• Molecules and Cells
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• v.26 no.3
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• pp.285-290
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• 2008

Estrogen-induced proliferation in estrogen receptor (ER)-positive breast cancer cells is primarily mediated through two distinct intracellular receptors, $ER{\alpha}$ and $ER{\beta}$. Although tumor necrosis factor alpha ($TNF{\alpha}$) and $E2/ER{\alpha}$ are known to exert opposing effects on cell proliferation in MCF-7 cells, the mechanism by which $TNF{\alpha}$ antagonizes $E2/ER{\alpha}$-mediated cell proliferation is not well understood. The present study suggests that reduced cell survival in response to $TNF{\alpha}$ treatment in MCF-7 cells may be associated with the down-regulation of $ER{\alpha}$ protein. The decrease in $ER{\alpha}$ protein level was accompanied by an inhibition of $ER{\alpha}$ gene transcription. Cell viability was decreased synergistically by the combined treatment with $ER{\alpha}$-siRNA and $TNF{\alpha}$. Furthermore, pretreatment of cells with the PI3-kinase (PI3K)/ Akt inhibitor, LY294002, markedly enhanced $TNF{\alpha}$-induced down-regulation of the $ER{\alpha}$ protein, suggesting that the PI3K/Akt pathway might be involved in control of the $ER{\alpha}$ level. Moreover, down-regulation of $ER{\alpha}$ by $TNF{\alpha}$ was not inhibited in cells that were pretreated with the proteasome inhibitors, MG132 and MG152, which suggests that proteasome-dependent proteolysis does not significantly influence $TNF{\alpha}$-induced down-regulation of $ER{\alpha}$ protein. In contrast, the effect of the PI3K/Akt inhibitor on $ER{\alpha}$ was blocked in cells that were treated with LY294002 in the presence of the proteasome inhibitors. Collectively, our findings show that the $TNF{\alpha}$ may partly regulate the growth of MCF-7 breast cancer cells through the down-regulation of $ER{\alpha}$ expression, which is primarily mediated by a PI3K/Akt signaling.

• Journal of Integrative Natural Science
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• v.15 no.4
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• pp.145-152
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• 2022

Colon rectal cancer is one of the frequently diagnosed cancers worldwide. In recent times the drug discovery for colon cancer is challenging because of their speedy metastasis and morality of these patients. C-jun N-terminal kinase signaling pathway controls the cell cycle survival and apoptosis. Evidence has shown that JNK1 promotes the tumor progression in various types of cancers like colon cancer, breast cancer and lung cancer. Recent study has shown that inhibiting, JNK1 pathway is identified as one of the important cascades in drug discovery. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened ChEMBL dataset against JNK1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top compounds to be more specific with JNK1 comparing the affinity with JNK2 and JNK3.The drugs which exhibited higher binding were subjected to Conceptual - Density functional theory. The results showed mainly Entrectinib and Exatecan showed better binding to the target.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2657-2662
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• 2013

Background: Intraoperative sentinel lymph node biopsy has now become the standard of care for patients with clinically node negative breast cancer for diagnosis and also in order to determine the need for immediate axillary clearance. Several large scale studies confirmed the diagnostic reliability of this method. However, micrometastases are frequently missed on frozen sections. Recent studies showed that both disease free interval and overall survival are significantly affected by the presence of micrometastatic disease. The aim of this study was to determine the sensitivity and specificity of intraoperative frozen section analysis of sentinel lymph nodes (SLNs) for the detection of breast cancer micrometastasis and to evaluate the status of non-sentinel lymph nodes (non-SLNs) in those patients subjected to further axillary sampling. Materials and Methods: We performed a retrospective study on 154 patients who underwent SLN biopsy from January 2008 till October 2011. The SLNs were sectioned at 2 mm intervals and submitted entirely for frozen sections. Three levels of each section submitted are examined and the results were compared with further levels on paraffin sections. Results: Overall 40% of patients (62/154) were found to be SLN positive on final (paraffin section) histology, out of which 44 demonstrated macrometastases (>2mm) and 18 micrometastases (<2mm). The overall sensitivity and specificity of frozen section analysis of SLN for the detection of macrometastasis was found to be 100% while those for micrometastasis were 33.3% and 100%, respectively. Moreover 20% of patients who had micrometastases in SLN had positive non-SLNs on final histology. Conclusions: Frozen section analysis of SLNs lacks sufficient accuracy to rule out micrometastasis by current protocols. Therefore these need to be revised in order to pick up micrometastasis which appears to have clinical significance. We suggest that this can be achieved by examining more step sections of blocks.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4549-4553
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• 2012

