Srinivas Rajamahanty

Flexible ureteroscopy update: indications, instrumentation and technical advances.

Retrograde ureteroscopy has recently gained a broadened indication for use from diagnostic to a variety of complex minimally invasive therapies. This review aims to look at the recent advances in the instrumentation and accessories, the widened indications of its use, surgical techniques and complications. With minimization of ureteroscopic instruments manufacturers are challenged to develop new, smaller and sturdier instruments that all will also survive the rigors of surgical therapy.

Synergistic potentiation of interferon activity with maitake mushroom d‐fraction on bladder cancer cells

To examine whether the combination of interferon (IFN)‐α and maitake mushroom D‐fraction (PDF), a bioactive mushroom extract, might potentiate the anticancer activity of IFN‐α in bladder cancer T24 cells in vitro.

Possible immunotherapeutic potentiation with D-Fraction in prostate cancer cells

BackgroundProstate cancer remains the most common malignancy among elderly men and the second leading cause of cancer death in the United States. Although several conventional therapies are currently available, they have a low efficacy and the more effective treatment modalities need to be established. Interferons (IFNs) are one of such options known as immunotherapy and demonstrated their antitumor effects on certain cancer types. Yet such antitumor activity should be improved or potentiated to have the satisfactory outcomes. In fact, combination therapy has been proposed as an alternative approach and is being underway in human and animal studies. Accordingly, we studied whether the combination of IFN-α and D-fraction (PDF), a bioactive mushroom extract, might potentiate anticancer activity of IFN-α in prostate cancer PC-3 cells in vitro.ResultsPotential effects of recombinant IFN-α2b (0–100,000 IU/ml), PDF (0–1,000 μg/ml), or their combinations were assessed on the growth of PC-3 cells at 72 h. Cell cycle analysis using a flow cytometer and Western blot analysis were performed to explore antiproliferative mechanism of these agents. The dose-dependent study showed that IFN-α2b up to 20,000 (20 K) IU/ml had no significant effects, but >60% growth reduction was attained ≤50 K IU/ml. Similarly, PDF showed no effects up to 250 μg/ml but ~65% growth reduction was seen at 1,000 μg/ml. When IFN-α2b and PDF were combined, a relatively low concentration (10 K IU/ml) of IFN-α2b and PDF (250 μg/ml) resulted in a ~65% growth reduction. This was accompanied by a G1 cell cycle arrest, indicated by cell cycle analysis. Western blots also revealed that the G1-specific cell cycle regulators, CDK2, CDK4, CDK6, cyclin D1, and cyclin E, had been significantly (>60%) down-regulated in IFN/PDF-treated cells.ConclusionThe combination of IFN-α2b (10 K IU/ml) and PDF (250 μg/ml) is capable of inducing a ~65% reduction in PC-3 cell growth. This appears to be due to a synergistic potentiation of two agents, leading to a G1 cell cycle arrest. Thus, it is conceivable that PDF may potentiate IFN-α2b activity, improving immunotherapy for prostate cancer.

Growth inhibition of androgen-responsive prostate cancer cells with brefeldin A targeting cell cycle and androgen receptor

BackgroundAndrogen ablation is one of the viable therapeutic options for patients with primary hormone (androgen)-dependent prostate cancer. However, an antibiotic brefeldin A (BFA) has been shown to exhibit the growth inhibitory effect on human cancer cells. We thus investigated if BFA might inhibit proliferation of androgen-responsive prostate cancer LNCaP cells and also explored how it would be carried out, focusing on cell cycle and androgen receptor (AR).MethodsAndrogen-mediated cellular events in LNCaP cells were induced using 5α-dihydrotestosterone (DHT) as an androgenic mediator. Effects of BFA on non-DHT-stimulated or DHT-stimulated cell growth were assessed. Its growth inhibitory mechanism(s) was further explored; performing cell cycle analysis on a flow cytometer, assessing AR activity by AR binding assay, and analyzing AR protein expression using Western blot analysis.ResultsDHT (1 nM) was capable of stimulating LNCaP cell growth by ~40% greater than non-stimulated controls, whereas BFA (30 ng/ml) completely inhibited such DHT-stimulated proliferation. Cell cycle analysis showed that this BFA-induced growth inhibition was associated with a ~75% reduction in the cell number in the S phase and a concomitant increase in the G1 cell number, indicating a G1 cell cycle arrest. This was further confirmed by the modulations of specific cell cycle regulators (CDK2, CDK4, cyclin D1, and p21WAF1), revealed by Western blots. In addition, the growth inhibition induced by BFA was accompanied by a profound (~90%) loss in AR activity, which would be presumably attributed to the significantly reduced cellular AR protein level.ConclusionsThis study demonstrates that BFA has a potent growth inhibitory activity, capable of completely inhibiting DHT (androgen)-stimulated LNCaP proliferation. Such inhibitory action of BFA appears to target cell cycle and AR: BFA led to a G1 cell cycle arrest and the down-regulation of AR activity/expression, possibly accounting for its primary growth inhibitory mechanism. Thus, it is conceivable that BFA may provide a more effective therapeutic modality for patients with hormone-dependent prostate cancer.

