Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells from growth arrest to undergoing apoptosis.
The cyclin-dependent kinase inhibitor p21waf1/Cip1 is a downstream effector of the p53-dependent cell growth arrest. We report herein that p21 was cleaved by caspase-3/CPP32 at the site of DHVD112L during the DNA damage-induced apoptosis of cancer cells. The cleaved p21 fragment could no more arrest the cells in G1 phase nor suppress the cells undergoing apoptosis because it failed to bind to the proliferating cell nuclear antigen (PCNA) and lost its capability to localize in the nucleus. Thus, caspase-3-mediated cleavage and inactivation of p21 protein may convert cancer cells from growth arrest to undergoing apoptosis, leading to the acceleration of chemotherapy-induced apoptotic process in cancer cells. (+info)
Respiratory symptoms and long-term risk of death from cardiovascular disease, cancer and other causes in Swedish men.
BACKGROUND: Depressed respiratory function and respiratory symptoms are associated with impaired survival. The present study was undertaken to assess the relation between respiratory symptoms and mortality from cardiovascular causes, cancer and all causes in a large population of middle-aged men. METHODS: Prospective population study of 6442 men aged 51-59 at baseline, free of clinical angina pectoris and prior myocardial infarction. RESULTS: During 16 years there were 1804 deaths (786 from cardiovascular disease, 608 from cancer, 103 from pulmonary disease and 307 from any other cause). Men with effort-related breathlessness had increased risk of dying from all of the examined diseases. After adjustment for age, smoking habit and other risk factors, the relative risk (RR) associated with breathlessness of dying from coronary disease was 1.43 (95% CI : 1.16-1.77), from stroke 1.77 (95% CI: 1.07-2.93), from any cardiovascular disease 1.48 (95% CI : 1.24-1.76), cancer 1.36 (95% CI : 1.11-1.67) and from any cause 1.62 (95% CI: 1.44-1.81). An independent effect of breathlessness on cardiovascular death, cancer death and mortality from all causes was found in life-time non-smokers, and also if men with chest pain not considered to be angina were excluded. An independent effect was also found if all deaths during the first half of the follow-up were excluded. Men with cough and phlegm, without breathlessness, also had an elevated risk of dying from cardiovascular disease and cancer, but after adjustment for smoking and other risk factors this was no longer significant. However, a slightly elevated independent risk of dying from any cause was found (RR = 1.18 [95% CI: 1.02-1.36]). CONCLUSION: A positive response to a simple question about effort related breathlessness predicted subsequent mortality from several causes during a follow-up period of 16 years, independently of smoking and other risk factors. (+info)
Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity.
Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism. We report lymphocytic DPD data concerning a group of 53 patients (23 men, 30 women, mean age 58, range 36-73), treated by 5-FU-based chemotherapy in different French institutions and who developed unanticipated 5-FU-related toxicity. Lymphocyte samples (standard collection procedure) were sent to us for DPD determination (biochemical method). Among the whole group of 53 patients, 19 had a significant DPD deficiency (DD; below 150 fmol min(-1) mg(-1) protein, i.e. less than 70% of the mean value observed from previous population study). There was a greater majority of women in the DD group (15 out of 19, 79%) compared with the remaining 34 patients (15 out of 34, 44%, P<0.014). Toxicity was often severe, leading to patient death in two cases (both women). The toxicity score (sum of WHO grading, theoretical range 0-20) was twice as high in patients with marked DD (below 100 pmol min(-1) mg(-1) protein, n = 11, mean score = 13.2) compared with patients with moderate DD (between 150 and 100 pmol min(-1) mg(-1) protein, n = 8, mean score = 6.8), P = 0.008. In the DD group, there was a high frequency of neurotoxic syndromes (7 out of 19, 37%). The two deceased patients both had severe neurotoxicity. The occurrence of cardiac toxicity was relatively rare (1 out of 19, 5%). These data suggest that women are particularly prone to DPD deficiency and allow a more precise definition of the DD toxicity profile. (+info)
Cancer incidence in the south Asian population of England (1990-92).
