• Molecules and Cells
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• 제46권6호
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• pp.387-398
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• 2023

Microtubule acetylation has been proposed as a marker of highly heterogeneous and aggressive triple-negative breast cancer (TNBC). The novel microtubule acetylation inhibitors GM-90257 and GM-90631 (GM compounds) cause TNBC cancer cell death but the underlying mechanisms are currently unknown. In this study, we demonstrated that GM compounds function as anti-TNBC agents through activation of the JNK/AP-1 pathway. RNA-seq and biochemical analyses of GM compound-treated cells revealed that c-Jun N-terminal kinase (JNK) and members of its downstream signaling pathway are potential targets for GM compounds. Mechanistically, JNK activation by GM compounds induced an increase in c-Jun phosphorylation and c-Fos protein levels, thereby activating the activator protein-1 (AP-1) transcription factor. Notably, direct suppression of JNK with a pharmacological inhibitor alleviated Bcl2 reduction and cell death caused by GM compounds. TNBC cell death and mitotic arrest were induced by GM compounds through AP-1 activation in vitro. These results were reproduced in vivo, validating the significance of microtubule acetylation/JNK/AP-1 axis activation in the anti-cancer activity of GM compounds. Moreover, GM compounds significantly attenuated tumor growth, metastasis, and cancer-related death in mice, demonstrating strong potential as therapeutic agents for TNBC.

• Korean Journal of Radiology
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• 제21권8호
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• pp.946-954
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• 2020

Objective: To investigate preoperative magnetic resonance imaging (MRI) findings associated with resection margin status in patients with invasive lobular carcinoma (ILC) who underwent breast-conserving surgery. Materials and Methods: One hundred and one patients with ILC who underwent preoperative MRI were included. MRI (tumor size, multifocality, type of enhancing lesion, distribution of non-mass enhancement [NME], and degree of background parenchymal enhancement) and clinicopathological features (age, pathologic tumor size, presence of ductal carcinoma in situ [DCIS] or lobular carcinoma in situ, presence of lymph node metastases, and estrogen receptor/progesterone receptor/human epidermal growth factor receptor type 2 status) were analyzed. A positive resection margin was defined as the presence of invasive cancer or DCIS at the inked surface. Logistic regression analysis was performed to determine pre- and postoperative variables associated with positive resection margins. Results: Among the 101 patients, 21 (20.8%) showed positive resection margins. In the univariable analysis, NME, multifocality, axillary lymph node metastasis, and pathologic tumor size were associated with positive resection margins. With respect to preoperative MRI findings, multifocality (odds ratio [OR] = 3.977, p = 0.009) and NME (OR = 2.741, p = 0.063) were associated with positive resection margins in the multivariable analysis, although NME showed borderline significance. Conclusion: In patients with ILC, multifocality and the presence of NME on preoperative breast MRI were associated with positive resection margins.

• Investigative Magnetic Resonance Imaging
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• 제17권3호
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• pp.207-214
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• 2013

목적: BRCA 유전자 변이가 있는 유방암의 MRI 소견을 알아보고자 하였다. 대상과 방법: 2007년 1월에서 2010년 12월 사이에 BRCA 유전자 검사와 수술전 유방 MRI를 시행한 185명의 유방암 환자를 대상으로 하였다. 그 중 33명은 유전자 변이가 있었고 152명은 유전자 변이가 없었다. 총 231개의 유방암이 발견되었고, 유전자 변이가 있었던 환자의 47개의 유방암과 변이가 없었던 환자의 184개의 유방암에 대하여 MRI에서의 형태 및 조영증강 양상을 비교하였다. 결과: MRI에서의 유방암의 형태는 두 환자군 간에 유의한 차이가 없었다. 그러나 조영증강은 BRCA 유전자 변이가 있는 환자군에서 지속형을 보이는 경우가 더 많았고 (p < 0.233), 림프절 전이는 유전자 변이가 없는 환자군에서 더 많았다. BRCA 2 유전자 변이 환자군에서 BRCA 1 유전자 변이 환자군보다 지속형 조영증강을 보이는 경우가 더 많았다. 결론: MRI에서 BRCA 유전자 변이가 있는 유방암은 변이가 없는 유방암과 형태에서 유의한 차이를 보이지 않았으나 지속형 조영증강과 같이 양성종괴에서 보이는 형태학적 특징을 보이는 경우가 더 많았다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.1725-1729
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• 2013

Background: Breast cancer is the second leading cancer causing death in women. Circulating tumor cells are among the prognostic factors while tumor markers are of diagnostic value and can be used for follow-up. The aim of this study was to investigate the correlation between the prognostic significance of the serum CA15-3 levels, number of circulating tumor cells and histopathological tumor factors. Materials and Methods: Thirty patients recently diagnosed with breast cancer were included in the study. Number of circulating tumor cells and serum CA15-3 level were assessed when metastasis was detected and diagnostic value was assessed. Presence of associations with estrogen and progesterone receptors, c-erbB2, Ki-67 proliferation index and histological grade were also evaluated. Results: Median overall survival of the patients with serum CA15-3 levels of >108 ng/dl was 19 months whereas for those with a low serum level it was 62 months. Median overall survival for CTC ${\geq}5$ vs CTC<5 patients was 19 months and 40 months respectively. The difference between the two groups was statistically significant. Conclusions: Prognostic significance of the CTC count and CA15-3 levels in metastatic breast cancer patients was demonstrated.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4119-4123
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• 2012

Background: Neoadjuvant systemic chemotherapy is the accepted approach for women with locally advanced breast cancer. