Jason Woo

Bio: Jason Woo is an academic researcher from University of California, San Diego. The author has contributed to research in topics: Prostate cancer & Prostate. The author has an hindex of 7, co-authored 15 publications receiving 272 citations. Previous affiliations of Jason Woo include Veterans Health Administration & UC San Diego Health System.

Tumor infiltrating B-cells are increased in prostate cancer tissue.

Abstract: The presence of increased B-cell tumor infiltrating lymphocytes (TILs) was seen in mouse prostate cancer (PCa) but has not been fully documented in human PCa. We, therefore, investigated the density of infiltrating B cells within human PCa utilizing a quantitative computational method. Archived radical prostatectomy specimens from 53 patients with known clinical outcome and D’Amico risk category were obtained and immunohistochemically (IHC) stained for the B cell marker, CD20. Slides were reviewed by a genitourinary pathologist who manually delineated the tumoral regions of PCa. Slides were digitally scanned and a computer algorithm quantified the area of CD20 stained B-cells as a measure of B cell density within the outlined regions of prostate cancer (intra-tumoral region), versus extra-tumoral prostate tissue. Correlations were analyzed between B-cell density and demographic and clinical variables, including D’Amico risk groups and disease recurrence. For the entire cohort, the mean intra-tumoral B cell density was higher (3.22 SE = 0.29) than in the extra-tumoral region of each prostatectomy section (2.24, SE = 0.19) (paired t test; P < 0.001). When analyzed according to D’Amico risk group, the intra-tumoral B cell infiltration in low risk (0.0377 vs. 0.0246; p = 0.151) and intermediate risk (0.0260 vs. 0.0214; p = 0.579) patient prostatectomy specimens did not show significantly more B-cells within the PCa tumor. However, patient specimens from the high-risk group (0.0301 vs. 0.0197; p < 0.001) and from those who eventually had PCa recurrence or progression (0.0343 vs. 0.0246; p = 0.019) did show significantly more intra-tumoral CD20+ B-cell staining. Extent of B-cell infiltration in the prostatectomy specimens did not correlate with any other clinical parameters. Our study shows that higher B-cell infiltration was present within the intra-tumoral PCa regions compared to the extra-tumoral benign prostate tissue regions in prostatectomy sections. For this study we developed a new method to measure B-cells using computer-assisted digitized image analysis. Accurate, consistent quantitation of B-cells in prostatectomy specimens is essential for future clinical trials evaluating the effect of B cell ablating antibodies. The interaction of B-cells and PCa may serve as the basis for new therapeutic targets.

Dyslipidemia is associated with an increased risk of nephrolithiasis

Abstract: The pathophysiology of nephrolithiasis is multifactorial. Obesity, diabetes mellitus and hypertension are implicated in its formation. Dyslipidemia (DLD) recently has received attention as well. Congruent with a vascular etiology in stone formation, DLD theoretically would predispose patients to nephrolithiasis. We investigated a possible association of DLD with nephrolithiasis. A random cohort of 60,000 patients was established by collecting the first 5,000 patient charts per month in the year 2000. After excluding pediatric patients, a retrospective study was performed by reviewing age, sex, comorbidities, and last patient follow-up. Median lipid laboratory levels also were reviewed. Descriptive statistics were performed as well as Cox proportional-hazards regression analysis, and univariate and multivariate analyses. 52,184 (22,717 women/29,467 men) patient charts were reviewed. The average age was 31.0 ± 15.2 years. On univariate analysis, DLD was associated with nephrolithiasis with a hazard ratio (HR) of 2.2 [Confidence Interval (CI), 1.9–2.5; p < 0.001] and on multivariate analysis HR = 1.2 (1.0–1.5; p = 0.033). Low-density lipoprotein and triglycerides had no association with stone disease. Patients with high-density lipoprotein (HDL) values <45 for men and <60 for women had an HR of 1.4 (1.1–1.7, 95% CI, p = 0.003) on univariate analysis and on multivariate analysis; HR = 1.27 (1.03–1.56; p = 0.024) for nephrolithiasis. DLD was associated with an increased risk of stone disease though the only specific lipid panel associated with lower nephrolithiasis was HDL. Clinicians should consider obtaining lipid levels with the intent that treatment could potentially not only mitigate atherosclerotic disease but also decrease nephrolithiasis risk.

