The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Vincenzo Bagnardi - One of the best experts on this subject based on the ideXlab platform.
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a nomogram based on the expression of ki 67 Steroid Hormone Receptors status and number of chemotherapy courses to predict pathological complete remission after preoperative chemotherapy for breast cancer
European Journal of Cancer, 2010Co-Authors: Marco Colleoni, Vincenzo Bagnardi, Nicole Rotmensz, Giuseppe Viale, Paolo Veronesi, Mauro G Mastropasqua, Anna Cardillo, Rosalba Torrisi, Alberto LuiniAbstract:Abstract Background Tools able to predict pathological complete response (pCR) to preoperative chemotherapy might improve treatment outcome. Patients and methods Data from 783 patients with invasive ductal carcinoma treated with preoperative chemotherapy and operated at the European Institute of Oncology were used to develop a nomogram using logistic regression model based on both categorical (clinical T and N, HER2/neu, grade and primary therapy) and continuous variables (age, oestrogen receptor (ER), progesterone receptor (PgR), Ki-67 expression and number of chemotherapy courses). The performance of the resulting nomogram was internally evaluated through bootstrapping methods. Finally the model was externally validated on a patient set treated in other institutions and subsequently operated at the EIO. Results At multivariable analysis the probability of pCR was directly associated with Ki-67 expression (OR for 10% increase in the percentage of positive cells, 1.15, 95% confidence interval (CI), 1.03, 1.29) and number of chemotherapy courses (OR for one cycle increase, 1.31, 95% CI, 1.12, 1.53) and inversely associated with ER and PgR expression (ORs for 10% increase in the percentage of positive cells, 0.86, 95% CI 0.79, 0.93 and 0.82, 95% CI 0.69, 0.99, respectively). The nomogram for pCR based on these variables had good discrimination in training as well in validation set (AUC, 0.78 and 0.77). Conclusion The use of a nomogram based on the number of preoperative courses, degree of Ki-67 and Steroid Hormone Receptors expression may be useful for predicting the probability of pCR and for the design of the proper therapeutic algorithm in locally advanced breast cancer.
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increasing Steroid Hormone Receptors expression defines breast cancer subtypes non responsive to preoperative chemotherapy
Breast Cancer Research and Treatment, 2009Co-Authors: Marco Colleoni, Vincenzo Bagnardi, Nicole Rotmensz, Richard D Gelber, Giuseppe Viale, Giancarlo Pruneri, Paolo VeronesiAbstract:The predictive role of the degree of endocrine responsiveness to preoperative chemotherapy (PCT) is unclear. We reviewed pretreatment biopsies of 553 patients with locally advanced breast cancer who were treated with PCT. The incidence of pathological complete remission (pCR) and outcome were assessed with respect to the degree of estrogen (ER) and progesterone receptor (PgR) expression (ER and PgR absent, vs. ER or PgR 0–49%, vs. ER and PgR ≥50% of the cells positive). A statistically significant higher pCR rate was observed at the multivariate analysis for patients with ER and PgR absent tumors (17.7%) versus patients with tumors expressing high ER and PgR (0%) (OR 14.4 P < 0.001). Despite the higher incidence of pCR, a statistically significant worse disease-free survival (DFS), and overall survival (OS) was observed for patients with ER and PgR absent tumors versus patients with tumors expressing high ER and PgR (HR 6.4, 95% CI 3.5–11.6, for DFS; HR 3.6 95% CI 2.4–5.6 for OS). Response and outcome after PCT are correlated with the degree of expression of Steroid Hormone Receptors. Studies on tailored preoperative therapies are needed.
Paolo Veronesi - One of the best experts on this subject based on the ideXlab platform.
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a nomogram based on the expression of ki 67 Steroid Hormone Receptors status and number of chemotherapy courses to predict pathological complete remission after preoperative chemotherapy for breast cancer
European Journal of Cancer, 2010Co-Authors: Marco Colleoni, Vincenzo Bagnardi, Nicole Rotmensz, Giuseppe Viale, Paolo Veronesi, Mauro G Mastropasqua, Anna Cardillo, Rosalba Torrisi, Alberto LuiniAbstract:Abstract Background Tools able to predict pathological complete response (pCR) to preoperative chemotherapy might improve treatment outcome. Patients and methods Data from 783 patients with invasive ductal carcinoma treated with preoperative chemotherapy and operated at the European Institute of Oncology were used to develop a nomogram using logistic regression model based on both categorical (clinical T and N, HER2/neu, grade and primary therapy) and continuous variables (age, oestrogen receptor (ER), progesterone receptor (PgR), Ki-67 expression and number of chemotherapy courses). The performance of the resulting nomogram was internally evaluated through bootstrapping methods. Finally the model was externally validated on a patient set treated in other institutions and subsequently operated at the EIO. Results At multivariable analysis the probability of pCR was directly associated with Ki-67 expression (OR for 10% increase in the percentage of positive cells, 1.15, 95% confidence interval (CI), 1.03, 1.29) and number of chemotherapy courses (OR for one cycle increase, 1.31, 95% CI, 1.12, 1.53) and inversely associated with ER and PgR expression (ORs for 10% increase in the percentage of positive cells, 0.86, 95% CI 0.79, 0.93 and 0.82, 95% CI 0.69, 0.99, respectively). The nomogram for pCR based on these variables had good discrimination in training as well in validation set (AUC, 0.78 and 0.77). Conclusion The use of a nomogram based on the number of preoperative courses, degree of Ki-67 and Steroid Hormone Receptors expression may be useful for predicting the probability of pCR and for the design of the proper therapeutic algorithm in locally advanced breast cancer.
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increasing Steroid Hormone Receptors expression defines breast cancer subtypes non responsive to preoperative chemotherapy
Breast Cancer Research and Treatment, 2009Co-Authors: Marco Colleoni, Vincenzo Bagnardi, Nicole Rotmensz, Richard D Gelber, Giuseppe Viale, Giancarlo Pruneri, Paolo VeronesiAbstract:The predictive role of the degree of endocrine responsiveness to preoperative chemotherapy (PCT) is unclear. We reviewed pretreatment biopsies of 553 patients with locally advanced breast cancer who were treated with PCT. The incidence of pathological complete remission (pCR) and outcome were assessed with respect to the degree of estrogen (ER) and progesterone receptor (PgR) expression (ER and PgR absent, vs. ER or PgR 0–49%, vs. ER and PgR ≥50% of the cells positive). A statistically significant higher pCR rate was observed at the multivariate analysis for patients with ER and PgR absent tumors (17.7%) versus patients with tumors expressing high ER and PgR (0%) (OR 14.4 P < 0.001). Despite the higher incidence of pCR, a statistically significant worse disease-free survival (DFS), and overall survival (OS) was observed for patients with ER and PgR absent tumors versus patients with tumors expressing high ER and PgR (HR 6.4, 95% CI 3.5–11.6, for DFS; HR 3.6 95% CI 2.4–5.6 for OS). Response and outcome after PCT are correlated with the degree of expression of Steroid Hormone Receptors. Studies on tailored preoperative therapies are needed.
Giuseppe Viale - One of the best experts on this subject based on the ideXlab platform.
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a nomogram based on the expression of ki 67 Steroid Hormone Receptors status and number of chemotherapy courses to predict pathological complete remission after preoperative chemotherapy for breast cancer
European Journal of Cancer, 2010Co-Authors: Marco Colleoni, Vincenzo Bagnardi, Nicole Rotmensz, Giuseppe Viale, Paolo Veronesi, Mauro G Mastropasqua, Anna Cardillo, Rosalba Torrisi, Alberto LuiniAbstract:Abstract Background Tools able to predict pathological complete response (pCR) to preoperative chemotherapy might improve treatment outcome. Patients and methods Data from 783 patients with invasive ductal carcinoma treated with preoperative chemotherapy and operated at the European Institute of Oncology were used to develop a nomogram using logistic regression model based on both categorical (clinical T and N, HER2/neu, grade and primary therapy) and continuous variables (age, oestrogen receptor (ER), progesterone receptor (PgR), Ki-67 expression and number of chemotherapy courses). The performance of the resulting nomogram was internally evaluated through bootstrapping methods. Finally the model was externally validated on a patient set treated in other institutions and subsequently operated at the EIO. Results At multivariable analysis the probability of pCR was directly associated with Ki-67 expression (OR for 10% increase in the percentage of positive cells, 1.15, 95% confidence interval (CI), 1.03, 1.29) and number of chemotherapy courses (OR for one cycle increase, 1.31, 95% CI, 1.12, 1.53) and inversely associated with ER and PgR expression (ORs for 10% increase in the percentage of positive cells, 0.86, 95% CI 0.79, 0.93 and 0.82, 95% CI 0.69, 0.99, respectively). The nomogram for pCR based on these variables had good discrimination in training as well in validation set (AUC, 0.78 and 0.77). Conclusion The use of a nomogram based on the number of preoperative courses, degree of Ki-67 and Steroid Hormone Receptors expression may be useful for predicting the probability of pCR and for the design of the proper therapeutic algorithm in locally advanced breast cancer.
