The Expression and Correlation of Cyclin E, P21WAF1Protein and P53 Variant Protein in Colorectal Adenoma and Carcinoma

Cyclins are proteins that activate different cyclin-dependent kinases(CDKs) and promote the cell cycles. Their correlations with several human cancers have been identified. Cyclin E, as one of G1 cylins, produces DNA replication through the progression of cell cycle G1 --> S phase. In contrast, cyclin-dependent kinase inhibitors(CDKI) bound with cyclin E-cdk2 complex control the cell cycle and inhibit the cell proliferation. P21(WAF1) proteins, which are CDKIs, are transcripted by a p53 gene and participate in the cell cycle inhibition. Variant p53 proteins produced by a mutated p53 gene lose the ability to control of the cell cycle resulting in cell proliferation. This study is aimed to reveal the expressions of cyclin E, p21(WAF1) protein, p53 variant protein in colorectal adenomas and carcinomas, and also reveal their correlations in the process of carcinogenesis. Twenty-one colorectal adenomas or adenomatous polyps, and thirty colorectal carcinoma tissues were obtained by operative resections or endoscopic polypectomies. Immuno histochemical stains of the above-mentioned three proteins and a statistical analysis of their correlations were made. The results were as follows: 1. P21 proteins were expressed in the upper-one third layer of all normal colonic mucosa, but cyclin E and variant p53 protein were not identified. 2. Cyclin E was expressed in 23.8% of adenomas and 76.7% of carcinomas. Variant p53 protein was expressed in 71.4% of adenomas and 83.3% in carcinomas. The degree of positivity of variant p53 expression was correlated with cancer staging. P21 protein was expressed in all adenomas, similar to normal mucosa, but was not expressed in 43.3% of carcinomas. 3. Expression of cyclin E was increased as to the positivity of variant p53 proteins but the correlations of p21 proteins and cyclin E, and p21 proteins and variant p53 proteins were not identified. Cancer staging was not correlated with the expressions of the three proteins. In conclusion, it can be thought that the overexpression of cyclin E and variant p53 proteins, and the loss of p21 proteins are related with the colorectal carcinogenesis. We can also identify the relationship of cyclin E and variant p53 proteins.

The Expression of DCC Protein in Colorectal Carcinomas

Colorectal cancer is one of the malignant tumours of which molecular genetic alterations have been much unveiled among the human cancers. In the multi-stepwise process to the carcinogenesis, it has been recently revealed that the neoplastic growth is originated either from the activiation of oncogene through its mutation, rearragement and amplification, or from the inactivation of the tumour suppression gene through its mutation and deletion. DCC(Deleted in colon cancer) protein is the product of DCC gene, the representative of tumor suppressor genes. The alteration of DCC protein may be related with the aggressiveness of carcinoma and metastasis. As a result, the prognosis of the cancer may be also thought to be affected. Now the prognosis of colorectal cancer mainly depends on pathologic staging, but there are some variations of survival and recurrence among the patients in same stage. Then this study is aimed to reveal the significance of alteration of DCC protein as an independent factor related to prognosis. Twenty three cancer tissues were obtained from the rejected specimens of colorectal carcinomas. We exacted the DCC gene products in the cancer tissues by the methods of immunohistochemical stains and Western blots. We also analyzed the relationships between the alteration of DCC proteins and the status of regional lymph node metastasis or the serum levels of CEA's(carcinoembryonic antigen). As results, we found the abscence or very scanty stains of DCC protein by Western lot in 14 cancer tissues of available 19 cases, but there were all negative responses in immunohistochemical stains. In contrast with above results, there were all positively stains of DCC proteins in corresponding 23 normal colorectal tissues by both the methods. There was no significantly statistical relation between the alteration of DCC proteins and the status of regional lymph node metastasis or the serum level of CEA. In conclusion, we can confirm that the DCC proteins are abscent or very scanty in colorectal cancer tissues and that may be related with the process of carcinogenesis. But the role of DCC protein loss as an independent prognostic factor was not found in this study.

