the STAMPEDE multiarm, multistage, randomised controlled trial

    PubMed Central

    James, Nicholas D; Sydes, Matthew R; Mason, Malcolm D; Clarke, Noel W; Anderson, John; Dearnaley, David P; Dwyer, John; Jovic, Gordana; Ritchie, Alastair WS; Russell, J Martin; Sanders, Karen; Thalmann, George N; Bertelli, Gianfilippo; Birtle, Alison J; O'Sullivan, Joe M; Protheroe, Andrew; Sheehan, Denise; Srihari, Narayanan; Parmar, Mahesh KB

    2012-01-01

    Summary Background Long-term hormone therapy alone is standard care for metastatic or high-risk, non-metastatic prostate cancer. STAMPEDE—an international, open-label, randomised controlled trial—uses a novel multiarm, multistage design to assess whether the early additional use of one or two drugs (docetaxel, zoledronic acid, celecoxib, zoledronic acid and docetaxel, or zoledronic acid and celecoxib) improves survival in men starting first-line, long-term hormone therapy. Here, we report the preplanned, second intermediate analysis comparing hormone therapy plus celecoxib (arm D) with hormone therapy alone (control arm A). Methods Eligible patients were men with newly diagnosed or rapidly relapsing prostate cancer who were starting long-term hormone therapy for the first time. Hormone therapy was given as standard care in all trial arms, with local radiotherapy encouraged for newly diagnosed patients without distant metastasis. Randomisation was done using minimisation with a random element across seven stratification factors. Patients randomly allocated to arm D received celecoxib 400 mg twice daily, given orally, until 1 year or disease progression (including prostate-specific antigen [PSA] failure). The intermediate outcome was failure-free survival (FFS) in three activity stages; the primary outcome was overall survival in a subsequent efficacy stage. Research arms were compared pairwise against the control arm on an intention-to-treat basis. Accrual of further patients was discontinued in any research arm showing safety concerns or insufficient evidence of activity (lack of benefit) compared with the control arm. The minimum targeted activity at the second intermediate activity stage was a hazard ratio (HR) of 0·92. This trial is registered with ClinicalTrials.gov, number NCT00268476, and with Current Controlled Trials, number ISRCTN78818544. Findings 2043 patients were enrolled in the trial from Oct 17, 2005, to Jan 31, 2011, of whom 584 were randomly

  4. Evaluation of Therapy Management and Patient Compliance in Postmenopausal Patients with Hormone Receptor-positive Breast Cancer Receiving Letrozole Treatment: The EvaluateTM Study

    PubMed Central

    Fasching, P. A.; Fehm, T.; Kellner, S.; de Waal, J.; Rezai, M.; Baier, B.; Baake, G.; Kolberg, H.-C.; Guggenberger, M.; Warm, M.; Harbeck, N.; Würstlein, R.; Deuker, J.-U.; Dall, P.; Richter, B.; Wachsmann, G.; Brucker, C.; Siebers, J. W.; Fersis, N.; Kuhn, T.; Wolf, C.; Vollert, H.-W.; Breitbach, G.-P.; Janni, W.; Landthaler, R.; Kohls, A.; Rezek, D.; Noesslet, T.; Fischer, G.; Henschen, S.; Praetz, T.; Heyl, V.; Kühn, T.; Krauß, T.; Thomssen, C.; Kümmel, S.; Hohn, A.; Tesch, H.; Mundhenke, C.; Hein, A.; Rauh, C.; Bayer, C. M.; Jacob, A.; Schmidt, K.; Belleville, E.; Hadji, P.; Wallwiener, D.; Grischke, E.-M.; Beckmann, M. W.; Brucker, S. Y.

    2014-01-01

    Introduction: The EvaluateTM study (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor-positive breast cancer patients receiving letrozole treatment) is a prospective, non-interventional study for the assessment of therapy management and compliance in the routine care of postmenopausal women with invasive hormone receptor-positive breast cancer receiving letrozole. The parameters for inclusion in the study are presented and discussed here. Material and Methods: Between January 2008 and December 2009 a total of 5045 patients in 310 study centers were recruited to the EvaluateTM study. Inclusion criteria were hormone receptor-positive breast cancer and adjuvant treatment or metastasis. 373 patients were excluded from the analysis for various reasons. Results: A total of 4420 patients receiving adjuvant treatment and 252 patients with metastasis receiving palliative treatment were included in the study. For 4181 patients receiving adjuvant treatment, treatment with the aromatase inhibitor letrozole commenced immediately after surgery (upfront). Two hundred patients had initially received tamoxifen and started aromatase inhibitor treatment with letrozole at 1–5 years after diagnosis (switch), und 39 patients only commenced letrozole treatment 5–10 years after diagnosis (extended endocrine therapy). Patient and tumor characteristics were within expected ranges, as were comorbidities and concurrent medication. Conclusion: The data from the EvaluateTM study will offer a good overview of therapy management in the routine care of postmenopausal women with hormone receptor-positive breast cancer. Planned analyses will look at therapy compliance and patient satisfaction with how information is conveyed and the contents of the conveyed information. PMID:25568468

  5. Intralesional lymphokine-activated killer cells as adjuvant therapy for primary glioblastoma.

    PubMed

    Dillman, Robert Owen; Duma, Christopher Michael; Ellis, Robin Anne; Cornforth, Andrew Nimitz; Schiltz, Patric Michael; Sharp, Shari Lynn; DePriest, Madeline Carol

    2009-01-01

    Despite recent advances, median survival for patients with resectable glioblastoma multiforme (GBM) is only 12 to 15 months. We previously observed minimal toxicity and a 9.0-month median survival after treatment with intralesional autologous lymphokine-activated killer (LAK) cells in 40 patients with recurrent GBM. In this study, GBM patients were treated with adjuvant intralesional LAK cells. Eligible patients had completed primary therapy for GBM without disease progression. LAK cells were produced by incubating autologous peripheral blood mononuclear cells with interleukin-2 for 3 to 7 days and then placed into the surgically exposed tumor cavity by a neurosurgeon. The 19 men and 14 women had a median age of 57 years. Prior therapy included surgical resection (97%), partial brain irradiation (97%), gamma knife radiosurgery (97%), and temozolomide chemotherapy (70%). Median time from diagnosis to LAK cell therapy was 5.3 months (range: 3.0 to 11.1 mo). LAK cell treatment was well tolerated; average length of hospitalization was 3 days. At the time of this analysis, 27 patients have died; the median survival from the date of original diagnosis is 20.5 months with a 1-year survival rate of 75%. In subset analyses, superior survival was observed for patients who received higher numbers of CD3+/CD16+/CD56+ (T-LAK) cells in the cell products, which was associated with not taking corticosteroids in the month before leukopheresis. Intralesional LAK cell therapy is safe and the survival sufficiently encouraging to warrant further evaluation in a randomized phase 2 trial of intralesional therapies with LAK or carmustine-impregnated wafers.

  6. Initiating growth hormone therapy for children and adolescents.

    PubMed

    Acerini, Carlo; Albanese, Assunta; Casey, Angela; Denvir, Louise; Jones, Julie; Mathew, Verghese; Musson, Pauline; Sparrow, Susan

    It is common for children and adolescents on growth hormone (GH) treatment to miss one or more injections per week, thereby compromising their linear growth outcome. Among factors likely to affect treatment concordance are patient education and support in the selection of the most appropriate GH injection device. The authors discovered inconsistencies in the process of starting patients on GH therapy throughout the UK, and found that there were no clinical recommendations to support health professionals starting patients on treatment. This article describes the issues involved and the development of practical recommendations for use when starting paediatric patients on long-term GH therapy.

  7. Adjuvant cytostatic therapy of breast cancer as an important factor in the postponing of a relapse and longer survival period.

    PubMed

    Stula, N

    1992-01-01

    This prospective clinical study shows the results of the adjuvant cytostatic therapy (ACT) in breast cancer applied to patients in the premenopausal age. Cyclophosphamide, methotrexate, 5-fluorouracil (CMF) group (70 patients): after operative and radiotherapeutic treatment the ACT is applied over the period of six months (six cycles). Control group (71 patients): only operative and radiotherapeutic treatment. Protocol of the ACT: cyclophosphamide, methotrexate, 5-fluorouracil (CMF) over 5 days with a 4-week break. Total 6 cycles. Control period: 10 years. Stratification of patients was made on the basis of the following risk factors: size of the tumour, number of positive lymph nodes of ipsilateral axilla, grade of the differentiation of the tumour, hormonal dependence of the tumour. Statistical method of analysis: actuary calculation, the Hi square test. The results show that the application of the ACT is statistically significant (P < 0.05) in regard to the disease-free interval. However, concerning the survival, the usefulness of its application is present but not statistically significant on the significance level of 5%. The usefulness of the ACT application as regards high risk factors (T3, T4 > or = 4 lymph nodes, grade of differentiation II, III, ER-PR-) is statistically significant (P < 0.05) both in regard to the DFI and survival. Regarding low risk factors the ACT application adversely influenced the results in the control group. This is probably the result of the ACT toxicity. The patients have a favourable prognosis in this subgroup in regard to the staging and biological nature of the tumour. The ACT in the premenopausal age of patients with high risk factors gives a significantly better results concerning the procrastination of relapse and the length of the survival period.

  8. Evaluation of monophosphoryl lipid A as an immune adjuvant for photodynamic therapy in a rat sarcoma model: preliminary results

    NASA Astrophysics Data System (ADS)

    Lucroy, Michael D.; Edwards, Benjamin F.; Griffey, Stephen M.; Madewell, Bruce R.

    1999-06-01

    Photodynamic therapy (PDT) is a treatment option for several forms of human cancer, and like traditional chemotherapy and ionizing radiation therapy, PDT alone is not curative for some cases. Recent efforts have aimed at developing strategies for adjuvant therapy for PDT. Given the nature of PDT-mediated cell damage, immunotherapy is a promising adjuvant for long-term control of solid tumors. A candidate immune stimulant for use with PDT is monophosphoryl lipid A (MLA), a non-toxic fraction of the endotoxin molecule. The hypothesis is that adjuvant MLA immunotherapy with PDT will improve local tumor control and prevent growth of subsequently implanted tumor cells when compared to PDT alone. To date, no significant differences in circulating leukocyte populations or tumor infiltrating lymphocyte populations have been identified in 9L tumor-bearing F344 rats after systemic administrations of MLA. Likewise, no significant difference has been identified in local tumor control following PDT of 9L tumors with or without adjuvant MLA. Further results are pending.

  9. Efficacy of switching therapy of luteinizing hormone-releasing hormone analogue for advanced prostate cancer.

    PubMed

    Shen, Yuan-Chi; Kang, Chih-Hsiung; Chiang, Po-Hui

    2016-11-01

    This study was conducted to determine the efficacy of switching therapy with a second-line luteinizing hormone-releasing hormone (LHRH) analogue after prostate-specific antigen (PSA) progression for advanced prostate cancer. We enrolled 200 patients, from December 2005 to September 2013, with nodal positive, metastatic prostate cancer or disease progression after definite treatment receiving continuous LHRH analogue therapy with monthly depot leuprorelin(sc) acetate 3.75 mg/vial (LA) or goserelin acetate(sc) 3.6 mg/vial (GA). If the patients had castration-resistant prostate cancer, the treatment choice of switching therapy (from LA to GA or from GA to LA) prior to starting chemotherapy was given. The LH, testosterone level, and PSA change were recorded. The records showed that there were 127 patients receiving LA as initial ADT therapy, whereas the other 73 patients were in GA therapy. A total of 92 patients received LHRH analogue switching therapy (54 patients switched from LA to GA and 38 switched from GA to LA). The effect of LH and testosterone reduction prior to and after switching therapy was comparable between the two groups, and increased PSA level after 3 months of treatment was seen in both groups (median PSA: 15.7-67.7 ng/mL in the LA to GA group; 15.2-71.4 ng/mL in the GA to LA group). This study concluded that switching therapy for patients with PSA progression after ADT has no efficacy of further PSA response.

  10. Survival in gastric cancer in relation to postoperative adjuvant therapy and determinants

    PubMed Central

    Ozden, Sevgi; Ozgen, Zerrin; Ozyurt, Hazan; Gemici, Cengiz; Yaprak, Gokhan; Tepetam, Huseyin; Mayadagli, Alpaslan

    2015-01-01

    AIM: To evaluate survival data in patients with gastric cancer in relation to postoperative adjuvant therapy and survival determinants METHODS: A total of 201 patients (mean ± SD age: 56.0 ± 11.9 years, 69.7% were males) with gastric carcinoma who were operated and followed up at Lutfi Kirdar Kartal Training and Research Hospital between 1998 and 2010 were included in this retrospective study. Follow up was evaluated divided into two consecutive periods (before 2008 and 2008-2010, respectively) based on introduction of 3-D conformal technique in radiotherapy at our clinic in 2008. Data on patient demographics, clinical and histopathological characteristics of gastric carcinoma and the type of treatment applied after surgery [postoperative adjuvant treatment protocols including chemoradiotherapy (CRT) and chemotherapy (CT), supportive therapy or follow up without any treatment] were recorded. The median duration and determinants of local recurrence free (LRF) survival, distant metastasis free (DMF) survival and overall survival were evaluated in the overall population as well as with respect to follow up years [1998-2008 (n = 127) vs 2008-2010 (n = 74)]. RESULTS: Median duration for LRF survival, DMF survival and overall survival were 31.9, 24.1 and 31.9 mo, respectively in patients with postoperative adjuvant CRT. No significant difference was noted in median duration for LRF survival, DMF survival and overall survival with respect to treatment protocols in the overall population and also with respect to followed up periods. In the overall population, CT protocols FUFA [5-fluorouracil (400 mg/m2) and leucovorin-folinic acid (FA, 20 mg/m2)] (29.9 mo) and UFT® + Antrex® [a fixed combination of the oral FU prodrug tegafur (flouroprymidine, FT, 300 mg/m2 per day) with FA (Antrex®), 15 mg tablet, two times a day] (42.5 mo) was significantly associated with longer LRF survival times than other CT protocols (P = 0.036), while no difference was noted between CT

  11. A review of hormonal therapy for female pattern (androgenic) alopecia.

    PubMed

    Scheinfeld, Noah

    2008-03-15

    Female pattern hair loss (female androgenetic alopecia) is a common, but puzzling, condition in women. Approximately 10 percent of pre-menopausal women show evidence of androgenetic alopecia. Age increases the incidence and 50-75 percent of women 65 years or older suffer from this condition. Only 2 percent topical mindoxidil is approved for treating female androgenetic alopecia. Reviews suggest that anti-hormonal therapy (e.g. cyproterone acetate, spironolactone) is helpful in treating female pattern alopecia in some women who have normal hormone levels. The use of hormonal therapies is most extensively studied in post-menopausal women. Several studies have suggested that cyproterone acetate with or without ethinyl estradiol and spironolactone can ameliorate female androgenetic alopecia in women with normal hormone levels, but larger controlled studies need to be done. Flutamide was found to be more effective than spironolactone or cyproterone in one study. Testosterone conversion inhibitors have been tried in post-menopausual women with normal hormone levels to treat alopecia. No study has shown that 1 mg of finasteride effectively treats female androgenetic alopecia but doses of 2.5 and 5 mg finasteride have helped some women in a few open studies. One case report notes the utility of dutasteride after finasteride failed. The role and place of anti-androgentic agents in female androgenetic alopecia in both pre and post-menopausal women remains to be fully defined. The need for effective agents is highlighted by the paucity of effective treatments and the substantial psychosocial impact of alopecia on women.

  12. Influence of Adjuvant Therapy in Cancer Survivors on Endothelial Function and Skeletal Muscle Deoxygenation

    PubMed Central

    Ederer, Austin K.; Didier, Kaylin D.; Reiter, Landon K.; Brown, Michael; Hardy, Rachel; Caldwell, Jacob; Black, Christopher D.; Larson, Rebecca D.; Ade, Carl J.

    2016-01-01

    The cardiotoxic effects of adjuvant cancer treatments (i.e., chemotherapy and radiation treatment) have been well documented, but the effects on peripheral cardiovascular function are still unclear. We hypothesized that cancer survivors i) would have decreased resting endothelial function; and ii) altered muscle deoxygenation response during moderate intensity cycling exercise compared to cancer-free controls. A total of 8 cancer survivors (~70 months post-treatment) and 9 healthy controls completed a brachial artery FMD test, an index of endothelial-dependent dilation, followed by an incremental exercise test up to the ventilatory threshold (VT) on a cycle ergometer during which pulmonary V˙O2 and changes in near-infrared spectroscopy (NIRS)-derived microvascular tissue oxygenation (TOI), total hemoglobin concentration ([Hb]total), and muscle deoxygenation ([HHb] ≈ fractional O2 extraction) were measured. There were no significant differences in age, height, weight, and resting blood pressure between cancer survivors and control participants. Brachial artery FMD was similar between groups (P = 0.98). During exercise at the VT, TOI was similar between groups, but [Hb]total and [HHb] were significantly decreased in cancer survivors compared to controls (P < 0.01) The rate of change for TOI (ΔTOIΔ/V˙O2) and [HHb] (Δ[HHb]/ΔV˙O2) relative to ΔV˙O2 were decreased in cancer survivors compared to controls (P = 0.02 and P = 0.03 respectively). In cancer survivors, a decreased skeletal muscle microvascular function was observed during moderate intensity cycling exercise. These data suggest that adjuvant cancer therapies have an effect on the integrated relationship between O2 extraction, V˙O2 and O2 delivery during exercise. PMID:26807572

  13. Triacetin-based acetate supplementation as a chemotherapeutic adjuvant therapy in glioma.

    PubMed

    Tsen, Andrew R; Long, Patrick M; Driscoll, Heather E; Davies, Matthew T; Teasdale, Benjamin A; Penar, Paul L; Pendlebury, William W; Spees, Jeffrey L; Lawler, Sean E; Viapiano, Mariano S; Jaworski, Diane M

    2014-03-15

    Cancer is associated with epigenetic (i.e., histone hypoacetylation) and metabolic (i.e., aerobic glycolysis) alterations. Levels of N-acetyl-L-aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate, are reduced in glioma; yet, few studies have investigated acetate as a potential therapeutic agent. This preclinical study sought to test the efficacy of the food additive Triacetin (glyceryl triacetate, GTA) as a novel therapy to increase acetate bioavailability in glioma cells. The growth-inhibitory effects of GTA, compared to the histone deacetylase inhibitor Vorinostat (SAHA), were assessed in established human glioma cell lines (HOG and Hs683 oligodendroglioma, U87 and U251 glioblastoma) and primary tumor-derived glioma stem-like cells (GSCs), relative to an oligodendrocyte progenitor line (Oli-Neu), normal astrocytes, and neural stem cells (NSCs) in vitro. GTA was also tested as a chemotherapeutic adjuvant with temozolomide (TMZ) in orthotopically grafted GSCs. GTA-induced cytostatic growth arrest in vitro comparable to Vorinostat, but, unlike Vorinostat, GTA did not alter astrocyte growth and promoted NSC expansion. GTA alone increased survival of mice engrafted with glioblastoma GSCs and potentiated TMZ to extend survival longer than TMZ alone. GTA was most effective on GSCs with a mesenchymal cell phenotype. Given that GTA has been chronically administered safely to infants with Canavan disease, a leukodystrophy due to ASPA mutation, GTA-mediated acetate supplementation may provide a novel, safe chemotherapeutic adjuvant to reduce the growth of glioma tumors, most notably the more rapidly proliferating, glycolytic and hypoacetylated mesenchymal glioma tumors.

  14. The iBRA-2 (immediate breast reconstruction and adjuvant therapy audit) study: protocol for a prospective national multicentre cohort study to evaluate the impact of immediate breast reconstruction on the delivery of adjuvant therapy

    PubMed Central

    Dave, Rajiv; O'Connell, Rachel; Rattay, Tim; Tolkien, Zoe; Barnes, Nicola; Skillman, Joanna; Williamson, Paula; Conroy, Elizabeth; Gardiner, Matthew; Harnett, Adrian; O'Brien, Ciara; Blazeby, Jane; Holcombe, Chris

    2016-01-01

    Introduction Immediate breast reconstruction (IBR) is routinely offered to improve quality of life for women with breast cancer requiring a mastectomy, but there are concerns that more complex surgery may delay the delivery of adjuvant oncological treatments and compromise long-term oncological outcomes. High-quality evidence, however, is lacking. iBRA-2 is a national prospective multicentre cohort study that aims to investigate the effect of IBR on the delivery of adjuvant therapy. Methods and analysis Breast and plastic surgery centres in the UK performing mastectomy with or without (±) IBR will be invited to participate in the study through the trainee research collaborative network. All women undergoing mastectomy ± IBR for breast cancer between 1 July and 31 December 2016 will be included. Patient demographics, operative, oncological and complication data will be collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR will be compared to determine the impact that IBR has on the time of delivery of adjuvant therapy. Prospective data on 3000 patients from ∼50 centres are anticipated. Ethics and dissemination Research ethics approval is not required for this study. This has been confirmed using the online Health Research Authority decision tool. This novel study will explore whether IBR impacts the time to delivery of adjuvant therapy. The study will provide valuable information to help patients and surgeons make more informed decisions about their surgical options. Dissemination of the study protocol will be via the Mammary Fold Academic and Research Collaborative (MFAC) and the Reconstructive Surgery Trials Network (RSTN), the Association of Breast Surgery (ABS) and the British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS). Participating units will have access to their own data and collective results will be presented at relevant surgical conferences and

  15. Lack of long-lasting effects of mitotane adjuvant therapy in a mouse xenograft model of adrenocortical carcinoma.

    PubMed

    Doghman, Mabrouka; Lalli, Enzo

    2013-12-05

    Mitotane is a widely used drug in the therapy of adrenocortical carcinoma (ACC). It is important to set up preclinical protocols to study the possible synergistic effects of its association with new drugs for ACC therapy. We assessed the efficacy of different routes of administration of mitotane (i.p. and oral) in inhibiting growth of H295R ACC cell xenografts in an adjuvant setting. Both formulations of mitotane could inhibit H295R xenografts growth only at short times after carcinoma cells inoculation, even though plasma mitotane levels approached or fell within the therapeutic range in humans. Our results show that mitotane adjuvant therapy is inadequate to antagonize long-term growth of H295R cancer cells xenografts and that care should then be taken in the design of preclinical protocols to evaluate the performance of new drugs in association with mitotane.

  16. Transcutaneous electrical nerve stimulation therapy: An adjuvant pain controlling modality in TMD patients — A clinical study

    PubMed Central

    Shanavas, Muhammad; Chatra, Laxmikanth; Shenai, Prashanth; Rao, Prasanna Kumar; Jagathish, Veena; Kumar, Sreeja Prasanna; Naduvakkattu, Bilahari

    2014-01-01

    Background: The use of transcutaneous electrical nerve stimulation (TENS) in dentistry was first described in 1967, by Shane and Kessler, but it has yet to gain widespread acceptance in dentistry. A study was undertaken to evaluate the effectiveness of TENS therapy as an adjuvant modality and to compare it with the conventional medication in controlling pain in temporomandibular disorder (TMD) patients. Materials and Methods: The study was carried out in the Department of Oral Medicine and Radiology, Yenepoya Dental College and Hospital, Mangalore. A total of 40 patients with the clinical symptom of pain associated with TMDs were randomly divided into two groups. Group A (control) patients were treated with medication (analgesics and muscle relaxants) alone, while group B patients were treated with TENS therapy in combination with medication. The intensity of the pain was assessed using the Visual Analog Scale (VAS). The results were analyzed with the student's ‘t’ test. A P-value < 0.05 was considered as significant. Results: A significant improvement was observed in both the TENS and the control group in terms of pain control. On comparative analysis, adjuvant TENS therapy was found to be more effective than medication alone, in controlling pain. (P value = 0.019). Conclusion: The observed data suggest that TENS therapy can be used as an adjuvant modality in the management of pain associated with TMDs. This study justifies the use of TENS therapy in the management of TMD. PMID:25540662

  17. Anti-invasive adjuvant therapy with imipramine blue enhances chemotherapeutic efficacy against glioma.

    PubMed

    Munson, Jennifer M; Fried, Levi; Rowson, Sydney A; Bonner, Michael Y; Karumbaiah, Lohitash; Diaz, Begoña; Courtneidge, Sara A; Knaus, Ulla G; Brat, Daniel J; Arbiser, Jack L; Bellamkonda, Ravi V

    2012-03-28

    The invasive nature of glioblastoma (GBM) represents a major clinical challenge contributing to poor outcomes. Invasion of GBM into healthy tissue restricts chemotherapeutic access and complicates surgical resection. Here, we test the hypothesis that an effective anti-invasive agent can "contain" GBM and increase the efficacy of chemotherapy. We report a new anti-invasive small molecule, Imipramine Blue (IB), which inhibits invasion of glioma in vitro when tested against several models. IB inhibits NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-mediated reactive oxygen species generation and alters expression of actin regulatory elements. In vivo, liposomal IB (nano-IB) halts invasion of glioma, leading to a more compact tumor in an aggressively invasive RT2 syngeneic astrocytoma rodent model. When nano-IB therapy was followed by liposomal doxorubicin (nano-DXR) chemotherapy, the combination therapy prolonged survival compared to nano-IB or nano-DXR alone. Our data demonstrate that nano-IB-mediated containment of diffuse glioma enhanced the efficacy of nano-DXR chemotherapy, demonstrating the promise of an anti-invasive compound as an adjuvant treatment for glioma.

  18. An Update of the Phase III Trial Comparing Whole Pelvic to Prostate Only Radiotherapy and Neoadjuvant to Adjuvant Total Androgen Suppression: Updated Analysis of RTOG 94-13, With Emphasis on Unexpected Hormone/Radiation Interactions

    SciTech Connect

    Lawton, Colleen A. DeSilvio, Michelle; Roach, Mack; Uhl, Valery; Kirsch, Robert; Seider, Michael; Rotman, Marvin; Jones, Christopher; Asbell, Sucha; Valicenti, Richard; Hahn, Stephen; Thomas, Charles R.

    2007-11-01

    Purpose: This trial was designed to test the hypothesis that total androgen suppression and whole pelvic radiotherapy (WPRT) followed by a prostate boost improves progression-free survival (PFS) by {>=}10% compared with total androgen suppression and prostate only RT (PORT). This trial was also designed to test the hypothesis that neoadjuvant hormonal therapy (NHT) followed by concurrent total androgen suppression and RT improves PFS compared with RT followed by adjuvant hormonal therapy (AHT) by {>=}10%. Methods and Materials: Patients eligible for the study included those with clinically localized adenocarcinoma of the prostate and an elevated prostate-specific antigen level of <100 ng/mL. Patients were stratified by T stage, prostate-specific antigen level, and Gleason score and were required to have an estimated risk of lymph node involvement of >15%. Results: The difference in overall survival for the four arms was statistically significant (p = 0.027). However, no statistically significant differences were found in PFS or overall survival between NHT vs. AHT and WPRT compared with PORT. A trend towards a difference was found in PFS (p = 0.065) in favor of the WPRT + NHT arm compared with the PORT + NHT and WPRT + AHT arms. Conclusions: Unexpected interactions appear to exist between the timing of hormonal therapy and radiation field size for this patient population. Four Phase III trials have demonstrated better outcomes when NHT was combined with RT compared with RT alone. The Radiation Therapy Oncology Group 9413 trial results have demonstrated that when NHT is used in conjunction with RT, WPRT yields a better PFS than does PORT. It also showed that when NHT + WPRT results in better overall survival than does WPRT + short-term AHT. Additional studies are warranted to determine whether the failure to demonstrate an advantage for NHT + WPRT compared with PORT + AHT is chance or, more likely, reflects a previously unrecognized biologic phenomenon.

  19. Isolated growth hormone deficiency type 2: from gene to therapy.

    PubMed

    Miletta, Maria Consolata; Lochmatter, Didier; Pektovic, Vibor; Mullis, Primus-E

    2012-01-01

    Isolated growth hormone deficiency type-2 (IGHD-2), the autosomal-dominant form of GH deficiency, is mainly caused by specific splicing mutations in the human growth hormone (hGH) gene (GH-1). These mutations, occurring in and around exon 3, cause complete exon 3 skipping and produce a dominant-negative 17.5 kD GH isoform that reduces the accumulation and secretion of wild type-GH (wt-GH). At present, patients suffering from IGHD-2 are treated with daily injections of recombinant human GH (rhGH) in order to reach normal height. However, this type of replacement therapy, although effective in terms of growth, does not prevent toxic effects of the 17.5-kD mutant on the pituitary gland, which can eventually lead to other hormonal deficiencies. Considering a well-known correlation between the clinical severity observed in IGHD-2 patients and the increased expression of the 17.5-kD isoform, therapies that specifically target this isoform may be useful in patients with GH-1 splicing defects. This chapter focuses on molecular strategies that could represent future directions for IGHD-2 treatment.

  20. Hormone therapy and asymmetrical dimethylarginine in postmenopausal women.

    PubMed

    Karkanaki, Artemis; Vavilis, Dimitrios; Traianos, Alexandros; Kalogiannidis, Ioannis; Panidis, Dimitrios

    2010-01-01

    Women present an estradiol-dependent cardiovascular risk profile. Based on various studies, it was considered that estrogen therapy (ET) in postmenopausal women could probably reduce the higher cardiovascular risk in this group. Assymetric dimethylarginine (ADMA) is an endogenous methylated arginine which inhibits nitric oxide (NO) synthesis by competing with the substrate of NO, L-arginine, leading to endothelial dysfunction and, consequently, to atherosclerosis. Moreover, ADMA has been considered as an independent risk factor for cardiovascular disease. It has also been found that hormone therapy (HT), and mainly oral estrogen therapy, lowers ADMA concentrations in healthy postmenopausal women. The effect of estrogens on ADMA levels, although small, is considered important, as physiological variation of ADMA is limited. Nevertheless, larger randomized trials are necessary to establish that estrogens substantially lower ADMA levels and that these changes really reflect improved cardiovascular prognosis in postmenopausal women.

  1. Stroke in women - oral contraception, pregnancy, and hormone replacement therapy.

    PubMed

    Rantanen, Kirsi; Tatlisumak, Turgut

    2013-01-01

    Stroke is a devastating disease affecting millions of people worldwide every year. Female stroke victims have higher mortality rates and they do not re-cover as well as men. Women's longevity and different vascular risk factor burden like a larger prevalence of atrial fibrillation play a role. Women also have unique risk factors such as oral contraception, pregnancy, estrogen decrease after the menopause and hormone replacement therapy, which should all be evaluated and taken into consideration in treatment decisions both in the acute phase of stroke and in secondary prevention. In this review, the evidence regarding these hormonal aspects and the risk of stroke in women are evaluated. The relevant guidelines are studied and research gaps identified. Future topics for research are recommended and current treatment possibilities and their risks discussed.

  2. Hormone replacement therapy and physical function in healthy older men. Time to talk hormones?

    PubMed

    Giannoulis, Manthos G; Martin, Finbarr C; Nair, K Sreekumaran; Umpleby, A Margot; Sonksen, Peter

    2012-06-01

    Improving physical function and mobility in a continuously expanding elderly population emerges as a high priority of medicine today. Muscle mass, strength/power, and maximal exercise capacity are major determinants of physical function, and all decline with aging. This contributes to the incidence of frailty and disability observed in older men. Furthermore, it facilitates the accumulation of body fat and development of insulin resistance. Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones and local load-sensitive autocrine/paracrine growth factors. GH, IGF-I, and testosterone (T) are directly involved in muscle adaptation to exercise because they promote muscle protein synthesis, whereas T and locally expressed IGF-I have been reported to activate muscle stem cells. Although exercise programs improve physical function, in the long-term most older men fail to comply. The GH/IGF-I axis and T levels decline markedly with aging, whereas accumulating evidence supports their indispensable role in maintaining physical function integrity. Several studies have reported that the administration of T improves lean body mass and maximal voluntary strength in healthy older men. On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and T are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and T, albeit in only a few studies, has resulted in greater efficacy than either hormone alone. Although it is clear that this combined approach is effective, this review concludes that further studies are needed to assess the long-term efficacy and safety of combined hormone replacement therapy in older men before the medical rationale of prescribing hormone replacement therapy for combating the sarcopenia of aging can be established.

  3. Postmenopausal hormone therapy and the risk of breast cancer: a contrary thought.

    PubMed

    Speroff, Leon

    2008-01-01

    The most important unanswered question regarding postmenopausal hormone therapy and the risk of breast cancer is whether hormone therapy initiates the growth of new breast cancers or whether the epidemiologic data reflect a hormonal impact on preexisting tumors. In this perspective I review the evidence favoring hormonal effects on preexisting tumors and suggest that exposure to combined estrogen and progestin is beneficial, causing greater differentiation and earlier detection of breast cancers.

  4. Impact of Adjuvant External-Beam Radiation Therapy in Early-Stage Uterine Papillary Serous and Clear Cell Carcinoma

    SciTech Connect

    Kim, Anne; Schreiber, David; Rineer, Justin; Choi, Kwang; Rotman, Marvin

    2011-11-15

    Purpose: Adjuvant radiation therapy (RT) in early-stage high- to intermediate-risk endometrioid adenocarcinoma is well established and has been shown to improve locoregional control. Its role in the management of early-stage clear cell carcinoma and uterine papillary serous carcinoma (UPSC) remains controversial. Methods and Materials: Using the Surveillance Epidemiology and End Results database, we identified women with American Joint Committee on Cancer Stage Sixth Edition. Stage IA-IIB clear cell carcinoma or UPSC who underwent hysterectomy with or without adjuvant RT between 1988 and 2003. We used Kaplan-Meier and Cox regression analysis to compare overall survival (OS) for all patients. Results: We identified 1,333 women of whom 451 had clear cell carcinoma and 882 had UPSC. Of those patients, 775 underwent surgery alone and 558 received adjuvant RT as well. For Stages I-IIB disease, the median OS with surgery alone was 106 months, vs. 151 months with adjuvant RT (p = 0.006). On subgroup analysis, we saw the benefit from adjuvant RT only in Stage IB-C patients. For Stage IB disease, patients undergoing surgery alone had a median OS of 117 months, vs. median survival not reached with the addition of RT (p = 0.006). For Stage IC disease, surgery alone had a median OS of 35 months vs. 120 months with RT (p = 0.001). Although the apparent benefit of RT diminished when measured via multivariate analysis, the impact of RT on survival did show a trend toward significance (hazard ration 0.808, confidence interval 95% 0.651-1.002, p = 0.052) Conclusion: In FIGO Stage IB-C papillary serous and clear cell uterine carcinoma, adjuvant RT seems to play an important role in improving survival.

  5. Adjuvant intraperitoneal chromic phosphate therapy for women with apparent early ovarian carcinoma who have not undergone comprehensive surgical staging

    SciTech Connect

    Soper, J.T.; Berchuck, A.; Clarke-Pearson, D.L. )

    1991-08-15

    Forty-nine women with apparent Stage 1 and 2 ovarian carcinoma received intraperitoneal phosphate 32 as the only adjuvant therapy after primary surgery. In addition to bilateral salpingo-oophorectomy, 40 (82%) had analysis of peritoneal cytology, and 35 (71%) underwent omentectomy. Random peritoneal biopsies and retroperitoneal lymph node sampling were not done in any of these patients. The overall and disease-free survival rates were 86% and 75%, respectively, with no significant differences by stage, histologic grade, histologic type, or low-risk versus high-risk subsets recognized in patients who received comprehensive surgical staging. Seven (58%) of 12 patients had lymph node metastasis as the first site of recurrence, including two of three with late recurrences. Significant morbidity related to intraperitoneal chromic phosphate (32P) occurred in one (2%) woman. These results emphasize the need for comprehensive surgical staging of women with apparent early ovarian carcinoma to aid in the selection of appropriate initial adjuvant therapy.

  6. Informing women about hormone replacement therapy: the consensus conference statement

    PubMed Central

    Mosconi, Paola; Donati, Serena; Colombo, Cinzia; Mele, Alfonso; Liberati, Alessandro; Satolli, Roberto

    2009-01-01

    Background The risks/benefits balance of hormone replacement therapy is controversial. Information can influence consumers' knowledge and behavior; research findings about hormone replacement therapy are uncertain and the messages provided by the media are of poor quality and incomplete, preventing a fully informed decision making process. We therefore felt that an explicit, rigorous and structured assessment of the information needs on this issue was urgent and we opted for the organisation of a national consensus conference (CC) to assess the current status of the quality of information on hormone replacement therapy (HRT) and re-visit recent research findings on its risks/benefits. Methods We chose a structured approach based on the traditional CC method combined with a structured preparatory work supervised by an organising committee (OC) and a scientific board (SB). The OC and SB chose the members of the CC's jury and appointed three multidisciplinary working groups (MWG) which were asked to review clinical issues and different aspects of the quality of information. Before the CC, the three MWGs carried out: a literature review on the risk/benefit profile of HRT and two surveys on the quality of information on lay press and booklets targeted to women. A population survey on women's knowledge, attitude and practice was also carried out. The jury received the documents in advance, listened the presentations during the two-day meeting of the CCs, met immediately after in a closed-door meeting and prepared the final document. Participants were researchers, clinicians, journalists as well as consumers' representatives. Results Key messages in the CC's deliberation were: a) women need to be fully informed about the transient nature of menopausal symptoms, about HRT risks and benefits and about the availability of non-pharmacological interventions; b) HRT is not recommended to prevent menopausal symptoms; c) the term "HRT" is misleading and "post menopausal hormone

  7. Growth hormone therapy and craniofacial bones: a comprehensive review.

    PubMed

    Litsas, G

    2013-09-01

    Growth hormone (GH) has significant effects on linear bone growth, bone mass and bone metabolism. The primary role of GH supplementation in children with GH deficiency, those born small for gestational age or with other types of disorders in somatic development is to increase linear growth. However, GH therapy seems to elicit varying responses in the craniofacial region. Whereas the effects of GH administration on somatic development are well documented, comparatively little is known of its effects on the craniofacial region. The purpose of this review was to search the literature and compile results from both animal and human studies related to the impact of GH on craniofacial growth.

  8. 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.

  9. Anti-metastatic functions of type 1 interferons: Foundation for the adjuvant therapy of cancer.

    PubMed

    Ortiz, Angélica; Fuchs, Serge Y

    2017-01-01

    The anti-tumorigenic effects that type 1 interferons (IFN1) elicited in the in vitro studies prompted consideration of IFN1 as a potent candidate for clinical treatment. Though not all patients responded to IFN1, clinical trials have shown that patients with high risk melanoma, a highly refractory solid malignancy, benefit greatly from intermediate IFN1 treatment in regards to relapse-free and distant-metastasis-free survival. The mechanisms by which IFN1 treatment at early stages of disease suppress tumor recurrence or metastatic incidence are not fully understood. Intracellular IFN1 signaling is known to affect cell differentiation, proliferation, and apoptosis. Moreover, recent studies have revealed specific IFN1-regulated genes that may contribute to IFN1-mediated suppression of cancer progression and metastasis. In concert, expression of these different IFN1 stimulated genes may impede numerous mechanisms that mediate metastatic process. Though, IFN1 treatment is still utilized as part of standard care for metastatic melanoma (alone or in combination with other therapies), cancers find the ways to develop insensitivity to IFN1 treatment allowing for unconstrained disease progression. To determine how and when IFN1 treatment would be most efficacious during disease progression, we must understand how IFN1 signaling affects different metastasis steps. Here, we specifically focus on the anti-metastatic role of endogenous IFN1 and parameters that may help to use pharmaceutical IFN1 in the adjuvant treatment to prevent cancer recurrence and metastatic disease.

  10. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism

    PubMed Central

    Allen, Bryan G.; Bhatia, Sudershan K.; Anderson, Carryn M.; Eichenberger-Gilmore, Julie M.; Sibenaller, Zita A.; Mapuskar, Kranti A.; Schoenfeld, Joshua D.; Buatti, John M.; Spitz, Douglas R.; Fath, Melissa A.

    2014-01-01

    Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2•−and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses. PMID:25460731

  11. 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

  12. [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.

