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R I Cutress

Publications and source records attributed to R I Cutress.

6 recordsLinked to original sources

BAG-1 expression and function in human cancer.

BAG-1 is a multifunctional protein that interacts with a wide range of target molecules to regulate apoptosis, proliferation, transcription, metastasis and motility. Interaction with chaperone molecules may mediate many of the effects of BAG-1. The pathways regulated by BAG-1 play key roles in the development and progression of cancer and determining response to therapy, and there has been considerable interest in determining the clinical significance of BAG-1 expression in malignant cells. There is an emerging picture that BAG-1 expression is frequently altered in a range of human cancers relative to normal cells and a recent report suggests the exciting possibility that BAG-1 expression may have clinical utility as a prognostic marker in early breast cancer. However, other studies of BAG-1 expression in breast cancer and other cancer types have yielded differing results. It is important to view these findings in the context of current knowledge of BAG-1 expression and function. This review summarises recent progress in understanding the clinical significance of BAG-1 expression in cancer in light of our understanding of BAG-1 function.

Apoptosis↗

BAG-i expression in human breast cancer: interrelationship between BAG-1 RNA, protein, HSC70 expression and clinico-pathological data.

BAG-1 (BCL-2 athanogene-1), a multifunctional protein which associates with steroid hormone receptors (including the oestrogen receptor) and the anti-apoptotic BCL-2 protein, regulates steroid hormone-dependent transcription and apoptosis. Direct interaction with 70 kD heat-shock proteins, HSC70 and HSP70, may mediate the diverse functions of BAG-1. Immunohistochemistry was used to examine the expression of BAG-1 and HSC70 in 160 cases of invasive breast cancer. BAG-1 was expressed in 92% of cases; most tumours exhibited cytoplasmic BAG-1, while a smaller proportion also had nuclear immunostaining. There was a significant inverse correlation between histological grade and nuclear BAG-1 expression, with higher-grade tumours tending to have reduced nuclear BAG-1 expression, but there was no association with cytoplasmic BAG-1. There was also no significant correlation between nuclear or cytoplasmic BAG-1 expression and oestrogen receptor positivity. Since BAG-1 may be influenced by hormonal background, the relationship between grade and oestrogen receptor was examined separately in pre-menopausal and post-menopausal women. The statistically significant correlation between nuclear BAG-1 expression and low tumour grade was strong in pre-menopausal, but not apparent in postmenopausal women. A statistically significant correlation was observed between cytoplasmic, but not nuclear, BAG-1 expression and oestrogen receptor status in pre-menopausal, but not postmenopausal, women. There was no correlation between BAG-1 protein expression and RNA, suggesting that important post-transcriptional mechanisms control BAG-1 expression in vivo. HSC70 was also detected in the majority (97%) of cases, although expression was not correlated with BAG-1 levels, oestrogen receptor status or tumour grade. Overall survival in cases with high levels of nuclear BAG-1 expression was improved, though not significantly. These results are consistent with the hypothesis that BAG-1 plays an important but variable role in breast cancers developing in pre-menopausal and post-menopausal women.

Adult↗

Clinical outcome and bromodeoxyuridine derived proliferation indices in 100 colonic and rectal carcinomas.

AIM: In vivo labelling of human colonic and rectal tumours with bromodeoxyuridine (BrdUrd) and analysis by flow cytometry (FCM) allows the labelling index (LI), S phase duration (Ts) and the potential doubling time (Tpot) of the tumour to be estimated in vivo. METHODS: The data for a series of 100 tumour specimens from 97 patients with colonic and rectal carcinoma was reported in 1991, and correlated with Dukes' classification and histological differentiation. RESULTS: This study reports the eventual outcome of the 97 patients after 12 years. There were no significant associations between proliferation data of the index tumours and patient outcome. No adverse events were identified which could be attributed to the use of the halogenated pyrimidine label in vivo. CONCLUSION: Dynamic cell proliferation indices provide detailed information on the cell kinetics of colorectal tumours but these do not correlate with clinical prognostic markers or outcome.

Adenocarcinoma↗

Might patients benefit from oral iron therapy following operative treatment of breast carcinoma?

AIMS: To assess the changes in blood haemoglobin concentration and serum iron indices as a consequence of breast operations for cancer in our unit. METHODS: Haematological parameters were measured in 109 patients undergoing definitive operative treatment for breast carcinoma. RESULTS: A mean fall in haemoglobin of 2.1 g (P=0.001) occurred in patients undergoing mastectomy and axillary clearance and of 1.3 g (P<0.001) in patients undergoing wide local excision and axillary clearance. The transferrin saturation (serum iron/total iron binding capacity) in both sets of patients after surgery fell on average to levels that would be expected to impair subsequent red cell production. CONCLUSION: The changes in iron indices that occurred were unrelated to the degree of blood loss consistent with a possible inflammatory effect of the operation. Oral iron therapy is unlikely to be of benefit to operative breast patients if they have normal pre-operative iron stores.

Anemia, Iron-Deficiency↗

Clinical outcome and bromodeoxyuridine-derived proliferation indices in 75 invasive breast carcinomas.

INTRODUCTION: In vivo labelling of human breast tumours with bromodeoxyuridine (BrdUrd) and analysis by flow cytometry (FCM) allows the labelling index (LI), S phase duration (t(s)) and the potential doubling time (t(pot)) of the tumour to be estimated. METHODS: The data for a series of tumour specimens from 75 patients with invasive breast carcinoma were reported in 1991, correlated with their lymph-node status, tumour size and grade. RESULTS AND CONCLUSIONS: This study reports the follow-up data over 10 years in respect of time to recurrence and death from the disease. There were no significant correlations between proliferation data and outcome measures. No adverse events were identified which could be attributed to the use of the halogenated pyrimidine label in vivo.

Adult↗