[Effects of 5-Aza-2'-deoxycytidine on the carcinogenesis of colorectal cancer in mouse and the in vivo expression of p16/CDKN(2) mRNA].

OBJECTIVE: To explore the effects and relationship of specific demethylation agent 5-Aza-2'-deoxycytidine (5-Aza-CdR) on colorectal cancer (CRC) induced by 1, 2-dimethylhydrazine (DMH) in mouse and the in vivo expression of cyclin-dependent kinases inhibitor p16/CDKN(2) mRNA. METHODS: A total of 40 male KM mice were randomized into 2 groups and CRC was induced by a 22-week injection of DMH. One group was interfered by specific DNA methyltransferase inhibitor 5-Aza-CdR. Another 10 the same source male KM mice were induced by a 22-week injection of saline as none induced cancer control group (negative control group). All mice were sacrificed to examine for colorectal neoplasm. Immunohistochemical staining was used to assess the expression of proliferating cell nuclear antigen (PCNA). The expression of p16/CDKN(2) mRNA was detected by in situ hybridization. RESULTS: The average numbers of neoplasm was higher in the DMH group (7.6 ± 3.1) than that of the group DMH + 5-Aza-CdR (3.4 ± 1.8, P < 0.05). Immunohistochemical staining showed there was a significant elevation of PCNA in the group DMH (16/19) as compared with that in the group DMH + 5-Aza-CdR (11/19, P < 0.05). In situ hybridization revealed that the level of tumor suppressor gene p16/CDKN(2) mRNA was significantly lower in the group DMH than that in the group DMH + 5-Aza-CdR. CONCLUSION: The specific demethylation agent 5-Aza-2'-deoxycytidine may inhibit the carcinogenesis of CRC. Its mechanism may be related with a high expression of p16/CDKN(2) mRNA.

The potential effect of proteasome inhibitor PS-341 on severe acute pancreatitis detected by positron emission tomography in ICR mice.

INTRODUCTION: Severe acute pancreatitis is a life threatening disease with a high rate of mortality, and its treatments are still controversial. The purpose of this study is to investigate the potential effects of proteasome inhibitor PS-341 on severe acute pancreatitis induced by cerulein and lipopolysaccharide in mice. MATERIALS AND METHODS: Severe acute pancreatitis was induced by seven intraperitoneal injections of 50 ug/kg cerulein at hourly intervals and one injection of 10mg/kg lipopolysaccharide in mice. Thirty min before the administration of lipopolysaccharide, mice were treated either with PS-341 or vehicle. The severity of acute pancreatitis was then evaluated by serum and pancreatic biochemical assays as well as histologic examination. Positron emission tomography (PET) was used for the first time to determine the therapeutic effects of interventions in situ. RESULTS: PS-341 significantly inhibited NF-kappaB activation, while the pancreatic cell apoptosis was significantly enhanced, resulting in the improved parameters such as serum amylase, C-reactive protein, lactate dehydrogenase, interleukin-1beta, interleukin-6, and pancreatic myeloperoxidase activity. Accordingly, pancreatic damage, including inflammatory cell infiltration, hemorrhage, and necrosis, was markedly reduced. (18)F-fluorodeoxyglucose-positron emission tomography demonstrated that PS-341 significantly reduced the uptake of (18)F-fluorodeoxyglucose within the pancreas. CONCLUSIONS: These observations demonstrate that PS-341 was able to significantly reduce the severity of acute pancreatitis induced by cerulein and lipopolysaccharide in mice. The potential effect is associated with the inhibition of NF-kappaB activation and increased pancreatic cell apoptosis within the pancreas. (18)F-fluorodeoxyglucose-positron emission tomography could be a sensitive and promising means in evaluating the therapeutic effect and adjusting medical interventions for pancreatitis.

[Detection of chromosomal aberration in sporadic colorectal cancer with comparative genomic hybridization].

OBJECTIVE: To investigate the chromosomal aberration in sporadic colorectal carcinoma and its association with clinicopathological features. METHODS: Comparative genomic hybridization(CGH) was used to screen the changes in the number of DNA sequence copies in 40 sporadic colorectal cancer patients in order to identify regions that contain genes important for the development and progression of colorectal cancer. RESULTS: In 40 sporadic colorectal cancer, frequent gain at 20 q, 12 q, 13 q, 7 p, 7 q and 16 q were found, while loss was also found at 18 q, 5 q, 4 q, 8 pand 17 p. The number of chromosomal aberration was closely associated with tumor stage(P<0.05). No significant association was found between the number of chromosomal aberration and tumor site, histopathologic type and histologic grade. CONCLUSIONS: Chromosomal aberration exists generally in sporadic colorectal carcinoma. The number of chromosomal aberration and gain of 20q are closely associated with tumor stage.