  13. Magnetic resonance imaging in infantile spasms: effects of hormonal therapy.

    PubMed

    Konishi, Y; Yasujima, M; Kuriyama, M; Konishi, K; Hayakawa, K; Fujii, Y; Ishii, Y; Sudo, M

    1992-01-01

    Magnetic resonance imaging (MRI) was performed on five patients with infantile spasms who were treated with relatively low doses of adrenocorticotrophic hormone (ACTH) to study the extent of brain shrinkage induced by ACTH therapy. MRI prior to ACTH therapy revealed periventricular hyperintensity (PVH) areas and poor myelination in four patients. In one case, MRI performed 2 days after initiation of ACTH therapy also showed PVH and poor myelination. Brain shrinkage was observed 2 weeks after initiation of ACTH therapy. The most impressive follow-up finding upon MRI was the decrease in PVH found in four patients. The differentiation between myelinated white matter and surrounding cortex became poorer in three cases. Cortical atrophy progressed in all patients but ventricular dilation progressed in only one patient. At the end of ACTH therapy, ventricular dilation progressed in all cases. These findings suggest that loss of water not only from periventricular white matter but also from cortex is the main etiological factor of brain shrinkage induced by ACTH.

  14. 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.

  15. CATIONIC CERAMIDES AND ANALOGUES, LCL30 AND LCL85, AS ADJUVANTS TO PHOTODYNAMIC THERAPY OF TUMORS

    PubMed Central

    Korbelik, Mladen; Zhang, Wei; Saw, Kyi Min; Szulc, Zdzislaw M.; Bielawska, Alicja; Separovic, Duska

    2013-01-01

    Photodynamic therapy (PDT) is known to alter the expression of various genes in treated cells. This prompted us to examine the activity of genes encoding two important enzymes in sphingolipid (SL) metabolism, dihydroceramide desaturase (DES) and sphingosine kinase (SPHK), in mouse SCCVII tumor cells treated by PDT using either the porphyrin-based photosensitizer Photofrin or silicon phthalocyanine Pc4. The results revealed that PDT induced an upregulation in the expression of two major isoforms of both genes (DES1 and DES2 as well as SPHK1 and SPHK2). While the changes were generally moderate (2-3 fold gains), the increase in DES2 expression was more pronounced and it was much greater with Photofrin-PDT than with Pc4-PDT (over 23-fold vs. less than 5-fold). Combining either Photofrin-PDT or Pc4-PDT with the cationic C16-ceramide LCL30 (20 mg/kg i.p.) for treatment of subcutaneously growing SCCVII tumors rendered important differences in the therapy outcome. Photofrin-PDT, used at a dose that attained good initial response but no tumor cures, produced 50% cures when combined with a single LCL30 treatment. In contrast, the same LCL30 treatment combined with Pc4-PDT had no significant effect on tumor response. The optimal timing of LCL30 injection was immediately after Photofrin-PDT. The therapeutic benefit was lost when LCL30 was given in two 20 mg/kg injections encompassing intervals before and after PDT. LCL85, the cationic B13 ceramide analogue and SL-modulating agent, also increased cure rates of Photofrin-PDT treated tumors, but the therapeutic benefit was less pronounced than with LCL30. These results with LCL30 and LCL85, and our previous findings for LCL29 (another SL analogue), assert the potential of SLs for use as adjuvants to augment the efficacy of PDT-mediated tumor destruction. PMID:23911762

  16. Cationic ceramides and analogues, LCL30 and LCL85, as adjuvants to photodynamic therapy of tumors.

    PubMed

    Korbelik, Mladen; Zhang, Wei; Saw, Kyi Min; Szulc, Zdzislaw M; Bielawska, Alicja; Separovic, Duska

    2013-09-05

    Photodynamic therapy (PDT) is known to alter the expression of various genes in treated cells. This prompted us to examine the activity of genes encoding two important enzymes in sphingolipid (SL) metabolism, dihydroceramide desaturase (DES) and sphingosine kinase (SPHK), in mouse SCCVII tumor cells treated by PDT using either the porphyrin-based photosensitizer Photofrin or silicon phthalocyanine Pc4. The results revealed that PDT induced an upregulation in the expression of two major isoforms of both genes (DES1 and DES2 as well as SPHK1 and SPHK2). While the changes were generally moderate (2-3-fold gains), the increase in DES2 expression was more pronounced and it was much greater with Photofrin-PDT than with Pc4-PDT (over 23-fold vs. less than 5-fold). Combining either Photofrin-PDT or Pc4-PDT with the cationic C16-ceramide LCL30 (20mg/kg i.p.) for treatment of subcutaneously growing SCCVII tumors rendered important differences in the therapy outcome. Photofrin-PDT, used at a dose that attained good initial response but no tumor cures, produced 50% cures when combined with a single LCL30 treatment. In contrast, the same LCL30 treatment combined with Pc4-PDT had no significant effect on tumor response. The optimal timing of LCL30 injection was immediately after Photofrin-PDT. The therapeutic benefit was lost when LCL30 was given in two 20mg/kg injections encompassing intervals before and after PDT. LCL85, the cationic B13 ceramide analogue and SL-modulating agent, also increased cure rates of Photofrin-PDT treated tumors, but the therapeutic benefit was less pronounced than with LCL30. These results with LCL30 and LCL85, and our previous findings for LCL29 (another SL analogue), assert the potential of SLs for use as adjuvants to augment the efficacy of PDT-mediated tumor destruction.

  17. Bioidentical menopausal hormone therapy: registered hormones (non-oral estradiol ± progesterone) are optimal.

    PubMed

    L'Hermite, M

    2017-03-16

    The many advantages of registered bioidentical sex hormones over registered, conventional, non-bioidentical menopausal hormone therapy (MHT) are considered. The transdermal route of estrogen administration avoids excess venous thromboembolic and ischemic stroke events. There is some indication that conjugated equine estrogens are more thrombogenic and most likely induce some hypertensive responses; estradiol might also be superior to conjugated equine estrogens (CEE) in terms of global cardiovascular health. The most valid evidence presently suggests that CEE-only treatment does not increase the risk of breast cancer and even may reduce it. But its combination with a synthetic progestogen (mainly medroxyprogesterone acetate) is a critical issue since it seems to be primarily associated with an increased incidence of breast cancer, however similar to or lower than that associated with some common lifestyle factors. Though not yet proven in a randomized, controlled trial, MHT continuously combining oral micronized progesterone with transdermal estradiol can presently be considered as the optimal MHT. It is not only safer than custom-compounded bioidentical hormones but also than oral conventional MHT and has the best breast profile; registered products for such optimal MHT are available around the world and must be preferred.

  18. Hormone therapy in transgender adults is safe with provider supervision; A review of hormone therapy sequelae for transgender individuals

    PubMed Central

    Weinand, Jamie D.; Safer, Joshua D.

    2016-01-01

    Introduction Some providers report concern for the safety of transgender hormone therapy (HT). Methods This is a systematic literature review of HT safety for transgender adults. Results Current literature suggests HT is safe when followed carefully for certain risks. The greatest health concern for HT in transgender women is venous thromboembolism. HT among transgender men appears to cause polycythemia. Both groups experienced elevated fasting glucose. There is no increase in cancer prevalence or mortality due to transgender HT. Conclusion Although current data support the safety of transgender HT with physician supervision, larger, long-term studies are needed in transgender medicine. PMID:28090436

  19. Alzheimer's disease, apolipoprotein E and hormone replacement therapy.

    PubMed

    Depypere, H; Vierin, A; Weyers, S; Sieben, A

    2016-12-01

    Alzheimer's disease is the most frequent cause of dementia in older patients. The prevalence is higher in women than in men. This may be the result of both the higher life expectancy of women and the loss of neuroprotective estrogen after menopause. Earlier age at menopause (spontaneous or surgical) is associated with an enhanced risk of developing Alzheimer's disease. Therefore, it is postulated that estrogen could be protective against it. If so, increasing exposure to estrogen through the use of postmenopausal hormone replacement could also be protective against Alzheimer's disease. The results of the clinical studies that have examined this hypothesis are inconclusive, however. One explanation for this is that estrogen treatment is protective only if it is initiated in the years immediately after menopause. Another possibility is that the neuroprotective effects of estrogen are negated by a particular genotype of apolipoprotein E. This protein plays an important role in cholesterol transport to the neurons. Studies that have examined the link between estrogen replacement therapy, Alzheimer's disease and the E4 allele of ApoE are inconclusive. This article reviews the literature on the influence of hormone replacement therapy on the incidence and progression of Alzheimer's disease.

  20. Limited Advantages of Intensity-Modulated Radiotherapy Over 3D Conformal Radiation Therapy in the Adjuvant Management of Gastric Cancer

    SciTech Connect

    Alani, Shlomo; Soyfer, Viacheslav; Strauss, Natan; Schifter, Dan; Corn, Benjamin W.

    2009-06-01

    Purpose: Although chemoradiotherapy was considered the standard adjuvant treatment for gastric cancer, a recent Phase III trial (Medical Research Council Adjuvant Gastric Infusional Chemotherapy [MAGIC]) did not include radiotherapy in the randomization scheme because it was considered expendable. Given radiotherapy's potential, efforts needed to be made to optimize its use for treating gastric cancer. We assessed whether intensity-modulated radiotherapy (IMRT) could improve upon our published results in patients treated with three-dimensional (3D) conformal therapy. Methods and Materials: Fourteen patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a noncoplanar four-field arrangement. Subsequently, a nine-field IMRT plan was designed using a CMS Xio IMRT version 4.3.3 module. Two IMRT beam arrangements were evaluated: beam arrangement 1 consisted of gantry angles of 0 deg., 53 deg., 107 deg., 158 deg., 204 deg., 255 deg., and 306 deg.. Beam arrangement 2 consisted of gantry angles of 30 deg., 90 deg., 315 deg., and 345 deg.; a gantry angle of 320 deg./couch, 30 deg.; and a gantry angle of 35{sup o}/couch, 312{sup o}. Both the target volume coverage and the dose deposition in adjacent critical organs were assessed in the plans. Dose-volume histograms were generated for the clinical target volume, kidneys, spine, and liver. Results: Comparison of the clinical target volumes revealed satisfactory coverage by the 95% isodose envelope using either IMRT or 3D conformal therapy. However, IMRT was only marginally better than 3D conformal therapy at protecting the spine and kidneys from radiation. Conclusions: IMRT confers only a marginal benefit in the adjuvant treatment of gastric cancer and should be used only in the small subset of patients with risk factors for kidney disease or those with a preexisting nephropathy.

  1. Adjuvant and salvage therapy with leflunomide for recalcitrant cytomegalovirus infections in hematopoietic cell transplantation recipients: A case series.

    PubMed

    El Chaer, Firas; Mori, Nobuyoshi; Shah, Dimpy; Oliver, Nora; Wang, Emily; Jan, Anna; Doan, Vi; Tverdek, Frank; Tayar, Jean; Ariza-Heredia, Ella; Chemaly, Roy F

    2016-11-01

    Cytomegalovirus (CMV) reactivation is a clinically significant complication in hematopoietic stem cell transplant (HCT) recipients. Alternative therapy for multidrug-resistant CMV is limited and often fails. Leflunomide has been used to treat resistant CMV infections, however, data on efficacy, safety, and guidance for therapeutic drug level monitoring are lacking. In this report, we describe 3 HCT recipients with multi-drug resistant CMV infections who received leflunomide as adjuvant and salvage therapy. The therapeutic effect of leflunomide as an anti-CMV agent based on virologic responses and therapeutic drug monitoring were evaluated.

  2. Compounded bioidentical hormone therapy: identifying use trends and knowledge gaps among US women

    PubMed Central

    Pinkerton, JoAnn V.; Santoro, Nanette

    2015-01-01

    Abstract Objective: Two surveys (Harris and Rose surveys) were conducted to quantify the use of compounded hormone therapy (CHT; or bioidentical hormone therapy) among perimenopausal and postmenopausal women in the United States, to assess women's knowledge of CHT versus Food and Drug Administration (FDA)–approved hormone therapy, and to gather information on menopausal experience. Methods: The Harris survey was administered to 801 women aged 45 to 60 years who had experienced at least one menopausal symptom. The Rose survey was administered to 2,044 women aged 40 years or older who were ever users of hormone therapy. Women were queried about menopausal symptoms, hormone therapy use, and knowledge of CHT. Findings from the Rose survey were extrapolated using US Census Bureau data and prescription claims for FDA-approved hormone therapy to estimate the prevalence of CHT use. Results: According to extrapolations using Rose data, up to 2.5 million US women aged 40 years or older may use CHT annually, accounting for 28% to 68% of hormone therapy prescriptions. Harris data showed that 86% of women surveyed were unaware that CHT products are not FDA-approved. The Rose survey asked a subset of 1,771 women whether their hormone therapy had been personalized based on hormone levels; 21% (378) answered “yes” whereas 27% (476) did not know. In both surveys, most hormone therapy users stated that their physician had recommended the treatment. Conclusions: We estimate that 1 million to 2.5 million US women aged 40 years or older use CHT. The data suggest that many women are unaware that compounded hormones have not been evaluated or approved by the FDA. Providers have an educational opportunity to ensure that women considering hormone therapy understand the risks and benefits of inadequately regulated CHT. PMID:25692877

  3. Adjuvant Radiation Therapy Improves Local Control After Surgical Resection in Patients With Localized Adrenocortical Carcinoma

    SciTech Connect

    Sabolch, Aaron; Else, Tobias; Griffith, Kent A.; Ben-Josef, Edgar; Williams, Andrew; Miller, Barbra S.; Worden, Francis; Jolly, Shruti

    2015-06-01

    Purpose: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. Methods and Materials: We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. Results: From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. Conclusions: Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed.

  4. Desmoplasia Influenced Recurrence of Disease and Mortality in Stage III Colorectal Cancer within Five Years after Surgery and Adjuvant Therapy

    PubMed Central

    Zippi, Maddalena; De Toma, Giorgio; Minervini, Giovanni; Cassieri, Claudio; Pica, Roberta; Colarusso, Diodoro; Stock, Simon; Crispino, Pietro

    2017-01-01

    Background/Aims: In patients with colon cancer who undergo resection for potential cure, 40–60% have advanced locoregional disease (stage III). Those who are suitable for adjuvant treatment had a definite disease-free-survival benefit. The aim of the present study was to demonstrate whether the presence of desmoplasia influenced the mortality rate of stage III colorectal cancer (CRC) within 5 years from the surgery and adjuvant therapy. Patients and Methods: Sixty-five patients with stage III CRC underwent resection and adjuvant therapy. Qualitative categorization of desmoplasia was obtained using Ueno's stromal CRC classification. Desmoplasia was related to mortality using Spearman correlation and stratified with other histological variables (inflammation, grading) that concurred to the major determinant of malignancy (venous invasion and lymph nodes) using the Chi-square test. Result: The 5-year survival rate was 65% and the relapse rate was 37%. The mortality rate in patients with immature desmoplasia was 86%, 27% in intermediate desmoplasia, and 0% in mature desmoplasia (Spearman correlation coefficient: −0.572, P = 0.05). Conclusion: Immature desmoplasia appears to be associated with disease recurrence and mortality in stage III CRC patients. PMID:28139499

  5. 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

  6. 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.

  7. Improving adherence to hormone replacement therapy with effective patient-physician communication.

    PubMed

    Sarrel, P M

    1999-03-01

    Surgically menopausal women are 5 times more likely to begin hormone replacement therapy than are naturally menopausal women, and they continue therapy for longer periods. The primary reasons that women refuse hormone replacement are fear of cancer and perceived side effects. In contrast, withdrawal bleeding is the major reason that women discontinue hormone replacement therapy. Physician-patient communication plays an important role in a woman's decision to use hormone replacement therapy, to fill her prescription, and to adhere to the regimen. The first visit at which hormone replacement therapy is discussed is crucial to establishing an effective patient-physician relationship. At least 15 minutes, and preferably 45 minutes, should be reserved for this visit. Patient follow-up-either by phone or in person-during the first month can help improve adherence because this is when many women may have nuisance side effects and discontinue therapy.

  8. Search for novel therapies for triple negative breast cancers (TNBC): analogs of luteinizing hormone-releasing hormone (LHRH) and growth hormone-releasing hormone (GHRH).

    PubMed

    Buchholz, Stefan; Seitz, Stephan; Engel, Jörg B; Montero, Alberto; Ortmann, Olaf; Perez, Roberto; Block, Norman L; Schally, Andrew V

    2012-04-01

    Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that is clinically negative for the expression of estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor-2 (HER2). Patients with TNBC have a worse clinical outcome, as measured by time to metastasis and median overall survival. Chemotherapy has been the mainstay of treatment of TNBC but responses are disappointing. A substantial proportion of TNBC expresses luteinizing hormone-releasing hormone (LHRH), receptors for LHRH, in addition to receptors for growth hormone-releasing hormone (GHRH). These receptors represent potential therapeutic targets. Potent antagonists of GHRH and LHRH receptors have been developed in recent years and these antagonists inhibit the growth, tumorigenicity and metastatic potential of various human experimental malignancies. These antagonists could be utilized for the treatment of TNBC. The targeted cytotoxic analog of LHRH, AN-152 (AEZS-108) containing doxorubicin, must also be strongly considered for therapy of TNBC. Experimental studies suggest the merit of clinical trials with LHRH antagonists and AEZS-108 in TNBC patients.

  9. A review of systematic reviews of the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer

    PubMed Central

    Diaby, Vakaramoko; Xiao, Hong; Montero, Alberto J.

    2015-01-01

    early-stage breast cancer, evidence about trastuzumab value differed by age. Trastuzumab was cost-effective only in women with HER2-positive breast cancer younger than 65 years and over a life-time horizon. The cost-effectiveness of trastuzumab in HER2-positive metastatic breast cancer yielded conflicting results. The same conclusions were reached in comparisons between vinorelbine and taxanes. In both early stage and advanced/metastatic breast cancer, newer aromatase inhibitors (AIs) have proved cost-effective compared to older treatments. This overview of systematic reviews shows that there is heterogeneity in the evidence concerning the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer. The cost-effectiveness of these treatments depends not only on the comparators but the context, i.e., adjuvant or metastatic setting, subtype of patient population, and perspective adopted. Decisions involving the cost-effectiveness of breast cancer treatments could be made easier and more transparent by better harmonizing the reporting of economic evaluations assessing the value of these treatments. PMID:25893588

  10. A review of systematic reviews of the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer.

    PubMed

    Diaby, Vakaramoko; Tawk, Rima; Sanogo, Vassiki; Xiao, Hong; Montero, Alberto J

    2015-05-01

    cancer, evidence about trastuzumab value differed by age. Trastuzumab was cost-effective only in women with HER2-positive breast cancer younger than 65 years and over a life-time horizon. The cost-effectiveness of trastuzumab in HER2-positive metastatic breast cancer yielded conflicting results. The same conclusions were reached in comparisons between vinorelbine and taxanes. In both early stage and advanced/metastatic breast cancer, newer aromatase inhibitors (AIs) have proved cost-effective compared to older treatments. This overview of systematic reviews shows that there is heterogeneity in the evidence concerning the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer. The cost-effectiveness of these treatments depends not only on the comparators but the context, i.e., adjuvant or metastatic setting, subtype of patient population, and perspective adopted. Decisions involving the cost-effectiveness of breast cancer treatments could be made easier and more transparent by better harmonizing the reporting of economic evaluations assessing the value of these treatments.

  11. Adjuvant intraoperative photodynamic therapy (AIOPDT) after photosensitization with mTHPC in a CC531 colon carcinoma model in mice

    NASA Astrophysics Data System (ADS)

    Winkler, Steffi; Prosst, Ruediger L.; Stern, Josef; Rheinwald, Markus; Haase, Thomas; Herfarth, Christian; Gahlen, Johannes

    2001-01-01

    The effectiveness of PDT as an adjuvant alternative therapy method for diverse malignant tumors has been investigated in numerous studies. The therapeutic benefit and extent of side effects is mainly determined by the applied photoactive substance. The second generation photosensitizer (PS) mTHPC is capable of causing selective tumor cell death in colon carcinoma when combined with laser irradiation of a PS specific wavelength. Our study revealed PDT with mTHPC as an efficient adjuvant intraoperative modality after R1/R2 resection of a subcutaneously implanted colon tumor. There was a significant increase of postoperative recurrence-free survival time using PDT compared to a control group in a colon cancer model in nude mice. The accumulation of the PS determined by point spectrometry showed a high tumor-selectivity in the tumor, tumor bed, and overlying skin compared to muscle tissue as reference parameter.

  12. Benefit/risk for adjuvant breast cancer therapy with tamoxifen or aromatase inhibitor use by age, and race/ethnicity.

    PubMed

    Chlebowski, R T; Haque, R; Hedlin, H; Col, N; Paskett, E; Manson, J E; Kubo, J T; Johnson, K C; Wactawski-Wende, J; Pan, K; Anderson, G

    2015-12-01

    In early adjuvant breast cancer trial reports, aromatase inhibitors more effectively reduced breast recurrence with lower risk of thromboembolic events and endometrial cancer than tamoxifen, while aromatase inhibitors had higher fracture and cardiovascular disease risk. We used data from updated patient-level meta-analyses of adjuvant trials in analyses to summarize the benefits and risks of these agents in various clinical circumstances. Baseline incidence rates for health outcomes by age and race/ethnicity, absent aromatase inhibitor, or tamoxifen use were estimated from the Women's Health Initiative. Aromatase inhibitor and tamoxifen effects on distant recurrence were obtained from a meta-analysis of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) and Breast International Group (Big-1-98) clinical trials. Impact on other health outcomes were obtained from meta-analyses of randomized trials comparing aromatase inhibitor to tamoxifen use and from placebo-controlled chemoprevention trials. All health outcomes were given equal weight when modeling net benefit/risk for aromatase inhibitor compared to tamoxifen use by breast cancer recurrence risk, age (decade), race/ethnicity, hysterectomy (yes/no), and by prior myocardial infarction. Over a 10-year period, the benefit/risk index was more favorable for aromatase inhibitor than for tamoxifen as adjuvant breast cancer therapy in almost all circumstances regardless of patient age, race/ethnicity, breast cancer recurrence risk, or presence or absence of a uterus. Only in older women with prior myocardial infarction and low recurrence risk was an advantage for tamoxifen seen. Using a benefit/risk index for endocrine adjuvant breast cancer therapy in postmenopausal women, benefit was higher for aromatase inhibitor use in almost all circumstances.

  13. Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial: overview of efficacy, safety, and cost-effectiveness.

    PubMed

    Twelves, Chris J

    2006-11-01

    The X-ACT (Xeloda in Adjuvant Colon Cancer Therapy) trial compared the efficacy and safety of the oral fluoropyrimidine capecitabine with bolus 5-fluorouracil (5-FU)/leucovorin (LV; Mayo Clinic regimen) as adjuvant therapy for stage III colon cancer. A total of 1987 patients were enrolled at 164 centers worldwide. Disease-free survival (primary study endpoint) in the capecitabine arm was at least equivalent to that in the 5-FU/LV arm; the upper limit of the hazard ratio was significantly (P < 0.001) below the predefined margins for noninferiority. Capecitabine was also associated with significantly fewer fluoropyrimidine-related grade 3/4 adverse events (AEs; P < 0.001) and fewer AE-related hospital admissions/days than 5-FU/LV. Pharmacoeconomic analyses performed in several countries show that the savings in direct costs (drug administration and AE-related costs) associated with capecitabine versus 5-FU/LV offset the acquisition costs of the drug. Furthermore, capecitabine reduces patient travel time and costs, making it a "dominant" strategy (ie, less costly and more effective) in the adjuvant setting. In conclusion, efficacy, safety, convenience, and cost findings from the X-ACT trial show that capecitabine offers at least equivalent clinical benefit compared with bolus 5-FU/LV and can replace intravenous 5-FU/LV in the adjuvant treatment of stage III colon cancer. The X-ACT trial has not only helped to better define the role of capecitabine but has also broadened the options available to patients with early-stage disease to include a uniquely effective oral outpatient treatment.

  14. Hormone replacement therapy benefits meibomian gland dysfunction in perimenopausal women

    PubMed Central

    Jin, Xiuming; Lin, Zhenyun; Liu, Yufang; Lin, Lin; Zhu, Binbin

    2016-01-01

    Abstract Meibomian gland dysfunction (MGD) is believed to be the leading cause of dry eye (DE) disease worldwide. The connection between aging and MGD has long been recognized. However, few studies have addressed the relationship between MGD and hormone replacement therapy (HRT) in perimenopausal women, and not have examined the prevalence of MGD in perimenopausal women. The purpose of this study was to address and evaluate the possible relationship between MGD and HRT in perimenopausal women. The results suggest that perimenopausal women have a high prevalence of DE related to perimenopausal symptoms. The study also shows that perimenopausal women who use HRT can gain benefits for DE as well as for perimenopausal symptoms. Physicians caring for women who are experiencing DE related to perimenopausal symptoms should consider HRT. PMID:27495030

  15. Past, present, and future of hormonal therapy in recurrent endometrial cancer

    PubMed Central

    Carlson, Matthew J; Thiel, Kristina W; Leslie, Kimberly K

    2014-01-01

    Endometrial cancer is a heterogeneous disease. Type I cancers are hormonally driven, typically present with a low grade at an early stage, and are of endometrioid histology. These cancers are often cured by surgery, and the rate of recurrence is low. Type II cancers are less differentiated, often appear at a later stage, and are of serous, clear cell, or high grade endometrioid histology. The risk of recurrence in these cancers is much higher than with type I tumors. Isolated pelvic recurrences can be treated with radiation or exenteration, but systemic disease is fatal. It is in these recurrent patients, where prolongation of progression-free survival is the goal, that hormonal therapy can have the greatest benefit. In selected patients, hormonal therapy can be as effective as cytotoxic chemotherapy, without the toxicity and at a much lower cost. Here we review the evidence for treatment of patients suffering from recurrent endometrial cancer with hormonal therapy and explore avenues for the future of hormonal treatment of endometrial cancer. Currently, progesterone is the hormonal treatment of choice in these patients. Other drugs are also used, including selective estrogen receptor modulators, aromatase inhibitors, and gonadotropin-releasing hormone antagonists. Hormonal treatment of recurrent endometrial cancer relies on expression of the hormone receptors, which act as nuclear transcription factors. Tumors that express these receptors are the most sensitive to therapy; it is for this reason that patient selection is vitally important to the successful treatment of recurrent endometrial cancer with hormonal therapy. PMID:24833920

  16. Adjuvant Radiation Therapy Alone for HPV Related Oropharyngeal Cancers with High Risk Features

    PubMed Central

    Su, William; Liu, Jerry; Miles, Brett A.; Genden, Eric M.; Misiukiewicz, Krzysztof J.; Posner, Marshall; Gupta, Vishal; Bakst, Richard L.

    2016-01-01

    Background Current standard of care for oropharyngeal cancers with positive surgical margins and/or extracapsular extension is adjuvant chemoradiotherapy. It is unknown whether HPV+ oropharyngeal cancer benefits from this treatment intensification. Objective To investigate the outcomes of HPV+ patients treated with adjuvant radiotherapy alone when chemoradiotherapy was indicated based on high risk pathological features. They were compared with high risk HPV+ patients treated with adjuvant chemoradiotherapy. Methods All high risk HPV+ oropharyngeal cancer patients (9) who received radiotherapy alone were identified. We also identified 17 patients who received chemoradiotherapy as a comparison group. Median follow up time was 37.3 months. Results No local failures developed in adjuvant radiotherapy group. There was 1 distant recurrence in this cohort and 3 in CRT cohort. Regarding toxicity, 8 (47.1%) chemoradiotherapy patients had >10 lb. weight loss (p = 0.013), despite 75% of them having a percutaneous endoscopic gastrostomy tube placed. No individuals in radiotherapy group experienced a >10 lb. weight loss and none required a gastrostomy tube. Conclusions This series provides preliminary evidence suggesting that the omission of concurrent chemotherapy to adjuvant radiotherapy may offer comparative local control rates with a lower toxicity profile in the setting of HPV+ patients with traditional high risk features. PMID:27930732

  17. Sex hormones in postmenopausal women receiving low-dose hormone therapy: the effect of BMI.

    PubMed

    Lambrinoudaki, Irene; Armeni, Eleni; Rizos, Demetrios; Deligeoroglou, Eythimios; Kofinakos, Panagiotis; Kaparos, George; Alexandrou, Andreas; Creatsa, Maria; Logothetis, Emmanuel; Kouskouni, Evangelia

    2011-05-01

    The aim of our study was to evaluate the effect of BMI on the change in circulating sex hormone in postmenopausal women during 6 months of oral continuous combined low-dose hormone therapy (HT). Fifty postmenopausal women were allocated to receive daily one tablet containing combination of 17β-estradiol (1 mg)/norethindrone acetate (0.5 mg) for 6 months. Serum levels of follicle-stimulating hormone (FSH), estradiol, total testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), free estrogen index (FEI), Δ4-androstendione (Δ4A), and dehydroepiandrosterone sulfate were assessed at baseline and at the end of 6 months. Mean absolute values and percent changes from baseline were compared between lean and overweight women. Mean FSH decreased and mean 17β-estradiol increased significantly in both groups (FSH lean: 82.3 ± 26.7 decreased to 45.0 ± 17.0 mIU/ml, P = 0.0001; FSH overweight: 85.5 ± 22.1 decreased to 52.3 ± 23.8 mIU/ml, P = 0.003; P between groups = 0.661; E2 lean: 23.24 ± 12.55 increased to 53.62 ± 28.29 pg/ml, P = 0.006; E2 overweight: 24.17 ± 10.88 increased to 68.36 ± 53.99 pg/ml, P = 0.0001; P between groups = 0.619). Lean individuals had statistically significant higher increments of FAI and specifically FEI compared to overweight (FEI lean; 0.14 ± 0.09 increased to 0.29 ± 0.14, P = 0.009; overweight 0.23 ± 0.18 increased to 0.52 ± 0.40, P = 0.126; P between groups = 0.034). Although BMI does not affect total 17β-estradiol changes, free sex steroid concentrations increase more steeply in lean compared to overweight women receiving oral low-dose HT.

  18. Adjuvant Trastuzumab in HER2-Positive Early Breast Cancer by Age and Hormone Receptor Status: A Cost-Utility Analysis

    PubMed Central

    Leung, William; Kvizhinadze, Giorgi; Nair, Nisha; Blakely, Tony

    2016-01-01

    the same result. A key limitation was a lack of treatment-effect data by hormone receptor subtype. Heterogeneity was restricted to age and hormone receptor status; tumour size/grade heterogeneity could be explored in future work. Conclusions This study highlights how cost-effectiveness can vary greatly by heterogeneity in age and hormone receptor subtype. Resource allocation and licensing of subsidised therapies such as trastuzumab should consider demographic and clinical heterogeneity; there is currently a profound disconnect between how funding decisions are made (largely agnostic to heterogeneity) and the principles of personalised medicine. PMID:27504960

  19. Growth hormone replacement therapy reduces risk of cancer in adult with growth hormone deficiency: A meta-analysis

    PubMed Central

    Li, Zhanzhan; Zhou, Qin; Li, Yanyan; Fu, Jun; Huang, Xinqiong; Shen, Liangfang

    2016-01-01

    The risk of growth hormone on cancer in adult with growth hormone deficiency remains unclear. We carried out a meta-analysis to evaluate the risk of cancer in adult with and without growth hormone replacement therapy. We searched PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang databases up to 31 July 2016 for eligible studies. Pooled risk ratio (RR) with 95% confidence interval (CI) was calculated using fixed-or random-effects models if appropriate. The Newcastle-Ottawa Scale was used to assess the study quality. Two retrospective and seven prospective studies with a total of 11191 participants were included in the final analysis. The results from fixed-effects model showed this therapy was associated with the deceased risk of cancer in adult with growth hormone deficiency (RR=0.69, 95%CI: 0.59-0.82), with low heterogeneity within studies (I2=39.0%, P=0.108). We performed sensitivity analyses by sequentially omitting one study each time, and the pooled RRs did not materially change, indicating that our results were statistically stable. Begger's and Egger's tests suggested that there was no publication bias (Z=-0.63, P=0.520; t=0.16, P=0.874). Our study suggests that growth hormone replacement therapy could reduce risk of cancer in adult with growth hormone deficiency. PMID:27835910

  20. Locally Advanced Stage High-Grade Mucoepidermoid Carcinoma of Salivary Gland in a 9-Year-Old Girl: The Controversy of Adjuvant Therapy.

    PubMed

    Martínez, Olga Micol; Dorado, Elena Daghoum; García, María Dolores Amorós; Ramírez, María Isabel Oviedo; de la Fuente Muñoz, Isabel; Soler, Jose Luis Fuster

    2016-09-05

    Malignant salivary gland tumors are rare in children, mostly represented by low-grade mucoepidermoid carcinomas. For these patients, long-term survival rates above 95% are reported after surgical resection. Here we report a case of a 9-year-old girl with a high grade locally advanced mucoepidermoid carcinoma undergoing adjuvant radiotherapy and chemotherapy after surgery. We emphasize the controversy and lack of evidence-based indication for these highly toxic adjuvant therapy modalities in children.

  1. Locally Advanced Stage High-Grade Mucoepidermoid Carcinoma of Salivary Gland in a 9-Year-Old Girl: The Controversy of Adjuvant Therapy

    PubMed Central

    Martínez, Olga Micol; Dorado, Elena Daghoum; García, María Dolores Amorós; Ramírez, María Isabel Oviedo; de la Fuente Muñoz, Isabel; Soler, Jose Luis Fuster

    2016-01-01

    Malignant salivary gland tumors are rare in children, mostly represented by low-grade mucoepidermoid carcinomas. For these patients, long-term survival rates above 95% are reported after surgical resection. Here we report a case of a 9-year-old girl with a high grade locally advanced mucoepidermoid carcinoma undergoing adjuvant radiotherapy and chemotherapy after surgery. We emphasize the controversy and lack of evidence-based indication for these highly toxic adjuvant therapy modalities in children. PMID:27746885

  2. Gemcitabine-Based Combination Chemotherapy Followed by Radiation With Capecitabine as Adjuvant Therapy for Resected Pancreas Cancer

    SciTech Connect

    Desai, Sameer; Ben-Josef, Edgar; Griffith, Kent A.; Simeone, Diane; Greenson, Joel K.; Francis, Isaac R.; Hampton, Janet; Colletti, Lisa; Chang, Alfred E.; Lawrence, Theodore S.; Zalupski, Mark M.

    2009-12-01

    Purpose: To report outcomes for patients with resected pancreas cancer treated with an adjuvant regimen consisting of gemcitabine-based combination chemotherapy followed by capecitabine and radiation. Patients and Methods: We performed a retrospective review of a series of patients treated at a single institution with a common postoperative adjuvant program. Between January 2002 and August 2006, 43 resected pancreas cancer patients were offered treatment consisting of 4, 21-day cycles of gemcitabine 1 g/m{sup 2} intravenously over 30 min on Days 1 and 8, with either cisplatin 35 mg/m{sup 2} intravenously on Days 1 and 8 or capecitabine 1500 mg/m{sup 2} orally in divided doses on Days 1-14. After completion of combination chemotherapy, patients received a course of radiotherapy (54 Gy) with concurrent capecitabine (1330 mg/m{sup 2} orally in divided doses) day 1 to treatment completion. Results: Forty-one patients were treated. Median progression-free survival for the entire group was 21.7 months (95% confidence interval 13.9-34.5 months), and median overall survival was 45.9 months. In multivariate analysis a postoperative CA 19-9 level of >=180 U/mL predicted relapse and death. Toxicity was mild, with only two hospitalizations during adjuvant therapy. Conclusions: A postoperative adjuvant program using combination chemotherapy with gemcitabine and either cisplatin or capecitabine followed by radiotherapy with capecitabine is tolerable and efficacious and should be considered for Phase III testing in this group of patients.

  3. Elapsed time from breast cancer detection to first adjuvant therapy in a Canadian province, 1999–2000

    PubMed Central

    Rayson, Daniel; Chiasson, Darrell; Dewar, Ron

    2004-01-01

    Background A number of studies have examined time intervals between care steps in breast cancer diagnosis and treatment. The objective of this study was to document the elapsed time from first clinical or mammographic detection of breast abnormality to initiation of first adjuvant therapy in women with invasive breast cancer in Nova Scotia and to examine the effect of age, disease stage and place of residence on these intervals. Methods All dates were abstracted from patient charts and the Oncology Patient Information System. Eligible women were those with invasive breast cancer detected by Sept. 1, 1999, who were referred to 1 of 2 provincial cancer treatment centres by Sept. 1, 2000. All time intervals were calculated in days, and only patients experiencing both care events defining an interval were included in the analysis of time to event for that interval. We used proportional hazards regression analysis to evaluate the influence of patient age, disease stage and place of residence on times between care events. Results A total of 776 new diagnoses of breast cancer were reported to the Nova Scotia Cancer Registry over the study period. Of the 776, 467 met the inclusion criteria, and 364 patients were eligible for analysis. The overall median time from clinical or mammographic detection of breast cancer to initiation of first adjuvant therapy was 91 days (interquartile range 72–123 days). Disease stage was the strongest predictor of elapsed time: the median interval from disease detection to initiation of first adjuvant therapy for patients with stage I disease was 118 days, as compared with 85 days for those with stage II disease and 75 days for those with stage III disease (adjusted hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.6–2.8). Patients aged 70 years or more at diagnosis experienced longer elapsed times (median interval 98 days) than did younger patients (93 days for those aged 50–69 years and 82 days for those aged 49 years or less

  4. [Hormonal deficiencies in the elderly: is there a role for replacement therapy?].

    PubMed

    Racaru-Honciuc, Valentina; Betea, Daniela; Scheen, André J

    2014-08-27

    Biological aging is characterized by a progressive loss of the secretion of various hormones, a phenomenon that leads some physicians to propose an anti-aging hormonal therapy. It is mandatory to differentiate: 1) the physiological functional loss, which is a natural phenomenon without clear deleterious consequences on health and should not be compensated by the administration of hormones only to restore plasma levels similar to those measured in young people and 2) a pathological defect that deserves a replacement therapy to correct the endocrine deficiency and improve the health status of older individuals. This article considers the deficiencies in insulin, thyroid hormones, growth hormone, dehydroepiandrosterone (DHEA) and testosterone. For each hormone, a benefit/risk ratio of a so-called replacement therapy will be analyzed.

  5. Identification of high-risk factors as indicators for adjuvant therapy in stage II colon cancer patients treated at a single institution

    PubMed Central

    YAMAGUCHI, KEIZO; OGATA, YUTAKA; AKAGI, YOSHITO; SHIROUZU, KAZUO

    2013-01-01

    Although post-operative adjuvant chemotherapy (ACT) is only recommended for patients with stage II colon cancer who are at a high risk of recurrence, the definition of high risk remains unclear. The present study aimed to identify the risk factors for recurrence, which may also be indicators for adjuvant therapy, using a retrospective analysis of clinicopathological data obtained from stage II colon cancer patients who had undergone a curative resection. The present study also investigated the effects of ACT in patients who displayed the risk factors for recurrence. Univariate and multivariate analyses of the data collected from 377 stage II colon cancer patients, treated at Kurume University Hospital (Fukuoka, Japan) between 1982 and 2005, was conducted in order to determine and compare the risk factors for recurrence between the 163 patients who had undergone adjuvant therapy and the 214 patients who had not undergone adjuvant therapy. The risk factors for recurrence in patients who had not undergone adjuvant therapy were a serum carcinoembryonic antigen (CEA) level that was twice the cut-off value and pre-operative bowel obstruction. Adjuvant therapy provided no benefit to patients who presented with neither risk factor, but significantly decreased the recurrence rate in patients presenting with one or both risk factors. Based on these findings, serum CEA levels of twice the cut-off value and pre-operative bowel obstruction were proposed as indicators in the assessment for adjuvant chemotherapy following a curative resection for stage II colon cancer. These results warrant further clinical study of ACT in patients with one or both risk factors. PMID:24137386

  6. Breast cancer and post-menopausal hormone therapy.

    PubMed

    Kenemans, P; Bosman, A

    2003-03-01

    From the introduction of post-menopausal hormone replacement therapy (HRT) there has been great concern that HRT could possibly increase the risk of breast cancer. Prolonged exposure to endogenous oestrogens undeniably increases the risk of breast cancer. Questions that are important and until now only partly answered, are the following. Are oestrogens tumour promoters, as they induce mitosis, lead to proliferation and, therefore, accelerated growth of clinically occult pre-existing tumours? In addition to this, are they genotoxic mutagenic carcinogens, or could they initiate tumours by way of accumulation of incessant DNA-replication damage mechanism? Opinions vary as to the effect of the addition of a progestogen. There is a multitude of different progestogens which could bind with differing affinity to progesterone receptor PR-A or PR-B, and which have different physiological functions via differential gene regulation. The action of a progestogen on the oestrogen-induced cellular mitotic activity could be synergistic or antagonistic (by different pathways: oestrogen receptor downregulation, activating of metabolic pathways within the breast or stimulation of apoptosis)? Over 60 observational studies and two randomized trials provide evidence that the small but significant increase in risk appears with long-term current post-menopausal hormone use. The addition of a progestogen does not decrease the risk as seen with oestrogens alone and might increase the risk further. It is not clear whether there is a difference in risk with sequentially combined versus continuously combined HRT. Many questions nevertheless still remain. Is the risk increase limited to lean women only? What about risk-modifying factors such as alcohol use and a positive family history for breast cancer? Are tumours detected under HRT less aggressive, is there a better prognosis and is the mortality not increased while morbidity is? And is HRT contraindicated for women with a positive family

  7. Orthopedic complications related to growth hormone therapy in a pediatric population.

    PubMed

    Haidar, Rachid K; Nasrallah, Mona P; Der-Boghossian, Asdghig H; Ghanem, Ismat B

    2011-01-01

    Since the introduction of recombinant growth hormone, its use has diversified and multiplied. Growth hormone is now the recommended therapy for a growing indication to all forms of short stature because of its direct and indirect role on bone growth. Hereby, we discuss the orthopedic complications associated with growth hormone treatment in pediatric patients. These complications include carpal tunnel syndrome, Legg-Calve-Perthes' disease, scoliosis, and slipped capital femoral epiphysis. Their incidence rates recorded in several growth hormone therapy-related pharmacovigilance studies will be summarized in this study with focused discussion on their occurrence in the pediatric and adolescent age groups. The pathogenesis of these complications is also reviewed.

  8. Effect of combined hormonal and insulin therapy on the steroid hormone receptors and growth factors signalling in diabetic mice prostate

    PubMed Central

    Fávaro, Wagner J; Cagnon, Valéria H A

    2010-01-01

    Diabetes causes harmful effects on prostatic morphology and function. However, there still are doubts about the occurrence of various diseases in the prostate, as well as abnormal angiogenesis in relation to diabetes. Thus, the aim of this study was to correlate and quantify the level of the steroid hormone receptors and the angiogenic and antiangiogenic factors in non-obese diabetic mice (Nod) after combined hormonal and insulin therapy. Sixty mice were divided into six groups after 20 days of diabetes: the control group received 0.9% NaCl, as did the diabetic group. The diabetic-insulin group received insulin, the diabetic-testosterone group received testosterone cypionate, the diabetic-oestrogen group received 17β-oestradiol, and the diabetic-insulin–testosterone–oestrogen group received insulin, testosterone and oestrogen simultaneously. After 20 days, the ventral lobe was processed for immunocytochemical and hormonal analyses. The results showed that the lowest serum testosterone and androgen receptor levels were found in the diabetic group and the highest testosterone and androgen receptor levels in the diabetic-insulin–testosterone–oestrogen group. The serum oestrogen level and its receptor showed changes opposite to those of testosterone and its receptor. The endostatin reactivity was mainly decreased in diabetic mice. The greatest IGFR-1 and VEGF reactivities occurred in diabetic mice. Thus, diabetes led to the prostatic hormonal imbalance, affecting molecular dynamics and angiogenesis in this organ. Combined insulin and steroid hormone therapy partially restored the hormonal and angiogenic imbalance caused by diabetes. PMID:21039986

  9. Effect of combined hormonal and insulin therapy on the steroid hormone receptors and growth factors signalling in diabetic mice prostate.

    PubMed

    Fávaro, Wagner J; Cagnon, Valéria H A

    2010-12-01

    Diabetes causes harmful effects on prostatic morphology and function. However, there still are doubts about the occurrence of various diseases in the prostate, as well as abnormal angiogenesis in relation to diabetes. Thus, the aim of this study was to correlate and quantify the level of the steroid hormone receptors and the angiogenic and antiangiogenic factors in non-obese diabetic mice (Nod) after combined hormonal and insulin therapy. Sixty mice were divided into six groups after 20 days of diabetes: the control group received 0.9% NaCl, as did the diabetic group. The diabetic-insulin group received insulin, the diabetic-testosterone group received testosterone cypionate, the diabetic-oestrogen group received 17β-oestradiol, and the diabetic-insulin-testosterone-oestrogen group received insulin, testosterone and oestrogen simultaneously. After 20 days, the ventral lobe was processed for immunocytochemical and hormonal analyses. The results showed that the lowest serum testosterone and androgen receptor levels were found in the diabetic group and the highest testosterone and androgen receptor levels in the diabetic-insulin-testosterone-oestrogen group. The serum oestrogen level and its receptor showed changes opposite to those of testosterone and its receptor. The endostatin reactivity was mainly decreased in diabetic mice. The greatest IGFR-1 and VEGF reactivities occurred in diabetic mice. Thus, diabetes led to the prostatic hormonal imbalance, affecting molecular dynamics and angiogenesis in this organ. Combined insulin and steroid hormone therapy partially restored the hormonal and angiogenic imbalance caused by diabetes.

  10. The Impact of Adjuvant Radiation Therapy for High-Grade Gliomas by Histology in the United States Population

    SciTech Connect

    Rusthoven, Chad G.; Carlson, Julie A.; Waxweiler, Timothy V.; Dally, Miranda J.; Barón, Anna E.; Yeh, Norman; Gaspar, Laurie E.; Liu, Arthur K.; Ney, Douglas E.; Damek, Denise M.; Lillehei, Kevin O.; Kavanagh, Brian D.

    2014-11-15

    Purpose: To compare the survival impact of adjuvant external beam radiation therapy (RT) for malignant gliomas of glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and mixed anaplastic oligoastrocytoma (AOA) histology. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1998 to 2007 for patients aged ≥18 years with high-grade gliomas managed with upfront surgical resection, treated with and without adjuvant RT. Results: The primary analysis totaled 14,461 patients, with 12,115 cases of GBM (83.8%), 1312 AA (9.1%), 718 AO (4.9%), and 316 AOA (2.2%). On univariate analyses, adjuvant RT was associated with significantly improved overall survival (OS) for GBMs (2-year OS, 17% vs 7%, p<.001), AAs (5-year OS, 38% vs 24%, p<.001), and AOAs (5-year OS, 55% vs 44%, p=.026). No significant differences in OS were observed for AOs (5-year OS, with RT 50% vs 56% without RT, p=.277). In multivariate Cox proportional hazards models accounting for extent of resection, age, sex, race, year, marital status, and tumor registry, RT was associated with significantly improved OS for both GBMs (HR, 0.52; 95% CI, 0.50-0.55; P<.001) and AAs (HR, 0.57; 95% CI, 0.48-0.68; P<.001) but only a trend toward improved OS for AOAs (HR, 0.70; 95% CI, 0.45-1.09; P=.110). Due to the observation of nonproportional hazards, Cox regressions were not performed for AOs. A significant interaction was observed between the survival impact of RT and histology overall (interaction P<.001) and in a model limited to the anaplastic (WHO grade 3) histologies. (interaction P=.024), characterizing histology as a significant predictive factor for the impact of RT. Subgroup analyses demonstrated greater hazard reductions with RT among patients older than median age for both GBMs and AAs (all interaction P≤.001). No significant interactions were observed between RT and extent of resection. Identical patterns of significance were

  11. Benefit of adjuvant interferon alfa-2b (IFN-α) therapy in melanoma patients with high serum MMP-8 levels.

    PubMed

    Vihinen, Pia; Tervahartiala, Taina; Sorsa, Timo; Hansson, Johan; Bastholt, Lars; Aamdal, Steinar; Stierner, Ulrika; Pyrhönen, Seppo; Syrjänen, Kari; Lundin, Johan; Hernberg, Micaela

    2015-02-01

    Matrix metalloproteinases (MMPs) are important enzymes in tissue turnover and various inflammatory processes. In this study, it was evaluated whether serum MMP-8 can predict the response to adjuvant interferon alfa-2b (IFN-α) therapy in patients with operated high-risk cutaneous melanoma. Pre-treatment sera from 460 patients with stage IIB-IIIC melanoma were analyzed for MMP-8. The patients were randomized after surgery to adjuvant IFN-α for 12 or 24 months (n = 313) or observation only (n = 147). The median serum MMP-8 level was used to classify the patients into a low MMP-8 (n = 232) and a high MMP-8 (n = 228) group. In the high MMP-8 subgroup, IFN-α therapy significantly improved relapse-free survival (RFS). RFS was 36.8 months in patients with high MMP-8 levels receiving IFN-α therapy, whereas RFS for those with high MMP-8 levels with observation only was 10.6 months (P = 0.027). Median overall survival for patients with high MMP-8 and observation only was 36.7 versus 71.7 months in those receiving IFN-α (P = 0.13). In a multivariate model, IFN-α therapy was a significant predictor of favorable RFS (HR 0.74; 95 % CI 0.55-0.99; P = 0.048), after adjustment for pre-treatment MMP-8 (HR 1.17; 95 % CI 0.88-1.55; P = 0.28), gender (HR 1.16; 95 % CI 0.86-1.56; P = 0.32), age (HR 1.00; 95 % CI 1.00-1.02; P = 0.12), ulceration (HR 1.09; 95 % CI 0.81-1.46; P = 0.58), and the presence of node metastases (HR 1.36; 95 % CI 1.17-1.58; P < 0.0001). In conclusion, patients with high serum MMP-8 levels may benefit from adjuvant IFN-α therapy, but this observation should be further investigated.

  12. A case of Turner syndrome (46XXp-/45X) complicated with Crohn's disease after hormone therapy.

    PubMed

    Ihara, Yutaro; Hizawa, Kazuoki; Fujita, Kouhei; Iida, Masahiro; Washio, Ema; Kai, Takahiro; Nitahata, Tomoki; Esaki, Motohiro; Iida, Mitsuo

    2017-01-01

    A 19-year-old woman, who had been receiving hormone replacement therapy for 13 months before the diagnosis of mosaic Turner syndrome (46XXp-/45X), developed Crohn's colitis and erythema nodosum of the lower legs. Colonoscopy revealed an anal fistula and the presence of deep longitudinal ulcers with cobblestoning in the colorectum. Therapy with prednisolone and adalimumab was effective for the intestinal and skin lesions. To date, all seven case reports of Turner syndrome in Japan have also developed Crohn's disease after hormone therapy, suggesting a possible association of sex hormones in the pathogenesis.

  13. The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer.

    PubMed

    Lesiuk, Teresa

    2016-08-09

    Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attention and decreased negative mood and fatigue in women with breast cancer. This paper delineates the design and development of the mindfulness-based music therapy (MBMT) program implemented in that pilot study and includes clients' narrative journal responses. Conclusions and recommendations, including recommendation for further exploration of the function of music in mindfulness practice are provided.

  14. The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer

    PubMed Central

    Lesiuk, Teresa

    2016-01-01

    Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attention and decreased negative mood and fatigue in women with breast cancer. This paper delineates the design and development of the mindfulness-based music therapy (MBMT) program implemented in that pilot study and includes clients’ narrative journal responses. Conclusions and recommendations, including recommendation for further exploration of the function of music in mindfulness practice are provided. PMID:27517966

  15. Hormone replacement therapy and the prevention of postmenopausal osteoporosis.

    PubMed

    Gambacciani, Marco; Levancini, Marco

    2014-09-01

    Fracture prevention is one of the public health priorities worldwide. Estrogen deficiency is the major factor in the pathogenesis of postmenopausal osteoporosis, the most common metabolic bone disease. Different effective treatments for osteoporosis are available. Hormone replacement therapy (HRT) at different doses rapidly normalizes turnover, preserves bone mineral density (BMD) at all skeletal sites, leading to a significant, reduction in vertebral and non-vertebral fractures. Tibolone, a selective tissue estrogenic activity regulator (STEAR), is effective in the treatment of vasomotor symptoms, vaginal atrophy and prevention/treatment of osteoporosis with a clinical efficacy similar to that of conventional HRT. Selective estrogen receptor modulators (SERMs) such as raloxifene and bazedoxifene reduce turnover and maintain or increase vertebral and femoral BMD and reduce the risk of osteoporotic fractures. The combination of bazedoxifene and conjugated estrogens, defined as tissue selective estrogen complex (TSEC), is able to reduce climacteric symptoms, reduce bone turnover and preserve BMD. In conclusion, osteoporosis prevention can actually be considered as a major additional benefit in climacteric women who use HRT for treatment of climacteric symptoms. The use of a standard dose of HRT for osteoporosis prevention is based on biology, epidemiology, animal and preclinical data, observational studies and randomized, clinical trials. The antifracture effect of a lower dose HRT or TSEC is supported by the data on BMD and turnover, with compelling scientific evidence.

  16. Hormone Replacement Therapy and Risk for Neurodegenerative Diseases

    PubMed Central

    Dye, Richelin V.; Miller, Karen J.; Singer, Elyse J.; Levine, Andrew J.

    2012-01-01

    Over the past two decades, there has been a significant amount of research investigating the risks and benefits of hormone replacement therapy (HRT) with regards to neurodegenerative disease. Here, we review basic science studies, randomized clinical trials, and epidemiological studies, and discuss the putative neuroprotective effects of HRT in the context of Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and HIV-associated neurocognitive disorder. Findings to date suggest a reduced risk of Alzheimer's disease and improved cognitive functioning of postmenopausal women who use 17β-estradiol. With regards to Parkinson's disease, there is consistent evidence from basic science studies for a neuroprotective effect of 17β-estradiol; however, results of clinical and epidemiological studies are inconclusive at this time, and there is a paucity of research examining the association between HRT and Parkinson's-related neurocognitive impairment. Even less understood are the effects of HRT on risk for frontotemporal dementia and HIV-associated neurocognitive disorder. Limits to the existing research are discussed, along with proposed future directions for the investigation of HRT and neurodegenerative diseases. PMID:22548198

  17. Manufacturing heterosexuality: hormone replacement therapy and menopause in urban Oaxaca.

    PubMed

    Ramirez, Michelle

    2006-01-01

    For several decades, hormone replacement therapies have been prescribed to women, not only to prevent disease but to improve the sexual functioning of menopausal women. The medical promotion of continued sexual activity in a woman's post-reproductive years is exported to locations outside of North America and Europe, which provides an opportunity to critically examine the cultural roots that have informed expert biomedical representations. This ethnographic study examined menopause and social class in Oaxaca de Juarez, Mexico using interviews, questionnaires, and textual analysis. The research found that biomedicine in conjunction with the pharmaceutical industry promoted culturally constructed gender hierarchies under the guise of optimal menopausal health. However, women's actual experience of gender and sexuality in mid-life diverged significantly from these expert representations. Themes that emerged in interviews and questionnaires included the importance of motherhood in old age, diminished sexual desire as not problematic, and greater sexual freedom at a post-reproductive age. Ultimately, biomedical discourse was not the sole arbiter of appropriate menopausal womanhood and femininity.

  18. Phase 1 study on S-1 and oxaliplatin therapy as an adjuvant after hepatectomy for colorectal liver metastases.

    PubMed

    Takahashi, Michiro; Hasegawa, Kiyoshi; Oba, Masaru; Saiura, Akio; Arita, Junichi; Sakamoto, Yoshihiro; Shinozaki, Eiji; Mizunuma, Nobuyuki; Matsuyama, Yutaka; Kokudo, Norihiro

    2016-08-01

    of Background Data The effectiveness of adjuvant chemotherapy in patients with stage II/III colorectal cancer has been confirmed in various studies. However, no adjuvant chemotherapy for colorectal liver metastasis (CLM) classified to stage IV has been established. Objectives We conducted a phase 1 study of S-1 and oxaliplatin to determine the recommended dose (RD) in patients with CLM as adjuvant therapy in two institutes. Methods S-1 and oxaliplatin were administered from day 1 to day 14 of a 3-week cycle as a 2-h infusion every 3 weeks, respectively. The initial doses of S-1 and oxaliplatin were fixed to 80 mg/m(2) and 100 mg/m(2), respectively (level 1). We scheduled in the protocol a dose change of S-1 and oxaliplatin to level 2 (S-1: 80 mg/m(2) and oxaliplatin: 130 mg/m(2)) or level 0 (S-1: 65 mg/m(2) and oxaliplatin: 100 mg/m(2)) depending on the incidence of dose-limiting toxicity (DLT) at level 1 in six patients. Results Because DLT occurred in one among the initial six patients at level 1, the doses were increased to level 2 in the next six patients. At level 2, grade 3 leukopenia and neutropenia occurred in one (16.7 %) and two (33.3 %) patients, respectively, in the absence of non-hematological event. Because no DLT occurred at level 2, we suggest that the RD can be set to the level 2 dose. The median number of cycles delivered at RD was 8. The mean relative dose intensity of S-1 and oxaliplatin at RD was 0.90 and 0.63, respectively. Conclusion In a patient undergoing hepatectomy for CLM, 80 mg/m(2) of S-1 and 130 mg/m(2) of oxaliplatin are recommended as adjuvant therapy. A further study is required to confirm the efficacy and safety of this regimen on a larger scale.

  19. Linking Estrogen-Induced Apoptosis With Decreases in Mortality Following Long-term Adjuvant Tamoxifen Therapy

    PubMed Central

    2014-01-01

    The impressive first results of the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) and the adjuvant Tamoxifen To offer more (aTTom) trials both demonstrate that 10 years of tamoxifen is superior to five years of treatment. Tamoxifen is a nonsteroidal antiestrogen that blocks estrogen-stimulated tumor growth. Paradoxically, mortality decreases dramatically only in the decade after long-term tamoxifen is stopped. It is proposed that the evolution and clonal selection of micrometastases that acquire tamoxifen resistance now become increasingly vulnerable to endogenous estrogen-induced apoptosis. Laboratory and clinical studies confirm the concept, and supporting clinical evidence from the estrogen-alone trial in the Women’s Health Initiative (WHI), demonstrate that long-term estrogen-deprived women given exogenous physiologic estrogen have a decreased incidence of breast cancer and decreased mortality. It is proposed that a natural process of apoptosis is recruited to execute the long-term survival benefit of stopping ten years of adjuvant tamoxifen, but only after clonal selection of vulnerable breast cancer cells in an estrogen-deprived environment. PMID:25269699

  20. 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.

  1. 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.

  2. Thyroid hormone therapy and procurement of livers from brain-dead donors.

    PubMed

    Novitzky, Dimitri; Mi, Zhibao; Videla, Luis A; Collins, Joseph F; Cooper, David K C

    2016-08-01

    Hormonal therapy to brain-dead potential organ donors remains controversial. A retrospective study was carried out of hormonal therapy on procurement of organs in 63,593 donors in whom information on T3/T4 therapy was available. In 40,124 donors, T3/T4 and all other hormonal therapy was recorded. The percentages of all organs procured, except livers, were greater in T3/T4-treated donors. Nevertheless, if T3/T4 therapy had been administered to the donor, liver transplantation was associated with significantly increased graft and recipient survival at 1 month and 12 months. The potential reasons for the lack of effect of T3/T4 therapy on the number of livers procured are discussed.

  3. Role of chemotherapy in combination with hormonal therapy in first-line treatment of metastatic hormone-sensitive prostate cancer.

    PubMed

    Ceresoli, G L; De Vincenzo, F; Sauta, M G; Bonomi, M; Zucali, P A

    2015-12-01

    Prostate cancer (PC) is a heterogeneous disease, whose growth is driven by androgens and androgen receptors. Androgen deprivation therapy (ADT) is the standard treatment of hormone-naïve metastatic disease. The majority of patients are treated with medical castration with GnRH agonists or antagonists, which usually determines a profound PSA decline and a radiological and clinical benefit. However, essentially all patients experience progression to castration-resistant prostate cancer (CRPC), and overall prognosis remains disappointing. Early targeting of cells that survive hormonal therapy may potentially prevent the development of CRPC. Several trials have explored the use of combination therapy with ADT and chemotherapy, targeting both the androgen dependent and independent cells simultaneously. Docetaxel was administered in combination with ADT to men with hormone-naïve metastatic prostate cancer, in the attempt to improve the duration and quality of patient survival. Three large randomized trials (the GETUG-15, CHAARTED and more recently the STAMPEDE study) have assessed these endpoints, with partially conflicting results. Overall, the results from these trials seem to support the use of early docetaxel combined with ADT in selected hormone-naïve metastatic PC patients. Full publication of the results of all studies, with longer follow-up, and the results of other ongoing trials in this setting will hopefully further define the role and the indications of this therapeutic strategy.

  4. Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients

    PubMed Central

    Sawada, Yu; Yoshikawa, Toshiaki; Ofuji, Kazuya; Yoshimura, Mayuko; Tsuchiya, Nobuhiro; Takahashi, Mari; Nobuoka, Daisuke; Gotohda, Naoto; Takahashi, Shinichiro; Kato, Yuichiro; Konishi, Masaru; Kinoshita, Taira; Ikeda, Masafumi; Nakachi, Kohei; Yamazaki, Naoya; Mizuno, Shoichi; Takayama, Tadatoshi; Yamao, Kenji; Uesaka, Katsuhiko; Furuse, Junji; Endo, Itaru; Nakatsura, Tetsuya

    2016-01-01

    ABSTRACT The recurrence rates of Hepatocellular carcinoma (HCC) are high, necessitating novel and effective adjuvant therapies. Therefore, we conducted a phase II study of glypican-3 (GPC3) peptide vaccine as an adjuvant therapy for HCC patients. Forty-one patients with initial HCC who had undergone surgery or radiofrequency ablation (RFA) were analyzed in this phase II, open-label, single-arm trial. Ten vaccinations were performed for 1 y after curative treatment. We also investigated case-control subjects, where selected patients treated surgically during the same period were analyzed. The expression of GPC3 in the available primary tumors was determined by immunohistochemical analysis. Six patients received RFA therapy while 35 received surgery. The recurrence rate tended to be lower in the 35 patients treated with surgery plus vaccination compared to 33 patients who underwent surgery alone (28.6% vs. 54.3% and 39.4% vs. 54.5% at 1 and 2 y, respectively; p = 0.346, 0.983). Twenty-five patients treated with surgery and vaccination had GPC3-positive tumors; the recurrence rate in this group was significantly lower compared to that in 21 GPC3-positive patients who received surgery only (24% vs. 48% and 52.4% vs. 61.9% at 1 and 2 y, respectively; p = 0.047, 0.387). The GPC3 peptide vaccine improved the 1-y recurrence rate in patients with GPC3-positive tumors. This study demonstrated that GPC3 expression by the primary tumor may be used as a biomarker in a putative larger randomized clinical trial to determine the efficacy of the GPC3-derived peptide vaccine. PMID:27467945

  5. Prescription drug coverage: implications for hormonal therapy adherence in women diagnosed with breast cancer.

    PubMed

    Bradley, Cathy J; Dahman, Bassam; Jagsi, Reshma; Katz, Steven; Hawley, Sarah

    2015-11-01

    In spite of its demonstrated benefits, many women do not initiate hormonal therapy, and among those who do, many discontinue it prematurely. We examined whether differences in hormonal therapy adherence may be at least partially explained by the availability of prescription drug coverage. Women aged 20-79 years diagnosed with stage I-III breast cancer between June 2005 and February 2007 were enrolled in the study. Women completed a mailed survey, on average 9 months after diagnosis, and again approximately 4 years later (N = 712). Adjusted logistic regression was used to predict the likelihood of initiating hormonal therapy and hormonal therapy continuation. Women who had prescription drug coverage were more likely to initiate hormonal therapy relative to women without prescription drug coverage (OR 2.91, 95 % CI 1.24-6.84). Women with prescription drug coverage were also more likely to continue hormonal therapy (OR 2.23; 95 % CI 0.99-5.05, p = 0.0543). The lowest income women were also less likely to continue hormonal therapy relative to women with annual household income that exceeded $70,000 (OR 0.55; 95 % CI 0.29-1.04) with a borderline significance of (p = 0.08). This study demonstrates the critical role of prescription drug coverage in hormonal therapy initiation and continuation, independent of health insurance coverage. These findings add to the body of literature that addresses medication adherence. Financial factors must be considered along with behavioral factors that influence adherence, which is becoming increasingly relevant to oncology as treatments are shifted to oral medications, many of which are very expensive.

  6. Postmenopausal hormone therapy and the risk of breast cancer. A clinician's view.

    PubMed

    Speroff, Leon

    2004-09-24

    Reports from the Women's Health Initiative (WHI) and the Million Women Study have indicated that postmenopausal hormone therapy increases the risk of breast cancer. At this point in time, it is not certain whether these data reflect a small increase in risk or an impact of hormone therapy on pre-existing tumors. The purpose of this review is to provide an analysis of the epidemiologic data that can help the clinician inform patients and assist patients in their decision-making.

  7. Should Psychiatrists Prescribe Gender-Affirming Hormone Therapy to Transgender Adolescents?

    PubMed

    Crall, Cary S; Jackson, Rachel K

    2016-11-01

    Gender-affirming hormone therapy is a safe and effective way to improve quality of life and mental health outcomes for transgender adolescents. Access to this treatment is limited, with the most vulnerable transgender people experiencing the greatest gaps in care. Because some psychiatrists help transgender patients receive needed medical interventions, we analyze the ethical values they must balance when deciding whether to provide hormone therapy to patients who seek it.

  8. Postmenopausal hormone therapy is not associated with risk of all-cause dementia and Alzheimer's disease.

    PubMed

    O'Brien, Jacqueline; Jackson, John W; Grodstein, Francine; Blacker, Deborah; Weuve, Jennifer

    2014-01-01

    The relationship of postmenopausal hormone therapy with all-cause dementia and Alzheimer's disease dementia has been controversial. Given continued interest in the role of hormone therapy in chronic disease prevention and the emergence of more prospective studies, we conducted a systematic review to identify all epidemiologic studies meeting prespecified criteria reporting on postmenopausal hormone therapy use and risk of Alzheimer's disease or dementia. A systematic search of Medline and Embase through December 31, 2012, returned 15 articles meeting our criteria. Our meta-analysis of any versus never use did not support the hypothesis that hormone therapy reduces risk of Alzheimer's disease (summary estimate = 0.88, 95% confidence interval: 0.66, 1.16). Exclusion of trial findings did not change this estimate. There were not enough all-cause dementia results for a separate meta-analysis, but when we combined all-cause dementia results (n = 3) with Alzheimer's disease results (n = 7), the summary estimate remained null (summary estimate = 0.94, 95% confidence interval: 0.71, 1.26). The limited explorations of timing of use-both duration and early initiation-did not yield consistent findings. Our findings support current recommendations that hormone therapy should not be used for dementia prevention. We discuss trends in hormone therapy research that could explain our novel findings and highlight areas where additional data are needed.

  9. Predictors of Breast Discomfort among Women Initiating Menopausal Hormone Therapy

    PubMed Central

    Crandall, Carolyn J.; Markovic, Daniela; Huang, Mei-Hua; Greendale, Gail A.

    2009-01-01

    Objective To study the determinants of breast discomfort among postmenopausal women initiating menopausal hormone therapy (HT). Methods We analyzed questionnaire, anthropometric, and serum estrone data from the Postmenopausal Estrogen/Progestin Interventions Trial (PEPI), a randomized trial comparing placebo, conjugated equine estrogen (CEE) alone, or CEE with a progestogen (continuous or cyclical medroxyprogesterone acetate or cyclical micronized progesterone) among postmenopausal women. HT users could join PEPI after stopping HT for 2 months. We modeled the relation between smoking, body weight, alcohol consumption, age, quitting HT to join PEPI, physical activity and alpha-tocopherol consumption and new-onset breast discomfort at 12-month follow-up among 662 participants without baseline breast discomfort. Results The associations of new-onset breast discomfort with weight and with strenuous exercise varied by treatment assignment. Among women assigned to CEE + progestogen, strenuous exercise was associated with a 49% lower odds of new-onset breast discomfort (OR 0.51, 95% CI 0.29–0.89, P = 0.02), whereas among women assigned to placebo or CEE alone, strenuous exercise was not significantly associated with new-onset breast discomfort. Surprisingly, among women taking CEE alone, each kilogram higher weight was associated with 6% lower odds of new-onset breast discomfort (P=0.04), whereas among women taking placebo, the association was in the opposite direction (P=0.04). Adjustment for estrone level had neglible effects on odds ratios. Alpha-tocopherol intake, age, smoking, and alcohol intake were not significantly associated with new-onset breast discomfort in adjusted analyses. Conclusion Strenuous exercise and higher body weight may decrease the odds of new-onset breast discomfort among postmenopausal women initiating HT. PMID:20009961

  10. [Postmenopausal hormone replacement therapy and the cardiovascular system].

    PubMed

    Yildirir, Aylin

    2010-03-01

    Women suffer from cardiovascular diseases 10 years later than men, therefore female sex has been considered to be a 'protective factor'. However, the risk in women increases rapidly after menopause and the declining levels of endogenous estrogen is thought to be responsible. Postmenopausal hormone replacement therapy (HRT) decreases the severity and intensity of menopausal symptoms and improves women's quality of life. Until the last 10 years, based on the results of observational studies, postmenopausal HRT was thought to protect women against cardiovascular events and decrease the risk of coronary artery disease by 35-50%. However, recent randomized primary and secondary prevention trials did not support the cardioprotective effect of HRT. The different results of observational and randomized controlled trials are discussed to be related to the differences in the study population. The study population in observational and prospective cohort studies included relatively young women at the earlier stages of menopause, whereas studies showing neutral or negative effects of HRT included women older than 50 years old at least 10 years in menopause. Furthermore, the effects of estrogen depend on the state of vascular pathology. In relatively healthy vessels with no or early signs of atherosclerosis, estrogen prevent the development or progression of atherosclerotic lesions, whereas in the presence of established atherosclerotic lesions, estrogen promotes atherosclerosis or may even trigger acute events. Therefore, it is critically important to predict which women can safely receive HRT and which are at increased risk from HRT. Under the light of current knowledge, HRT should not be used for prevention from cardiovascular disease in postmenopausal women and the many other preventive strategies, (diet, exercise, blood pressure or cholesterol control) that are proven to be effective but underused, should be kept in mind.

  11. Hormonal therapy for endometriosis: from molecular research to bedside.

    PubMed

    Tosti, Claudia; Biscione, Antonella; Morgante, Giuseppe; Bifulco, Giuseppe; Luisi, Stefano; Petraglia, Felice

    2017-02-01

    Endometriotic lesions are associated with hormonal imbalance, including increased estrogen synthesis, metabolism and progesterone resistance. These hormonal changes cause increased proliferation, inflammation, pain and infertility. Hormonal imbalances are targets for treatment. Therapeutic strategies and innovations of hormonal drugs for endometriosis are increasing. Acting on estrogen receptors are hormonal drugs decreasing systemic and local estrogen synthesis (GnRH analogs, GnRH antagonists, Aromatase inhibitors) or estrogen activity (selective estrogen receptor modulators). The progesterone resistance is counteracted by progestins (Medroxyprogesterone acetate, Dienogest, Danazol, Levonorgestrel) or by Selective progesterone receptor modulators, a class of drugs under development. The future trend will be to define new drugs to use for prolonged period of time and with poor side effects considering endometriosis a chronic disease.

  12. Anti-tumor necrosis factor agent PEG-sTNFRI improves the growth hormone/insulin-like growth factor-I system in adjuvant-induced arthritic rats.

    PubMed

    Granado, Miriam; Priego, Teresa; Martín, Ana Isabel; Vara, Elena; López-Calderón, Asunción; Angeles Villanúa, María

    2006-04-24

    Adjuvant-induced arthritis is associated with body weight loss and decreased pituitary growth hormone (GH) and hepatic insulin-like growth factor-I (IGF-I) synthesis. Cytokines as tumor necrosis factor (TNF) mediate wasting associated with chronic inflammation. The aim of this study was to analyse whether the inhibition of TNF is able to revert the decrease in the body weight and the GH/IGF-I axis in arthritic rats. Male Wistar rats were injected with Freund's adjuvant, and 15 days later arthritic and control rats were daily injected with polyethylene glycol linked to soluble TNF receptor p55 (PEG-sTNFRI) (1 mg/kg, s.c.) or saline for 8 days. There was a significant decrease in pituitary GH mRNA (P<0.05), hepatic IGF-I mRNA (P<0.01) and serum concentrations of IGF-I (P<0.01) in arthritic rats. The 8-day administration of PEG-sTNFRI resulted in an increase in food intake (P<0.05) and body weight gain (P<0.01) in arthritic but not in control rats. There was an increase in pituitary GH mRNA after PEG-sTNFRI treatment both in control and in arthritic rats. There was a significant increase in IGF-I serum concentrations (P<0.05) and hepatic IGF-I mRNA expression (P<0.05) in control rats treated with PEG-sTNFRI, whereas the effect of this anti-TNF agent in arthritic rats was only statistically significant in hepatic IGF-I mRNA expression (P<0.05). These data suggest that TNF seems to be involved in the decrease in GH and IGF-I synthesis in arthritic rats.

  13. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

    SciTech Connect

    Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

    2015-07-01

    Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.

  14. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials

    PubMed Central

    Early Breast Cancer Trialists' Collaborative Group (EBCTCG)

    2011-01-01

    Summary Background As trials of 5 years of tamoxifen in early breast cancer mature, the relevance of hormone receptor measurements (and other patient characteristics) to long-term outcome can be assessed increasingly reliably. We report updated meta-analyses of the trials of 5 years of adjuvant tamoxifen. Methods We undertook a collaborative meta-analysis of individual patient data from 20 trials (n=21 457) in early breast cancer of about 5 years of tamoxifen versus no adjuvant tamoxifen, with about 80% compliance. Recurrence and death rate ratios (RRs) were from log-rank analyses by allocated treatment. Findings In oestrogen receptor (ER)-positive disease (n=10 645), allocation to about 5 years of tamoxifen substantially reduced recurrence rates throughout the first 10 years (RR 0·53 [SE 0·03] during years 0–4 and RR 0·68 [0·06] during years 5–9 [both 2p<0·00001]; but RR 0·97 [0·10] during years 10–14, suggesting no further gain or loss after year 10). Even in marginally ER-positive disease (10–19 fmol/mg cytosol protein) the recurrence reduction was substantial (RR 0·67 [0·08]). In ER-positive disease, the RR was approximately independent of progesterone receptor status (or level), age, nodal status, or use of chemotherapy. Breast cancer mortality was reduced by about a third throughout the first 15 years (RR 0·71 [0·05] during years 0–4, 0·66 [0·05] during years 5–9, and 0·68 [0·08] during years 10–14; p<0·0001 for extra mortality reduction during each separate time period). Overall non-breast-cancer mortality was little affected, despite small absolute increases in thromboembolic and uterine cancer mortality (both only in women older than 55 years), so all-cause mortality was substantially reduced. In ER-negative disease, tamoxifen had little or no effect on breast cancer recurrence or mortality. Interpretation 5 years of adjuvant tamoxifen safely reduces 15-year risks of breast cancer recurrence and death. ER status was the

  15. Functional Alteration of Tumor-infiltrating Myeloid Cells in RNA Adjuvant Therapy.

    PubMed

    Seya, Tsukasa; Shime, Hiroaki; Matsumoto, Misako

    2015-08-01

    Macrophages, as well as dendritic cells (DCs), are derived from myeloid progenitor cells. Recent evidence suggests that tumor-infiltrating macrophages differ in many aspects from conventional tissue macrophages, including nature, function and markers. Tumors usually contain various myeloid lineage cells in their non-parenchymal environment. In immunotherapy for cancer, tumor cells and non-parenchymal cells are exposed to tumor-associated antigens (TAA) and tumor-cell-derived nucleic acids. In addition, a dsRNA mimic, polyinosinic:polycytidylic acid (polyI:C), exhibits strong adjuvant activity, which acts both on the immune system and tumor constituents. Herein we discuss the RNA recognition system and unique cellular output in tumor-associated myeloid cells in response to immunotherapy. We especially focus on the mechanism by which RNA adjuvant alters the tumor-supportive nature of tumor-infiltrated myeloid cells to those with tumoricidal activity. We discuss how RNA administration makes tumor cells collapse and its significance of evoking cell death signals in tumor cells and macrophages. This knowledge will be applicable to the development of an alternative immunotherapy for cancer.

  16. Postoperative adjuvant combination therapy with doxorubicin and noncytotoxic suramin in dogs with appendicular osteosarcoma.

    PubMed

    Alvarez, Francisco J; Kisseberth, William; Hosoya, Kenji; Lara-Garcia, Ana; Kosarek, Carrie; Murahari, Sridhar; Au, Jessie L-S; Wientjes, M Guillaume; Couto, Jason; Couto, Guillermo

    2014-01-01

    Although conventional treatment of dogs with osteosarcoma (OSA) by amputation and chemotherapy results in reported survival times (STs) of 262-413 days, no major improvements in STs have occurred in the past 2 decades. Suramin is a polysulfonated napthylurea, which at noncytotoxic concentrations in vitro, increases tumor sensitivity to chemotherapy, including doxorubicin. The study authors evaluated the combination of noncytotoxic suramin and doxorubicin after amputation in dogs with OSA. The hypothesis was that treatment of dogs with appendicular OSA with amputation, adjuvant doxorubicin, and noncytotoxic suramin would be well tolerated and result in STs at least comparable to those of doxorubicin alone. Forty-seven dogs received 6.75 mg/kg of suramin IV followed by 30 mg/m(2) of doxorubicin IV 4 hr later. Treatment was repeated q 2 wk for five doses. The median disease free time (DFI) was 203 days (range, 42-1,580+ days) and the median ST for all dogs was 369 days (range, 92-1,616+ days). There was no statistical difference in ST and DFI between greyhounds and nonngreyhounds. Adjuvant doxorubicin and noncytotoxic suramin was well tolerated in dogs with OSA following amputation. Additional studies are needed to determine if this combination treatment protocol provides additional clinical benefit compared with doxorubicin alone.

  17. 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

  18. 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

  19. 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.

  20. Adjuvant pamidronate therapy prevents the development of bone metastases in breast cancer patients with four or more positive nodes.

    PubMed

    Kokufu, Ikuo; Kohno, Norio; Yamamoto, Masayuki; Takao, Shintaro

    2010-03-01

    Bisphosphonates are strongly efficacious in inhibiting osteoclast bone resorption and have beneficial effects on bone metastasis. Due to their mechanism of action, bisphosphonates are expected to prevent the development of bone metastases in breast cancer patients. Pamidronate is a potent inhibitor of osteoclast activity. We examined whether pamidronate was able to prevent the development of bone metastases in breast cancer patients at high risk for bone metastasis. Between 1997 and 2001, 90 patients with primary breast cancer with ≥4 positive nodes were assigned to receive 45 mg pamidronate 4 times every 2 weeks (33 patients) or standard follow-up (57 patients) based on patient self-preference. Patients underwent surgery and adjuvant therapy. The characteristics of the patients in the two groups were well-balanced. The median follow-up period was 5 years. Bone metastases were detected in 12.1% of patients in the pamidronate group and 40.4% in the control group (p=0.005). Distant metastases (36.4 vs. 56.1%, p=0.071) and non-osseous metastases (33.3 vs. 52.6%, p=0.077) were detected at a lower frequency in the pamidronate group. Thus, the rate of bone metastasis-free survival was significantly higher in the pamidronate group (85.9 vs. 64.0% at 5 years, p=0.023). Overall and disease-free survival rates did not differ between the two groups. In the pamidronate group, the incidence of bone metastases was significantly reduced and bone metastasis-free survival was significantly higher. Adjuvant pamidronate therapy therefore prevents the development of bone metastases in breast cancer patients with ≥4 positive nodes.

