68 results on '"Mark Schoenberg"'
Search Results
2. Correction: Identification and Validation of Protein Biomarkers of Response to Neoadjuvant Platinum Chemotherapy in Muscle Invasive Urothelial Carcinoma.
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Alexander S Baras, Nilay Gandhi, Enrico Munari, Sheila Faraj, Luciana Shultz, Luigi Marchionni, Mark Schoenberg, Noah Hahn, Mohammad Obaidul Hoque, David Berman, Trinity J Bivalacqua, and George Netto
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Medicine ,Science - Published
- 2015
- Full Text
- View/download PDF
3. Natural History of Multiple Recurrences in Intermediate-Risk Non-Muscle Invasive Bladder Cancer: Lessons From a Prospective Cohort
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Vidit Sharma, Karim Chamie, Mark Schoenberg, Valerie S. Lee, Katherine Fero, Patrick Lec, Julie R. Munneke, David S. Aaronson, Lawrence H. Kushi, Charles P. Quesenberry, Li Tang, and Marilyn L. Kwan
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Urology - Abstract
To describe the risk of multiple recurrences in intermediate-risk non-muscle invasive bladder cancer (IR-NMIBC) and their impact on progression. Prognostic studies of IR-NMIBC have focused on initial recurrences, yet little is known about subsequent recurrences and their impact on progression.IR-NMIBC patients from the Be-Well Study, a prospective cohort study of NMIBC patients diagnosed from 2015-2019 at Kaiser Permanente Northern California, were identified. The frequency of first, second, and third intravesical recurrences of urothelial carcinoma were characterized using conditional Kaplan-Meier analyses and random-effects shared-frailty models. The association of multiple recurrences with progression was examined.In 291 patients with IR-NMIBC (median follow-up 38 months), the 5-year risk of initial recurrence was 54.4%. After initial recurrence (n=137), 60.1% of patients had a second recurrence by 2 years. After second recurrence (n=70), 51.5% of patients had a third recurrence by 3 years. In multivariable analysis, female sex (Hazard Ratio 1.51, p0.01), increasing tumor size (HR 1.14, p0.01) and number of prior recurrences (HR 1.24, p0.01) were associated with multiple recurrences; whereas maintenance BCG (HR 0.66, p=0.03) was associated with reduced recurrences. The 5-year risk of progression varied significantly (p0.01) by number of recurrences: 9.5%, 21.9%, and 37.9% for patients with 1, 2, and 3+ recurrences, respectively.Multiple recurrences are common in IR-NMIBC and are associated with progression. Female sex, larger tumors, number of prior recurrences, and lack of maintenance BCG were associated with multiple recurrences. Multiple recurrences may prove useful as a clinical trial endpoint for IR-NMIBC.
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- 2023
4. Supplementary Table 1 from TERT Promoter Mutations Occur Early in Urothelial Neoplasia and Are Biomarkers of Early Disease and Disease Recurrence in Urine
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George J. Netto, Nickolas Papadopoulos, Bert Vogelstein, Kenneth W. Kinzler, Luis A. Diaz, Yuxuan Wang, Simeon Springer, Mohamad Allaf, Trinity Bivalacqua, Mark Schoenberg, Ralph H. Hruban, Sheila F. Faraj, Enrico Munari, and Isaac Kinde
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PDF file - 8K, Table S1. TERT promoter mutation status in 59 pTa and 17 carcinoma in situ (CIS) patients.
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- 2023
5. Safety and Efficacy of Reproductive Organ-Sparing Radical Cystectomy in Women With Variant Histology and Advanced Stage
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Armine K. Smith, Mark Schoenberg, Andrew T. Gabrielson, Sunil H. Patel, Trinity J. Bivalacqua, Noah Hahn, Phil Pierorazio, Meredith R. Metcalf, Jean H. Hoffman-Censits, Shirley Wang, Mary Rostom, Max Kates, Natasha Gupta, and Esther Lee
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Male ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,Ovary ,Cystectomy ,medicine ,Humans ,Genitalia ,Retrospective Studies ,Bladder cancer ,business.industry ,Advanced stage ,Muscle invasive ,Margins of Excision ,medicine.disease ,Treatment Outcome ,medicine.anatomical_structure ,Urinary Bladder Neoplasms ,Oncology ,Female ,Histopathology ,Neoplasm Recurrence, Local ,Reactive Oxygen Species ,business ,Variant histology ,Reproductive organ - Abstract
Purpose Muscle invasive bladder cancer surgical management has been historically a radical cystoprostatectomy in males and an anterior exenteration in females. Uterine, ovarian, and vaginal preservation are utilized, but raise concerns regarding risk to oncologic control, especially in variant histopathology or advanced stage. Materials and Methods A retrospective single institutional analysis identified radical cystectomies performed in women, including those with variant histology, which were defined as reproductive organ sparing (uterine, vaginal, and ovary sparing) or non-organ sparing. The Kaplan-Meier method was used for recurrence-free (RFS) cancer specific survival (CSS) and overall (OS) survival in patients with advanced disease. Results From 2000 to 2020, 289 women were identified, 188 underwent reproductive organ-sparing cystectomy. No statistical differences were noted for clinical parameters or presence of variant histology for organ-sparing (ROS) and non-organ sparing (non-ROS). Positive margin rates did not differ for ROS and non-ROS; 4.3% vs 7.9%, p=0.19, respectively. Median RFS was not statistically significantly different for ROS vs non-ROS (26.1 vs 15.3 months) p=0.937 HR 1.024. CSS was not statistically different for ROS vs non-ROS (36.3 vs 28.6 months), p=0.755 HR 0.9. OS was not statistically different for ROS vs non-ROS (25.8 v 23.8 months), p=0.5 HR=1.178. Variant histology did not change survival (HR 1.1, p=0.643). Conclusions In this analysis, ROS in women with advanced disease did not increase positive margin rates or decrease RFS, CSS, or OS compared to non-ROS. Variant histology did not decrease survival odds. Based on preoperative assessment and intraoperative findings, ROS in patients with variant histology and advanced disease should be considered.
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- 2022
6. PD26-08 LOW-GRADE UROTHELIAL CARCINOMA RECURS AT A TEMPO THAT NATURALLY ACCELERATES FROM ADAGIO TO ALLEGRO
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Alex Sankin, Louise-Rae Cherrill, Rebecca H. Boucher, Maurice P. Zeegers, K. K. Cheng, Nicholas D. James, Mark Schoenberg, Ilir Agalliu, and Richard T. Bryan
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Urology - Published
- 2022
7. Clinical Restaging and Tumor Sequencing are Inaccurate Indicators of Response to Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer
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Kelly T. Harris, Michael H. Johnson, Woonyoung Choi, Trinity J. Bivalacqua, Adam C. Reese, Russell E.N. Becker, Jean H. Hoffman-Censits, Alexander S. Baras, David J. McConkey, Andres Matoso, Max Kates, Noah M. Hahn, Aaron Brant, George J. Netto, Mark Schoenberg, Alexa R. Meyer, Michael J. Biles, and Phillip M. Pierorazio
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Oncology ,Cisplatin ,medicine.medical_specialty ,Chemotherapy ,Bladder cancer ,medicine.diagnostic_test ,business.industry ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Muscle invasive ,Cystoscopy ,Disease ,medicine.disease ,Cystectomy ,03 medical and health sciences ,Exact test ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,business ,medicine.drug - Abstract
Background: Standard of care for patients with muscle-invasive bladder cancer (MIBC) includes neoadjuvant cisplatin-based chemotherapy (NAC) followed by consolidative therapy with either chemoradiation or radical cystectomy (RC). Some patients experience robust pathologic responses to NAC, and these have been reported to associate with somatic mutations in specific gene pathways including DNA damage response genes. Objective: To evaluate the ability of post-NAC clinical restaging, with or without tumor sequencing, to predict final RC pathologic staging. Design, setting, and participants: We reviewed our institutional review board–approved institutional database to identify patients with MIBC who underwent NAC followed by RC from 2003 to 2016. Following NAC prior to RC, cystoscopy was performed routinely, with resection of residual visible tumor and/or tumor base (transurethral resection [TUR]). For patients with pre-NAC tumor tissue available, tumor sequencing was performed. Outcome measurements and statistical analysis: Clinical restaging and tumor sequencing were evaluated for their ability to predict the final pathologic stage accurately at RC using chi-square or Fisher’s exact test. Results and limitations: A total of 114 patients underwent restaging TUR following NAC and prior to RC. The diagnostic accuracy of post-NAC clinical restaging including TUR was poor, with 32% of patients being downstaged falsely when compared with their final RC pathology. Forty-nine patients had sequencing of pre-NAC tumor tissue, of whom 32 showed at least one mutation of interest. However, NAC responses and rates of false downstaging did not differ significantly according to tumor mutation status. Conclusions: This study highlights the inaccuracy of post-NAC clinical restaging TUR with or without adjunctive tumor mutation analysis, to assess pathologic residual disease accurately. Caution must be taken when performing post-NAC restaging, especially when considering conservative management strategies such as active surveillance on this basis. Patient summary: Several groups are evaluating whether certain patients, whose bladder cancer responds well to upfront chemotherapy, may be able to forego cystectomy safely. We demonstrate that currently available staging tools and tumor DNA sequencing cannot identify such patients reliably and accurately.
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- 2021
8. Reply by Authors
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Surena F. Matin, Phillip M. Pierorazio, Nir Kleinmann, John L. Gore, Ahmad Shabsigh, Brian Hu, Karim Chamie, Guilherme Godoy, Scott G. Hubosky, Marcelino Rivera, Michael O’Donnell, Marcus Quek, Jay D. Raman, John J. Knoedler, Douglas Scherr, Christopher Weight, Alon Weizer, Michael Woods, Hristos Kaimakliotis, Angela B. Smith, Jennifer Linehan, Jonathan Coleman, Mitchell R. Humphreys, Raymond Pak, David Lifshitz, Michael Verni, Ifat Klein, Marina Konorty, Dalit Strauss-Ayali, Gil Hakim, Elyse Seltzer, Mark Schoenberg, and Seth P. Lerner
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Urology - Published
- 2022
9. Durability of Response to Primary Chemoablation of Low-Grade Upper Tract Urothelial Carcinoma Using UGN-101, a Mitomycin-Containing Reverse Thermal Gel: OLYMPUS Trial Final Report
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Surena F. Matin, Phillip M. Pierorazio, Nir Kleinmann, John L. Gore, Ahmad Shabsigh, Brian Hu, Karim Chamie, Guilherme Godoy, Scott G. Hubosky, Marcelino Rivera, Michael O’Donnell, Marcus Quek, Jay D. Raman, John J. Knoedler, Douglas Scherr, Christopher Weight, Alon Weizer, Michael Woods, Hristos Kaimakliotis, Angela B. Smith, Jennifer Linehan, Jonathan Coleman, Mitchell R. Humphreys, Raymond Pak, David Lifshitz, Michael Verni, Ifat Klein, Marina Konorty, Dalit Strauss-Ayali, Gil Hakim, Elyse Seltzer, Mark Schoenberg, and Seth P. Lerner
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Male ,Antibiotics, Antineoplastic ,Urinary Bladder Neoplasms ,Urology ,Mitomycin ,Carcinoma ,Humans ,Female ,Hydrogels ,Middle Aged ,Neoplasm Grading ,Urothelium ,Aged - Abstract
Our goal was to evaluate long-term safety and durability of response to UGN-101, a mitomycin-containing reverse thermal gel, as primary chemoablative treatment for low-grade upper tract urothelial carcinoma.In this open-label, single-arm, multicenter, phase 3 trial (NCT02793128), patients ≥18 years of age with primary or recurrent biopsy-proven low-grade upper tract urothelial carcinoma received 6 once-weekly instillations of UGN-101 via retrograde catheter to the renal pelvis and calyces. Those with complete response (defined as negative ureteroscopic evaluation, negative cytology and negative for-cause biopsy) 4-6 weeks after the last instillation were eligible for up to 11 monthly maintenance instillations and were followed for ≥12 months with quarterly evaluation of response durability. Durability of complete response was determined by ureteroscopic evaluation; duration of response was estimated by the Kaplan-Meier method. Treatment-emergent adverse events (TEAEs) were monitored.Of 71 patients who initiated treatment, 41 (58%) had complete response to induction therapy and consented to long-term followup; 23/41 patients (56%) remained in complete response after 12 months (95% CI 40, 72), comprising 6/12 (50%) who did not receive any maintenance instillations and 17/29 (59%) who received ≥1 maintenance instillation. Kaplan-Meier analysis of durability was estimated as 82% (95% CI 66, 91) at 12 months. Ureteric stenosis was the most frequently reported TEAE (31/71, 44%); an increasing number of instillations appeared to be associated with increased incidence of urinary TEAEs.Durability of response to UGN-101 with or without maintenance treatment is clinically meaningful, offering a kidney-sparing therapeutic alternative for patients with low-grade disease.