[Effect of microRNA143 expression on cell proliferation in colonic carcinoma].

OBJECTIVE: To investigate the effect of microRNA143 on cell proliferation and K-ras expression in colorectal carcinoma. METHODS: Northern blot was used to examine the expression of miR-143 in colorectal carcinoma and adjacent normal tissues. A miR-143 expression vector was constructed and transfected into a human colon adenocarcinoma cell line SW480. Cell proliferation was evaluated by MTT assay. RT-PCR and Western blot were used to examine the expression of K-ras oncogene in transfected cells. RESULTS: The level of mature miR-143 was lower in tumors compared with adjacent normal tissues in 81% of colorectal carcinoma specimens. In transfected cells, the increased accumulation of miR-143 inhibited the cell proliferation, and resulted in approximately 40.3% decrease of K-ras protein levels, but had no effect on level of K-ras mRNA. CONCLUSION: The increased accumulation of miR-143 inhibits the proliferation of transfected cells, and results in down-regulation of K-ras protein in colorectal carcinoma.

[Influence of microencapsulated ovary cells modified with maspin gene on the microvessel density and lung metastasis of breast carcinoma].

OBJECTIVE: To observe the inhibition of maspin on the angiogenesis in tumor and lung metastasis of breast carcinoma and the feasibility of treatment of tumor by microencapsulated transgene cells in vivo. METHODS: Microencapsulated Chinese hamster ovarian epithelial cells (CHO) modified with maspin gene, CHO/pcDNA3.1/maspin cells, were prepared. Twenty BALB/C nude rats underwent subcutaneous injection of breast carcinoma cells of the line Bcap37 to establish tumor-loaded animal models and then randomly divided into 2 groups: maspin group, undergoing subcutaneous injection of CHO/pcDNA3.1/maspin cells next to the transplanted tumor, and control group undergoing subcutaneous injection of microencapsulated CHO/pcDNA3.1 cells. One month later, the rats were killed and the size and microvessel density (MVD) of the transplanted tumor and metastatic tumor in lung were observed. RESULTS: The MVD of the transplanted tumor of the maspin group was 26 +/- 9, significantly lower than that of the control group (60 +/- 16, P < 0.05). The lung metastatic rate of the maspin group was 15%, significantly lower than that of the control group (55%, P < 0.05). CONCLUSION: Maspin may inhibit the MVD in tumor and the occurrence of metastatic tumor in lung. It is feasible to use microencapsulated transgene cells as tumor-killer.

Expression of SNC73, a transcript of the immunoglobulin alpha-1 gene, in human epithelial carcinomas.

AIM: To investigate the expression of SNC73, a trans-cript of the immunoglobulin alpha-1 gene (IgA1-H chain), in human epithelia-derived tumor cells. METHODS: Total RNAs and cell lysates were prepared from five different human epithelial cell lines derived from lung, stomach, liver, skin, and breast, respectively. RT-PCR and immunoblot analysis of these five cell lines were done. Both RT-PCR and immunochemistry were used to detect the expression of SNC73 in these cell lines. We also examined the expression of SNC73 in normal epithelial cells of colon mucosa by in situ hybridization. RT-PCR and immunoblot analysis were used to determine whether the recombination activating gene1/2 (RAG1 and RAG2) is present. The expression of three immunoglobulin transcription factors, EBF, E2A and Pax5, and the heavy chain of IgA1 and two types of light chains of immunoglobulin (kappa and lambda) in the aforementioned cell lines were analyzed by RT-PCR and immunochemistry, respectively. All the RT-PCR products were analyzed by sequencing. RESULTS: The results of RT-PCR and immunochemistry showed that both mRNA and protein of SNC73 were expressed in five human epithelia-derived cancer cell lines. These data were further confirmed in the normal epithelial cells of colon mucosa by in situ hybridization. Also, the heavy chain of IgA1 and kappa light chain were detected in these cells, but no lambda light chain was obse-rved. Both RAG1 and RAG2 were expressed in these human epithelia-derived cancer cell lines and the sequence was identical to that expressed in pre-B and pre-T cells. In addition to RAG1 and RAG2, the mRNA in one of the immunoglobulin transcription factors, EBF, was also detected in these cell lines, and Pax5 was only expressed in SW480 cells, but no expression of E2A was observed in all the five cell lines. CONCLUSION: Immunoglobulin A1 is originally expressed and V(D)J recombination machine is also present in non-lymphoid cells, suggesting that V(D)J recombination machine mediates the assembly of immunoglobulin A1 in non-lymphoid cells as in pre-lymphocytes.

