Biomedical subjects

Thomas A Gardner

Publications and source records attributed to Thomas A Gardner.

At least 37 records · Page 2Linked to original sources

PubMed2004

Transitional cell carcinoma of the bladder following augmentation cystoplasty for the neuropathic bladder.

PURPOSE: Cancer following augmentation cystoplasty is a recognized risk factor. The procedure has only gained popularity in pediatric urology within the last 25 years, limiting the population being studied by statistical power and the lack of long-term followup. The majority of reported cases of post-augmentation malignancy have occurred in adults with multiple risk factors. Currently the most common indication for augmentation cystoplasty in children and adolescents is neuropathic bladder. We review 3 cases of transitional cell carcinoma (TCC) following augmentation cystoplasty in this unique population with no additional risk factors for bladder cancer. MATERIALS AND METHODS: We reviewed our clinical database of children and adolescents who underwent bladder augmentation since 1978 to evaluate the incidence of cancer. This study represents a captured population within a single institutional practice. There were 483 cases entered into the database, and particular attention was paid to 260 augmentations with at least 10 years of followup. We reviewed medical history, clinical outcomes, cancer risk factors, augmentation type and pathology of the 3 patients who presented with TCC after augmentation cystoplasty. RESULTS: Three patients presented with grade 2 to 3 TCC following bladder augmentation, all of whom underwent exploratory laparotomy and eventually died of metastatic disease. No patient had a history of smoking exposure greater than 10 packs per year or other known risk factors for bladder cancer. Two patients had an ileocecal augmentation and 1 had a cecal augmentation for neuropathic bladder. Patient age at augmentation was 8, 20 and 24 years, and age at diagnosis of TCC was 29, 37 and 44 years, respectively. Mean time from augmentation to TCC was 19 years. Assuming a 10-year lag period before the risk of cancer, in at least 1.2% of bladder augmentation cases in our database cancer has developed. CONCLUSIONS: This study supports the hypothesis that bladder augmentation appears to be an independent risk factor for TCC, with a lag time of less than 20 years. We recommend endoscopic surveillance of all patients with a history of bladder augmentation beginning 10 years after initial surgery.

Adult↗

PubMed2004

Allelic loss of the active X chromosome during bladder carcinogenesis.

CONTEXT: Previous studies have shown that loss of the X chromosome is involved in the carcinogenesis of certain human malignancies. OBJECTIVE: To determine whether X-linked allelic losses occur during bladder tumorigenesis and whether such losses involve the active or the inactive X chromosome. DESIGN: We analyzed the deletion status of the X-linked human androgen receptor gene locus in 6 female patients who underwent radical cystectomies for muscle-invasive urothelial carcinoma of the urinary bladder. Four patients had coexisting urothelial carcinoma in situ. Analysis for inactivation of the X chromosome was carried out in parallel. RESULTS: Three cases were informative. Invasive tumor samples showed loss of heterozygosity involving the active allele at the androgen receptor locus in all 3 positive cases, whereas carcinoma in situ showed nonrandom X chromosome inactivation but not allelic deletion. CONCLUSIONS: Our data suggest that allelic loss of the activated X chromosome is involved in bladder carcinogenesis and cancer progression.

Carcinoma↗

PubMed2003

Anatomic distribution of periprostatic adipose tissue: a mapping study of 100 radical prostatectomy specimens.

BACKGROUND: Because the prostatic capsule is often indistinct, recognition of extraprostatic extension by carcinoma depends heavily on the identification of carcinoma cells in the periprostatic adipose tissue. However, the distribution of adipose tissue along the prostatic surfaces has not been studied extensively. METHODS: The authors analyzed the periprostatic adipose tissue in specimens from 100 patients treated with radical retropubic prostatectomy and bilateral pelvic lymphadenectomy for prostatecarcinoma. Each specimen was totally embedded and examined by the whole mount method. The presence or absence of adipose tissue on the anterior, posterior, right, and left surfaces of the prostate was determined and analyzed. RESULTS: Periprostatic adipose tissue was present on 48% of all prostatic surfaces examined. The distribution of periprostatic adipose tissue varied among the different surfaces of the prostate, with the anterior, posterior, right, and left surfaces showing 44%, 36%, 59%, and 57% adipose tissue, respectively. The amount of periprostatic adipose tissue was similar among specimens from operations performed by different surgeons (P = 0.72). However, nerve-sparing procedures resulted in less adipose tissue (46%) than non-nerve-sparing procedures (54%) (P = 0.01). CONCLUSIONS: Less than half of the prostatic surfaces examined were covered by adipose tissue. The absence of adipose tissue over large areas of the prostatic surface, especially the posterior surface, makes the evaluation of extraprostatic extension difficult and unreliable. Further refinement of the prostate carcinoma staging system is needed.