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- 2021
10. PD43-02 PRIMARY CHEMOABLATION OF LOW-GRADE INTERMEDIATE-RISK NON-MUSCLE-INVASIVE BLADDER CANCER USING UGN-102, A MITOMYCIN-CONTAINING REVERSE THERMAL GEL (OPTIMA II): A PHASE 2b, OPEN-LABEL, SINGLE-ARM TRIAL
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Kent Chevli, Neal Shore, Andrew Trainer, Angela B. Smith, Daniel Saltzstein, Yaron Ehrlich, Jay D. Raman, Boris Friedman, Richard D'Anna, David Morris, Brian Hu, Mark Tyson, Alexander Sankin, Max Kates, Jennifer Linehan, Douglas Scherr, Steven Kester, Michael Verni, Karim Chamie, Lawrence Karsh, Arnold Cinman, Soumi Lahiri, Andrew Meads, Madlen Malinowski, Nimrod Gabai, Sunil Raju, Elyse Seltzer, Mark Schoenberg, and William C. Huang
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Urology - Published
- 2021
11. Thermo Reversible Hydrogel Based Delivery of Mitomycin C (UGN-101) for Treatment of Upper Tract Urothelial Carcinoma (UTUC)
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Seth P. Lernerc, J. Alfred Witjes, Mark Schoenberg, Ifat Klein, Gil Mayer, Ofer Nativ, Helen A. Kopelen, Asaf Shvero, Nir Kleinmann, Angela B. Smith, Surena F. Matin, Yael Agmon-Gerstein, Jeffrey S. Lin, Karim Chamie, Grégory Johann Wirth, Gil Hakim, Michal Jeshurun-Gutshtat, Allan J. Pantuck, and Nadav Malchi
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medicine.medical_specialty ,Oncology ,Upper tract ,business.industry ,Urology ,Mitomycin C ,medicine ,Urologic Neoplasms ,business ,Upper urinary tract ,Urothelial carcinoma - Published
- 2019
12. Testing New Ways to Measure How Patients Rate Quality of Life
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Brieyona Reaves, Bernard H. Bochner, Marisa Cortese, Yuelin Li, Bruce D. Rapkin, Alexander Sankin, Tom Atkinson, Jie Zhang, Leah Goldstein, Seth P. Lerner, Carolyn E. Schwartz, Mark Schoenberg, Iliana Garcia, Wes Michael, and Una Hopkins
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Gerontology ,Quality of life (healthcare) ,Measure (physics) ,Psychology - Published
- 2020
13. Safety of repeat blue light cystoscopy with hexaminolevulinate (HAL) in the management of bladder cancer: Results from a phase III, comparative, multi-center study
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Kamal S. Pohar, Sanjay Patel, Yair Lotan, Edouard Trabulsi, Michael Woods, Tracy Downs, William C. Huang, Jeffrey Jones, Jennifer Taylor, Michael O'Donnell, Trinity J. Bivalacqua, Joel DeCastro, Gary Steinberg, Ashish M. Kamat, Matthew J. Resnick, Badrinath Konety, Mark Schoenberg, J. Stephen Jones, and Siamak Daneshmand
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Oncology ,Urinary Bladder Neoplasms ,Urology ,Humans ,Aminolevulinic Acid ,Cystoscopy ,Cystectomy - Abstract
The therapeutic benefit of intravesical instillation of hexaminolevulinate (HAL) at the time of transurethral resection of bladder tumor (TURBT) has been demonstrated in multiple studies. The purpose of this study was to prospectively assess the safety of repeated administration of HAL from a phase III pre-trial planned analysis.All patients evaluated in the study received at least 1 dose of HAL at the time of office cystoscopy, and a subset of these patients (n = 103, 33.2%) received a second dose a few weeks later at the time of TURBT. Adverse events (AEs) were recorded, and the safety of repeat use of HAL was determined by comparing the proportion of patients with AEs considered causally related to HAL in the surveillance examination compared to the OR examination. Association between categorical variables was tested using Fisher's Exact Test, and a P0.05 was considered statistically significant.HAL-related AEs were experienced by 6 patients (2.2%) during surveillance cystoscopy and 3 patients (3.4%) following TURBT (P = 0.76); 181 patients (59.5%) had prior exposure to HAL before enrolling in the study with no difference in the number of AEs when comparing prior exposure to HAL to no prior exposure (P = 0.76). Of the patients who previously received intravesical therapy, 8 (2.9%) had at least 1 AE during surveillance compared to 3 (9.7%) who had no prior intravesical therapy (P = 0.09).Repeat use of HAL is safe even when administered within a few weeks of receiving a dose of intravesical therapy.
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- 2020
14. Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial
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Mitchell R. Humphreys, Gil Hakim, John L. Gore, Ifat Klein, Michael Woods, Karim Chamie, David A. Lifshitz, Mehrad Adibi, Joshua Stern, Raymond Pak, Michael A. O’Donnell, Scott G. Hubosky, Brian Hu, Guilherme Godoy, Mahul B. Amin, Marcus L. Quek, Phillip M. Pierorazio, Dalit Strauss-Ayali, Angela B. Smith, Surena F. Matin, Jonathan A. Coleman, Seth P. Lerner, Hristos Z. Kaimakliotis, Jay D. Raman, Marcelino E. Rivera, Douglas S. Scherr, Nir Kleinmann, Michael Verni, Christopher J. Weight, John J. Knoedler, Ahmad Shabsigh, Alon Z. Weizer, Jennifer M Linehan, Marina Konorty, Elyse Seltzer, and Mark Schoenberg
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,Drug Compounding ,Mitomycin ,030232 urology & nephrology ,Urology ,03 medical and health sciences ,0302 clinical medicine ,Cytology ,Biopsy ,Carcinoma ,medicine ,Humans ,Urothelium ,Israel ,Aged ,Aged, 80 and over ,Drug Carriers ,Antibiotics, Antineoplastic ,medicine.diagnostic_test ,business.industry ,Hydrogels ,Middle Aged ,medicine.disease ,Kidney Neoplasms ,United States ,Clinical trial ,Catheter ,medicine.anatomical_structure ,Treatment Outcome ,Oncology ,Upper tract ,030220 oncology & carcinogenesis ,Female ,Neoplasm Grading ,business ,Renal pelvis - Abstract
Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel.In this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5-15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4-6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with ClinicalTrials.gov, NCT02793128.Between April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47-71; p0·0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11·0 months (IQR 5·1-12·4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment.Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients.UroGen Pharma.
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- 2019
15. Outcomes of Trimodal Therapy for cT2-3 Urothelial Carcinoma in a Racially Diverse Population: A Single Institution Experience in the Bronx
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Ahmed Aboumohamed, Keyur J. Mehta, Alexander Sankin, Evan Z. Kovac, Benjamin A. Gartrell, Mark Schoenberg, Josh Gottlieb, Madhur Garg, Chandan Guha, and William Bodner
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Oncology ,medicine.medical_specialty ,Bladder cancer ,business.industry ,Urology ,medicine.disease ,Diverse population ,Internal medicine ,medicine ,Erratum ,Single institution ,business ,Urothelial carcinoma - Published
- 2021
16. A review of the PD-1/PD-L1 checkpoint in bladder cancer: From mediator of immune escape to target for treatment 1 1MPS is an investor in and consultant for Urogen. SAP is consultant and advisor for Vaccinex. The remaining authors have nothing to disclose
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Steven A. Porcelli, Alexander Sankin, Xingxing Zang, David S. Perlin, Tian C. Zhou, and Mark Schoenberg
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0301 basic medicine ,Bladder cancer ,Metastatic Urothelial Carcinoma ,biology ,business.industry ,Urology ,medicine.medical_treatment ,Immunotherapy ,medicine.disease ,Biomarker (cell) ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Oncology ,030220 oncology & carcinogenesis ,PD-L1 ,Immunology ,Cancer cell ,medicine ,biology.protein ,Cancer research ,business - Abstract
Purpose Recent observations have focused attention on the means that human tumors employ to evade host defense systems critical to immune surveillance. The concepts of immunotherapy are familiar to urologists because of the use of bacillus Calmette-Guerin in bladder cancer. Research demonstrating the importance of checkpoint inhibitors in suppressing immune responses against tumors has heightened interest in immunotherapy at a time when there is a need for alternatives to bacillus Calmette-Guerin. We review the literature on the application of immunotherapeutic agents targeting a key checkpoint pathway, programmed death 1 (PD-1) and its ligand (PD-L1), in the field of bladder cancer. Materials and methods A comprehensive literature review was performed using Medline/Pubmed and Embase. Results The PD-1/PD-L1 pathway may be manipulated by cancer cells to subvert the immune system. PD-1/PD-L1 blockade has been tested in clinical trials for various malignancies including metastatic urothelial carcinoma, with significant response rates and limited side effects. PD-L1 expression has also been proposed as a prognostic marker for bladder cancer with mixed results. Conclusions PD-1 is one of several key receptors mediating immune escape, and agents targeting its ligand PD-L1 have already been successfully applied to patients with metastatic urothelial cancer. More research is needed to standardize criteria for PD-L1 positivity, explore its use as a biomarker, and optimize its use in the treatment for bladder cancer.