[Establishment of DNA oxidative damage model in colorectal crypt cells by hydrogen peroxide].

OBJECTIVE: To induce DNA oxidative damage in colorectal crypt cells by hydrogen peroxide in vitro. METHODS: Hydrogen peroxide was diluted into 100, 50, 10, 5 and 1 micromol/L with RPMI 1640. Colorectal crypt cells were treated with peroxide for 10 min, 30 min, 1 h, 1.5 h, 12 h and 24 h respectively. The survival of colorectal crypt cell was measured by MTT method, and the DNA oxidative damage special product, 8-OhdG was detected with immunohistochemical staining. Liner regression was used to measure the time trend of survival rate with SPSS 10.0 software. RESULT: Survival rate of colorectal crypt cell was 60% and 80% after 10 min of hydrogen peroxide treatment. The longer treatment of hydrogen peroxide, the lower survival rate; the survival rate was reduced to 30% in 24 h. After 10 or 30 min treatment of 100 or 50 micromol/L hydrogen peroxide, the survival rates of colorectal crypt cells were reduced by 20% compared with those of 10, 5 and 1 micromol/L hydrogen peroxide. However, while cells were treated with different concentrations of hydrogen peroxide for 1.0 h or above, there were no differences in cell survival rates. The time trend test results demonstrated that the survival rates of colorectal crypt cells treated with 10, 5 and 1 micromol/L hydrogen peroxide were significantly decreased with the time length of treatment. Colorectal crypt cells treated with different concentrations of hydrogen peroxide for 15 minutes were positively stained brown in cytoplasm and nuclear by immunohistochemistry with 8-OhdG monoclonal antibody. CONCLUSION: Hydrogen peroxide could induce DNA oxidative damage in colorectal crypt cells. And treated with 1 - 10 micromol/L hydrogen peroxide for 10 - 30 min, DNA oxidative damage is apt to be induced in colorectal crypt cell.

Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma.

OBJECTIVE: This study was designed to detect the expression of bcl-2 and p53 proteins in colorectal carcinomas and to determine their association with the patient survival and stage of the diseases. METHODS: Immunohistochemistry method was used to detect the expression of bcl-2 and p53 proteins in 93 cases of colorectal carcinoma. The stain results were obtained by analyzing the clinic-pathological characteristics of patients. RESULTS: Fifty-seven percent (53/93) of the colorectal carcinomas were bcl-2 protein positive. The positive rate of bcl-2 protein in lymph node involvement cases was lower (15/37) than the cases without node involvement (38/58, P<0.01). The positive rate of p53 protein was 43% (40/93) in colon-rectum carcinomas. No significant correlation was observed between p53 protein expression and clinic-pathological manifestations (P>0.05) but the survival was significantly worse (P=0.0001) in the p53 protein positive cases. Neither bcl-2 nor p53 alone was correlated with stage of the disease. When combined bcl-2/p53 status was analyzed, a group with bcl-2(+) and p53(-) had the best prognosis. This group was significantly associated with earlier Dukes' stages (P=0.1763). In multivariate Cox regression analysis, lymph node involvement and p53 protein expression were two independent factors correlated with survival time. CONCLUSION: The expression of bcl-2 and p53 represent biological characteristics of colorectal carcinomas. Assessment of both bcl-2 and p53 status may be valuable in predicting the prognosis of patients.

[Development of ZM-1 tissue microarrayer].

ZM-1 tissue microarrayer designed by our group is manufactured in stainless steel and brass. It features an easier and faster preparation for tissue microarrays. By means of it, a group of biopsy needles are used to punch the donor tissue specimens respectively, and all the needles with the punched specimen cylinders are arranged into the array-board, where small holes have been digged to fit the needles. All the specimen cylinders arraying and the tissue microarray block's shaping are finished simultaneously. ZM-1 tissue microarrayer with a lower cost of manufacture, is capable of preparing the tissue microarrays conveniently, efficiently and quality-controllably.

Application of new tissue microarrayer-ZM-1 without recipient paraffin block.

