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P Guinan

Publications and source records attributed to P Guinan.

At least 19 recordsLinked to original sources
PubMed2000

Changes in radical prostatectomy and radiation therapy rates for African Americans and whites.

There are racial differences in prostate cancer outcomes. One variable influencing end results is treatment for cure: either radical prostatectomy (RP) or radiation therapy (RT). The purpose of this report is to determine changes in diagnosis rates of localized prostate cancer between the years before prostate-specific antigen (PSA) use (1973-1988) and the years after PSA use (1989-1996), to evaluate differences in RP and RT rates between the pre-PSA and post-PSA eras, to assess differences in RP and RT rates between African Americans and whites between these intervals. The Surveillance, Epidemiology, and End Results (SEER) data were used and evaluated. Both African Americans and whites had statistically increased rates of localized prostate cancer diagnosed (70.4 and 49.0 in 1973 through 1988 and 123.1 and 84.9 in 1989 through 1996, respectively [p < 0.05]). The differences between the pre-PSA and post-PSA eras for African Americans and whites for RP (3.6 vs. 44.3 and 5.0 vs. 44.9, respectively) and RT (23.6 vs. 61.6 and 17.0 vs. 38.1, respectively) were all significant (p < 0.05). Both African Americans and whites had increased rates of RP from 3.6 and 5.0 to 44.3 and 44.9, respectively, and RT from 23.6 and 17.0 to 61.6 and 38.1 during the pre- and post-PSA years.

Black or African American↗
PubMed1998

An evaluation of the markers p53 and Ki-67 for their predictive value in prostate cancer.

BACKGROUND AND OBJECTIVES: p53 and Ki-67 are but two markers being evaluated for their predictive value in prostate cancer. The purpose of this study was to compare p53 and Ki-67 with age, stage, Gleason score, and ploidy for their prognostic abilities in prostate cancer. METHODS: Prostate cancer specimens from 134 patients were immunohistochemically stained for p53 and Ki-67 expression and differences evaluated by SPSS analysis of variance (ANOVA) methods. The dependent variable was patient survival and the independent variables were age, stage, Gleason score, and ploidy. RESULTS: In decreasing order of prediction of survival were stage (P < 0.001), Gleason score (P < 0.001), age (P = 0.1869), Ki-67 (P = 0.2284), p53 (P = 0.4282) and ploidy (P = 0.8141). CONCLUSION: It is concluded that stage and Gleason score are significant predictors of survival while p53, Ki-67, age and ploidy are not.

Aged↗
PubMed1998

Growth factor deprivation therapy of hormone insensitive prostate and breast cancers utilizing antisense oligonucleotides.

Antisense oligonucleotides (oligos) are artificial sequences of nucleotide bases which may be synthesized complementary to known regions within specific mRNAs. When these constructed oligos interact with protein encoding mRNA they may regulate expression of various growth factors and/or their receptors. Oligos directed against transforming growth factor-alpha (TGF-alpha) and its binding site, the epidermal growth factor receptor (EGFR), were employed: A) in vitro to affect the growth of hormone insensitive human derived PC-3 prostate cancer cells as well as the human derived UACC-893 breast cancer cell line; and B) in vivo to treat tumors established by these cell lines in athymic nude mice. The in vitro results for each oligo, and their combination, produced significant inhibition of both prostate and breast cell lines. In addition, the combination of oligos most efficiently diminished the immunohistochemical expression of both TGF-alpha and EGFR in PC-3 cells. Direct in vivo inoculation of oligos into established PC-3 or UACC-893 tumors in nude mice produced hemorrhagic necrosis within 2-3 days. Such therapy could represent a new tier of therapy for recurrent, hormone insensitive, tumors based upon the concept of growth factor deprivation.

Animals↗
PubMed1998

Paclitaxel, bropirimine and linomide: effect on growth inhibition in a murine prostate cancer model by different growth regulatory mechanisms.

Paclitaxel, bropirimine and linomide therapy was evaluated in a murine prostate cancer model. All drugs were effective in impeding tumor growth but the mechanisms of action varied. Paclitaxel inhibited bcl-2 expression suggesting an apoptotic mechanism. Bropirimine, while inhibiting bcl-2 expression also significantly depressed tumor necrosis factor-alpha (TNF-alpha) expression. In the bropirimine treated group there was also a correlation between angiogenesis and cyclin D expression. Finally, linomide significantly decreased angiogenesis. Since the mechanism of action of these drugs differ, combining them at lower doses might maintain therapeutic efficacy while reducing toxicity.

Animals↗
PubMed1998

Paclitaxel is more effective than thalidomide in inhibiting LNCaP tumor growth in a prostate cancer model.

LNCaP tumors were treated by either administration of paclitaxel, thalidomide or by orchiectomy in order to determine their relationship with markers pertaining to the process of tumor growth, apoptosis or angiogenesis. Forty rats bearing LNCaP tumors were divided into 4 groups of 10 and treated by either paclitaxel (20 mg/kg x 5 days); thalidomide (200 mg/kg x 5 days/week x 5 weeks); or orchiectomy. After 6 weeks serum samples were removed for PSA determination and the animals sacrificed for evaluation of: A) tumor volume; B) tissue bcl-2, cyclin D, PSA and factor VIII immunohistochemically graded (0-5 scale) for marker expression; and C) serum PSA. Comparisons were made to untreated LNCaP tumors. Statistically significant differences were determined using the nonparametric Mann-Whitney test. Paclitaxel produced significant differences in volume (p < 0.001), expression of bcl-2 (p < 0.043), cyclin D (p < 0.023), tissue PSA (p < 0.001) and serum PSA (p < 0.019) levels. Thalidomide altered expression of bcl-2 (p < 0.011) and tissue PSA (p < 0.002). Orchiectomy altered volume (p < 0.002) and bcl-2 expression (p < 0.001). All three therapies have been suggested for prostate cancer and each produced alterations in accepted markers for treatment response (either reduced volume or serum PSA). Paclitaxel significantly influenced the most markers. Of interest was that all treatments, especially thalidomide, a known antiangiogenesis agent, reduced factor VIII, although not significantly. Evidently each treatment evokes different pathways of activity.

Androgen Antagonists↗
PubMed1998

Decreased survival of black Americans with testicular cancer.

PURPOSE: A 14-year review of 215 consecutive patients with testicular cancer at the University of Illinois hospitals revealed that 25% were black. This large experience with this relatively rare cancer in black men provides a unique opportunity to compare the disease stage at presentation, histological tumor type and 5-year survival rates of black, white and Hispanic men. MATERIALS AND METHODS: We reviewed the records of patients with a diagnosis of testicular cancer treated at University of Illinois hospitals. The Kaplan-Meier method was used to calculate actuarial 5-year survival rates. RESULTS: The overall percentages of white, black and Hispanic men were 55 (119 men), 25 (53) and 18% (38), respectively. We found no significant differences in tumor types among the 3 racial groups. Overall 42 and 58% of the patients had seminoma and nonseminoma, respectively. Black men with some types of cancer have been shown to present with higher stages of disease but we noted no differences in clinical stage at presentation in all groups with testicular cancer (average stage I disease in 45%, II in 31% and III in 24%). Survival rates were 88% in white, 79% in Hispanic and 71% in black patients. CONCLUSIONS: Black men had significantly decreased (z <0.02) 5-year disease specific survival, which was 17% less than white patients. The difference in disease specific survival for Hispanic men was not statistically significant. This review of 215 patients with testicular cancer revealed no differences in tumor type or stage at presentation for white, black or Hispanic men. However, a review of these data suggests that disease specific survival outcomes are more ominous in black men.

Actuarial Analysis↗
PubMed1997

Differential expression of p53, c-kit, and CD34 in prepubertal and postpubertal testicular germ cell tumors.

BACKGROUND: The origin of testicular germ cell tumors (TGCTs) in children is poorly understood. There are clear differences between tumors in young children and those in adolescents and adults, which may suggest that they follow different pathways of tumorigenesis. METHODS: Tissue sections from 25 TGCTs (15 from patients age 4 years or younger and 10 from adolescents or adults) were stained immunohistochemically with anti-p53 (DO-1), CD34, and c-kit proto-oncogene protein product. RESULTS: CD34 expression was noted only in 5 prepubertal tumors. Expression of c-kit was observed in 9 of the 15 prepubertal tumors versus 2 of the 10 postpubertal cases. The intensity of expression was equal to that of the adjacent normal tubules in the prepubertal tumors, whereas the intensity was less in the postpubertal tumors. Expression of p53 was strong in 8 of the 10 tumors in adolescents or adults, with a 40-70% positivity, whereas only 6 of 15 prepubertal tumors expressed p53, with < 10% positivity. CONCLUSIONS: CD34 expression in tumors in the group of young children suggests a possible link to teratomas and further provides insight into the fundamental differences between this group and the adolescent/adult group. The expression of c-kit and p53 provides further evidence that c-kit/SCF signaling and p53 play potentially different roles in the initiation and progression of these tumors. Future studies will be required to clarify this issue.