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- 2017
17. Efficacy and Safety of Blue Light Flexible Cystoscopy with Hexaminolevulinate in the Surveillance of Bladder Cancer: A Phase III, Comparative, Multicenter Study
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Siamak, Daneshmand, Sanjay, Patel, Yair, Lotan, Kamal, Pohar, Edouard, Trabulsi, Michael, Woods, Tracy, Downs, William, Huang, Jeffrey, Jones, Michael, O'Donnell, Trinity, Bivalacqua, Joel, DeCastro, Gary, Steinberg, Ashish, Kamat, Matthew, Resnick, Badrinath, Konety, Mark, Schoenberg, J Stephen, Jones, and Christopher, Weight
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Adult ,Male ,medicine.medical_specialty ,Urology ,030232 urology & nephrology ,Malignancy ,03 medical and health sciences ,0302 clinical medicine ,Bladder Neoplasm ,Medicine ,Humans ,Prospective Studies ,Papillary urothelial neoplasm of low malignant potential ,Blue light ,Aged ,Aged, 80 and over ,Bladder cancer ,Photosensitizing Agents ,medicine.diagnostic_test ,business.industry ,Carcinoma in situ ,Cystoscopy ,Aminolevulinic Acid ,Middle Aged ,medicine.disease ,Urinary Bladder Neoplasms ,030220 oncology & carcinogenesis ,Hexaminolevulinate ,Female ,Radiology ,Neoplasm Recurrence, Local ,business - Abstract
We compared blue light flexible cystoscopy with white light flexible cystoscopy for the detection of bladder cancer during surveillance.Patients at high risk for recurrence received hexaminolevulinate intravesically before white light flexible cystoscopy and randomization to blue light flexible cystoscopy. All suspicious lesions were documented. Patients with suspicious lesions were referred to the operating room for repeat white and blue light cystoscopy. All suspected lesions were biopsied or resected and specimens were examined by an independent pathology consensus panel. The primary study end point was the proportion of patients with histologically confirmed malignancy detected only with blue light flexible cystoscopy. Additional end points were the false-positive rate, carcinoma in situ detection and additional tumors detected only with blue light cystoscopy.Following surveillance 103 of the 304 patients were referred, including 63 with confirmed malignancy, of whom 26 had carcinoma in situ. In 13 of the 63 patients (20.6%, 95% CI 11.5-32.7) recurrence was seen only with blue light flexible cystoscopy (p0.0001). Five of these cases were confirmed as carcinoma in situ. Operating room examination confirmed carcinoma in situ in 26 of 63 patients (41%), which was detected only with blue light cystoscopy in 9 of the 26 (34.6%, 95% CI 17.2-55.7, p0.0001). Blue light cystoscopy identified additional malignant lesions in 29 of the 63 patients (46%). The false-positive rate was 9.1% for white and blue light cystoscopy. None of the 12 adverse events during surveillance were serious.Office based blue light flexible cystoscopy significantly improves the detection of patients with recurrent bladder cancer and it is safe when used for surveillance. Blue light cystoscopy in the operating room significantly improves the detection of carcinoma in situ and detects lesions that are missed with white light cystoscopy.
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- 2017
18. Non-invasive detection of bladder cancer through the analysis of driver gene mutations and aneuploidy
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Simeon Springer, Maria Del Carmen Rodriguez Pena, Lu Li, Christopher Douville, Yuxuan Wang, Josh Cohen, Diana Taheri, Bahman Afsari, Natalie Silliman, Joy Schaeffer, Janine Ptak, Lisa Dobbyn, Maria Papoli, Isaac Kinde, Aline C. Tregnago, Stephania M. Bezerra, Christopher VandenBussche, Kazutoshi Fujita, Dilek Ertoy, Isabela W. Cunha, Lijia Yu, Mark Schoenberg, Trinity J. Bivalacqua, Kathleen G. Dickman, Arthur P. Grollman, Luis A. Diaz, Rachel Karchin, Ralph Hruban, Cristian Tomasetti, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, and George J. Netto
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0303 health sciences ,medicine.medical_specialty ,Bladder cancer ,business.industry ,Aneuploidy ,Chromosome ,Urine ,Gene mutation ,medicine.disease ,Gastroenterology ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Cytology ,medicine ,Dysuria ,Microscopic hematuria ,medicine.symptom ,business ,030304 developmental biology - Abstract
Current non-invasive approaches for bladder cancer (BC) detection are suboptimal. We report the development of non-invasive molecular test for BC using DNA recovered from cells shed into urine. This “UroSEEK” test incorporates assays for mutations in 11 genes and copy number changes on 39 chromosome arms. We first evaluated 570 urine samples from patients at risk for BC (microscopic hematuria or dysuria). UroSEEK was positive in 83% of patients that developed BC, but in only 7% of patients who did not develop BC. Combined with cytology, 95% of patients that developed BC were positive. We then evaluated 322 urine samples from patients soon after their BCs had been surgically resected. UroSEEK detected abnormalities in 66% of the urine samples from these patients, sometimes up to 4 years prior to clinical evidence of residual neoplasia, while cytology was positive in only 25% of such urine samples. The advantages of UroSEEK over cytology were particularly evident in low-grade tumors, wherein cytology detected none while UroSEEK detected 67% of 49 cases. These results establish the foundation for a new, non-invasive approach to the detection of BC in patients at risk for initial or recurrent disease.
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- 2017
19. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one
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Andreas Lundqvist, Vincent van Hoef, Xiaonan Zhang, Erik Wennerberg, Julie Lorent, Kristina Witt, Laia Masvidal Sanz, Shuo Liang, Shannon Murray, Ola Larsson, Rolf Kiessling, Yumeng Mao, John-William Sidhom, Catherine A. Bessell, Jonathan Havel, Jonathan Schneck, Timothy A. Chan, Eliot Sachsenmeier, David Woods, Anders Berglund, Rupal Ramakrishnan, Andressa Sodre, Jeffrey Weber, Roberta Zappasodi, Yanyun Li, Jingjing Qi, Philip Wong, Cynthia Sirard, Michael Postow, Walter Newman, Henry Koon, Vamsidhar Velcheti, Margaret K. Callahan, Jedd D. Wolchok, Taha Merghoub, Lawrence G. Lum, Minsig Choi, Archana Thakur, Abhinav Deol, Gregory Dyson, Anthony Shields, Cara Haymaker, Marc Uemura, Ravi Murthy, Marihella James, Daqing Wang, Julie Brevard, Catherine Monaghan, Suzanne Swann, James Geib, Mark Cornfeld, Srinivas Chunduru, Sudhir Agrawal, Cassian Yee, Jennifer Wargo, Sapna P. Patel, Rodabe Amaria, Hussein Tawbi, Isabella Glitza, Scott Woodman, Wen-Jen Hwu, Michael A. Davies, Patrick Hwu, Willem W. Overwijk, Chantale Bernatchez, Adi Diab, Erminia Massarelli, Neil H. Segal, Vincent Ribrag, Ignacio Melero, Tara C. Gangadhar, Walter Urba, Dirk Schadendorf, Robert L. Ferris, Roch Houot, Franck Morschhauser, Theodore Logan, Jason J. Luke, William Sharfman, Fabrice Barlesi, Patrick A. Ott, Laura Mansi, Shivaani Kummar, Gilles Salles, Cecilia Carpio, Roland Meier, Suba Krishnan, Dan McDonald, Matthew Maurer, Xuemin Gu, Jaclyn Neely, Satyendra Suryawanshi, Ronald Levy, Nikhil Khushalani, Jennifer Wu, Jinyu Zhang, Fahmin Basher, Mark Rubinstein, Mark Bucsek, Guanxi Qiao, Cameron MacDonald, Bonnie Hylander, Elizabeth Repasky, Shilpak Chatterjee, Anusara Daenthanasanmak, Paramita Chakraborty, Kyle Toth, Megan Meek, Elizabeth Garrett-Mayer, Michael Nishimura, Chrystal Paulos, Craig Beeson, Xuezhong Yu, Shikhar Mehrotra, Fei Zhao, Kathy Evans, Christine Xiao, Alisha Holtzhausen, Brent A. Hanks, Nicole Scharping, Ashley V. Menk, Rebecca Moreci, Ryan Whetstone, Rebekah Dadey, Simon Watkins, Robert Ferris, Greg M. Delgoffe, Jonathan Peled, Sean Devlin, Anna Staffas, Melissa Lumish, Kori Porosnicu Rodriguez, Katya Ahr, Miguel Perales, Sergio Giralt, Ying Taur, Eric Pamer, Marcel R. M. van den Brink, Robert Jenq, Nicola Annels, Hardev Pandha, Guy Simpson, Hugh Mostafid, Kevin Harrington, Alan Melcher, Mark Grose, Bronwyn Davies, Gough Au, Roberta Karpathy, Darren Shafren, Jacob Ricca, Dmitriy Zamarin, Luciana Batista, Florence Marliot, Angela Vasaturo, Sabrina Carpentier, Cécile Poggionovo, Véronique Frayssinet, Jacques Fieschi, Marc Van den Eynde, Franck Pagès, Jérôme Galon, Fabienne Hermitte, Sean G. Smith, Khue Nguyen, Sruthi Ravindranathan, Bhanu Koppolu, David Zaharoff, Gustavo Schvartsman, Roland Bassett, Jennifer L. McQuade, Lauren E. Haydu, Douglas Kline, Xiufen Chen, Dominick Fosco, Justin Kline, Abigail Overacre, Maria Chikina, Erin Brunazzi, Gulidanna Shayan, William Horne, Jay Kolls, Tullia C. 