This study was designed to investigate the frequency of CYP2D6 polymorphisms and evaluate the association between genetic polymorphisms of CYP2D6 and tamoxifen therapeutic outcome in Thai breast cancer patients. We recruited 48 breast cancer patients who received adjuvant tamoxifen for evaluating CYP2D6 genetic polymorphisms using microarray-based technology. Associations between genotypes-phenotypes and disease free survival were analyzed. Median follow up time was 5.6 years. The mean age of the subjects was 50 years. The 3 common allelic frequencies were 43.8% ($^*10$), 36.5 ($^*1$) and 10.4% ($^*2$) which are related to extensive metabolizer (EM) and intermediate metabolizer (IM) with 70.8% and 29.2 %, respectively. No association between CYP2D6 genotypes and DFS was demonstrated. Nevertheless, exploratory analysis showed statistically significant shorter DFS in the IM group of post-menopause patients (HR, 6.85; 95%CI, 1.48-31.69; P=0.005). Furthermore, we observed statistically significant shorter DFS of homozygous $CYP2D6^*10$ when compared with heterozygous CYP2D6*10 and other genotypes (P=0.005). $CYP2D6^*10$ was the most common genotype in our subjects. Post-menopause patients with homozygous $CYP2D6^*10$ and IM have shorter DFS. To confirm this relationship, larger samples and comprehensively designed trials in Thailand are required.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.823-829
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• 2015

The aim of the present study was to investigate the expression of the transcription factor Ki-67, ER, PR, Her2/neu, p21, EGFR, and TOP II-${\alpha}$ in the tumor tissue of patients with invasive ductal carcinoma(IDC); in addition, we examined correlations between these markers. Two hundred and sixteen IDC patients, who were not previously been treated with chemo- or radiotherapy, were included in the study. All tumors were grade I-III. Expression of molecular markers was determined by immunohistochemical analysis on paraffin-embedded tissue sections. Follow-up data were collected for 3 months to 10 years and analyzed for tumor recurrence, survival time, and prognostic risk factors. We determined Ki-67 expression correlates with the expression of ER, PR, HER-2, EGFR, and TOP-${\alpha}$, as well as lymph node involvement, high tumor grade, lymphovascular invasion, high tumor stage, and high TNM stage in IDC. Positive Ki-67 expression was a risk factor for rapid tumor recurrence and may help tumor progression, leading to poor prognosis in IDC. Ki-67 was directly correlated with EGFR, TOP II-${\alpha}$, lymph node involvement, high tumor grade, lymphovascular invasion, high tumor stage, and high TNM stage in the hormone receptor subtypes of breast cancer. In triple negative breast cancer, Ki-67 correlated with TOP II-${\alpha}$. Expression of Ki-67 correlated with that of ER, PR, HER-2, EGFR, TOP II-${\alpha}$, and p21. In addition, the biomarker Ki-67 has a role as a prognostic factor and indicates a poor prognosis in IDC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.331-334
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• 2014

