The study was designed to compare the anti-carcinogenic effect of conjugated linoleic acid (CLA) isomers on colon carcinogenesis in 1,2-dimethylhydrazine (DMH)-treated rats by determining the levels of apoptosis, cell proliferation, eicosanoids and 1,2-diacylglycerol (DAG) in colonic mucosa. Sixty male Sprague Dawley rats were randomly divided into 3 groups depending on the types of CLA isomers, i.e. BT group (no CLA contained), CLA-C group (cis-9, trans11 isomer contained), and CLA- T group (trans-10, cis-12 isomer contained). The experimental diet was composed of protein at 20%, carbohydrate at 56.2%, and fat at 14.5% including 0.8% CLA isomers by weight. The experimental diet was fed for 14 weeks with the initiation of intramuscular injection of DMH, which was injected twice a week for 6 weeks to give total dose of l80mg per kg body weight. Two CLA isomers (c9t11 and t10c12) significantly increased the relative percentage of apoptosis but reduced cell proliferation in mucosal cell and also the levels of PGE2, TXB2, and DAG in colonic mucosa. However, there was no significant differences in anti-carcinogenic effect between c9t11 isomer and t10c12 isomer. Overall, colon carcinogenesis could be significantly inhibited by CLA isomers by increasing apoptosis and reducing cell proliferation, the levels of eicosanoids and DAG in colonic mucosa.
1,2-Dimethylhydrazine ; Animals ; Anticarcinogenic Agents ; Apoptosis* ; Body Weight ; Carcinogenesis ; Cell Proliferation* ; Colon* ; Colonic Neoplasms ; Diet ; Dimenhydrinate ; Dinoprostone ; Eicosanoids ; Humans ; Injections, Intramuscular ; Linoleic Acid ; Male ; Mucous Membrane* ; Rats* ; Rats, Sprague-Dawley

PURPOSE: We investigated the clinical characteristics of breast cancers and its significance. MATERIAL AND METHOD: We evaluated the clinical characteristics of 500 women with breast cancer who were diagnosed and treated by one surgeon between March 1991 and August 1996. RESULTS: The median age was 46.7 years and the most common age group was 40's. The presenting symptoms for most patients were palpable mass (75.2%) followed by abnormal mammographic findings (8.4%), pain (6.3%) and nipple discharges (4.7%), and the duration of symptoms was less than 1 month in 41.4%. Fifty three percent of the 500 cases had T2 lesion (size; 2 to 5 cm). With the increase of tumor size, overall and disease free survival rates (OS, DFS) were decreased. Surgical treatment consisted of modified radical mastectomy (52.8%) and partial mastectomy (33.6%) The most common stage was II (42.3%) and the early breast cancer (stage 0, I, II) was 388cases (78.1%) and the stage were inversely correlated with DFS and OS. The positivity of axillary lymph node was 39.3% and the number of the metastatic lymph nodes was inversely correlated with DFS and OS. The pathologic types were infiltrating ductal carcinoma (83.0%), ductal carcinoma in situ (12.8%), infiltrating lobular carcinoma (1.2%), lobular carcinoma in situ (0.4%) and Paget's disease (2.0%). ER positivity was 48.9% and PR 46.9%. ER positive patients showed survival benefit compared to ER negative patients. The common sites of distant metastases were lung, bone and liver. CONCLUSIONS: Our patients with breast cancer were younger than those of western and showed the impacts on survival according to the lymph node status,tumor size.
Breast Neoplasms* ; Breast* ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Carcinoma, Lobular ; Disease-Free Survival ; Female ; Humans ; Liver ; Lung ; Lymph Nodes ; Mastectomy, Modified Radical ; Mastectomy, Segmental ; Neoplasm Metastasis ; Nipples ; Survival Rate

We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression of angiogenic factors and CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2 mRNAs were not statistically different between DCIS and invasive ductal carcinomas, nor did they differ statistically when grouped by tumor size, histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel density and expression of VEGF and TGF-beta were not statistically different between DCIS and invasive ductal carcinoma. CD44std expression was significantly increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was also significantly increased in lower clinical stage, histologic grade and nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis was significantly correlated with MT1-MMP mRNA, VEGF and TGF-beta expression (p < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2 mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive ductal carcinoma suggest that the invasive potential of breast carcinoma is already achieved before morphologically overt invasive growth is observed. As MT1-MMP mRNA expression is significantly correlated with axillary nodal metastasis, it may be useful as a prognostic indicator of invasive ductal carcinoma. Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer.
Tissue Inhibitor of Metalloproteinase-2/genetics ; RNA, Messenger/metabolism ; Matrix Metalloproteinases, Membrane-Associated ; Matrix Metalloproteinases/*genetics ; Matrix Metalloproteinase 9/genetics ; Matrix Metalloproteinase 2/genetics ; Matrix Metalloproteinase 1/genetics ; Humans ; Gene Expression Regulation, Neoplastic ; Gene Expression Regulation, Enzymologic ; Female ; Carcinoma, Ductal, Breast/genetics/*physiopathology ; Carcinoma in Situ/genetics/*physiopathology ; Breast Neoplasms/genetics/*physiopathology