Adipose Tissue↗

PubMed2003

Phase I dose escalation clinical trial of adenovirus vector carrying osteocalcin promoter-driven herpes simplex virus thymidine kinase in localized and metastatic hormone-refractory prostate cancer.

Osteocalcin (OC), a major noncollagenous bone matrix protein, is expressed prevalently in prostate cancer epithelial cells, adjacent fibromuscular stromal cells, and osteoblasts in locally recurrent prostate cancer and prostate cancer bone metastasis [Matsubara, S., Wada, Y., Gardner, T.A., Egawa, M., Park, M.S., Hsieh, C.L., Zhau, H.E., Kao, C., Kamidono, S., Gillenwater, J.Y., and Chung, L.W. (2001). Cancer Res. 61, 6012-6019]. We constructed an adenovirus vector carrying osteocalcin promoter-driven herpes simplex virus thymidine kinase (Ad-OC-hsv-TK) to cotarget prostate cancer cells and their surrounding stromal cells. A phase I dose escalation clinical trial of the intralesional administration of Ad-OC-hsv-TK followed by oral valacyclovir was conducted at the University of Virginia (Charlottesville, VA) in 11 men with localized recurrent and metastatic hormone-refractory prostate cancer (2 local recurrent, 5 osseous metastasis, and 4 lymph node metastasis) in order to determine the usefulness of this vector for the palliation of androgen-independent prostate cancer metastasis. This is the first clinical trial in which therapeutic adenoviruses are injected directly into prostate cancer lymph node and bone metastasis. Results show that (1). all patients tolerated this therapy with no serious adverse events; (2). local cell death was observed in treated lesions in seven patients (63.6%) as assessed by TUNEL assay, and histomorphological change (mediation of fibrosis) was detected in all posttreated specimens; (3). one patient showed stabilization of the treated lesion for 317 days with no alternative therapy. Of the two patients who complained of tumor-associated symptoms before the treatment, one patient with bone pain had resolution of pain, although significant remission of treated lesions was not observed by image examination; (4). CD8-positive T cells were predominant compared with CD4-positive T cells, B cells (L26 positive), and natural killer cells (CD56 positive) in posttreated tissue specimens; (5). levels of HSV TK gene transduction correlated well with coxsackie-adenovirus receptor expression but less well with the titers of adenovirus injected; and (6). intrinsic OC expression and the efficiency of HSV TK gene transduction affected the levels of HSV TK protein expression in clinical specimens. Our data suggest that this form of gene therapy requires further development for the treatment of androgen-independent prostate cancer metastasis although histopathological and immunohistochemical evidence of apoptosis was observed in the specimens treated. Further studies including the development of viral delivery will enhance the efficacy of Ad-OC-hsv-TK.

Adenoviridae↗

PubMed2003

High-level expression of EphA2 receptor tyrosine kinase in prostatic intraepithelial neoplasia.

