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

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

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: PTEN is a novel tumor suppressor gene located at chromosome 10q23.3. Loss of PTEN function has been implicated in the progression of several types of cancer. Angiogenesis is a critical factor in tumor growth and metastasis. We investigated PTEN expression in invasive breast cancers and described its role in the regulation of angiogenesis related to vascular endothelial growth factor (VEGF). METHODS: Forty-five, surgically resected, formalin-fixed and paraffin embedded breast cancer tissue samples were analyzed for PTEN and VEGF expressions by immunohistochemistry and for microvessel density (MVD) by CD34 immunostaining. RESULTS: Loss of PTEN expression was found in 35.6% (16/45) of the breast cancer tissues, all of which showed positive VEGF expression. Among 29 cases with normal PTEN expression, 15 (51.7%) were VEGF positive. MVD was significantly higher in tumors with a loss of PTEN expression than in those with normal PTEN expression. CONCLUSION: A loss of PTEN expression might increase the VEGF-related angiogenesis in breast cancer. There was no correlation between PTEN expression and clinicopathologic parameters. Detection of the loss of PTEN expression may serve as a useful biologic marker for progression in invasive breast cancer.
Biomarkers ; Breast Neoplasms* ; Breast* ; Genes, Tumor Suppressor* ; Immunohistochemistry ; Microvessels ; Neoplasm Metastasis ; Paraffin ; Vascular Endothelial Growth Factor A

PURPOSE: Phyllodes tumors (PTs) of the breast have been classified as benign, borderline, or malignant based on their histopathologic features. However, predicting clinical behavior based on these features has proven to be difficult given that local recurrence occurs in both benign and malignant PTs. Recurrence has been shown to mirror the histologic pattern of the primary tumor or to show dedifferentiation. The aim of this study was to assess the value of the histopathologic parameters, expression or mutation of c-Kit and platelet derived growth factor receptor alpha (PDGFRA) in predicting tumor recurrence. METHODS: Representative areas from 39 benign, 16 borderline, and 12 malignant PTs were selected for construction of tissue microarrays. Immunohistochemical analyses for p53, Ki-67, c-Kit, and PDGFRA were performed and SSCP-PCR analysis was carried out to identify mutations in exons 9, 11, 13, and 17 of the c-Kit gene and exons 12 and 18 of the PDGFRA gene. Clinicopathologic features, including tumor recurrence and margin status, were also evaluated. RESULTS: Of the 67 PTs, 11 cases (16.4%) recurred from 3 to 92 months following initial diagnosis (4 benign, 2 borderline, and 5 malignant). One benign PT case recurred as a borderline tumor and two borderline PT cases recurred as malignancies. Three patients died of malignant PT. No mutations of the c-Kit or PDGFRA genes were found and there was no statistically significant association of either p53 or p16 immunostaining with recurrent disease (p>0.05). However, histologic grade (p=0.033), margin status (p<0.001), Ki-67 (p=0.012), c-Kit (p=0.002), and PDGFRA (p=0.007) stromal immunopositivity were significantly correlated with recurrence. CONCLUSION: Even though positive or close margins were significantly associated with tumor recurrence, stromal c-Kit, PDGFRA positivity, and the Ki-67 index were useful for predicting recurrent PTs. Despite this, no c-Kit or PDGFRA mutations were found.
Breast ; Exons ; Humans ; Phyllodes Tumor ; Proto-Oncogene Proteins c-kit ; Receptors, Platelet-Derived Growth Factor ; Recurrence

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*

To analyze a wide variety of polymorphisms in patients with endometriosis is important since this disease has a strong genetic component. Until now, more than 30 Korean studies have been performed in order to elucidate the possible role of specific polymorphisms in the susceptibility to endometriosis. The most meaningful polymorphisms in Korean patients with endometriosis came from studies investigating GSTM1, AhRR, ER-alpha, VEGF, AHSG, and TNF-alpha. However, following studies should be made to confirm the consistency of the data to have some implications in the prediction of endometriosis. In this review, we also present the future direction of the association studies in complex trait disease such as endometriosis.
Endometriosis ; Female ; Humans ; Polymorphism, Genetic ; Porphyrins ; Tumor Necrosis Factor-alpha ; Vascular Endothelial Growth Factor A