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increasing Steroid Hormone Receptors expression defines breast cancer subtypes non responsive to preoperative chemotherapy
Breast Cancer Research and Treatment, 2009Co-Authors: Marco Colleoni, Vincenzo Bagnardi, Nicole Rotmensz, Richard D Gelber, Giuseppe Viale, Giancarlo Pruneri, Paolo VeronesiAbstract:The predictive role of the degree of endocrine responsiveness to preoperative chemotherapy (PCT) is unclear. We reviewed pretreatment biopsies of 553 patients with locally advanced breast cancer who were treated with PCT. The incidence of pathological complete remission (pCR) and outcome were assessed with respect to the degree of estrogen (ER) and progesterone receptor (PgR) expression (ER and PgR absent, vs. ER or PgR 0–49%, vs. ER and PgR ≥50% of the cells positive). A statistically significant higher pCR rate was observed at the multivariate analysis for patients with ER and PgR absent tumors (17.7%) versus patients with tumors expressing high ER and PgR (0%) (OR 14.4 P < 0.001). Despite the higher incidence of pCR, a statistically significant worse disease-free survival (DFS), and overall survival (OS) was observed for patients with ER and PgR absent tumors versus patients with tumors expressing high ER and PgR (HR 6.4, 95% CI 3.5–11.6, for DFS; HR 3.6 95% CI 2.4–5.6 for OS). Response and outcome after PCT are correlated with the degree of expression of Steroid Hormone Receptors. Studies on tailored preoperative therapies are needed.
Marco Colleoni - One of the best experts on this subject based on the ideXlab platform.
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a nomogram based on the expression of ki 67 Steroid Hormone Receptors status and number of chemotherapy courses to predict pathological complete remission after preoperative chemotherapy for breast cancer
European Journal of Cancer, 2010Co-Authors: Marco Colleoni, Vincenzo Bagnardi, Nicole Rotmensz, Giuseppe Viale, Paolo Veronesi, Mauro G Mastropasqua, Anna Cardillo, Rosalba Torrisi, Alberto LuiniAbstract:Abstract Background Tools able to predict pathological complete response (pCR) to preoperative chemotherapy might improve treatment outcome. Patients and methods Data from 783 patients with invasive ductal carcinoma treated with preoperative chemotherapy and operated at the European Institute of Oncology were used to develop a nomogram using logistic regression model based on both categorical (clinical T and N, HER2/neu, grade and primary therapy) and continuous variables (age, oestrogen receptor (ER), progesterone receptor (PgR), Ki-67 expression and number of chemotherapy courses). The performance of the resulting nomogram was internally evaluated through bootstrapping methods. Finally the model was externally validated on a patient set treated in other institutions and subsequently operated at the EIO. Results At multivariable analysis the probability of pCR was directly associated with Ki-67 expression (OR for 10% increase in the percentage of positive cells, 1.15, 95% confidence interval (CI), 1.03, 1.29) and number of chemotherapy courses (OR for one cycle increase, 1.31, 95% CI, 1.12, 1.53) and inversely associated with ER and PgR expression (ORs for 10% increase in the percentage of positive cells, 0.86, 95% CI 0.79, 0.93 and 0.82, 95% CI 0.69, 0.99, respectively). The nomogram for pCR based on these variables had good discrimination in training as well in validation set (AUC, 0.78 and 0.77). Conclusion The use of a nomogram based on the number of preoperative courses, degree of Ki-67 and Steroid Hormone Receptors expression may be useful for predicting the probability of pCR and for the design of the proper therapeutic algorithm in locally advanced breast cancer.
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increasing Steroid Hormone Receptors expression defines breast cancer subtypes non responsive to preoperative chemotherapy
Breast Cancer Research and Treatment, 2009Co-Authors: Marco Colleoni, Vincenzo Bagnardi, Nicole Rotmensz, Richard D Gelber, Giuseppe Viale, Giancarlo Pruneri, Paolo VeronesiAbstract:The predictive role of the degree of endocrine responsiveness to preoperative chemotherapy (PCT) is unclear. We reviewed pretreatment biopsies of 553 patients with locally advanced breast cancer who were treated with PCT. The incidence of pathological complete remission (pCR) and outcome were assessed with respect to the degree of estrogen (ER) and progesterone receptor (PgR) expression (ER and PgR absent, vs. ER or PgR 0–49%, vs. ER and PgR ≥50% of the cells positive). A statistically significant higher pCR rate was observed at the multivariate analysis for patients with ER and PgR absent tumors (17.7%) versus patients with tumors expressing high ER and PgR (0%) (OR 14.4 P < 0.001). Despite the higher incidence of pCR, a statistically significant worse disease-free survival (DFS), and overall survival (OS) was observed for patients with ER and PgR absent tumors versus patients with tumors expressing high ER and PgR (HR 6.4, 95% CI 3.5–11.6, for DFS; HR 3.6 95% CI 2.4–5.6 for OS). Response and outcome after PCT are correlated with the degree of expression of Steroid Hormone Receptors. Studies on tailored preoperative therapies are needed.
