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C Marsh

Publications and source records attributed to C Marsh.

At least 19 recordsLinked to original sources
PubMed2003

FGF8 isoform b expression in human prostate cancer.

Overexpression of fibroblast growth factor 8 (FGF8) mRNA has been previously described in prostate cancer. Of its four isoforms, FGF8b is thought to be the most important in carcinogenesis. We hypothesised that immunodetection of FGF8b in archival prostate cancer specimens is of potential prognostic value. Using a selected cohort of prostate tumours from transurethral (n=30) and radical prostatectomies (n=59), an optimised protocol for FGF8b immunoreactivity was used to corroborate expression with clinical parameters. No expression was observed in benign prostates (n=10). In prostate cancer, immunoreactivity was localised to the malignant epithelium with weak signals in the adjacent stroma. Expression of FGF8b in stage T1 and T2 cancers were 40 and 67%, respectively. In contrast, FGF8b expression was present in 94% of T3 and 100% of T4 cancers. By histological grade, FGF8b was found in 41% of low-grade cancers (Gleason score 4-6), 60% of intermediate-grade cancers (Gleason score 7 and 92% of high-grade cancers (Gleason score 8-10). The intensity of expression was significantly associated with stage (P=0.0004) and grade (P<0.0001) of disease. We further hypothesised that FGF8b overexpression resulted from enhanced transcription and translation rather than from abnormalities involving the FGF8 gene locus. This was tested by means of fluorescent in situ hybridisation in 20 cancer specimens to map the FGF8 gene locus. FGF8 gene copy number in benign and malignant nuclei was found to be similar (2.33+/-0.57 and 2.0+/-0.81, respectively P=0.51). Based on these findings, we propose a multicentre study on cohorts of patients to further evaluate FGF8b as a potential prognostic marker in prostate cancer.

Fibroblast Growth Factor 8↗
PubMed2002

Hock injuries in cattle kept in straw yards or cubicles with rubber mats or mattresses.

Hock damage is one of the most common traumatic injuries suffered by dairy cows, but most hock injuries should be avoidable. This study investigated the effect of housing system on the development of hock damage in first lactation Holstein heifers. After calving, 60 heifers were randomly allocated to either straw yards, cubicles with butyl rubber mats or cubicles with mattresses filled with chopped tyres. The hocks of these heifers were examined in the first week after calving (week 1) and in weeks 6, 12 and 26 of lactation. Hock damage was scored as either 1 (hair loss only) or 2 (all other damage). Heifers housed in cubicles with mats had significantly worse lesions at week 26 than at week 1, while there was no change in heifers housed in cubicles with matresses, and heifers housed on straw had significantly lower lesion scores. Additionally, heifers with no lesions at calving were significantly more likely to develop lesions when kept on mats than heifers kept on straw or mattresses. These data suggest that replacing mats with mattresses in cubicles can result in a significant reduction in traumatic hock injury.

Animals↗
PubMed2002

Cytokeratin 7: a useful adjunct in the diagnosis of chromophobe renal cell carcinoma.

AIMS: The histopathological diagnosis of chromophobe renal cell carcinoma can present a diagnostic challenge, as these tumours can resemble either conventional renal cell carcinoma or oncocytoma. The aim of this study was to determine whether cytokeratin 7 expression is of practical use in the distinction of these three entities. METHODS AND RESULTS: A total of 40 cases previously diagnosed as either chromophobe renal cell carcinoma, conventional renal cell carcinoma or oncocytoma were identified. A representative section of each was stained with H&E and cytokeratin 7. Following independent review of the cases by three pathologists, a consensus diagnosis for each case was reached and the pattern of cytokeratin 7 staining was assessed. There were 12 cases of chromophobe renal cell carcinoma in the study, all of which showed a characteristic peripheral membrane pattern of staining for cytokeratin 7. Seventeen of the 18 cases of conventional renal cell carcinoma studied were negative for cytokeratin 7, while one case showed weak focal staining of <5% of the cells. The 10 cases of oncocytoma showed patchy weak to moderate cytoplasmic expression of cytokeratin 7, without the characteristic peripheral membrane accentuation seen in the chromophobe carcinomas. CONCLUSIONS: Immunohistochemical staining for cytokeratin 7 appears to be a useful adjunct in the diagnosis of chromophobe renal cell carcinoma, and in distinguishing this tumour from both oncocytoma and conventional renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed2001

Combined p21WAF1/CIP1 and p53 overexpression predict improved survival in muscle-invasive bladder cancer treated by radical radiotherapy.

