Objective: The purpose of the present study was to investigate the relation between the dose of tumor cell inoculation (especially the doses less than minimum required to evoke tumor growth) and the anti-tumor immune system, particularly lymphoblast formation and cytotoxic activity of lymphcytes. Method: We inoculated rats with various doses of SST-2 tumor cells and examined natural killer (NK) cell activity and lymphoblast formation in vitro. Result: The results showed that the cytotoxicities against SST-2 cells and lymphoblast formation of lymphocytes were enhanced by small dose inoculation of tumor cells that could not induce tumor growth. Conclusion: It was suggested that was lymphocutes play an important role as an anti-tumor immune system at small doses of tumor inoculation, which appears to reflect an early stage of tumor growth in vivo. It was also suggested that SST-2 tumor inoculation might be a useful model for studying the anti-tumor immune response in SHR rats.
Neoplasms ; SST ; tumor growth ; Immune response ; Lymphoblast

OBJECTIVE: As for growth hormone(GH) secreting pituitary adenoma, it's remission should be declared on the basis of satisfactory controlling of the tumor, normalization of hormonal level, and symptomatic improvement of the patient. Several modalities of treatment have been applied and administered, and yet, this disease still remains as inveterate one to be fully treated. The purpose of this study is to evaluate the outcome of gamma knife radiosurgery(GKRS) for GH secreting pituitary adenoma, and to identify various factors affecting the outcome of the treatment. METHOD: A group of 24 out of 35 patients, treated by Leksell gamma knife unit during the period of March of 1992 through October of 1997, had been observed for more than two years. The mean target volume of microadenoma was 449.3mm3(range 216-880mm3), and that of macroadenoma was 3183.1mm3(range 1456-13125mm3). The tumor margin was covered with 50% isodose profile, and mean marginal dose was 25.2Gy(range 15-32.4Gy). The mean number of isocenter was 4.3(range 1-6). The exposed dose to the optic apparatus was less than 8Gy. The mean follow-up period was 37.8months(range 24-102months). RESULT: No patients showed any increase in the tumor volume during the follow-up period. And definite shrinkage of tumor volume(tumor volume reduction rate, TVRR: more than 50%) was obtained in 10 patients(41.7%). Twenty one patients(87.5%) had reduced hormonal level compared than pre-treatment level. Among them, normalization of the hormonal level was achieved in 12 patients(50%). Clinicoendocrinological remission was seen in 3 patients (12.5%). According to the results of statistical analysis, tumor volume(p=0.016),duration of symptoms(p=0.046), initial GH level(p=0.017), and the invasion of cavernous sinus(p=0.036) were significantly favorable to post-radiosurgical outcome. The TVRR was significantly related to post-radiosurgical reduction of serum GH level. Permanent complication was not seen. CONCLUSION: The authors concluded that GKRS is a safe and effective treatment modality for acromegaly. To otain the better outcome of GKRS in GH secreting pituitary adenoma, more careful and sophisticated treatment-planning is recommended.
Acromegaly ; Follow-Up Studies ; Growth Hormone ; Growth Hormone-Secreting Pituitary Adenoma ; Humans ; Pituitary Neoplasms* ; Radiosurgery* ; Treatment Outcome* ; Tumor Burden

Aspergillus fumigatus, a type of endophytic fungi from Erthrophleum fordii, was fermented with GPY culture medium. Fermented liquid and mycelium were extracted from fermented products after freezing and thawing treatment. After alcohol extraction, mycelium was extracted with ethyl acetate and n-butyl alcohol, respectively. According to the results of cytotoxity of tumor cells, ethyl acetate extracts were studied for their chemical constituents. Five diketopiperazine compounds were separated and purified with silica gel, MCI and Sephadex LH-20 column chromatography, reversed-phase chromatographic column and preparative HPLC, their structures were identified as cyclo- (R-Pro-R-Phe) (1), cyclo- (trans-4-OH-D-Pro-D-Phe) (2), cyclo- (R-Tyr-S-Ile) (3), cyclo-(R-Phe-S-Ile) (4), and cyclo-(R-Val-S-Tyr) (5) by using spectral methods.
Aspergillus fumigatus ; chemistry ; growth & development ; metabolism ; Cell Line, Tumor ; Diketopiperazines ; chemistry ; isolation & purification ; metabolism ; pharmacology ; Endophytes ; chemistry ; growth & development ; metabolism ; Fabaceae ; microbiology ; Humans ; Mycelium ; chemistry ; growth & development ; metabolism

OBJECTIVETo search for a new diagnostic biomarker for prostate cancer by comparing the differences in the expressions of netrin-1 and UNC5B in prostate cancer cells with different invasive abilities.

METHODSWe examined the expressions of netrin-1 and UNC5B in five prostate cancer cell lines DU145, 22RV1, PC3, PC3M and RWPE-1 using RT-PCR and Western blot, and positioned the ligands netrin-1 and its receptor UNC5B in the prostate cancer cells by immunofluorescence.

RESULTSBoth netrin-1 and UNC5B were expressed in the prostate cancer cells, and the expression of netrin-1 was significantly increased in highly invasive cells (P < 0.05), while that of UNC5B in RWPE-1 (normal) cells (P < 0.05).

CONCLUSIONThe expressions of netrin-1 and UNC5B are closely related to the infiltration and progression of prostate cancer, and expected to be as potential biomarkers for predicting the malignancy degree of prostate cancer.

Biomarkers, Tumor ; metabolism ; Cell Line, Tumor ; Humans ; Male ; Nerve Growth Factors ; metabolism ; Netrin-1 ; Prostatic Neoplasms ; metabolism ; pathology ; Receptors, Cell Surface ; metabolism ; Tumor Suppressor Proteins ; metabolism

OBJECTIVETo evaluate the mechanism of increased invasion and migration of hepatocellular carcinoma (HCC) cells induced by vascular endothelial growth factor receptor-1 (VEGFR-1) activation.

METHODSVascular endothelial growth factor-B (VEGF-B) was used to induce and stimulate hepatocellular carcinoma cell line MHCC97-H. Morphologic changes of MHCC97-H were investigated. The expression of E-cadherin and alpha-catenin (two epithelial markers) and Vimentin and N-cadherin (two mesenchymal markers) was detected by reverse transcriptase polymerase chain reaction (RT- PCR), western blotting, and immunofluorescence staining. Cell invasion and migration test was performed.

RESULTSTreatment of MHCC97-H cells with VEGF-B led to morphologic changes characteristic of epithelial to mesenchymal transition (EMT), including loss of polarity, increased intercellular separation, and the presence of pseudopodia. Expression of the epithelial adhesion molecules, including E-cadherin and alpha-catenin, was decreased after VEGF-B treatment. Conversely, an increase in the expression of the mesenchymal cell markers, including N-cadherin and vimentin, was observed after VEGF-B treatment (P less than 0.05). VEGF-B-treated cells exhibited a change in E-cadherin from an organized, membrane-bound structure to a disorganized state in which it was noted to be dispersed throughout the cytoplasm. Pretreatment with VEGFR-1 blocking antibody 18F1 inhibited the change in localization of E-cadherin induced by VEGF-B treatment. The ability of invasion and migration of MHCC97-H was enhanced by VEGF-B reatment (P less alpha 0.05).

CONCLUSIONIncreased invasion and migration of HCC cells induced by VEGFR-1 activation was mediated by epithelial to mesenchymal transition.

Carcinoma, Hepatocellular ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Humans ; Liver Neoplasms ; Vascular Endothelial Growth Factor A ; metabolism

PURPOSE: Recent studies have indicated that the p53 tumor suppressor gene and vascular endothelial growth factor (VEGF) play an important role in the angiogenic process of tumors. In this study, the correlation of the expressions of p53 and VEGF and the clinical features in gastric cancer were investigated. METHODS: The expressions of p53 and VEGF in gastric cancer were determined using immunohistochemistry on 98 randomly selected gastric cancer patients that had received curative resection. RESULTS: The expression of p53 and VEGF were observed in 51% and 50% of tumors, respectively. A significant correlation was found between p53 expression and the tumor histological type (P=0.045). The higher the TNM stage, the higher the observed level of p53 expression. The p53 and VEGF expression stati coincided in 70.4% of tumors, with a significant correlation found between the p53 and VEGF stati. Significantly worse survival rates were found in p53-positive and VEGF-positive patients than in those that were p53-negative and VEGF-negative. CONCLUSION: The present results indicated that p53 and VEGF expressions are useful in predicting the prognosis of patients with gastric cancer.
Genes, Tumor Suppressor ; Humans ; Immunohistochemistry ; Prognosis ; Stomach Neoplasms* ; Survival Rate ; Vascular Endothelial Growth Factor A*

OBJECTIVETo investigate the effect of transfection with human soluble vascular endothelial growth factor receptor-1(sFlt-1) gene on cell growth and vascular endothelial growth factor (VEGF) concentration of the culture supernatant in human colon cancer cell line Lovo.

METHODSThe recombinant plasmid pcDNA3-sFlt-1 containing sFlt-1 gene was transfected into Lovo cells by Lipofectamine 2000, which was identified by RT-PCR and ELISA. The effect of sFlt-1 protein on cell growth and VEGF expression in Lovo cells were investigated by MTT and ELISA.

RESULTSThe recombinant plasmid pcDNA3-sFlt-1 was successfully transfected into Lovo cells. The sFlt-1 expression was identified by RT-PCR and ELISA, which inhibited the growth of Lovo cells and reduced the VEGF concentration in the culture supernatant compared with control. The inhibitory rates of proliferation of Lovo cells via MTT assay after 2,14,21 and 28 days were(23.92+/-9.16)%, (13.98+/-10.21)%,(22.54+/-11.92)% and (33.43+/-9.34)% respectively. Compared with the control groups, the differences were significant (P<0.05, P<0.01).