EphA2 is a transmembrane receptor tyrosine kinase that is overexpressed in many carcinomas. Specific targeting of EphA2 with monoclonal antibodies is sufficient to inhibit the growth, migration and invasiveness of aggressive cancers in animal models. Using immunohistochemical analyses, we measured the expression of EphA2 in prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia, and adjacent benign prostate tissue from ninety-three radical prostatectomy specimens. These results were related to multiple clinical and pathologicalcharacteristics. The fraction of cells staining positively with EphA2 in benign prostatic epithelium (mean, 12%) was significantly lower than that in high-grade prostatic intraepithelial neoplasia (mean, 67%, P < 0.001) and prostatic adenocarcinoma (mean, 85%, P < 0.001). Moreover, the intensity of EphA2 immunoreactivity in prostatic adenocarcinoma was significantly higher than in benign prostatic tissue (P < 0.001) or high-grade prostatic intraepithelial neoplasia (P < 0.001). Benign prostatic epithelium showed weak or no immunoreactivity for EphA2 in all cases examined. Whereas EphA2 immunoreactivity related to neoplastic transformation, it did not correlate with other clinical and pathological parameters examined. Our data suggest that EphA2 levels increase as prostatic epithelial cells progress toward a more aggressive phenotype. Progressively higher levels of EphA2 in high-grade prostatic intraepithelial neoplasia and prostatic carcinoma are consistent with recent evidence that EphA2 functions as a powerful oncogene. Moreover, the presence of high levels of EphA2 in these cells suggests opportunities for prostate cancer prevention and treatment.

Adenocarcinoma↗

PubMed2003

Laparoscopic partial kidney ablation with high intensity focused ultrasound.

PURPOSE: High intensity focused ultrasound has been performed for transrectal and extracorporeal thermal ablation of tissues. We developed and tested a laparoscopic probe that allows real-time ultrasound imaging during partial renal ablation using high intensity focused ultrasound. METHODS: A Sonablate 200 (Focus Surgery, Indianapolis, Indiana) high intensity focused ultrasound system with a modified 18 mm. laparoscopic probe was used in all experiments. In 13 Yucatan mini-pigs a 5Fr ureteral catheter was inserted into the renal pelvis and 10 cc air were instilled into the collecting system. The kidney was laparoscopically dissected, the high intensity focused ultrasound probe was inserted through a 33 mm. laparoscopic port and the targeted renal pole was treated. RESULTS: Renal lesions were created in 12 of 13 treated kidneys under real-time ultrasound visualization. Median operative time was 180 minutes, average high intensity focused ultrasound activation time was 18.3 minutes and lesion size was 23 x 17 x 11 mm. At 4 and 14 days 4 (acute group) and 6 (subacute group) animals were available for renal functional and anatomical evaluation, respectively. No difference in renal function was seen in treated and untreated kidneys. Pathological examination at 14 days revealed homogenous and complete tissue necrosis throughout the whole volume of the lesion with sharp demarcation from adjacent normal tissue. CONCLUSIONS: We were able to refine a probe for laparoscopic high intensity focused ultrasound delivery capable of simultaneous ultrasound imaging. Partial renal ablation using this probe is feasible and safe, and resulted in homogenous, complete and reproducible lesions.

Animals↗

PubMed2003

New targets for therapy in prostate cancer: modulation of stromal-epithelial interactions.

Changes in genomic and phenotypic expression of progressing prostate tumors and their stroma occur in a dynamic fashion based on bidirectional signaling from stromal-epithelial interactions. These interactions may underlie the ability of prostate cancer cells to survive and proliferate in the prostate and bone. By investigating the phenotypic and genotypic changes of stromal cells adjacent to cancer cells and the reciprocal changes of cancer cells, novel molecular markers may be developed to diagnose cancer earlier before pathologic appearance of cancer cells at the primary site. Attacking epithelial and stromal elements together is a unique approach to both localized and metastatic prostate cancer therapy. Co-targeting both tumor cells and stroma requires identifying a reliable tumor and tissue-specific cis-DNA element, such as osteocalcin (OC) promoter. OC expression is elevated in prostate tumor cells and in prostate and bone stromal cells interdigitating with both localized and metastatic prostate epithelium. We have previously designed an adenovirus-based therapeutic gene vehicle and demonstrated that a replication-competent adenoviral vector (Ad vector) is highly efficient in blocking the growth of cancer cells in culture, including cells without androgen receptor as well as cells that do or do not make prostate-specific antigen. In vivo, intravenous administration of an Ad-OC vector was effective against preexisting human prostate cancer subcutaneous and bone xenografts. The addition of vitamin D(3) enhanced further viral replication at target sites. Co-targeting tumor cells and stroma using systemic Ad vector is a viable and promising option for treatment of both localized and metastatic prostate cancer.