Adolescent↗
PubMed1997

Report of 337 patients with renal cell carcinoma emphasizing 110 with stage IV disease and review of the literature.

BACKGROUND: In the literature, the interdependence of variables, including stage, sex, age, tumor size, therapy, and survival, is complex. The size variable has heretofore received relatively little emphasis. METHOD: This was a retrospective evaluation of 337 patients with kidney cancer treated at the University of Illinois Affiliated Hospitals. Data were collected on stage, sex, age, tumor size, TNM stage, therapy, and survival. Statistical analyses included Kaplan-Meier 5-year survivals, as well as multivariate analysis utilizing the Cox regression model. A subset of 110 patients with TNM Stage IV disease is further evaluated employing a multivariate analysis. The principal form of therapy was nephrectomy. RESULT: Five-year survivals by stage varied from 100% for Stage I, 96% for Stage II, 59% for Stage III, to 16% for Stage IV. In the subset of 110 patients with TNM Stage IV disease, those with a single metastasis had better survivals than those with two or more. Those having nephrectomy had better survivals (P < 0.05). Therapy (in addition to nephrectomy) was curative (defined as cytotoxic chemotherapy or immunotherapy) in 40 patients and palliative (defined as radiation to bone metastases, hormone therapy, or supportive) in 70 patients. Multivariate analysis of TNM Stage IV variable differences indicated that only tumor size differences and nephrectomy significantly affected survival. CONCLUSIONS: Of importance is the observation that among these patients. Survival is directly correlated with tumor size.

Adenocarcinoma↗
PubMed1997

Enhanced expression of bcl-2 following antisense oligonucleotide mediated growth factor deprivation.

Although the role of bcl-2 in apoptosis has been described, its involvement in prostate cancer (CAP) progression is less well understood, but thought to be involved with the transition of CAP from androgen-sensitivity to androgen-independence, where its expression is augmented following androgen ablation. For treating these recurrent androgen-independent tumors, following hormone treatment failure, a new tier of therapy based upon growth factor deprivation has been suggested, implemented by antisense oligonucleotides (oligos) directed against mRNA encoding a critical growth regulatory autocrine loop (comprised of transforming growth factor-alpha (TGF-alpha) and its binding site, the epidermal growth factor receptor (EGFR). To determine whether oligo-induced growth factor deprivation therapy similarly enhanced expression of bcl-2 (as follows androgen deprivation) human prostate cancer derived PC-3 cells were treated in vitro with oligos directed against TGF-alpha (MR-1) and/or EGFR (MR-2). After 5 days of treatment cells were immunochemically stained for human bcl-2. In similar experiments, cells were treated for 3 days prior to extraction of proteins, Western blot analysis, photography and computer evaluation of protein density by SigmaScan software. Immunostained cells treated with oligos directed against mRNA encoding TGF-alpha (MR-1) either alone or in combination with that directed against EGFR (MR-2) had increased bcl-2 expression (+3 to +5). In addition, the intensity of Western blots scanned for bcl-2 expression were 19%, 32% and 30% greater in cells treated with oligos directed against TGF-alpha, EGFR or their combination, respectively. We conclude that enhanced bcl-2 expression followed antisense oligo induced growth factor deprivation. This result is similar to that found upon androgen deprivation therapy, and also demonstrates additional biologic activity of this new class of molecular therapeutic agents.

Apoptosis↗
PubMed1997

Spontaneous expulsion of an intravesical bullet.

Gunshot wounds of the pelvis are not uncommon. Penetrating injuries of the bladder are usually documented by means of a cystogram. The patient reported here was shot with a small caliber bullet. No extravasation was demonstrated. The authors caution that not all penetrating injuries to the bladder will demonstrate extravasation on a properly performed cystogram.

Adult↗
PubMed1997

Bropirimine as neoadjuvant therapy decreases residual disease and expression of markers PCNA and TGF-beta 1 in a rat orthotopic prostate adenocarcinoma.

