Isaac Yi Kim

Preoperative Plasma Levels of Transforming Growth Factor Beta1 (TGF-β1) Strongly Predict Progression in Patients Undergoing Radical Prostatectomy

PURPOSE Elevated local and circulating levels of transforming growth factor beta(1) (TGF-beta(1)) have been associated with prostate cancer invasion and metastasis. We tested the hypothesis that preoperative plasma TGF-beta(1) levels would independently predict cancer stage and prognosis in patients who undergo radical prostatectomy. PATIENTS AND METHODS The study group consisted of 120 consecutive patients who underwent radical prostatectomy for clinically localized prostate cancer (median follow-up, 53.8 months). Preoperative plasma levels of TGF-beta(1) were measured and correlated with pathologic parameters and clinical outcomes. TGF-beta(1) levels also were measured in 44 healthy men without cancer, in 19 men with prostate cancer metastatic to regional lymph nodes, and in 10 men with prostate cancer metastatic to bone. RESULTS Plasma TGF-beta(1) levels in patients with lymph node metastases (14.2 +/- 2.6 ng/mL) and bone metastases (15.5 +/- 2.4 ng/mL) were higher than those in radical prostatectomy patients (5.2 +/- 1.3 ng/mL) and healthy subjects (4.5 +/- 1.2 ng/mL) (P <.001). In a preoperative analysis, preoperative plasma TGF-beta(1) level and biopsy Gleason sum both were predictors of organ-confined disease (P =.006 and P =.006, respectively) and PSA progression (P <.001 and P =.021, respectively). In a postoperative multivariate analysis, preoperative plasma TGF-beta(1) level, pathologic Gleason sum, and surgical margin status were predictors of PSA progression (P =.020,P =.020, and P =.022, respectively). In patients who progressed, preoperative plasma TGF-beta(1) levels were higher in those with presumed distant compared with local-only failure (P =.019). CONCLUSION Plasma TGF-beta(1) levels are markedly elevated in men with prostate cancer metastatic to regional lymph nodes and bone. In men without clinical or pathologic evidence of metastases, the preoperative plasma TGF-beta(1) level is a strong predictor of biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.

Preoperative plasma levels of transforming growth factor β1 strongly predict clinical outcome in patients with bladder carcinoma

Elevated local and circulating levels of transforming growth factor (TGF)‐β1 have been associated with cancer invasion, progression, and metastasis. The authors tested the hypothesis that preoperative plasma TGF‐β1 levels would independently predict cancer stage and prognosis in patients with transitional cell carcinoma (TCC) of the urinary bladder.

Predictive value of expression of transforming growth factor-β1 and its receptors in transitional cell carcinoma of the urinary bladder

The purpose of this study was to describe the expression patterns of transforming growth factor (TGF)‐β1 and its receptors in transitional cell carcinoma (TCC) of the bladder, to investigate the relation between the TGF‐β1 and its receptors, and to determine whether altered expression of TGF‐β or its receptors is associated with disease progression and survival in patients with TCC of the bladder.

Raloxifene, a mixed estrogen agonist/antagonist, induces apoptosis through cleavage of BAD in TSU-PR1 human cancer cells

Selective estrogen receptor modulator is a proven agent for chemoprevention and chemotherapy of cancer. Raloxifene, a mixed estrogen agonist/antagonist, was developed to prevent osteoporosis and potentially reduce the risk of breast cancer. In this study, we examined the effect of raloxifene on the TSU-PR1 cell line. This cell line was originally reported to be a prostate cancer cell line, but recently it has been shown to be a human bladder transitional cell carcinoma cell line. The TSU-PR1 cell line contains high levels of estrogen receptor β. Following treatment with raloxifene, evidence of apoptosis, including change in nuclear morphology, DNA fragmentation, and cytochrome c release, was observed in a dose-dependent manner in the TSU-PR1 cells (10−9 to 10−6 m range). We observed no detectable change in the steady-state levels of Bax, Bcl-2, and Bcl-XL following raloxifene treatment. However, raloxifene induced caspase-dependent cleavage of BAD to generate a 15-kDa truncated protein. Overexpression of a double mutant BAD resistant to caspase 3 cleavage blocked raloxifene-induced apoptosis. These results demonstrate that raloxifene induces apoptosis through the cleavage of BAD in TSU-PR1 cells. This molecular mechanism of apoptosis suggests that raloxifene may be a therapeutic agent for human bladder cancer.

Absence of proximal duct apoptosis in the ventral prostate of transgenic mice carrying the C3(1)‐TGF‐β type II dominant negative receptor

Prostatic epithelial cells are sensitive to the inhibitory effects of TGF‐β. However, TGF‐β signaling in the prostate is dependent on androgenic status. Under the in vivo conditions, it is difficult to dissociate the effect of TGF‐β from that of androgen on the prostate.

Bacillus Calmette-Guerin induced peritonitis in a patient on dialysis

Intravesical bacillus Calmette-Guerin (BCG) is now a widely accepted treatment for patients with high grade Ta, T1 and carcinoma in situ bladder cancer. With the increased use of intravesical BCG different types of complications have been reported. We report a case of BCG induced peritonitis.

An unusual presenting symptom of sarcoidosis: neurogenic bladder dysfunction.

Approximately 5% to 16% of patients with sarcoidosis have involvement of the nervous system.1 In a series of 37 patients with neurosarcoidosis 50% to 85% of the presenting symp- toms were neurological in origin. These symptoms ranged from cranial nerve palsies, polyneuritis, meningeal involve- ment, muscle disease and Guillain-Barresyndrome.2 We re- port on a patient with neurosarcoidosis whose initial present- ing symptom of urinary frequency was secondary to neurogenic bladder dysfunction. CASE REPORT A 40-year-old black man without significant medical his- tory presented with progressive paraplegia and urinary fre- quency. He denied any history of gross hematuria, decreased force of stream or dysuria, and urinalysis demonstrated no infection. Urodynamic evaluation revealed a hyperreflexic bladder contraction with evidence of detrusor-sphincter dys- synergia on urethral pressure profile (fig. 1). Cystoscopy was unremarkable. Magnetic resonance imaging (MRI) revealed enhancement of the spinal cord at T8 to T9 consistent with inflammation (fig. 2). A subsequent chest x-ray revealed mul- tiple lesions consistent with granulomas. Biopsies of a lesion near the left upper lobe bronchus revealed noncaseating granulomas with giant cells. Potassium hydroxide and silver stains, and stains for fungus and tuberculosis were negative. Diagnosis was neurosarcoidosis and the patient was started on 40 mg. prednisone daily. DISCUSSION