We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression of angiogenic factors and CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2 mRNAs were not statistically different between DCIS and invasive ductal carcinomas, nor did they differ statistically when grouped by tumor size, histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel density and expression of VEGF and TGF-beta were not statistically different between DCIS and invasive ductal carcinoma. CD44std expression was significantly increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was also significantly increased in lower clinical stage, histologic grade and nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis was significantly correlated with MT1-MMP mRNA, VEGF and TGF-beta expression (p < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2 mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive ductal carcinoma suggest that the invasive potential of breast carcinoma is already achieved before morphologically overt invasive growth is observed. As MT1-MMP mRNA expression is significantly correlated with axillary nodal metastasis, it may be useful as a prognostic indicator of invasive ductal carcinoma. Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer.
Tissue Inhibitor of Metalloproteinase-2/genetics ; RNA, Messenger/metabolism ; Matrix Metalloproteinases, Membrane-Associated ; Matrix Metalloproteinases/*genetics ; Matrix Metalloproteinase 9/genetics ; Matrix Metalloproteinase 2/genetics ; Matrix Metalloproteinase 1/genetics ; Humans ; Gene Expression Regulation, Neoplastic ; Gene Expression Regulation, Enzymologic ; Female ; Carcinoma, Ductal, Breast/genetics/*physiopathology ; Carcinoma in Situ/genetics/*physiopathology ; Breast Neoplasms/genetics/*physiopathology

PURPOSE: Epidemiological and laboratory studies suggest that nonsteroidal antiinflammatory drugs (NSAIDs) reduce the risk of colon cancer and that the inhibition of colon cancer is mediated through modulation of eicosanoid production. The present study examined the effect of cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors on colon cancer cell growth and prostaglandin E(2) (PGE(2)) or leukotriene B(4) (LTB(4)) secretion by these cells. MATERIALS AND METHODS: The human colon adenocarcinoma cell lines, Caco-2 and HT-29 cells, were cultured in serum-free medium with various concentrations of indomethacin, piroxicam or esculetin in the presence of 0.15nM or 10nM linoleic acid. Cell number was estimated by MTT assay and PGE(2) and LTB(4) were analyzed by enzyme immunoassay. RESULTS: The NSAIDs inhibited cell proliferation in a concentration-dependent manner. However, the potency and efficacy of each drug varied in the two cell lines. In Caco-2 cells, the effect of esculetin was higher than that of indomethacin, and piroxicam had no effect. In HT-29 cells, only indomethacin significantly inhibited cell proliferation. All three agents inhibited PGE(2) secretion in a dose-dependent manner; the effect of indomethacin was highest and that of esculetin lowest. The secretion of LTB4 was increased by indomethacin and piroxicam but decreased by esculetin. The effects of these drugs on cell proliferation and eicosanoid secretion were not influenced by linoleic acid concentrations in the culture media. Neither exogenous PGE2 nor LTB4 affected cell proliferation. The results of Pearson correlation analyses revealed that changes in cell proliferation were somewhat related to both concentrations of NSAIDs in the culture medium and production of PGE(2) and LTB(4). CONCLUSION: The present data suggests that the anti-proliferative effect of NSAIDs may not be entirely attributed to changes in the production of PGE2 and/or LTB4 in the two colon cancer cell lines. These NSAIDs may inhibit cell proliferation largely independent of their ability to modulate eicosanoid synthesis.
Adenocarcinoma ; Anti-Inflammatory Agents, Non-Steroidal ; Caco-2 Cells ; Cell Count ; Cell Line ; Cell Proliferation ; Colon* ; Colonic Neoplasms* ; Culture Media ; Dinoprostone ; Eicosanoids* ; HT29 Cells ; Humans ; Immunoenzyme Techniques ; Indomethacin ; Leukotriene B4 ; Linoleic Acid ; Lipoxygenase Inhibitors* ; Lipoxygenase* ; Piroxicam ; Prostaglandin-Endoperoxide Synthases*