  1. A Systematic Review of the Effects of Hormone Therapy on Psychological Functioning and Quality of Life in Transgender Individuals

    PubMed Central

    White Hughto, Jaclyn M.; Reisner, Sari L.

    2016-01-01

    Objectives To review evidence from prospective cohort studies of the relationship between hormone therapy and changes in psychological functioning and quality of life in transgender individuals accessing hormone therapy over time. Data Sources MEDLINE, PsycINFO, and PubMed were searched for relevant studies from inception to November 2014. Reference lists of included studies were hand searched. Results Three uncontrolled prospective cohort studies, enrolling 247 transgender adults (180 male-to-female [MTF], 67 female-to-male [FTM]) initiating hormone therapy for the treatment of gender identity disorder (prior diagnostic term for gender dysphoria), were identified. The studies measured exposure to hormone therapy and subsequent changes in mental health (e.g., depression, anxiety) and quality of life outcomes at follow-up. Two studies showed a significant improvement in psychological functioning at 3–6 months and 12 months compared with baseline after initiating hormone therapy. The third study showed improvements in quality of life outcomes 12 months after initiating hormone therapy for FTM and MTF participants; however, only MTF participants showed a statistically significant increase in general quality of life after initiating hormone therapy. Conclusions Hormone therapy interventions to improve the mental health and quality of life in transgender people with gender dysphoria have not been evaluated in controlled trials. Low quality evidence suggests that hormone therapy may lead to improvements in psychological functioning. Prospective controlled trials are needed to investigate the effects of hormone therapy on the mental health of transgender people. PMID:27595141

  2. Postmenopausal hormone replacement therapy and risk of acute pancreatitis: a prospective cohort study

    PubMed Central

    Oskarsson, Viktor; Orsini, Nicola; Sadr-Azodi, Omid; Wolk, Alicja

    2014-01-01

    Background: Several case reports have suggested that women’s use of exogenous sex hormones is associated with acute pancreatitis; however, relevant epidemiologic data are sparse. We examined the association between postmenopausal hormone replacement therapy and risk of acute pancreatitis. Methods: We conducted a prospective study involving 31 494 postmenopausal women (aged 48–83 yr) from the population-based Swedish Mammography Cohort. Participants completed a baseline questionnaire in 1997 assessing their use of hormone replacement therapy. We linked the cohort to the hospital-based Swedish National Patient Register to determine hospital admissions for acute pancreatitis through 2010. Relative risks (RRs) were calculated using Cox proportional hazard models. Results: Over a total follow-up of 389 456 person-years, we identified 237 cases of incident acute pancreatitis. The age-standardized incidence rates per 100 000 person-years were 71 cases among women who had ever used hormone replacement therapy and 52 cases among women who had never used such hormones. Among ever users of hormone replacement therapy, the multivariable-adjusted RR of acute pancreatitis was 1.57 (95% confidence interval [CI] 1.20–2.05) compared with never users. The risk did not differ by current or past use, but it seemed to be higher among women who used systemic therapy (RR 1.92, 95% CI 1.38–2.66) and among those with duration of therapy of more than 10 years (RR 1.87, 95% CI 1.11–3.17). Interpretation: Use of postmenopausal hormone replacement therapy was associated with increased risk of acute pancreatitis. Physicians should consider this potential increase in risk when prescribing such therapy. PMID:24468693

  3. The role of hormonal factors and endocrine therapy in ovarian cancer

    PubMed Central

    Sinacki, Marcin; Jassem, Jacek

    2013-01-01

    The efficacy of the second-line chemotherapy commonly used in both relapsed ovarian cancer patients and those with primary treatment failure remains unsatisfactory. This therapy has a small effect on survival, whereas associated toxicity may diminish the patient's quality of life. Hormonal factors play a role in ovarian tumorigenesis, and inhibition of the stimulating effects of estrogens may exert a clinical benefit. The role of hormonal therapy as a palliative therapeutic alternative for ovarian cancer remains undetermined. This modality may result in long-term stabilization of disease in individual patients and less frequently in tumor remission. In this article the role of hormonal factors and recent literature of various forms of hormonal therapy for ovarian cancer are presented. PMID:23788955

  4. [Decrease of labor absenteeism associated with hormone replacement therapy in postmenopausal women].

    PubMed

    Blümel, J E; Sáez, L; Roncagliolo, M E; Tacla, X; Brandt, A

    1995-08-01

    Absenteeism affects efficiency and costs of health care. Most of health workers are middle age women, whose climacteric symptoms may reduce their work capacity working at a public hospital in Santiago during 1992. Fifty-eight percent were postmenopausal and 34.8% of these were receiving hormone replacement therapy. Global absenteeism rate was 17.1 days/year. These figures were 14.8 days/year for premenopausal and 17.8 days/year for postmenopausal women (NS). Among the latter, those women receiving hormone replacement therapy had a significantly lower absenteeism rate (9.4 days/year compared to 20.4 days/year among those not receiving hormones). Osteoarticular diseases were responsible for 44.3% and psychiatric diseases for 18.1% of sick leaves. No differences in absenteeism were observed between different professional levels. We conclude that hormone replacement therapy is associated with a better working capacity in postmenopausal women.

  5. Effects of relaxin in a model of rat adjuvant-induced arthritis.

    PubMed

    Santora, Karen; Rasa, Cordelia; Visco, Denise; Steinetz, Bernard; Bagnell, Carol

    2005-05-01

    A reduction in the incidence and severity of rheumatoid arthritis is seen in pregnant women. Relaxin, a hormone of pregnancy, has been implicated in decreased immune responsiveness. Consequently, the effects of relaxin and estradiol valerate, alone or in combination, were assessed in the development of adjuvant-induced arthritis in the rat. Combination hormone therapy reduced adjuvant-induced paw inflammation. Radiographic analysis of the tarsal joints showed that estradiol valerate plus relaxin treatment minimized soft tissue damage and bone changes when compared to vehicle-treated arthritic controls. These results indicate that relaxin may be a factor in reducing inflammation during pregnancy.

  6. Stress hormone regulation: biological role and translation into therapy.

    PubMed

    Holsboer, Florian; Ising, Marcus

    2010-01-01

    Stress is defined as a state of perturbed homeostasis following endangerment that evokes manifold adaptive reactions, which are summarized as the stress response. In the case of mental stress, the adaptive response follows the perception of endangerment. Different peptides, steroids, and biogenic amines operate the stress response within the brain and also after they have been released into circulation. We focus in this review on the biological roles of corticosteroids, corticotrophin-releasing hormone (CRH), and arginine vasopressin (AVP), and we evaluate the effects of treatments directed against the actions of these hormones. CRH and AVP are the central drivers of the stress hormone system, but they also act as neuromodulators in the brain, affecting higher mental functions including emotion, cognition, and behavior. When released toward the pituitary, these central neuropeptides elicit corticotrophin into the periphery, which activates corticosteroid release from the adrenal cortex. These stress hormones are essential for the adequate adaptation to stress, but they can also evoke severe clinical conditions once persistently hypersecreted. Depression and anxiety disorders are prominent examples of stress-related disorders associated with an impaired regulation of stress hormones. We summarize the effects of drugs acting at specific targets of the stress hormone axis, and we discuss their potential use as next-generation antidepressant medications. Such treatments require the identification of patients that will optimally benefit from such specific interventions. These could be a first step into personalized medicine using treatments tailored to the specific pathology of the patients.

  7. Influence of definitive radiation therapy for primary breast cancer on ability to deliver adjuvant chemotherapy

    SciTech Connect

    Lippman, M.E.; Edwards, B.K.; Findlay, P.; Danforth, D.W. Jr.; MacDonald, H.; D'Angelo, T.; Gorrell, C.

    1986-01-01

    Primary radiotherapy as a means of managing stage I and II breast cancer is receiving increasing attention. In a prospectively randomized trial comparing modified radical mastectomy to lumpectomy followed by definitive radiotherapy, we evaluated whether radiotherapy has a deleterious effect on the ability to administer adjuvant doxorubicin and cyclophosphamide to patients with histologically positive axillary lymph nodes. All patients were treated with an identical regimen, and doses were escalated to the same degree until myelosuppression occurred. There were no significant differences in the amount of chemotherapy administered to either treatment group. Patients in both groups received approximately 100% of the predicted dose of doxorubicin and approximately 117% of the predicted dose of cyclophosphamide. At present, we have no evidence that there are differences in recurrence rates as a function of the quantity of drug received, although longer follow-up is required.

  8. Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach

    PubMed Central

    Jiang, Meng-jie; Weng, Shan-Shan; Cao, Ying; Li, Xiao-Fen; Wang, Liu-Hong; Xu, Jing-Hong; Yuan, Ying

    2015-01-01

    Abstract Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common. Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes. Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients. PMID:26356712

  9. A Critical Appraisal of Growth Hormone Therapy in Growth Hormone Deficiency and Turner Syndrome Patients in Turkey

    PubMed Central

    Yavaş Abalı, Zehra; Darendeliler, Feyza; Neyzi, Olcay

    2016-01-01

    Early detection of abnormal growth, identification of the underlying cause, and appropriate treatment of the medical condition is an important issue for children with short stature. Growth hormone (GH) therapy is widely used in GH-deficient children and also in non-GH-deficient short stature cases who have findings conforming to certain indications. Efficacy of GH therapy has been shown in a multitude of short- and long-term studies. Age at onset of GH therapy is the most important factor for a successful treatment outcome. Optimal dosing is also essential. The aim of this review was to focus on challenges in the early diagnosis and appropriate management of short stature due to GH deficiency (GHD) and Turner syndrome. These are the most frequent two indications for GH therapy in Turkey approved by the Ministry of Health for coverage by the national insurance system. PMID:27354120

  10. Combination therapies in adjuvant with topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    NASA Astrophysics Data System (ADS)

    Yang, Deng-Fu; Hsu, Yih-Chih

    2012-03-01

    In Taiwan, oral cancer has becomes the fastest growth male cancer disease due to the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people. In order to eliminate the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when ALA reached its peak level in the lesional epithelial cells after topical application of ALA gel. We found that ALA reached its peak level in precancerous lesions about 2.5 hrs after topical application of ALA gel. The cancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 150 J/cm2 using LED 635 nm fiber-guided light device. Visual examination demonstrated that adjuvant topical ALA -mediated PDT group has shown better therapeutic results in compared to those of non-adjuvant topical ALA-mediated PDT group for DMBA-induced hamster buccal pouch precancerous lesions.

  11. Postmenopausal hormone therapy and breast cancer: a clinician's message for patients.

    PubMed

    Speroff, Leon

    2004-08-01

    The Women's Health Initiative agrees with some but not all case-control and cohort studies that current use of postmenopausal estrogen-progestin therapy is associated with a small increase in the risk of breast cancer. It is not known whether this is because of new tumor growth or an effect of hormonal therapy on preexisting tumors. Many studies indicate that women who develop breast cancer while using postmenopausal hormone therapy have a reduced risk of dying from breast cancer; this is consistent with an effect on preexisting tumors so that tumors appear at a less virulent and aggressive stage.

  12. Breast Cancer Risk in Relation to the Interval Between Menopause and Starting Hormone Therapy

    PubMed Central

    Reeves, Gillian; Bull, Diana; Green, Jane

    2011-01-01

    Background Although breast cancer risk is greater in users of estrogen–progestin than estrogen-only formulations of menopausal hormonal therapy, reports on their effects have been somewhat inconsistent. We investigated whether the timing of these therapies affected breast cancer incidence. Methods A total of 1 129 025 postmenopausal UK women provided prospective information on hormonal therapy use and other factors relevant for breast cancer risk. We used Cox regression to estimate adjusted relative risks (RRs) of breast cancer in hormonal therapy users vs never users and calculated standardized incidence rates. All statistical tests were two-sided. Results During 4.05 million woman-years of follow-up, 15 759 incident breast cancers occurred, with 7107 in current users of hormonal therapy. Breast cancer incidence was increased in current users of hormonal therapy, returning to that of never users a few years after use had ceased. The relative risks for breast cancer in current users were greater if hormonal therapy was begun before or soon after menopause than after a longer gap (Pheterogeneity < .001, for both estrogen-only and estrogen-progestin formulations). Among current users of estrogen-only formulations, there was little or no increase in risk if use began 5 years or more after menopause (RR = 1.05, 95% confidence interval [CI] = 0.89 to 1.24), but risk was statistically significantly increased if use began before or less than 5 years after menopause (RR = 1.43, 95% CI = 1.35 to 1.51). A similar pattern was observed among current users of estrogen–progestin formulations (RR = 1.53, 95% CI = 1.38 to 1.70, and RR = 2.04, 95% CI = 1.95 to 2.14, respectively). At 50–59 years of age, annual standardized incidence rates for breast cancer were 0.30% (95% CI = 0.29% to 0.31%) among never users of hormone therapy and 0.43% (95% CI = 0.42% to 0.45%) and 0.61% (95% CI = 0.59% to 0.64%), respectively, among current users of estrogen-only and estrogen

  13. Impact of postmenopausal hormone therapy on cardiovascular events and cancer: pooled data from clinical trials.

    PubMed Central

    Hemminki, E.; McPherson, K.

    1997-01-01

    OBJECTIVE: To examine the incidence of cardiovascular diseases and cancer from published clinical trials that studied other outcomes of postmenopausal hormone therapy as some surveys have suggested that it may decrease the incidence of cardiovascular diseases and increase the incidence of hormone dependent cancers. DESIGN: Trials that compared hormone therapy with placebo, no therapy, or vitamins and minerals in comparable groups of postmenopausal women and reported cardiovascular or cancer outcomes were searched from the literature. SUBJECTS: 22 trials with 4124 women were identified. In each group, the numbers of women with cardiovascular and cancer events were summed and divided by the numbers of women originally allocated to the groups. RESULTS: Data on cardiovascular events and cancer were usually given incidentally, either as a reason for dropping out of a study or in a list of adverse effects. The calculated odds ratios for women taking hormones versus those not taking hormones was 1.39 (95% confidence interval 0.48 to 3.95) for cardiovascular events without pulmonary embolus and deep vein thrombosis and 1.64 (0.55 to 4.18) with them. It is unlikely that such results would have occurred if the true odds ratio were 0.7 or less. For cancers, the numbers of reported events were too low for a useful conclusion. CONCLUSIONS: The results of these pooled data do not support the notion that postmenopausal hormone therapy prevents cardiovascular events. PMID:9251544

  14. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use

    PubMed Central

    Lensing, Anthonie W. A.; Middeldorp, Saskia; Levi, Marcel; Beyer-Westendorf, Jan; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A.; Cohen, Alexander T.; Trajanovic, Mila; Gebel, Martin; Lam, Phuong; Wells, Philip S.; Prins, Martin H.

    2016-01-01

    Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an “unacceptable health risk” during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence densities in percentage per year were computed for the on and off estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy (on vs off) as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration. PMID:26696010

  15. Clinical evolution of mediastinitis in patients undergoing adjuvant hyperbaric oxygen therapy after coronary artery bypass surgery

    PubMed Central

    do Egito, Julyana Galvão Tabosa; Abboud, Cely Saad; de Oliveira, Aline Pâmela Vieira; Máximo, Carlos Alberto Gonçalves; Montenegro, Carolina Moreira; Amato, Vivian Lerner; Bammann, Roberto; Farsky, Pedro Silvio

    2013-01-01

    ABSTRACT Objective: To evaluate the use of hyperbaric oxygen therapy as an adjunctive treatment in mediastinitis after coronary artery bypass surgery. Methods: This is a retrospective descriptive study, performed between October 2010 and February 2012. Hyperbaric oxygen therapy was indicated in difficult clinical management cases despite antibiotic therapy. Results: We identified 18 patients with mediastinitis during the study period. Thirty three microorganisms were isolated, and polymicrobial infection was present in 11 cases. Enterobacteriaceae were the most prevalent pathogens and six were multi-resistant agents. There was only 1 hospital death, 7 months after the oxygen therapy caused by sepsis, unrelated to hyperbaric oxygen therapy. This treatment was well-tolerated. Conclusion: The initial data showed favorable clinical outcomes. PMID:24136762

  16. Cancer incidence attributable to the use of oral contraceptives and hormone therapy in Alberta in 2012

    PubMed Central

    Grevers, Xin; Grundy, Anne; Poirier, Abbey E.; Khandwala, Farah; Feldman, Matthew; Friedenreich, Christine M.; Brenner, Darren R.

    2016-01-01

    Background: Hormonal contraceptives and hormone replacement therapies are classified as carcinogenic to humans (group 1) by the International Agency for Research on Cancer. We sought to estimate the proportion and total number of cancers attributable to the use of oral contraceptives and hormone therapy in Alberta in 2012. Methods: Population attributable risks were used to estimate the proportion of attributable cases for each associated cancer site. Relative risk estimates were obtained from the most relevant and recent epidemiologic literature. Prevalences of the use of oral contraceptives and hormone therapy in Alberta were collected from Alberta's Tomorrow Project. Specific cancer incidence data were obtained from the Alberta Cancer Registry for the year 2012. Results: Overall, 6.3% of breast cancers (n = 135) diagnosed in Alberta in 2012 were estimated to be attributable to the use of oral contraceptives, and the exposure potentially prevented about 57.3% of endometrial cancers (n = 276) and 29.1% of ovarian cancers (n = 52). About 15.5% of breast cancers (n = 258) and 8.9% of ovarian cancers (n = 13) were estimated to be attributable to the use of hormone therapy, whereas 11.3% of endometrial cancers (n = 48) were possibly prevented by the exposure. Interpretation: Based on our estimates, oral contraceptive use resulted in a net protective effect among the cancer sites studied, thus reducing the cancer burden in Alberta in 2012. The use of hormone therapy was estimated to increase the cancer burden in the province, therefore the risk and benefit of hormone therapy should be carefully considered before use. PMID:28018891

  17. Hormonal therapy in the senescence: Prostatic microenvironment structure and adhesion molecules.

    PubMed

    Montico, Fábio; Hetzl, Amanda Cia; Cândido, Eduardo Marcelo; Fávaro, Wagner José; Cagnon, Valéria Helena Alves

    2011-08-01

    Hormonal replacement has been utilized to minimize the harmful effects of hormonal imbalance in elderly men. The development and progression of prostatic diseases and their relation to hormone therapy is still unclear. Thus, the aim herewith was to characterize the structure and dystroglycan molecule (DGs) reactivities in the ventral prostatic lobe from elderly rats submitted to steroid hormone replacement. Male rats (Sprague-Dawley) were divided into one Young group and six senile groups. The Young group (YNG) (4 months old) received peanut oil (5mL/kg, s.c.). The senile rats (10 months old) were submitted to the following treatments: Senile group (SEN) (5mL/kg peanut oil, s.c.); Testosterone group (TEST) (5mg/kg testosterone cipionate, s.c.); Estrogen group (EST) (25μg/kg 17β-estradiol, s.c.); Castrated group (CAS) (surgical castration); Castrated-Testosterone (CT) (surgical castration and treatment similar to TEST group); and Castrated-Estrogen (CE) (surgical castration and treatment similar to EST group). After 30 days treatment, blood samples were collected for hormonal analysis and ventral prostate samples were processed for light and transmission electron microscopies, morphometrical analysis, immunohistochemistry and Western Blotting. The results showed decreased serum testosterone levels in the senescence and increased testosterone and estrogen plasmatic levels after hormone administration in the TEST and EST groups, respectively, highlighting the therapy efficiency. Hypertrophied stroma and inflammatory cells were verified in the SEN group. After hormone replacement in the senescence or following castration, atrophic epithelium, epithelial cells with clear cytoplasmic halo around the nucleus, microacini and maintenance of hypertrophied stroma were seen. Decreased DG levels were verified in the senescence. After hormonal therapy, increased protein levels of these molecules were observed, especially in those groups which received estradiol. Thus, the

  18. 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

  19. 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.

  20. Indocyanine green (ICG) as a new adjuvant for the antimicrobial photo-dynamic therapy (aPDT) in dentistry

    NASA Astrophysics Data System (ADS)

    Meister, Joerg; Hopp, Michael; Schäfers, Johannes; Verbeek, Jonas; Kraus, Dominik; Frentzen, Matthias

    2014-02-01

    Clinical surveys show a continuous increase of antimicrobial resistance related to the frequency of the administrated medication. The antimicrobial photodynamic therapy (aPDT) is an effective adjuvant to reduce the need of antibiotics in dentistry, especially in periodontics. The antimicrobial effect of lightactivated photosensitizers in periodontics is demonstrated in clinical studies and case reports. Indocyanine green (ICG) as a new adjuvant shows the high potential of antiphlogistic and antimicrobial effects in combination with laser-light activation. In trying to answer the question of just how far the influence of temperature is acting on bacteria, this study was carried out. The influences of ICG at different concentrations (0.01 up to 1 mg/ml) in combination with a culture medium (brain-heart-infusion) and a bacteria culture (Streptococcus salivarius) at different optical densities (OD600 0.5 and 0.1) were investigated under laser-light activation. Laser activation was carried out with diode laser at 810 nm and two different power settings (100 mW/300 mW). The pulse repetition rate was 2 kHz. Taking account of the fiber diameter, distance and spot size on the sample surface, the applicated intensities were 6.2 and 18.7 W/cm2. Total irradiation time was 20 s for all meaurements. Transmitted laser power and temperature increase in the culture medium as well as in the bacteria culture were determined. Additionally the influence of ICG regarding bacterial growth and bactericidal effect was investigated in the bacteria culture without laser irradiation. Without laser, no bactericidal effect of ICG was observed. Only a bacteriostatic effect could be proved. In dependence of the ICG concentration and the applied intensities a temperature increase of ΔT up to 80°C was measured.

  1. Does Adjuvant Radiation Therapy Improve Outcomes In pT1-3N0 Oral Cavity Cancer With Tumor-Free Margins and Perineural Invasion?

    SciTech Connect

    Liao, C.-T.; Chang, J.T.-C.; Wang, H.-M.; Ng, S.-H.; Hsueh Chuen; Lee, L.-Y.; Lin, C.-H.

    2008-06-01

    Purpose: The criteria for administration of adjuvant radiation therapy (RT) in oral cavity squamous cell carcinoma (OSCC) remain controversial, and it is unclear whether patients with pT1-3N0 disease benefit from adjuvant radiation in the presence of free margins and perineural invasion. The goal of this report was to determine whether this group would benefit from adjuvant radiation therapy in terms of 5-year local control rate and overall survival rate. Methods and Materials: We retrospectively reviewed our case records from January 1996 to May 2005. In all, 460 pT1-3N0 OSCC patients had tumor-free margins, of whom 68 had perineural invasion. Postoperative adjuvant RT was performed in patients with pT4 tumors, positive lymph nodes, or close margins ({<=}4 mm). In addition, selected OSCC patients with large pT3 tumors or perineural invasion received postoperative adjuvant RT. Local control and overall survival rates were plotted by Kaplan-Meier analysis. Results: There were no significant differences in 5-year local control (p 0.1936) and overall survival (p = 0.5580) rates between patients with perineural invasion compared with those without. Among patients with perineural invasion, the addition of adjuvant radiotherapy did not significantly alter the 5-year local control rate (p = 0.3170) or the overall survival rate (p = 0.0935). Conclusion: Altogether, these data seem to indicate that radical surgical resection alone should be considered a sufficient treatment for OSCC patients with pT1-3N0 disease, even in the presence of perineural invasion.

  2. Adjuvant radiation therapy for bladder cancer: A dosimetric comparison of techniques

    SciTech Connect

    Baumann, Brian C.; Noa, Kate; Wileyto, E. Paul; Bekelman, Justin E.; Deville, Curtiland; Vapiwala, Neha; Kirk, Maura; Both, Stefan; Dolney, Derek; Kassaee, Ali; Christodouleas, John P.

    2015-01-01

    Trials of adjuvant radiation after cystectomy are under development. There are no studies comparing radiation techniques to inform trial design. This study assesses the effect on bowel and rectal dose of 3 different modalities treating 2 proposed alternative clinical target volumes (CTVs). Contours of the bowel, rectum, CTV-pelvic sidewall (common/internal/external iliac and obturator nodes), and CTV-comprehensive (CTV-pelvic sidewall plus cystectomy bed and presacral regions) were drawn on simulation images of 7 post-cystectomy patients. We optimized 3-dimensional conformal radiation (3-D), intensity-modulated radiation (IMRT), and single-field uniform dose (SFUD) scanning proton plans for each CTV. Mixed models regression was used to compare plans for bowel and rectal volumes exposed to 35% (V{sub 35%}), 65% (V{sub 65%}), and 95% (V{sub 95%}) of the prescribed dose. For any given treatment modality, treating the larger CTV-comprehensive volume compared with treating only the CTV-pelvic sidewall nodes significantly increased rectal dose (V{sub 35%} {sub rectum}, V{sub 65%} {sub rectum}, and V{sub 95%} {sub rectum}; p < 0.001 for all comparisons), but it did not produce significant differences in bowel dose (V{sub 95%} {sub bowel}, V{sub 65%} {sub bowel}, or V{sub 35%} {sub bowel}). The 3-D plans, compared with both the IMRT and the SFUD plans, had a significantly greater V{sub 65%} {sub bowel} and V{sub 95%} {sub bowel} for each proposed CTV (p < 0.001 for all comparisons). The effect of treatment modality on rectal dosimetry differed by CTV, but it generally favored the IMRT and the SFUD plans over the 3-D plans. Comparison of the IMRT plan vs the SFUD plan yielded mixed results with no consistent advantage for the SFUD plan over the IMRT plan. Targeting a CTV that spares the cystectomy bed and presacral region may marginally improve rectal toxicity but would not be expected to improve the bowel toxicity associated with any given modality of adjuvant radiation

  3. Adjuvant radiation therapy for bladder cancer: a dosimetric comparison of techniques.

    PubMed

    Baumann, Brian C; Noa, Kate; Wileyto, E Paul; Bekelman, Justin E; Deville, Curtiland; Vapiwala, Neha; Kirk, Maura; Both, Stefan; Dolney, Derek; Kassaee, Ali; Christodouleas, John P

    2015-01-01

    Trials of adjuvant radiation after cystectomy are under development. There are no studies comparing radiation techniques to inform trial design. This study assesses the effect on bowel and rectal dose of 3 different modalities treating 2 proposed alternative clinical target volumes (CTVs). Contours of the bowel, rectum, CTV-pelvic sidewall (common/internal/external iliac and obturator nodes), and CTV-comprehensive (CTV-pelvic sidewall plus cystectomy bed and presacral regions) were drawn on simulation images of 7 post-cystectomy patients. We optimized 3-dimensional conformal radiation (3-D), intensity-modulated radiation (IMRT), and single-field uniform dose (SFUD) scanning proton plans for each CTV. Mixed models regression was used to compare plans for bowel and rectal volumes exposed to 35% (V35%), 65% (V65%), and 95% (V95%) of the prescribed dose. For any given treatment modality, treating the larger CTV-comprehensive volume compared with treating only the CTV-pelvic sidewall nodes significantly increased rectal dose (V35% rectum, V65% rectum, and V95% rectum; p < 0.001 for all comparisons), but it did not produce significant differences in bowel dose (V95% bowel, V65% bowel, or V35% bowel). The 3-D plans, compared with both the IMRT and the SFUD plans, had a significantly greater V65% bowel and V95% bowel for each proposed CTV (p < 0.001 for all comparisons). The effect of treatment modality on rectal dosimetry differed by CTV, but it generally favored the IMRT and the SFUD plans over the 3-D plans. Comparison of the IMRT plan vs the SFUD plan yielded mixed results with no consistent advantage for the SFUD plan over the IMRT plan. Targeting a CTV that spares the cystectomy bed and presacral region may marginally improve rectal toxicity but would not be expected to improve the bowel toxicity associated with any given modality of adjuvant radiation. Using the IMRT or the SFUD plans instead of the 3-D conformal plan may improve both bowel and rectal toxicity.

  4. Massage Therapy for Reducing Stress Hormones and Enhancing Immune Function in Breast Cancer Survivors

    DTIC Science & Technology

    2003-08-01

    effects suggesting that like many other interventions (e.g., exercise, diet, etc), for therapy effects to persist, continued massage treatments may be...In this study massage and relaxation therapies were examined for women with early stages of breast cancer for 1) reducing anxiety and stress hormone...16). Women in the massage and relaxation therapies received 3-30 minute sessions a week for 5 weeks. On the first and last days of the 5-week study

  5. The Two Faces of Fractionated Photodynamic Therapy: Increasing Efficacy With Light Fractionation or Adjuvant Use of Fractional Laser Technology.

    PubMed

    Juhasz, Margit L W; Levin, Melissa K; Marmur, Ellen S

    2016-11-01

    "Fractionated photodynamic therapy (PDT)" is a new term being used by dermatologists to describe advances in PDT technology including fractionated light or the adjuvant use of fractional lasers. Although dermatologists have used PDT since the early 1990s for the treatment of photodamage and precancerous lesions, newer developments in technology have allowed for the treatment of non-melanoma skin cancers (NMSCs), in ammatory disorders, and even uses in the eld of anti-aging. Recent developments in fractionated light therapy have allowed for PDT with dark intervals and two-fold illumination schemes to increase cellular damage and apoptosis. Combining PDT with fractional laser technology has allowed for enhanced dermal penetration of topical photosensitizers including 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL), as well as increased ef cacy of treatment. These advances in PDT technology will allow for increased convenience, decreased treatment time, only one application of topical photosensitizer, and decreased cost to the patient and dermatologist. J Drugs Dermatol. 2016;15(11):1324-1328..

  6. New Natural Pigment Fraction Isolated from Saw Palmetto: Potential for Adjuvant Therapy of Hepatocellular Carcinoma

    PubMed Central

    Tan, Hor-Yue; Wang, Ning; Takahashi, Masao; Feng, Yigang; Li, Hongyun; Feng, Yibin

    2016-01-01

    For the first time, we discovered a small proportion of aqueous fraction from Saw Palmetto apart from the fatty acid-rich fraction exhibited pharmacological activity. Therefore, this study aims to explore the anti-tumor potential of red pigmented aqueous fraction of Saw Palmetto, NYG on human hepatocellular carcinoma and its possible targets. Subcutaneous xenograft and orthotopic implantation models of HCC were used to evaluate the tumor inhibitory effect of NYG. Human hepatocellular carcinoma (HCC) cell lines and human umbilical vein endothelial cells (HUVEC) were used as in vitro model. The mRNA expression was conducted by qPCR. Protein expression was monitored by immunoblotting and immunohistochemistry. Cell migration and blood vessel formation were determined by chamber assay and tube formation assay, respectively. Significant tumor inhibition of NYG in dose-dependent manner was observed on subcutaneous xenograft and orthotopic HCC model. NYG has no direct action on cell viability or VEGF secretion of HCC cells. However, NYG reduced in vitro migration and vessel formation activities of HUVEC cells, as well as in vivo intratumoral neovascularization. NYG attenuated extracellular signal-regulated kinases (ERK) activation in endothelial cells, which may be associated with the suppression of migration and tube formation of HUVEC. NYG suppressed tumor expansion of HCC via inhibiting neovascularization, and may be potential adjuvant treatment for HCC. PMID:27527161

  7. New Natural Pigment Fraction Isolated from Saw Palmetto: Potential for Adjuvant Therapy of Hepatocellular Carcinoma.

    PubMed

    Tan, Hor-Yue; Wang, Ning; Takahashi, Masao; Feng, Yigang; Li, Hongyun; Feng, Yibin

    2016-08-05

    For the first time, we discovered a small proportion of aqueous fraction from Saw Palmetto apart from the fatty acid-rich fraction exhibited pharmacological activity. Therefore, this study aims to explore the anti-tumor potential of red pigmented aqueous fraction of Saw Palmetto, NYG on human hepatocellular carcinoma and its possible targets. Subcutaneous xenograft and orthotopic implantation models of HCC were used to evaluate the tumor inhibitory effect of NYG. Human hepatocellular carcinoma (HCC) cell lines and human umbilical vein endothelial cells (HUVEC) were used as in vitro model. The mRNA expression was conducted by qPCR. Protein expression was monitored by immunoblotting and immunohistochemistry. Cell migration and blood vessel formation were determined by chamber assay and tube formation assay, respectively. Significant tumor inhibition of NYG in dose-dependent manner was observed on subcutaneous xenograft and orthotopic HCC model. NYG has no direct action on cell viability or VEGF secretion of HCC cells. However, NYG reduced in vitro migration and vessel formation activities of HUVEC cells, as well as in vivo intratumoral neovascularization. NYG attenuated extracellular signal-regulated kinases (ERK) activation in endothelial cells, which may be associated with the suppression of migration and tube formation of HUVEC. NYG suppressed tumor expansion of HCC via inhibiting neovascularization, and may be potential adjuvant treatment for HCC.

  8. ω3 Polyunsaturated Fatty Acids as Immunomodulators in Colorectal Cancer: New Potential Role in Adjuvant Therapies

    PubMed Central

    Miccadei, Stefania; Masella, Roberta; Mileo, Anna Maria; Gessani, Sandra

    2016-01-01

    Diet composition may affect the onset and progression of chronic degenerative diseases, including cancer, whose pathogenesis relies on inflammatory processes. Growing evidence indicates that diet and its components critically contribute to human health, affecting the immune system, secretion of adipokines, and metabolic pathways. Colorectal cancer (CRC) is one of the leading causes of death worldwide. Antineoplastic drugs are widely used for CRC treatment, but drug resistance and/or off-target toxicity limit their efficacy. Dietary ω3 polyunsaturated fatty acids (PUFA) have been gaining great interest in recent years as possible anti-inflammatory and anticancer agents, especially in areas such as the large bowel, where the pro-inflammatory context promotes virtually all steps of colon carcinogenesis. Growing epidemiological, experimental, and clinical evidence suggests that ω3 PUFA may play a role in several stages of CRC management exhibiting antineoplastic activity against human CRC cells, improving the efficacy of radiation and chemotherapy, ameliorating cancer-associated secondary complications, and preventing CRC recurrence. These effects are most likely related to the immunomodulatory activities of ω3 PUFA that are able to influence several aspects of the inflammatory process ranging from inflammasome activation, leukocyte recruitment, production of immune mediators to differentiation, and activation of immune cells. In this review, we will focus on the potential use of ω3 PUFA as adjuvant agents together with chemo/radiotherapy, highlighting the immunomodulatory effects most likely responsible for their beneficial effects in different stages of CRC management. PMID:27895640

  9. Bone health management of Australian breast cancer survivors receiving hormonal therapy.

    PubMed

    Roberts, R; Miller, M; O'Callaghan, M; Koczwara, B

    2015-11-01

    Breast cancer survivors are at risk of bone loss due to hormonal treatment. We conducted a case note audit to investigate patterns of care and adherence to guidelines for initial management of risk of bone loss in 42 women receiving hormonal therapy. All those receiving aromatase inhibitors (n = 14) and 10 on tamoxifen had a bone density assessment. Eleven (26%) women had osteopenia and four (9.5%) osteoporosis. Management was variable and not always aligned with the guidelines.

  10. Hormone Replacement Therapy: MedlinePlus Health Topic

    MedlinePlus

    ... time in a woman's life when her period stops. It is a normal part of aging. In the years before and during menopause, the ... every six months. NIH: National Heart, Lung, and Blood Institute Start Here ... Menopause (Food and Drug Administration) Menopause and Hormones ( ...

  11. Comparative Efficacy and Safety of Adjuvant Letrozole Versus Anastrozole in Postmenopausal Patients With Hormone Receptor-Positive, Node-Positive Early Breast Cancer: Final Results of the Randomized Phase III Femara Versus Anastrozole Clinical Evaluation (FACE) Trial.

    PubMed

    Smith, Ian; Yardley, Denise; Burris, Howard; De Boer, Richard; Amadori, Dino; McIntyre, Kristi; Ejlertsen, Bent; Gnant, Michael; Jonat, Walter; Pritchard, Kathleen I; Dowsett, Mitch; Hart, Lowell; Poggio, Susan; Comarella, Lisa; Salomon, Herve; Wamil, Barbara; O'Shaughnessy, Joyce

    2017-04-01

    Purpose The Letrozole (Femara) Versus Anastrozole Clinical Evaluation (FACE) study compared the efficacy and safety of adjuvant letrozole versus anastrozole in postmenopausal patients with hormone receptor (HR) -positive and node-positive early breast cancer (eBC). Methods Postmenopausal women with HR-positive and node-positive eBC were randomly assigned to receive adjuvant therapy with either letrozole (2.5 mg) or anastrozole (1 mg) once per day for 5 years or until recurrence of disease. Patients were stratified on the basis of the number of lymph nodes and human epidermal growth factor receptor 2 status. The primary end point was 5-year disease-free survival (DFS), and the key secondary end points were overall survival and safety. Results A total of 4,136 patients were randomly assigned to receive either letrozole (n = 2,061) or anastrozole (n = 2,075). The final analysis was done at 709 DFS events (letrozole, 341 [16.5%]; anastrozole, 368 [17.7%]). The 5-year estimated DFS rate was 84.9% for letrozole versus 82.9% for anastrozole arm (hazard ratio, 0.93; 95% CI, 0.80 to 1.07; P = .3150). Exploratory analysis showed similar DFS with letrozole and anastrozole in all evaluated subgroups. The 5-year estimated overall survival rate was 89.9% for letrozole versus 89.2% for anastrozole arm (hazard ratio, 0.98; 95% CI, 0.82 to 1.17; P = .7916). Most common grade 3 to 4 adverse events (> 5% of patients) reported for letrozole versus anastrozole were arthralgia (3.9% v 3.3%, and 48.2% v 47.9% for all adverse events), hypertension (1.2% v 1.0%), hot flushes (0.8% v 0.4%), myalgia (0.8% v 0.7%), dyspnea (0.8% v 0.5%), and depression (0.8% v 0.6%). Conclusion Letrozole did not demonstrate significantly superior efficacy or safety compared with anastrozole in postmenopausal patients with HR-positive, node-positive eBC.

  12. The bifunctional role of steroid hormones: implications for therapy in prostate cancer.

    PubMed

    Mathew, Paul

    2014-05-01

    Ablation of the androgen-signaling axis is currently a dominant theme in developmental therapeutics in prostate cancer. Highly potent inhibitors of androgen biosynthesis and androgen receptor (AR) function have formally improved survival in castration-resistant metastatic disease. Resistance to androgen-ablative strategies arises through diverse mechanisms. Strategies to preserve and extend the success of hormonal therapy while mitigating the emergence of resistance have long been of interest. In preclinical models, intermittent hormonal ablative strategies delay the emergence of resistant stem-cell-driven phenotypes, but clinical studies in hormone-naive disease have not observed more than noninferiority over continual androgen ablation. In castration-resistant disease, response and improvement in subjective quality of life with therapeutic testosterone has been observed, but so too has symptomatic and life-threatening disease acceleration. The multifunctional and paradoxical role of steroid hormones in regulating proliferation and differentiation, as well as cell death, requires deeper understanding. The lack of molecular biomarkers that predict the outcome of hormone supplementation in a particular clinical context remains an obstacle to individualized therapy. Biphasic patterns of response to hormones are identifiable in vitro, and endocrine-regulated neoplasms that proliferate after prolonged periods of hormone deprivation appear preferentially sex steroid-suppressible. This review examines the relevance of a translational framework for studying therapeutic androgens in prostate cancer.

  13. Adjuvant Therapy for Resected Gastric Cancer-Rapid, Yet Incomplete Adoption Following Results of Intergroup 0116 Trial

    SciTech Connect

    Coburn, Natalie G. Guller, Ulrich; Baxter, Nancy N.; Kiss, Alex; Ringash, Jolie; Swallow, Carol J.; Law, Calvin H.L.