Raj Kumar - One of the best experts on this subject based on the ideXlab platform.
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allosteric modulators of Steroid Hormone Receptors structural dynamics and gene regulation
Endocrine Reviews, 2012Co-Authors: Raj Kumar, Iain J McewanAbstract:Steroid Hormones are synthesized from cholesterol primarily in the adrenal gland and the gonads and play vital roles in normal physiology, the control of development, differentiation, metabolic homeostasis, and reproduction. The actions of these small lipophilic molecules are mediated by intracellular receptor proteins. It is just over 25 yr since the first cDNA for Steroid Receptors were cloned, a development that led to the birth of a superfamily of ligand-activated transcription factors: the nuclear Receptors. The receptor proteins share structurally and functionally related ligand binding and DNA-binding domains but possess distinct N-terminal domains and hinge regions that are intrinsically disordered. Since the original cloning experiments, considerable progress has been made in our understanding of the structure, mechanisms of action, and biology of this important class of ligand-activated transcription factors. In recent years, there has been interest in the structural plasticity and function of the N-terminal domain of Steroid Hormone Receptors and in the allosteric regulation of protein folding and function in response to Hormone, DNA response element architecture, and coregulatory protein binding partners. The N-terminal domain can exist as an ensemble of conformers, having more or less structure, which prime this region of the receptor to rapidly respond to changes in the intracellular environment through Hormone binding and posttranslation modifications. In this review, we address the question of receptor structure and function dynamics with particular emphasis on the structurally flexible N-terminal domain, intra- and interdomain communications, and the allosteric regulation of receptor action.
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Steroid Hormone Receptors in cancer development a target for cancer therapeutics
Cancer Letters, 2011Co-Authors: Nihal Ahmad, Raj KumarAbstract:The Steroid Hormone Receptors (SHRs) are ligand-dependent intracellular transcription factors that are known to influence the development and growth of many human cancers. SHRs pass signals from a Steroid/Hormone to the target genes by interacting with specific response element DNA sequences and various coregulatory proteins that consists of activators and/or corepressors. Disruptions in physiological functions of SHRs leads to several types of malignancies such as breast cancer, leukemia and lymphoma, prostate cancer, ovarian cancer, and lung cancer among others. Steroids/Hormones/SHRs and their coregulators have opened up a unique window for novel Steroid-based targeted therapies for cancer. Thus, dysregulation of SHR signaling in cancers compared with normal tissues can be exploited to target drugs that prevent and treat human cancers. In recent years, hormonal therapy has made a major contribution to the treatment of several cancers including reduced recurrence rates and longer survival rates. Development of various Steroid receptor modulators and their potential therapeutic efficacies has provided us a great opportunity to effectively manage diseases like cancer in future. In this review article, we have summarized up-to-date knowledge of the role of SHRs in the development and progression of cancers, and potential endocrine-based therapeutic approaches to tackle these diseases.
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Structural and functional relationships of the Steroid Hormone Receptors' N-terminal transactivation domain.
Steroids, 2009Co-Authors: Raj Kumar, Gerald LitwackAbstract:Steroid Hormone Receptors are members of a family of ligand inducible transcription factors, and regulate the transcriptional activation of target genes by recruiting coregulatory proteins to the pre-initiation machinery. The binding of these coregulatory proteins to the Steroid Hormone Receptors is often mediated through their two activation functional domains, AF1, which resides in the N-terminal domain, and the ligand-dependent AF2, which is localized in the C-terminal ligand-binding domain. Compared to other important functional domains of the Steroid Hormone Receptors, our understanding of the mechanisms of action of the AF1 are incomplete, in part, due to the fact that, in solution, AF1 is intrinsically disordered (ID). However, recent studies have shown that AF1 must adopt a functionally active and folded conformation for its optimal activity under physiological conditions. In this review, we summarize and discuss current knowledge regarding the molecular mechanisms of AF1-mediated gene activation, focusing on AF1 conformation and coactivator binding. We further propose models for the binding/folding of the AF1 domains of the Steroid Hormone Receptors and their protein:protein interactions. The population of ID AF1 can be visualized as a collection of many different conformations, some of which may be assuming the proper functional folding for other critical target binding partners that result in the ultimate assembly of AF1:coactivator complexes and subsequent gene regulation. Knowledge of the mechanisms involved therein will significantly help in understanding how signals from a Steroid to a specific target gene are conveyed.