PubMed Health⌕ Search

Biomedical subjects

J Pow-Sang

Publications and source records attributed to J Pow-Sang.

At least 19 recordsLinked to original sources
PubMed2006

Novel role of Stat1 in the development of docetaxel resistance in prostate tumor cells.

A major obstacle for clinicians in the treatment of advanced prostate cancer is the inevitable progression to chemoresistance, especially to docetaxel. It is essential to understand the molecular events that lead to docetaxel resistance in order to identify means to prevent or interfere with chemoresistance. In initial attempts to detect these events, we analysed genomic differences between non-resistant and docetaxel-resistant prostate tumor cells and, of the genes modulated by docetaxel treatment, we observed Stat1 and clusterin gene expression heightened in the resistant phenotype. In this study, we provide biochemical and biological evidence that these two gene products are related. Stat1 and clusterin protein expression was induced upon docetaxel treatment of DU145 cells and highly overexpressed in the docetaxel-resistant DU145 cells (DU145-DR). The increase in total Stat1 corresponded to an increase in phosphorylated Stat1. Interestingly, there was no detectable difference between DU145 and DU145-DR cells expression of total Stat3 and phosphorylated Stat3. Treatment of DU145-DR cells with small interfering RNA targeted for Stat1 not only resulted in the knockdown of Stat1 expression, but it also caused the inhibition of clusterin expression. Thus, Stat1 appears to play a key role in the regulation of clusterin. Remarkably, inhibition of Stat1 or clusterin expression resulted in the re-sensitization of DU145-DR cells to docetaxel. These results offer the first evidence that Stat1, and its subsequent regulation of clusterin, are essential for docetaxel resistance in prostate cancer. Targeting this pathway could be a potential therapeutic means for intervention of docetaxel resistance.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Genetic adaptive neural network to predict biochemical failure after radical prostatectomy: a multi-institutional study.

BACKGROUND AND PURPOSE: Despite many new procedures, radical prostatectomy remains one of the commonest methods of treating clinically localized prostate cancer. Both from the physician's and the patient's point of view, it is important to have objective estimation of the likelihood of recurrence, which forms the foundation for treatment selection for an individual patient. Currently, it is difficult to predict the probability of biochemical recurrence (rising serum prostate specific antigen [PSA] concentration) in an individual patient, and approximately 30% of the patients do experience recurrence. Tools predicting the recurrence will be of immense practical utility in the treatment selection and planning follow up. We have utilized preoperative parameters through a computer based genetic adaptive neural network model to predict recurrence in such patients, which can help primary care physicians and urologists in making management recommendations. PATIENTS AND METHODS: Fourteen hundred patients who underwent radical prostatectomy at participating institutions form the subjects of this study. Demographic data such as age, race, preoperative PSA, systemic biopsy based staging and Gleason scores were used to construct a neural network model. This model simulated the functioning of a trained human mind and learned from the database. Once trained, it was used to predict the outcomes in new patients. RESULTS: The patients in this comprehensive database were representative of the average prostate cancer patients as seen in USA. Their mean age was 68.4 years, the mean PSA concentration before surgery was 11.6 ng/mL, and 67% patients had a Gleason sum of 5 to 7. The mean length of follow-up was 41.5 months. Eighty percent of the cancers were clinical stage T2 and 5% T3. In our series, 64% of patients had pathologically organ-confined cancer, 33% positive margins, and 14% had seminal vesicle invasion. Lymph node positive patients were not included in this series. Progression as judged by serum PSA was noted in 30.6%. With entry of a few routinely used parameters, the model could correctly predict recurrence in 76% of the patients in the validation set. The area under the curve was 0.831. The sensitivity was 85%, the specificity 74%, the positive predictive value 77%, and the negative predictive value of 83%. CONCLUSION: It was possible to predict PSA recurrence with a high accuracy (76%). Physicians desiring objective treatment counseling can use this model, and significant cost savings are anticipated because of appropriate treatment selection and patient-specific follow-up protocols. This technology can be extended to other treatments such as watchful waiting, external-beam radiation, and brachytherapy.

