The effects of sodium butyrate and sodium bromo-octanoate (an inhibitor of P oxidation) on colonic mucus glycoprotein (mucin) synthesis have been assessed using tissue from colonic resection samples. Epithelial by normal epithelium at least 10 cm distant from colonic cancer was increased in the presence of sodium butyrate in a dose dependent manner, with maximum effect (476%) at a concentration of 0.1 mM (number of specimens=24 from six patients, p<0*001). The increase in response to butyrate was not seen when specimens were incubated in the presence of the P oxidation inhibitor sodium bromo-octanoate 0.05 M. The striking increase in mucin synthesis that results when butyrate is added to standard nutrient medium suggests that this may be an important mechanism affecting the rate of mucin synthesis in vivo and may also explain the therapeutic effect of butyrate in colitis. (Gut 1995; 36: 93-99)
Summary Both cell adhesion and cell signalling events are mediated by components of the cadherin-catenin complex. Loss of expression of the components of this complex have been shown to correlate with invasive behaviour in many tumour types although their exact role in colorectal cancer remains unclear. Immunohistochemical analysis of the expression of components of the cadherin-catenin complex in colorectal cancers from 60 patients was undertaken. Loss of memberanous expression of E-cadherin, α-catenin and β-catenin was demonstrated in 52%, 85% and 40% of tumours respectively. Focal nuclear expression of β-catenin (< 75% of cells per section), usually associated with cytoplasmic expression, was clearly demonstrated in 19 (32%) tumours while widespread nuclear expression (> 75% of tumour cells per section) was seen in 11 (18%) tumours. Loss of membranous α-catenin expression significantly correlated with tumour dedifferentiation (P = 0.009). There was a trend towards an association between advanced tumour stage and loss of membranous expression of α-catenin or β-catenin, although these associations were not statistically significant. Univariate analysis revealed that advanced Dukes' stage, tumour de-differentiation, loss of membranous β-catenin expression, cytoplasmic β-catenin expression and widespread nuclear expression of β-catenin all correlated with short survival following apparently curative resection of the primary tumour. However, only Dukes' stage (P = 0.002), tumour grade (P = 0.02) and widespread nuclear expression of β-catenin (P = 0.002) were independent predictors of short survival. Disturbed growth signalling events in colorectal tumours are thought to result in nuclear accumulation of β-catenin. Consequently, tumours with widespread nuclear expression of β-catenin are likely to have severely abnormal growth characteristics, and which therefore might be predictive of short survival in these patients.
The possible production of gastrin by colorectal carcinomas has been studied.
Current evidence leads to uncertainty whether mild CDAD needs to be treated. The studies provide little evidence for antibiotic treatment of severe CDAD as many studies excluded these patients. Considering the two goals of therapy: improvement of the patient's clinical condition and prevention of spread of C. difficile infection to other patients, one should choose the antibiotic that brings both symptomatic cure and bacteriologic cure. A recommendation to achieve these goals cannot be made because of the small numbers of patients in the included studies and the high risk of bias in these studies, especially related to dropouts. Most of the active comparator studies found no statistically significant difference in efficacy between vancomycin and other antibiotics including metronidazole, fusidic acid, nitazoxanide or rifaximin. Teicoplanin may be an attractive choice but for its limited availability (Teicoplanin is not available in the USA) and great cost relative to the other options. More research of antibiotic treatment and other treatment modalities of CDAD is required.