    2008-03-15

    Purpose: The Southwest Oncology Group/Intergroup 0116 (INT-0116) trial showed that adjuvant chemoradiotherapy improves survival in high-risk gastric adenocarcinoma patients. This study examined the adoption of adjuvant treatment following the trial results and the factors associated with its use. Methods and Materials: Between 1996 and 2003, patients aged 18-85 years with resected gastric adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results (SEER) database and classified as diagnosed before (January 1996 to April 2000) or after (May 2000 to December 2003) presentation of the INT-0116 trial findings. Univariate and multivariable models were used to determine the factors associated with use of adjuvant radiotherapy (RT). Results: Of 10,230 patients studied, 14.6% were given adjuvant RT before the INT-0116 trial, increasing to 30.4% afterward (p < 0.001). Significant increases in adjuvant RT from before to after INT-0116 were seen in all demographic categories. Younger patients were significantly more likely to receive adjuvant RT (44.5%, 18-59 years; 31.0%, 60-74 years; and 12.6%, 75-85 years, p < 0.0001). Married patients were significantly more likely to receive adjuvant RT (30.9%) than were unmarried patients (23.6%, p < 0.001). A greater depth of tumor invasion, worse nodal status, and more lymph nodes assessed were associated with adjuvant RT (p < 0.0001). The rate of adjuvant RT varied from 22.9-44.2% across SEER regions. On multiple logistic regression analysis, age, SEER region, marital status, assessed lymph nodes, tumor depth, and nodal status were all significant independent predictors of the use of adjuvant RT. Conclusion: Use of adjuvant RT doubled after the INT-0116 trial results became public; however, the fraction of patients receiving adjuvant RT is still low. Additional examination of the statistically significant and clinically relevant variability between different SEER regions, tumor characteristics, and patient

  14. The selection of hormonal therapy in prostate cancer: who, when, and for how long?

    PubMed

    Ryan, Charles J; Small, Eric J

    2004-05-01

    Androgen deprivation is the foundation for the systemic therapy of advanced prostate cancer. Multiple trials have tested combined androgen blockade versus androgen deprivation alone in patients with advanced disease. These studies suggest a slight advantage to the combined approaches that contain flutamide and bicalutamide, but the lack of dramatic differences in outcome makes monotherapy reasonable, especially in patients with more indolent disease. Intermittent androgen deprivation is an alternative that may allow patients to reduce the total time on androgen suppression as well as possibly delay the onset of androgen independence. A number of secondary hormonal therapies, including deferred and secondary antiandrogens, ketoconazole, and estrogens have shown modest response proportions. Patients with less advanced disease such as a rising prostate-specific antigen have varied outcomes, and no standard approach exists. In this group, noncastrating forms of hormonal therapy are being evaluated. Patients undergoing definitive local therapy who have high-risk features may benefit from early, as opposed to deferred, androgen deprivation. This review examines the evidence for the current state of the art in hormonal therapy in patients with prostate cancer and focuses, in particular, on treatment composition and timing as well as the rationale for the use of hormonal therapy in early stage disease.

  15. Adjuvant therapy of Dukes' C colon cancer by intra-arterial P-32 colloid for internal radiation therapy of the liver

    SciTech Connect

    Grady, E.D.

    1984-09-01

    To prevent probable occult metastatic liver cancer from progressing to clinical disease, the author used internal radiation therapy as an effective adjuvant to surgical excision of primary Dukes' C colonic cancer. A calculated radiation dose of 5000 rads was delivered to the liver by injecting radioactive 32-P chromic phosphate colloid through the superior mesenteric and celiac arteries. When this was done, the colloid passed through the intestines and was mixed thoroughly with the blood and delivered to the liver by the portal vein. The Kupffer cells in the liver trapped the colloid, and a minimum amount passed through the liver and got into the general circulation. This kept the amount of colloid deposited in the bone marrow to a minimum. In a phase-I pilot study in which nine patients were treated, no serious side effects were noted. In eight patients, the liver has remained free of cancer for more than 1 year.

  16. BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received

    PubMed Central

    Dawson, S-J; Makretsov, N; Blows, F M; Driver, K E; Provenzano, E; Le Quesne, J; Baglietto, L; Severi, G; Giles, G G; McLean, C A; Callagy, G; Green, A R; Ellis, I; Gelmon, K; Turashvili, G; Leung, S; Aparicio, S; Huntsman, D; Caldas, C; Pharoah, P

    2010-01-01

    Background: Breast cancer is heterogeneous and the existing prognostic classifiers are limited in accuracy, leading to unnecessary treatment of numerous women. B-cell lymphoma 2 (BCL2), an antiapoptotic protein, has been proposed as a prognostic marker, but this effect is considered to relate to oestrogen receptor (ER) status. This study aimed to test the clinical validity of BCL2 as an independent prognostic marker. Methods: Five studies of 11 212 women with early-stage breast cancer were analysed. Individual patient data included tumour size, grade, lymph node status, endocrine therapy, chemotherapy and mortality. BCL2, ER, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) levels were determined in all tumours. A Cox model incorporating the time-dependent effects of each variable was used to explore the prognostic significance of BCL2. Results: In univariate analysis, ER, PR and BCL2 positivity was associated with improved survival and HER2 positivity with inferior survival. For ER and PR this effect was time dependent, whereas for BCL2 and HER2 the effect persisted over time. In multivariate analysis, BCL2 positivity retained independent prognostic significance (hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.66–0.88, P<0.001). BCL2 was a powerful prognostic marker in ER− (HR 0.63, 95% CI 0.54–0.74, P<0.001) and ER+ disease (HR 0.56, 95% CI 0.48–0.65, P<0.001), and in HER2− (HR 0.55, 95% CI 0.49–0.61, P<0.001) and HER2+ disease (HR 0.70, 95% CI 0.57–0.85, P<0.001), irrespective of the type of adjuvant therapy received. Addition of BCL2 to the Adjuvant! Online prognostic model, for a subset of cases with a 10-year follow-up, improved the survival prediction (P=0.0039). Conclusions: BCL2 is an independent indicator of favourable prognosis for all types of early-stage breast cancer. This study establishes the rationale for introduction of BCL2 immunohistochemistry to improve prognostic stratification. Further work

  17. TERT promoter mutations contribute to IDH mutations in predicting differential responses to adjuvant therapies in WHO grade II and III diffuse gliomas.

    PubMed

    Zhang, Zhen-Yu; Chan, Aden Ka-Yin; Ding, Xiao-Jie; Qin, Zhi-Yong; Hong, Christopher S; Chen, Ling-Chao; Zhang, Xin; Zhao, Fang-Ping; Wang, Yin; Wang, Yang; Zhou, Liang-Fu; Zhuang, Zhengping; Ng, Ho-Keung; Yan, Hai; Yao, Yu; Mao, Ying

    2015-09-22

    IDH mutations frequently occur in WHO grade II and III diffuse gliomas and have favorable prognosis compared to wild-type tumors. However, whether IDH mutations in WHO grade II and II diffuse gliomas predict enhanced sensitivity to adjuvant radiation (RT) or chemotherapy (CHT) is still being debated. Recent studies have identified recurrent mutations in the promoter region of telomerase reverse transcriptase (TERT) in gliomas. We previously demonstrated that TERT promoter mutations may be promising biomarkers in glioma survival prognostication when combined with IDH mutations. This study analyzed IDH and TERT promoter mutations in 295 WHO grade II and III diffuse gliomas treated with or without adjuvant therapies to explore their impact on the sensitivity of tumors to genotoxic therapies. IDH mutations were found in 216 (73.2%) patients and TERT promoter mutations were found in 112 (38%) patients. In multivariate analysis, IDH mutations (p < 0.001) were independent prognostic factors for PFS and OS in patients receiving genotoxic therapies while TERT promoter mutations were not. In univariate analysis, IDH and TERT promoter mutations were not significant prognostic factors in patients who did not receive genotoxic therapies. Adjuvant RT and CHT were factors independently impacting PFS (RT p = 0.001, CHT p = 0.026) in IDH mutated WHO grade II and III diffuse gliomas but not in IDH wild-type group. Univariate and multivariate analyses demonstrated TERT promoter mutations further stratified IDH wild-type WHO grade II and III diffuse gliomas into two subgroups with different responses to genotoxic therapies. Adjuvant RT and CHT were significant parameters influencing PFS in the IDH wt/TERT mut subgroup (RT p = 0.015, CHT p = 0.015) but not in the IDH wt/TERT wt subgroup. Our data demonstrated that IDH mutated WHO grade II and III diffuse gliomas had better PFS and OS than their IDH wild-type counterparts when genotoxic therapies were administered after surgery

  18. A Hybrid Systems Approach to Hormonal Therapy of Prostate Cancer and its Nonlinear Dynamics

    SciTech Connect

    Aihara, Kazuyuki; Tanaka, Gouhei; Suzuki, Taiji; Hirata, Yoshito

    2007-07-13

    This talk is to review our recent work on mathematical modeling of prostate cancer and its application to hormonal therapy of intermittent androgen suppression. First, we model the tumor growth of prostate cancer composed of a mixed dynamical assembly of androgen-dependent and androgen-independent cancer cells. Then, we introduce the intermittent androgen suppression to the model as feedback control with monitoring the serum prostate-specific antigen, where the controlled model is described as a hybrid system with continuous and discrete variables. Next, we analyze nonlinear dynamics and bifurcations of the hybrid system. Finally, we discuss a possibility to improve the hormonal therapy.

  19. Hormone Therapy Plus Chemotherapy for Metastatic Prostate Cancer

    Cancer.gov

    A trial of androgen deprivation therapy (ADT) plus six cycles of docetaxel versus ADT alone found that after a median follow-up of nearly 29 months, median overall survival was 13.6 months longer with the combination therapy than with ADT alone.

  20. MRI in predicting the response of ovarian endometriomas to hormone therapy

    SciTech Connect

    Sugimura, Kazuro; Okizuka, Hiromi; Kaji, Yasushi

    1996-01-01

    Our goal was to investigate the usefulness of MRI in predicting the response of endometriomas to hormone therapy. MRI and laparoscopy at the onset of treatment and follow-up MRI after 6 months of hormone therapy were performed in 21 patients with 49 endometriomas. T1- and T2-weighted images were obtained with a 1.5 T apparatus using a body coil. The lesions were divided into a responder group and a nonresponder group according to whether the lesion size decreased by 50% or not. With MRI, shading was seen in 25 of 27 lesions (93%) from the nonresponder group, but in only 6 of 22 (27%) from the responder group. Low SI rim was seen in 59% of the responders and 89% of the nonresponders. Multiplicity in 68% of the responders and in 85% of the nonresponders and irregularity in 41% of the responders and in 78% of the nonresponders were shown. Multiple logistic analysis revealed shading was the most important factor in prediction of the response to hormone therapy. Shading was an important sign in evaluating the response of endometriomas to hormone therapy. MRI may assist in selecting the appropriate therapy for endometriomas. 16 refs., 3 figs., 2 tabs.

  1. Rapid enlargement of an intracranial germ cell tumor after gonadotropin hormone therapy.

    PubMed

    Sasagawa, Yasuo; Tachibana, Osamu; Nakagawa, Athushi; Nakada, Satoko; Nojima, Takayuki; Koya, Daisuke; Iizuka, Hideaki

    2016-09-01

    We report a case of an intracranial germ cell tumor (iGCT) that showed rapid enlargement after human chorionic gonadotropin (hCG) hormone therapy for pituitary hypogonadism. A 16-year-old boy presented with headache and was diagnosed with a suprasellar tumor. He was initially observed without surgery. Intranasal desmopressin therapy was started for central diabetes insipidus, but there was no change in the tumor size on MRI. The diagnosis of the tumor remained unknown for 4years. Levels of serum gonadotropin hormones (follicle-stimulating and luteinizing hormone) and testosterone progressively decreased, and the patient developed pituitary hypogonadism and complained about his undeveloped beard, lack of underarm hair, and erectile dysfunction. Intramuscular gonadotropin injection (hCG 5000U×2/week) was started at age 20. Eight months after the first gonadotropin injection, the MRI showed tumor growth with vivid enhancement. Craniotomy was performed and the tumor was partially resected. The histological diagnosis was immature teratoma. After surgery, the patient was treated with 5 cycles of chemotherapy with carboplatin and etoposide. He also received radiation therapy of 50Gy (20Gy tumor bed and 30Gy whole ventricles) to the residual tumor, after which the tumor decreased in size. We postulate that iGCT may be at risk of progression during hCG hormone therapy. Thus, careful monitoring is required for a patient with iGCT who receives this therapy.

  2. Replacement therapy: arginine vasopressin (AVP), growth hormone (GH), cortisol, thyroxine, testosterone and estrogen.

    PubMed

    Mitchell, D H; Owens, B

    1996-06-01

    Replacement therapy is routinely used to treat hormone deficiencies of patients who have had surgery or radiation therapy that damages the hypothalamus or pituitary gland. Hormones commonly replaced include: arginine vasopressin (AVP), growth hormone (GH), cortisol, thyroxine (T4), testosterone and estrogen. AVP, synthesized in the hypothalamus, is stored in and released by the posterior lobe of the pituitary gland. GH is synthesized and released by the anterior pituitary gland. The other hormones are produced and released by target glands each of which is stimulated by a specific anterior pituitary hormone, which in turn is controlled by release of a specific hypothalamic hormone. Feedback control by a high circulating concentration of the target gland's hormone regulates hypothalamic hormone release. Deficiency of AVP, important for water balance in the body, is restored with the synthetic analogue, 1-desamino-8-D-arginine vasopressin (DDAVP); it is given as a nasal spray or by injection. GH is required for normal growth in the developing child; recombinant GH, produced in bacteria, is injected subcutaneously. Adrenocorticotropic hormone (ACTH) controls release of cortisol which is produced by the adrenal cortex and enables the body to cope with stress; cortisol is replaced with prednisolone given orally. Thyroid stimulating hormone (TSH) controls release of the thyroid hormones, T4 and triiodothyronine (T3), which promote growth and development, and regulate energy metabolism; for replacement of T4, oral synthetic L-thyroxine is given. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) control release of testosterone, which promotes maturation of sperm and development of male sexual characteristics; replacement testosterone is administered intramuscularly. In females, FSH and LH control release of estrogens and progesterone which prepare the reproductive tract for release of the ovum, fertilization, implantation and development of the embryo

  3. Hormones

    MedlinePlus

    ... affect many different processes, including Growth and development Metabolism - how your body gets energy from the foods you eat Sexual function Reproduction Mood Endocrine glands, which are special groups of cells, make hormones. The major endocrine glands are the ...

  4. Long-term hormone therapy for perimenopausal and postmenopausal women.

    PubMed

    Marjoribanks, Jane; Farquhar, Cindy; Roberts, Helen; Lethaby, Anne; Lee, Jasmine

    2017-01-17

    BACKGROUND: Hormone therapy (HT) is widely provided for control of menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005. OBJECTIVES: To assess effects of long-term HT (at least 1 year's duration) on mortality, cardiovascular outcomes, cancer, gallbladder disease, fracture and cognition in perimenopausal and postmenopausal women during and after cessation of treatment. SEARCH METHODS: We searched the following databases to September 2016: Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and PsycINFO. We searched the registers of ongoing trials and reference lists provided in previous studies and systematic reviews. SELECTION CRITERIA: We included randomised double-blinded studies of HT versus placebo, taken for at least 1 year by perimenopausal or postmenopausal women. HT included oestrogens, with or without progestogens, via the oral, transdermal, subcutaneous or intranasal route. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the quality of the evidence by using GRADE methods. MAIN RESULTS: We included 22 studies involving 43,637 women. We derived nearly 70% of the data from two well-conducted studies (HERS 1998; WHI 1998). Most participants were postmenopausal American women with at least some degree of comorbidity, and mean participant age in most studies was over 60 years. None of the studies focused on perimenopausal women.In relatively healthy postmenopausal women (i.e. generally fit, without overt disease), combined continuous HT increased the risk of a coronary event (after 1 year's use

  5. Expression of testicular androgen receptor in non-obstructive azoospermia and its change after hormonal therapy.

    PubMed

    Kato, Y; Shiraishi, K; Matsuyama, H

    2014-09-01

    Several trials aimed at improving the sperm retrieval from men with non-obstructive azoospermia (NOA) by optimizing intratesticular testosterone (ITT) have reported partial responses, however, an appropriate level of ITT has not been identified. In this study, we examined the expression of the testicular androgen receptor (AR) in NOA and investigated its correlation with clinical and pathological parameters. Expression of the testicular AR was investigated in 52 men with NOA and 22 men with obstructive azoospermia (OA). Twenty-two patients for whom sperm retrieval failed during microdissection testicular sperm extraction (micro-TESE) were enrolled in hormonal therapy using hCG with or without recombinant human follicle stimulating hormone (rhFSH) prior to a second micro-TESE. Sertoli cells were identified by vimentin immunostaining, and positivity in Sertoli cells was used as the AR index. AR immunostaining was robust in the nuclei of Sertoli cells [Sertoli cell androgen receptor (SCAR)] in both OA and NOA. The mean AR index in NOA was significantly higher than that in OA (p < 0.05). In NOA patients, there was no correlation between the AR index and the clinical parameters, whereas the AR index of early maturation arrest (MA) was significantly lower than that of Sertoli cell only, late MA and hypospermatogenesis (p < 0.05). A significant increase in the AR index after salvage hormonal therapy was shown, particularly when using rhFSH. The AR index in patients from whom spermatozoa could be retrieved at the second micro-TESE increased significantly after hormonal therapy. In human testes, the expression of AR is dominant in Sertoli cells, and the expression of SCAR is upregulated by FSH. Germ cell maturation, especially during spermatogonia to spermatocyte stage, has been shown to be SCAR-dependent. Taken together, the results indicate that SCAR elevation is closely associated with sperm retrieval after hormonal therapy and that FSH-based hormonal therapy is

  6. Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair

    PubMed Central

    Sánchez, Mikel; Garate, Ane; Delgado, Diego; Padilla, Sabino

    2017-01-01

    Therapies such as direct tension-free microsurgical repair or transplantation of a nerve autograft, are nowadays used to treat traumatic peripheral nerve injuries (PNI), focused on the enhancement of the intrinsic regenerative potential of injured axons. However, these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases, the functional recovery of nerve injuries is incomplete. Thus, new biomedical engineering strategies based on tissue engineering approaches through molecular intervention and scaffolding offer promising outcomes on the field. In this sense, evidence is accumulating in both, preclinical and clinical settings, indicating that platelet-rich plasma products, and fibrin scaffold obtained from this technology, hold an important therapeutic potential as a neuroprotective, neurogenic and neuroinflammatory therapeutic modulator system, as well as enhancing the sensory and motor functional nerve muscle unit recovery. PMID:28250739

  7. The management of intractable pain with adjuvant pulsed electromagnetic field therapy.

    PubMed

    Niezgoda, Jeffrey A; Hardin, Scott T; Kubat, Nicole; Acompanado, Jocelyn

    2014-05-01

    This case describes a 51-year-old woman who reported experiencing severe, constant pain, diffusely located in the region of her right mandible neck (primarily involving the mandible, lower right molars, the neck, the upper back, and the shoulder) during the course of several years. Surgical interventions (root canal, spinal fusion) were performed to address potential sources of pain. Despite these interventions, the patient reported severe pain after both surgeries, which persisted beyond the acute postoperative period. Additional pharmacological interventions and physical therapy were also attempted; nonetheless, the patient reported that pain remained severe and constant for approximately 2 years. On the basis of the patient's poor response to conventional treatments, a novel approach of botulinum toxin (BTX) injections was initiated. When pulsed electromagnetic field therapy was added, the need for BTX injections decreased, with the patient reporting a noticeable decrease in pain intensity and an improvement in quality of life measures. Currently, the patient continues to use pulsed electromagnetic field therapy regularly for pain management, which has allowed her to reduce the use of other interventions and avoid continued use of narcotic medications. Considering the need for multifaceted pain management approaches in the treatment of chronic pain, this case is relevant for wound care practitioners attending to patients with chronic postincisional wound pain because the outcome highlights the utility of a nonpharmacological, complementary pain management intervention for closed, yet persistently painful, postoperative wounds.

  8. Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

    DTIC Science & Technology

    2015-09-01

    1 Award Number: W81XWH-10-1-0699 TITLE: Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural...WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy 5a. CONTRACT NUMBER 5b...malignant pleural mesothelioma (MPM), and is a rational target for immunotherapy. We have developed a vaccine comprised of four WT1 heteroclitic

  9. Potential Role of Thymosin-α1 Adjuvant Therapy for Glioblastoma

    PubMed Central

    Sungarian, Arno; Cielo, Deus; Sampath, Prakash; Bowling, Nathaniel; Moskal, Peter; Wands, Jack R.; de la Monte, Suzanne M.

    2009-01-01

    Glioblastomas are high-grade, malignant CNS neoplasms that are nearly always fatal within 12 months of diagnosis. Immunotherapy using proinflammatory cytokines such as IL-2 or IL-12 may prolong survival with glioblastoma. Thymosin-α1 (Talpha1) is a thymic hormone and immunemodulator that increase IL-2 production and T-cell proliferation. We examined potential therapeutic effects of Talpha1 in experimental in vivo glioblastoma, and characterized Talpha1's anti-tumor effects in vitro. Rar 9L cells (104) were implanted into the right frontal lobe of adult Long Evans rats that were subsequently treated with vehicle, BCNU, Talpha1, or Talpha1+BCNU from postoperative day 6. Talpha1+BCNU significantly lowered tumor burdens, and increased cure rates. In vitro experiments demonstrated that Talpha1 had no direct effect on viability or mitochondrial function, and instead, it increased expression of pro-apoptosis genes, including FasL, FasR and TNFα-R1 (65.89%, 44.08%, and 22.18%, resp.), and increased 9L cell sensitivity to oxidative stress. Moreover, Talpha1 enhanced 9L cell sensitivity to both Granzyme B- and BCNU-mediated killing. The findings suggest that Talpha1 enhances BCNUmediated eradication of glioblastoma in vivo, and that Talpha1 mediates its effects by activating pro-apoptosis mechanisms, rendering neoplastic cells more sensitive to oxidative stress and immune-mediated killing by Granzyme B and chemotherapeutic agents. PMID:20111737

  10. Nomogram Prediction of Survival and Recurrence in Patients With Extrahepatic Bile Duct Cancer Undergoing Curative Resection Followed by Adjuvant Chemoradiation Therapy

    SciTech Connect

    Song, Changhoon; Kim, Kyubo; Chie, Eui Kyu; Kim, Jin Ho; Jang, Jin-Young; Kim, Sun Whe; Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue; Ha, Sung W.

    2013-11-01

    Purpose: To develop nomograms for predicting the overall survival (OS) and relapse-free survival (RFS) in patients with extrahepatic bile duct cancer undergoing adjuvant chemoradiation therapy after curative resection. Methods and Materials: From January 1995 through August 2006, a total of 166 consecutive patients underwent curative resection followed by adjuvant chemoradiation therapy. Multivariate analysis using Cox proportional hazards regression was performed, and this Cox model was used as the basis for the nomograms of OS and RFS. We calculated concordance indices of the constructed nomograms and American Joint Committee on Cancer (AJCC) staging system. Results: The OS rate at 2 years and 5 years was 60.8% and 42.5%, respectively, and the RFS rate at 2 years and 5 years was 52.5% and 38.2%, respectively. The model containing age, sex, tumor location, histologic differentiation, perineural invasion, and lymph node involvement was selected for nomograms. The bootstrap-corrected concordance index of the nomogram for OS and RFS was 0.63 and 0.62, respectively, and that of AJCC staging for OS and RFS was 0.50 and 0.52, respectively. Conclusions: We developed nomograms that predicted survival and recurrence better than AJCC staging. With caution, clinicians may use these nomograms as an adjunct to or substitute for AJCC staging for predicting an individual's prognosis and offering tailored adjuvant therapy.

  11. Estrogen receptor activation by tobacco smoke condensate in hormonal therapy-resistant breast cancer cells.

    PubMed

    Niwa, Toshifumi; Shinagawa, Yuri; Asari, Yosuke; Suzuki, Kanae; Takanobu, Junko; Gohno, Tatsuyuki; Yamaguchi, Yuri; Hayashi, Shin-Ichi

    2017-01-01

    The relationship between tobacco smoke and breast cancer incidence has been studied for many years, but the effect of smoking on hormonal therapy has not been previously reported. We investigated the effect of smoking on hormonal therapy by performing in vitro experiments. We first prepared tobacco smoke condensate (TSC) and examined its effect on estrogen receptor (ER) activity. The ER activity was analyzed using MCF-7-E10 cells into which the estrogen-responsive element (ERE)-green fluorescent protein (GFP) reporter gene had been stably introduced (GFP assay) and performing an ERE-luciferase assay. TSC significantly activated ERs, and upregulated its endogenous target genes. This activation was inhibited by fulvestrant but more weakly by tamoxifen. These results suggest that the activation mechanism may be different from that for estrogen. Furthermore, using E10 estrogen depletion-resistant cells (EDR cells) established as a hormonal therapy-resistant model showing estrogen-independent ER activity, ER activation and induction of ER target genes were significantly higher following TSC treatment than by estradiol (E2). These responses were much higher than those of the parental E10 cells. In addition, the phosphorylation status of signaling factors (ERK1/2, Akt) and ER in the E10-EDR cells treated with TSC increased. The gene expression profile induced by estrogenic effects of TSC was characterized by microarray analysis. The findings suggested that TSC activates ER by both ligand-dependent and -independent mechanisms. Although TSC constituents will be metabolized in vivo, breast cancer tissues might be exposed for a long period along with hormonal therapy. Tobacco smoke may have a possibility to interfere with hormonal therapy for breast cancer, which may have important implications for the management of therapy.

  12. An Intervention to Control Vasomotor Symptoms for Advanced PC Patients on Hormone Therapy

    DTIC Science & Technology

    2014-08-01

    gmail.com Student discounts are available on our Facebook page. Go to PosterPresentations.com and click on the FB icon. Androgen deprivation therapy (ADT...mountsinai.org 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT...NOTES 14. ABSTRACT Vasomotor Symptom (Hot Flashes) is a common side- effect of hormone therapy for prostate cancer survivors who experience a rising

  13. Chemotherapy, IL-12 gene therapy and combined adjuvant therapy of HPV 16-associated MHC class I-proficient and -deficient tumours.

    PubMed

    Indrová, Marie; Bieblová, Jana; Jandlová, Tána; Vonka, Vladimír; Pajtasz-Piasecka, Elzbieta; Reinis, Milan

    2006-01-01

    Moderately immunogenic HPV 16-associated murine tumour cell line mimicking human HPV 16-associated neoplasms TC-1 (MHC class I(+)) and its variants, TC-1/P3C10 and TC-1/A9, with a marked down-regulation of MHC I molecules, were used to examine the effect of local interleukin 12 (IL-12) gene therapy for the treatment of early tumour transplants and minimal residual tumour disease obtained after cytoreductive chemotherapy (CMRTD). Experiments were designed to examine whether down-regulation of MHC class I molecules plays a role during chemotherapy and gene therapy of early tumour transplants. It was found that peritumoral administration of IL-12-producing tumour cell vaccines (single dose, day 8 after tumour cell administration) inhibited the growth of both TC-1 (MHC class I positive) tumours and their MHC class I-deficient variants. To investigate the antitumour effects in a clinically relevant setting, IL-12 gene therapy was utilised for the treatment of minimal residual tumour disease after cytoreductive chemotherapy. Intra-peritoneal treatment of tumour-bearing mice with ifosfamide derivative, CBM-4A, produced a significant tumour-inhibitory effect. This treatment was followed by peritumoral s.c. administration of genetically modified TC-1 (MHC class I positive) or MK16/I/IIIABC (MHC class I negative) vaccines producing IL-12 (single dose, day 7 after chemotherapy) or with recombinant interleukin 12 (rIL-12) in two cycles of 5 daily doses (days 8-19) after chemotherapy. This combined therapy significantly inhibited the growth of TC-1 and TC-1/A9 (MHC class I-) tumours. When the combined therapy of TC-1 (MHC class I positive) tumours was followed by peritumoral administration of bone marrow dendritic cell (BMDC) vaccines, the IL-12-mediated inhibitory effect was significantly boosted. In the next set of experiments, the impacts of chemotherapy and IL-12 adjuvant therapy on MHC class I surface expression were assessed. Chemotherapy and gene therapy of tumours led

  14. Adjuvant Chemoradiation Therapy in Gastric Cancer: Critically Reviewing the Past and Visualizing the Next Step Forward

    PubMed Central

    Papadimitriou, Konstantinos; Antoniou, Georgios; Bronte, Giuseppe; Vassiliou, Vassilios; Papamichael, Demetris; Peeters, Marc; Kountourakis, Panteleimon

    2015-01-01

    Gastric cancer remains one of the most common malignancies worldwide. Despite the significant advances in surgical treatment and multimodality strategies, prognosis has modestly improved over the last two decades. Locoregional relapse remains one of the main issues and the combined chemoradiation treatment seems to be one of the preferred approaches. However, more than ten years after the hallmark INT-0116 trial, minimal progress has been made both in terms of effectiveness and toxicity. Moreover, new regimens added to combined therapy failed to prove favourable results. Herein, we attempt a thorough literature review comparing pros and cons of all relative studies and potential bias, targeting well-designed future approaches. PMID:26101524

  15. The future of postmenopausal hormone therapy: It's time to move forward.

    PubMed

    Speroff, Leon

    2007-05-20

    There are good reasons why the use of postmenopausal hormone therapy is at a contemporary low level. But an analysis of these factors provides explanations that offer a basis for appropriate and renewed use. A more optimistic position is supported by an up-to-date appraisal of clinical studies.

  16. An Intervention to Control Vasomotor Symptoms for Advanced PC Patients on Hormone Therapy

    DTIC Science & Technology

    2012-08-01

    2012 2. REPORT TYPE Annual 3. DATES COVERED 15 July 2011 – 14 July 2012 4. TITLE AND SUBTITLE An Intervention to Control Vasomotor Symptoms for...of Defense. We have also held three focus groups with prostate cancer patients undergoing hormone therapy and multiple research team meetings were

  17. Endometrial Hyperplasia Risk in Relation to Recent Use of Oral Contraceptives and Hormone Therapy

    PubMed Central

    Epplein, Meira; Reed, Susan D.; Voigt, Lynda F.; Newton, Katherine M.; Holt, Victoria L.; Weiss, Noel S.

    2008-01-01

    Purpose Examine the relationship between recent use of oral contraceptives and hormone therapy and endometrial hyperplasia (EH) risk. Methods Cases comprised women diagnosed with complex EH (n=289) or atypical EH (n=173) between 1985-2003. One age-matched control was selected for each case; excluded were women with a prior hysterectomy or diagnosis of EH or endometrial cancer. Hormone use in the six months prior to the date of the case’s first symptoms was ascertained using a pharmacy database and medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Results Three (1.1%) cases had used oral contraceptives, compared to sixteen (6.0%) controls (OR = 0.2, 95% CI: 0.0–0.6). Fifty-one (16.8%) cases had taken estrogen-only hormone therapy, in contrast to two (0.7%) controls (OR = 37.6, 95% CI: 8.8–160.0). The risk of EH among estrogen plus progestin hormone users did not differ from that of non-users (OR = 0.7, 95% CI: 0.4–1.1). Conclusions This study suggests that previous findings of the association of estrogen-only hormone therapy with increased risk of EH and the lack of an association between estrogen plus progestin hormone therapy and EH risk are likely to apply to both complex EH and atypical EH. Further examination of the association between oral contraceptives and EH, with greater numbers of OC users, is warranted. PMID:19064186

  18. Neo-adjuvant chemo(radio)therapy in gastric cancer: Current status and future perspectives

    PubMed Central

    Biondi, Alberto; Lirosi, Maria C; D’Ugo, Domenico; Fico, Valeria; Ricci, Riccardo; Santullo, Francesco; Rizzuto, Antonia; Cananzi, Ferdinando CM; Persiani, Roberto

    2015-01-01

    In the last 20 years, several clinical trials on neoadjuvant chemotherapy and chemo-radiotherapy as a therapeutic approach for locally advanced gastric cancer have been performed. Even if more data are necessary to define the roles of these approaches, the results of preoperative treatments in the combined treatment of gastric adenocarcinoma are encouraging because this approach has led to a higher rate of curative surgical resection. Owing to the results of most recent randomized phase III studies, neoadjuvant chemotherapy for locally advanced resectable gastric cancer has satisfied the determination of level I evidence. Remaining concerns pertain to the choice of the optimal therapy regimen, strict patient selection by accurate pre-operative staging, standardization of surgical procedures, and valid criteria for response evaluation. New well-designed trials will be necessary to find the best therapeutic approach in pre-operative settings and the best way to combine old-generation chemotherapeutic drugs with new-generation molecules. PMID:26690252

  19. Adjuvant Therapy in the Treatment of Complications Following Surgery for Hepatic Echinococcal Cysts

    SciTech Connect

    Haddad, Maurice C.; Huwaijah, Said H.; Mourad, Fadi H.; Sharara, Alaa I.; Al-Kutoubi, Aghiad O.

    2000-09-15

    Thirty-two patients had surgery for hepatic echinococcal cysts (HEC). Serious complications were observed in 16 patients (50%): cyst recurrence (n = 4), infected residual cyst cavity (n = 7), infected residual cyst cavity with biliary and duodenal fistulae (n = 2), recurrent biliary obstruction following open surgery for a ruptured HEC into the biliary tree (n = 2), delayed rupture of an HEC into the biliary tree following laparoscopic surgery with secondary biliary obstruction (n = 1). These major complications were successfully managed by percutaneous methods in 8 of 16 patients while antihelmintic therapy was sufficient in two patients with a small recurrent cyst and ERCP was used in one patient to relieve biliary obstruction. Surgery was required in two patients only. With a success rate of 87.5%, the nonsurgical approach is the preferred method for treating a post-surgical complication.

  20. Inferior Vena Cava Filter Placement during Pregnancy: An Adjuvant Option When Medical Therapy Fails

    PubMed Central

    Serrano, Fátima; Torres, Rita; Borges, Augusta

    2013-01-01

    The authors present a case of a 27-year-old multiparous woman, with multiple thrombophilia, whose pregnancy was complicated with deep venous thrombosis requiring placement of a vena cava filter. At 15th week of gestation, following an acute deep venous thrombosis of the right inferior limb, anticoagulant therapy with low-molecular-weight heparin (LMWH) was instituted without improvement in her clinical status. Subsequently, at 18 weeks of pregnancy, LMWH was switched to warfarin. At 30th week of gestation, the maintenance of high thrombotic risk was the premise for placement of an inferior vena cava filter for prophylaxis of pulmonary embolism during childbirth and postpartum. There were no complications and a vaginal delivery was accomplished at 37 weeks of gestation. Venal placement of inferior vena cava filters is an attractive option as prophylaxis for pulmonary embolism during pregnancy. PMID:23781361

  1. Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy

    PubMed Central

    Woolf, Eric C.; Syed, Nelofer; Scheck, Adrienne C.

    2016-01-01

    Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD). The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate (βHB) in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma. PMID:27899882

  2. Ozone therapy as an adjuvant for endondontic protocols: microbiological – ex vivo study and citotoxicity analyses

    PubMed Central

    NOGALES, Carlos Goes; FERREIRA, Marina Beloti; MONTEMOR, Antonio Fernando; RODRIGUES, Maria Filomena de Andrade; Lage-MARQUES, José Luiz; ANTONIAZZI, João Humberto

    2016-01-01

    ABSTRACT Objectives This study evaluated the antimicrobial efficacy of ozone therapy in teeth contaminated with Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus using a mono-species biofilm model. Parallel to this, the study aimed to evaluate the cytotoxicity of ozone for human gingival fibroblasts. Material and Methods: One hundred and eighty single-root teeth were contaminated with a mono-species biofilm of Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus. Groups were formed: Group I – control; Group II – standard protocol; Group III – standard protocol + ozone gas at 40 µg/mL; and Group IV – standard protocol + aqueous ozone at 8 µg/mL. In parallel, human gingival fibroblasts were submitted to the MTT test. Cells were plated, then ozone was applied as follows: Group I (control) – broth medium; Group II – aqueous ozone at 2 µg/mL; Group III – aqueous ozone at 5 µg/mL; and Group IV – aqueous ozone at 8 µg/mL. Data were submitted to the Kruskal Wallis test and Bonferroni post hoc analyses to assess microbiology and cytotoxicity, respectively (p<0.05%). Results The results revealed antimicrobial efficacy by Group IV with no CFU count. The cytotoxicity assay showed Groups III and IV to be the most aggressive, providing a decrease in cell viability at hour 0 from 100% to 77.3% and 68.6%, respectively. Such a decrease in cell viability was reverted, and after 72 hours Groups III and IV provided the greatest increase in cell viability, being statistically different from Groups I and II. Conclusion According to the applied methodology and the limitations of this study, it was possible to conclude that ozone therapy improved the decontamination of the root canal ex vivo. Ozone was toxic to the cells on first contact, but cell viability was recovered. Thus, these findings suggest that ozone might be useful to improve root canal results. PMID:28076466

  3. Luteinizing hormone-releasing hormone agonists in premenopausal hormone receptor-positive breast cancer.

    PubMed

    Tan, Sing-Huang; Wolff, Antonio C

    2007-02-01

    Ovarian function suppression for the treatment of premenopausal breast cancer was first used in the late 19th century. Traditionally, ovarian function suppression had been accomplished irreversibly via irradiation or surgery, but analogues of the luteinizing hormone-releasing hormone (LH-RH) have emerged as reliable and reversible agents for this purpose, especially the LH-RH agonists. Luteinizing hormone-releasing hormone antagonists are in earlier stages of development in breast cancer and are not currently in clinical use. Luteinizing hormonereleasing hormone agonists act by pituitary desensitization and receptor downregulation, thereby suppressing gonadotrophin release. Limited information is available comparing the efficacies of the depot preparations of various agonists, but pharmacodynamic studies have shown comparable suppressive capabilities on estradiol and luteinizing hormone. At present, only monthly goserelin is Food and Drug Administration-approved for the treatment of estrogen receptor-positive, premenopausal metastatic breast cancer in the United States. Luteinizing hormone-releasing hormone agonists have proven to be as effective as surgical oophorectomy in premenopausal advanced breast cancer. They offer similar outcomes compared with tamoxifen, but the endocrine combination appears to be more effective than LH-RH agonists alone. In the adjuvant setting, LH-RH agonists versus no therapy reduce the annual odds of recurrence and death in women aged>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). Outcomes of chemotherapy with or without LH-RH agonists are comparable, though a few trials favor the combination in young premenopausal women (aged<40 years). Adjuvant LH-RH agonists with or without tamoxifen might be as efficacious as tamoxifen alone

  4. Growth hormones therapy in immune response against Trypanosoma cruzi.

    PubMed

    Frare, Eduardo Osório; Santello, Fabricia Helena; Caetano, Leony Cristina; Caldeira, Jerri C; Toldo, Míriam Paula Alonso; Prado, José Clóvis do

    2010-04-01

    Growth hormone (GH) is an important hypophyseal hormone that is primarily involved in body growth and metabolism. In mammals, control of Trypanosoma cruzi parasitism during the acute phase of infection is considered to be critically dependent on direct macrophage activation by cytokines. To explore the possibility that GH might be effective in the treatment of Chagas' disease, we investigated its effects on the course of T. cruzi infection in rats, focusing our analyses on its influences on parasitemia, NO, TNF-alpha and IFN-gamma concentration and on histopathological alterations and parasite burden in heart tissue. T. cruzi-infected male Wistar rats were intraperitoneally treated with 5 ng/10 g body weight/day of GH. Animals treated with GH showed a significant reduction in the number of blood trypomastigotes during the acute phase of infection compared with untreated animals (P<0.05). For all experimental days (7, 14 and 21 post infection) of the acute phase, infected and GH treated animals reached higher concentrations of TNF-alpha, IFN-gamma and nitric oxide as compared to untreated and infected counterparts (P<0.05) Histopathological observations of heart tissue revealed that GH administration also resulted in fewer and smaller amastigote burdens, and less inflammatory infiltrate and tissue disorganization, indicating a reduced parasitism of this tissue. These results show that GH can be considered as an immunomodulator substance for controlling parasite replication and combined with the current drug used may represent in the future a new therapeutic tool to reduce the harmful effects of Chagas' disease.

  5. 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

  6. Durable response of glioblastoma to adjuvant therapy consisting of temozolomide and a weekly dose of AMD3100 (plerixafor), a CXCR4 inhibitor, together with lapatinib, metformin and niacinamide

    PubMed Central

    Rios, Adan; Hsu, Sigmund H.; Blanco, Angel; Buryanek, Jamie; Day, Arthur L.; McGuire, Mary F.; Brown, Robert E.