Adenocarcinoma↗

PubMed2002

Fas and Fas ligand expression is elevated in prostatic intraepithelial neoplasia and prostatic adenocarcinoma.

BACKGROUND: Fas is a Type I membrane receptor of the tumor necrosis factor/nerve growth factor family. On binding to Fas ligand, a Type II transmembrane protein, the Fas/Fas ligand complex, induces apoptosis in target cells. Dysregulation of Fas and Fas ligand expression has been found in some malignant neoplasms. METHODS: Using immunohistochemical analysis, the authors studied the expression of Fas and Fas ligand in prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia (PIN), and adjacent benign prostate tissue from 95 radical prostatectomy specimens. RESULTS: The percentage of cells that stained positively with Fas in benign prostate tissue (mean, 2%) was statistically significantly lower compared with that in prostatic intraepithelial neoplasia (mean, 13%; P = 0.0014) and prostatic adenocarcinoma (mean, 31%; P = 0.0001). The staining intensity of Fas was significantly less in benign prostate tissue compared with the staining intensity in PIN and prostatic adenocarcinoma. The percentage of cells that stained positively with Fas ligand in benign prostate tissue (mean, 13%) was statistically significantly lower compared with that in PIN (mean, 47%; P = 0.0001) and in prostatic adenocarcinoma (mean, 53%; P = 0.0001). The staining intensity of Fas ligand was significantly less in benign prostate tissue compared with that in PIN and prostatic adenocarcinoma. CONCLUSIONS: Data from the current study indicate that Fas/Fas ligand is elevated in prostatic malignancy, suggesting that Fas-mediated apoptosis may be a potential target for therapeutic intervention.

Adenocarcinoma↗

PubMed2002

Relative promoter strengths in four human prostate cancer cell lines evaluated by particle bombardment-mediated gene transfer.

BACKGROUND: The particle bombardment (gene gun) method for gene transfer provides a new and efficient means for transfection of various cell types in culture. In this study we evaluate its application to human prostate tumor cells. METHODS: Transient expression of the firefly luciferase gene driven by five viral and five cellular promoters was assessed after in vitro gene transfer using the gene gun method. The relative strengths of these promoters were quantitatively determined in four different human prostate tumor cell lines: DU145, PC-3, LNCaP, and CWR22Rv1 cells. In situ histochemical staining of cells, transfected with bacterial beta-galactosidase cDNA as a reporter gene, was also performed to evaluate the transfection efficiency. Time course of gene expression was determined using the luciferase reporter gene. RESULTS: The peak levels of transient expression of firefly luciferase are observed within 24 hr after gene transfer. Sustained but reduced luciferase levels were also detected as long as 5 days post transfection. Up to 35% of bombarded cells in vitro were found to express transgenic beta-galactosidase activity. Among tested viral promoters, cytomegalovirus early enhancer/promoter activity was observed to confer consistently the highest activity in each test cell line, whereas phosphoglycerate kinase gene promoter possessed the highest activity among the cellular promoters tested. CONCLUSIONS: The particle bombardment gene-transfer technology can be effectively employed as an efficient method for in vitro gene-transfer into prostate tumor cells. The characterization of relative promoter strength and preference may be useful for future studies of cancer gene therapy approaches.

Biolistics↗

PubMed2002

Novel prostate-specific promoter derived from PSA and PSMA enhancers.