The ZM-1 tissue microarrayer designed by our groups is manufactured in stainless steel and brass and contains many features that make TMA (tissue microarray) paraffin blocks construction faster and more convenient. By means of ZM-1 tissue microarrayer, biopsy needles are used to punch the donor tissue specimens respectively. All the needles with the punched specimen cylinders are arrayed into the array-board, with an array of small holes dug to fit the needles. All the specimen cylinders arraying and the TMA paraffin block shaping are finished in only one step so that the specimen cylinders and the paraffin of the TMA block can very easily be incorporated and the recipient paraffin blocks need not be made in advance, and the paraffin used is the same as that for conventional pathology purpose. ZM-1 tissue microarrayer is easy to be manufactured, does not need any precision location system, and so is much cheaper than the currently used instrument. Our method's relatively cheap and simple ZM-1 tissue microarrayer technique of constructing TMA paraffin block may facilitate popularization of the TMA technology.

Preparation and in vitro studies of microencapsulated cells releasing human tissue inhibitor of metalloproteinase-2.

OBJECTIVE: To prepare microencapsulated cells releasing human tissue inhibitor of metalloproteinase-2 (TIMP-2), and investigate their biological characteristics in vitro. METHODS: Chinese hamster ovary (CHO) cells were stably transfected with a human TIMP-2 expression vector, encapsulated in barium alginate microcapsules and cultured in vitro. Morphological appearance of the microcapsules was observed under a light microscope. Cell viability was assessed using MTT (3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide) assay. Enzyme linked immunosorbent assay (ELISA) and reverse zymography were used to confirm the release of biologically active TIMP-2 from the microcapsules. Cryopreservation study of the microencapsulated cells was carried out using dimethyl sulfoxide (DMSO) as preservative agent. RESULTS: The microcapsules appeared like a sphere with diameter of 300 - approximately 600 microm. The surface of the capsule wall was clearly smooth. The microencapsulated cells survived well and kept proliferating over the 6 weeks observed. No significant difference in TIMP-2 secretion was found between encapsulated and unencapsulated cells. Reverse zymography confirmed the bioactivity of MMP (matrix metalloproteinase) inhibition of TIMP-2. The cryopreservation process did not damage the microcapsule morphology nor the viability of the cells inside. CONCLUSION: Microencapsulated engineered CHO cells survive at least 6 weeks after preparation in vitro, and secrete bioactive TIMP-2 freely from the microcapsules.

[Effects of microencapsulated CHO cells modified with maspin gene on the motility and adhesiveness of breast carcinoma cells Bcap37].

OBJECTIVE: To investigate the effects of microencapsulated Chinese hamster ovary (CHO) cells modified with maspin gene on the motility and adhesiveness of breast carcinoma cells Bcap37 and to explore the possibility and feasibility of its clinical application in treatment of malignant tumors. METHODS: After the Bcap37 cells were co-cultured with the microencapsulated CHO cells modified with maspin gene, their motility and adhesion to vascular endothelial cells (ECV304), changes in CD44v6 and E-cadherin expression were examined. RESULTS: After the treatment, the motility of Bcap37 cells, their adhesion to vascular endothelial cells ECV304 and the CD44v6 expression were significantly reduced. The adhesiveness of Bcap37 cells and their E-cadherin expression were significantly enhanced. CONCLUSION: The microencapsulated CHO cells modified with maspin gene decrease motility and adhesiveness of breast carcinoma cells Bcap37, which help explain the anti-metastatic effects of maspin.

[Clinical analysis of 39 cases of heterotopic gastric mucosa in the upper esophagus].

OBJECTIVE: To determine accurately the incidence of heterotopic gastric mucosa in the upper esophagus (HGMUE) in China, and to study the macroscopic and microscopic aspects of the lesions and to evaluate the clinical importance of HGMUE. METHODS: A prospective study was made among a total of 15,228 consecutive patients, 8,573 male and 6,655 female, aged 54 (8-95), undergoing gastroscopy. Disease histories of all patients were carefully inquired, especially those regarding possible complaints including discomfort of throat and swallowing pain and so on. Special care was taken in the upper esophageal sphincter area to make sure whether the area was adequately inspected. Biopsy specimens from aberrant mucosa were obtained and the sections were stained with haematoxylin and eosin, and Giemsa stain for Helicobacter pylori. RESULTS: HGMUE was found in 39 patients (0.26%) with an average age of 50. Five patients with H. pylori infection in heterotopic gastric mucosa also presented the infection in the stomach. The gastric mucosa was gastric body type in 8 patients, transitional type in 11 patients, and antral pattern in 7 patients. Intestinal metaplasia was found in 5 patients, and mild atypical hyperplasia in 2 patients. An impressive finding was coexistent erosive gastritis in 14 patients (35.9%), Barrett's esophagus in one patient (2.6%), peptic ulcer in 8 patients (20.5%), and a patient had the complication of constriction in the upper esophagus. CONCLUSION: HGMUE is not rare in China. The presence of inlet patches is possibly correlated with specific symptoms. There are some severe complications in HGMUE, especially esophageal constriction. Close surveillance should be taken for rare cases with metaplasia or dysplasia in HGMUE.