Cancer incidence among English south Asians (residents in England with ethnic origins in India, Pakistan or Bangladesh) is described and compared with non-south Asian and Indian subcontinent rates. The setting for the study was areas covered by Thames, Trent, West Midlands and Yorkshire cancer registries. The study identified 356 555 cases of incident cancer (ICD9:140-208) registered between 1990 and 1992, including 3845 classified as English south Asian. The main outcome measures were age specific and directly standardized incidence rates for all cancer sites (ICD9:140-208). English south Asian incidence rates for all sites combined were significantly lower than non-south Asian rates but higher than Indian subcontinent rates. English south Asian rates were substantially higher than Indian subcontinent rates for a number of common sites including lung cancer in males, breast cancer in females and lymphoma in both sexes. English south Asian rates for childhood and early adult cancer (0-29 years) were similar or higher than non-south Asian rates. English south Asian rates were significantly higher than non-south Asian rates for Hodgkin's disease in males, cancer of the tongue, mouth, oesophagus, thyroid gland and myeloid leukaemia in females, and cancer of the hypopharynx, liver and gall bladder in both sexes. The results are consistent with a transition from the lower cancer risk of the country of ethnic origin to that of the country of residence. They suggest that detrimental changes in lifestyle and other exposures have occurred in the migrant south Asian population. (+info)
Cancer mortality by educational level in the city of Barcelona.
The objective of this study was to examine the relationship between educational level and mortality from cancer in the city of Barcelona. The data were derived from a record linkage between the Barcelona Mortality Registry and the Municipal Census. The relative risks (RR) of death and 95% confidence intervals (CIs) according to level of education were derived from Poisson regression models. For all malignancies, men in the lowest educational level had a RR of death of 1.21 (95% CI 1.13-1.29) compared with men with a university degree, whereas for women a significant decreasing in risk was observed (RR 0.81; 95% CI 0.74-0.90). Among men, significant negative trends of increasing risk according to level of education were present for cancer of the mouth and pharynx (RR 1.70 for lowest vs. highest level of education), oesophagus (RR 2.14), stomach (RR 1.99), larynx (RR 2.56) and lung (RR 1.35). Among women, cervical cancer was negatively related to education (RR 2.62), whereas a positive trend was present for cancers of the colon (RR 0.76), pancreas (RR 0.59), lung (RR 0.55) and breast (RR 0.65). The present study confirms for the first time, at an individual level, the existence of socioeconomic differences in mortality for several cancer sites in Barcelona, Spain. There is a need to implement health programmes and public health policies to reduce these inequities. (+info)
p27kip1: a multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers.
p27kip1 (p27) is a member of the universal cyclin-dependent kinase inhibitor (CDKI) family. p27 expression is regulated by cell contact inhibition and by specific growth factors, such as transforming growth factor (TGF)-beta. Since the cloning of the p27 gene in 1994, a host of other functions have been associated with this cell cycle protein. In addition to its role as a CDKI, p27 is a putative tumor suppressor gene, regulator of drug resistance in solid tumors, and promoter of apoptosis; acts as a safeguard against inflammatory injury; and has a role in cell differentiation. The level of p27 protein expression decreases during tumor development and progression in some epithelial, lymphoid, and endocrine tissues. This decrease occurs mainly at the post-translational level with protein degradation by the ubiquitin-proteasome pathway. A large number of studies have characterized p27 as an independent prognostic factor in various human cancers, including breast, colon, and prostate adenocarcinomas. Here we review the role of p27 in the regulation of the cell cycle and other cell functions and as a diagnostic and prognostic marker in human neoplasms. We also review studies indicating the increasingly important roles of p27, other CDKIs, and cyclins in endocrine cell hyperplasia and tumor development. (+info)
Angiogenesis: a new theory for endometriosis.
Excessive endometrial angiogenesis is proposed as an important mechanism in the pathogenesis of endometriosis. Evidence is reviewed for the hypothesis that the endometrium of women with endometriosis has an increased capacity to proliferate, implant and grow in the peritoneal cavity. Data is summarized indicating that the endometrium of patients with endometriosis shows enhanced endothelial cell proliferation. Results are also reviewed indicating that the cell adhesion molecule integrin alphavbeta3 is expressed in more blood vessels in the endometrium of women with endometriosis when compared with normal women. Taken together, these results provide evidence for increased endometrial angiogenesis in women with endometriosis when compared with normal subjects. Endometriosis is one of the family of angiogenic diseases. Other angiogenic diseases include solid tumours, rheumatoid arthritis, psoriasis and diabetic retanopathy. Excessive endometrial angiogenesis suggests novel new medical treatments for endometriosis aimed at the inhibition of angiogenesis. (+info)
Osteopenia in the patient with cancer.
Osteopenia is defined as a reduction in bone mass. It is commonly known to occur in elderly people or women who are postmenopausal due to hormonal imbalances. This condition, however, can result because of many other factors, such as poor nutrition, prolonged pharmacological intervention, disease, and decreased mobility. Because patients with cancer experience many of these factors, they are often predisposed to osteopenia. Currently, patients with cancer are living longer and leading more fulfilling lives after treatment. Therefore, it is imperative that therapists who are responsible for these patients understand the risk factors for osteopenia and their relevance to a patient with cancer. (+info)