The expression of prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA), two well characterized marker proteins, remains highly active in the hormone refractory stage of prostate cancer. In this study, an artificial chimeric enhancer (PSES) composed of two modified regulatory elements controlling the expression of PSA and PSMA genes was tested for its promoter activity and tissue specificity using the reporter system. As a result, this novel PSES promoter remained silent in PSA- and PSMA-negative prostate and non-prostate cancer cell lines, but mediated high levels of luciferase in PSA- and PSMA-expressing prostate cancer cell lines in the presence and absence of androgen. To determine whether PSES could be used for in vivo gene therapy of prostate cancer, a recombinant adenovirus, Ad-PSES-luc, was constructed. Luciferase activity in prostate cancer cell lines mediated by Ad-PSES-luc was 400- to 1000-fold higher than in several other non-prostate cell lines, suggesting the high tissue-specificity of the PSES promoter in an adenoviral vector. Finally, recombinant virus Ad-PSES-luc was injected into mice to evaluate the tissue-discriminatory promoter activity in an experimental animal. Unlike Ad-CMV-luc, the luciferase activity from systemic injection of Ad-PSES-luc was fairly low in all major organs. However, when injected into prostate, Ad-PSES-luc drove high luciferase activity almost exclusively in prostate and not in other tissues. Our results demonstrated the potential use of PSES for the treatment of androgen-independent prostate cancer patients.

Adenoviridae↗

PubMed2002

Major complications in 213 laparoscopic nephrectomy cases: the Indianapolis experience.

PURPOSE: We assessed the incidence of and analyzed factors that may help prevent major complications and open conversion during laparoscopic nephrectomy at our institutions. MATERIALS AND METHODS: We retrospectively analyzed all laparoscopic nephrectomies performed between August 1, 1999 and July 31, 2001. Data were stratified for nephrectomy type, intraoperative and postoperative complications. Conversion to open surgery was stratified for emergency versus elective procedures. RESULTS: Of the 292 laparoscopic procedures performed at our institutions in 2 years 213 (73%) involved laparoscopic nephrectomy, including 84 live donor nephrectomies, 61 radical nephrectomies, 55 simple nephrectomies and 13 nephroureterectomies. A total of 16 major complications (7.5%) occurred, including access related, intraoperative and postoperative complications in 3, 9 and 4 cases, respectively. The conversion rate was 6.1% (13 patients), the transfusion rate was 1.9% and the mortality rate was 0.5% (1 death). Only 1 complication was related to simple laparoscopic nephrectomy, although this group showed the highest rate of elective conversion (7 of 8 elective conversions). Laparoscopic live donor nephrectomy showed the highest rate for emergency conversion (3 of 5 emergency conversions). CONCLUSIONS: Our results reinforce the importance of thorough preoperative imaging, careful patient selection, surgeon experience and skill maintenance in laparoscopy as well as a low threshold for conversion to open surgery. This series provides additional evidence to support the evolution of laparoscopic nephrectomy into a standard of care.

Adult↗

PubMed2002

Manual specimen retrieval without a pneumoperitoneum preserving device for laparoscopic live donor nephrectomy.

PURPOSE: We present a novel method of kidney retrieval based on a modified Pfannenstiel incision and insertion of the assistant hand into the abdominal cavity without a device for pneumoperitoneum preservation. This maneuver is performed as the last step in pure laparoscopic live donor nephrectomy. Also, we assessed the effect of this technique on warm ischemia time compared with the standard laparoscopic bag retrieval technique. MATERIALS AND METHODS: A total of 70 laparoscopic live donor nephrectomies were performed at our institutions between October 1998 and March 2001. The first 43 cases were completed using an EndoCatch bag device (Auto Suture, Norwalk, Connecticut) for specimen retrieval, while the last 27 were done using a novel manual retrieval technique through a modified Pfannenstiel incision. We retrospectively analyzed the results in regard to warm ischemia time and intraoperative complications related to the procedure. RESULTS: A statistically significant difference was noted in the EndoCatch and manual retrieval groups in regard to warm ischemia time (p <0.001). There were 2 complications related to the EndoCatch device and none related to the manual technique. No differences were detected regarding recipient outcomes. CONCLUSIONS: Manual specimen retrieval after live donor nephrectomy allows shorter warm ischemia time, while saving the cost of an EndoCatch bag or pneumoperitoneum preserving device that would be used during hand assisted live donor nephrectomy. It was shown to be a safe method without increased donor morbidity.

Humans↗

PubMed2002

Transrectal high-intensity focused ultrasound for treatment of patients with stage T1b-2n0m0 localized prostate cancer: a preliminary report.