PCSD1, a new patient-derived model of bone metastatic prostate cancer, is castrate-resistant in the bone-niche

Abstract: Prostate cancer bone metastasis occurs in 50-90% of men with advanced disease for which there is no cure. Bone metastasis leads to debilitating fractures and severe bone pain. It is associated with therapy resistance and rapid decline. Androgen deprivation therapy (ADT) is standard of care for advanced prostate cancer, however, bone metastatic prostate cancer (PCa) often becomes resistant to ADT. There are few pre-clinical models to understand the interaction between the bone microenvironment and prostate cancer. Here we report the castrate resistant growth in the bone niche of PCSD1, a patient-derived intra-femoral xenograft model of prostate bone metastatic cancer treated with the anti-androgen, bicalutamide. PCSD1 bone-niche model was derived from a human prostate cancer femoral metastasis resected during hemiarthroplasty and serially transplanted into Rag2 −/− ;γ c −/− mice intra-femorally (IF) or sub-cutaneously (SC). At 5 weeks post-transplantation mice received bicalutamide or vehicle control for 18 days. Tumor growth of PCSD1 was measured with calipers. PSA expression in PCSD1 xenograft tumors was determined using quantitative RT-PCR and immunohistochemistry. Expression of AR and PSMA, were also determined with qPCR. PCSD1 xenograft tumor growth capacity was 24 fold greater in the bone (intra-femoral, IF) than in the soft tissue (sub-cutaneous, SC) microenvironment. Treatment with the anti-androgen, bicalutamide, inhibited tumor growth in the sub-cutaneous transplantation site. However, bicalutamide was ineffective in suppressing PCSD1 tumor growth in the bone-niche. Nevertheless, bicalutamide treatment of intra-femoral tumors significantly reduced PSA expression (p < =0.008) and increased AR (p < =0.032) relative to control. PCSD1 tumors were castrate resistant when growing in the bone-niche compared to soft tissue. Bicalutamide had little effect on reducing tumor burden in the bone yet still decreased tumor PSA expression and increased AR expression, thus, this model closely recapitulated castrate-resistant, human prostate cancer bone metastatic disease. PCSD1 is a new primary prostate cancer bone metastasis-derived xenograft model to study bone metastatic disease and for pre-clinical drug development of novel therapies for inhibiting therapy resistant prostate cancer growth in the bone-niche.