    2016-01-01

    Glioblastoma multiforme (GBM) is a CNS (central nervous system) malignancy with a low cure rate. Median time to progression after standard treatment is 7 months and median overall survival is 15 months [1]. Post-treatment vasculogenesis promoted by recruitment of bone marrow derived cells (BMDCs, CD11b+ myelomonocytes) is one of main mechanisms of GBM resistance to initial chemoradiotherapy treatment [2]. Local secretion of SDF-1, cognate ligand of BMDCs CXCR4 receptors attracts BMDCs to the post-radiation tumor site.[3]. This SDF-1 hypoxia-dependent effect can be blocked by AMD3100 (plerixafor) [4]. We report a GBM case treated after chemo- radiotherapy with plerixafor and a combination of an mTOR, a Sirt1 and an EGFRvIII inhibitor. After one year temozolomide and the EGFRvIII inhibitor were stopped. Plerixafor, and the MTOR and Sirt-1 inhibitors were continued. He is in clinical and radiologic remission 30 months from the initiation of his adjuvant treatment. To our knowledge, this is the first report of a patient treated for over two years with a CXCR4 inhibitor (plerixafor), as part of his adjuvant treatment. We believe there is sufficient experimental evidence to consider AMD3100 (plerixafor) part of the adjuvant treatment of GBM. Significance The adjuvant inhibition of GBM vasculogenesis(a process different from local angiogenesis) by specifically blocking the migration of BMDCs to the primary tumor site with inhibitors of the CXCR4/SDF-1 axis represents a potential novel therapeutic approach to GBM. There is significant pre-clinical evidence and validation for its use as demonstrated in a patient derived tumor xenograft model of GBM. Together with other specific anti-tumoral therapies, the active inhibition of vasculogenesis in the adjuvant treatment of GBM is deserving of further exploration. PMID:27489862

  7. 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.

  8. 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

  9. Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for Stage II or III breast cancer

    SciTech Connect

    Burstein, Harold J. . E-mail: hburstein@partners.org; Bellon, Jennifer R.; Galper, Sharon; Lu, H.-M.; Kuter, Irene; Wong, Julia; Gelman, Rebecca; Bunnell, Craig A.; Parker, Leroy M.; Garber, Judy E.; Winer, Eric P.; Harris, Jay R.; Powell, Simon N.

    2006-02-01

    Purpose: To evaluate the safety and feasibility of concurrent radiation therapy and paclitaxel-based adjuvant chemotherapy, given either weekly or every 3 weeks, after adjuvant doxorubicin and cyclophosphamide (AC). Methods and Materials: After definitive breast surgery and AC chemotherapy, 40 patients with operable Stage II or III breast cancer received protocol-based treatment with concurrent paclitaxel and radiation therapy. Paclitaxel was evaluated on 2 schedules, with treatment given either weekly x 12 weeks (60 mg/m{sup 2}), or every 3 weeks x 4 cycles (135-175 mg/m{sup 2}). Radiation fields and schedules were determined by the patient's surgery and pathology. The tolerability of concurrent therapy was evaluated in cohorts of 8 patients as a phase I study. Results: Weekly paclitaxel treatment at 60 mg/m{sup 2} per week with concurrent radiation led to dose-limiting toxicity in 4 of 16 patients (25%), including 3 who developed pneumonitis (either Grade 2 [1 patient] or Grade 3 [2 patients]) requiring steroids. Efforts to eliminate this toxicity in combination with weekly paclitaxel through treatment scheduling and CT-based radiotherapy simulation were not successful. By contrast, dose-limiting toxicity was not encountered among patients receiving concurrent radiation with paclitaxel given every 3 weeks at 135-175 mg/m{sup 2}. However, Grade 2 radiation pneumonitis not requiring steroid therapy was seen in 2 of 24 patients (8%) treated in such a fashion. Excessive radiation dermatitis was not observed with either paclitaxel schedule. Conclusions: Concurrent treatment with weekly paclitaxel and radiation therapy is not feasible after adjuvant AC chemotherapy for early-stage breast cancer. Concurrent treatment using a less frequent paclitaxel dosing schedule may be possible, but caution is warranted in light of the apparent possibility of pulmonary injury.

  10. Reimann's “Habitual Hyperthermia” Responding to Hormone Therapy

    PubMed Central

    Yang, Otto O.; Currier, Judith S.

    2016-01-01

    A 25-year-old woman presented with fever of unknown origin, exhibiting malaise and low-grade fevers in evenings. These fevers exhibited a pattern of starting mid-menstrual cycle with resolution around the onset of menses, matching a pattern of “habitual hyperthermia” reported by H. Reimann in the 1930s. Extensive workup was unremarkable, and the fevers improved on oral synthetic estrogen and progesterone therapy. PMID:27800522

  11. Growth hormone deficiency following radiation therapy of primary brain tumors in children.

    PubMed

    Kanev, P M; Lefebvre, J F; Mauseth, R S; Berger, M S

    1991-05-01

    The medical records of 123 patients treated for brain tumors at Children's Hospital and Medical Center, Seattle, Washington, between 1985 and 1987 were reviewed. The endocrinological complications of radiation therapy and the effectiveness of growth hormone (GH) replacement therapy were assessed. These were the first 2 years after synthetic GH became available. The disease pathology was confirmed at craniotomy or biopsy in 108 patients. Ninety-five children completed radiation therapy and 65 of these were alive at the time of review; these 65 children represent the study population. The most common tumor types were medulloblastoma, craniopharyngioma, and ependymoma. Endocrine evaluation was initiated with changes in the patients' growth velocity. Patient workup included skeletal x-ray films for determination of bone and analysis of thyroxin, thyroid-stimulating hormone, and somatomedin-C levels. Following 1-dopa and clonidine stimulation, provocative studies of GH levels were performed. Growth hormone failure and short stature were observed in 26 children, most commonly in the 2nd year after tumor treatment. Eight patients with GH failure were also hypothyroid. Hormone replacement therapy was initiated with recombinant GH, 0.05 mg/kg/day, and all children so treated showed an increase in height, with eight patients experiencing catch-up growth. There were no complications of therapy or tumor recurrence. Studies of baseline bone age and somatomedin-C levels on completion of radiation therapy are recommended. Comprehensive endocrine studies should follow changes in the patients' growth velocity. With early GH replacement, catch-up growth is possible and normal adult heights may be achieved.

  12. The probiotic Propionibacterium freudenreichii as a new adjuvant for TRAIL-based therapy in colorectal cancer

    PubMed Central

    Théret, Nathalie; Brenner, Catherine; Jouan, Elodie; Le Moigne-Muller, Gwénaëlle; Dimanche-Boitrel, Marie-Thérèse

    2016-01-01

    TNF-Related Apoptosis-Inducing Ligand (TRAIL) is a well-known apoptosis inducer, which activates the extrinsic death pathway. TRAIL is pro-apoptotic on colon cancer cells, while not cytotoxic towards normal healthy cells. However, its clinical use is limited by cell resistance to cell death which occurs in approximately 50% of cancer cells. Short Chain Fatty Acids (SCFA) are also known to specifically induce apoptosis of cancer cells. In accordance, we have shown that food grade dairy propionibacteria induce intrinsic apoptosis of colon cancer cells, via the production and release of SCFA (propionate and acetate) acting on mitochondria. Here, we investigated possible synergistic effect between Propionibacterium freudenreichii and TRAIL. Indeed, we hypothesized that acting on both extrinsic and intrinsic death pathways may exert a synergistic pro-apoptotic effect. Whole transcriptomic analysis demonstrated that propionibacterial supernatant or propionibacterial metabolites (propionate and acetate), in combination with TRAIL, increased pro-apoptotic gene expression (TRAIL-R2/DR5) and decreased anti-apoptotic gene expression (FLIP, XIAP) in HT29 human colon cancer cells. The revealed synergistic pro-apoptotic effect, depending on both death receptors (TRAIL-R1/DR4, TRAIL-R2/DR5) and caspases (caspase-8, -9 and -3) activation, was lethal on cancer cells but not on normal human intestinal epithelial cells (HIEC), and was inhibited by Bcl-2 expression. Finally, milk fermented by P. freudenreichii induced HT29 cells apoptosis and enhanced TRAIL cytotoxic activity, as did P. freudenreichii DMEM culture supernatants or its SCFA metabolites. These results open new perspectives for food grade P. freudenreichii-containing products in order to potentiate TRAIL-based cancer therapy in colorectal cancer. PMID:26771233

  13. [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

  14. 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

  15. Role of resection and adjuvant therapy in long-term disease outcomes for low-grade pediatric intramedullary spinal cord tumors.

    PubMed

    Ahmed, Raheel; Menezes, Arnold H; Torner, James C

    2016-11-01

    OBJECTIVE Surgical excision is the mainstay treatment for resectable low-grade intramedullary spinal cord tumors (IMSCTs) in the pediatric age group. Chemotherapy and radiation treatments are generally reserved for progressive or recurrent disease. Given the indolent nature of low-grade tumors and the potential side effects of these approaches, their long-term treatment benefits are unclear. The aim of the study was to determine long-term disease outcomes and the therapeutic roles of surgery and adjuvant therapies in pediatric patients with low-grade IMSCTs over an extended follow-up period. METHODS Case records for all pediatric patients (< 21 years of age) with a histopathological diagnosis of low-grade IMSCT were selected over a period from January 1975 to January 2010. Outcome variables including McCormick functional grade, overall survival (OS), and progression-free survival (PFS) were analyzed with respect to demographic and treatment variables. RESULTS Case records of 37 patients with low-grade IMSCTs were identified, with a mean follow-up duration of 12.3 ± 1.4 years (range 0.5-37.2 years). Low-grade astrocytomas were the most prevalent histological subtype (n = 22, 59%). Gross-total resection (GTR) was achieved in 38% of patients (n = 14). Fusion surgery was required in 62% of patients with pre- or postoperative deformity (10 of 16). On presentation, functional improvement was observed in 87% and 46% of patients in McCormick Grades I and II, respectively, and in 100%, 100%, and 75% in Grades III, IV, and V, respectively. Kaplan-Meier PFS rates were 63% at 5 years, 57% at 10 years, and 44% at 20 years. OS rates were 92% at 5 years, 80% at 10 years, and 65% at 20 years. On multivariate analysis, shunt placement (hazard ratio [HR] 0.33, p = 0.01) correlated with disease progression. There was a trend toward improved 5-year PFS in patients who received adjuvant chemotherapy and radiation therapy (RT; 55%) compared with those who did not (36%). Patients who

  16. Long-Term Results After High-Dose Radiotherapy and Adjuvant Hormones in Prostate Cancer: How Curable Is High-Risk Disease?

    SciTech Connect

    Zapatero, Almudena; Garcia-Vicente, Feliciano; Martin de Vidales, Carmen; Cruz Conde, Alfonso; Ibanez, Yamile; Fernandez, Inmaculada; Rabadan, Mariano

    2011-12-01

    Purpose: To analyze long-term outcome and prognostic factors for high-risk prostate cancer defined by National Comprehensive Cancer Network criteria treated with high-dose radiotherapy and androgen deprivation in a single institution. Methods and Materials: A total of 306 patients treated between 1995 and 2007 in a radiation dose-escalation program fulfilled the National Comprehensive Cancer Network high-risk criteria. Median International Commission on Radiation Units and Measurements radiation dose was 78 Gy (range, 66.0-84.1 Gy). Long-term androgen deprivation (LTAD) was administered in 231 patients, short-term androgen deprivation (STAD) in 59 patients, and no hormones in 16 patients. The Phoenix (nadir plus 2 ng/mL) consensus definition was used for biochemical control. Multivariate analysis was performed to determine the independent prognostic impact of clinical and treatment factors. Median follow-up time was 64 months (range, 24-171 months). Results: The actuarial overall survival at 5 and 10 years was 95.7% and 89.8%, respectively, and the corresponding biochemical disease-free survival (bDFS) was 89.5% and 67.2%, respectively. Fourteen patients (4.6%) developed distant metastasis. Multivariate analysis showed that Gleason score >7 (p = 0.001), pretreatment prostate-specific antigen (PSA) level >20 ng/mL (p = 0.037), higher radiation dose (p = 0.005), and the use of adjuvant LTAD vs. STAD (p = 0.011) were independent prognostic factors affecting bDFS in high-risk disease. The 5-year bDFS for patients treated with LTAD plus radiotherapy dose >78 Gy was 97%. Conclusions: For high-risk patients the present series showed that the use of LTAD in conjunction with higher doses (>78 Gy) of radiotherapy was associated with improved biochemical tumor control. We observed that the presence of Gleason sum >7 and pretreatment PSA level >20 ng/mL in the same patient represents a 6.8 times higher risk of PSA failure. These men could be considered for clinical trials with

  17. Combination growth hormone and gonadotropin releasing hormone analog therapy in 11beta-hydroxylase deficiency.

    PubMed

    Bajpai, Anurag; Kabra, Madhulika; Menon, P S N

    2006-06-01

    Diagnosis of 11beta-hydroxylase deficiency was made in a boy at the age of 2 1/2 years on the basis of peripheral precocious puberty, growth acceleration (height standard deviation score +4.4) with advanced skeletal maturation (bone age 8.4 years) and elevated deoxycortisol levels. Glucocorticoid supplementation led to normalization of blood pressure but was associated with progression to central precocious puberty and increase in bone age resulting in decrease in predicted adult height to 133.7 cm (target height 163 cm). The child was started on GnRH analog (triptorelin 3.75 mg every 28 days), which led to improvement in predicted adult height by 3.1 cm over 15 months. Addition of growth hormone (0.1 IU/kg/day) resulted in improvement in predicted adult height (151 cm) and height deficit (12 cm) over the next 3.6 years. Final height (151 cm) exceeded predicted height at the initiation of GnRH analog treatment by 17.3 cm. This report suggests that combination GH and GnRH analog treatment may be useful in improving height outcome in children with 11beta-hydroxylase deficiency and compromised final height.

  18. Are Estrogen Receptor Genomic Aberrations Predictive of Hormone Therapy Response in Breast Cancer?

    PubMed Central

    Tabarestani, Sanaz; Motallebi, Marzieh; Akbari, Mohammad Esmaeil

    2016-01-01

    Context Breast cancer is the most common cancer in women worldwide. Estrogen receptor (ER) positive breast cancer constitutes the majority of these cancers. Hormone therapy has significantly improved clinical outcomes for early- and late-stage hormone receptor positive breast cancer. Although most patients with early stage breast cancer are treated with curative intent, approximately 20% - 30% of patients eventually experience a recurrence. During the last two decades, there have been tremendous efforts to understand the biological mechanisms of hormone therapy resistance, with the ultimate goal of implementing new therapeutic strategies to improve the current treatments for ER positive breast cancer. Several mechanisms of hormone therapy resistance have been proposed, including genetic alterations that lead to altered ER expression or ERs with changed protein sequence. Evidence Acquisition A Pubmed search was performed utilizing various related terms. Articles over the past 20 years were analyzed and selected for review. Results On the basis of published studies, the frequencies of ESR1 (the gene encoding ER) mutations in ER positive metastatic breast cancer range from 11% to 55%. Future larger prospective studies with standardized mutation detection methods may be necessary to determine the true incidence of ESR1 mutations. ESR1 amplification in breast cancer remains a controversial issue, with numerous studies either confirmed or challenged the reports of ESR1 amplification. The combination of intra-tumor heterogeneity regarding ESR1 copy number alterations and low level ESR1 copy number increase may account for these discrepancies. Conclusions While numerous unknown issues on the role of ESR1 mutations in advanced breast cancer remain, these new findings will certainly deepen current knowledge on molecular evolution of breast cancer and acquired resistance to hormone therapy. PMID:27761212

  19. 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

  20. Senescence and steroid hormone receptor reactivities in accessory sex glands of elderly rats (Sprague-Dawley) following exogenous hormonal therapy.

    PubMed

    Cândido, Eduardo Marcelo; Fávaro, Wagner José; Montico, Fabio; Hetzl, Amanda Cia; Cagnon, Valéria Helena Alves

    2012-08-01

    The aim of this study was to characterize the stromal and epithelial distribution of AR, ERα and ERβ reactivities in the different accessory sex glands of elderly rats and during strong hormonal changes. Ten month old male rats were divided into six senile groups and submitted to treatment: Senile/Control group (SC); Senile/Testosterone group (ST): Senile/Estrogen group (SE); Castrated group (CA); Castrated/Testosterone group (CT); Castrated/Estrogen group (CE). After a 30-day treatment, the prostatic ventral lobe (VL), dorsal lobe (DL) and coagulating gland (CG) samples were processed for immunohistochemistry and Western Blotting. The results showed that AR immunoreactivity was characterized in the epithelium of VL and DL in senile/control rats and senile rats submitted to exogenous hormonal therapy. AR reactivity in the coagulating gland was verified predominantly in the stromal cells in the different experimental groups. ERα reactivity occurred predominantly in the stromal compartment in all accessory sex glands. In the DL and CG, ERα immunoreactivities were intense in the groups which received testosterone (ST) and estrogen (SE). ERβ immunoreactivity in the CG was verified in the stromal compartment in the different experimental groups, showing a positive response to both increased testosterone and estrogen levels. ERβ reactivity, in the DL, was intensified in the stroma of senile rats with higher serum testosterone levels, and in senile rats with increased serum estrogen levels, especially in the glandular epithelium. Thus, the results revealed different distribution pattern of steroid hormone receptors in each one of the prostatic lobes in senescence, especially in the prostate dorsal lobe and coagulating gland, which is a fundamental factor due to the fact that major prostatic diseases occur in a later period of life.

  1. Effects of aerobic exercise on ectopic lipids in patients with growth hormone deficiency before and after growth hormone replacement therapy

    PubMed Central

    Christ, Emanuel R.; Egger, Andrea; Allemann, Sabin; Buehler, Tania; Kreis, Roland; Boesch, Chris

    2016-01-01

    Growth hormone replacement therapy (GHRT) increases exercise capacity and insulin resistance while it decreases fat mass in growth hormone-deficient patients (GHD). Ectopic lipids (intramyocellular (IMCL) and intrahepatocellular lipids (IHCL) are related to insulin resistance. The effect of GHRT on ectopic lipids is unknown. It is hypothesized that exercise-induced utilization of ectopic lipids is significantly decreased in GHD patients and normalized by GHRT. GHD (4 females, 6 males) and age/gender/waist-matched control subjects (CS) were studied. VO2max was assessed on a treadmill and insulin sensitivity determined by a two-step hyperinsulinaemic-euglycaemic clamp. Visceral (VAT) and subcutaneous (SAT) fat were quantified by MR-imaging. IHCL and IMCL were measured before and after a 2 h exercise at 50–60% of VO2max using MR-spectroscopy (∆IMCL, ∆IHCL). Identical investigations were performed after 6 months of GHRT. VO2max was similar in GHD and CS and significantly increased after GHRT; GHRT significantly decreased SAT and VAT. 2 h-exercise resulted in a decrease in IMCL (significant in CS and GHRT) and a significant increase in IHCL in CS and GHD pre and post GHRT. GHRT didn’t significantly impact on ∆IMCL and ∆IHCL. We conclude that aerobic exercise affects ectopic lipids in patients and controls. GHRT increases exercise capacity without influencing ectopic lipids. PMID:26792091

  2. 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.

  3. Bifurcation analysis on a hybrid systems model of intermittent hormonal therapy for prostate cancer

    NASA Astrophysics Data System (ADS)

    Tanaka, Gouhei; Tsumoto, Kunichika; Tsuji, Shigeki; Aihara, Kazuyuki

    2008-10-01

    Hybrid systems are widely used to model dynamical phenomena that are characterized by interplay between continuous dynamics and discrete events. An example of biomedical application is modeling of disease progression of prostate cancer under intermittent hormonal therapy, where continuous tumor dynamics is switched by interruption and reinstitution of medication. In the present paper, we study a hybrid systems model representing intermittent androgen suppression (IAS) therapy for advanced prostate cancer. Intermittent medication with switching between on-treatment and off-treatment periods is intended to possibly prevent a prostatic tumor from developing into a hormone-refractory state and is anticipated as a possible strategy for delaying or hopefully averting a cancer relapse which most patients undergo as a result of long-term hormonal suppression. Clinical efficacy of IAS therapy for prostate cancer is still under investigation but at least worth considering in terms of reduction of side effects and economic costs during off-treatment periods. In the model of IAS therapy, it depends on some clinically controllable parameters whether a relapse of prostate cancer occurs or not. Therefore, we examine nonlinear dynamics and bifurcation structure of the model by exploiting a numerical method to clarify bifurcation sets in the hybrid system. Our results suggest that adjustment of the normal androgen level in combination with appropriate medication scheduling could enhance the possibility of relapse prevention. Moreover, a two-dimensional piecewise-linear system reduced from the original model highlights the origin of nonlinear phenomena specific to the hybrid system.

  4. Does hormonal therapy have a therapeutic role in metastatic primary small cell neuroendocrine breast carcinoma? Case report and literature review.

    PubMed

    Alkaied, Homam; Harris, Kassem; Brenner, Arnold; Awasum, Michael; Varma, Seema

    2012-06-01

    Primary neuroendocrine carcinoma of breast (NECB) is a very rare tumor; the World Health Organization(WHO) subcategorized these tumors into 3 major histologic subtypes: solid, small cell carcinoma (SMCC), and large cell NE carcinoma. The SMCC subtype is the least common and most aggressive and has been reported to be as aggressive as its pulmonary counterpart. SMCC is usually confirmed based on clinical, pathologic,and imaging studies. Local disease is usually managed in a fashion similar to that of the usual ductal breast cancer; in the metastatic SMCC setting, regimens that are implemented in small cell lung cancer are usually attempted, according to case reports and published small case series. Hormone receptors can be expressed in more than 90% of the solid tumor subtype; however its expression is manifested in about 50% of cases of SMCC. Although hormonal therapy can be used successfully to treat the usual metastatic ductal breast cancer,its utility in metastatic SMCC has not been reported. We report an impressive response to hormonal therapy in a patient with late relapse of breast carcinoma with a metastatic SMCC subtype that expressed hormone receptors. The response to hormonal therapy was sustained for about 12 months. The response to hormonal therapy is definitely an interesting finding that, to our knowledge, has not been described before in the setting of metastatic SMCC. We suggest considering adding hormonal therapy to the treatment pipeline for primary SMCC of the breast that express hormone receptors.

  5. The effects of postmenopausal hormone therapy on serum estrogen, progesterone and sex hormone binding globulin levels in healthy post-menopausal women

    PubMed Central

    Edlefsen, Kerstin L.; Jackson, Rebecca D.; Prentice, Ross L.; Janssen, Imke; Rajkovic, Aleksandar; O'Sullivan, Mary Jo; Anderson, Garnet

    2010-01-01

    Objective Differences in disease outcomes between users and non-users of hormone therapy (HT) and between users of estrogen alone (ET) and users of estrogen plus progesterone therapy (EPT) may relate to differences in serum hormone concentrations between these populations. In this study, we examine the response of serum hormone levels in healthy post-menopausal women after one year of HT. Methods A representative sub-sample of 200 healthy adherent participants from the active and placebo groups of the Women's Health Initiative randomized, controlled clinical trials of ET (conjugated equine estrogen 0.625 mg daily) or EPT (ET plus medroxyprogesterone actetate 2.5 mg daily) were selected for determination of selected sex hormone levels at baseline and one year after randomization. Results In participants receiving active ET intervention compared to placebo, estrogenic hormone levels increased from baseline to year 1 by 3.6-fold for total estrone, 2.7-fold for total estradiol, and 1.8-fold for bioavailable and free estradiol concentrations. Serum SHBG concentrations also increased 2.5-fold. In contrast, progesterone levels decreased slightly in women taking exogenous EPT. The response of serum estrogens and SHBG did not differ substantially with the addition of progesterone. In subgroup analyses, hormone response varied by age, ethnicity, BMI, smoking, vasomotor symptoms, and baseline hormone levels. Conclusions These data provide a reference point for the serum hormone response to HT, and demonstrate that response of serum estrogens is similar for ET and EPT. The implications of the slight decrease in serum progesterone levels with EPT therapy are uncertain. Potential treatment interactions for estrogenic hormones were identified, which suggest a larger response to HT in women with low endogenous levels. PMID:20215977

  6. Impact of short course hormonal therapy on overall and cancer specific survival after permanent prostate brachytherapy

    SciTech Connect

    Beyer, David C. . E-mail: dbeyer@azoncology.com; McKeough, Timothy; Thomas, Theresa

    2005-04-01

    Purpose: To review the impact of prior hormonal therapy on 10-year overall and prostate cancer specific survival after primary brachytherapy. Methods and Materials: A retrospective review was performed on the Arizona Oncology Services tumor registry for 2,378 consecutive permanent prostate brachytherapy cases from 1988 through 2001. Hormonal therapy was administered before the implant in 464 patients for downsizing of the prostate or at the discretion of the referring physician. All deceased patients with known clinical recurrence were considered to have died of prostate cancer, irrespective of the immediate cause of death. Risk groups were defined, with 1,135 favorable (prostate-specific antigen [PSA] < 10, Gleason < 7, Stage T1-T2a), 787 intermediate (single adverse feature), and 456 unfavorable (two or more adverse features) patients. Kaplan-Meier actuarial survival curves were generated for both overall and cause-specific survival from the time of treatment. Multivariate analysis was performed to assess the impact of hormonal intervention in comparison with known risk factors of grade, PSA, and age. Results: With follow-up ranging up to 12.6 years and a median of 4.1 year, a total of 474 patients died, with 67 recorded as due to prostate cancer. Overall and cause-specific 10-year survival rates are 43% and 88%, respectively. Overall survival is 44% for the hormone naive patients, compared with 20% for the hormone-treated cohort (p = 0.02). The cancer-specific survival is 89% vs. 81% for the same groups (p = 0.133). Multivariate analysis confirms the significance of age > 70 years (p = 0.0013), Gleason score {>=} 7 (p = 0.0005), and prior hormone use (p = 0.0065) on overall survival. Conclusions: At 10 years, in prostate cancer patients receiving brachytherapy, overall survival is worse in men receiving neoadjuvant hormonal therapy, compared with hormone naive patients. This does not appear to be due to other known risk factors for survival (i.e., stage, grade

  7. Promotional Tone in Reviews of Menopausal Hormone Therapy After the Women's Health Initiative: An Analysis of Published Articles

    PubMed Central

    Fugh-Berman, Adriane; McDonald, Christina Pike; Bell, Alicia M.; Bethards, Emily Catherine; Scialli, Anthony R.

    2011-01-01

    Background Even after the Women's Health Initiative (WHI) found that the risks of menopausal hormone therapy (hormone therapy) outweighed benefit for asymptomatic women, about half of gynecologists in the United States continued to believe that hormones benefited women's health. The pharmaceutical industry has supported publication of articles in medical journals for marketing purposes. It is unknown whether author relationships with industry affect promotional tone in articles on hormone therapy. The goal of this study was to determine whether promotional tone could be identified in narrative review articles regarding menopausal hormone therapy and whether articles identified as promotional were more likely to have been authored by those with conflicts of interest with manufacturers of menopausal hormone therapy. Methods and Findings We analyzed tone in opinion pieces on hormone therapy published in the four years after the estrogen-progestin arm of the WHI was stopped. First, we identified the ten authors with four or more MEDLINE-indexed reviews, editorials, comments, or letters on hormone replacement therapy or menopausal hormone therapy published between July 2002 and June 2006. Next, we conducted an additional search using the names of these authors to identify other relevant articles. Finally, after author names and affiliations were removed, 50 articles were evaluated by three readers for scientific accuracy and for tone. Scientific accuracy was assessed based on whether or not the findings of the WHI were accurately reported using two criteria: (1) Acknowledgment or lack of denial of the risk of breast cancer diagnosis associated with hormone therapy, and (2) acknowledgment that hormone therapy did not benefit cardiovascular disease endpoints. Determination of promotional tone was based on the assessment by each reader of whether the article appeared to promote hormone therapy. Analysis of inter-rater consistency found moderate agreement for scientific

  8. Polymorphisms in genes involved in sex hormone metabolism, estrogen plus progestin hormone therapy use, and risk of postmenopausal breast cancer

    PubMed Central

    Diergaarde, Brenda; Potter, John D.; Jupe, Eldon R.; Manjeshwar, Sharmila; Shimasaki, Craig D.; Pugh, Thomas W.; DeFreese, Daniele C.; Gramling, Bobby A.; Evans, Ilonka; White, Emily

    2009-01-01

    Hormone therapy, estrogen plus progestin (E+P) particularly, is associated with increased risk of breast cancer. Functionally relevant polymorphisms in genes involved in sex hormone metabolism may alter exposure to exogenous sex hormones and affect risk of postmenopausal breast cancer. We evaluated associations of common polymorphisms in genes involved in estrogen and/or progesterone metabolism, E+P use, and their interactions with breast cancer risk in a case-control study of postmenopausal women (324 cases; 651 controls) nested within the VITAL cohort. None of the polymorphisms studied was, by itself, statistically significantly associated with breast cancer risk. E+P use was significantly associated with increased breast cancer risk (≥10 years versus never, odds ratio: 1.9; 95% confidence interval: 1.3–2.8; Ptrend: 0.0002). Statistically significant interactions between CYP1A1 Ile462Val (Pinteraction: 0.04), CYP1A1 MspI (Pinteraction: 0.003), CYP1B1 Val432Leu (Pinteraction: 0.007), CYP1B1 Asn453Ser (Pinteraction: 0.04) and PGR Val660Leu (Pinteraction: 0.01), and E+P use were observed. The increased risk of breast cancer associated with E+P use was greater among women with at least one rare allele of the CYP1A1 Ile462Val, CYP1A1 MspI, CYP1B1 Asn453Ser and PGR Val660Leu polymorphisms than among women homozygous for the common allele of these polymorphisms. Risk of breast cancer increased little with increasing years of E+P use among women with at least one CYP1B1 Val432 allele; a large increase in risk was seen among women homozygous for CYP1B1 Leu432. Our results support the hypothesis that specific polymorphisms in genes involved in sex hormone metabolism may modify the effect of E+P use on breast cancer risk. PMID:18628428

  9. Development of a growth-hormone-conjugated nanodiamond complex for cancer therapy.

    PubMed

    Chu, Hsueh-Liang; Chen, Hung-Wei; Tseng, Shin-Hua; Hsu, Ming-Hua; Ho, Li-Ping; Chou, Fu-Hsuan; Li, Md Phd Hsing-Yuan; Chang, Yu-Chuan; Chen, Pei-Hsin; Tsai, Li-Yun; Chou, Ching-Chung; Chen, Jyh Shin; Cheng, Tsai-Mu; Chang, Chia-Ching

    2014-05-01

    It is highly desirable to develop a therapeutic, observable nanoparticle complex for specific targeting in cancer therapy. Growth hormone (GH) and its antagonists have been explored as cancer cell-targeting molecules for both imaging and therapeutic applications. In this study, a low toxicity, biocompatible, therapeutic, and observable GH-nanoparticle complex for specifically targeting growth hormone receptor (GHR) in cancer cells was synthesized by conjugating GH with green fluorescence protein and carboxylated nanodiamond. Moreover, we have shown that this complex can be triggered by laser irradiation to create a "nanoblast" and induce cell death in the A549 non-small-cell lung cancer cell line via the apoptotic pathway. This laser-mediated, cancer-targeting platform can be widely used in cancer therapy.

  10. Distinctive Tooth-Extraction Socket Healing: Bisphosphonate Versus Parathyroid Hormone Therapy

    PubMed Central

    Kuroshima, Shinichiro; Mecano, Rodan B.; Tanoue, Ryuichiro; Koi, Kiyono; Yamashita, Junro

    2014-01-01

    Background Patients with osteoporosis who receive tooth extractions are typically on either oral bisphosphonate or parathyroid hormone (PTH) therapy. Currently, the consequence of these therapies on hard- and soft-tissue healing in the oral cavity is not clearly defined. The aim of this study is to determine the differences in the therapeutic effect on tooth-extraction wound healing between bisphosphonate and PTH therapies. Methods Maxillary second molars were extracted in Sprague Dawley rats (n = 30), and either bisphosphonate (zoledronate [Zol]), PTH, or saline (vehicle control [VC]) was administered for 10 days (n = 10 per group). Hard-tissue healing was evaluated by microcomputed tomography and histomorphometric analyses. Collagen, blood vessels, inflammatory cell infiltration, and cathepsin K expression were assessed in soft tissue using immunohistochemistry, quantitative polymerase chain reaction, and immunoblotting. Results Both therapies significantly increased bone fill and suppressed vertical bone loss. However, considerably more devital bone was observed in the sockets of rats on Zol versus VC. Although Zol increased the numbers of blood vessels, the total blood vessel area in soft tissue was significantly smaller than in VC. PTH therapy increased osteoblastic bone formation and suppressed osteoclasts. PTH therapy promoted soft-tissue maturation by suppressing inflammation and stimulating collagen deposition. Conclusion Zoledronate therapy deters whereas PTH therapy promotes hard- and soft-tissue healing in the oral cavity, and both therapies prevent vertical bone loss. PMID:23688101

  11. Generation of "virtual" control groups for single arm prostate cancer adjuvant trials.

    PubMed

    Jia, Zhenyu; Lilly, Michael B; Koziol, James A; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-Guo; McLaren, Christine E; Gurley, Michael J; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W; Mercola, Dan

    2014-01-01

    It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies.

  12. An Intervention to Control Vasomotor Symptoms for Advanced PC Patients on Hormone Therapy

    DTIC Science & Technology

    2013-08-14

    develop a breathing exercise application for the iPod touch platform; and (2) assess the feasibility and acceptability of this intervention among...advanced prostate cancer survivors on hormone therapy. To reach these goals, we have developed an application, titled “2Breathe,” for Apple’s iPod Touch...2Breathe and 2Play programs on the iPod Touch for its usability; 2) refined recruitment strategies with our collaborators at the VA; 3) successfully

  13. Hormonal Resistance And Metastasis ER-Coregulartor-Src Signaling Targeted Therapy

    DTIC Science & Technology

    2011-09-01

    essential role in hormonal responsiveness and cancer progression (4-6). Proline, Glutamic-acid and Leucine-rich Protein 1 (PELP1) is a recently...Glutamic Acid-, Leucine-Rich Protein 1/Modulator of the Nongenomic Actions of the Estrogen Receptor. Cancer Res 2007;67:5505-12. (10) Rajhans R, Nair HB...mitogen-activated protein kinase (MAPK), and protein kinase B (AKT) pathways in development of therapy resistance [5, 6]. In addition to its well

  14. A phase II study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapy-resistant breast cancer

    PubMed Central

    Munster, P N; Thurn, K T; Thomas, S; Raha, P; Lacevic, M; Miller, A; Melisko, M; Ismail-Khan, R; Rugo, H; Moasser, M; Minton, S E

    2011-01-01

    Background: Histone deacetylases (HDACs) are crucial components of the oestrogen receptor (ER) transcriptional complex. Preclinically, HDAC inhibitors can reverse tamoxifen/aromatase inhibitor resistance in hormone receptor-positive breast cancer. This concept was examined in a phase II combination trial with correlative end points. Methods: Patients with ER-positive metastatic breast cancer progressing on endocrine therapy were treated with 400 mg of vorinostat daily for 3 of 4 weeks and 20 mg tamoxifen daily, continuously. Histone acetylation and HDAC2 expression in peripheral blood mononuclear cells were also evaluated. Results: In all, 43 patients (median age 56 years (31–71)) were treated, 25 (58%) received prior adjuvant tamoxifen, 29 (67%) failed one prior chemotherapy regimen, 42 (98%) progressed after one, and 23 (54%) after two aromatase inhibitors. The objective response rate by Response Evaluation Criteria in Solid Tumours criteria was 19% and the clinical benefit rate (response or stable disease >24 weeks) was 40%. The median response duration was 10.3 months (confidence interval: 8.1–12.4). Histone hyperacetylation and higher baseline HDAC2 levels correlated with response. Conclusion: The combination of vorinostat and tamoxifen is well tolerated and exhibits encouraging activity in reversing hormone resistance. Correlative studies suggest that HDAC2 expression is a predictive marker and histone hyperacetylation is a useful pharmacodynamic marker for the efficacy of this combination. PMID:21559012

  15. Altered radiation responses of breast cancer cells resistant to hormonal therapy.

    PubMed

    Luzhna, Lidiya; Lykkesfeldt, Anne E; Kovalchuk, Olga

    2015-01-30

    Endocrine therapy agents (the selective estrogen receptor (ER) modulators such as tamoxifen or the selective ER down-regulators such as ICI 182,780) are key treatment regimens for hormone receptor-positive breast cancers. While these drugs are very effective in controlling ER-positive breast cancer, many tumors that initially respond well to treatment often acquire drug resistance, which is a major clinical problem. In clinical practice, hormonal therapy agents are commonly used in combination or sequence with radiation therapy. Tamoxifen treatment and radiotherapy improve both local tumor control and patient survival. However, tamoxifen treatment may render cancer cells less responsive to radiation therapy. Only a handful of data exist on the effects of radiation on cells resistant to hormonal therapy agents. These scarce data show that cells that were resistant to tamoxifen were also resistant to radiation. Yet, the existence and mechanisms of cross-resistance to endocrine therapy and radiation therapy need to be established. Here, we for the first time examined and compared radiation responses of MCF-7 breast adenocarcinoma cells (MCF-7/S0.5) and two antiestrogen resistant cell lines derived from MCF-7/S0.5: the tamoxifen resistant MCF-7/TAMR-1 and ICI 182,780 resistant MCF-7/182R-6 cell lines. Specifically, we analyzed the radiation-induced changes in the expression of genes involved in DNA damage, apoptosis, and cell cycle regulation. We found that the tamoxifen-resistant cell line in contrast to the parental and ICI 182,780-resistant cell lines displayed a significantly less radiation-induced decrease in the expression of genes involved in DNA repair. Furthermore, we show that MCF-7/TAMR-1 and MCF-7/182R-6 cells were less susceptible to radiation-induced apoptosis as compared to the parental line. These data indicate that tamoxifen-resistant breast cancer cells have a reduced sensitivity to radiation treatment. The current study may therefore serve as a

  16. Blood pressure, arterial function, structure, and aging: the role of hormonal replacement therapy in postmenopausal women.

    PubMed

    Scuteri, Angelo; Ferrucci, Luigi

    2003-01-01

    The occurrence of natural menopause may indicate that a woman is entering a period of increased risk for cardiovascular disease, due to both chronologic aging and lower levels of estrogen. This brief review aims to demonstrate the relevance of changes in blood pressure and large artery structure and function occurring after menopause. These changes, i.e., thickening and stiffening of large arteries (which, in turn would also result in increased systolic and pulse pressures), were found to predict subsequent cardiovascular events, independently of other known cardiovascular risk. The benefits of early hormone replacement therapy on the life expectancy of women have dramatically lost consensus since publication of the Womens Health Initiative study results. However, the authors believe that those results should increase the attention paid by clinicians and public health researchers to the individualization of hormone replacement therapy prescription for postmenopausal women, and to a better characterization of those vascular parameters and profiles identifying postmenopausal women who are most likely to benefit from specific hormone replacement therapy in terms of cardiovascular protection.

  17. 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.

  18. The Role of Sex Hormone Replacement Therapy on Self-Perceived Competence in Adolescents with Delayed Puberty.

    ERIC Educational Resources Information Center

    Schwab, Jacqueline; Kulin, Howard E.; Susman, Elizabeth J.; Finkelstein, Jordan W.; Chinchilli, Vernon M.; Kunselman, Susan J.; Liben, Lyye S.; D'Arcangelo, M. Rose; Demers, Lawrence M.

    2001-01-01

    Examined role of sex steroids in development of self-perceived competence among adolescents receiving hormone therapy for delayed puberty. Found that hormone treatments had a significant positive effect for both males and females in perceived job competence. Significant positive effects were also obtained for perceptions of romantic appeal and…

  19. Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall

    SciTech Connect

    Jebsen, Nina L.; Engellau, Jacob; Engström, Katarina; Bauer, Henrik C.; Monge, Odd R.; Muren, Ludvig P.; Eide, Geir E.; Trovik, Clement S.; Bruland, Øyvind S.