PURPOSE: The prognostic value of p21 and p53 expression was evaluated for patients with muscle-invasive bladder cancer treated by radical radiotherapy. METHODS AND MATERIALS: Sixty-eight paraffin-embedded sections from surgically resected tumors taken prior to irradiation were immunostained for p21 and p53. RESULTS: Nuclear staining for p21 and p53 was demonstrated in 32/68 (47%) and 46/68 (68%) tumors, respectively. There was no correlation between p21 and p53 immunopositivity in this group (r = 0.067, p = 0.56). Patients were stratified into four distinct groups depending on staining for p21 and p53: p21+p53+, p21+p53-, p21-p53+, and p21-p53-. Patients with p21+p53+ tumors had the best prognosis with a 3-year survival of 82% compared to 12% for p21-p53+ tumors (p = 0.0031), 29% for p21+p53- tumors (p = 0.0108); and 45% for p21-p53- tumors (p = 0.0375). The p21+p53+ group also demonstrated significantly improved survival when a combined analysis was performed of p21-p53+, p21-p53-, and p21+p53- tumors (3-year survival = 30%, p = 0.0062). In a multivariate model, p21+p53+ tumors (p = 0.0108, relative risk [RR] = 5.18) and complete/partial response (p = 0.0019, RR = 3.76) were the only independent predictors of improved survival. CONCLUSIONS: With muscle-invasive bladder tumors treated by radical radiotherapy, stratification for p21 and p53 identifies distinct prognostic groups, with p21+p53+ tumors being associated with the best survival and p21-p53+ the worst.

Aged↗
PubMed1999

FGF8 over-expression in prostate cancer is associated with decreased patient survival and persists in androgen independent disease.

Identification of prostate cancers at high risk of progression is difficult and a better understanding of how peptide growth factors influence cellular function might be useful. Fibroblast growth factors (FGFs) have been implicated in prostate cancer development. FGF8 was identified in the Shionogi mouse mammary carcinoma SC-3 cell line as an androgen-induced mitogen. We tested if FGF8 was over-expressed in human prostate cancer and if its expression correlated with clinical data and outcome. One hundred and six cases of prostate cancer and ten cases of BPH were examined. In situ hybridization was employed to detect FGF8 mRNA expression, which was identified within the malignant prostatic epithelium in 85/106 (80.2%) cases. Increased expression of FGF8 correlated significantly with higher Gleason scores (P=0.0004) and advanced tumour stage (P=0.0016). Using immunohistochemistry, we confirmed over-expression of the FGF8b isoform. Men with tumours which expressed high levels of FGF8 had worse survival (P=0.034), although FGF8 mRNA was not able to provide additional prognostic information in a multivariate analysis. Additionally, FGF8 expression was shown to persist in androgen independent prostate cancer. Using a range of normal adult tissues, FGF8 expression was restricted to neurones and the germinal epithelium in addition to the prostate. In vitro studies demonstrated that in the presence of neutralizing antibody to FGF8b there was significant inhibition of prostate cancer cell growth, confirming the biological significance of FGF8 in prostate carcinogenesis.

Adult↗
PubMed1999

aFGF immunoreactivity in prostate cancer and its co-localization with bFGF and FGF8.