OBJECTIVES: To present our preliminary clinical results of transrectal high-intensity focused ultrasound (HIFU) in Stage T1b-2N0M0 prostate cancer. Efforts are being made to provide minimally invasive alternative treatment options with equal efficacy and fewer side effects. HIFU delivers ultrasound energy with rapid thermal necrosis of tissue in the focal region without damaging the surrounding tissue. METHODS: We performed 28 HIFU treatments in 20 patients with biopsy-proven localized prostate cancer using a modified Sonablate-200 HIFU device. All patient characteristics and the clinical outcome of 20 patients followed up more than 6 months (mean 13.5) were analyzed. RESULTS: A complete response was obtained in 100% (20 of 20) of patients, as evidenced by a negative postoperative prostate biopsy and no elevation on three successive prostate-specific antigen (PSA) determinations. Of the 20 patients, 13 (65%), 5 (25%), and 2 (10%) had PSA nadirs of less than 0.50 ng/mL, 0.50 to 1.00 ng/mL, and 1.01 to 2.00 ng/mL, respectively. Rectourethral fistula and urethral stricture were noted in 1 and 2 patients, respectively, and 1 patient underwent transurethral resection of the prostate because of prolonged urinary retention. CONCLUSIONS: Our results show that HIFU can be performed without an incision, with a less severe side effect profile, and, unlike most other prostate treatments, is repeatable. Transrectal HIFU may be a useful option for patients with localized prostate cancer. Its long-term efficacy will be determined by additional follow-up and a Phase II trial.

Aged↗

PubMed2002

One versus two proficient laparoscopic surgeons for laparoscopic live donor nephrectomy.

OBJECTIVES: To compare the laparoscopic donor nephrectomy (LDN) results obtained by two different surgical teams, one consisting of a proficient laparoscopic surgeon assisted by an inexperienced laparoscopic surgeon and another consisting of two proficient laparoscopic surgeons. With more centers embarking on LDN programs, it is important to identify the factors that can improve overall outcomes during the initial learning curve. METHODS: A retrospective review was performed of the initial 70 sequential LDNs performed between October 1998 and March 2001 at our institutions. The procedures were stratified into two groups. Group 1 consisted of LDN cases performed by one proficient laparoscopic surgeon and an inexperienced laparoscopic surgeon (resident, fellow, or faculty) as the first assistant; group 2 consisted of cases performed by two proficient laparoscopic surgeons. RESULTS: Twenty-six LDNs were performed by group 1 and 44 by group 2. The total operative time and estimated blood loss showed a statistically significant decrease in group 2 compared with group 1, 143 +/- 32 minutes versus 218 +/- 38 minutes (P <0.001) and 92 +/- 115 mL versus 158 +/- 148 mL (P = 0.044), respectively. Two major complications occurred in group 1 (7.7%) and two major complications occurred in group 2 (4.5%). The 3-month postoperative recipient creatinine levels were similar for both groups, 1.6 +/- 1.3 versus 1.4 +/- 0.4 (P = 0.408). CONCLUSIONS: A surgical team composed of two proficient laparoscopic surgeons during the early learning curve of LDN may allow safe and efficient development of a laparoscopic live donor renal transplantation program.

Clinical Competence↗

PubMed2002

Prostate cancer gene therapy: past experiences and future promise.

Gene therapy has been used to target prostate cancer with excellent pre-clinical efficacy but limited clinical efficacy. The concept of delivering genetic material to prostate cancer cells to alter their phenotype and ultimately their behavior has been demonstrated in the laboratory over the last decade. Translating those pre-clinical findings into novel therapies for prostate cancer has been difficult. The stigma of gene therapy and the aggressive regulation of clinical trials involving transfer of genetic material to patients are two major impediments to clinical successes in gene therapy. This review hopes to provide a snapshot of prior gene transfer protocol findings and forecast the exciting future directions investigators are heading.

Animals↗

PubMed2002

Adenovirus-mediated suicide-gene therapy in an orthotopic murine bladder tumor model.