Campbell-Walsh urology

Abstract: Section I: Anatomy Surgical Anatomy of the Retroperitoneum, Kidneys, and Ureters Anatomy of the Lower Urinary Tract and Male Genitalia Section II: Clinical Decision Making Evaluation of the Urologic Patient: History, Physical Examination, and Urinalysis Urinary Tract Imaging: Basic Principles Outcomes Research Section III: Basics of Urologic Surgery Basic Instrumentation and Cystoscopy Basics of Laparoscopic Urologic Surgery Section IV: Infections and Inflammation Infections of the Urinary Tract-A. Schaeffer Inflammatory Conditions of the Male Genitourinary Tract Interstitial Cystitis and Related Disorders Sexually Transmitted and Associated Diseases Urological Implications of AIDS and Related Conditions Cutaneous Diseases of the External Genitalia Tuberculosis and Other Opportunistic Infections of the Genitourinary System Section V: Molecular and Cellular Biology Basic Principles of Immunology Molecular Genetics and Cancer Biology Tissue Engineering Perspectives for Reconstructive Surgery Section VI: Reproductive and Sexual Function Male Reproductive Physiology Male Infertility Surgical Management of Male Infertility Physiology of Erectile Dysfunction: Pathophysiology, Evaluation, Nonsurgical Management Epidemiology, Evaluation, and Nonsurgical Management of Erectile Dysfunction Prosthetic Surgery for Erectile Dysfunction Vascular Surgery for Erectile Dysfunction Peyronie's Disease Priapism Androgen Deficiency in the Aging Male Female Sexual Function and Dysfunction Section VII: Male Genitalia Neoplasms of the Testis Surgery of Testicular Tumors Tumors of the Penis Surgery of Penile and Urethral Carcinoma Surgery of the Penis and Urethra Surgery of the Scrotum and Seminal Vesicles Section VIII: Renal Physiology and Pathophysiology Renal Physiology and Pathophysiology Renovascular Hypertension Section IX: Upper Urinary Tract Obstruction and Trauma Pathophysiology of Obstruction Management of Upper Urinary Tract Obstruction Upper Urinary Tract Trauma Section X: Renal Failure and Transplantation Renal Transplantation Etiology, Pathogenesis, and Management of Renal Failure Section XI: Urinary Lithiasis and Endourology Urinary Lithiasis: Etiology, Epidemiology, and Pathophysiology Evaluation and Medical Management of Urinary Lithiasis Surgical Management of Upper Urinary Tract Calculi Ureteroscopy and Retrograde Ureteral Access Percutaneous Approaches to the Upper Urinary Tract Section XII: Neoplasms of the Upper Urinary Tract Renal Tumors Urothelial Tumors of the Upper Urinary Tract Urothelial Tumors of the Renal Pelvis and Ureter Open Surgery of the Kidney Laparoscopic Surgery of the Kidney Ablative Therapy for Renal Tumors Section XIII: The Adrenals Pathophysiology, Evaluation, and Medical Management of Adrenal Disorders Surgery of the Adrenals Section XIV: Urine Transport, Storage, and Emptying Physiology and Pharmacology of the Renal Pelvis and Ureter Physiology and Pharmacology of the Bladder and Urethra Pathophysiology, Categorization, and Management of Voiding Dysfunction Urodynamic and Video dynamic Evaluation of Voiding Dysfunction Neuromuscular Dysfunction of the Lower Urinary Tract Urinary Incontinence: Epidemiology, Pathophysiology, Evaluation, and Overview of Management The Overactive Bladder Pharmacologic Management of Storage and Emptying Failure Conservative Management of Urinary Incontinence: Behavioral and Pelvic Floor Therapy, Urethral and Pelvic Devices Electrical Stimulation and Neuromodulation in Storage and Emptying Failure Retropubic Suspension Surgery for Incontinence in Women Vaginal Reconstructive Surgery for Sphincteric Incontinence Pubovaginal Slings Tension-Free Vaginal Tape Procedures Injection Therapy for Urinary Incontinence Additional Treatment for Storage and Emptying Failure Geriatric Voiding Dysfunction and Urinary Incontinence Urinary Tract Fistulae Bladder and Urethral Diverticula Surgical Procedures for Sphincteric Incontinence in the Male: The Artificial Genitourinary Sphincter Perineal Sling Procedures Section XV: Bladder Lower Genitourinary Calculi and Trauma Urothelial Tumors of the Bladder Management of Superficial Bladder Cancer Management of Metastatic and Invasive Bladder Cancer Surgery of Bladder Cancer Laparoscopic Bladder Surgery Use of Intestinal Segments in Urinary Diversion Cutaneous Continent Urinary Diversion Orthotopic Urinary Diversion Genital and Lower Urinary Tract Trauma Lower Urinary Tract Calculi Section XVI: Prostate Molecular Biology, Endocrinology, and Physiology of the Prostate and Seminal Vesicles Etiology, Pathophysiology, and Epidemiology of Benign Prostatic Hyperplasia Natural History, Evaluation, and Nonsurgical Management of Benign Prostatic Hyperplasia Minimally Invasive and Endoscopic Management of Benign Prostatic Hyperplasia Retropubic and Superpubic Open Radical Prostatectomy Epidemiology, Etiology, and Prevention of Prostate Cancer Pathology of Prostatic Neoplasms Ultrasonography and Biopsy of the Prostate Tumor Markers in Prostate Cancer Early Detection, Diagnosis, and Staging of Prostate Cancer Definitive Therapy of Localized Prostate Cancer: Outcomes Expectant Management of Prostate Cancer Anatomic Retrograde Retropubic Prostatectomy Radical Perineal Prostatectomy Laparoscopic and Robotic Radical Prostatectomy and Pelvic Lymphadenectomy Radiation Therapy for Prostate Cancer Cryotherapy of Prostate Cancer Treatment of Locally Advanced Prostate Cancer Management of Rising Prostate-Specific Antigen after Definitive Therapy Hormonal Therapy for Prostate Cancer Management of Hormone-Resistant Prostate Cancer Section XVII: Pediatric Urology Normal and Anomalous Development of the Urinary Tract Renal Function in the Fetus Congenital Obstructive Uropathy Perinatal Urology Evaluation of Pediatric Urologic Patient Renal Disease in Childhood Urinary Tract Infections in Infants and Children Anomalies of the Kidney Renal Dysplasia and Cystic Disease of Kidney Anomalies and Surgery of the Ureteropelvic Junction Ectopic Ureter Vesicoureteral Reflux Prune-Belly Syndrome Exstrophy and Epispadias Complex Surgical Technique for One-Stage Exstrophy Reconstruction Bladder Anomalies in Children Posterior Urethral Valves and Other Urethral Anomalies Voiding Dysfunction in Children: Neurogenic and Non-neurogenic Urinary Tract Reconstruction Hypospadias Abnormalities of External Genitalia in Boys Abnormalities of Testis and Scrotum: Surgical Management Sexual Differentiation: Normal and Abnormal Surgical Management of Intersex Pediatric Oncology Pediatric Endourology and Laparoscopy Pediatric Genitourinary Trauma