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Powell, Marco Donia, Julie Westerlin Kjeldsen, Rikke Andersen, Marie Christine Wulff Westergaard, Valentina Bianchi, Mateusz Legut, Meriem Attaf, Garry Dolton, Barbara Szomolay, Sascha Ott, Rikke Lyngaa, Sine Reker Hadrup, Andrew Kelvin Sewell, Inge Marie Svane, Aaron Fan, Takumi Kumai, Esteban Celis, Ian Frank, Amanda Stramer, Michelle A. Blaskovich, Seth Wardell, Maria Fardis, James Bender, Michael T. Lotze, Stephanie L. Goff, Nikolaos Zacharakis, Yasmine Assadipour, Todd D. Prickett, Jared J. Gartner, Robert Somerville, Mary Black, Hui Xu, Harshini Chinnasamy, Isaac Kriley, Lily Lu, John Wunderlich, Paul F. Robbins, Steven Rosenberg, Steven A. Feldman, Kasia Trebska-McGowan, Parisa Malekzadeh, Eden Payabyab, Richard Sherry, Aishwarya Gokuldass, Charlene Kopits, Brian Rabinovich, Daniel S. Green, Olena Kamenyeva, Kathryn C. Zoon, Christina M. Annunziata, Joanne Hammill, Christopher Helsen, Craig Aarts, Jonathan Bramson, Yui Harada, Yoshikazu Yonemitsu, Kenneth Mwawasi, Galina Denisova, Rajanish Giri, Benjamin Jin, Tracy Campbell, Lindsey M. Draper, Sanja Stevanovic, Zhiya Yu, Bianca Weissbrich, Nicholas P. Restifo, Cornelia L. Trimble, Christian S. Hinrichs, Kwong Tsang, Massimo Fantini, James W. Hodge, Rika Fujii, Ingrid Fernando, Caroline Jochems, Christopher Heery, James Gulley, Patrick Soon-Shiong, Jeffrey Schlom, Weiqing Jing, Jill Gershan, Grace Blitzer, James Weber, Laura McOlash, Bryon D. Johnson, Simin Kiany, Huang Gangxiong, Eugenie S. Kleinerman, Michael Klichinsky, Marco Ruella, Olga Shestova, Saad Kenderian, Miriam Kim, John Scholler, Carl H. June, Saar Gill, Duane Moogk, Shi Zhong, Ivan Liadi, William Rittase, Victoria Fang, Janna Dougherty, Arianne Perez-Garcia, Iman Osman, Cheng Zhu, Navin Varadarajan, Alan Frey, Michelle Krogsgaard, Daniel Landi, Kristen Fousek, Malini Mukherjee, Ankita Shree, Sujith Joseph, Kevin Bielamowicz, Tiara Byrd, Nabil Ahmed, Meenakshi Hegde, Sylvia Lee, David Byrd, John Thompson, Shailender Bhatia, Scott Tykodi, Judy Delismon, Liz Chu, Siddiq Abdul-Alim, Arpy Ohanian, Anna Marie DeVito, Stanley Riddell, Kim Margolin, Isabelle Magalhaes, Jonas Mattsson, Michael Uhlin, Satoshi Nemoto, Patricio Pérez Villarroel, Ryosuke Nakagawa, James J. Mule, Adam W. 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Omilian, Wiam Bshara, Omilian Angela, Joseph M. Obeid, Gulsun Erdag, Mark E. Smolkin, Donna H. Deacon, James W. Patterson, Lieping Chen, Timothy N. Bullock, Craig L. Slingluff, John T. Loffredo, Raja Vuyyuru, Sophie Beyer, Vanessa M. Spires, Maxine Fox, Jon M. Ehrmann, Katrina A. Taylor, Alan J. Korman, Robert F. Graziano, David Page, Katherine Sanchez, Maritza Martel, Mariana Petaccia De Macedo, Yong Qin, Alex Reuben, Christine Spencer, Michele Guindani, Adriana Racolta, Brian Kelly, Tobin Jones, Nathan Polaske, Noah Theiss, Mark Robida, Jeffrey Meridew, Iva Habensus, Liping Zhang, Lidija Pestic-Dragovich, Lei Tang, Ryan J. Sullivan, Thomas Olencki, Thomas Hutson, Joanna Roder, Shauna Blackmon, Heinrich Roder, John Stewart, Asim Amin, Marc S. Ernstoff, Joseph I. Clark, Michael B. Atkins, Jeffrey Sosman, David F. McDermott, Harriet Kluger, Ruth Halaban, Mario Snzol, Senait Asmellash, Arni Steingrimsson, Chichung Wang, Kristin Roman, Amanda Clement, Sean Downing, Clifford Hoyt, Nathalie Harder, Guenter Schmidt, Ralf Schoenmeyer, Nicolas Brieu, Mehmet Yigitsoy, Gabriele Madonna, Gerardo Botti, Antonio Grimaldi, Paolo A. Ascierto, Ralf Huss, Maria Athelogou, Harald Hessel, Alexander Buchner, Christian Stief, Gerd Binnig, Thomas Kirchner, Shankar Sellappan, Sheeno Thyparambil, Sarit Schwartz, Fabiola Cecchi, Andrew Nguyen, Charles Vaske, Todd Hembrough, Jan Spacek, Michal Vocka, Eva Zavadova, Helena Skalova, Pavel Dundr, Lubos Petruzelka, Nicole Francis, Rau T. Tilman, Arndt Hartmann, Irena Netikova, Julia Stump, Amanda Tufman, Frank Berger, Michael Neuberger, Rudolf Hatz, Michael Lindner, Rachel E. Sanborn, John Handy, Rudolf M. Huber, Hauke Winter, Simone Reu, Cheng Sun, Weihua Xiao, Zhigang Tian, Kshitij Arora, Niyati Desai, Anupriya Kulkarni, Mihir Rajurkar, Miguel Rivera, Vikram Deshpande, David Ting, Katy Tsai, Adi Nosrati, Simone Goldinger, Omid Hamid, Alain Algazi, Paul Tumeh, Jimmy Hwang, Jacqueline Liu, Lawrence Chen, Reinhard Dummer, Michael Rosenblum, Adil Daud, Tsu-Shuen Tsao, Julia Ashworth-Sharpe, Donald Johnson, Srabani Bhaumik, Christopher Bieniarz, Joseph Couto, Michael Farrell, Mahsa Ghaffari, Antony Hubbard, Jerome Kosmeder, Cleo Lee, Erin Marner, Diana Uribe, Hongjun Zhang, Jian Zhang, Wenjun Zhang, Yifei Zhu, Larry Morrison, Takahiro Tsujikawa, Rohan N. Borkar, Vahid Azimi, Sushil Kumar, Guillaume Thibault, Motomi Mori, Edward El Rassi, Daniel R. Clayburgh, Molly F. Kulesz-Martin, Paul W. Flint, Lisa M. Coussens, Lisa Villabona, Giuseppe V. Masucci, Gary Geiss, Brian Birditt, Qian Mei, Alan Huang, Maribeth A. 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Timmer, Nebiyu Wondyfraw, Susan Johnson, Johanna Park, Amanda Chen, Mikayel Mkrtichyan, Amir S. Razai, Kyle S. Jones, Chelsie Y. Hata, Denise Gonzalez, Quinn Deveraux, Brendan P. Eckelman, Luis Borges, Rukmini Bhardwaj, Raj K. Puri, Akiko Suzuki, Pamela Leland, Bharat H. Joshi, Todd Bartkowiak, Ashvin Jaiswal, Casey Ager, Midan Ai, Pratha Budhani, Renee Chin, David Hong, Michael Curran, William D. Hastings, Maria Pinzon-Ortiz, Masato Murakami, Jason R. Dobson, David Quinn, Joel P. Wagner, Xianhui Rong, Pamela Shaw, Ernesta Dammassa, Wei Guan, Glenn Dranoff, Alexander Cao, Ross B. Fulton, Steven Leonardo, Kathryn Fraser, Takashi O. Kangas, Nadine Ottoson, Nandita Bose, Richard D. Huhn, Jeremy Graff, Jamie Lowe, Keith Gorden, Mark Uhlik, Thomas O’Neill, Jenifer Widger, Andrea Crocker, Li-Zhen He, Jeffrey Weidlick, Karuna Sundarapandiyan, Venky Ramakrishna, James Storey, Lawrence J. Thomas, Joel Goldstein, Henry C. Marsh, Jamison Grailer, Julia Gilden, Pete Stecha, Denise Garvin, Jim Hartnett, Frank Fan, Mei Cong, Zhi-jie Jey Cheng, Marlon J. Hinner, Rachida-Siham Bel Aiba, Corinna Schlosser, Thomas Jaquin, Andrea Allersdorfer, Sven Berger, Alexander Wiedenmann, Gabriele Matschiner, Julia Schüler, Ulrich Moebius, Christine Rothe, Olwill A. Shane, Brendan Horton, Stefani Spranger, Dayson Moreira, Tomasz Adamus, Xingli Zhao, Piotr Swiderski, Sumanta Pal, Marcin Kortylewski, Alyssa Kosmides, Kevin Necochea, Kathleen M. Mahoney, Sachet A. Shukla, Nikolaos Patsoukis, Apoorvi Chaudhri, Hung Pham, Ping Hua, Xia Bu, Baogong Zhu, Nir Hacohen, Catherine J. Wu, Edward Fritsch, Vassiliki A. Boussiotis, Gordon J. Freeman, Amy E. Moran, Fanny Polesso, Lisa Lukaesko, Emelie Rådestad, Lars Egevad, Berit Sundberg, Lars Henningsohn, Victor Levitsky, William Rafelson, John L. Reagan, Loren Fast, Pottayil Sasikumar, Naremaddepalli Sudarshan, Raghuveer Ramachandra, Nagesh Gowda, Dodheri Samiulla, Talapaneni Chandrasekhar, Sreenivas Adurthi, Jiju Mani, Rashmi Nair, Amit Dhudashia, Nagaraj Gowda, Murali Ramachandra, Alexander Sankin, Benjamin Gartrell, Kerwin Cumberbatch, Hongying Huang, Joshua Stern, Mark Schoenberg, Xingxing Zang, Ryan Swanson, Michael Kornacker, Lawrence Evans, Erika Rickel, Martin Wolfson, Sandrine Valsesia-Wittmann, Tala Shekarian, François Simard, Rodrigo Nailo, Aurélie Dutour, Anne-Catherine Jallas, Christophe Caux, and Aurélien Marabelle
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Pharmacology ,0303 health sciences ,Cancer Research ,Side effect ,business.industry ,medicine.drug_class ,Immunology ,Phases of clinical research ,Monoclonal antibody ,Phase i study ,Clinical trial ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Pharmacokinetics ,030220 oncology & carcinogenesis ,Molecular Medicine ,Immunology and Allergy ,Medicine ,In patient ,Programmed death 1 ,business ,030304 developmental biology - Published
- 2016
20. Editorial Commentary
- Author
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Mark Schoenberg
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Urology - Published
- 2018
21. Gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma: Predicting response and assessing outcomes
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Mark Schoenberg, Jen-Jane Liu, David M. Berman, Mario A. Eisenberger, Max Kates, Sheila F. Faraj, Trinity J. Bivalacqua, George J. Netto, Nilay M. Gandhi, Noah M. Hahn, Mohammad O. Hoque, Alexander S. Baras, Leonardo Oliveira Reis, and Enrico Munari
- Subjects
Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Urologic Neoplasms ,Urology ,medicine.medical_treatment ,Deoxycytidine ,Article ,Cystectomy ,Cohort Studies ,chemistry.chemical_compound ,Internal medicine ,Outcome Assessment, Health Care ,medicine ,Humans ,Dosing ,Survival rate ,Neoadjuvant therapy ,Aged ,Cisplatin ,Aged, 80 and over ,Chemotherapy ,Bladder cancer ,business.industry ,Muscle invasive ,Middle Aged ,medicine.disease ,Gemcitabine ,Neoadjuvant Therapy ,Surgery ,Survival Rate ,chemistry ,Cohort ,Female ,business ,medicine.drug - Abstract
To evaluate gemcitabine-cisplatin (GC) neoadjuvant cisplatin-based chemotherapy (NAC) for pathologic response (pR) and cancer-specific outcomes following radical cystectomy (RC) for muscle-invasive bladder cancer and identify clinical parameters associated with pR.We studied 150 consecutive cases of muscle-invasive bladder cancer that received GC NAC followed by open RC (2000-2013). A cohort of 121 patients treated by RC alone was used for comparison. Pathologic response and cancer-specific survival (CSS) were compared. We created the Johns Hopkins Hospital Dose Index to characterize chemotherapeutic dosing regimens and accurately assess sufficient neoadjuvant dosing regarding patient tolerance.No significant difference was noted in 5-year CSS between GC NAC (58%) and non-NAC cohorts (61%). The median follow-up was 19.6 months (GC NAC) and 106.5 months (non-NAC). Patients with residual non-muscle-invasive disease after GC NAC exhibit similar 5-year CSS relative to patients with no residual carcinoma (P = 0.99). NAC pR (≤ pT1) demonstrated improved 5-year CSS rates (90.6% vs. 27.1%, P0.01) and decreased nodal positivity rates (0% vs. 41.3%, P0.01) when compared with nonresponders (≥ pT2). Clinicopathologic outcomes were inferior in NAC pathologic nonresponders when compared with the entire RC-only-treated cohort. A lower pathologic nonresponder rate was seen in patients tolerating sufficient dosing of NAC as stratified by the Johns Hopkins Hospital Dose Index (P = 0.049), congruent with the National Comprehensive Cancer Network guidelines. A multivariate classification tree model demonstrated 60 years of age or younger and clinical stage cT2 as significant of NAC response (P0.05).Pathologic nonresponders fare worse than patients proceeding directly to RC alone do. Multiple predictive models incorporating clinical, histopathologic, and molecular features are currently being developed to identify patients who are most likely to benefit from GC NAC.
- Published
- 2015
22. Examining gemcitabine and docetaxel for recurrent NMIBC
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Meera Chappidi, Niv Milbar, Max Kates, Trinity J. Bivalacqua, and Mark Schoenberg
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Logistic regression ,Bladder preservation ,Gemcitabine ,Surgery ,Cystectomy ,Docetaxel ,Internal medicine ,medicine ,Stage (cooking) ,business ,medicine.drug - Abstract
322 Background: BCG relapsing/unresponsive patients who are poor surgical candidates or prefer bladder preservation vs. radical cystectomy (RC) may be offered intravesical therapies. Often in the literature, a “recurrence” after these therapies includes low-grade (LG) lesions, though stage progression and RC may be more meaningful outcomes for therapeutic efficacy. Including LG endpoints may make 2nd line therapies appear less efficacious. 2nd line intravesical Gemcitabine (GEM) with Docetaxel (DOCE) has been offered at Johns Hopkins Hospital (JHH). Our objective was to evaluate JHH experience with GEM/DOCE, and to address whether LG vs high-grade (HG) recurrence endpoints influenced outcomes. Methods: 33 patients who received full induction courses of GEM/DOCE since 2011, per the protocol adapted from Michael O’Donnell at U. Iowa, were identified in the IRB-approved JHH NMIBC database. Multivariable logistic regression determined factors associated with recurrence. Cox proportional hazard models evaluated risk factors for all-grade recurrence-free survival (AG-RFS) and HG recurrence-free survival (HG-RFS). Results: Median AG-RFS was 7.6 months with 42% 1-year and 27% 2-year AG-RFS. Median HG-RFS was 17.5 months with 57% 1-year and 44% 2-year HG-RFS. No adverse effects of GEM/DOCE were observed. There were 5 LG recurrences, 11 HG recurrences, and 3 progressions. Of these, 7 patients had RCs. Within initial LGTa presentation, 80% (4/5) had LG and 20% (1/5) had HG recurrence. Within initial HG-NMIBC presentation, 46% (13/28) had HG recurrence. Only in univariable cox models, LGTa presentation showed increased risk of AG-RFS (HR 3.18, 95% CI 1.08-9.40, p=0.036), but comparable HG-RFS (HR 0.32, 95% CI 0.04-2.47, p=0.275). Conclusions: GEM/DOCE is a well-tolerated alternative to immediate RC for highly selected patients with HG-NMIBC. As anticipated, including LG recurrence as an endpoint for RFS made GEM/DOCE appear less efficacious. However, since standard of care for LG recurrence is further intravesical therapy, this endpoint may not be appropriate, as its recurrence often does not result in RC or worse cancer outcomes. Future studies of 2nd line therapies for NMIBC should identify HG endpoints based on clinically meaningful outcomes.
- Published
- 2017
23. Reply by the authors
- Author
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Jonathan Jarow, Paul G. Kluetz, Seth P. Lerner, Ke Liu, Rajeshwari Sridhara, Dean Bajorin, Sam Chang, Colin P.N. Dinney, Susan Groshen, Ronald A. Morton, Michael O’Donnell, Diane Zipursky Quale, Mark Schoenberg, John Seigne, and Bhadrasain Vikram
- Subjects
Clinical Trials as Topic ,Urinary Bladder Neoplasms ,Urology ,Humans - Published
- 2014
24. MP61-16 PRE-CLINICAL AND CLINICAL TRANSLATION OF A TISSUE ENGINEERED NEO−URINARY CONDUIT USING ADIPOSE DERIVED SMOOTH MUSCLE CELLS FOR URINARY RECONSTRUCTION
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Trinity Bivalacqua, Gary Steinberg, Norm Smith, Seth Lerner, Bernie Bochner, Cheryl Lee, Elias Rivera, Deepak Jain, Timothy Bertram, and Mark Schoenberg
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Urology - Published
- 2014
25. Accuracy of urethral frozen section during radical cystectomy for bladder cancer
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Jonathan I. Epstein, Jennifer Gordetsky, Phillip M. Pierorazio, Meera Chappidi, Mark Schoenberg, Max Kates, Trinity J. Bivalacqua, Alexander S. Baras, Mark W. Ball, Aaron Brant, and Nikolai A. Sopko
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Male ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Antineoplastic Agents ,Kaplan-Meier Estimate ,Cystectomy ,03 medical and health sciences ,0302 clinical medicine ,Urethra ,Predictive Value of Tests ,Positive predicative value ,Urethrectomy ,medicine ,Frozen Sections ,Humans ,False Positive Reactions ,Neoadjuvant therapy ,Aged ,Retrospective Studies ,Carcinoma, Transitional Cell ,Bladder cancer ,business.industry ,Margins of Excision ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Neoadjuvant Therapy ,Surgery ,medicine.anatomical_structure ,Urinary Bladder Neoplasms ,Oncology ,030220 oncology & carcinogenesis ,Predictive value of tests ,Female ,Neoplasm Recurrence, Local ,business - Abstract
Objective Our objective was to determine the accuracy of urethral frozen section (FS) by analyzing our clinical experience. Materials and methods A total of 298 patients undergoing radical cystectomy for bladder cancer with benign or malignant urethral FS were identified between 2000 and 2012. Urethral FS were compared with rereviewed FS to calculate the positive and negative predictive values of the FS. To assess the ability of the positive FS to be cleared with further sampling/resection, FS were then compared with the final urethral margin. The cases of positive urethral FS were then specifically analyzed to assess rates of urethral recurrence and survival. Results All negative FS were confirmed to be negative on FS rereview and on final pathology, resulting in a NPV of 100%. Urethral FS were positive in 28 (8.7%) patients, of whom 2 (7%) were negative on FS rereview, yielding a positive predictive value of 93%. Both false positives were because of contamination of detached cancer from the bladder being present in the FS. After additional sampling/resection, the final margin was negative in 13 (46%) patients. Conclusions A negative urethral FS reliably identifies individuals for whom urethrectomy is unnecessary and provides robust information for decision-making regarding the safety of orthotopic reconstruction. Nearly half of the patients with a positive FS were ultimately determined to have a negative final margin. Accordingly, we recommend that surgeons and pathologists discuss positive FS findings at the time of surgery and consider whether additional tissue should be analyzed in real time.
- Published
- 2016
26. THE MOLECULAR CHARACTERISTICS OF BLADDER CANCER IN YOUNG PATIENTS
- Author
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Jurgen F. Linn, Fathollah K. Mostofi, Isabell A. Sesterhenn, and Mark Schoenberg
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Adult ,Male ,Monosomy ,Pathology ,medicine.medical_specialty ,Adolescent ,Urology ,Gene Expression ,Aneuploidy ,Chromosome 9 ,medicine ,Humans ,Child ,In Situ Hybridization ,Neoplasm Staging ,Retrospective Studies ,Chromosome Aberrations ,Carcinoma, Transitional Cell ,Bladder cancer ,Urinary bladder ,business.industry ,Carcinoma in situ ,medicine.disease ,Immunohistochemistry ,Chromosome 17 (human) ,medicine.anatomical_structure ,Transitional cell carcinoma ,Urinary Bladder Neoplasms ,Female ,Tumor Suppressor Protein p53 ,Chromosomes, Human, Pair 9 ,business ,Chromosomes, Human, Pair 17 - Abstract
The molecular characteristics of bladder cancer in children and young adults remain largely undefined. We sought to identify common molecular changes in bladder tumors in young patients using standard immunohistochemical and interphase cytogenetic methods.We retrospectively evaluated 73 bladder tumors removed from patients younger than 30 years for the p53 tumor suppressor gene product using immunohistochemical techniques and numerical aberrations of chromosomes 9, 17, X and Y.Regardless of stage, immunohistochemical evidence of p53 gene product over expression was found in the majority of tumors studied. Numerical aberrations (monosomy) of chromosome 9 were rare. Aneuploidy of chromosome 17 was common, particularly in carcinoma in situ and invasive bladder cancer.These data suggest that immunohistochemical evidence of p53 gene product over expression is common in bladder cancer in young patients. Further prospective analysis of lesions in this population may help to establish a comprehensive molecular progression model for urothelial neoplasms.
- Published
- 1998
27. Behavior of N-Phenylmaleimide-Reacted Muscle Fibers in Magnesium-Free Rigor Solution
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S. Xu, Mark Schoenberg, and L.C. Yu
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Diffraction ,Time Factors ,Molar concentration ,Muscle Fibers, Skeletal ,Biophysics ,chemistry.chemical_element ,macromolecular substances ,In Vitro Techniques ,Maleimides ,chemistry.chemical_compound ,Adenosine Triphosphate ,X-Ray Diffraction ,medicine ,Animals ,Magnesium ,Muscle, Skeletal ,integumentary system ,Solutions ,Crystallography ,Binding conformation ,chemistry ,X-ray crystallography ,Rabbits ,N-phenylmaleimide ,medicine.symptom ,Adenosine triphosphate ,Muscle Contraction ,Research Article ,Muscle contraction - Abstract
Using x-ray diffraction and mechanical stiffness, the response of N-phenylmaleimide (NPM)-reacted cross-bridges to solutions containing different amounts of ATP and Mg2+ has been studied. In relaxing solution containing greater than millimolar amounts of ATP and Mg2+, NPM-treated muscle fibers give x-ray diffraction patterns and stiffness records, which are nearly indistinguishable from those of untreated relaxed fibers. In a solution devoid of added ATP, but with Mg2+ (rigor(+Mg) solution), the muscle fibers still give x-ray diffraction patterns and mechanical responses characteristic of relaxed muscle. The new finding reported here is that in a solution devoid of both ATP and Mg2+ (rigor(−Mg) solution containing EDTA with no added ATP), NPM-reacted cross-bridges do give rigor-like behavior. This is the first report that NPM-reacted cross-bridges, at least in the presence of EDTA, are capable of going into a strongly binding conformation.
