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David G Ball - One of the best experts on this subject based on the ideXlab platform.
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assisted reproductive technology use and outcomes among women with a history of Cancer
Human Reproduction, 2016Co-Authors: Barbara Luke, Morton B Brown, Stacey A Missmer, Logan G Spector, Richard E Leach, Melanie Williams, Lori Koch, Yolanda R Smith, Judy E Stern, David G BallAbstract:STUDY QUESTION: How do the assisted reproductive technology (ART) outcomes of women presenting for ART after Cancer diagnosis compare to women without Cancer? SUMMARY ANSWER: The likelihood of a live birth after ART among women with prior Cancer using autologous oocytes is reduced and varies by Cancer diagnosis but is similar to women without Cancer when donor oocytes are used. WHAT IS KNOWN ALREADY: Premenopausal patients faced with a Cancer diagnosis frequently present for fertility preservation. STUDY DESIGN, SIZE, DURATION: Population-based cohort study of women treated with ART in NY, TX and IL, USA. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with their first ART treatment between 2004 and 2009 were identified from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database and linked to their respective State Cancer Registries based on name, date of birth and social security number. Years were rounded, i.e. year 1 = 6-18 months before treatment. This study used reports of Cancer from 5 years, 6 months prior to treatment until 6 months after first ART treatment. Women who only presented for embryo banking were omitted from the analysis. The likelihood of pregnancy and of live birth with ART using autologous oocytes was modeled using logistic regression, with women without prior Cancer as the reference group, adjusted for woman's age, parity, cumulative FSH dosage, infertility diagnosis, number of diagnoses, number of ART cycles, State of residency and year of ART treatment. Results of the modeling are reported as adjusted odds ratios (AORs) and (95% confidence intervals). MAIN RESULTS AND THE ROLE OF CHANCE: The study population included 53 426 women; 441 women were diagnosed with Cancer within 5 years prior to ART cycle start. Mean (±SD) age at Cancer diagnosis was 33.4 ± 5.7 years; age at start of ART treatment was 34.9 ± 5.8 for women with Cancer compared with 35.3 ± 5.3 years for women without Cancer (P = 0.03). Live birth rates among women using autologous oocytes differed substantially by Cancer status (47.7% without Cancer versus 24.7% with Cancer, P < 0.0001), and Cancer diagnosis (ranging from 53.5% for melanoma to 14.3% for breast Cancer, P < 0.0001. The live birth rates among women using donor oocytes did not vary significantly by Cancer status (60.4% for women with any Cancer versus 64.5% for women without Cancer), or by Cancer diagnosis (ranging from 57.9% for breast Cancer to 63.6% for Endocrine Cancer). Women with breast Cancer make up about one-third of all Cancers in this cohort. Among women with breast Cancer, 2.8% of the 106 women who underwent ART within 6 months of being diagnosed with Cancer used donor oocytes compared with 34.8% of the 46 women who received ART treatment a longer time after being diagnosed with Cancer (P < 0.0001). We conjecture that the former group were either unaware that they had Cancer or decided to undergo ART therapy prior to Cancer treatment. However, their live birth rate was only 11.7% compared with 28.8%, the overall live birth rate for all women with Cancer using autologous oocytes (P < 0.0001). The live birth rate for women diagnosed with breast Cancer more than 6 months before ART (23.3%) did not differ significantly from the overall live birth rate for Cancer (P = 0.49). If this difference is substantiated by a larger study, it would indicate a negative effect of severe recent illness itself on ART success, rather than the poor outcome being only related to the destructive effects of chemotherapies on ovarian follicles. Alternatively, because of the short time difference between Cancer diagnosis and ART treatment, these pre-existing Cancers may have been detected due to the increased medical surveillance during ART therapy. In women who only used autologous oocytes, women with prior Cancers were significantly less likely to become pregnant and to have a live birth than those without Cancer (adjusted odds ratio (AOR): 0.34, [95% confidence interval (CI): 0.27, 0.42] and 0.36 [0.28, 0.46], respectively). This was also evident with specific Cancer diagnoses: breast Cancer (0.20 [0.13, 0.32] and 0.19 [0.11, 0.30], respectively), cervical Cancer (0.36 [0.15, 0.87] and 0.33 [0.13, 0.84], respectively) and all female genital Cancers (0.49 [0.27, 0.87] and 0.47 [0.25, 0.86], respectively). Of note, among women with Cancer who became pregnant, their likelihood of having a live birth did not differ significantly from women without Cancer (85.8 versus 86.7% for women using autologous oocytes, and 85.3 versus 86.9% for women using donor oocytes). LIMITATIONS, REASONS FOR CAUTION: Women may not have been residents of the individual States for the entire 5-year pre-ART period, and therefore some Cancers may not have been identified through this linkage. As a result, the actual observed number of Cancers may be an underestimate. In addition, the overall prevalence is low due to the age distributions. Also, because we restricted the pre-ART period to 5 years prior, we would not have identified women who were survivors of early childhood Cancers (younger than age 13 years at Cancer diagnosis), or who had ART more than 5 years after being diagnosed with Cancer. Additional analyses are currently underway evaluating live birth outcomes after embryo banking among women with Cancer prior to ART, cycles which were excluded from the analyses in this paper. Future studies are planned which will include more States, as well as linkages to vital records to obtain information on spontaneous conceptions and births, to further clarify some of the issues raised in this analysis. WIDER IMPLICATIONS OF THE FINDINGS: Since the live birth rates using donor oocytes were not reduced in women with a prior Cancer, but were reduced with autologous cycles, this suggests that factors acting in the pre- or peri-conceptional periods may be responsible for the decline. STUDY FUNDING/COMPETING INTERESTS: The study was funded by grant R01 CA151973 from the National Cancer Institute, National Institutes of Health, USA. B.L. is a research consultant for the Society for Assisted Reproductive Technology. All other authors report no conflict of interest.
