Studies from model systems suggest that matrix metalloproteinases (MMPs) are causally involved in tumor progression while tissue inhibitors of MMPs (TIMPs) prevent this progression. Here, we show that concentrations of TIMP‐1 are significantly higher in breast carcinomas than in fibroadenomas. In primary breast cancers, TIMP‐1 concentrations increased with increasing tumor size but showed an inverse relationship with estrogen receptor concentrations. In primary breast cancers also, TIMP‐1 levels were weakly but significantly correlated with those for MMP‐1, proMMP‐2, active MMP‐2, MMP‐3 and proMMP‐9. Contrary to what might be expected from published data on model systems, high concentrations of TIMP‐1 predicted a poor outcome in patients with breast cancer. We conclude that in human breast cancer, endogenous TIMP‐1 does not inhibit tumor progression but may enhance the process. Int. J. Cancer (Pred. Oncol.) 84:44–48, 1999. © 1999 Wiley‐Liss, Inc.

BackgroundDiabetes is an increasingly prevalent chronic illness that places a huge burden on the individual, the health system and society. Patients with active foot disease and lower limb amputations due to diabetes have a significant amount of interaction with the health care services. The purpose of this study was to explore the attitudes and experiences of foot care services in Ireland among people with diabetes and active foot disease or lower limb amputations.MethodsA purposive sample of individuals who had either active foot disease or a lower limb amputation as a result of diabetes were recruited from the Prosthetic, Orthotic and Limb Absence Rehabilitation (POLAR) Unit of an Irish hospital. One-to-one interviews were conducted in the POLAR unit using a semi-structured topic guide. Thematic analysis was used to identify, analyse and describe patterns within the data.ResultsTen males participated in the study. Most participants expressed a need for emotional support alongside the medical management of their condition. There were substantial differences between participants with regard to the level of education and information they appeared to have received regarding their illness. There were also variations in levels of service received. Transport and medication costs were considered barriers. Having a medical card, which entitles the holder to free medical care, eased the burden of the patient’s illness. A number of participants attributed some of the problems they faced with services to the health care system as a whole rather than health care professionals.ConclusionResults suggest that rehabilitation services should place a strong focus on psychological as well as physical adjustment to active foot disease or lower limb amputations. The delivery of services needs to be standardised to ensure equal access to medical care and supplies among people with or at risk of lower extremity amputations. The wider social circumstances of patients should be taken into consideration by health care professionals to provide effective support while patients adjust to this potentially life changing complication. The patient’s perspective should also be used to inform health service managers and health professionals on ways to improve services.

The Ets family of transcription factors regulate expression of multiple genes involved in tumour progression. The aim of this study was to investigate the expression of Ets-1 in a large panel of human breast cancers and relate its levels to the parameters of tumour progression and metastasis. Using RT -PCR, Ets-1 mRNA was detected in 30 out of 42 (71%) fibroadenomas and 131 out of 179 (73%) primary breast carcinomas. Similarly, levels of Ets-1 mRNA were not significantly different in fibroadenomas and primary breast carcinomas. Using Western blotting, four forms of the Ets-1 protein were detected, that is, p33, p42, p51 and p52. Levels of both p51 and p52 but not p33 and p42 were present at significantly higher levels in the carcinomas compared to the fibroadenomas (for p51, Po0.007; for p52, Po0.02; Mann -Whitney U-test). Levels of p52, p51 and p33 correlated significantly with uPA protein levels (Po0.01), while only levels of p52 correlated significantly with HER-2/neu protein levels (Po0.01). Using immunohistochemistry, Ets-1 was found predominantly in tumour cells, but was also detected in some stromal cells surrounding tumour islands. We conclude that, while at the mRNA level, Ets-1 was found at similar levels in fibroadenomas and primary breast carcinomas, higher protein levels were detected in the cancers compared to the benign specimens. Since p52, p51 and p33 correlate with uPA levels, these forms of Ets-1 may play a role in breast cancer metastasis.

This study provided accurate documentation of the morbidity associated with axillary clearance, together with a reproducible method of arm volume measurement.