- Published
- 1998
28. Graphical Evaluation of Alkylation of Myosin's SH1 and SH2
- Author
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Vincent A. Barnett, Ling Xie, Mark Schoenberg, and Wan Xia Li
- Subjects
Cyclic N-Oxides ,Chemistry ,Stereochemistry ,Myosin ,Kinetics ,Biophysics ,N-phenylmaleimide ,Calcium-Transporting ATPases ,Alkylation ,After treatment - Abstract
Previous assertions about the effect of alkylation of SH1 and SH2 on the myosin high-salt calcium and EDTA ATPases have been summarized, and a simple procedure for obtaining the fractional labeling of SH1 and SH2 after treatment of myosin with alkylating agents has been derived. A simple graphical procedure for illustrating the degree of preference of a particular alkylating agent for SH1 over SH2 has also been developed. The procedures we developed were validated by applying them to two previously studied compounds, 4-(2-iodoacetamido)-TEMPO and 2,4-dinitrofluorobenzine, and then were used to determine a procedure for maximizing the extent of labeling of SH1 alone by N -phenylmaleimide, a compound not previously studied in this manner. It was found that ∼80% of the SH1 sites could be alkylated without significant alkylation of SH2.
- Published
- 1997
- Full Text
- View/download PDF
29. Familial Transitional Cell Carcinoma
- Author
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Lambertus A. L. M. Kiemeney and Mark Schoenberg
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Urology - Published
- 1996
30. The ratio of CD8 to Treg tumor-infiltrating lymphocytes is associated with response to cisplatin-based neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder
- Author
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Mohamed O Hoque, Noah M. Hahn, Alexander S. Baras, Jen-Jane Liu, Charles G. Drake, Max Kates, Janis M. Taube, Nilay M. Gandhi, Alan K. Meeker, Trinity J. Bivalacqua, Mark Schoenberg, and George J. Netto
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,chemical and pharmacologic phenomena ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Biopsy ,Immunology and Allergy ,Medicine ,Original Research ,Cisplatin ,Chemotherapy ,Tissue microarray ,Bladder cancer ,medicine.diagnostic_test ,business.industry ,Tumor-infiltrating lymphocytes ,FOXP3 ,hemic and immune systems ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Biomarkers ,bladder cancer ,chemotherapy ,immunology ,neoadjuvant ,business ,medicine.drug - Abstract
Introduction: Randomized controlled trials of platinum-based neoadjuvant chemotherapy (NAC) for bladder cancer have shown that patients who achieve a pathologic response to NAC exhibit 5 y survival rates of approximately 80–90% while NAC resistant (NR) cases exhibit 5 y survival rates of approximately 30–40%. These findings highlight the need to predict who will benefit from conventional NAC and the need for plausible alternatives. Methods: The pre-treatment biopsy tissues from a cohort of 41 patients with muscle invasive bladder who were treated with NAC were incorporated in tissue microarray and immunohistochemistry for PD-L1, CD8, and FOXP3 was performed. Percentage of PD-L1 positive tumor cells was measured. Tumor-infiltrating lymphocytes (TIL) densities, along with CD8 and Treg-specific TILs, were measured. Results: TIL density was strongly correlated with tumor PD-L1 expression, consistent with the mechanism of adaptive immune resistance in bladder cancer. Tumor cell PD-L1 expression was not a significant predictor of response. Neither was the CD8 nor Treg TIL density associated with response. Intriguingly though, the ratio of CD8 to Treg TIL densities was strongly associated with response (p = 0.0003), supporting the hypothesis that the immune system plays a role in the response of bladder cancer to chemotherapy. Discussion: To our knowledge, this is the first report in bladder cancer showing that the CD8 to Treg TIL density in the pre-treatment tissues is predictive for conventional NAC response. These findings warrant further investigations to both better characterize this association in larger cohorts and begin to elucidate the underlying mechanism(s) of this phenomenon.
- Published
- 2016
31. POSITIVE SURGICAL MARGINS CONTRIBUTE TO DELAYED FAILURES IN PATIENTS UNDERGOING RADICAL CYSTECTOMY FOR BLADDER CANCER
- Author
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EDWIN MORALES, 7., Shahrokh, Shariat, Pierre, Karakiewicz, Bjorn, Volkmer, Wassim, Kassouf, Yves, Fradet, Novara, Giacomo, HANS MARTIN FRITSCHE, Patrick, Bastian, Jonathan, Izawa, Christian, Stief, Vicenzo, Ficarra, Michael, Rink, Seth, Lerner, Mark, Schoenberg, Colin, Dinney, Eila, Skinner, Yair, Lotan, Arthur, Sagalowsky, and Robert, Svatek
- Published
- 2012
32. Coronary stent management in elective genitourinary surgery
- Author
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Angela D, Gupta, Michael, Streiff, Jon, Resar, and Mark, Schoenberg
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Urologic Diseases ,Coronary Artery Disease ,Risk Assessment ,Perioperative Care ,Clinical Protocols ,Elective Surgical Procedures ,Second-Look Surgery ,Practice Guidelines as Topic ,Humans ,Urologic Surgical Procedures ,Stents ,Angioplasty, Balloon, Coronary ,Intraoperative Complications ,Platelet Aggregation Inhibitors - Abstract
What's known on the subject? and What does the study add? Withdrawal of dual antiplatelet therapy before the recommended, 12 months for drug-eluting stents and 1 month for bare-metal stents increases the rate of major adverse coronary events and mortality. However, in those undergoing surgery the risk of bleeding is increased substantially for those on antiplatelet agents. Successful management in patients with coronary stents who must undergo elective or non-elective urological surgery should be a multidisciplinary decision. This article reviews the literature and recommends a protocol for clinical management of patients undergoing urological procedures after coronary stent placement. To review the literature on coronary stents and genitourinary surgery and provide a protocol for perioperative. The keywords, 'elective surgery', 'aspirin', 'clopidogrel', 'guidelines for percutaneous coronary intervention', and 'antiplatelet therapy after coronary stent placement' were used to search PubMed for any relevant articles relating to coronary stents. Recommendations were made based on the whether the procedures patients were exposed to placed them at low-, moderate- or high-bleeding risk based on the extent of the procedure. All elective procedures should be delayed for 1 month after bare-metal stent placement and 1 year after drug-eluting stent placement. In patients classified as low risk (endoscopy and laser prostatectomy), aspirin should be continued throughout the perioperative period and dual antiplatelet therapy should continue 24-48 h postoperatively, if there is no concern for active bleeding. In those classified as moderate risk (scrotal procedures, transurethral resection of bladder tumours, transurethral resection of the prostate, urinary sphincter placement) dual antiplatelet therapy should be discontinued 5-7 days before the procedure and continued within 7 days after procedure, if there is no concern for active bleeding, in consultation with cardiology. In high-risk procedures (cystectomy, nephrectomy, prostatectomy, penile prosthesis placement) dual antiplatelet therapy should be discontinued 10 days before the procedure and continued postoperatively within 7-10 days of the procedure, when there is no longer a concern for active bleeding with the assistance of a cardiologist. Coronary artery disease is becoming more prominent in our society, increasing the use of coronary stents and antiplatelet agents. With the proposed protocol, it is safe to proceed with surgical intervention in those that have adequate stent endothelialisation.
- Published
- 2011
33. Long Term-Survival after Radical Prostatectomy for men with High Gleason Sum
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Phillip M, Pierorazio, Thomas J, Guzzo, Misop, Han, Trinity J, Bivalacqua, Jonathan I, Epstein, Edward M, Schaeffer, Mark, Schoenberg, Patrick C, Walsh, and Alan W, Partin
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Article - Published
- 2011
34. Equilibrium muscle crossbridge behavior: The interaction of myosin crossbridges with actin
- Author
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Mark Schoenberg
- Subjects
Chemistry ,Muscles ,Equilibrium conditions ,Biophysics ,macromolecular substances ,Myosins ,Models, Biological ,Biochemistry ,Actins ,Kinetics ,Crystallography ,CrossBridge ,Myosin ,Animals ,Actin ,Muscle Contraction ,Protein Binding - Abstract
The interaction of myosin crossbridges with actin under equilibrium conditions is reviewed. Similarities and differences between the weakly- and strongly-binding interactions of myosin crossbridges with actin filaments are discussed. A precise, narrow definition of weakly-binding crossbridges is given. It is postulated that the fundamental difference between the weakly- and strongly-binding equilibrium interaction of crossbridges with actin is that the crossbridge heads are mobile after attachment in the first case but not in the second. It is argued that because the weakly-binding crossbridge heads are mobile after attachment, the heads appear to function independently of each other. The lack of head mobility in attached strongly-binding crossbridges makes the strongly-binding crossbridge heads appear to act cooperatively. This model of the strongly-binding crossbridge gives an explanation for two important and otherwise unexplained observations. It explains why the rate constant of force decay after a small stretch is a sigmoidal function of nucleotide analogue concentration, and why, in the presence of analogues or in rigor, the rate constant of force decay after a small stretch is often significantly slower than the rate constant for myosin subfragment-1 detachment from actin in solution. The model of the weakly-binding crossbridge accurately describes the behavior of the myosin-ATP crossbridge.
- Published
- 1993
35. Equilibrium muscle cross-bridge behavior. Theoretical considerations. II. Model describing the behavior of strongly-binding cross-bridges when both heads of myosin bind to the actin filament
- Author
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Mark Schoenberg
- Subjects
Chemistry ,Muscles ,Biophysics ,Plasma protein binding ,Myosins ,Microfilament ,Models, Biological ,Actins ,Protein filament ,Kinetics ,Biochemistry ,CrossBridge ,Myosin ,medicine ,Animals ,Head (vessel) ,medicine.symptom ,Mathematics ,Software ,Actin ,Research Article ,Muscle Contraction ,Protein Binding ,Muscle contraction - Abstract
A model has been developed for characterizing the interaction between strongly-binding myosin cross-bridges and actin in muscle fibers under equilibrium conditions where both heads of the myosin cross-bridge bind to actin. The model, that of Anderson and Schoenberg (1987. Biophys. J. 52:1077–1082) is quite similar to that of Schoenberg (1985. Biophys. J. 48:467–475), except that explicit account is taken of the fact that each crossbridge has two heads which can bind to actin. The key assumption that allows this model to explain a large body of data unexplained by the Schoenberg (1985) model is that the two crossbridge heads are not totally independent of one another after attachment. After the first head attaches, the second head is then free to attach only to an actin site distal to the first head. This means that when the more distally attached head subsequently detaches and reattaches (as the heads continually do), it will not reattach in a position of lesser strain and reduce the force it supports, but instead will remain attached in its strained position until the proximally attached head also detaches. This model gives an explanation for two important and otherwise unexplained observations made previously: it explains why at ionic strengths in the range of 50–120 mM, (a) the rate constant of force decay after a small stretch is a sigmoidal function of nucleotide analogue concentration, and (b) why in the presence of analogues or in rigor the rate constant of force decay after a small stretch is significantly slower than the rate constant for myosin subfragment-1 detachment from actin in solution.