Mixed hepatoblastoma in an adult--a case report and literature review

Hepatoblastoma is thought to originate from embryonal hepatic tissue, and most of these tumors occur in children under the age of 2 years. Hepatoblastoma in adults is extremely rare, and the prognosis is much worse than the mixed hepatoblastoma of childhood. We experienced a case of mixed hepatoblastoma in a 51 year old female patient. She had been suffering from a mild pain and a palpable lump in the epigastric area. Serum AFP was 43,850 ng/ml. Computerized tomography and selective abdominal angiography showed a large low-density mass. With a suspicion of hepatocellular carcinoma of the left lobe, a left lateral segmentectomy was performed. The external surface showed a huge protruding mass and the capsule was previously ruptured. On section, the tumor was a 11 x 7 cm sized expanding mass which had a variegated surface composed of yellow-white friable tissue with multifocal hemorrhagic areas. Microscopic examination revealed a tumor consisted of epithelial and mesenchymal elements. The mesenchymal cells were spindle in shape and proliferated over the whole tumor with focal osteosarcomatous differentiation. The epithelial components showed well-differentiated hepatocellular carcinoma-like areas, poorly differentiated acinar or tubular structures.

Construction of Three Dimensional Vascular Wall Model :Effects of low density lipoprotein and oxidized low density lipoprotein on endothelial cells and smooth muscle cells

To study the biology of the endothelium and media under conditions that mimic the architecture of the vascular wall and the effects of low density lipoprotein(LDL) and oxidized lipoprotein(ox-LDL), three dimensional vascular wall model was constructed in vitro. In the vascular wall model, endothelial cells(EC) were grown on a collagen lattice containing multilayer of smooth muscle cells(SMC) and endothelial cell-free portion was made by a cloning ring on the culture disc. The availability of this vascular wall model promptly us to examine the extent LDL and ox-LDL affect ECs and SMCs when these cells were maintained with or without each other in coculture. The results were as follows; 1) Morphologic characteristics of three dimensional vascular wall model Artificial vascular wall was a whitish, non-transparent membrane. Outer boundaries and the zone of no ECs were thicker than that of central portion. By light microscope imaging, luminal surface was EC monolayer, and SMCs and collagen fibers were distributed between the PET membrane and EC monolayer. SMCs and collagen fibers were mainly located near the PET membrane. Venous SMCs were densely infiltrated as compared to arterial SMCs. By scanning electron microscopy, EC monolayer was clearly shown. 2) The effects of LDL and oxidized LDL on ECs and SMCs in artificial vascular wall (1) The effects of LDL Collagen fibers are infiltrated just beneath EC monolayer in venous SMCs-EC coculture model. In the zone of no EC, marked proliferation and synthesis of collagen fibers were noted. (2) The effects of ox-LDL Injured EC monolayer were clearly shown in both venous and arterial SMCs-EC coculture model. On high power field light microscopic examination, collagen fibers were exposed outside to the luminal surface and were pendendicularly arranged, and looked like as ciliary projection. Artificial wall of these experimental model were thicker than that of control, and proliferation of SMCs and collagen synthesis were increased than those of control and LDL experiment groups. On scanning electromicroscopic examination, ECs were more slender and cell-to-cell contact was loosened. As a conclusion, this vascular wall model is to be good experimental model for vascular research. And LDL and ox-LDL have toxic effects on vascular EC layer and stimulate proliferation of SMCs and collagen synthesis in vitro three dimensionally constructed vascular wall model.

Carotid Body Tumors

Carotid body tumor is relatively rare neoplasm of the extra-adrenal paraganglion system. We have experienced two cases of carotid body tumors and successfully resected without any complication. Pre-operative intravascular embolization of the major arterial feeders was used. The cases and literatures were briefly reviewed.

Ultrastructural study on the cerebellar lateral nucleus of the hand-irradiated rats / 대한해부학회지

No abstract available.