Oxaliplatin-induced Peripheral Neuropathy, Symptoms, Distress and Quality of Life among Korean Patients with Gastrointestinal Cancer

PURPOSE: This study was conducted to identify the level of oxaliplatin-induced peripheral neuropathy (OIPN), symptoms, distress, and quality of life (QoL) in gastrointestinal (GI) cancer patients and to identify the factors influencing QoL.METHODS: A total of 123 patients were recruited for this cross-sectional study. Surveys used were the Therapy-Induced Neuropathy Assessment Scale (TNAS) for OIPN, the MD Anderson Symptom Inventory (MDASI-GI) for general symptoms associated with gastrointestinal cancer and its treatment, a distress thermometer, and the Euro Quality of Life Questionnaire 5-Dimensional Classification (EQ-5D) for QoL.RESULTS: The patients were classified into three groups based on their treatment completion time (current, completed less than one year ago, completed more than one year ago). The scores of MDASI-GI and distress were significantly lower in patients who had completed chemotherapy compared to those who were undergoing treatment (p=.04 and .02 respectively). However, TNAS score was significantly higher in patients who completed chemotherapy less than one year ago than the other two groups (p=.001). In multivariate regression models, the OIPN and distress or general symptoms were identified as factors associated with QoL.CONCLUSION: In this study, we identified the symptoms that are factors related to the QoL in patients with GI cancer. In particular, the symptoms of OIPN are reported at significantly increased levels for patients who have finished chemotherapy less than one year ago, so efforts to prevent and manage the symptoms of OIPN are needed in this timeframe. To improve QoL of patients with GI cancer, continuous attention and care are required not only during the treatment of cancer but also after the completion of treatment.

The Effects of Tibolone in Breast Cancer Cell Lines: The Role of Tibolone in Phospholipase D Signal Transduction Pathway / 한국유방암학회지

PURPOSE: Tibolone is a tissue specific steroid hormone newly recognized as an estrogenic agent for hormone replacement therapy (HRT). The aim of the study is to characterize the basic mechanism of tibolone in the PLD signal transduction pathway of breast cancer cell lines. METHODS: The levels of phospholipase D (PLD), caspase 3 mRNA and protein, and the cell counts were measured in estrogen receptor positive MCF-7 and negative MDA-MB-231 cell lines treated with estradiol, tamoxifen and tibolone and three metabolite forms of tibolone (3 beta-OH-tibolone, delta4 isomer, 3 alpha-OH-tibolone). Multimodality methods such as RT-PCR, immunoblot analysis and in vivo enzyme activity assay were used. RESULTS: The addition of estradiol to MCF-7 cell line resulted in cell proliferation in a time-dependent manner while that of tamoxifen and tibolone showed antiproliferative effects. The addition of tamoxifen or tibolone to MCF-7 and MDA- MB-231 cell lines resulted in the elevation of caspase 3 mRNA levels, indicating the induction of apoptosis. PLD mRNA level was elevated in both cell lines treated with tamoxifen, but decreased in those treated with the various tibolones, except for 3 beta- OH-tibolone. In immunoblot analysis, while MCF-7 cell line treated with tamoxifen showed an increased level of PLD expression, in MDA-MB-231 cell line the expression was decreased. Similar results were observed in the addition of tibolones, which resulted in an increase of PLD expression level in MCF-7 cell line and a decrease in MDA-MB-231 cell line. In vitro PLD activity assay showed decreased activity after estradiol treatment and increased activity after tamoxifen and tibolone treatment in MDA-MB231 cell line. In MCF-7 cell line, among the tibolones only delta4 isomer increased PLD activity. Tiboloneshowed antiproliferative and apoptosis-inducing effects on MCF-7 and MDA-MB-231 cell lines. But its influence on the signal transduction pathway varied slightly between the two cell lines. CONCLUSION: we were able to find the antiestrogenic properties of the estrogenic agent tibolone.