The role of bropirimine in prostate cancer remains unexplored. To address the efficacy of this immune modulator as neoadjuvant therapy we utilized the orthotopic placement of the Dunning AT-3 tumor. 2.4-2.6 x 10(6) Dunning AT-3 cells were injected into the ventral prostates of 50 Copenhagen X Fischer rats. Animals were then divided into 5 groups consisting of: 1) untreated controls; 2) those treated with ventral prostatectomy alone (performed 10-12 days following tumor cell inoculation); 3) those treated with ventral prostatectomy plus bropirimine (10 mg/kg) on postimplantation days 1, 3, 5, 10 and 11; 4) those treated with ventral prostatectomy plus bropirimine (100 mg/kg), at the same schedule; and 5) those treated with ventral prostatectomy plus bropirimine (500 mg/kg), at the same schedule. Animals were sacrificed 10 days after prostatectomy, autopsied, and residual disease was weighed. Prostate weights upon removal following neoadjuvant treatment and residual disease remaining after 20-22 days were expressed in grams (g). Following prostatectomy, mean prostate weights were: Group 2, 0.67 +/- 0.11; Group 3, 0.53 +/- 0.11; Group 4, 0.54 +/- 0.12; Group 5, 0.44 +/- 0.09. The effect of bropirimine was significant (p = 0.0001) by multiple regression analysis. In addition, mean residual tumor weights (expressed in grams) after 20-22 days were: Group 1, 12.7 +/- 1.9; Group 2, 6.7 +/- 4.8; Group 3, 5.2 +/- 5.9; Group 4, 3.8 +/- 3.5; and Group 5, 2.8 +/- 3.5. The effect of bropirimine was not significant (p = 0.07) by multiple regression analysis. However, prostatectomy alone, by Student's test, significantly (p = 0.04) reduced residual mean tumor weights by 47% and the additional effect of bropirimine upon residual disease was significant (p = 0.038) if a Chi-square analysis is applied. Finally, a multivariate analysis of the overall effect of bropirimine in rats treated with prostatectomy was significant (p = 0.002). The effect of bropirimine on expression of proliferating cell nuclear antigen (PCNA) and transforming growth factor beta 1 (TGF-beta 1) was also evaluated immunohistochemically and expression of both tumor markers was significantly reduced (p < 0.05). We conclude that bropirimine may have a role as a neoadjuvant therapy when combined with prostatectomy.

Adenocarcinoma↗
PubMed1996

Antisense oligonucleotide intralesional therapy for human PC-3 prostate tumors carried in athymic nude mice.

Previously we reported hemorrhagic necrosis in human-derived PC-3 prostate tumors, in athymic nude mice, produced by the intralesional injection of antisense oligonucleotides (oligos) directed against mRNAs encoding transforming growth factor-alpha (TGF-alpha) and its target, the epidermal growth factor receptor (EGFR). We now describe our experience with these oligos in treating additional mice with various doses and modes of administration. During prolonged treatment, a dose-response effect was observed, with the optimal dosage consisting of the combination of 400 micrograms of each oligo. Although responses varied, based upon amount and how oligos were administered, we found that tumors were best treated when initially less than 156 mm3. Intralesional inoculations produced necrosis and yielded responses, ranging from complete response (CR) or cure to partial responses (PR) in 9 of 12 tumors treated with full dose (400 micrograms of each oligo) and 1 of 1 treated with 800 micrograms of each oligo, against a large tumor. Included among the 9 positive responses with full-dose administration were 2 tumors that regressed (one completely). A single tumor treated with twice (2X) the normal dosage (800 micrograms of each oligo) also regressed. A single tumor treated with half (1/2) dose (200 micrograms of each) progressed similar to controls, as did 3 of 12 treated with the full dose. Limited experience with ALZET diffusion pumps gave CR (1 of 3) or PR (2 of 3) in 100% of tumors treated (including one mouse cured of multiple tumors in a five day period). It appears that multiple inoculations consisting of 400 micrograms of each oligo is most effective against these tumors, particularly when administered against tumors of <156 mm3 in initial size.

Animals↗
PubMed1996

Suramin as adjuvant therapy with radical prostatectomy.