Aged↗
PubMed1999

A feasibility study of gene gun mediated immunotherapy for renal cell carcinoma.

PURPOSE: Gene modified autologous tumor cell vaccines have demonstrated a protective and therapeutic effect in murine tumor model systems. The majority of trials to date have used viral methods of gene transfer for vaccine construction. An alternative approach to transfer genes into tumor cells is to use the gene gun, which is a physical method of gene transfection that produces high levels of gene expression without viral agents. We establish the feasibility of generating cytokine secreting autologous renal tumor cell vaccines for use in gene therapy for metastatic renal cell carcinoma. MATERIALS AND METHODS: We obtained 1 cm3 tumor tissue from 12 patients undergoing resection of primary or metastatic renal cell carcinoma. The tumor was disaggregated and placed in culture. The phenotype of the primary renal cell lines was established by microscopy and immunohistochemistry. The 1x10(7) lethally irradiated tumor cells were transfected with plasmid deoxyribonucleic acid containing the human (h) granulocyte-macrophage colony-stimulating factor (GM-CSF) gene under control of a cytomegalovirus promoter using the gene gun. The hGM-CSF production was assayed by enzyme-linked immunosorbent assay in the cell culture media 24 hours after transfection. RESULTS: Of 12 tumor samples 8 grew rapidly to produce a mean of 1.8x10(8) cells after 4 to 5 passages in culture, which was sufficient to produce between 24 and 32 vaccines. Immunocytochemistry confirmed that all cultures were almost exclusively renal tumor cells. Gene gun mediated transfection of lethally irradiated tumor cells resulted in high levels of hGM-CSF production (mean 330 ng./10(6) cells per 24 hours). CONCLUSIONS: We have demonstrated the feasibility of producing cytokine secreting tumor cell vaccines from primary and metastatic human renal tumors, and plan to use this approach in phase I clinical trials of gene therapy for metastatic renal cell carcinoma.

Biolistics↗
PubMed1997

Evaluation and management of parastomal hernia in association with continent urinary diversion.

PURPOSE: We discuss the incidence and diagnosis of parastomal hernias in association with continent urinary reservoirs. We also present a surgical technique appropriate for correction of this complication. MATERIALS AND METHODS: We evaluated 21 patients with parastomal hernia after construction of a continent urinary reservoir. The hernia developed secondary to diversion with an ileocecal segment in 19 patients and a Kock procedure in 2. Subsequent to development of the parastomal hernia 13 patients (61.9%) had simultaneous urinary incontinence, 2 (9.5%) had difficulty catheterizing the reservoir and 4 (19.047%) had associated pain over the stomal area. Evaluation was primarily by physical examination. However, 2 patients (9.5%) required abdominal computerized tomography to confirm the diagnosis of parastomal hernia. Surgical repair was recommended for all patients, and 19 underwent repair with or without revision of the anti-incontinence segment. Reconstruction included transabdominal takedown of the anti-incontinence segment from the abdominal wall with parastomal hernia closure through a midline incision, external reinforcement of the hernia opening with Marlex mesh when the diameter exceeded 6 cm., revision of the anti-incontinence mechanism when simultaneous urinary incontinence existed preoperatively and repositioning of the stoma site through a new selected area in the abdominal wall. RESULTS: The success rate (mean followup 23.4 months) with this surgical approach was 89.5%. Incontinence due to failure of the anti-incontinence mechanism was successfully corrected in 13 patients (100%). CONCLUSIONS: Long-term followup of continent urinary reservoirs is often associated with development of parastomal hernia. This complication can be associated with urinary incontinence, peristomal pain and difficult catheterization. Evaluation is primarily by physical examination but selected clinical situations require abdominal computerized tomography to confirm the diagnosis. The surgical technique following the steps described has been associated with minimal morbidity and has provided excellent surgical results (89.5% success rate).