BACKGROUND: Patients with high-grade transitional-cell carcinoma (TCC) of the bladder frequently experience recurrence and progress and have a low response rate to chemotherapy in metastatic TCC. In this study, we evaluated the feasibility and long-term efficacy of suicide-gene therapy using adenovirus (Ad)-mediated herpes simplex virus thymidine kinase gene (HSV-TK) and prodrug ganciclovir (GCV) as a potential therapeutic approach in murine-orthotopic models of TCC. METHODS: A replication defective adenoviral vectors containing toxic HSV-TK gene under the transcriptional control of RSV (Rous sarcoma virus) promoter (Ad-RSV-TK) was used. Orthotopic bladder TCC was established with 1 x 106 murine (MBT-2) TCC cells in syngenic C3H/He female mice. Intratumoral injection of Ad-RSV-TK in combination with GCV (20 mg/kg body weight/day i.p. b.i.d. x 7 days) was administered in vivo for the determination of treatment efficacy and long-term host survival in separate controlled experiments. RESULTS: In vivo experiments demonstrated greater than three-fold reductions in MBT-2 tumor growth for the animals treated with Ad-RSV-TK (5 x 108 plaque forming units (pfu)/GCV therapy (P < 0.01)). Central tumor necrosis and apoptosis were revealed by histomorphology and immunohistochemistry compared with other control animals (non-treated, GCV alone, Ad-RSV-TK alone). Direct intratumoral injection with Ad-RSV-TK/GCV also resulted in significantly improved survival over the control groups in separated experiment (log-rank test, P < 0.05). CONCLUSIONS: Suicide-gene therapy using Ad-RSV-TK/GCV provides an effective therapy in an experimental murine orthotopic bladder cancer by significantly inhibiting tumor growth and improving long-term host survival.

Adenoviridae↗

PubMed2002

Transperitoneal laparoscopic renal surgery using blunt 12-mm trocar without fascial closure.

BACKGROUND AND PURPOSE: Conical blunt trocar insertion may eliminate the need for fascial closure (FC) in transperitoneal laparoscopic renal surgery. This concept applies to 12-mm blunt trocar placement through muscular parts of the abdominal wall, relying on muscle splitting and eventual muscle retraction when the trocar is removed. We retrospectively assessed the safety of fascial nonclosure (FNC) after 12-mm blunt port insertion. PATIENTS AND METHODS: Ninety transperitoneal laparoscopic renal procedures were performed between August 1999 and May 2000. Four ports (two 12 mm and two 5 mm) were usually used except for 30 donor nephrectomies, where an additional 5-mm port was used. The 12-mm trocars were inserted at the lateral border of the rectus muscle 5 cm below the costal margin and in the anterior axillary line 8 cm below the costal margin. Fascial closure was performed in 62 patients and nonclosure in 28 patients. Exclusion criteria for FNC included midline location, malnutrition, renal failure, and chronic use of steroids. Postoperative outcomes were compared in 20 patients with FNC matched with 20 patients with FC. RESULTS: At an average of 4.8 months of follow-up, none of the patients developed a trocar site hernia. No significant statistical differences were observed between the groups with regard to intraoperative and postoperative data. CONCLUSIONS: These two approaches appear to be equivalent in terms of patient morbidity and postoperative hospital stay. Fascial nonclosure after transperitoneal 12-mm blunt trocar insertion, through muscular parts of the abdominal wall may be safe and efficacious and eliminates the last step in transperitoneal laparoscopic renal surgery.

Adult↗

PubMedDate not supplied

Current status of anti-angiogenesis therapy for prostate cancer.

Prostate cancer is the second leading cause of cancer mortality in American men and the single most diagnosed cancer in men. Despite advances in early detection and conventional treatment strategies, prostate cancer progresses and becomes resistant to treatment. Because tumor growth and establishment of metastases are dependent on angiogenesis, interest in the development of anti-angiogenesis therapies has grown. Preclinical studies and early clinical evaluation show promise in the adjunctive use of anti-angiogenesis to overcome the limitations of current therapeutic approaches. In this review, we outline the basic science principles of angiogenesis and their application in the development of anticancer therapies.

Angiogenesis Inhibitors↗