Protective Role of Prx(Peroxiredoxin) I and II against H2O2-Induced Apoptosis of MCF7 Cell Lines / 한국유방암학회지

PURPOSE: Apoptosis is known to be induced either by direct oxidative damage from oxygen free radicals or hydrogen peroxide, or from their generation in cells by injurious agents. Peroxiredoxin plays an important role in eliminating peroxides generated during metabolism. The aim of this study is to elucidate the role of Prx (peroxiredoxin) enzymes during the cellular response to oxidative stress. METHODS: The presence of Prx isoforms was demonstrated by immunoblot analysis using Prx isoforms-specific antibodies, and RT-PCR using Prx isozyme coding sequences. Annexin V-FITO apoptosis detection method was used to measure the cell death following exposure to H2O2. RESULTS: Treatment of MCF7 cell lines with H2O2 resulted in the dose-dependent expression of Prx I and II. Observed decreases in the mRNA expressions of Prx I and II, analyzed by RT-PCR, correlated well with the results of immunoblot analysis. The treatment of normal breast cell line, MCF10A, with H2O2 resulted in rapid cell death, while the breast cancer cell line, MCF7, was resistant. In addition, we confirmed that Prx I and II transfected MCF10A cells were more prone to cell death than MCF10A transfected with vector alone, after H2O2 treatment. CONCLUSION: These findings suggest that Prx I and II have an important function as inhibitors of cell death during the cellular response to oxidative stress.

Gene Expression Profiles of Primary Breast Cancer Tissue Using cDNA Microarray / 한국유방암학회지

PURPOSE: Breast cancer is characterized by an extensive heterogeneity that complicates the precise assessment of tumor aggressiveness and makes therapeutic decisions difficult. Variation in transcriptional programs accounts for much of the biological diversity of the tumors. We tried to investigate the gene expression profile of Korean breast cancer with cDNA microarray technique. METHODS: We have characterized variation in gene expression patterns in 7 tissue samples of infiltrating ductal carcinoma from different individuals and 1 tissue sample of malignant phyllodes tumor using cDNA microarray representing 7,500 human genes. Breast cancer cell line, MCF7 and T lymphoblastoid cell line, CCRF-CEM were also included in this study. RNA xtracted from normal breast tissue of 3 non-cancer individuals were pooled and used as a control sample. We analyzed the data with Cluster and TreeView program. RESULTS: Tissues from infiltrating ductal carcinoma and tissue from phyllodes tumor and 2 celllines are clearly differ entiated by hierarchical clustering as their pathologic features and showed characteristic genetic expression. Some inter esting clusters were found. They were 'stromal cluster','immune cluster', 'proliferation and transcription cluster', and a cluster including FOS and JUNB gene. Phylldes tumor showed distinctive genetic expression pattern compared with ductal carcinoma tissues. Two patients whose c-erbB2 protein had been measured as highest level in immuno histochemistry showed overexpression of ERBB2 gene. GRB7, MLN51, and PPARBP in 17q21 that are known to coexpress with ERBB2 also showed overexpression in these patients. CONCLUSION: We found some interesting clusters and confirmed the feasibility of cDNA microarray in the study of breast cancer. This preliminary study will help the further research of DNA microarray with lager sample size.

The Pattern of Expression of Phospholipase C-gamma in Benign and Malignant Tumors of the Breast

PURPOSE: The activation of phospholipase C (PLC) is one of the early events in various growth processes, including malignant transformation. Among PLC-isozymes, PLC-gamma is activated through direct interaction with growth factor receptor tyrosine kinase. In this study, we evaluated the patterns of PLC-gamma expression in benign and malignant tumors of the breast and compared the patterns with their normal counterpart. METHODS: Using immunoblot assay, we evaluated the patterns of expression in PLC-gamma in 20 breast cancer tissues, 13 fibroadenoma tissues, and normal tissues. The level of expression was analyzed by densitometry. RESULTS: All of 20 breast cancer tissues and 13 fibroadenoma tissues showed overexpression of PLC-gamma when compared with their normal counterparts. The level of the PLC-gamma expression was 3.9-fold and 17.3-fold higher in fibroadenomas and breastcancers, respectively, than in normal tissues. CONCLUSION: The result suggested that the level of PLC-gamma expression increases as the normal tissue undergoes progression to fibroadenoma, and finally to carcinoma. The pattern of expression of PLC-gamma in breast tissue implies that the PLC-gamma-mediated signal transduction may play a significant role in the progression of breast cancer from normal tissue.