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assisted reproductive technology use and outcomes among women with a history of Cancer
Human Reproduction, 2016Co-Authors: Barbara Luke, Morton B Brown, Stacey A Missmer, Logan G Spector, Richard E Leach, Melanie Williams, Lori Koch, Yolanda R Smith, Judy E Stern, David G BallAbstract:STUDY QUESTION How do the assisted reproductive technology (ART) outcomes of women presenting for ART after Cancer diagnosis compare to women without Cancer? SUMMARY ANSWER The likelihood of a live birth after ART among women with prior Cancer using autologous oocytes is reduced and varies by Cancer diagnosis but is similar to women without Cancer when donor oocytes are used. WHAT IS KNOWN ALREADY Premenopausal patients faced with a Cancer diagnosis frequently present for fertility preservation. STUDY DESIGN, SIZE, DURATION Population-based cohort study of women treated with ART in NY, TX and IL, USA. PARTICIPANTS/MATERIALS, SETTING, METHODS Women with their first ART treatment between 2004 and 2009 were identified from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database and linked to their respective State Cancer Registries based on name, date of birth and social security number. Years were rounded, i.e. year 1 = 6-18 months before treatment. This study used reports of Cancer from 5 years, 6 months prior to treatment until 6 months after first ART treatment. Women who only presented for embryo banking were omitted from the analysis. The likelihood of pregnancy and of live birth with ART using autologous oocytes was modeled using logistic regression, with women without prior Cancer as the reference group, adjusted for woman's age, parity, cumulative FSH dosage, infertility diagnosis, number of diagnoses, number of ART cycles, State of residency and year of ART treatment. Results of the modeling are reported as adjusted odds ratios (AORs) and (95% confidence intervals). MAIN RESULTS AND THE ROLE OF CHANCE The study population included 53 426 women; 441 women were diagnosed with Cancer within 5 years prior to ART cycle start. Mean (±SD) age at Cancer diagnosis was 33.4 ± 5.7 years; age at start of ART treatment was 34.9 ± 5.8 for women with Cancer compared with 35.3 ± 5.3 years for women without Cancer (P = 0.03). Live birth rates among women using autologous oocytes differed substantially by Cancer status (47.7% without Cancer versus 24.7% with Cancer, P < 0.0001), and Cancer diagnosis (ranging from 53.5% for melanoma to 14.3% for breast Cancer, P < 0.0001. The live birth rates among women using donor oocytes did not vary significantly by Cancer status (60.4% for women with any Cancer versus 64.5% for women without Cancer), or by Cancer diagnosis (ranging from 57.9% for breast Cancer to 63.6% for Endocrine Cancer). Women with breast Cancer make up about one-third of all Cancers in this cohort. Among women with breast Cancer, 2.8% of the 106 women who underwent ART within 6 months of being diagnosed with Cancer used donor oocytes compared with 34.8% of the 46 women who received ART treatment a longer time after being diagnosed with Cancer (P < 0.0001). We conjecture that the former group were either unaware that they had Cancer or decided to undergo ART therapy prior to Cancer treatment. However, their live birth rate was only 11.7% compared with 28.8%, the overall live birth rate for all women with Cancer using autologous oocytes (P < 0.0001). The live birth rate for women diagnosed with breast Cancer more than 6 months before ART (23.3%) did not differ significantly from the overall live birth rate for Cancer (P = 0.49). If this difference is substantiated by a larger study, it would indicate a negative effect of severe recent illness itself on ART success, rather than the poor outcome being only related to the destructive effects of chemotherapies on ovarian follicles. Alternatively, because of the short time difference between Cancer diagnosis and ART treatment, these pre-existing Cancers may have been detected due to the increased medical surveillance during ART therapy. In women who only used autologous oocytes, women with prior Cancers were significantly less likely to become pregnant and to have a live birth than those without Cancer (adjusted odds ratio (AOR): 0.34, [95% confidence interval (CI): 0.27, 0.42] and 0.36 [0.28, 0.46], respectively). This was also evident with specific Cancer diagnoses: breast Cancer (0.20 [0.13, 0.32] and 0.19 [0.11, 0.30], respectively), cervical Cancer (0.36 [0.15, 0.87] and 0.33 [0.13, 0.84], respectively) and all female genital Cancers (0.49 [0.27, 0.87] and 0.47 [0.25, 0.86], respectively). Of note, among women with Cancer who became pregnant, their likelihood of having a live birth did not differ significantly from women without Cancer (85.8 versus 86.7% for women using autologous oocytes, and 85.3 versus 86.9% for women using donor oocytes). LIMITATIONS, REASONS FOR