PURPOSE: The natural history of patients with ductal carcinoma in situ (DCIS) with microinvasion is poorly defined, and the clinical management of these patients, with particular reference to management of the axilla, has been controversial. Previous studies of this lesion have used arbitrary criteria for the evaluation of microinvasion. METHODS: In order to compare the clinicopathologic features and treatment outcomes between DCIS and DCIS with microinvasion, the medical records of 101 patients of DCIS with or without microinvasion who had been treated at Yongdong Severance hospital from April 1991, to October 1998, were reviewed retrospectively. RESULTS: The mean age of the DCIS with microinvasion group was 44.8 years-old and that of the DCIS group was 47.4 years-old. The peak age group within both study groups was the 5th decade. The primary tumors of the DCIS-MI group were larger (2.16 vs 1.93 cm) and more easily palpated (66.3% vs 36.6%) upon the physical examination than that of the DCIS group. The rate of axillary lymph node metastasis was higher in the DCIS-MI group (10% vs 1.3%). In terms of nuclear grade, comedo type, hormone receptor status, and c-erbB2 immunohistochemical positivity, there were no statistically significant differences between the DCIS and DCIS-MI groups. The recurrence rate within the DCIS-MI group was higher than that of DCIS group (10% vs 1.4%). The 5-year disease free survival rate of the DCIS and DCIS-MI groups were 98% and 89% respectively. CONCLUSION: Ductal carcinoma in situ with microinvasion is thought to be a transitional disease entity between ductal carcinoma in situ and invasive ductal carcinoma. However, the treatment options for ductal carcinoma in situ with microinvasion have been similar to that of the invasive carcinoma. More long-term follow-up and a multicenter study seem to be necessary to identify differences in the clinical features and to determine the optimal methods of treatment.
Axilla ; Breast Neoplasms ; Carcinoma, Ductal* ; Carcinoma, Intraductal, Noninfiltrating* ; Disease-Free Survival ; Humans ; Lymph Nodes ; Medical Records ; Natural History ; Neoplasm Metastasis ; Physical Examination ; Recurrence ; Retrospective Studies

BACKGROUND: The natural history of the patients of ductal carcinoma in situ(DCIS) with microinvasion is poorly defined, and the clinical management of these patients, with particular reference to management of the axilla, has been controversial. Previous studies of this lesion have used and/or arbitrary criteria for the evaluation of microinvasion. METHODS: To compare the clinicopathologic features and the outcomes of treatment between DCIS and DCIS with microinvasion, the medical records of 101 patients of DCIS with/without microinvasion who had been treated at Yongdong Severance hospital from Apr. 1991, to Oct 1998, were reviewed retrospectively. RESULTS: The mean age of the patients of DCIS with microinvasion group was 44.8 years and that of the patients of DCIS group was 47.4 years. The peak age group of both was 5th decade. The primary tumors of DCIS-MI group were larger(2.16 vs 1.93cm) and more easily palpated(66.3% vs 36.6%) on the physical examination than that of DCIS group. The rate of the axillary lymph node metastasis was higher in DCIS-MI group.(10% vs 1.3%) In terms of nuclear grade, comedo type, hormone receptor status, and c-erbB2 immunohistochemical positivity, there were no statistical significances between DCIS group and DCIS-MI group. The recurrence rate of DCIS-MI group was higher than that of DCIS group.(10% vs 1.4%) The 5-year disease free survival rate of the DCIS group and DCIS-MI group were 98% and 89% respectively. CONCLUSIONS: Ductal carcinoma in situ with microinvasion is thought to be transitional disease entity between ductal carcinoma in situ and invasive ductal carcinoma. But the treatment options of ductal carcinoma in situ with microinvasion were similar to that of the invasive carcinoma. More long-term follow-up and multicenter studies seem to be necessary to identify differences in clinical features and to determine the optimal methods of treatment.
Axilla ; Breast Neoplasms ; Carcinoma, Ductal* ; Carcinoma, Intraductal, Noninfiltrating* ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Lymph Nodes ; Medical Records ; Natural History ; Neoplasm Metastasis ; Physical Examination ; Recurrence ; Retrospective Studies