Detection of Breast Cancer Micrometastases in Sentinel Lymph Nodes / 한국유방암학회지

PURPOSE: Axillary lymph node status is a powerful prognostic factor in breast carcinomas. However, patients without axillary lymph node metastases are not completely devoid of risk for relapse. Also, the axillary lymph node micrometastases significantly contribute to the selection of high-risk patients. Recently, sentinel lymph node (SLN) biopsy has been proposed as a potential alternative to full axillary lymph node dissection for staging breast carcinomas. To validate this hypothesis, we evaluated the distribution of occult metastases in sentinel and nonsentinel lymph nodes. METHODS: Twenty patients who had breast carcinomas and who underwent a SLN biopsy followed by an axillary lymph node dissection during March and July 2000 at Seoul National University Hospital were evaluated. Thirty SLNs devoid of metastasis, as determined by hematoxylin and eosin (H&E) staining, were evaluated for micrometastases by pan- cytokeratin immunohistochemistry (IHC) and reverse transcriptase polymerase chain reaction (RT-PCR) using Keratin 19 mRNA and MUC1 mRNA. Nonsentinel lymph nodes (NSLN) were also evaluated by pan-cytokeratin IHC. RESULTS: One out of the 30 SLNs (3.3%) had occult metastases which were identified by IHC and 4 out of the 30 SLNs (13.3%) had occult metastases which were identified by RT-PCR. NSLNs devoid of metastases by H&E staining proved to be free of micrometastases by IHC. CONCLUSION: IHC and RT-PCR are more sensitive methods for detecting micrometastases than conventional H&E stain-ing alone. If an SLN is tumor free by IHC or RT-PCR, we can assume that the remaining lymph nodes in the axilla are also tumor free, consequently, an SLN biopsy can bea substitute for axillary lymph node dissection.

Detection of Breast Cancer Micrometastases in Sentinel Lymph Nodes

PURPOSE: Axillary lymph node status is a powerful prognostic factor in breast carcinomas. However, patients without axillary lymph node metastases are not completely devoid of risk for relapse. Also, the axillary lymph node micrometastases significantly contribute to the selection of high-risk patients. Recently, sentinel lymph node (SLN) biopsy has been proposed as a potential alternative to full axillary lymph node dissection for staging breast carcinomas. To validate this hypothesis, we evaluated the distribution of occult metastases in sentinel and nonsentinel lymph nodes. METHODS: Twenty patients who had breast carcinomas and who underwent a SLN biopsy followed by an axillary lymph node dissection during March and July 2000 at Seoul National University Hospital were evaluated. Thirty SLNs devoid of metastasis, as determined by hematoxylin and eosin (H&E) staining, were evaluated for micrometastases by pan- cytokeratin immunohistochemistry (IHC) and reverse transcriptase polymerase chain reaction (RT-PCR) using Keratin 19 mRNA and MUC1 mRNA. Nonsentinel lymph nodes (NSLN) were also evaluated by pan-cytokeratin IHC. RESULTS: One out of the 30 SLNs (3.3%) had occult metastases which were identified by IHC and 4 out of the 30 SLNs (13.3%) had occult metastases which were identified by RT-PCR. NSLNs devoid of metastases by H&E staining proved to be free of micrometastases by IHC. CONCLUSION: IHC and RT-PCR are more sensitive methods for detecting micrometastases than conventional H&E staining alone. If an SLN is tumor free by IHC or RT-PCR, we can assume that the remaining lymph nodes in the axilla are also tumor free, consequently, an SLN biopsy can bea substitute for axillary lymph node dissection.

Detection of Breast Cancer Micrometastases in Sentinel Lymph Nodes / 한국유방암학회지

PURPOSE: Axillary lymph node status is a powerful prognostic factor in breast carcinoma. However, patients without axillary lymph node metastases are not completely devoid of risk for relapse. And the axillary lymph node micrometastases will significantly contribute to the selection of high-risk patients. Recently, sentinel lymph node(SLN) biopsy has been proposed as a potential alternative to full axillary lymph node dissection for staging breast carcinoma. To validate this hypothesis, the distribution of occult metastases in sentinel and nonsentinel lymph node was evaluated. MATERIALS & METHODS: Twenty patients who underwent SLN biopsy followed by axillary lymph node dissection during March and July 2000 due to breast carcinoma at Seoul National University Hospital were evaluated. Thirty SLN devoid of metastasis by hematoxylin and eosin(H&E) staining were evaluated for micrometastases by Pan-cytokeratin immunohistochemistry(IHC) and Reverse Transcriptase Polymerase Chain Reaction(RT-PCR) using Keratin 19 mRNA and MUC1 mRNA. Nonsentinel lymph nodes(NSLN) were also evaluated by Pan-cytokeratin IHC. RESULTS: One out of 30 SLNs(3.3%) had occult metastases by IHC and 4 out of 30 SLNs(13.3%) had occult metastases by RT-PCR. NSLNs devoid of metastases by H&E stain were proved to be free of micrometastases by IHC. CONCLUSION: IHC and RT-PCR are sensitive methods for detecting micrometastases than conventional H&E staining alone. If SLN is tumor free by IHC or RT-PCR, we can assume that the remaining lymph nodes in the axilla are also tumor free and SLN biopsy can be a substitute for axillary lymph node dissection.