Expression of ST13 in colorectal cancer and adjacent normal tissues.

AIM: To investigate the in situ expression of suppression of tumorigenecity 13 (ST13) mRNA in both colorectal cancer and adjacent normal tissues. METHODS: Colorectal cancer cell lines SW1116, SW620 and CoLo205 were enrolled to confirm the feasibility of the in situ hybridization procedure. Seven colorectal cancer and adjacent normal tissues were included for RNA-RNA in situ hybridization. RESULTS: The expression of ST13 in the seven normal colon tissues was positive and the positive signals appeared in mucosal cells. Only three of the seven colorectal cancer tissues had positive hybridization signals that appeared in adenocarcinoma cells. CONCLUSION: The expression of ST13 decreases in colorectal cancer tissue compared with that in adjacent normal tissue. ST13 is mostly expressed in colorectal epithelia and adenocarcinoma cells.

[A study of the abnormalities of human epiderm in keloids and hypertrophic scars].

OBJECTIVE: To investigate the abnormalities of human epiderm in keloids and hypertrophic scars. METHODS: Biopsies from ten untreated keloids (duration of disease 3 - 30 years) and ten hypertrophic scars (duration of disease 6 - 10 months) and five normal adult skin specimens. Total RNA was isolated from normal adult skin. A cDNA fragment (base 5941 - 6481 bp) of the full-length human Tenascin-C cDNA was synthesized by polymerase chain reaction and subcloned in pGEM-T-easy. Dioxigen-labeled anti-sense and sense probes were synthesized by using a Sp6/T7 in vitro RNA synthesis kit in the present of Dig-UTP. In situ hybridization was performed on 4% paraformaldehyde-fixed and wax-embedded sections of keloids and hypertrophic scars. NBT-NCIP was used in color detection. Immunohistochemical procedure. The sections were incubated with antibodies (anti-Tenascin-C, anti-CK-16 and anti-Ki-67). Ultrasensitive Streptavidin Peroxidase staining was performed following established procedures. RESULTS: The study show that the proliferation of epidermal keratinocytes in keloids and hypertrophic scars is very clear. The expressions of Tenascin-C mRNA in keloids epidermal keratinocytes markedly increased in contrast with epidermal keratinocytes of hypertrophic scars and adult skin. The CK-16 and Ki-67 stainings significantly enhanced in the epidermal keratinocytes of keloids and hypertrophic scars. CONCLUSIONS: The different expressions of Tenascin-C, CK-16 and Ki-67 among normal adult skin, keloids and hypertrophic scars show the abnormalities of epidermal keratinocytes proliferation and differentiation in keloids and hypertrophic scars.

Significance of vascular endothelial growth factor expression and its correlation with inducible nitric oxide synthase in gastric cancer.

AIM: To investigate the clinical significance of the expression of VEGF165mRNA and the correlation with vascular endothelial growth factor (VEGF) protein and inducible nitric oxide synthase (iNO) in human gastric cancer. METHODS: We tested VEGF165mRNA expression in 31 cases of resected gastric cancer specimens and normal paired gastric mucosae by RT-PCR. Total RNA was extracted with TRIzol reagents, transcribed into cDNA with oligo (dT15) priming, inner controlled with beta-actin expression and agarose gel isolated after PCR. VEGF expression was quantitated with IS1000 imaging system. Meanwhile we also examined expression levels of VEGF protein and iNOS in 85 cases of gastric cancer. All paraffin-embedded samples were immunohistochemically stained by streptavidin -peroxidase method (SP). RESULTS: The mean expression of VEGF165mRNA in gastric cancer was 1.125+/-0.356, significantly higher than that of normal paired mucosae, which was 0.760+/-0.278. The data indicated that the expression level of VEGF165mRNA was well related to lymph node metastasis and TNM stages of UICC. The expression levels in patients with lymph node metastasis and without lymph node metastasis were 1.219+/-0.377 and 0.927+/-0.205 respectively (P<0.05). The expression in stages I, II, III, IV was 0.934+/-0.194, 1.262+/-0.386 respectively (P<0.01). Further analysis showed the lymph node metastasis rate in the group with over-expression of VEGF was higher than that in the group with low expression of VEGF (83.3% vs 46.2%), and the ratio of stage III+IV in the group with over-expression of VEGF was also higher than that in the group with low expression with VEGF (77.8% vs 33.8%) (P<0.05). The positive rates of expression of VEGF protein and iNOS in 85 cases of gastric cancer were 75.4% and 58.8% respectively, and 50.1% of the patients showed positive staining both for iNOS and VEGF, the correlation with the two factors was significant (P=0.018). But more intensive analysis showed the immunoreactive grades of VEGF were not associated with that of iNOS. CONCLUSIONS: The expression of VEGF165mRNA is well related with lymph node metastasis and TNM stages of UICC in gastric cancer, and is concerned with the invasiveness and metastasis of gastric cancer. The relationship can be observed between the expression of VEGF and iNOS in gastric cancer.