Fibroblast growth factors (FGFs) have been implicated in the development of numerous malignancies including prostate cancer. In a pilot study it has been shown that FGF8 mRNA is up-regulated in prostate cancer. The aim of the present study was to determine whether aFGF and bFGF were co-expressed with FGF8 in human prostate cancer. Twenty-nine cases of prostate cancer of different histological grades were examined. Immunohistochemical analysis was employed to study aFGF and bFGF expression. In the light of the results, aFGF immunoreactivity was studied in a further 43 cases. aFGF and bFGF immunoreactivity was identified in the cytoplasm of the malignant prostatic epithelium. aFGF was overexpressed in 62/72 (86.1 per cent) cases and bFGF in 19/29 (65.5 per cent). High levels of aFGF immunoreactivity were noted in areas of high-grade prostatic intraepithelial neoplasia (PIN). In this series, aFGF immunoreactivity was most commonly observed and correlated closely with Gleason score and tumour stage ( p=0.007 and 0.007, respectively). Co-localization of aFGF, bFGF, and FGF8 was detected in 9/29 (31.0 per cent) cases. There was a significant correlation between aFGF and FGF8 expression. In conclusion, aFGF, bFGF, and FGF8 are co-localized in human prostate cancer; they may have a synergistic effect in prostate cancer growth and progression.

Aged↗
PubMed1999

TP53 accumulation predicts improved survival in patients resistant to systemic cisplatin-based chemotherapy for muscle-invasive bladder cancer.

To examine retrospectively the prognostic significance of TP53 immunoreactivity for both tumor response and patient survival in 83 patients with nonmetastatic muscle-invasive bladder cancer treated with a single transurethral resection (TUR) of tumor and combined cisplatin-based systemic chemotherapy followed by repeat TUR, paraffin-embedded sections of a bladder tumor obtained at TUR before chemotherapy (1 T2, 52 T3, and 30 T4) were immunostained for TP53 using monoclonal PAb1801 and DO-7 antibodies. For the entire cohort, TP53 immunopositivity (PAb1801 or DO-7) did not predict complete response (CR), complete or partial response (PR), progressive disease, or time to death from bladder cancer. There was a highly significant correlation between PAb1801 and DO-7 nuclear immunoreactivity (r = 0.8242; P<0.0001). In 76 patients in which complete clinical data were available, tumor stage (T2/T3; P = 0.0499), CR and PR (P = 0.0016) and CR (P<0.0001) were associated with patient survival. In a multivariate model, CR (P<0.0001) was the only independent predictor of improved survival. In complete responders, neither TP53 immunostaining nor clinicopathological factors stratified patients into prognostic groups. However, in the subset of patients (n = 38) who were chemoresistant (PR or progressive disease), improved survival was associated with > or =20% TP53 immunoreactivity (PAb1801; P = 0.0191) and tumor stage (T2/T3; P = 0.0358). TP53 immunopositivity (PAb1801 or DO-7) did not predict overall survival or response to systemic chemotherapy in patients with nonmetastatic but predominantly clinical stage > or =T3 bladder cancer, but it had prognostic significance within the chemoresistant subgroup.

Aged↗
PubMed1998

Expression of Bcl-2, Bax, and p53 in high-grade prostatic intraepithelial neoplasia and localized prostate cancer: relationship with apoptosis and proliferation.

BACKGROUND: Apoptosis-regulating genes have been shown to be important in the biology of prostate cancer. The aim of this study was to examine and correlate the expression of the apoptosis-regulating genes bcl-2, bax, and p53 with the frequency of apoptosis and rate of proliferation in benign prostatic epithelium (BP), prostate cancer, and high-grade prostatic intraepithelial neoplasia (HGPIN), which is currently considered the most likely precursor of prostate cancer. METHODS: Forty-four patients with histologically proven prostate cancer were investigated. All the men underwent radical prostatectomy. Immunohistochemistry was performed to assess expression of bcl-2, bax, and p53, and proliferation rate, as measured by the Ki-67 index. The frequency of apoptotic bodies was assessed by morphological criteria. RESULTS: The apoptotic index (AI) was highest in prostate cancer, and was significantly greater in HGPIN compared to benign prostate. The Ki-67 index was greatest in cancer, intermediate in HGPIN, and lowest in BP. The AI was increased in areas of BP in patients treated with neoadjuvant androgen ablation. No change in AI was seen in treated cases of HGPIN or cancer. Accumulation of p53 protein was infrequent in prostate cancer (2/43: 4.6%), and was absent in HGPIN. Bcl-2 overexpression was present in 2.3% of cancers (1/43) and in 34.9% of cases of HGPIN (15/43). Bax expression was seen in all cases of cancer and HGPIN. There was no correlation between bcl-2 expression and the apoptotic and Ki-67 indices in HGPIN. CONCLUSIONS: p53 and bcl-2 expression is infrequent in clinically organ confined prostate cancer. Bcl-2 expression is significantly higher in HGPIN than in both the associated prostate cancer and BP. The AI and Ki-67 index appeared intermediate in the putative precursor lesion HGPIN compared to prostate cancer and BP.