Mode of cytotoxic action of nephrotoxic agents: oxidative stress and glutathione-dependent enzyme.

To investigate the cytotoxic action of nephrotoxic agents using an in vitro renal cell model, focusing on the cellular oxidative status and a specific glutathione (GSH)‐dependent enzyme, glyoxalase I (Gly‐I).

Possible disease remission in patient with invasive bladder cancer with D-fraction regimen

Superficial bladder tumors are the most prevalent form of bladder cancers and transurethral resection is the primary surgical modality for those tumors. However, nearly 65% of patients will have tumor recurrence in five years while about 15% will have progression to muscle invasion. Thus, the primary therapeutic aim is to prevent multiple recurrences and progression to a more advanced, invasive disease. We here report an 87-year-old white male patient with invasive bladder cancer who received an unconventional oral regimen of D-fraction, the bioactive extract of Maitake mushroom (Grifola frondosa), following endoscopic transurethral resection of bladder tumor. Despite a high risk for disease recurrence, follow-up yet indicated no clinical evidence of progression of residual disease or recurrence of invasive cancer. It has been nearly two years but the patient remains remarkably well and appears to be in remission. To our knowledge, this is the first and only case report of possible disease remission in a bladder cancer patient after the two-year follow-up of D-fraction regimen, so that further studies with long terms are required for drawing a relevant conclusion. Nevertheless, it is conceivable that D-fraction is a natural agent that may have clinical implications in patients with superficial bladder tumors.

Intracorporeal Antegrade and Retrograde Stenting During Robot-Assisted Urinary Tract Reconstruction: Is It the Ideal Choice?

Abstract Introduction and Objective: One of the pertinent steps in many urologic reconstructive procedures is the placement of a stent across the repair. With regard to upper urinary tract reconstruction, many surgeons perform this step cystoscopically and place the stent in a retrograde fashion. Herein, we present our simplified, efficient, and cost-saving technique of Double-J (JJ) stent placement intracorporeally during robot-assisted upper urinary tract reconstructive surgery. Methods: With Institutional Review Boards approval, we queried our database of robotic procedures to identify those reconstructive operations that involved intracorporeal JJ stent placement since 2008. We describe our step-by-step technique for intracorporeal JJ stent placement during robot-assisted pyeloplasty, pyelolithotomy, and upper, mid, and lower ureteral reconstructive surgeries. Briefly, the floppy tip of a guide wire is passed through the open end of the JJ stent until it straightens out the stent. After a certain amo...

POSSIBLE BIOCHEMICAL EVENTS CRITICALLY INVOLVED IN ACUTE RENAL CELL INJURY

INTRODUCTION AND OBJECTIVE: Among men, cancers of the prostate, lung and bronchus, and colon and rectum account for about 50% of all newly diagnosed cancers and prostate cancer alone accounts for about 25% of incident cases. Nuclear factorB (NFB) -activation plays a critical role in prostate cancer by NFB inhibitor kinase pathway mediated inflammatory-induced tumorigenesis. A functional insertion/ deletion polymorphism (-94 insertion/deletion ATTG) in the promoter of NFKB1 gene, which encodes the p50 subunit of NFB, was recently identified. METHODS: A total of 117 prostate cancer patients and 143 control subjects were recruited in this study. The NFKB1 -94 insertion/ deletion ATTG genotype was determined using polymerase chain reaction-polyacrylamide gel electrophoresis. RESULTS: The frequency of ATTG2 allele in prostate cancer patients was significantly higher than that in controls (63.7% vs. 54.5 P = 0.035, OR = 1.461). Prostate cancer patients with prostatitis history have 2.275 times higher risks for prostate cancer, compared to the control group (P = 0.001). CONCLUSIONS: The functional NFKB1 promoter polymorphism is associated with increased risk of prostate cancer.