    2013-08-01

    Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence interval [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma.

  20. Impact of growth hormone replacement therapy on sleep in adult patients with growth hormone deficiency of pituitary origin

    PubMed Central

    Morselli, Lisa L.; Nedeltcheva, Arlet; Leproult, Rachel; Spiegel, Karine; Martino, Enio; Legros, Jean-Jacques; Weiss, Roy E.; Mockel, Jean; Van Cauter, Eve; Copinschi, Georges

    2013-01-01

    Objectives We previously reported that adult patients with GH deficiency (GHD) due to a confirmed or likely pituitary defect, as compared to healthy controls individually matched for age, gender and BMI, have more slow-wave sleep (SWS) and higher delta activity (a marker of SWS intensity). Here we examined the impact of recombinant human GH (rhGH) therapy, compared to placebo, on objective sleep quality in a subset of patients from the same cohort. Design Single-blind randomized cross-over design study. Methods Fourteen patients with untreated GHD of confirmed or likely pituitary origin, aged 22–74 yr, participated in the study. Patients with associated hormonal deficiencies were on appropriate replacement therapy. Polygraphic sleep recordings, with bedtimes individually tailored to habitual sleep times, were performed after 4 months on rhGH or placebo. Results Valid data were obtained in 13 patients. At the end of rhGH treatment period, patients had a shorter sleep period time than at the end of the placebo period (479±11 vs 431±19 min respectively; p=0.005), primarily due to an earlier wake up time, and a decrease in the intensity of SWS (delta activity) (559±125 vs 794±219 μV2, respectively; p=0.048). Conclusions Four months of rhGH replacement therapy partly reversed sleep disturbances previously observed in untreated patients. The decrease in delta activity associated with rhGH treatment adds further evidence to the hypothesis that the excess of high intensity SWS observed in untreated pituitary GHD patients is likely to result from overactivity of the hypothalamic GHRH system due to the lack of negative feedback inhibition by GH. PMID:23447518

  1. The Na⁺/H⁺ exchanger (NHE1) as a novel co-adjuvant target in paclitaxel therapy of triple-negative breast cancer cells.

    PubMed

    Amith, Schammim Ray; Wilkinson, Jodi Marie; Baksh, Shairaz; Fliegel, Larry

    2015-01-20

    Dysregulation of Na⁺/H⁺ exchanger isoform one (NHE1) activity is a hallmark of cells undergoing tumorigenesis and metastasis, the leading cause of patient mortality. The acidic tumor microenvironment is thought to facilitate the development of resistance to chemotherapy drugs and to promote extracellular matrix remodeling leading to metastasis. Here, we investigated NHE1 as a co-adjuvant target in paclitaxel chemotherapy of metastatic breast cancer. We generated a stable NHE1-knockout of the highly invasive, triple-negative, MDA-MB-231 breast cancer cells. The NHE1-knockout cells proliferated comparably to parental cells, but had markedly lower rates of migration and invasion in vitro. In vivo xenograft tumor growth in athymic nude mice was also dramatically decreased compared to parental MDA-MB-231 cells. Loss of NHE1 expression also increased the susceptibility of knockout cells to paclitaxel-mediated cell death. NHE1 inhibition, in combination with paclitaxel, resulted in a dramatic decrease in viability, and migratory and invasive potential of triple-negative breast cancer cells, but not in hormone receptor-positive, luminal MCF7 cells. Our data suggest that NHE1 is critical in triple-negative breast cancer metastasis, and its chemical inhibition boosts the efficacy of paclitaxel in vitro, highlighting NHE1 as a novel, potential co-adjuvant target in breast cancer chemotherapy.

  2. A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902

    SciTech Connect

    Rosenthal, Seth A.; Hunt, Daniel; Sartor, A. Oliver; Pienta, Kenneth J.; Gomella, Leonard; Grignon, David; Rajan, Raghu; Kerlin, Kevin J.; Jones, Christopher U.; Dobelbower, Michael; Shipley, William U.; Zeitzer, Kenneth; Hamstra, Daniel A.; Donavanik, Viroon; Rotman, Marvin; Hartford, Alan C.; Michalski, Jeffrey; Seider, Michael; Kim, Harold; and others

    2015-10-01

    Purpose: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS). Methods and Materials: Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥7 or clinical stage ≥T2 and GS ≥8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was given as four 21-day cycles, delivered beginning 28 days after 70.2 Gy of RT. AS was given as luteinizing hormone-releasing hormone for 24 months, beginning 2 months before RT plus an oral antiandrogen for 4 months before and during RT. The study was designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90% power and a 2-sided alpha of 0.05. Results: A total of 397 patients (380 eligible) were randomized. The patients had high-risk PCa, 68% with GS 8 to 10 and 34% T3 to T4 tumors, and median prostate-specific antigen of 22.6 ng/mL. The median follow-up period was 9.2 years. The trial closed early because of excess thromboembolic toxicity in the CT arm. The 10-year results for all randomized patients revealed no significant difference between the AS + RT and AS + RT + CT arms in OS (65% vs 63%; P=.81), biochemical failure (58% vs 54%; P=.82), local progression (11% vs 7%; P=.09), distant metastases (16% vs 14%; P=.42), or disease-free survival (22% vs 26%; P=.61). Conclusions: NRG Oncology RTOG 9902 showed no significant differences in OS, biochemical failure, local progression, distant metastases, or disease-free survival with the addition of adjuvant CT to LT AS + RT. The trial results provide valuable data regarding the natural history of high-risk PCa treated with LT AS + RT and have implications for

  3. Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

    PubMed

    Khalil, Raouf A

    2013-12-15

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD.

  4. Estrogen, Vascular Estrogen Receptor and Hormone Therapy in Postmenopausal Vascular Disease

    PubMed Central

    Khalil, Raouf A.

    2013-01-01

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women’s Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject’s age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. PMID:24099797

  5. Building a better hormone therapy? How understanding the rapid effects of sex steroid hormones could lead to new therapeutics for age-related memory decline.

    PubMed

    Frick, Karyn M

    2012-02-01

    A wealth of data collected in recent decades has demonstrated that ovarian sex-steroid hormones, particularly 17β-estradiol (E2), are important trophic factors that regulate the function of cognitive regions of the brain such as the hippocampus. The loss of hormone cycling at menopause is associated with cognitive decline and dementia in women, and the onset of memory decline in animal models. However, hormone therapy is not currently recommended to prevent or treat cognitive decline, in part because of its detrimental side effects. In this article, it is proposed that investigations of the rapid effects of E2 on hippocampal function be used to further the design of new drugs that mimic the beneficial effects of E2 on memory without the side effects of current therapies. A conceptual model is presented for elucidating the molecular and biochemical mechanisms through which sex-steroid hormones modulate memory, and a specific hypothesis is proposed to account for the rapid memory-enhancing effects of E2. Empirical support for this hypothesis is discussed as a means of stimulating the consideration of new directions for the development of hormone-based therapies to preserve memory function in menopausal women.

  6. 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

  7. Optimal systemic therapy for premenopausal women with hormone receptor-positive breast cancer.

    PubMed

    Jankowitz, Rachel C; McGuire, Kandace P; Davidson, Nancy E

    2013-08-01

    Although systemic therapy is one of the cornerstones of therapy for premenopausal women with early stage breast cancer, there remain many unknowns regarding its optimal use. By accident of clinical trial design, much clinical investigation in premenopausal women has focused on chemotherapy. More recently the value of endocrine therapy (tamoxifen and ovarian suppression/ablation via surgery, LHRH agonists, or chemotherapy-induced menopause) has become apparent, and some form of endocrine therapy is viewed as standard for virtually all premenopausal women with early stage invasive breast cancer that expresses estrogen and/or progesterone receptor. Critical open questions include type and duration of endocrine therapy and the development of prognostic/predictive markers to help identify patients who are likely to benefit from chemotherapy in addition to endocrine therapy. For some years, five years of tamoxifen has been viewed as the standard endocrine therapy for premenopausal hormone-responsive breast cancer, although the ATLAS trial suggests that an additional five years of tamoxifen can be considered. The MA17 trial also suggests that an additional five years of an aromatase inhibitor can be considered for women who become postmenopausal during tamoxifen therapy. Information about the value of ovarian suppression continues to emerge, most recently with the demonstration of excellent outcome with goserelin plus tamoxifen in the ABCSG12 trial. The SOFT and TEXT trials, whose accrual is now complete, should help to define optimal endocrine therapy. In addition, use of the 21-gene recurrence score assay may help to delineate the additional value of chemotherapy for patients with node-negative breast cancer, and its utility in the setting of women with 1-3 positive lymph nodes is under study in the RxPONDER trial. Nonetheless, the need for other predictive biomarkers to select appropriate therapy remains real. Finally, attention to long term benefits and side effects

  8. The pharmacological and hormonal therapy of hot flushes in breast cancer survivors.

    PubMed

    Wiśniewska, Iwona; Jochymek, Bożena; Lenart-Lipińska, Monika; Chabowski, Mariusz

    2016-03-01

    The side effects of oncological treatment, which appear during or after therapy, are sometimes very annoying for patients and are not adequately treated by physicians. Among the symptoms experienced by breast cancer patients are hot flushes, which result from a natural or cancer therapy-induced menopause. The intensity of hot flushes in breast cancer patients may be more severe than those experienced by women undergoing a natural menopause. Taking into account the incidence of breast cancer and long-lasting hormone-suppression therapies, the problem of hot flushes will affect many women. Hormonal replacement therapy, the most effective therapeutic means for alleviating hot flushes, is usually contraindicated for breast cancer patients. For intense and severe hot flushes, pharmacological treatment using agents from a group of selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors such as venlafaxine or citalopram may be introduced. Other agents from different pharmacological groups, such as clonidine, gabapentin, or pregabalin, have also proved to be effective in treating hot flushes. The efficacy of phytoestrogens has not been proven in randomized clinical trials. The importance of the placebo effect in decreasing vasomotor symptoms has also been reported in many research papers. Educating breast cancer patients in lifestyle changes which decrease the frequency and intensity of vasomotor symptoms can offer significant help too. This paper reviews the current state of research in order to assess the options for the treatment of hot flushes in breast cancer survivors.

  9. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats

    PubMed Central

    Curtis, Ryan C.; Custis, James T.; Ehrhart, Nicole P.; Ehrhart, E. J.; Condon, Keith W.; Gookin, Sara E.; Donahue, Seth W.

    2016-01-01

    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma. PMID:27332712

  10. The role of hormone replacement therapy in the intensive care management of deceased organ donors: a primer for nurses.

    PubMed

    Smetana, Keaton S; Kimmons, Lauren A; Jones, G Morgan

    2015-01-01

    Donation after brain death remains the primary contributor to the supply of organs available for transplantation in the United States. After brain death, both a surge of catecholamines and a dysregulation of the neurohormonal axis may result in hypotension, decreased organ perfusion, and reduced viability of organs to be transplanted. Hormone replacement therapy is widely used to maintain organ perfusion and has been shown to increase the number of organs procured. This article reviews the literature and mechanisms supporting the use of hormone replacement therapy in brain-dead organ donors and provides clinicians with information regarding the administration, monitoring, and preparation of thyroid hormone, arginine vasopressin, and corticosteroids.

  11. What is the influence of hormone therapy on homocysteine and crp levels in postmenopausal women?

    PubMed Central

    Lakryc, Eli Marcelo; Machado, Rogério Bonassi; Soares, José Maria; Fernandes, César Eduardo; Baracat, Edmund Chada

    2015-01-01

    OBJECTIVE: To evaluate the influence of estrogen therapy and estrogen-progestin therapy on homocysteine and C-reactive protein levels in postmenopausal women. METHODS: In total, 99 postmenopausal women were included in this double-blind, randomized clinical trial and divided into three groups: Group A used estrogen therapy alone (2.0 mg of 17β-estradiol), Group B received estrogen-progestin therapy (2.0 mg of 17 β-estradiol +1.0 mg of norethisterone acetate) and Group C received a placebo (control). The length of treatment was six months. Serum measurements of homocysteine and C-reactive protein were carried out prior to the onset of treatment and following six months of therapy. RESULTS: After six months of treatment, there was a 20.7% reduction in homocysteine levels and a 100.5% increase in C-reactive protein levels in the group of women who used estrogen therapy. With respect to the estrogen-progestin group, there was a 12.2% decrease in homocysteine levels and a 93.5% increase in C-reactive protein levels. CONCLUSION: Our data suggested that hormone therapy (unopposed estrogen or estrogen associated with progestin) may have a positive influence on decreasing cardiovascular risk due to a significant reduction in homocysteine levels. PMID:25789519

  12. Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline

    PubMed Central

    Harris, Lyndsay N.; McShane, Lisa M.; Andre, Fabrice; Collyar, Deborah E.; Gonzalez-Angulo, Ana M.; Hammond, Elizabeth H.; Kuderer, Nicole M.; Liu, Minetta C.; Mennel, Robert G.; Van Poznak, Catherine; Bast, Robert C.; Hayes, Daniel F.

    2016-01-01

    Purpose To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer. Methods A literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations. Results The literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens. Recommendations In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences. PMID:26858339

  13. Chinese Medicines as an Adjuvant Therapy for Unresectable Hepatocellular Carcinoma during Transarterial Chemoembolization: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Wang, Xuanbin; Yuen, Man-Fung; Ziea, Tat-chi; Tong, Yao; Wong, Vivian Taam; Feng, Yibin

    2013-01-01

    Objective. To conduct a comprehensive PRISMA-compliant systematic review and meta-analysis to evaluate the efficacy and safety of Chinese medicines (CMs) as an adjuvant therapy for unresectable HCC during transarterial chemoembolization (TACE). Methods. Main databases were searched up to October 2012 for randomized controlled trials (RCTs) evaluating the effects of CMs plus TACE on unresectable HCC compared with TACE alone. References of relevant reviews and eligible studies were also assessed. Risk ratios with 95% confidence intervals and mean difference were calculated. Heterogeneity and publication bias were examined. Results. Sixty-seven trials (N = 5,211) were included in the meta-analysis. Sensitivity analysis and random-effects model were performed for assessing significant heterogeneity. CMs plus TACE showed beneficial effects on tumor response, survival at 6, 12, 18, 24, and 36 months, quality of life, and TACE toxicity reduction compared with TACE alone. Conclusion. The results show that the use of CMs may increase the efficacy and reduce the toxicity of TACE in treating patients with unresectable HCC. These findings suggest that CMs could be considered as an adjuvant therapy for unresectable HCC patients during TACE. Larger-scale RCTs using standard methods and long-term follow-up are warranted to confirm these findings. PMID:23956773

  14. Aging-induced alterations in female rat colon smooth muscle: the protective effects of hormonal therapy.

    PubMed

    Pascua, P; Camello-Almaraz, C; Pozo, M J; Martin-Cano, F E; Vara, E; Fernández-Tresguerres, J A; Camello, P J

    2012-06-01

    Aging is associated to oxidative damage and alterations in inflammatory and apoptotic pathways. Aging impairs secretion of several hormones, including melatonin and estrogens. However, the mechanisms involved in aging of smooth muscle are poorly known. We have studied the changes induced by aging in the colonic smooth muscle layer of female rats and the protective effect of hormonal therapy. We used young, aged, and ovariectomized aged female rats. Two groups of ovariectomized rats (22 months old) were treated either with melatonin or with estrogen for 10 weeks before sacrifice. Aging induced oxidative imbalance, evidenced by H(2)O(2) accumulation, lipid peroxidation, and decreased catalase activity. The oxidative damage was enhanced by ovariectomy. In addition, aged colonic muscle showed enhanced expression of the pro-inflammatory enzyme cyclooxygenase 2. Expression of the activated forms of caspases 3 and 9 was also enhanced in aged colon. Melatonin and estrogen treatment prevented the oxidative damage and the activation of caspases. In conclusion, aging of colonic smooth muscle induces oxidative imbalance and activation of apoptotic and pro-inflammatory pathways. Hormonal therapy has beneficial effects on the oxidative and apoptotic changes associated to aging in this model.

  15. Short-term therapy with recombinant growth hormone in polytransfused thalassaemia major patients with growth deficiency.

    PubMed

    Cavallo, L; Gurrado, R; Zecchino, C; Manolo, F; De Sanctis, V; Cisternino, M; Caruso-Nicoletti, M; Galati, M

    1998-01-01

    Growth failure is commonly described in polytransfused thalassaemia major patients (Th) with or without growth hormone (GH) releasing hormone-GH axis impairment. We have investigated the efficacy of short-term recombinant GH (rhGH) therapy (Saizen [Serono] 0.1 IU/kg/day 6 evenings/week administered s.c. for 12 months) on growth and predicted final height in 28 (19M, 9F) regularly transfused Th with growth deficiency (aged 14.8 +/- 2.0 yr) on long term desferrioxamine s.c. therapy. All Th had no evidence of congestive heart failure, hypothyroidism or impaired glucose tolerance; in all patients the GH peak (evaluated during both insulin and clonidine test) was < or = 20 mIU/l; hypergonadotropic hypogonadism was excluded in Th with delayed puberty. At the start of therapy height age (HA)/bone age (BA) ratio was 0.92 +/- 0.12. Bone age delay was positively correlated to chronological age (CA), serum ferritin levels (mean of the last three years), the age at the start of chelation therapy, growth velocity calculated for CA during the last year; a positive correlation was also found between circulating IGF-I levels and age at the start of chelation therapy. After 1 year on rhGH therapy there was a significant increase of height calculated for CA (not for BA), of growth velocity calculated for both CA and BA and of circulating IGF-I levels; the HA variation/BA variation ratio was 1.85 +/- 1.71, without any significant difference between predicted final height at the start (-1.08 +/- 1.28 SDS) and at the end of rhGH therapy (-0.88 +/- 1.13). The variation of height calculated for CA was positively correlated to both CA and growth velocity during the last year before rhGH therapy (calculated for CA) and negatively to the height at the start (calculated for CA). There were no side effects and haematological parameters did not show significant changes. In conclusion, our data, obtained in a relatively large group of Th, confirm the emerging results of short-term (12 months

  16. Managing the menopause - British Menopause Society Council consensus statement on hormone replacement therapy.

    PubMed

    Pitkin, Joan; Rees, Margaret C P; Gray, Sarah; Lumsden, Mary Ann; Stevenson, John; Williamson, Jennifer

    2003-09-01

    The British Menopause Society Council aims to aid health professionals to inform and advise women about the menopause. The oestrogen plus progestogen arm of the Women's Health Initiative was stopped in July 2002. This guidance regarding hormone replacement therapy (HRT) use responds to the results and analysis that have been published since then. Because there are few effective alternatives to HRT for vasomotor and urogenital symptoms, oestrogen-based treatments still have a major role. HRT is also most effective for prevention of osteoporosis. Unopposed oestrogens are contraindicated in women with an intact uterus, and hence a range of oestrogen and progestogen combinations, with differing routes of delivery, now exists under the title of "HRT". Treatment choice should be based on up to date information and targeted to individual women's needs. Hormone replacement still offers the potential for benefit to outweigh harm, providing the appropriate regimen has been instigated in terms of dose, route and combination.

  17. The immune system in menopause: pros and cons of hormone therapy.

    PubMed

    Ghosh, Mimi; Rodriguez-Garcia, Marta; Wira, Charles R

    2014-07-01

    With aging, a general decline in immune function is observed leading to immune-senescence. Several of these changes are gender specific affecting postmenopausal women. Menopause is a normal part of a woman's lifecycle and consists of a series of body changes that can last from one to ten years. It is known that loss of sex hormones due to aging results in a reduction of immune functions. However, there remains a major gap in our understanding regarding the loss of immune functions particularly in the female reproductive tract (FRT) following menopause and the role of menopausal hormone therapy (MHT) in protecting against immune senescence. The current review presents an overview of changes in the immune system due to aging, focusing on genital tract immunity in menopausal women and the risks and benefits of using MHT. This article is part of a Special Issue entitled 'Menopause'.

  18. Live birth rates after combined adjuvant therapy in IVF-ICSI cycles: a matched case-control study.

    PubMed

    Motteram, C; Vollenhoven, B; Hope, N; Osianlis, T; Rombauts, L J

    2015-04-01

    The effectiveness of combined co-treatment with aspirin, doxycycline, prednisolone, with or without oestradiol patches, was investigated on live birth (LBR) rates after fresh and frozen embryo transfers (FET) in IVF and intracytoplasmic sperm injection cycles. Cases (n = 485) and controls (n = 485) were extensively matched in a one-to-one ratio on nine physical and clinical parameters: maternal age, body mass index, smoking status, stimulation cycle number, cumulative dose of FSH, stimulation protocol, insemination method, day of embryo transfer and number of embryos transferred. No significant differences were found in fresh cycles between cases and controls for the pregnancy outcomes analysed, but fewer surplus embryos were available for freezing in the combined adjuvant group. In FET cycles, LBR was lower in the treatment group (OR: 0.49, 95% CI 0.25 to 0.95). The lower LBR in FET cycles seemed to be clustered in patients receiving combined adjuvant treatment without luteal oestradiol (OR 0.37, 95% CI 0.17 to 0.80). No difference was found in LBR between cases and controls when stratified according to the number of previous cycles (<3 or ≥3). There is no benefit of this combined adjuvant strategy in fresh IVF cycles, and possible harm when used in frozen cycles.

  19. Long-term hormone replacement therapy and risk of breast cancer in postmenopausal women.

    PubMed

    Newcomb, P A; Longnecker, M P; Storer, B E; Mittendorf, R; Baron, J; Clapp, R W; Bogdan, G; Willett, W C

    1995-10-15

    Despite extensive study, concerns remain about a possible association between long-term postmenopausal hormone treatment--particularly use of combination preparations--and risk of breast cancer. The authors evaluated the use of postmenopausal hormone replacement therapy in relation to breast cancer risk in a large multicenter, population-based case-control study. Women with a new diagnosis of breast cancer were identified through statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls were randomly selected from population lists in each state. For this analysis of postmenopausal women, data were available from 3,130 breast cancer cases and 3,698 controls interviewed between 1989 and 1991. Replacement hormone use was not associated with breast cancer risk in women who had ever undergone this treatment (relative risk (RR) = 1.05, 95% confidence interval (CI) 0.93-1.18). Among women who had used replacement hormones for 15 years or more, there was no clear increase in risk, although the small sample size did not preclude the possibility of a modest association (RR = 1.11, 95% CI 0.87-1.43). Risk among women using progestins in combination with estrogens was similar to that in women using estrogens alone. Risk did not vary according to type of menopause, family history of breast cancer, history of benign breast disease, or alcohol intake. These results are consistent with the majority of reports which find no overall increased risk associated with the use of replacement hormones. However, in contrast to several other studies, this study did not find long-term use to be associated with increased risk. These results also do not support a hypothesized effect of combined progestin and estrogen use on the risk of breast cancer.

  20. Hormone replacement therapy may reduce the return of endogenous lead from bone to the circulation

    SciTech Connect

    Webber, C.E.; Beaumont, L.F.; Gordon, C.L.

    1995-12-01

    Hormone replacement therapy (HRT) in postmenopausal women suppress the increase in bone resorption expected as circulating levels of endogenous estrogen decline. We tested the hypothesis that bone lead content might remain elevated in women on HRT. Fifty-six women who at recruitment were on average 3.5 years postmenopausal were placed on calcium supplementations. Six months later, 33 of these women were prescribed either low dose or moderate dose hormone replacement in addition to the calcium supplementation. After approximately 4 years of hormone replacement, lead content was measured at the tibia and calcaneus by in vivo fluorescence excitation, and lead concentrations were measured in serum, whole blood, and urine. Women not taking hormones had significantly lower lead concentrations in cortical bone compared to all women on HRT (p=0.007). Tibia lead content (mean {plus_minus} SD) for women on calcium only was 11.13 {plus_minus}6.22 {mu}g/g bone mineral. For women on HRT, tibia bone lead was 19.37 {plus_minus}8.62 {mu}g/g bone mineral on low-dose HRT and 16.87 {plus_minus} 11.68 {mu}g/g bone mineral on moderate-dose HRT. There were no differences between groups for lead concentrations measured in trabecular bone, whole blood, serum, or urine. Hormone replacement maintains cortical bone lead content. In women not on HRT, there will be a perimenopausal release of lead from bone. 27 refs., 1 fig., 1 tab.

  1. Influence of modified transdermal hormone replacement therapy on the concentrations of hormones, growth factors, and bone mineral density in women with osteopenia.

    PubMed

    Stanosz, Staniaław; Zochowska, Ewa; Safranow, Krzysztof; Sieja, Krzysztof; Stanosz, Małgorzta

    2009-01-01

    The metabolic and therapeutic action of estrogens depends on their type, dosage, form, route of administration, and treatment-free interval during the therapeutic cycle. Hormone therapy is generally subclassified into 2 forms that differ in the type of hormones. In hormonal replacement therapy (HRT), estrogens and progesterone components do not differ in chemical structure and molecular mass from those naturally produced by the female organism. In hormonal supplementary therapy (HST), the estrogen and progestagen components do differ from the natural hormones in structure and mass. The aim of the study was to compare 2 kinds of hormonal therapy in early postmenopausal women with osteopenia. These forms of therapy are modified transdermal HRT and orally given HST. The objective of this study was the estimation of sex hormone, insulin-like growth factor I (IGF-I), prolactin (PRL), osteocalcin, and procollagen concentration in serum as well as the degree of mineralization of the lumbar spine in women in the early postmenopausal period with osteopenia under different kinds of hormonal therapy. The study was conducted in 75 women with an average age of 52.4 +/- 3.5 years and with primary osteopenia, in the early postmenopausal period, who were randomly assigned to 3 groups depending on the form and route of administration of therapy: Group I (n = 25, control) was receiving placebo in the form of patches. Group II (n = 25) was treated with modified transdermal HRT. This group obtained micronized 17beta-estradiol at increasing-decreasing doses and progesterone in the second phase of the therapeutic cycle. Group III (n = 25) was receiving orally given HST and obtained Cyclo-Menorette (Wyeth, Munster, Germany). The therapeutic cycle in each group lasted 21 days, followed by a 7-day medication-free interval. Estradiol concentration in serum was increased 5-fold and estrone (E(1)) was increased about 11-fold in the group of women receiving orally given HST (P < .0001

  2. Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art.

    PubMed

    Milecki, Piotr; Martenka, Piotr; Antczak, Andrzej; Kwias, Zbigniew

    2010-10-11

    Androgen-deprivation therapy (ADT) is used routinely in combination with definitive external beam radiation therapy (EBRT) in patients with high-risk clinically localized or locally advanced disease. The combined treatment (ADT-EBRT) also seems to play a significant role in improving treatment results in the intermediate-risk group of prostate cancer patients. On the other hand, there is a growing body of evidence that treatment with ADT can be associated with serious and lifelong adverse events including osteoporosis, cardiovascular disease, diabetes, and many others. Almost all ADT adverse events are time dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, it is crucial to clearly state the optimal schedule for ADT in combination with EBRT, that maintaining the positive effect on treatment efficacy would keep the adverse events risk at reasonable level. To achieve this goal, treatment schedule may have to be highly individualized on the basis of the patient-specific potential vulnerability to adverse events. In this study, the concise and evidence-based review of current literature concerning the general rationales for combining radiotherapy and hormonal therapy, its mechanism, treatment results, and toxicity profile is presented.

  3. A Mathematical Model of Prostate Tumor Growth Under Hormone Therapy with Mutation Inhibitor

    NASA Astrophysics Data System (ADS)

    Tao, Youshan; Guo, Qian; Aihara, Kazuyuki

    2010-04-01

    This paper extends Jackson’s model describing the growth of a prostate tumor with hormone therapy to a new one with hypothetical mutation inhibitors. The new model not only considers the mutation by which androgen-dependent (AD) tumor cells mutate into androgen-independent (AI) ones but also introduces inhibition which is assumed to change the mutation rate. The tumor consists of two types of cells (AD and AI) whose proliferation and apoptosis rates are functions of androgen concentration. The mathematical model represents a free-boundary problem for a nonlinear system of parabolic equations, which describe the evolution of the populations of the above two types of tumor cells. The tumor surface is a free boundary, whose velocity is equal to the cell’s velocity there. Global existence and uniqueness of solutions of this model is proved. Furthermore, explicit formulae of tumor volume at any time t are found in androgen-deprived environment under the assumption of radial symmetry, and therefore the dynamics of tumor growth under androgen-deprived therapy could be predicted by these formulae. Qualitative analysis and numerical simulation show that controlling the mutation may improve the effect of hormone therapy or delay a tumor relapse.

  4. Transdermal hormone therapy in postmenopausal women: A review of metabolic effects and drug delivery technologies

    PubMed Central

    Kopper, Nathan W; Gudeman, Jennifer; Thompson, Daniel J

    2008-01-01

    Vasomotor symptoms (VMS) associated with menopause can cause significant discomfort and decrease the quality of life for women in the peri-menopausal and post-menopausal stages of life. Hormone therapy (HT) is the mainstay of treatment for menopausal symptoms and is currently the only therapy proven effective for VMS. Numerous HT options are available to treat VMS, including estrogen-only and estrogen-progestogen combination products to meet the needs of both hysterectomized and nonhysterectomized women. In addition to selecting an appropriate estrogen or estrogen-progestogen combination, consideration should be given to the route of administration to best suit the needs of the patient. Delivery systems for hormone therapy include oral tablets, transdermal patches, transdermal topical (nonpatch) products, and intravaginal preparations. Oral is currently the most commonly utilized route of administration in the United States. However, evidence suggests that oral delivery may lead to some undesirable physiologic effects caused by significant gut and hepatic metabolism. Transdermal drug delivery may mitigate some of these effects by avoiding gut and hepatic first-pass metabolism. Advantages of transdermal delivery include the ability to administer unmetabolized estradiol directly to the blood stream, administration of lower doses compared to oral products, and minimal stimulation of hepatic protein production. Several estradiol transdermal delivery technologies are available, including various types of patches, topical gels, and a transdermal spray. PMID:19920906

  5. Poor Compliance to Hormone Therapy and Decreased Bone Mineral Density in Women with Premature Ovarian Insufficiency

    PubMed Central

    Bachelot, Anne; Nicolas, Carole; Gricourt, Solenne; Dulon, Jérôme; Leban, Monique; Golmard, Jean Louis; Touraine, Philippe

    2016-01-01

    Premature ovarian insufficiency leads to through infertility and estrogen deficiency. Optimal management encompasses estrogen replacement therapy. Long-term outcome of women with POI is not known. We design a study to evaluate the medical care, hormone replacement therapy compliance and bone mineral density (BMD) in POI women with at least a five-year follow-up after the first evaluation. One hundred and sixty-two patients (37.3±8.0 years) were evaluated (follow-up 7.9±2.8 years). Sixty-nine patients (42.6%) had stopped their hormone replacement therapy (HRT) for at least one year during the follow up period. BMD determination at initial evaluation and at follow-up visit was completed in 92 patients. At first evaluation, 28 patients (30%) had osteopenia and 7 (8%) had osteoporosis. At follow up, 31 women (34%) had BMD impairment with osteopenia in 61% and osteoporosis in 5%. In univariate analysis and multivariate analysis, there was a significant loss of femoral BMD in women who had stopped their HRT for over a year. In conclusion, this first study concerning long-term follow-up of POI patients shows the poor compliance to their HRT, despite its importance in the prevention of bone demineralization. This study reinforces the need for follow up and specific care for POI women. PMID:27906970

  6. Effects of external radiation therapy for cancer of the prostate on the serum concentrations of testosterone, follicle-stimulating hormone, luteinizing hormone and prolactin

    SciTech Connect

    Tomic, R.; Bergman, B.; Damber, J.E.; Littbrand, B.; Loefroth, P.O.

    1983-08-01

    Testosterone, luteinizing hormone, follicle-stimulating hormone and prolactin were analyzed in serum from 31 patients with carcinoma of the prostate treated primarily with megavoltage radiation therapy. The total tumor dose varied between 58 and 71 gray (mean 63.5 gray). Absorbed doses to the testes were measured at approximately 1 to more than 10 gray. We investigated retrospectively 17 patients 3 to 60 months (mean 20 months) after therapy and found significantly lower serum testosterone concentrations and significantly higher luteinizing and follicle-stimulating hormone concentrations than in age-matched controls. Of the patients, 14 were followed before and after radiation treatment. Testosterone concentrations were reduced significantly 1 week as well as 3 months after treatment but pre-treatment values were found on analysis 6 and 12 months after treatment. The values for luteinizing and follicle-stimulating hormones were significantly higher 3, 6 and 12 months after radiation treatment compared to pre-treatment values. The follicle-stimulating hormone value already increased after 1 week. The greatest observed testosterone alteration occurred 1 week after treatment in patients who received more than 10 gray over the gonads. The use of lead shields protecting the testes reduced the dose absorbed to the gonads by approximately 50 percent.

  7. The hormonal profile of norethindrone acetate: rationale for add-back therapy with gonadotropin-releasing hormone agonists in women with endometriosis.

    PubMed

    Chwalisz, Kristof; Surrey, Eric; Stanczyk, Frank Z

    2012-06-01

    Gonadotropin-releasing hormone agonists (GnRHa) are an effective treatment of endometriosis-associated pelvic pain. The use of hormonal add-back therapy can alleviate the hypoestrogenic symptoms associated with GnRHa therapy, while preserving therapeutic efficacy. Norethindrone acetate (NETA) is a unique progestin that has both estrogenic and androgenic properties and is effective as an add-back regimen without estrogen supplementation. Through its estrogenic activity, NETA exerts beneficial effects on bone mineral density and vasomotor symptoms in women treated with GnRHa. In addition, NETA exhibits strong endometrial antiproliferative effects, which may result in further benefits for the endometriosis patient population. However, NETA add-back may be associated with progestogenic side effects and may lower high-density lipoprotein due to androgenic activity. These effects must be balanced with the overall benefits of NETA add-back therapy.

  8. Incremental value of hormonal therapy for deep vein thrombosis prediction: an adjusted Wells score for women.

    PubMed

    Barros, Márcio Vinícius Lins de; Arancibia, Ana Elisa Loyola; Costa, Ana Paula; Bueno, Fernando Brito; Martins, Marcela Aparecida Corrêa; Magalhães, Maria Cláudia; Silva, José Luiz Padilha; Bastos, Marcos de

    2016-04-01

    Deep venous thrombosis (DVT) management includes prediction rule evaluation to define standard pretest DVT probabilities in symptomatic patients. The aim of this study was to evaluate the incremental usefulness of hormonal therapy to the Wells prediction rules for DVT in women. We studied women undertaking compressive ultrasound scanning for suspected DVT. We adjusted the Wells score for DVT, taking into account the β-coefficients of the logistic regression model. Data discrimination was evaluated by the receiver operating characteristic (ROC) curve. The adjusted score calibration was assessed graphically and by the Hosmer-Lemeshow test. Reclassification tables and the net reclassification index were used for the adjusted score comparison with the Wells score for DVT. We observed 461 women including 103 DVT events. The mean age was 56 years (±21 years). The adjusted logistic regression model included hormonal therapy and six Wells prediction rules for DVT. The adjusted score weights ranged from -4 to 4. Hosmer-Lemeshow test showed a nonsignificant P value (0.69) and the calibration graph showed no differences between the expected and the observed values. The area under the ROC curve was 0.92 [95% confidence interval (CI) 0.90-0.95] for the adjusted model and 0.87 (95% CI 0.84-0.91) for the Wells score for DVT (Delong test, P value < 0.01). Net reclassification index for the adjusted score was 0.22 (95% CI 0.11-0.33, P value < 0.01). Our results suggest an incremental usefulness of hormonal therapy as an independent DVT prediction rule in women compared with the Wells score for DVT. The adjusted score must be evaluated in different populations before clinical use.

  9. Combined Hypofractionated Radiation and Hormone Therapy for the Treatment of Intermediate-Risk Prostate Cancer

    SciTech Connect

    Yassa, Michael; Fortin, Bernard; Fortin, Marie-Andree; Lambert, Carole; Van Nguyen, Thu; Bahary, Jean-Paul

    2008-05-01

    Purpose: Because of the low alpha/beta value of prostate cancer, a therapeutic gain may be possible with a hypofractionated radiation scheme, and this gain may be further increased with the adjunct of hormone therapy. A Phase II study was undertaken to study the toxicity of such a treatment. Methods and Materials: Forty-two patients with intermediate-risk prostate cancer were recruited for this study. Neoadjuvant and concomitant hormone therapy consisted of one injection of leuprolide acetate (4-month preparation) and 1 month of oral nonsteroidal, anti-androgen medication starting on the day of the injection. Radiation treatment was started 8 weeks after the injection and patients received 57 Gy in 19 fractions. Results: Median follow-up was 46 months. The treatment was well tolerated and no interruptions occurred. The majority (59%) had Grade 0 or 1 acute genitourinary (GU) toxicity, whereas 36% had Grade 2 and 5% had Grade 3 acute GU toxicity. Only Grade 1 or 2 gastrointestinal toxicity was seen. All chronic toxicity was of Grade 1 or 2 except for 3 patients (8%) with Grade 3 toxicity. Sixty-eight percent (68%) of patients had no long-term side effects from the treatment. At time of analysis, 79% showed no sign of treatment failure. Conclusions: Hypofractionated radiation with neoadjuvant and concomitant hormone therapy is well tolerated with no significant short- or long-term morbidity. Control for this risk group is good, and comparative Phase III studies should be undertaken to determine whether this treatment is superior to new evolving treatments.

  10. Compounded non-FDA–approved menopausal hormone therapy prescriptions have increased: results of a pharmacy survey

    PubMed Central

    Pinkerton, JoAnn V.; Constantine, Ginger D.

    2016-01-01

    Abstract Objective: From a survey of compounding pharmacists, specific questions regarding compounded menopausal hormone therapy were used to estimate compounded hormone therapy (CHT) prescribing in the United States. Methods: A national online survey was conducted by Rose Research—a market research company consisting of 12,250 US pharmacists from independent community pharmacies (ICPs) and compounding pharmacies (CPs). Pharmacists who completed the survey and met the prespecified criteria were eligible. Data from the survey were extrapolated to estimate overall CHT prescription volume and annual costs of CHT prescriptions for the United States based upon industry data from the National Community Pharmacists Association and IBISWorld. Results: Surveys were completed by 483 pharmacies, including 365 ICPs and 118 CPs. On the basis of the survey responses and extrapolated industry data, an estimated 26 to 33 million CHT prescriptions were filled annually, with total sales estimated at $1.3 to $1.6 billion. CPs (vs ICPs) accounted for a higher proportion of CHT prescriptions. More than half of the ICPs (52%) and CPs (75%) expected continued compounding business growth, with most predicting 5% to 25% growth within 2 years, despite the potential effect of restrictive legislation regarding compounding. Conclusions: On the basis of extrapolated data from numbers of prescriptions reported by pharmacists participating in the survey, the volume of CHT seems to approach that of Food and Drug Administration (FDA)-approved menopausal hormone therapy, and growth in the CHT market is expected. Thus, physicians should educate themselves and the women consulting them about the differences between the FDA-approved and the less-tested CHT formulations. More research on the efficacy, safety, and consistency of non-FDA–approved CHT is needed. PMID:26645819

  11. Adjuvant Intravesical Bacillus Calmette-Guérin Therapy and Survival Among Elderly Patients With Non–Muscle-Invasive Bladder Cancer

    PubMed Central

    Spencer, Benjamin A.; McBride, Russell B.; Hershman, Dawn L.; Buono, Donna; Herr, Harry W.; Benson, Mitchell C.; Gupta-Mohile, Supriya; Neugut, Alfred I.