Androgens↗
PubMed1998

Dacryocystorhinostomy in south west England.

PURPOSE: To assess the pre-operative management, surgical technique employed, success rate and patient satisfaction following surgery in patients undergoing dacryocystorhinostomy (DCR) in South West England. METHOD: Two hundred and forty-two patients who underwent DCR were retrospectively studied. A telephone questionnaire was used to assess patient satisfaction in 100 patients. RESULTS: One hundred and thirteen (46%) patients had nasolacrimal duct obstruction, half of whom had a history of dacryocystitis, 70 (29%) had canalicular obstruction and 8 (3%) had mixed blockage. The site of blockage was not known or recorded in 51 patients (22%). Seventy-five (31%) patients underwent DCR, 151 (62%) DCR with insertion of silicon tubes, 9 (4%) DCR and Lester Jones tube, and 7 (3%) canaliculodacryocystorhinostomy (CDCR). Overall an 83.5% success rate was reported by the surgeons. The success rate for patients with a history of dacryocystitis was 98%, for nasolacrimal duct obstruction 96% and for canalicular obstruction 82%. When the site of blockage was not known or recorded the success rate was 60%. Where the name of the surgeon was not recorded there was a 15% successful outcome. Eighty per cent of patients reported some improvement in their symptoms following surgery. CONCLUSIONS: DCR is an effective surgical procedure with a high rate of patient satisfaction. Pre-operative identification of the site of the blockage is likely to improve surgical outcome.

Adolescent↗
PubMed1998

The effect of intracameral, per-operative antibiotics on microbial contamination of anterior chamber aspirates during phacoemulsification.

PURPOSE: To assess the effect of per-operative antibiotics on contamination of anterior chamber (AC) aspirates during phacoemulsification. METHODS: Two hundred and twenty patients undergoing phacoemulsification of cataract were randomly allocated to receive an irrigation infusion fluid containing either balanced salt solution (BSS) alone or BSS with vancomycin (20 mg/l) and gentamicin (8 mg/l) during surgery. Conjunctival swabs were obtained from all patients immediately before pre-operative preparation. At the end of surgery 20 ml of the AC aspirate was sent for direct and enrichment cultures. Qualitative and quantitative microbiological studies were undertaken. The chi-squared test was used to compare differences between the two groups. RESULTS: There was no significant difference between the positive culture rates of the conjunctival swabs (28 vs 27; p > 0.8). In the group that received BSS alone there were 22 (20%) positive AC aspirate cultures, 18 of which were from enrichment cultures. There were 3 positive (2.7%) cultures from the group that received antibiotics added to the BSS (p < 0.0001). CONCLUSION: The addition of gentamicin and vancomycin to the irrigation fluid during phacoemulsification results in a highly significant reduction in the microbial contamination of AC aspirates.

Anterior Chamber↗
PubMed1997

Association of hepatitis C virus infection with mortality and graft survival in kidney-pancreas transplant recipients.