Adult↗
PubMed1997

Prostate cancer.

Prostate cancer is the most common cancer in American men and the second leading cause of death in men aged 65 years or older. This article reviews the epidemiology and the principles of screening and management of prostate cancer.

Aged↗
PubMed1996

Alpha-V/beta-3 and alpha-V/beta-5 integrin distribution in neoplastic kidney.

Integrins are transmembrane glycoproteins that mediate cell-cell and cell-matrix interactions. Altered integrin expression may contribute to tumor progression, invasiveness and metastases. The alpha-V/beta-3 (alpha v beta 3; osteopontin/ vitronectin receptor) has recently been implicated in neovascularization and tumor-induced angiogenesis. alpha v-Subunit also associates with beta 5 to form an alpha v beta 5-complex, another vitronectin receptor. We studied tissue distribution of alpha v beta 3-and alpha v beta 5-integrins, as well as alpha 1- and beta 1-subunits in nephrectomy samples from 7 subjects with localized renal cell carcinoma. Grossly and histologically uninvolved regions ('normal') from the same nephrectomy specimens were used for comparison. Integrin expression was studied with specific monoclonal antibodies and the immunoperoxidase technique. alpha v beta 3 was expressed in the glomerular epithelial cells, Bowman's capsule, vascular endothelium, and weakly in tubular epithelial cells. alpha v beta 5 had a similar distribution except for minimal expression on vascular endothelium. alpha 1-Expression was observed in mesangium and but weakly in Bowman's capsule. beta 1-Expression was seen in glomerular epithelial cells, Bowman's capsule, vascular epithelium and tubular epithelial cells. Unlike in 'normals', neoplastic expression was more heterogeneous alpha v beta 3 was expressed in tumor cells in 4/7 cases, vascular endothelium in 6/6, and in stroma in 4/7. alpha v beta 5 was weakly expressed in tumor cells in 4/5, vascular endothelium in 5/5, and stroma in 4/5 cases. alpha 1-Expression was seen in tumor cells in 3/7, vascular endothelium in 4/7 and in stroma in 7/7 cases. beta 1-Expression was seen in tumor cells in 7/7 cases, vascular endothelium in 7/7, and in stroma in 4/7 cases. This study delineates the pattern of expression of the alpha v beta 3-and alpha v beta 5-integrins in 'normal' and neoplastic human kidney. Variations in alpha v beta 3-and alpha v beta 5-integrin expression may play a role in normal and neoplastic processes of the kidney.

Adult↗
PubMed1995

Quality-of-Life Issues Associated With the Treatment of Prostate Cancer.

The incidence of prostate cancer in the United States has dramatically increased over the last several years. As a result of prostate-specific antigen testing, many more men have localized, asymptomatic prostate cancer at the time of initial diagnosis. Treatment options for patients with prostate-confined adenocarcinoma of the prostate include observation, radical prostatectomy, external beam radiotherapy, radioactive prostate implantation, hormonal therapy, cryotherapy, and various combinations of the above modalities. Quality of life can be affected by the tumor and by any of the hormonal, surgical, or radiotherapeutic interventions. These treatments raise complex and multidimensional issues. Although quality-of-life issues are becoming integral and important components of clinical research in prostate cancer, many challenges in research and practice remain.

Journal Article↗
PubMed1995

A trans-reservoir technique for correction of ureterointestinal obstruction in continent urinary diversion.