There is a scarcity of reports addressing patients with multiple primary malignancies (MPM), especially for Chinese cses. The aim of this study was to present a detailed analysis of Chinese patients presenting with at least two primary malignancies. Particularly, the clinical characteristics and survival between synchronous and metachronous MPM were compared. Out of 6,545 cases, 72 patients (1.1%) including 39 males (54.2%) and 33 females (45.8%) were diagnosed as MPM, giving a male: female sex ratio of 1.2:1. Of these, there were 16 (22.2%) cases of synchronous MPM (7 males, 9 females), 55(76.4%) metachronous (31 males, 24 females), and 1 "mixed form". For first tumor diagnosis time, synchronous MPM patients generally presented later than the metachronous cases. The top three sites for malignancies with metachronous MPM were colorectum, head and neck, and lung, while for synchronous they were lung, colorectum and breast. Among MPM patients, the median survival time was 15.7 years and the 5-year survival was 56%, and there was statistical difference in MPM categories (P < 0.05). The median survival time was 17.3 years and 3.8 years for metachronous and synchronous MPM patients, respectively. In comparison with synchronous MPM patients, those metachronous had a longer survival. This studies increase understanding of the clinical features of Chinese MPM patients and suggest that those presenting with metachronous cancers have a higher incidence and a better prognosis.

• Journal of Chest Surgery
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• v.25 no.9
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• pp.948-954
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• 1992

In spite of recent progress in anticancer chemotherapy, the survival of patients with metastases to the lung treated nonsurgically has been extremely poor. So we adopted more aggressive surgical approaches for the treatment of patients with pulmonary metastases since 1985. We experienced 22 operations of metastatic lung cancer in 19 patients in the department of Thoracic & Cardiovascular Surgery in Kosin Medical College since 1985, so we reviewed the results of treatment retrospectively. The results were as follows: 1. The primary organs of metastatic lung cancer were 4 cases in each of the breast, uterus, and extremities, 3 cases in the rectum, 2 cases in the kidney, 1 case in each of the pelvis and liver, and the pathological findings were 13 cases in carcinoma and 6 cases in sarcoma. 2. The treatments for primary lesions were 15 cases of the operations with anticancer chemotherapy or radiation therapy, 2 cases of choriocarcinoma with anticancer chemotherapy only, 1 cases of uterine cervical carcinoma with chemo-radiation therapy, and 1 case of pelvic synovia sarcoma with intra-arterial anticancer chemotherapy. 3. Disease free intrerval were as follows: 7 cases were in 2 years to 4 years, 4 cases were in 1 year to 2 years, and 5 cases were beyond one year, of them one case was discovered primary lesion and metastatic lung tumor concomittently. 3 cases were above 4 years, of them one case of breast cancer were above 13 years especially. 4. The sites of metastatic lung cancer was 15 lesions in the right lung, and 9 lesions in the left lung, And the lobar sites were 10 lesions in the upper lobe, 2 lesions in the middle lobe, and 12 lesions in the lower lobe. 5. The operative methods of metastatic lung cancer were 7 case of partial resection of lung, 12 cases of pulmonary lobectomy, 1 case of pneumonectomy and 1 case of dissection of mediastinal lymph node. 6. The postoperative complications were 1 case of mild respiratory insufficency, 1 cases of pyothorax, and 1 case of urethral stricture. 7. Postoperative adjuvant therapy were as follows: No adjuvant therapy were 4 cases, anti-cancer chemotherapy were 8 cases, radiation therapy was 1 case, and combined with chemo k radiation therapy were 8 cases. 8. The results of long term follow-up were as follows: The 5 patients were died at 2 months, 22 months, 24 months, 32 months, and 49 months postoperatively, so mean survival period was 32 months postoperatively excluding one patient who was died at 2 months postoperatively. And 14 patients are aliving, of them 3 patients are living in recurred state, and the other 11 patients are living without any evidence of recurrence.

