Expression of cyclin D1 and retinoblastoma protein in colorectal cancer

Abnormal expression of the retinoblastoma protein (pRb) and cyclin D1 have been reported in a variety of malignancies, but the frequencies of these deregulations and their relation to prognosis in colorectal cancer has not been clarified. We characterised 90 colorectal cancers with respect to immunohistochemical expression of cyclin D1, pRb and Ki-67. Two of 90 (2%) tumours lacked nuclear pRb staining, indicating inactivation of the protein, while 10 (11%) expressed high levels of pRb. Abnormal expression of pRb was significantly correlated to low levels of nuclear cyclin D1 observed in 32% of the tumours. Strong nuclear cyclin D1 expression was detected in 12% of the tumours. Cytoplasmic staining of cyclin D1 was observed in 17% of the tumours, showing an inverse relationship (P = 0.006) to the Ki-67 labelling index. Eight of 11 tumours with high nuclear overexpression of cyclin D1 and both tumours with pRb defects were located in the right colon in comparison with zero of 25 in the rectum (P = 0.009). Regarding prognosis, neither pRb nor cyclin D1 expression correlated with patient survival.     

Expression of CuZn- and Mn-superoxide dismutase in human colorectal neoplasms

Decreased intracellular SOD protein levels and activity have been related with malignancy in the past. To investigate their relevance in the carcinogenetic process in the colon, we determined quantitatively CuZn-SOD and Mn-SOD levels and total SOD activity by histochemical means in human normal colorectal mucosa, adenomas, and carcinomas. Protein levels and activity were significantly decreased in carcinomas. CuZn-SOD protein levels, but not Mn-SOD levels or total SOD activity were related with differentiation grade and to a lesser extent with Dukes stage. Moderately differentiated carcinomas and Dukes stage A carcinomas showed lowest levels. Some carcinomas expressed elevated levels of CuZn-SOD and this was an indication of poor survival. It is concluded that decreased SOD expression is not a prognostic marker and seems to be a secondary phenomenon rather than directly linked with the carcinogenetic process.     

联合检测Syk及nm23H1在大肠癌中的表达及其意义

目的:探讨候选抑癌基因脾酪氨酸激酶(spleen tyosine kinase,Syk)及转移抑制基因(metastasis suppressorgene,mn23H1)在大肠癌组织中的表达及其生物学行为之间的关系.方法:采用免疫组织化学SP法,分别检测60例大肠癌组织及30例癌旁正常组织中Syk及nm23H1蛋白的表达情况;并分析其与大肠癌病理特征及生物学行为之间的关系.结果:Syk及nm23H1蛋自在大肠癌组织中的阳性表达率分别为31.7%、53.3%,在癌旁组织中的阳性表达率分别为96.7%、93.3%,癌组织中的阳性表达率均较癌旁组织明显降低(p<0.05).单因素分析显示Syk及nm23H1蛋白分别与淋巴结转移、浸润深度、Dukes分期密切相关(p<0.05),但与患者的年龄、性别、肿瘤大小、发生部位和肿瘤分化程度无明显关系(p>0.05).结论:大肠癌组织中Syk和nm23H1蛋白表达均明显低于癌旁正常组织,可能与大肠癌的发生发展及恶性程度相关.联合检测syk及nm23H1的表达对大肠癌的临床治疗和预后判断有一定价值.     

Expression of the mismatch repair gene hMSH2 in sporadic colorectal cancer

At least four genes involved in DNA mismatch repair (MMR), hMSH2, hMLH1, hPMS1 and hPMS2, have been cloned and characterized. These genes have been demonstrated to be altered in the germline of patients with hereditary non-polyposis colorectal cancer (HNPCC). HNPCC is an autosomal dominant disease characterized by a preponderance of proximal colon, young age of onset, increased multiplicity, and improved stage-specific survival. In this study, we examined the expression of hMSH2 protein in sporadic colorectal cancer (CRC). As a result, the frequency of right-sided CRC and multiple CRCs were significantly higher in the patients with hMSH2-negative CRC than in those with hMSH2-positive CRC. The rate of p53 positivity was significantly lower in the hMSH2-negative tumours than that in the hMSH2-positive tumours. The disease-free survival rate tended to be higher in the patients with hMSH2-negative CRC than in the patients with hMSH2-positive CRC. Our findings suggest that both the clinicopathological and biological features of hMSH2-negative sporadic CRC seemed to be similar to those of HNPCC. To clarify the mechanism of carcinogenesis in HNPCC and sporadic CRC, further investigations of genetic alterations caused by MMR genes will be needed.     

Increased expression of human histocompatibility leukocyte antigen-G in colorectal cancer cells

Human histocompatibility leukocyte antigen (HLA)-G is a nonclassical major histocompatibility complex class I molecule. HLA-G is known to provide tolerance from recognition by natural killer cells. We studied HLA-G expression in 39 human colorectal cancers and 23 extra-neoplastic colon tissue samples by RT-PCR. The expression of HLA-G mRNA was significantly more frequent in colorectal cancer (34 of 39 cases) than in the extraneoplastic tissue (10 of 23 specimens; chi2 test, p = 0.0003). HLA-G expression was also confirmed on the cancer cells immunohistochemically. These results suggested that HLA-G on colorectal cancer cells may be correlated with escape from immunological surveillance during colon cancer development.     

Expressions of cell cycle regulators in human colorectal cancer cell lines

To study the altered mechanisms of cell cycle regulation in colorectal cancer, the expressions of cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors, p53 and retinoblastoma (Rb) protein were analyzed by western blotting in a series of human colorectal cancer cell lines. The colorectal cancer cell lines exhibited various expression patterns of cell cycle regulators, which may reflect differences in the biological characteristics of cancer cells and in the genetic backgrounds of carcinogenesis. A correlation was found between p53 gene alteration and p21 expression, suggesting that p53 gene mutation usually suppresses p21 expression, though p21 expression could be induced via both a p53-dependent and a p53-independent pathway in colorectal cancer. None of the cell lines studied expressed p16 protein, suggesting that inactivation of p16 may be a common alteration in colorectal cancer. Moreover, all the D-type cyclins, especially D2 and D3, were expressed at a high level in most of the cell lines. Loss of p16 expression and increased expression of D-type cyclins promote CDK-mediated Rb phosphorylation. All of the colorectal cancer cell lines studied herein expressed Rb protein, but the growth-suppressive properties of Rb may be inactivated by the loss of p16 expression and increased expressions of D-type cyclins. In view of the pivotal role of Rb in cell cycle regulation, loss of p16 expression and overexpression of D-type cyclins may be critical alterations in colorectal cancer.     

Expression of endothelin-1 immunoreactivity in breast cancer

This study performed immunohistochemical staining for human ET-1, utilizing avidinbiotin-peroxidase complex detection to examine 47 surgically resected primary breast cancers. Positive immunoreactivity was demonstrated in 19 of the 47 breast cancers (40.4%). There was no significant relationship between the expression of ET-1 and clinicopathological findings. A significant difference was found between ET-1 positive and negative groups in the incidence of recurrence and distant metastasis (P < 0.05). The 5-year overall survival rate was significantly poorer in patients with ET-1-positive cancer (84.2%), compared to 96.4% in patients with ET-1 negative cancer (P < 0.01). The 5-year disease-free survival rate was significantly poorer in patients with ET-1-positive cancer (73.7%) compared to 96.4% in patients with ET-1-negative cancer (P < 0.05). These results suggest that the expression of ET-1 could be used as a possible indicator for predicting the metastatic potential of breast cancer.     

Consistent hepatic metastasis of human colorectal cancer in severe combined immunodeficient mice

A major stumbling block in the study of human colorectal cancer metastasis has been the lack of an effective in vivo model producing liver metastasis on a consistent basis. In this study surgical specimens of colorectal carcinoma were implanted in scid mice and studied for engraftment, growth, and the capacity to produce hepatic metastases. Human colorectal cancers would engraft and propagate in the subcutis and intraperitoneally. Sporadic metastasis to the liver occurred in 3 of 54 (6%) animals with cancer implanted subcutaneously. Liver metastasis occurred in 24 of 25 (96%) mice with cancer implanted in the gonad fat pad. Tumor growth to extremely large volumes subcutaneously did not enhance metastatic potential, and neither did longer term growth in the subcutaneous space. Tumor placed in the gonad fat required no special manipulation and in most cases a single piece of solid tumor was implanted. In situ hybridization confirmed the persistence of the human tissue in these metastasizing tumors. Our model will allow for the study of the processes involved in metastasis of solid tumors, characterization of differences between the primary tumor and the metastatic one, and evaluation of possible therapeutic modalities.     

Expression of granulocyte-macrophage colony-stimulating factor receptors in human prostate cancer

