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

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

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

BACKGROUND: Release of Epidermal Growth Factor(EGF) af fects the growth of the lung cancer in various ways and tumor necrosis factor-alpha (TNF-alpha), which is known as acute immune reactants and now used in lung cancer t reatment, supress carcinogenesis of the lung. In this study, expression rates of EGF and TNF-alpha in the lung cancer tissue and the serum of lung cancer patients were measured. MATERIAL AND METHOD: In twenty cases of lung cancer and four cases of benign tumor or granuloma, all patient's peripheral blood was sampled pre, and postopertively, and tumor tissues and tumo r free lung tissues were obtained from resected surgical specimens in all patien ts. Then, all blood samples and tissues were frozen and kept safely in the liqui d nitrogen tank. Human EGF kit(Amersham pharmacia biotech, England) and TNF-alpha I RMA kit (Biosouce, Belgium) were used in quantitation of EGF and TNF-alpha respecti vely. RESULT: 1. Both EGF and TNF-alpha were expressed in all tissues and control tissue, benign tumor or granuloma tis sue, cancer tissue and pre- and postoperatively sampled serum. 2. The amount of EGF and TNF-alpha were significantly higher in cancer tissue than in control and be nign tumor tissues. 3. The expression of TNF-alpha was more potent in adenocarcinom a tissue. 4. The expressed amounts of serum EGF and TNF-alpha were 5.7 times and 1. 3 times higher than in tissue respectively. 5. The expression rates of TNF-alpha in cancer tissue was different according to histologic types of cancer but not dif ferent for EGF. 6. As TNM stages go up the amount of EGF in cancer tissue increa sed but TNF-alpha ecreased. 7. The amount of EGF in serum was increased at immediat e postoprative period but TNF-alpha was decreased. CONCLUSION: The presence of di fference in the expressed amount of EGF and TNF-alpha between cancer tissue and con trol tissue was proven, also the difference was found between tissue and serum r epresenting the concentration of EGF and TNF-alpha which were higher in serum than in tissues. EGF and TNF-alpha are released in all of normal tissue, benign tumor ti ssue and lung cancer tissue and their expression rates were variable according t o cell function. Further research is needed to for the expression of EGF and TN F-alpha in various kinds of cells.
Carcinogenesis ; Epidermal Growth Factor* ; Granuloma ; Humans ; Lung Neoplasms* ; Lung* ; Nitrogen ; Tumor Necrosis Factor-alpha*

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*

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