Suramin is a newer agent employed in the management of prostate cancer. One suggested method of action is growth factor inhibition. While suramin has been employed to treat advanced disease its adjuvant role remains unexplored. To address this question we have employed a new model: the orthotopic placement of the Dunning AT-3 tumor. The purpose of this research was to assess the efficacy of adjuvant therapy in controlling residual disease. The method consisted of the injection of 2.4 to 2.6 x 10(6) AT-3 cells (harvested from flank tumors) into the ventral prostates of 29 Copenhagen X Fischer rats. The animals were then divided into four groups: 1) untreated controls (6 rats); 2) ventral prostatectomy only (10 rats); 3) ventral prostatectomy plus suramin (300mg/Kg) on post-op day 3 (5 rats); and 4) ventral prostatectomy plus cytoxan (50 mg/Kg) on post-op day 3 (8 rats). Prostatectomies were performed 10-12 days following AT-3 cell inoculation. Animals were sacrificed 10 days following prostatectomy, autopsied, and residual diseased weighed. All operating procedures: tumor cell inoculations, ventral prostatectomies, and necropsies were performed microsurgically employing a Zeiss operating microscope. The results (in mean tumor weights) were: Group 1, 20 +/- 1.4 gms; Group 2, 6.7 +/- 11.5 gms; Group 3, 2.7 +/- 3.8 gms; and Group 4, 2.2 +/- 2.5 gms. The differences between control and all treatment groups were significant: Group 1 vs. Group 2, P < 0.02; and Group 1 vs. Groups 3 and 4, P < 0.001. We conclude that prostatectomy resulted in a diminished weight of residual disease. Of more importance was the fact that adjuvant therapy further reduced residual disease. The orthotopic placement of the Dunning tumor may serve as a model to evaluate the place of suramin following radical prostatectomy.

Animals↗
PubMed1996

Antitumor effect of CPT-11, a new derivative of camptothecin, against human prostate cancer (PC-3) in vitro and prostate rat tumor (AT-3) in vivo.

In an effort to evaluate the efficacy of CPT-11 on prostate cancer we utilized the PC-3 human prostate cancer cell line (in vitro), and the Dunning R3327 AT-3 rat prostate cancer tumor line (in vivo). PC-3 cells were initially seeded and cultured prior to the addition of CPT-11 at different concentrations 48 and 120 h later. After an additional 48 h the number of cells was determined using MTT dye uptake. CPT-11 at concentrations between 10 ng/ml and 50 micrograms/ml inhibited the growth of the PC-3 prostate human cancer cell line up < 0.001). AT-3 prostate rat cancer cells were injected into the right flank of 30 Copenhagen X Fischer rats, divided into treated and control groups. A total dose of CPT-11 (200 mg/kg) was given intraperitoneally, administered 1, 3 and 5 days postimplantation. We evaluated tumor growth by size and weight (5 and 10 days postimplantation). A total dose of 200 mg/kg inhibited the rapid growth of the prostate AT-3 tumor in vivo (p < 0.001).

Animals↗
PubMed1995

Renal cell carcinoma: comparison of the TNM and Robson stage groupings.

This review compares the two major staging systems for renal cell carcinoma: the TNM and Robson systems. For purposes of worldwide clinical and scientific consistency, the TNM system is recommended. However, the primary tumor size cutoff of 2.5 cm. does not prognostically differentiate between stages I and II. A review of 337 patients with renal cell carcinoma, of whom 122 had stage I or II disease revealed that a 2.5-cm cutoff did not predict survival differences, while cutoffs of 5.0, 7.5, and 10.0 cm did. Because 7.5 cm most closely approximates the mean renal cell cancer diameter as noted by SEER data, it is recommended that the TNM primary tumor cutoff be changed to 7.5 cm.

Carcinoma, Renal Cell↗
PubMed1995

Orthotopic placement of the Dunning R3327 AT-3 prostate tumor in the Copenhagen X Fischer rat.

Orthotopic placement of in vitro propagated Dunning R3327 AT-3 tumor cells resulted in a greater percentage of tumor takes and a two-fold shift in the exponential growth curve compared to flank implantation. The orthotopic tumor appeared to disseminate preferentially to regional lymph nodes, rather than to the lungs which is characteristic of flank tumors. The results suggest an important role of stromal-epithelial interactions in the growth of this tumor.

Adenocarcinoma, Papillary↗
PubMed1995

The impact of transrectal ultrasound on stage migration in a predominantly African-American population.

An important question left unanswered is whether transrectal ultrasound will result in earlier diagnosis in African Americans. Tumor registry data for 1985 and 1990 for a predominantly African-American population were reviewed to determine whether transrectal ultrasound influenced the stage at diagnosis of prostate cancer. Diagnosis by ultrasound increased from 0% to 60% of cases in those 5 years. Curable diseases (stages A and B) increased from 38% to 57% of cases. It is concluded that transrectal ultrasound can increase the diagnostic yield of potentially curable disease in a predominantly African-American population.

Aged↗