Roles of the immune system in cancer: from tumor initiation to metastatic progression.

Abstract: The presence of inflammatory immune cells in human tumors raises a fundamental question in oncology: How do cancer cells avoid the destruction by immune attack? In principle, tumor development can be controlled by cytotoxic innate and adaptive immune cells; however, as the tumor develops from neoplastic tissue to clinically detectable tumors, cancer cells evolve different mechanisms that mimic peripheral immune tolerance in order to avoid tumoricidal attack. Here, we provide an update of recent accomplishments, unifying concepts, and future challenges to study tumor-associated immune cells, with an emphasis on metastatic carcinomas.

Tertiary lymphoid structures improve immunotherapy and survival in melanoma.

Abstract: Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.

Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group Part 2 TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non–Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors

Abstract: Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecologic system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.

Immunosuppressive plasma cells impede T-cell-dependent immunogenic chemotherapy.

Abstract: Cancer-associated genetic alterations induce expression of tumour antigens that can activate CD8(+) cytotoxic T cells (CTLs), but the microenvironment of established tumours promotes immune tolerance through poorly understood mechanisms. Recently developed therapeutics that overcome tolerogenic mechanisms activate tumour-directed CTLs and are effective in some human cancers. Immune mechanisms also affect treatment outcome, and certain chemotherapeutic drugs stimulate cancer-specific immune responses by inducing immunogenic cell death and other effector mechanisms. Our previous studies revealed that B cells recruited by the chemokine CXCL13 into prostate cancer tumours promote the progression of castrate-resistant prostate cancer by producing lymphotoxin, which activates an IκB kinase α (IKKα)-BMI1 module in prostate cancer stem cells. Because castrate-resistant prostate cancer is refractory to most therapies, we examined B cell involvement in the acquisition of chemotherapy resistance. Here we focus on oxaliplatin, an immunogenic chemotherapeutic agent that is effective in aggressive prostate cancer. We show that mouse B cells modulate the response to low-dose oxaliplatin, which promotes tumour-directed CTL activation by inducing immunogenic cell death. Three different mouse prostate cancer models were refractory to oxaliplatin unless genetically or pharmacologically depleted of B cells. The crucial immunosuppressive B cells are plasmocytes that express IgA, interleukin (IL)-10 and programmed death ligand 1 (PD-L1), the appearance of which depends on TGFβ receptor signalling. Elimination of these cells, which also infiltrate human-therapy-resistant prostate cancer, allows CTL-dependent eradication of oxaliplatin-treated tumours.