BACKGROUND: Although most studies have not demonstrated decreased patient or graft survival in kidney-alone allograft recipients infected with hepatitis C virus (HCV), the impact of HCV infection on patient and graft survival in HCV-infected kidney-pancreas recipients has not been studied. METHODS: We undertook a retrospective cohort analysis of 137 kidney-pancreas transplant recipients who were transplanted between January 1989 and May 1996. HCV infection was determined by a positive polymerase chain reaction. Relative risk of death and graft failure was calculated using the Cox proportional hazards model with time-dependent covariates. Relative risks were adjusted (aRR) to control for the number of OKT3-treated rejections and cytomegalovirus status of the recipient at the time of transplantation. RESULTS: Mean length of follow-up was 30.4 months in the HCV-infected patients compared with 31.7 months in noninfected patients. Seven (5.1%) patients were infected with HCV before transplant, one (1%) relapsed after transplantation, and four (2.9%) acquired the infection after transplantation. The HCV-infected group had a 3.7-fold (95% confidence interval [CI], 1.0-13.5) increased risk of death after transplant compared with the HCV-negative group, with an aRR of 5.5 (95% CI, 1.5-20.0). Death in the HCV-infected group (n=3) was generally the result of liver failure and sepsis, whereas death for those in the uninfected group (n=11) was primarily of cardiovascular origin. Patients infected with HCV were 3.4-fold (95% CI, 1.1-10.1) more likely to develop kidney graft failure than HCV-negative patients with an aRR of 5.1 (95% CI, 1.7-15.4). The risk of pancreatic allograft failure was not significantly increased. CONCLUSIONS: We conclude that HCV infection in kidney-pancreas transplant patients results in a significantly increased risk of kidney allograft failure and death.

Adult↗
PubMed1996

Genetic progression, histological grade, and allelic loss in ductal carcinoma in situ of the breast.

To investigate the relationships of specific allelic losses to progression and histological grade of ductal carcinoma in situ (DCIS) of the breast, we studied PCR-amplified microsatellite markers on ten chromosomal arms in 41 cases of DCIS without synchronous invasive cancer. For all chromosomal arms combined, the number of allelic losses was significantly greater in lesions of intermediate or high nuclear grade (5.6 chromosomal arms/case) than in lesions of low nuclear grade (1.2 chromosomal arms/case). Allelic losses of 16q and 17p were commonly found in low nuclear grade DCIS (38 and 34%, respectively) as well as in intermediate and high nuclear grade DCIS (58 and 95%, respectively). Allelic losses of other chromosomal arms examined (1p, 1q, 6q, 9p, 11p, 11q, 13q, and 17q) were uncommonly seen in low-grade DCIS, but were seen at frequencies of greater than 40% in intermediate- and high-grade DCIS. In 10 of the cases (24%), we identified patterns of allelic loss heterogeneity suggestive of intralesional progression, findings that were possible because multiple tumor foci from each lesion were individually microdissected and studied. For these tumors with allelic loss heterogeneity, we reasoned that chromosomal losses common to all tumor foci most likely preceded the chromosomal losses observed only in tumor foci of a more advanced genetic stage. In 9 of these 10 cases, all tumor foci lost 16q, and in 8 of the 10 cases, all tumor foci lost 17p. Together, these observations indicate that chromosomal losses of 16q and 17p occur early in DCIS progression and are common even in low-grade DCIS. Tumors of intermediate and high nuclear grade usually have allelic losses of significantly more chromosomal arms, often including 1p, 1q, 6q, 9p, 11p, 11q, 13q, and 17q. Allelic loss of these chromosomal arms may occur later in DCIS progression.

Alleles↗
PubMed1996

Genetic divergence in the clonal evolution of breast cancer.

The progression of ductal carcinoma in situ (DCIS) to infiltrating and metastatic cancer of the breast is thought to be a consequence of clonal expansions of neoplastic cells with progressively more genetic alterations. To study this progression, we first dissected multiple foci from each of 23 breast tumors with DCIS only and 20 cases with synchronous DCIS and infiltrating cancer. We than tested microsatellite markers by PCR for allelic losses in the individual foci for loci on chromosomes 6q, 9p, 11q, 13q, 16q, 17q, and 17p. The patterns of allelic losses identified in the in situ cancers were generally conserved in the synchronous infiltrating tumors, supporting the paradigm that the infiltrating tumors are clonally derived from the in situ lesions. However, in 8 (40%) of the 20 cases with synchronous in situ and invasive cancer, heterogeneous patterns of allelic loss at one or more chromosomal loci were observed in adjacent DCIS foci. Moreover, some of the allelic losses recognized in in situ portions of the tumors were not conserved in the clonal progression to the synchronous invasive tumor. Such allelic loss heterogeneity was noted in only 1 of the 20 infiltrating tumors and only 3 of the 23 cases of DCIS without invasion that were studied in a similar manner. This heterogeneity indicated genetic divergence during the clonal evolution of breast cancer, particularly at the time when in situ cancers progress to invasive cancers.