Following construction of a continent colonic urinary reservoir, 5 uretero-colonic reimplantations became obstructed at the anastomotic site. In these obstructed units previous percutaneous balloon dilation and stent placement had failed and they were subsequently treated by a new reimplantation procedure. Preoperatively, in all ureteral units a percutaneous ureteral stent was inserted to facilitate intraoperative recognition of the ureteral meatus. The technique included a trans-reservoir approach, which allowed easy localization of the stent and anastomotic site. The ureter was dissected free from the intestinal wall and then was mobilized into the lumen of the reservoir. After excision of the scarred distal ureteral segment and spatulation of the proximal healthy ureter, a new direct mucosa-to-mucosa reimplantation was performed leaving the ureter stented. This trans-reservoir approach (occasionally done through an abdominal transverse muscle splitting incision) allows for shortening of the operation, and avoids the time-consuming and more complicated transabdominal lysis of adhesions. All newly reimplanted ureters (100%) showed evidence of adequate ureteral drainage without residual obstruction on followup excretory urography or furosemide renography up to 45 months postoperatively. The trans-reservoir approach for refractory ureteral reimplantation obstruction in continent colonic reservoirs has been associated with no morbidity or mortality, and facilitates the solution to a difficult clinical problem.

Adult↗
PubMed1993

Direct (nontunneled) ureterocolonic reimplantation in association with continent reservoirs.

A total of 190 patients underwent continent urinary diversion using the Florida pouch. Direct mucosa-to-mucosa ureterocolonic reimplantation was used in 165 patients (326 ureters). Of the first 30 ureters in patients who underwent antireflux tunneled reimplantation obstruction occurred in 4 (13.3%). Obstruction developed directly in 16 of the ureters reimplanted (4.9%), and 3 of the 6 plicated and reimplanted megaureters (50%). Among the obstructed units 3 (13%) were treated unexpectedly by autonephrectomy, while the other 20 units (87%) were treated with percutaneous balloon dilation and internal stenting for 6 to 8 weeks. In the latter group 12 units (60%) recovered function, 3 (15%) had pyelonephritis requiring nephrectomy and 5 (25%) stabilized following a new reimplantation. Reflux was demonstrated in 23 units (7%). All units with reflux are being followed conservatively and renal deterioration has not been demonstrated. The incidence of ureteral obstruction with direct reimplantation is lower compared to a tunneled technique. This reimplantation procedure is technically simpler than others and is safe in adults when performed in association with a large volume, continent colonic reservoir.

Colon↗
PubMed1987

Prostatic cancer in patients 80 years of age.

Thirty patients with adenocarcinoma of the prostate, Grade III-V, Stage IV, 80 years of age or more have been studied. Survival rate at 12 months was 19/30 (63.3%). Survival rate at 3 years was 18/30 (60%). The results of this study show that in spite of being a selected group of patients with high grade, high stage tumors, the survival rate at three years was even better when compared to a heterogeneous group of patients ten years younger (57.75%).

Adenocarcinoma↗
PubMed1985

Testicular yolk sac carcinoma in infants: natural history in 56 consecutive patients.

Fifty six patients with yolk sac tumor are registered in the "Instituto Nacional de Enfermedades Neoplásicas" (Lima-Peru), from 1952-1980: 48.22% were less than 2 years of age; 51.78% were beyond that age.- Seventeen patients survived 3 years post diagnosis: 44% when patients less than 2 years of age and 17.2% when over two years of age. 25.9% of the patients less than 2 years of age were found to have metastases whereas 48.5% when over 2 years of age. 21/56 already had metastases when first seen. All tumors were greater than or equal to 3 cm. in diameter when first seen. Metastases were found in 38% of cases when tumors were less than or equal to 6 cm., compared to 61.9% of cases in which tumors exceeded 6 cm. 51.8% of clinical stage I survived 3 years without evidence of disease; 14.3% when stage II while none survived at clinical stage IV. It is to be expected that young patients who survive 3 years after diagnosis and treatment will not suffer a recurrence of the disease.

Adolescent↗
PubMed1984

Biocarbon device for cutaneous ureterostomy.