This investigation examined the effects of NaHCO3 loading on lactate concentration ([La]), acid-base balance, and performance for a 603. 5-m sprint task. Ten greyhounds completed a NaHCO3 (300 mg/kg body weight) and control trial in a crossover design. Results are expressed as means +/- SE. Presprint differences (P < 0.05) were found for NaHCO3 vs. control, respectively, for blood pH (7.47 +/- 0.01 vs. 7.42 +/- 0.01), HCO-3 (28.4 +/- 0.4 vs. 23.5 +/- 0.3 meq/l), and base excess (5.0 +/- 0.3 vs. 0.2 +/- 0.3 meq/l). Peak blood [La] increased (P < 0.05) in NaHCO3 vs. control (20.4 +/- 1.6 vs. 16.9 +/- 1.3 mM, respectively). Relative to control, NaHCO3 produced a greater (P < 0.05) reduction in blood base excess (-18.5 +/- 1.4 vs. -14.1 +/- 0.8 meq/l) and HCO-3 (-17.4 +/- 1.2 vs. -12.8 +/- 0.7 meq/l) from presprint to postexercise. Postexercise peak muscle H+ concentration ([H+]) was higher (P < 0.05) in NaHCO3 vs. control (158.8 +/- 8.8 vs. 137.0 +/- 5.3 nM, respectively). Muscle [H+] recovery half-time (7.2 +/- 1.6 vs. 11.3 +/- 1.6 min) and time to predose values (22.2 +/- 2.4 vs. 32.9 +/- 4.0 min) were reduced (P < 0.05) in NaHCO3 vs. control, respectively. No differences were found in blood [H+] or blood [La] recovery curves or performance times. NaHCO3 increased postexercise blood [La] but did not reduce the muscle or blood acid-base disturbance associated with a 603.5-m sprint or significantly affect performance.     

Cholesterolemia in colorectal cancer

BACKGROUND/AIMS: Colorectal cancer incidence is higher in developed countries. High fat intake is one of the risk factors. However, many studies observed lower cholesterol serum levels on diagnosis of colorectal cancer. The aim of this assay was to study the serum cholesterol levels in patients with colorectal cancer and compare these values with individuals of the same age and sex. METHODOLOGY: Cholesterol serum levels of 85 patients with colorectal cancer were determined. Each of the patients with colorectal cancer were matched with an individual without cancer of the same age and sex. Total cholesterol concentrations were determined using an enzymatic colorimetric method. RESULTS: The mean serum of cholesterol was 183.4 for the colorectal group and 209.7 for the control group. This difference was statistically significant. This difference was more evident in patients with colon cancer and older than 60 years of age. There was no difference between the different Dukes' stage. CONCLUSIONS: Our study suggest an association between low blood cholesterol and colorectal cancer. We believe that the lower level of cholesterol observed in these patients is a consequence between the difference of colorectal carcinogenesis.     

Expression of interleukin-1 system genes in human gametes

Elevation of extracellular calcium has been shown to inhibit osteoclastic bone resorption and stimulate proliferation and chemotaxis of osteoblasts. Therefore, calcium released by bone resorption may have important roles in the coupling of bone resorption and bone formation. Although both osteoclasts and osteoblasts have calcium-sensing mechanisms, the responsible molecule in these cells seems to be different. Functional and histological studies show that calcium-sensing mechanism in osteoclasts is a ryanodine receptor-like molecule in plasma membrane. In contrast, calcium-sensing mechanism in osteoblasts has similar functional property to parathyroid calcium-sensing receptor (CaSR), but is a different molecule from CaSR. In addition, several bone marrow cells express CaSR. The elucidation of the identity and the physiological roles of these calcium-sensing mechanisms would give us a more clear view of bone remodeling.     

Expression of functional P2-purinergic receptors in primary cultures of human colorectal carcinoma cells

Primary cell cultures of human colorectal carcinomas were established and characterized immunocytochemically. In the isolated cancer cells intracellular Ca2+ concentrations ([Ca2+]i) were measured by the fura-2 method. Stimulation with either extracellular ATP or UTP caused a biphasic rise of [Ca2+]i in a dose-dependent manner and cross-desensitization between both nucleotides was observed. The rank order of potency was ATP >== UTP > ATP-gamma-S > ADP > adenosine which is characteristic for a P2U-receptor subtype. Selective agonists of P1-, or P2X- purinoceptors had no effect on [Ca2+]i. The initial rise in [Ca2+]i was independent of extracellular calcium [Ca2+]e, whereas the second phase was not observed under [Ca2+]e-free conditions suggesting a capacitative Ca2+-entry-mechanism. Intracellular Ca2+ mobilization was proven by use of the Ca2+-ATPase inhibitor thapsigargin. P2U-specific mRNA could be detected by RT-PCR in both colorectal tumor tissues and in the human colorectal cancer cell line HT 29. In HT 29 cells, the hydrolysis-resistant ATP analog ATP-gamma-S inhibited cell proliferation and, also, induced apoptosis in a dose-dependent manner. Thus, human colorectal cancer cells express functional P2U-receptors which may play a role in the regulation of cell proliferation and apoptosis.     

Germline mutation analysis in hMLH 1 and hMSH 2 genes in hereditary nonpolyposis colorectal cancer and colorectal cancer patients with familial history

Workplace violence has become a problem in modern American society. Health-care workers are particularly vulnerable because of the nature of their jobs dealing with clients, many of whom are emotionally disturbed. A brief review of the Occupational and Safety Health Administration (OSHA) "Guidelines for Preventing Workplace Violence Among Health Care and Social Workers" that was published in 1996 is presented. Some sensible ways to implement the OSHA guidelines are also discussed.