    2013-01-01

    Purpose: National guidelines recommend adjuvant intravesical Bacillus Calmette-Guérin (BCG) therapy for higher-risk non–muscle-invasive bladder cancer (NMIBC). Although a survival benefit has not been demonstrated, randomized trials have shown reduced recurrence and delayed progression after its use. We investigated predictors of BCG receipt and its association with survival for older patients with NMIBC. Patients and Methods: We identified individuals with NMIBC registered in the Surveillance, Epidemiology, and End Results–Medicare database from 1991 to 2003. We used logistic regression to compare those treated with BCG within 6 months of initial diagnosis with those not treated, adjusting for demographic and clinical factors. Cox proportional hazards modeling was used to analyze the association between BCG and overall survival (OS) and bladder cancer–specific survival (BCSS) for the entire cohort and within tumor grades. Results: Of 23,932 patients with NMIBC identified, 22% received adjuvant intravesical BCG. Predictors of receipt were stages Tis and T1, higher grade, and urban residence. Age > 80 years, fewer than two comorbidities, and not being married were associated with decreased use. In the survival analysis, BCG use was associated with better OS (hazard ratio [HR], 0.87; 95% CI, 0.83 to 0.92) in the entire cohort and BCSS among higher-grade cancers (poorly differentiated: HR, 0.78; 95% CI, 0.72 to 0.85; undifferentiated: HR, 0.66; 95% CI, 0.56 to 0.77). Conclusion: Despite guidelines recommending its use, BCG is administered to less than one quarter of eligible patients. This large population-based study found improved OS and BCSS were associated with use of adjuvant intravesical BCG among older patients with NMIBC. Better-designed clinical trials focusing on higher-grade cancers are needed to confirm these findings. PMID:23814517

  12. Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas.

    PubMed

    Nayak, Lakshmi; de Groot, John; Wefel, Jeffrey S; Cloughesy, Timothy F; Lieberman, Frank; Chang, Susan M; Omuro, Antonio; Drappatz, Jan; Batchelor, Tracy T; DeAngelis, Lisa M; Gilbert, Mark R; Aldape, Kenneth D; Yung, Alfred W K; Fisher, Joy; Ye, Xiaobu; Chen, Alice; Grossman, Stuart; Prados, Michael; Wen, Patrick Y

    2017-03-01

    Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor, depleting circulating levels of these growth factors. The Adult Brain Tumor Consortium conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed HGG with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen. Fifty-nine patients were enrolled, 21 in arm 1, 20 in arm 2 and 18 in arm 3. Median age was 56 years (24-69); median KPS 90 (60-100). The maximum tolerated dose (MTD) of aflibercept for all 3 arms was 4 mg/kg every 2 weeks. Dose limiting toxicities at the MTD were: Arm 1: 0/21 patients; Arm 2: 2/20 patients (G3 deep vein thrombosis, G4 neutropenia; Arm 3: 3/18 patients) (G4 biopsy-confirmed thrombotic microangiopathy, G3 rash, G4 thrombocytopenia). The median number of cycles of aflibercept was 5 (range, 1-16). All patients stopped treatment; 28 (47%) for disease progression, 21 (36%) for toxicities, 8 (14%) for other reasons, and 2 (3%) patients completed the full treatment course. This study met its primary endpoint and the MTD of aflibercept with radiation and concomitant and adjuvant temozolomide is 4 mg/kg every 2 weeks.

  13. 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.

  14. Managing the menopause: British Menopause Society Council consensus statement on hormone replacement therapy.

    PubMed

    Pitkin, Joan; Rees, Margaret C P; Gray, Sarah; Lumsden, Mary Ann; Marsden, Jo; Stevenson, John; Williamson, Jennifer

    2005-12-01

    The British Menopause Society Council aims to help health professionals inform and advise women about the menopause. This guidance regarding estrogen-based hormone replacement therapy (HRT), including tibolone, which is classified in the British National Formulary as HRT, responds to the results and analysis of the randomized Women's Health Initiative studies and the observational Million Women Study. Treatment choice should be based on up-to-date information and targeted to individual women's needs. HRT still offers the potential for benefit to outweigh harm, providing the appropriate regimen has been instigated in terms of dose, route and combination.

  15. Effect of menopausal hormone therapy on components of the metabolic syndrome.

    PubMed

    Lovre, Dragana; Lindsey, Sarah H; Mauvais-Jarvis, Franck

    2016-05-27

    The world population is aging, and women will spend an increasing share of their lives in a postmenopausal state that predisposes to metabolic dysfunction. Thus, the prevalence of metabolic syndrome (MetS) in women is likely to increase dramatically. This article summarizes the effects of menopause in predisposing to components of MetS including visceral obesity, dyslipidemia, type 2 diabetes (T2D) and hypertension (HTN). We also summarize the effects of menopausal hormone therapy (MHT) in reversing these metabolic alterations and discuss therapeutic advances of novel menopausal treatment on metabolic function.

  16. Effective role of hormonal therapy in metastatic primary neuroendocrine breast carcinoma.

    PubMed

    Buttar, Amanpreet; Mittal, Kriti; Khan, Ashraf; Bathini, Venu

    2011-10-01

    Primary neuroendocrine carcinoma (PNEC) of the breast is extremely rare.(1) Because of the rarity of this cancer, long-term prognosis, biologic behavior, and treatment are not well known. PNEC can have high expression of estrogen receptor (ER) and progesterone receptor (PR). It is important to differentiate PNEC of the breast from other metastatic diseases to the breast because of the differences in treatment. We herein report the successful treatment of a patient with PNEC of the breast and high expression of ER and PR by means of hormonal therapy.

  17. A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme.

    PubMed

    Rosenfeld, Myrna R; Ye, Xiaobu; Supko, Jeffrey G; Desideri, Serena; Grossman, Stuart A; Brem, Steven; Mikkelson, Tom; Wang, Daniel; Chang, Yunyoung C; Hu, Janice; McAfee, Quentin; Fisher, Joy; Troxel, Andrea B; Piao, Shengfu; Heitjan, Daniel F; Tan, Kay-See; Pontiggia, Laura; O'Dwyer, Peter J; Davis, Lisa E; Amaravadi, Ravi K

    2014-08-01

    Preclinical studies indicate autophagy inhibition with hydroxychloroquine (HCQ) can augment the efficacy of DNA-damaging therapy. The primary objective of this trial was to determine the maximum tolerated dose (MTD) and efficacy of HCQ in combination with radiation therapy (RT) and temozolomide (TMZ) for newly diagnosed glioblastoma (GB). A 3 + 3 phase I trial design followed by a noncomparative phase II study was conducted in GB patients after initial resection. Patients received HCQ (200 to 800 mg oral daily) with RT and concurrent and adjuvant TMZ. Quantitative electron microscopy and immunoblotting were used to assess changes in autophagic vacuoles (AVs) in peripheral blood mononuclear cells (PBMC). Population pharmacokinetic (PK) modeling enabled PK-pharmacodynamic correlations. Sixteen phase I subjects were evaluable for dose-limiting toxicities. At 800 mg HCQ/d, 3/3 subjects experienced Grade 3 and 4 neutropenia and thrombocytopenia, 1 with sepsis. HCQ 600 mg/d was found to be the MTD in this combination. The phase II cohort (n = 76) had a median survival of 15.6 mos with survival rates at 12, 18, and 24 mo of 70%, 36%, and 25%. PK analysis indicated dose-proportional exposure for HCQ. Significant therapy-associated increases in AV and LC3-II were observed in PBMC and correlated with higher HCQ exposure. These data establish that autophagy inhibition is achievable with HCQ, but dose-limiting toxicity prevented escalation to higher doses of HCQ. At HCQ 600 mg/d, autophagy inhibition was not consistently achieved in patients treated with this regimen, and no significant improvement in overall survival was observed. Therefore, a definitive test of the role of autophagy inhibition in the adjuvant setting for glioma patients awaits the development of lower-toxicity compounds that can achieve more consistent inhibition of autophagy than HCQ.

  18. Utilization of adjuvant arthritis model for evaluation of new approaches in rheumatoid arthritis therapy focused on regulation of immune processes and oxidative stress.

    PubMed

    Bauerová, Katarína; Poništ, Silvester; Mihalová, Danica; Dráfi, František; Kuncírová, Viera

    2011-03-01

    As a number of disease-modifying anti-rheumatic drugs often have side effects at high doses and/or during long-term administration, increased efficacy without increased toxicity is expected for combination therapy of rheumatoid arthritis (RA). The safety of long-term therapy of RA is very important as patients with RA are usually treated for two or more decades. This experimental overview is focused on some promising substances and their combinations with the standard antirheumatic drug - methotrexate (Mtx) for treatment of rheumatoid arthritis. The adjuvant arthritis model in Lewis rats was used for evaluation of antiinflammatory efficacy of the substances evaluated. Mtx was administered in the oral dose of 0.3 mg/kg b.w. twice a week. Natural and synthetic antioxidants were administered in the daily oral dose of 20 mg/kg b.w for coenzyme Q(10) (CoQ(10)), 150 mg/kg b.w for carnosine (Carn), 15 mg/kg b.w. for stobadine dipalmitate (Stb) and its derivative SMe1.2HCl (SMe1), and 30 mg/kg b.w. for pinosylvin (Pin) or pterostilbene (Pte). Mtx in the oral dose of 0.4 mg/kg b.w. twice a week was combined with Pin in the oral daily dose of 50 mg/kg b.w. Clinical (hind paw volume - HPV), biochemical (activity of GGT in joint and level of TBARS in plasma), and immunological (IL-1 in plasma) parameters were assessed. Our results achieved with different antioxidants in monotherapies showed a reduction of oxidative stress in adjuvant arthritis independently of the chemical structure of the compounds. Pin was the most effective antioxidant tested in decreasing HPV. All combinations tested showed a higher efficacy in affecting biochemical or immunological parameters than Mtx administered in monotherapy. The findings showed the benefit of antioxidant compounds for their use in combination therapy with methotrexate.

  19. Adjuvant photodynamic therapy (PDT) with photosensitizer photosens for superficial bladder cancer: experimental investigations to treat prostate cancer by PDT with photosens

    NASA Astrophysics Data System (ADS)

    Apolikhin, Oleg I.; Chernishov, Igor V.; Sivkov, Andrey V.; Altunin, Denis V.; Kuzmin, Sergey G.; Vorozhtsov, Georgy N.

    2007-07-01

    14 patients with transional-cell bladder cancer in stage T1N0M0G2 after transurethral bladder resection were offered adjuvant treatment with PDT. Adjuvant PDT was performed 1-1.5 months after transurethral bladder resection for superficial bladder cancer. Prior to PDT conventional and fluorescent cystoscopy were performed. In the absence of inflammation and after full epitalisation of postoperative wound a session of therapy was performed. 24 hours prior to PDT-session photosensitizer Photosens was injected intravenously in the dose of 0.8 mg per kg of body weight. Prior to PDT local anesthesia of urethra with lidocain-gel was performed. Cystoscopy was carried out. PDT was performed with diode laser "Biospec" (675 nm). During the session the place of standing diffuser and the volume of a bladder were controlled. After 7 months of observation no tumor recidivists were observed. Registered side effects were not life-threatened. 5 patients had pain or discomfort in suprapubic area, ceasing spontaneously or requiring administration of analgetics. No systemic side-effects or allergic reactions were observed. The method can be used in out-patient practice. Absence of early recidivists shows efficiency of PDT in the treatment of superficial bladder cancer. Further study is necessary to estimate optimal regimen of PDT. The further controlling of condition on the patients in this group is required. At the laboratory animals' experiment, we conducted the explorations devoted to the influence of the photodynamic effect at the prostate's tissues.

  20. Effects of Korean red ginseng as an adjuvant to bile acids in medical dissolution therapy for gallstones: a prospective, randomized, controlled, double-blind pilot trial.

    PubMed

    Lee, Jun Kyu; Kang, Hyoun Woo; Kim, Jae Hak; Lim, Yun Jeong; Koh, Moon-Soo; Lee, Jin Ho

    2013-01-01

    Although ginseng, the root of Panax quinquefolium and P. ginseng, was reported to have anti-cholelithogenic effects in animal experiments, there have, to date, been no human studies. We conducted this prospective, controlled, double-blind pilot trial to evaluate the safety and efficiency of Korean red ginseng (KRG), the steamed root of P. ginseng C.A. Meyer. Twenty eight consecutive patients were randomized to receive either KRG (7.5 g divided into three daily doses) or a placebo as an adjuvant to the standard regimen of bile acids for gallstones (500 mg of chenodeoxycholic acid and 500 mg of ursodeoxycholic acid divided into three daily doses) for 24 weeks. No case of serious adverse reaction occurred in both groups. Although the decrease in stone burden was larger in the KRG group (3.4 ± 0.6 ml3) than in the placebo group (2.3 ± 1.1 ml(3)), it did not reach statistical significance (p = 0.09). Also there were no differences in the rate of complete dissolution, subjective improvement in symptoms, and the rate of cholecystectomy due to worsening pain or the development of complications and changes in laboratory tests before and after treatment. In conclusion, the addition of KRG as an adjuvant was safe for patients undergoing bile acid dissolution therapy for gallstones although it did not affect the results. Large-scaled trials to optimize regimens are expectantly needed.

  1. Comparison of Efficacy and Side Effects of Oral Baclofen Versus Tizanidine Therapy with Adjuvant Botulinum Toxin Type A in Children With Cerebral Palsy and Spastic Equinus Foot Deformity.

    PubMed

    Dai, Alper I; Aksoy, Sefika N; Demiryürek, Abdullah T

    2016-02-01

    This retrospective study aimed to compare the therapeutic response, including side effects, for oral baclofen versus oral tizanidine therapy with adjuvant botulinum toxin type A in a group of 64 pediatric patients diagnosed with static encephalopathy and spastic equinus foot deformity. Following botulinum toxin A treatment, clinical improvement led to the gradual reduction of baclofen or tizanidine dosing to one-third of the former dose. Gross Motor Functional Measure and Caregiver Health Questionnaire scores were markedly elevated post-botulinum toxin A treatment, with scores for the tizanidine (Gross Motor Functional Measure: 74.45 ± 3.72; Caregiver Health Questionnaire: 72.43 ± 4.29) group significantly higher than for the baclofen group (Gross Motor Functional Measure: 68.23 ± 2.66; Caregiver Health Questionnaire: 67.53 ± 2.67, P < .001). These findings suggest that the combined use of botulinum toxin A and a low dose of tizanidine in treating children with cerebral palsy appears to be more effective and has fewer side effects versus baclofen with adjuvant botulinum toxin A.

  2. Hormone replacement therapy, cancer, controversies, and women's health: historical, epidemiological, biological, clinical, and advocacy perspectives

    PubMed Central

    Krieger, N.; Lowy, I.; Aronowitz, R.; Bigby, J.; Dickersin, K.; Garner, E.; Gaudilliere, J.; Hinestrosa, C.; Hubbard, R.; Johnson, P.; Missmer, S.; Norsigian, J.; Pearson, C.; Rosenberg, C.; Rosenberg, L.; Rosenkrantz, B.; Seaman, B.; Sonnenschein, C.; Soto, A.; Thornton, J.; Weisz, G.

    2005-01-01

    Routine acceptance of use of hormone replacement therapy (HRT) was shattered in 2002 when results of the largest HRT randomised clinical trial, the women's health initiative, indicated that long term use of oestrogen plus progestin HRT not only was associated with increased risk of cancer but, contrary to expectations, did not decrease, and may have increased, risk of cardiovascular disease. In June 2004 a group of historians, epidemiologists, biologists, clinicians, and women's health advocates met to discuss the scientific and social context of and response to these findings. It was found that understanding the evolving and contending knowledge on hormones and health requires: (1) considering its societal context, including the impact of the pharmaceutical industry, the biomedical emphasis on individualised risk and preventive medicine, and the gendering of hormones; and (2) asking why, for four decades, since the mid-1960s, were millions of women prescribed powerful pharmacological agents already demonstrated, three decades earlier, to be carcinogenic? Answering this question requires engaging with core issues of accountability, complexity, fear of mortality, and the conduct of socially responsible science. PMID:16100311

  3. Osteoprotective effect of hormone therapy on bone microarchitecture before impaired bone mineral density in ovariectomized rats

    PubMed Central

    Terzi, Hasan; Çırpan, Teksin; Terzi, Rabia; Yeniel, Ahmet Özgür; Aktuğ, Hüseyin; Bilgin, Onur

    2012-01-01

    Objective: We aimed to determine the effect of hormone replacement therapy on bone microarchitecture in ovariectomized rats. Material and Methods: In the Animal Ethics Committee approved-study, the effect of treatment with 17 β-estradiol 50 μg/kg and medroxyprogesterone 2.5 mg/kg on bone architecture and bone mineral density in rats versus ovariectomized control rats over the course of 20 days were evaluated. Femoral and lumbar bone mineral density levels and morphometric measurements were performed. Results: There were no significant differences in the femoral and lumbar bone mineral density levels between the groups. In the intact control group, the trabecular structures were significantly superior to those in the other groups. Additionally, the osteoblast count was significantly higher while the osteoclast count was significantly lower than in all other groups. Two parameters reflecting trabecular bone microarchitecture, which include the trabecular count and the trabecular area, demonstrated significant improvement in the hormone replacement group when compared to the ovariectomized control group. In the hormone replacement groups, the osteoblast count was significantly higher while the osteoclast count was significantly lower than in the ovariectomized control group. Conclusion: We suggest that offering estrogen alone or in combination with progestogen can be a beneficial approach in preventing early postmenopausal bone loss regardless of bone mineral density. PMID:24592053

  4. TOMOGRAFIC AND TENSIOMETRIC ASSESSMENT ON FEMURS FROM OOPHORECTOMIZED RATS SUBJECTED TO HORMONE REPLACEMENT THERAPY

    PubMed Central

    Martynetz, Fábio Alexandre; Pessole Biondo-Simões, Maria de Lourdes; Martynetz, Juliano Rodrigo; Martynetz, Tatiana Daher; Zimerman, Elise; Neto, Heraldo Mello

    2015-01-01

    Objective: To analyze the biomechanical and tomographic effects of hormone replacement therapy (HRT) on femurs from rats subjected to induced menopause. Methods: Forty-five adult Wistar rats were divided equally into three groups. The first and second groups consisted of rats subjected to oophorectomy, and the third was the control group, consisting of nonoophorectomized rates. After verifying that hormone failure had occurred (exfoliative cytological test), only the first group received HRT, over a two-month period. After this period, the femurs were disarticulated and subjected to biomechanical tests in a universal testing machine to evaluate their strength, and were subjected to tomographic evaluation to determine the bone mineral density. Results: The exfoliative cytological test showed that hormone failure was induced in all the oophorectomized animals. A significant difference (p = 0.030) in maximum strength measurements was observed between the groups (higher in the group with HRT). Greater bone fragility was observed in the oophorectomized animals without HRT than in those with HRT (p = 0.010), in relation to the control group (p = 0.0107). There was greater bone strength in the oophorectomized rats with HRT than in those without HRT, and these values were similar to those of the control group (p = 0.179). In the tomographic evaluation, no significant differences were found between the groups (p = 0.625). Conclusion: A significant increase in bone strength was observed with the use of HRT. However, treatment with HRT did not show any significant change in bone mineral density. PMID:27019837

  5. Use of Menopausal Hormone Therapy and Bioidentical Hormone Therapy in Australian Women 50 to 69 Years of Age: Results from a National, Cross-Sectional Study.

    PubMed

    Velentzis, Louiza S; Banks, Emily; Sitas, Freddy; Salagame, Usha; Tan, Eng Hooi; Canfell, Karen

    2016-01-01

    Menopausal Hormone Therapy (MHT) use in Australia fell by 55% from 2001 to 2005, following the release of large-scale findings on its risks and benefits. Comprehensive national data, including information on overall prevalence of MHT use as well as information on duration of use in Australia have not been reported since the 2004-5 National Health Survey, when 11% of women aged 45+ years were estimated to be current MHT users. No national data are available on prevalence of use of "bioidentical" hormone therapy (BHT). The objective of this study was to determine recent prevalence of MHT and BHT use. A cross-sectional, national, age-stratified, population survey was conducted in 2013. Eligible women, aged 50-69 years, resident in Australia were randomly sampled in 5-year age groups from the Medicare enrolment database (Australia's universal health scheme). The response rate was 22% based on return of completed questionnaires, and analyses were restricted to 4,389 women within the specified age range. The estimated population-weighted prevalence of current use of MHT was 13% (95%CI 12-14), which was broadly similar to the previously reported national figures in 2004-5, suggesting that the use of MHT in Australia has largely stabilised over the past decade. A total of 39% and 20% of current-users with an intact uterus reported use of oestrogen-progestagen MHT and oestrogen-only MHT, respectively, whereas 77% of hysterectomised current-users used oestrogen-only MHT. Almost three-quarters of current-users [population-weighted prevalence 9% (95%CI 8-10)] had used MHT for ≥5 years. In regard to BHT, estimated population-weighted prevalence of ever use was 6% (95%CI 6-7) and 2% (95%CI 2-3) for current use. The population-weighted prevalence of MHT and BHT combined, in current users in their fifties and sixties was 15% (95%CI 14-16). These data provide a recent national "snapshot" of Australian women's use of both conventional MHT and of BHT.

  6. Sources of information influencing the state-of-the-science gap in hormone replacement therapy usage

    PubMed Central

    Wu, Xianwei

    2017-01-01

    Objective Medical reviews and research comprise a key information source for news media stories on medical therapies and innovations as well as for physicians in updating their practice. The present study examined medical review journal articles, physician surveys and news media coverage of hormone replacement therapy (HT) to assess the relationship between the three information sources and whether/if they contributed to a state-of-the-science gap (a condition when the evaluation of a medical condition or therapy ascertained by the highest standards of investigation is incongruent with the science-in-practice such as physician recommendations and patient actions). Methods We content-analyzed 177 randomly sampled HT medical reviews between 2002 and 2014, and HT news valence in three major TV networks, newspapers and magazines/internet sites in 2002–2003, 2008–2009 and 2012–14. The focus in both analyses was whether HT benefits outweighed risks, risks outweighed benefits or both risks and benefits were presented. We also qualitatively content-analyzed all 19 surveys of US physicians’ HT recommendations from 2002 to 2009, and 2012 to 2014. Results Medical reviews yielded a mixed picture about HT (40.1% benefits, 26.0% risks, and 33.9% both benefits and risks). While a majority of physician surveys were pro-HT 10/19), eight showed varied attitudes and one was negative. Newspaper and television coverage reflected a pro and con balance while magazine stories were more positive in the later reporting period. Conclusion Medical journal review articles, physicians, and media reports all provide varying view points towards hormone therapy use thus leading to limited knowledge about the actual risks and benefits of HT among peri- and menopausal women and a state-of-the-science gap. PMID:28158240

  7. European Code against Cancer 4th Edition: Medical exposures, including hormone therapy, and cancer.

    PubMed

    Friis, Søren; Kesminiene, Ausrele; Espina, Carolina; Auvinen, Anssi; Straif, Kurt; Schüz, Joachim

    2015-12-01

    The 4th edition of the European Code against Cancer recommends limiting - or avoiding when possible - the use of hormone replacement therapy (HRT) because of the increased risk of cancer, nevertheless acknowledging that prescription of HRT may be indicated under certain medical conditions. Current evidence shows that HRT, generally prescribed as menopausal hormone therapy, is associated with an increased risk of cancers of the breast, endometrium, and ovary, with the risk pattern depending on factors such as the type of therapy (oestrogen-only or combined oestrogen-progestogen), duration of treatment, and initiation according to the time of menopause. Carcinogenicity has also been established for anti-neoplastic agents used in cancer therapy, immunosuppressants, oestrogen-progestogen contraceptives, and tamoxifen. Medical use of ionising radiation, an established carcinogen, can provide major health benefits; however, prudent practices need to be in place, with procedures and techniques providing the needed diagnostic information or therapeutic gain with the lowest possible radiation exposure. For pharmaceutical drugs and medical radiation exposure with convincing evidence on their carcinogenicity, health benefits have to be balanced against the risks; potential increases in long-term cancer risk should be considered in the context of the often substantial and immediate health benefits from diagnosis and/or treatment. Thus, apart from HRT, no general recommendations on reducing cancer risk were given for carcinogenic drugs and medical radiation in the 4th edition of European Code against Cancer. It is crucial that the application of these measures relies on medical expertise and thorough benefit-risk evaluation. This also pertains to cancer-preventive drugs, and self-medication with aspirin or other potential chemopreventive drugs is strongly discouraged because of the possibility of serious, potentially lethal, adverse events.

  8. Fatal Breast Cancer Risk in Relation to Use of Unopposed Estrogen and Combined Hormone Therapy

    PubMed Central

    Pocobelli, Gaia; Newcomb, Polly A.; Li, Christopher I.; Cook, Linda S.; Barlow, William E.; Weiss, Noel S.

    2014-01-01

    Background Use of combined hormone therapy (CHT) is associated with increased breast cancer incidence, but it is unclear whether this translates into increased breast cancer mortality. Methods We conducted a population-based nested case-control study in Saskatchewan, Canada, where a population-based prescription drug database has existed since 1975. We evaluated fatal breast cancer risk in relation to recency and duration of use of CHT and unopposed estrogen hormone therapy (EHT). Results A total of 1,288 cases and 12,535 controls were included in the analyses. Exclusive use of EHT was not associated with fatal breast cancer risk, either overall or within categories of recency or duration (odds ratio (OR) for current versus never use=1.1; 95% CI (confidence interval), 0.8–1.3). Use of CHT (includes women who had also used EHT) was also not associated with fatal breast cancer risk (OR for current versus never use=0.9; 95% CI, 0.7–1.3), except for a suggestion of an increased risk with current long-term use. Conclusion Consistent with prior studies, we observed no increased risk of fatal breast cancer associated with use of EHT. To date only a few studies have evaluated fatal breast cancer risk in relation to use of CHT, and collectively the results are inconsistent. PMID:24671356

  9. Neoadjuvant hormonal therapy for endocrine sensitive breast cancer: a systematic review.

    PubMed

    Charehbili, A; Fontein, D B Y; Kroep, J R; Liefers, G J; Mieog, J S D; Nortier, J W R; van de Velde, C J H

    2014-02-01

    In recent years, studies investigating neoadjuvant therapies have been emerging, because of the additional benefits it provides in terms of facilitating less extensive surgery and the possibility of investigating tumor biological features and response. Neoadjuvant hormonal therapy (NHT) is, in general, considered to be a suitable option for hormone receptor (HR)-positive patients who are unfit for chemotherapy or surgery, and is increasingly being utilized to achieve tumor downsizing before surgery in postmenopausal women. Studies investigating NHT were reviewed for tumor response data. NHT demonstrated similar efficacy to neoadjuvant chemotherapy (NCT) in HR-positive breast cancer patients. Clinical responses ranged from 13.5% to 100%, with treatment periods between 3 and 24 months. In studies comparing tamoxifen with aromatase inhibitors, the latter were superior in terms of tumor response and rates of breast-conserving surgery (BCS). In most studies with treatment durations longer than 3 months, tumor response rates increased. Therefore, longer durations of NHT are feasible and should be considered as an alternative to NCT in selected patients.

  10. Acceleration of puberty during growth hormone therapy in a child with septo-optic dysplasia.

    PubMed

    Catlı, Gönül; Altıncık, Ayça; Anık, Ahmet; Demir, Korcan; Güleryüz, Handan; Abacı, Ayhan; Böber, Ece

    2014-01-01

    Septo-optic dysplasia (SOD) is a heterogeneous disorder of the central nervous system characterized by various endocrinological and neurological findings. It is a complex disease caused by a combination of genetic and environmental factors. Herein, we report the case of a 5.5-year-old girl who presented with short stature and strabismus. Ophthalmological examination revealed bilateral optic nerve hypoplasia. Ectopic posterior pituitary and bilateral optic hypoplasia were detected on brain magnetic resonance imaging. The presence of bilateral optic nerve hypoplasia and hypopituitarism led to the diagnosis of SOD. An abated growth hormone (GH) response was found in the GH stimulation test and GH replacement therapy was initiated. At the end of the first year of clinical follow-up, secondary hypothyroidism was detected and L-thyroxine was added to the treatment. At the age of 8.25 years, thelarche was noted and 6 months later, the patient presented with menarche. At this time, the bone age was 12 years and the basal luteinizing hormone level was 7 mIU/mL. These findings indicated acceleration in the process of pubertal development. We report this case (i) to emphasize the need to investigate hypopituitarism in cases with bilateral optic nerve hypoplasia and (ii) to draw attention to the fact that during the follow-up of SOD cases receiving GH therapy, inappropriate acceleration of growth velocity and rapid improvement in bone age may be predictive of central precocious puberty development.

  11. Sequential Amniotic Fluid Thyroid Hormone Changes Correlate with Goiter Shrinkage following in utero Thyroxine Therapy.

    PubMed

    Munoz, Jessian L; Kessler, Alan A; Felig, Philip; Curtis, Jenifer; Evans, Mark I

    2016-01-01

    Several isolated reports of fetal goiter treatment have shown limited generalizability of approaches and provide no real guidance for optimal timing, dosages, and treatment strategies. Graves' disease accounts for >60% of these cases. Maternal treatments of hyperthyroidism include antithyroid medications such as methimazole and more commonly propylthiouracil (PTU). Here, our management of a patient with a fetal thyroid goiter from maternal exposure to PTU diagnosed at 23.6 weeks' gestation and the management of other cases allow us propose a general strategy for treatment. Intrauterine therapy with 200 and then 400 μg of levothyroxine (3 weeks apart) showed an 85% reduction in fetal thyroid goiter volume. We collected amniotic fluid samples at the time of treatments and assayed thyroid hormones and associated antibodies which closely reflected the changes in thyroid goiter mass volume. Our observations suggest a weekly or biweekly therapeutic intervention schedule. Utilizing both goiter size as well as a novel approach in using amniotic fluid hormone levels to monitor therapy efficacy might improve the quality of treatments. Only with a standardized approach and collection of amniotic fluid thyroid panels do we have the opportunity to develop the database required to determine the number and timing of treatments needed.

  12. Management of acne vulgaris with hormonal therapies in adult female patients.

    PubMed

    Husein-ElAhmed, Husein

    2015-01-01

    Acne vulgaris is a very common condition affecting up of 93% of adolescents. Although rare, this disease may persist in adulthood. In adult women with acne (those older than 25 years old), this condition is particularly relevant because of the refractory to conventional therapies, which makes acne a challenge for dermatologists in this group of patients. In order to its potential risk for chronicity and the involvement of visible anatomical sites such as face and upper torso, acne has been associated with a wide spectrum of psychological and social dysfunction such as depression, anxiety, suicidal ideation, somatization, and social inhibition. In particular, adult women with acne have been shown to be adversely impacted by the effect of acne on their quality of life. For the last four decades, dermatologists have used hormonal therapies for the management of acne vulgaris in adult women, which are considered a rational choice given the severity and chronicity of this condition in this group of patients. The aim of this work is to review the hormonal drugs for management of acne.

  13. Reduced pulsatile growth hormone secretion in children after therapy for acute lymphoblastic leukemia

    SciTech Connect

    Blatt, J.; Bercu, B.B.; Gillin, J.C.; Mendelson, W.B.; Poplack, D.G.

    1984-02-01

    Basal growth hormone levels were measured every 20 minutes over 24 hours in eight long-term survivors of acute lymphoblastic leukemia and in 13 age- and pubertal stage-matched normal children. Among the patients, the median total basal growth hormone output (AUC) was 43 units, compared with 341 units in the normal control group (P less than 0.001). In the patients, mean pulse amplitude (6.9 ng/ml) and frequency (4.6) over 24 hours also were reduced, compared with the control values (32 ng/ml and 8.5, P less than 0.001 and P less than 0.05, respectively). In addition, normal children secreted more GH at night (median AUC 280) than during the day (113, P less than 0.001). However, this diurnal pattern was absent in three of the patients studied. These data suggest that perturbations of spontaneous pulsatile GH secretion are common after standard therapy for ALL and may be a sensitive means of detecting therapy-related neuroendocrine damage. Blunting of spontaneous pulsatile GH secretion may contribute to the abnormalities in growth seen in children with ALL.

  14. Fatal breast cancer risk in relation to use of unopposed estrogen and combined hormone therapy.

    PubMed

    Pocobelli, Gaia; Newcomb, Polly A; Li, Christopher I; Cook, Linda S; Barlow, William E; Weiss, Noel S

    2014-06-01

    Use of combined hormone therapy (CHT) is associated with increased breast cancer incidence, but it is unclear whether this translates into increased breast cancer mortality. To address this question, we conducted a population-based nested case-control study in Saskatchewan, Canada, where a population-based prescription drug database has existed since 1975. We evaluated fatal breast cancer risk in relation to recency and duration of use of CHT and unopposed estrogen hormone therapy (EHT). A total of 1,288 cases and 12,535 controls were included in the analyses. Exclusive use of EHT was not associated with fatal breast cancer risk, either overall or within categories of recency or duration [odds ratio (OR) for current vs. never use = 1.1; 95 % confidence interval (CI) 0.8-1.3]. Use of CHT (includes women who had also used EHT) was also not associated with fatal breast cancer risk (OR for current vs. never use = 0.9; 95 % CI 0.7-1.3), except for a suggestion of an increased risk with current long-term use. Consistent with prior studies, we observed no increased risk of fatal breast cancer associated with use of EHT. To date only a few studies have evaluated fatal breast cancer risk in relation to use of CHT, and collectively the results are inconsistent.

  15. Paraneoplastic Dermatomyositis with Cutaneous and Myopathic Disease Responsive to Adrenocorticotropic Hormone Therapy

    PubMed Central

    Mancuso, Christopher; Lal, Karan; Dicostanzo, Damian; Gropper, Charles

    2017-01-01

    Dermatomyositis is a myopathic or amyopathic autoimmune connective tissue disease that presents with classic dermatologic findings ranging from: poikilodermatous photosensitivity (shawl sign), eyelid edema and violaceous-pigmentation (heliotrope sign), lichenoid eruptions on the knuckles and elbows (Gottron’s sign), periungual telangiectasias, and ragged cuticles (Samitz sign). Up to 30 percent of adult-onset cases of dermatomyositis may represent a paraneoplastic syndrome warranting a thorough work-up for malignancy. The authors present a case report of paraneoplastic dermatomyositis associated with triple negative, BRCA-1 positive, invasive intraductal carcinoma of the breast, whose myopathic and cuteanous symptoms were recalcitrant to high-dose corticosteroid therapy. Herein, the authors describe the first reported case of the use of an injectable adrenocorticotropic hormone agonist gel in a patient with myopathic paraneoplastic disease that achieved clinical resolution of both myopathic and cutaneous symptoms, but subseuqently developed significant hyperpigmentation of her face suspected to be secondary to a chemotherapeutic-induced pigmentary change which was augmented by adrenocorticotropic hormone therapy. PMID:28210382

  16. Gonadal suppressive and cross-sex hormone therapy for gender dysphoria in adolescents and adults.

    PubMed

    Smith, Katherine P; Madison, Christina M; Milne, Nikki M

    2014-12-01

    Individuals with gender dysphoria experience distress associated with incongruence between their biologic sex and their identified gender. Gender dysphoric natal males receive treatment with antiandrogens and estrogens to become feminized (transsexual females), whereas natal females with gender dysphoria receive treatment with androgens to become masculinized (transsexual males). Because of the permanence associated with cross-sex hormone therapy (CSHT), adolescents diagnosed with gender dysphoria receive gonadotropin-releasing hormone analogs to suppress puberty. High rates of depression and suicide are linked to social marginalization and barriers to care. Behavior, emotional problems, depressive symptoms, and global functioning improve in adolescents receiving puberty suppression therapy. Gender dysphoria, psychological symptoms, quality of life, and sexual function improve in adults who receive CSHT. Within the first 6 months of CSHT, changes in transsexual females include breast growth, decreased testicular volume, and decreased spontaneous erections, and changes in transsexual males include cessation of menses, breast atrophy, clitoral enlargement, and voice deepening. Both transsexual females and males experience changes in body fat redistribution, muscle mass, and hair growth. Desired effects from CSHT can take between 3 and 5 years; however, effects that occur during puberty, such as voice deepening and skeletal structure changes, cannot be reversed with CSHT. Decreased sexual desire is a greater concern in transsexual females than in transsexual males, with testosterone concentrations linked to sexual desire in both. Regarding CSHT safety, bone mineral density is preserved with adequate hormone supplementation, but long-term fracture risk has not been studied. The transition away from high-dose traditional regimens is tied to a lower risk of venous thromboembolism and cardiovascular disease, but data quality is poor. Breast cancer has been reported in

  17. The association of polymorphisms in hormone metabolism pathway genes, menopausal hormone therapy, and breast cancer risk: a nested case-control study in the California Teachers Study cohort

    PubMed Central

    2011-01-01

    Introduction The female sex steroids estrogen and progesterone are important in breast cancer etiology. It therefore seems plausible that variation in genes involved in metabolism of these hormones may affect breast cancer risk, and that these associations may vary depending on menopausal status and use of hormone therapy. Methods We conducted a nested case-control study of breast cancer in the California Teachers Study cohort. We analyzed 317 tagging single nucleotide polymorphisms (SNPs) in 24 hormone pathway genes in 2746 non-Hispanic white women: 1351 cases and 1395 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by fitting conditional logistic regression models using all women or subgroups of women defined by menopausal status and hormone therapy use. P values were adjusted for multiple correlated tests (PACT). Results The strongest associations were observed for SNPs in SLCO1B1, a solute carrier organic anion transporter gene, which transports estradiol-17β-glucuronide and estrone-3-sulfate from the blood into hepatocytes. Ten of 38 tagging SNPs of SLCO1B1 showed significant associations with postmenopausal breast cancer risk; 5 SNPs (rs11045777, rs11045773, rs16923519, rs4149057, rs11045884) remained statistically significant after adjusting for multiple testing within this gene (PACT = 0.019-0.046). In postmenopausal women who were using combined estrogen-progestin therapy (EPT) at cohort enrollment, the OR of breast cancer was 2.31 (95% CI = 1.47-3.62) per minor allele of rs4149013 in SLCO1B1 (P = 0.0003; within-gene PACT = 0.002; overall PACT = 0.023). SNPs in other hormone pathway genes evaluated in this study were not associated with breast cancer risk in premenopausal or postmenopausal women. Conclusions We found evidence that genetic variation in SLCO1B1 is associated with breast cancer risk in postmenopausal women, particularly among those using EPT. PMID:21457551

  18. International trial of adjuvant therapy in high risk stage I non-squamous cell carcinoma identified by a 14-gene prognostic signature.

    PubMed

    Kratz, Johannes R; Mann, Michael J; Jablons, David M

    2013-06-01

    There is widespread agreement amongst clinical oncologists that more refined risk-stratification in early-stage lung cancer patients beyond conventional TNM staging is needed. Over the past decade, a number of molecular prognostic signatures have been designed to meet this need by correlating patterns in the differences in gene expression or modification to patient prognosis. Unfortunately, the majority of proposed signatures are not amenable to practical widespread implementation or have not yet undergone large-scale, rigorous clinical validation. A practical 14-gene prognostic signature that has undergone large-scale blinded independent validation is now ready for widespread clinical use. An international clinical trial is underway that has been designed to document the precise degree of benefit derived from adjuvant therapy in high-risk stage I patients identified by the 14-gene prognostic assay.

  19. 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.

  20. The Influence of Menopausal Status and Postmenopausal Use of Hormone Therapy on Presentation of Major Depression in Women

    PubMed Central

    Kornstein, Susan G.; Young, Elizabeth A.; Harvey, Annie T.; Wisniewski, Stephen R.; Barkin, Jennifer L.; Thase, Michael E.; Trivedi, Madhukar H.; Nierenberg, Andrew A.; Rush, A. John

    2010-01-01

    Objective: The purpose of this study was to determine whether there are differences in depression characteristics among premenopausal, perimenopausal, and postmenopausal women with major depressive disorder. This study also evaluated these differences between postmenopausal women with major depressive disorder who are taking and not taking hormone therapy. Methods: Analyses conducted with data from the Sequenced Treatment Alternatives to Relieve Depression study focused on female outpatients with non-psychotic major depressive disorder seeking treatment in 41 primary or psychiatric care settings across the United States. Baseline demographic and clinical characteristics were compared among women not taking hormone therapy who were premenopausal (N=950), perimenopausal (N=380), or postmenopausal (N=562). These comparisons were also made betwee