The surgical technique for a new alternative to urinary diversion is described. The biocarbon conduit is an inert device implanted in the abdominal wall. Its inner end is anastomosed to the distal ureter, and the outlet is over the abdominal skin and connected to a collector tube into a urinary bag. Twenty implants were performed between March, 1980, and July, 1981. Seventeen patients had carcinoma of the uterine cervix, and 3 had carcinoma of the urinary bladder (age range 34 to 79 years). All had severe urinary tract infection, retrodilation, and were in poor general physical condition. Eight fistulas developed in the 20 implants.

Abdomen↗
PubMed1984

Cobalt therapy prophylaxis of recurrence of T1 bladder cancer.

Eighteen patients with T1 transitional cell carcinoma of the urinary bladder were submitted to transurethral resection of the tumor, followed by Cobalt therapy (5,500 rads to the pelvis and 6,500 rads to the bladder in six weeks). The recurrence rate at three years follow-up was 33% (6/18). Recurrence of transitional cell carcinoma of the urinary bladder is a well known condition in stage O and A, even when low grade is present. Recurrence rates at one year as high as 84% (Loening et al., 1983) are reported in the current literature. In recent years many studies have been performed which were oriented to the use of intravesical chemotherapy in order to reduce the recurrence rate (Adolphs and Bastian, 1983; Huland, 1983; Loening et al., 1983; National Bladder Cancer Collaborative Group A, 1977; Rodriguez and Caserta, 1983; Zincke et al., 1983) of this tumor. We started a protocol on treatment of the transitional cell carcinoma of the urinary bladder in 1963. The protocol calls for transurethral resection of the tumor followed by Cobalt therapy. This is an interim report on stage T1 (stage A) with such a treatment.

Adult↗
PubMed1982

Wilms' tumor: histologic grading as a prognostic factor in tumors beyond 10cm in diameter.

The progressive proportion of 25-50 and 75% of undifferentiated cells in the Wilms' tumor mass generate three grading categories: well differentiated (WD); the moderate differentiated (MD) and the poorly differentiated (PD). The Urology Department of the Instituto Nacional de Enfermedades Neoplásicas (Lima, Peru) has studied 60 selected cases registered at its Biostatistics Department. Only 6.9% were well differentiated; 69% were of the poorly differentiated type. In 58 patients our survival rate at two years after diagnosis is higher (39.53%) when the patients are over 2 years of age; while under 2 years of age this survival rate is 26.67%. In a group of 46 patients, the survival rate at two years after initial diagnosis is 44% with a tumor size between 10-14 cm; the survival rate drops to 39.3% when the tumor size is over 15 cm in diameter. There is a linear increasing scale of survival rate for the well differentiated (25%), moderate differentiated (27.3%) and for the patients bearing poorly differentiated types of tumors (48.4%). Further studies are encouraged in order to learn the reasons for this correlation.

Child↗
PubMed1979

Carcinoma of the penis: analysis of 192 consecutive cases at the Instituto Nacional de Enfermedades Neoplasicas.

Between 1952 and 1976 192 consecutive cases of penile epidermoid carcinoma were seen at the Instituto Nacional de Enfermedades Neoplascias of Lima, Peru. The mean age when the disease developed was 60.5 years, with a peak incidence between 60 and 64 years (32 patients). No correlation was observed between extensive lesions of the shaft of the penis to high pathological staging. Clinical examination of the inguino-crural nodes is not a good criterion for staging. We wait six weeks after eradication of primary lesion before lymphadenectomy. No correlation exists between grade and pathological stage. When no lymph node was positive, the overall survival rate over five years was 90.69%; when lymph nodes were metastasized there was an overall survival rate over five years of only 9.39 percent. The coefficient of cancer versus noncancer cause of death was 1.25 for pathological stage I, 3.09 for pathological stage II, 4.83 for pathological stage III, and 10.000 for pathological stage IV. Our patients did have advanced disease, as 57.14% of deaths occurred at two years and 25.21% more at five years.

Adult↗