Study on interleukin-18 gene transfer into human breast cancer cells to prevent tumorigenicity.

To study the effect of interleukin-18 gene transfection on the tumorigenesis of breast cancer cell line Bacp37, human breast cancer cell line Bcap37 were transfected with Lipofectamine and selected by G418. The biological expression of rhIL-18 was tested by RT-PCR and ELISA method; nude mice were injected with Bcap37 cell with or without the hIL-18 gene. The hIL-18 cDNA was successfully integrated into Bcap37 cell; 126.3+/-4.5 pg hIL-18 secreted by one million transduced cells in 24 hours. Nude mice injected with IL-18 gene engineered Bcap37 cell had no tumor growth. These findings indicated that human breast cancer cells were successfully modified by the gene of IL-18 cytokine; the IL-18 gene engineered Bcap37 cells secreted hIL-18 and lost their tumorigenicity. The Bcap37 cells transduced with IL-18 gene may be used as breast cancer vaccine.

[Expression and recombination mechanism of SNC73 (IgHalpha1) in human epithelial cancer cell line].

OBJECTIVE: To study if the gene SNC73 (IgHalpha1) is expressed in human epithelial cancer cell line and to interpret the recombination mechanism. METHODS: Human epithelial cancer cells of SW480 line were cultured. RT-PCR and Western blotting were used to examine the expression of SNC73, recombination activating gene 1 (RAG1), and RAG2. The RT-PCR products were confirmed by sequencing. Immunohistochemistry was used to detect the expression of IgHalpha1, Igkappa, and Iglambda in these epithelial cancer cells. RESULTS: The human epithelial cancer cell line (SW480) positively expressed SNC73, RAG1, and RAG2. IgHalpha1 and Igkappa was strongly expressed in SW480 cells, but Iglambda was undetectable. The sequence of the constant region of SNC73 in SW480 cells is identical to that of IgA1. Both sequencing and Western blotting showed that the RAG1 and RAG2 expressed in SW480 cells were identical to that expressed in pre-B lymphocytes. CONCLUSION: Immunoglobulin alpha-1 gene is expressed in non-lymphoid cells, which may be a potential genetic marker for the development of colorectal cancer. Recombination signal sequence (RSS)-mediated recombination may take part in the rearrangement of immunoglobulin alpha-1 gene in human epithelial cancer cell line.

Clinical significance of vascular endothelial growth factor expression and neovascularization in colorectal carcinoma.

AIM: To clarify the association of vascular endothelial growth factor (VEGF) and microvascular density (MVD) expression with the angiogenesis and prognosis of colorectal cancer. METHODS: A total of 97 cases of colorectal carcinomas were examined by immunohistochemical staining (SP method), using anti-VEGF and anti-factor CD34(+) monoclonal antibodies. RESULTS: VEGF positive staining was obtained in 68 out of 97 cases (70.1 %), and observed mainly in the cytoplasm of tumor cells, and also frequently in stromal cells. VEGF expression was more intense in poorly differentiated adenocarcinoma in comparison with others, but there was no significant correlation between VEGF expression and age, sex and stage. A significant correlation was found between the MVD and grades, and there was no significant relationship between the MVD and age, sex, and stage. The MVD in the VEGF positive group (68 cases) was higher than that in the negative group. Upon multivariate analysis, the significant variables were stage, tumor grade and MVD; VEGF expression was not an independent prognostic factor. CONCLUSION: The expression of VEGF has a significant correlation with MVD; MVD expression has prognostic value but VEGF has not in colon cancer.