PURPOSE: Although an axillary lymph node dissection (ALND) has been considered as an ultimate procedure for axilla in the breast carcinoma, complications after ALND and conceptual revolution for the role of axillary nodes have made it necessary to look for an alternative. Recent studies of sentinel lymphadenectomy (SLND) have shown that SLND accurately predict axillary nodal status. However, for a satisfying outcome in SLND, a learning period would be required, as other surgical procedures do. In this study, the necessity of the learning period for SLND were examined. METHODS: From Nov. 1998 to Dec. 2001, 178 patients with invasive breast carcinoma were treated with SLND simultaneously followed by ALND. The period for the first 54 patients, Nov. 1998 to May. 1999, was set as a 'learning period'. Differences of the detection rate and the false negative rate for the 'learning period' and 'after the learning period' were compared. Also changes in the detection rate and the false negative rate with the accumulated experiences for SLND were evaluated. RESULTS: The sentinel lymph nodes were not identified in 5 patients through the whole period. Three of them occurred in the 'learning period' (5.6%, 3/54) and the rest occurred 'after the learning period' (1.6%, 2/124)(P=0.04). The false negative rate was 16.7% (4/24) in the 'learning period' and 0.0% in 'after the learning period' (P=0.00). The detection rate and the false negative rate improved with the accumulation of experiences for SLND. CONCLUSION: It is certain that 'learning period' for SLND is crucial. During this period, the improvement and stabilization of this skill is achieved.
Axilla ; Breast Neoplasms* ; Breast* ; Humans ; Learning* ; Lymph Node Excision* ; Lymph Nodes

PURPOSE: The status of the axillary nodes in breast carcinoma patients is one of the most significant prognostic factors. Although many trials in order to gain information concerning axillary status, to date there is no satisfactory procedures other than axillary lymph node dissection (ALND) which has many complications. Recently sentinel lymphadenectomy has become accepted as an alternative to ALND. METHODS: Sentinel lymphadenectomy followed by ALND was performed in 157 patients with invasive breast carcinoma between Nov. 1998 and Dec. 2000. The period from Nov. 1998 to May. 1999, which included the first 54 patients was set as a learning period. 99m Tc antimony trisulfide colloid was used in the detection of the sentinel node, with a gamma camera preoperatively and then a gamma probe in the operating room. The dissected sentinel nodes were examined by both frozen section and serial section (SS) with immunohistochemical stains (IHC). RESULTS: The detection rate was 96.8%. The false negative rate was 22.6% for the frozen sections and 4.8% for the permanent sections. The detection rate and the false negative rate had improved after the learning period with statistic significance (P-value<0.05). The false negative rate for tumors less than 2 cm was significantly lower than that for tumors greater than 2 cm (P-value=0.000). CONCLUSION: Sentinel lymphadenectomy using 99m Tc anti-nomy trisulfide colloid showed high detection rate and low false negative rate. The learning period is thought to be necessary for its clinical application. In the future, sentinel lymphadenectomy may replace axillary lymph node dissection in certain subgroups of breast carcinoma patients.
Antimony ; Breast Neoplasms* ; Breast* ; Colloids ; Coloring Agents ; Frozen Sections ; Gamma Cameras ; Humans ; Learning ; Lymph Node Excision* ; Operating Rooms

PURPOSE: The status of the axillary nodes in breast carcinoma patients is one of the most significant prognostic factors. Although many trials in order to gain information concerning axillary status, to date there is no satisfactory procedures other than axillary lymph node dissection (ALND) which has many complications. Recently sentinel lymphadenectomy has become accepted as an alternative to ALND. METHODS: Sentinel lymphadenectomy followed by ALND was performed in 157 patients with invasive breast carcinoma between Nov. 1998 and Dec. 2000. The period from Nov. 1998 to May. 1999, which included the first 54 patients was set as a learning period. 99m Tc antimony trisulfide colloid was used in the detection of the sentinel node, with a gamma camera preoperatively and then a gamma probe in the operating room. The dissected sentinel nodes were examined by both frozen section and serial section (SS) with immunohistochemical stains (IHC). RESULTS: The detection rate was 96.8%. The false negative rate was 22.6% for the frozen sections and 4.8% for the permanent sections. The detection rate and the false negative rate had improved after the learning period with statistic significance (P-value<.05). The false negative rate for tumors less than 2 cm was significantly lower than that for tumors greater than 2 cm (P-value=0.000). CONCLUSION: Sentinel lymphadenectomy using 99m Tc antinomy trisulfide colloid showed high detection rate and low false negative rate. The learning period is thought to be necessary for its clinical application. In the future, sentinel lymphadenectomy may replace axillary lymph node dissection in certain subgroups of breast carcinoma patients.
Antimony ; Breast Neoplasms* ; Breast* ; Colloids ; Coloring Agents ; Frozen Sections ; Gamma Cameras ; Humans ; Learning ; Lymph Node Excision* ; Operating Rooms