Breast Neoplasms↗
PubMed1996

A multicenter analysis of the first experience with FK506 for induction and rescue therapy after pancreas transplantation.

Between May 1, 1993 and April 5, 1995, 154 pancreas allograft recipients at 9 institutions were given FK506 posttransplant. Three groups were studied: (1) recipients given FK506 initially for induction and maintenance therapy (n = 82), (2) recipients switched to FK506 for antirejection or rescue therapy (n = 61), and (3) recipients converted to FK506 for other reasons (n = 11). Of 82 patients in the induction group, 7 (9%) had simultaneous bone marrow (BM) and pancreas-kidney (SPK-BM) transplants, 54 (66%) had SPK transplants without BM, 14 (17%) had pancreas transplants alone (PTA), and 7 (9%) had pancreas after previous kidney transplants (PAK). All but 1 recipient was given quadruple immunosuppression (anti-T cell agents plus azathioprine and prednisone) for induction. The median FK506 starting dose was 4 mg/day p.o.; the median average FK506 blood level, 12 ng/ml. The most common side effects were neurotoxicity (16%), nephrotoxicity (13%), and gastrointestinal toxicity (9%). New-onset diabetes mellitus requiring permanent insulin therapy did not occur. Of 61 transplants in the rescue group, 44 (72%) were SPK, 11 (18%) PTA, and 6 (10%) PAK. All but 3 (95%) of the recipients had been on cyclosporine-azathioprine-prednisone triple immunosuppression before substitution of FK506 for cyclosporine; 46% of the recipients had one, and 54% > or = 2, rejection episodes preconversion. The most common side effects were nephrotoxicity (25%), neurotoxicity (23%), and gastrointestinal toxicity (21%). Two recipients were reconverted to cyclosporine because of transient hyperglycemia, and one recipient is on insulin. In the induction group, patient survival at 6 months was 90% for SPK, 100% for PTA, and 100% for PAK. According to a matched-pair analysis, pancreas graft survival for SPK recipients at 6 months was 87% for FK506 versus 70% for cyclosporine recipients (P = 0.04); for PTA recipients, 84% versus 66% (P = n.s.); and for PAK recipients, 80% versus 14% (P = 0.11). When technical failures and death with functioning grafts were censored, pancreas graft survival remained significantly better in the FK506 group. The incidence of first reversible rejection episodes by 6 months in FK506 recipients was 35% for SPK, 40% for PTA, and 20% for PAK. Of 75 pancreas grafts, 64 are currently functioning; in 5 recipients the pancreas failed (1 from rejection); 6 recipients died with a functioning pancreas graft. There were 3 posttransplant lymphomas (all EBV-positive); 2 recipients died and 1 is alive after subtotal colectomy and transplant pancreatectomy. In the antirejection rescue group, patient survival rates at 6 months were 91% for SPK, 100% for PTA, and 80% for PAK (P = n.s.). Pancreas graft survival rates at 6 months were 90% for SPK, 72% for PTA, and 40% for PAK. The incidence of first reversible rejection episodes after conversion to FK506 at 6 months was 44% in SPK, 54% in PTA, and 50% in PAK. Of 61 pancreas grafts, 51 are currently functioning; in 7 recipients the pancreas failed (5 from rejection); 3 recipients died with a functioning graft. There were no posttransplant lymphomas in the rescue group. This multicenter survey shows that FK506 in pancreas transplantation is associated with (1) a low rate of graft loss from rejection when used for induction therapy, (2) a high rate of graft salvage when used for rescue or rejection therapy, and (3) a very low rate of new-onset insulin-dependent diabetes mellitus. These encouraging results are tarnished by 3 posttransplant lymphomas in the induction group; a possible explanation is overimmunosuppression, but further (randomized) studies are necessary to analyze the long-term risk-benefit ratio of FK506 after pancreas transplantation.

Adolescent↗