Summary It has been suggested that the selective loss of E-cadherin expression can generate invasiveness in human carcinoma cells and might be a predictor of metastasis. Frozen sections of samples from 44 patients, 43 with suspected large bowel cancer and one with a liver recurrence were examined for E-cadherin expression using the antibody 6F9 specific for the human E-cadherin molecule. Twelve of the 40 patients with carcinoma already had lymph node involvement at the time of surgery. Samples from the primary carcinomas of only nine of these 12 patients showed reduced E-cadherin expression. However, the one lymph node with metastatic spread examined did show reduced E-cadherin expression. Four of the 40 carcinoma patients had liver involvement at the time of surgery. The primary carcinoma samples from only three of these four patients showed reduced E-cadherin expression. In addition only two out of the three liver metastases examined showed reduced expression. The primary carcinoma samples from seven patients with no evidence of tumour spread also exhibited reduced expression. Overall, analysis of the data suggests that there is no absolute correlation between reduced E-cadherin expression and tumour spread in carcinomas of the large bowel. E-cadherin (also known as Arc-1, uvomorulin and cell CAM 120/80) is one of a group of functionally related, integral membrane glycoproteins responsible for calcium-dependent cell-cell adhesion. Cadherins are responsible for the movement and rearrangement of cell collectives during embryogenesisi (Takeichi, 1988) and for the orderly structure of differentiated tissue. Cell transfection studies with E-cadherin cDNA in rodent systems have demonstrated directly that cadherin molecules are involved in cell-cell binding (Nagafuchi et al., 1987;Mege et al., 1988). Moreover, Behrens et al. (1989) demonstrated that epithelial cells deprived of their E-cadherin function by the addition of anti-E-cadherin antibodies, not only became less adhesive but became able to invade collagen gels and embryonal heart tissue. Shimoyama and co-workers (1989) also reported that colonies of cultured epithelial cells became dissociated and mobile after the addition of anti-E-cadherin antibody.Expression of E-cadherin has been studied in tissue sections from a variety of well and poorly differentiated human tumours, but not those arising in the large bowel, using immunohistochemical and immunofluorescence techniques (Eidelman et al., 1989;Shimoyama et al., 1989;Pfisterer et al., 1990; Shimoyama & Hirohashi, 1991a,b;Schipper et al., 1991). For the most part, E-cadherin expression has been shown to correlate with differentiation status, with lower levels of expression being observed in poorly differentiated tumours. This correlation with differentiation status has been observed for ovarian carcinomas (Pfisterer et al., 1990) and squamous carcinomas of the head and neck (Schipper et al., 1991 (Hashimoto et al., 1989) and the absence of expression in a grade IV hepatocellular carcinoma that went on to ...
Arsenic trioxide, an acute promyelocytic leukemia chemotherapeutic, may be an efficacious treatment for other cancers. Understanding the mechanism as well as genetic and molecular characteristics associated with sensitivity to arsenite-induced cell death is key to providing effective chemotherapeutic usage of arsenite. Arsenite sensitivity correlates with deficient p53 pathways in multiple cell lines. The role of p53 in preventing arsenite-induced mitotic arrest-associated apoptosis (MAAA), a form of mitotic catastrophe, was examined in TR9-7 cells, a model cell line with p53 exogenously regulated in a tetracycline-off expression system. Arsenite activated G 1 and G 2 cell cycle checkpoints independently of p53, but mitotic catastrophe occurred preferentially in p53 inhibit cyclin B/CDC2 by CDC2 tyrosine-15 phosphorylation and direct binding, respectively. CDC2-Y15-P was transiently elevated in arsenite-treated p53 (ϩ) cells but persisted in p53 (Ϫ) cells. Arsenite induced p53-S15-P and p21 CIP1/WAF1 only in p53 (ϩ) cells. P21 CIP1/WAF1 -siRNA-treated p53 (ϩ) cells were similar to p53(Ϫ) cells in mitotic index and cell cycle protein levels. p53-inducible proteins GADD45␣ and 14-3-3 are capable of inhibiting cyclin B/CDC2 but did not play a p53-dependent role in mitotic escape in TR9-7 cells. The data indicate that p53 mediates cyclin B/CDC2 inactivation and mitotic release directly via p21 CIP1/WAF1 induction.
Eighty-six patients who underwent regional node dissection (RND) for melanoma were reviewed with respect to short and long term postoperative morbidity, mortality and local recurrence rate. Twenty-eight per cent of dissections were prophylactic and seventy-two per cent therapeutic. There were significant wound related complications which tended to delay hospital discharge, in particular following axillary and groin dissections, but symptomatic long term complications were infrequent. The postoperative mortality rate was 1.2 per cent. Local recurrence in RND scars was particularly common in the neck (33 per cent). RND for melanoma is a safe procedure, with significant short term but relatively little long term morbidity. Both recurrence and morbidity should be borne in mind when considering patients for prophylactic RND. Surgeons should be prepared to use axial or myocutaneous flaps where extensive skin resection is necessary. A controlled trial of prophylactic antibiotics would be useful to try to reduce the incidence of wound infection.
The use of high-intensity statins following hospitalization for MI increased progressively from 2011 through 2014.
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