CAUTION Women may not have been residents of the individual States for the entire 5-year pre-ART period, and therefore some Cancers may not have been identified through this linkage. As a result, the actual observed number of Cancers may be an underestimate. In addition, the overall prevalence is low due to the age distributions. Also, because we restricted the pre-ART period to 5 years prior, we would not have identified women who were survivors of early childhood Cancers (younger than age 13 years at Cancer diagnosis), or who had ART more than 5 years after being diagnosed with Cancer. Additional analyses are currently underway evaluating live birth outcomes after embryo banking among women with Cancer prior to ART, cycles which were excluded from the analyses in this paper. Future studies are planned which will include more States, as well as linkages to vital records to obtain information on spontaneous conceptions and births, to further clarify some of the issues raised in this analysis. WIDER IMPLICATIONS OF THE FINDINGS Since the live birth rates using donor oocytes were not reduced in women with a prior Cancer, but were reduced with autologous cycles, this suggests that factors acting in the pre- or peri-conceptional periods may be responsible for the decline. STUDY FUNDING/COMPETING INTERESTS The study was funded by grant R01 CA151973 from the National Cancer Institute, National Institutes of Health, USA. B.L. is a research consultant for the Society for Assisted Reproductive Technology. All other authors report no conflict of interest.
Christopher Mccabe - One of the best experts on this subject based on the ideXlab platform.
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Mining the proteome: the application of tandem mass spectrometry to Endocrine Cancer research.
Endocrine-related cancer, 2012Co-Authors: Neil Sharma, Ashley Martin, Christopher MccabeAbstract:Tandem mass spectrometry (MS/MS) permits the detection of femtomolar quantities of protein from a wide variety of tissue sources. As Endocrine Cancers are frequently aetiologically complex, they are particularly amenable to mass spectrometry. The most widely studied aspect is the search for novel reliable biomarkers that would allow Cancers to be diagnosed earlier and distinguished from benign tumours. MS/MS allows for the rapid analysis of blood and urine in addition to tumour tissue, and in this regard it has been applied on research involving thyroid, pancreatic, adrenal and ovarian Cancers with varying degrees of success, as well as additional organ sites including breast and lung. The description of an individual Cancer proteome potentially allows for personalised management of each patient, avoiding unnecessary therapies and targeting treatments to those which will have the most effect. The application of MS/MS to interaction proteomics is a field that has generated recent novel targets for chemotherapy. However, the technology involved in MS/MS has a number of drawbacks that at present prevent its widespread use in translational Cancer research, including a poor reproducibility of results, in part due to the large amount of data generated and the inability to accurately differentiate true from false-positive results. Further, the current cost of running MS/MS restricts the number of times the experiments can be repeated, contributing to the lack of significance and concordance between studies. Despite these problems, however, MS/MS is emerging as a front line tool in Endocrine Cancer research and it is likely that this will continue over the next decade. Endocrine-Related Cancer (2012) 19 R149‐R161
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pituitary tumor transforming gene and its binding factor in Endocrine Cancer
Expert Reviews in Molecular Medicine, 2010Co-Authors: Vicki Smith, J A Franklyn, Christopher MccabeAbstract:: The pituitary tumor-transforming gene (PTTG1) encodes a multifunctional protein (PTTG) that is overexpressed in numerous tumours, including pituitary, thyroid, breast and ovarian carcinomas. PTTG induces cellular transformation in vitro and tumourigenesis in vivo, and several mechanisms by which PTTG contributes to tumourigenesis have been investigated. Also known as the human securin, PTTG is involved in cell cycle regulation, controlling the segregation of sister chromatids during mitosis. This review outlines current information regarding PTTG structure, expression, regulation and function in the pathogenesis of neoplasia. Recent progress concerning the use of PTTG as a prognostic marker or therapeutic target will be considered. In addition, the PTTG binding factor (PBF), identified through its interaction with PTTG, has also been established as a proto-oncogene that is upregulated in several Cancers. Current knowledge regarding PBF is outlined and its role both independently and alongside PTTG in Endocrine and related Cancers is discussed.