• Tuberculosis and Respiratory Diseases
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• v.74 no.4
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• pp.169-176
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• 2013

Background: Although the lung is a common site of metastasis, endobronchial metastases (EBM) from extrathoracic malignancies are rare. Previous studies were retrospective reviews of the cases from each single institute, and the last one was performed between 1992 and 2002. We evaluated the characteristics of patients with EBM who had been diagnosed in recent 10 years in our hospital. Methods: We retrospectively reviewed 1,275 patients who had undergone diagnostic bronchoscopic procedures between 2001 and 2011. An EBM was defined as bronchoscopically notable lesion, which was histopathologically identical to the primary tumor. Results: A total of 18 cases of EBM were identified. The mean age was 53 years, and 12 cases of the 18 patients were female. The most common primary malignancies were colorectal cancer and breast cancer (4 cases each), followed by cervix cancer (3 cases) and renal cell carcinoma (2 cases). Cough was the most common symptom. The most common radiologic finding was atelectasis, which was identified in 27.7% of the cases. The median interval from the diagnosis of primary malignancy to the diagnosis of EBM was 14 months (range, 0-112 months). The median survival time from the diagnosis of EBM was 10 months (range, 1-39 months). Conclusion: EBM from extrathoracic malignancies were rare. Colorectal cancer and breast cancer were common as primary malignancies. Fiberoptic bronchoscopy should be performed in all patients, who are suspected of having EBM. If atypical clinical and pathological features are present, appropriate diagnostic studies should be undertaken.

• IMMUNE NETWORK
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• v.20 no.4
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• pp.33.1-33.19
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• 2020

We tested how adjuvants effect in a cancer vaccine model using an epitope derived from an autoactivation loop of membrane-type protease serine protease 14 (PRSS14; loop metavaccine) in mouse mammary tumor virus (MMTV)-polyoma middle tumor-antigen (PyMT) system and in 2 other orthotopic mouse systems. Earlier, we reported that loop metavaccine effectively prevented progression and metastasis regardless of adjuvant types and TH types of hosts in tail-vein injection systems. However, the loop metavaccine with Freund's complete adjuvant (CFA) reduced cancer progression and metastasis while that with alum, to our surprise, were adversely affected in 3 tumor bearing mouse models. The amounts of loop peptide specific antibodies inversely correlated with tumor burden and metastasis, meanwhile both T_H1 and T_H2 isotypes were present regardless of host type and adjuvant. Tumor infiltrating myeloid cells such as eosinophil, monocyte, and neutrophil were asymmetrically distributed among 2 adjuvant groups with loop metavaccine. Systemic expression profiling using the lymph nodes of the differentially immunized MMTV-PyMT mouse revealed that adjuvant types, as well as loop metavaccine can change the immune signatures. Specifically, loop metavaccine itself induces T_H2 and T_H17 responses but reduces T_H1 and T_reg responses regardless of adjuvant type, whereas CFA but not alum increased follicular T_H response. Among the myeloid signatures, eosinophil was most distinct between CFA and alum. Survival analysis of breast cancer patients showed that eosinophil chemokines can be useful prognostic factors in PRSS14 positive patients. Based on these observations, we concluded that multiple immune parameters are to be considered when applying a vaccine strategy to cancer patients.

• The Korea Journal of Herbology
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• v.21 no.1
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• pp.57-62
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• 2006

Objectives : This study was carried out to investigate the inhibitive effects of cotton plant sectional extracts in cancer cell lines, Calu-6(human, Caucasian, lung, adenocarcinoma) and MCF-7(human, Caucasian, breast, adenocarcinoma). The incidence of cancer has been increasing even in korea due to the change of dietary life and westernization and becoming conspicuous as the disease threatening health. But cancer treatment have not been fully effective against the high incidence or low survival rate of most cancer. Methods : Calu-6 and MCF-7 cells were cultured and seeded in cell culture plates, respectively. And sectional extracts of cotton plant were treated to MCF-7 cells. Results and Conclusion : Sectional extracts of cotton plant showed no anti-proliferative effect on MCF-7 cells, but root and stem extracts showed strong anti-proliferative effects on Calu-6 cells. Fruit, leaf and flower extracts also showed anti-proliferative effects on Calu-6 cells but not so much like root and stem extracts. But seed extract showed no anti-proliferative effect on Calu-6 cells.