- Published
- 1991
36. Effect of ionic strength on skinned rabbit psoas fibers in the presence of magnesium pyrophosphate
- Author
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Mark Schoenberg
- Subjects
chemistry.chemical_classification ,Chemistry ,Magnesium ,Muscles ,Osmolar Concentration ,Kinetics ,Biophysics ,Magnesium Compounds ,chemistry.chemical_element ,In Vitro Techniques ,Models, Biological ,Diphosphates ,Reaction rate constant ,CrossBridge ,Biochemistry ,Ionic strength ,Myosin ,Animals ,Nucleotide ,Rabbits ,Muscle Contraction ,Research Article ,Half time - Abstract
The effect of ionic strength on the kinetics of myosin cross-bridges in the presence of the ATP analogue PP, has been examined. It was found that increasing ionic strength from moderate values (mu approximately 100 mM) to high values (mu approximately 200 mM) has three effects. It causes a big decrease in the half time for the force decay after a small stretch, it causes a significant decrease in the sigmoidicity of the nucleotide analogue concentration dependence of the "apparent rate constant" of force decay after a small stretch, and it causes a big decrease in the range of rate constants necessary to describe the multiexponential force decay. It causes the last of these by causing a much larger increase in the slowest rate constants of the decay than in the fastest rate constants. The results suggest that whereas the behavior of cross-bridges in the presence of ATP is well-described by the simple independent-head equilibrium cross-bridge model of Schoenberg (1985. Biophys. J. 48:467-475), cross-bridges in the presence of the ATP analogue PPi require the more complicated double-headed equilibrium cross-bridge model of Anderson and Schoenberg (1987. Biophys. J. 52: 1077-1082) to describe their behavior.
- Published
- 1991
- Full Text
- View/download PDF
37. The prognostic value of FOXA1 expression in prostatectomy specimens for patients undergoing salvage radiation therapy
- Author
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Nima Tishbi, Mark Schoenberg, Shyamal Patel, Rafi Kabarriti, Reza Ghavamian, Nitin Ohri, Madhur Garg, Shalom Kalnicki, Jidong Shan, Hongying Huang, Chandan Guha, Daniel Mark, and Yinghui Song
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Prostatectomy ,medicine.medical_treatment ,medicine.disease ,Prostate cancer ,Salvage radiation ,Internal medicine ,Cohort ,medicine ,Immunohistochemistry ,FOXA1 ,business - Abstract
e16129 Background: In this study, we evaluate the prognostic value of Forkhead box protein A1 (FOXA1), a pioneer transcription factor, Immunohistochemistry staining in a cohort of prostate cancer p...
- Published
- 2015
38. A Phase I/II study of vesigenurtacel-l (hs-410) or placebo in combination with Bacillus Calmette-Guérin (BCG) in patients with non-muscle invasive bladder cancer (NMIBC)
- Author
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Mark Schoenberg, James Bailen, Gary D. Steinberg, Michael Woods, Neal D. Shore, Melissa Price, Taylor H. Schreiber, and Lawrence Karsh
- Subjects
Pharmacology ,Oncology ,endocrine system ,Cancer Research ,medicine.medical_specialty ,PRAME ,Bladder cancer ,business.industry ,Immunology ,Placebo ,medicine.disease ,Bioinformatics ,Phase i ii ,Antigen ,Internal medicine ,Poster Presentation ,medicine ,Molecular Medicine ,Immunology and Allergy ,In patient ,Cancer vaccine ,Non muscle invasive ,business ,neoplasms - Abstract
Meeting abstracts Vesigenurtacel-L is an allogeneic cell-based therapeutic cancer vaccine that was selected based on its expression of a range of tumor antigens (surviving, LAGE-1, MAGE-A3, MAGE-A11, PRAME and others) that are known to be expressed amongst a high proportion of primary bladder
- Published
- 2014
39. High-throughput molecular analysis of urine sediment for the detection of bladder cancer by high-density single-nucleotide polymorphism array
- Author
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Mohammad Obaidul, Hoque, Juna, Lee, Shahnaz, Begum, Keishi, Yamashita, James M, Engles, Mark, Schoenberg, William H, Westra, and David, Sidransky
- Subjects
Adult ,Male ,Carcinoma, Transitional Cell ,Urinary Bladder Neoplasms ,Humans ,Loss of Heterozygosity ,Female ,DNA, Neoplasm ,Allelic Imbalance ,Middle Aged ,Polymorphism, Single Nucleotide ,Genomic Instability ,Aged - Abstract
The detection of urothelial malignancies remains challenging. The majority of patients diagnosed with bladder cancer require life-long surveillance for disease recurrence. Monitoring strategies rely predominantly on invasive endoscopic techniques, which are inconvenient and uncomfortable. Multiple in vitro diagnostic technologies have been developed to supplant the contemporary standard of care. The U.S. Food and Drug Administration has approved several assays, but [because of inferior performance characteristics (low sensitivity and specificity)] these tests have not made a significant impact on practice, to date. We sought to develop a test for bladder cancer with better performance characterization detection based on a novel molecular approach. Matched urine and peripheral blood lymphocyte samples were obtained before surgery from 31 patients with bladder cancer (10 pTa, 4 pT1, and 17 pT2or). DNA from these samples was subjected to allelic imbalance analysis using HuSNP chips and was validated in parallel with microsatellite analysis for loss of heterozygosity and microsatellite instability. Peripheral blood lymphocyte and urine DNA obtained from 14 individuals without clinical evidence of genitourinary malignancy served as controls. Thirty-one of 31 (100%) urine DNA samples from patients with bladder tumors were found to have 24 or more single-nucleotide polymorphism (SNP) DNA alterations. In general, SNP alterations were more common in urine samples from pT2or tumors than pTa or pT1 tumors. SNP alterations were not identified in nine normal control subjects and in four of five patients with hematuria. These data support the noninvasive HuSNP chip assay in urine DNA as a valuable tool for the detection of bladder cancer (on a high-throughput-automated platform).
- Published
- 2003
40. Genome-wide genetic characterization of bladder cancer: a comparison of high-density single-nucleotide polymorphism arrays and PCR-based microsatellite analysis
- Author
-
Mohammad Obaidul, Hoque, Chyi-Chia R, Lee, Paul, Cairns, Mark, Schoenberg, and David, Sidransky
- Subjects
Chromosome Aberrations ,Carcinoma, Transitional Cell ,Urinary Bladder Neoplasms ,Genome, Human ,Humans ,Loss of Heterozygosity ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Microsatellite Repeats ,Oligonucleotide Array Sequence Analysis - Abstract
Most human cancers are characterized by genomic instability, the accumulation of multiple genetic alterations, and allelic imbalance throughout the genome. Loss of heterozygosity (LOH) is a common form of allelic imbalance, and the detection of LOH has been used to identify genomic regions that harbor tumor suppressor genes and to characterize different tumor types, pathological stages and progression. Global patterns of LOH can be discerned by allelotyping of tumors with polymorphic genetic markers. Microsatellites are reliable genetic markers for studying LOH, but typically only a modest number of microsatellites are tested in LOH studies because the genotyping procedure can be laborious. Here we describe the use of a new alternative approach to comprehensive allelotyping in which samples are genotyped for nearly 1500 single-nucleotide polymorphism (SNP) loci distributed across all human autosomal arms. We examined the pattern of allelic imbalance in human transitional cell carcinomas of the urinary bladder including 36 primary tumors and 1 recurrent tumor with matched normal DNAs. The call rate for all SNPs was 78.5 +/- 1.87% overall samples. Overall, the median number of allelic imbalance was 47.5, ranging from 20 to 118. The mean number of allelic imbalances was 36.58, 51.30, and 67.78 for pT(a), pT(1), andor =pT(2), respectively, and also increased by grade. The SNP microarray analysis result was validated by comparison with microsatellite allelotype analysis of 118 markers in the same tumors. Overall, the two methods produced consistent loss patterns at informative loci. The SNP assay discovered previously undiscovered allelic imbalances at chromosomal arms 12q, 16p, 1p, and 2q. The detection of LOH and other chromosomal changes using large numbers of SNP markers should enable rapid and accurate identification of allelic imbalance patterns that will facilitate the mapping and identification of important cancer genes. Moreover, SNP analysis raises the possibility of individual tumor genome-wide allelotyping with potential prognostic and diagnostic applications.
- Published
- 2003
41. Plagiarism
- Author
-
Michael J, Droller, Robert R, Bahnson, Seth P, Lerner, Mark, Schoenberg, and George A, Thalmann
- Subjects
Duplicate Publications as Topic ,Oncology ,Urology ,Scientific Misconduct ,Humans ,Guidelines as Topic ,Periodicals as Topic ,Editorial Policies ,Plagiarism - Published
- 2012
42. Transient kinetic analysis of N-phenylmaleimide-reacted myosin subfragment-1
- Author
-
Troy E. Rhodes, Wan Xia Li, Mark Schoenberg, Ling Xie, and Howard D. White
- Subjects
Binding Sites ,Hydrolysis ,Myosin Subfragments ,macromolecular substances ,Phosphate ,Biochemistry ,Fluorescence ,Dissociation (chemistry) ,Actins ,Maleimides ,chemistry.chemical_compound ,Kinetics ,Reaction rate constant ,Adenosine Triphosphate ,Spectrometry, Fluorescence ,chemistry ,ATP hydrolysis ,Spectrophotometry ,Myosin ,Biophysics ,Animals ,Rabbits ,Actin ,Ethenoadenosine Triphosphate - Abstract
Alkylation of myosin's Cys-707 (SH1) and Cys-697 (SH2) has profound consequences for myosin's ability to interact with actin and hydrolyze MgATP. Pre-steady-state measurements of myosin-S1 alkylated at SH1 and SH2 by N-phenylmaleimide (NPM) in the presence of ATP were taken to identify the steps of the reaction that are altered. It was found that the rate constant most affected by this modification is the apparent rate of the ATP hydrolysis step. This rate constant is reduced 20000-fold, an effect comparable in magnitude to the effect of the same modification on the binding of MgATP to S1 or acto-S1 [Xie, L., and Schoenberg, M. (1998) Biochemistry 37, 8048]. In contrast, the rate constants of phosphate release and dissociation of acto-S1 by ATP were reduced
- Published
- 1999
43. Binding of SH1-SH2-modified myosin subfragment-1 to actin
- Author
-
Mark Schoenberg and Ling Xie
- Subjects
Alkylating Agents ,Myosin light-chain kinase ,Meromyosin ,Chemistry ,Sulfhydryl Reagents ,Myosin Subfragments ,Biochemistry ,Binding constant ,Actins ,Calcium ATPase ,Maleimides ,Myosin head ,Kinetics ,Adenosine Triphosphate ,Ionic strength ,Myosin ,Biophysics ,Animals ,Rabbits ,Sulfhydryl Compounds ,Actin ,Protein Binding - Abstract
Myosin subfragment-1 (S1) was labeled with NPM in the presence of ATP or with pPDM in the presence of ADP at 0 degreesC, conditions which favor linking of maleimide groups to both Cys-707 (SH1) and Cys-697 (SH2). Unmodified S1 was removed by sedimentation with a small amount of F-actin, and the modified protein in the supernatant thoroughly dialyzed. The myosin high-salt EDTA and calcium ATPase activities of the isolated modified S1 were close to zero, suggesting nearly complete modification of SH1 and SH2. The binding of control and these modified myosins to actin was measured at 100 mM ionic strength using a co-sedimentation assay. In the presence of high MgATP concentration, control and NPM- and pPDM-reacted S1 all bind weakly to actin, with binding constants K3 of 4.9, 2.2, and 1.9 x 10(4) M-1, respectively. In the absence of MgATP, the binding constant K2 of pPDM-reacted S1 remains weak, 4.6 x 10(4) M-1,while that of NPM-reacted and control S1 becomes strong, 4.7 and 31 x 10(6) M-1, respectively. The binding constant for ATP to acto-NPM-reacted-S1 is approximately 2 x 10(4) M-1. Our data suggest that the binding of NPM-S1 to F-actin, in contrast to that of pPDM-S1, is ATP sensitive and can be quite strong at very low ATP concentration. They also suggest that while simple alkylation of SH1 and SH2 may be sufficient to inhibit myosin's ability to hydrolyze ATP, actual covalent linkage of SH1 and SH2 may be necessary to inhibit the weakly to strongly binding conformational change.