Yuri E. Nikiforov - One of the best experts on this subject based on the ideXlab platform.
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RET/PTC rearrangements and BRAF mutations in thyroid tumorigenesis.
Endocrinology, 2006Co-Authors: Raffaele Ciampi, Yuri E. NikiforovAbstract:Thyroid papillary carcinoma is the most common type of Endocrine Cancer. It is frequently associated with genetic alterations leading to activation of the MAPK signaling pathway. The two most frequently affected genes, BRAF and RET, are activated by either point mutation or as a result of chromosomal rearrangement. These mutations are tumorigenic in thyroid follicular cells and correlate with specific phonotypical features and biological properties of papillary carcinomas, including tumor aggressiveness and response to radioiodine therapy. Molecular inhibitors that block RET/PTC or BRAF kinase activity have shown substantial therapeutic effects in the experimental systems and are currently being tested in clinical trials.
Monika Kellerer - One of the best experts on this subject based on the ideXlab platform.
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inhibition of ret oncogene activity by the protein tyrosine phosphatase shp1
Endocrinology, 2001Co-Authors: Anita M Hennige, Reiner Lammers, Wolfgang Hoppner, Dorit Arlt, Volker Strack, Reinhard Teichmann, Fausto Machicao, Axel Ullrich, Hansulrich Haring, Monika KellererAbstract:Germline mutations in the Ret protooncogene give rise to the inherited Endocrine Cancer syndromes MEN types 2A and 2B and familiar medullary thyroid carcinoma. Although it is well accepted that the constitutive active tyrosine kinase of Ret oncogenes ultimately leads to malignant transformation, it is not clear whether a decrease in the autophosphorylation of oncogenic Ret forms can affect the mitogenic and transforming activities of Ret. Potential modulators of the tyrosine kinase activity of Ret could be tyrosine phosphatases that are expressed in human thyroid tissue. Therefore, we investigated the impact of the tyrosine phosphatases SHP1 and SHP2 on the intrinsic tyrosine kinase activity and oncogenic potency of Ret with a 9-bp duplication in the cysteine-rich domain (codons 634–636), which was described in a patient with MEN type 2A recently. SHP1 and SHP2 were stably overexpressed in NIH3T3 fibroblasts together with Ret-9bp. Coexpression of SHP1 with Ret-9bp reduced the autophosphorylation of Ret-9b...
Donald Poirier - One of the best experts on this subject based on the ideXlab platform.
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Recent patents on new steroid agents targeting the steroidogenesis for Endocrine Cancer treatments.
Recent patents on endocrine metabolic & immune drug discovery, 2015Co-Authors: Donald PoirierAbstract:Cancer is a leading cause of death in the population and despite the significant technological advances that have been made over the last years, there is a great need for new and better treatments with fewer side effects. Among the various types, hormone-dependent Cancers are stimulated by the presence of certain steroidal hormones such as androgens and estrogens, which act through a nuclear receptor. The use of small molecules to block the biosynthesis (steroidogenesis) or the action of hormones (androgens or estrogens) is a therapeutic approach that has yielded interesting results and whose development continues. This review article emphasizes the patents and patent applications published over the last five years. It deals exclusively with steroid compounds developed as inhibitors of key enzymes (17α-hydroxylase/17,20-lyase, steroid sulfatase, 5α-reductases, aromatase and 17β-hydroxysteroid dehydrogenases) involved in the steroidogenesis and identified as therapeutic targets. Such inhibitors could be used as a drug to reduce the concentration of androgens or estrogens and, consequently, for treating hormone-dependent diseases such as prostate Cancer, breast Cancer and endometriosis.