CONCLUSIONTransfection with sFlt-1 gene into Lovo cells results in the expression of sFlt-1 protein, which possesses high biological activity and inhibits the growth of cancer cells.

Cell Line, Tumor ; Genetic Vectors ; Humans ; Transfection ; Vascular Endothelial Growth Factor Receptor-1 ; genetics ; metabolism

BACKGROUND: An ovarian surface epithelial tumor is a heterogenous disease, and various biological and molecular factors are important for its development and progression. Several findings support EGFR or c-erbB-2 as adverse prognostic indicators for an ovarian carcinoma. METHODS: We reviewed the histological and clinical findings of 52 carcinomas (17 endometrioid, 16 serous, 13 mucinous and 6 clear cell tumors), and 26 borderline (10 serous and 16 mucinous) tumors. Expression of c-erbB-2, EGFR, p53, and Ki-67 was evaluated on paraffinembedded tissue from a primary ovarian tumor by immunohistochemical methods. RESULTS: Expression of c-erbB-2 was found in 7.6% of tumors and expression of EGFR was found in 9.6% of tumors by immunohistochemical analysis. No significance was found between cerbB- 2 and EGFR expression as indicators of a poor prognosis. The expression of p53 and Ki-67 (>50%) correlated with the grade and type of tumor in the ovarian cancers. p53 and Ki- 67 overexpression (>50%) was absent in the borderline ovarian tumors, whereas ovarian carcinomas showed expression of both p53 and Ki-67. CONCLUSION: Expression of c-erbB- 2, EGFR, p53, and Ki-67 as determined by immunohistochemical analysis did not correlate with prognostic significance. However, p53 and Ki-67 expression may be used as markers to predict aggressive behavior, and to differentiate between malignant and borderline epithelial ovarian tumors. Further large-scale studies are required to clarify the significance of c-erbB-2 and EGFR expression in ovarian tumors.
Epidermal Growth Factor ; Female ; Ki-67 Antigen ; Mucins ; Ovarian Neoplasms ; Ovary* ; Prognosis ; Tumor Suppressor Protein p53

BACKGROUND/AIMS: A mutation occurs in p53, tumor suppressor gene, the cancer cells may lead to growing due to the inhibition in inducing apoptosis of cancer cells. It is known that CD34, the tumor precursor of hematopoietic cell, is associated with the major histocompatibility class II and affect the neovascularization and it is related with the growth and development of cancer. To investigated the correlation between prognosis of gallbladder cancer and p53 expression of the degree of mutation, CD34 expression and neovascularization. METHODS: Between March, 1991 and March, 2001, 53 cases of gallbladder cancer which had been confirmed histopathologically, were enrolled in this study and their clinico-athologic findings were anaylzed. We performed p53 and CD34 immunohistological staining and the analysis of Kaplan- Meier survival curve and log rank test. RESULTS: Among factors considered to determine the prognosis of gallbladder cancer, the presence of p53 overexpression and the degree of its mutation were not significantly correlated with patients survival rate. Also, there were no evidence that the CD34 expression and the degree of mutaion were significantly correlated with patients survival rate. The survival rate of patients with a gallbladder cancer is thought to be affected by the histologic classification, differentation and stage. CONCLUSION: In this study, p53 mutation and CD34 expression seem to be relatively correlated with progression of gallbladder cancer, but they are no evidence of correlation with survival rate. Therefore, we think p53 or CD34 can not be independent prognostic factor of gallbladder cancer.
Apoptosis ; Classification ; Gallbladder Neoplasms* ; Gallbladder* ; Genes, Tumor Suppressor ; Growth and Development ; Histocompatibility ; Humans ; Prognosis* ; Survival Rate

PURPOSE: Neovascularization has been shown to be essential for the growth of solid tumors. Vascular endothelial growth factor (VEGF) is one of the most important mediators of angiogenesis, and recent studies have demonstrated that the p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis. We examined the expression of VEGF and p53 as a function of microvessel density to evaluate its clinical significance in colorectal cancer and to investigate the correlation of VEGF and p53. METHODS: The study material included 20 patients who survived more than 5 years postoperatively without distant metastasis (non-metastasis group) and 21 patients who had synchronous (10 patients) and metachronous (11 patients) metastasis (metastasis group). Immunohistochemical staining for VEGF, p53 protein and factor VIII-related antigen was done. RESULTS: The expression rate of VEGF was 20% in non-metastatic tumors and 71% in metastatic tumors (p<0.05). The VEGF expression was not correlated with microvessel density. Otherwise, the microvessel density were 32.9 9.1 in non-metastatic tumors and 40.1 12.0 in metastatic tumors (p<0.05). VEGF expression was correlated with p53 over expression. CONCLUSION: VEGF expression might be a useful prognostic factor for metastasis in colorectal cancer. Also, our findings suggest the presence of a p53-VEGF pathway in colorectal cancer.
Colorectal Neoplasms* ; Genes, Tumor Suppressor ; Humans ; Microvessels ; Neoplasm Metastasis ; Vascular Endothelial Growth Factor A* ; von Willebrand Factor