- Published
- 1998
44. Crossbridge Head Detachment Rate Constants Determined from a Model that Explains the Behavior of Both Weakly-and Strongly-Binding Crossbridges
- Author
-
Mark Schoenberg
- Subjects
Myosin head ,Crystallography ,Reaction rate constant ,CrossBridge ,Chemistry ,Ionic strength ,Myosin ,Biophysics ,Head (vessel) ,Muscle fibre ,Actin - Abstract
Experimentally it is observed that the head regions of weakly-binding myosin cross-bridges (crossbridges with ATP or ADP.Pi at the nucleotide binding site) are mobile while attached to actin, while strongly-binding crossbridge heads, such as those with PPi or AMP-PNP at the nucleotide binding site, are immobile (Pate and Cooke, Biophys. J., 1988; Fajer et al., Biophys. J., 1988). I postulate that the fundamental difference between weakly-and strongly-binding crossbridges is not their difference in affinity for actin, but the difference in mobility of the myosin heads attached to actin. Because the heads of weakly-binding crossbridges are mobile while attached to actin, the heads function independently and their behavior can be described by a simple independent-head model. With strongly-binding crossbridges, when one head detaches, it cannot re-attach in a position of lesser strain while the other is attached immobile; both heads must be detached concurrently before the crossbridge can relocate to a position of less strain and relax any tension it supports. This makes the heads appear to act cooperatively. A double-headed cross-bridge model is presented which takes into account the difference between weakly-and strongly-binding crossbridges. The model is quite successful at describing the experimental data. In particular, for weakly-binding crossbridges the time constant of the response to stretch is shown to be relatively insensitive to ionic strength and for strongly-binding crossbridges, the model predicts with great accuracy the large ionic strength dependence of the rate constant for force decay. When the experimental results are interpreted according to the model, an important conclusion that emerges is that in all cases (for both weakly-and strongly-binding crossbridges) unstrained crossbridge heads in the muscle fiber detach from actin with approximately the same rate constant as myosin subfragment-1 detaches from actin in solution.
- Published
- 1998
45. REPLY
- Author
-
Angela D. Gupta, Michael Streiff, Jon Resar, and Mark Schoenberg
- Subjects
Urology - Published
- 2012
46. The Strength of Binding of the Weakly-Binding Crossbridge Created by Sulfhydryl Modification has very Low Calcium Sensitivity
- Author
-
Vincent A. Barnett and Mark Schoenberg
- Subjects
Protein filament ,Biochemistry ,CrossBridge ,Chemistry ,Myosin ,Biophysics ,Calcium sensitivity ,macromolecular substances ,Atpase reaction ,Low calcium ,Actin ,Cross bridge - Abstract
The acto-subfragment-1*ATP state is an important intermediate in the Ca-activated acto-S1 ATPase reaction, suggesting that the myosin• ATP crossbridge seen in muscle fibers similarly may be an important intermediate in the contractile cycle. Treatment of muscle fibers with either para-phenylenedimaleimide (pPDM) or N-phenylmaleimide (NPM) alters the myosin crossbridges so that they bind to the actin filament with about the same affinity as the myosin•ATP crossbridge. Additionally, the treated crossbridges and the myosin•ATP crossbridge have virtually identical attachment and detachment rate constants. Thus the treated crossbridges appear to be reasonable analogues of the weakly-binding myosin•ATP crossbridges of relaxed fibers and studies of the treated fibers may shed some light on the behavior of the physiologically important myosin•ATP crossbridge. We have examined the influence of Ca2+ on the binding and rate constants of pPDM- and NPM-treated weakly-binding crossbridges. In agreement with earlier solution studies, we found almost no Ca-sensitivity of the binding of pPDM- or NPM-treated crossbridges.
- Published
- 1993
47. Tumours in Urology
- Author
-
Mark Schoenberg
- Subjects
Urology - Published
- 1995
48. No Man's Land: Men's Changing Commitments to Family and Work
- Author
-
B. Mark Schoenberg, David C. Dollahite, Jane C. Hood, Kathleen Gerson, John Snarey, E. Anthony Rotundo, and Alan J. Hawkins
- Subjects
Generativity ,Casual ,media_common.quotation_subject ,Erikson's stages of psychosocial development ,Gender studies ,Scholarship ,Portrait ,Arts and Humanities (miscellaneous) ,Anthropology ,Masculinity ,Happiness ,Early childhood ,Sociology ,Social Sciences (miscellaneous) ,media_common - Abstract
No Man's Land: Men's Changing Commitments to Family and Work. Kathleen Gerson. New York: Basic. 1993. 355 pp. ISBN 0-465-06316-0. $25 cloth. Men, Work, and Family. Jane C. Hood (Ed.). Newbury Park, CA: Sage. 1993. 294 pp. Hardcover ISBN 0-8039-3890-X (cloth). $44 cloth, $19.95 paper. American Manhood: Transformations in Masculinity from the Revolution to the Modern Era. E. Anthony Rotundo. New York: Basic. 1993. 364 pp. ISBN 0-465-01409-7. $25 cloth. Growing Up Male: The Psychology of Masculinity. B. Mark Schoenberg. Westport, CT: Bergin & Garvey. 1993. 144 pp. ISBN 0-89789-3441. $49.95 cloth. How Fathers Care for the Next Generation: A Four-Decade Study. John Snarey. Cambridge, MA: Harvard University. 1993. 394 pp. ISBN 0-674-40940-X. $35 cloth. Men, masculinity, and fathers are "hot" topics in the social sciences, as any casual perusal of academic (and popular) bookshelves will demonstrate. But it's not just the quantity of books that is striking. The emerging diversity, depth, and level of scholarship exemplify the intellectual growth of this important field of study. In this review, we discuss five new scholarly books that focus in part or fully on men in families, and highlight how scholarship has matured in this area. Yet, despite the maturation, there is room for further development. Thus, we also include our personal concerns with current scholarship and hopes for future work on men in families. John Snarey's book, How Fathers Care for the Next Generation, is one of the finest examples of how studies of men in families have progressed. Snarey draws from a four-generation, four-decade study of men to assert that "good fathering ... really does matter. It matters over a long time, over a life time, and even over generations" (p. 356). Snarey, a developmental psychologist, firmly grounds his research on fathering in Erikson's theory of human development. This book is now the finest empirical test and the strongest support for Erikson's concept of generativity--caring for the next generation. With both rigorous quantitative methods and a number of in-depth, intergenerational case studies, Snarey documents that generative fathering significantly affects children's future well-being. Snarey found links between both sons' and daughters' educational and occupational mobility (the fathers in the sample were working-class men) and various measures of their fathers' involvement in their lives in early childhood and in adolescence. (Unfortunately, familial and relational outcome measures for adult children were unavailable in Snarey's study, thus limiting the scope of his work.) In addition, generative fathering also increased fathers' own well-being at midlife in terms of occupational success and marital happiness. Furthermore, more generative fathering behavior was related to fathers' psychosocial generativity beyond the family sphere at midlife, supporting Erikson's idea that parental experience is an important foundation for healthy development at midlife. The involved fathering that Snarey measured fits within the scope of traditional male parenting rather than the less gender-stereotyped parenting often called for today. Snarey's research should encourage more researchers to study men and fathering with developmental lenses in addition to the sociological lenses that have provided the focus for so long (Hawkins, 1993) . Both the intergenerational, longitudinal design of Snarey's study and the rich theoretical tools he used to frame his data are evidence of significant maturation in the study of men and fathers. E. Anthony Rotundo's book, American Manhood, also shows how current scholarship is maturing. Rotundo, a social historian, gives us a vivid portrait of how our cultural conceptions of manhood and masculinity have evolved over the last 250 years. Together with Griswold's (1993) history of fatherhood in 19th-and 20th-century America, scholars now can place contemporary conversations on men, masculinity, and fathers within a well-documented historical context, a much needed and valuable achievement. …
- Published
- 1994
49. Stiffness of skinned rabbit psoas fibers in MgATP and MgPPi solution
- Author
-
Mark Schoenberg, Joseph M. Chalovich, Evan Eisenberg, Lois E. Greene, and Bernhard Brenner
- Subjects
Sarcomeres ,musculoskeletal diseases ,Materials science ,animal structures ,Muscles ,Biophysics ,Stiffness ,Magnesium Compounds ,macromolecular substances ,In Vitro Techniques ,equipment and supplies ,musculoskeletal system ,Sarcomere ,Diphosphates ,Adenosine Triphosphate ,Ionic strength ,medicine ,Animals ,Magnesium ,Fiber ,Rabbits ,Composite material ,medicine.symptom ,Muscle Contraction ,Research Article - Abstract
The stiffness of single skinned rabbit psoas fibers was measured during rapid length changes applied to one end of the fibers. Apparent fiber stiffness was taken as the initial slope when force was plotted vs. change in sarcomere length. In the presence of MgATP, apparent fiber stiffness increased with increasing speed of stretch. With the fastest possible stretches, the stiffness of relaxed fibers at an ionic strength of 20 mM reached more than 50% of the stiffness measured in rigor. However, it was not clear whether apparent fiber stiffness had reached a maximum, speed independent value. The same behavior was seen at several ionic strengths, with increasing ionic strength leading to a decrease in the apparent fiber stiffness measured at any speed of stretch. A speed dependence of apparent fiber stiffness was demonstrated even more clearly when stiffness was measured in the presence of 4 mM MgPPi. In this case, stiffness varied with speed of stretch over about four decades. This speed dependence of apparent fiber stiffness is likely due to cross-bridges detaching and reattaching during the stiffness measurement (Schoenberg, 1985. Biophys. J. 48:467). This means that obtaining an estimate of the maximum number of cross-bridges attached to actin in relaxed fibers at various ionic strengths is not straightforward. However, the data we have obtained are consistent with other estimates of cross-bridge affinity for actin in fibers (Brenner et al., 1986. Biophys. J. In press.) which suggest that ~60-90% of the cross-bridges attached in rigor are attached in relaxed fibers at an ionic strength of 20 mM and ~2-10% of this number of cross-bridges are attached in a relaxed fiber at an ionic strength of 170 mM.
- Published
- 1986
- Full Text
- View/download PDF
50. Accreditation Guidelines for University and College Counseling Services
- Author
-
Robert L. Wrenn, R.B. Simono, James E. Smith, Kenneth F. Garni, Phillip W. Wierson, Douglas H. Lamb, B. Mark Schoenberg, Beverly Prosser Gelwick, and Donna L. McKinley
- Subjects
Medical education ,Student development ,Higher education ,business.industry ,Pedagogy ,Counselor education ,Psychology ,business ,Accreditation ,Ethical code - Published
- 1982
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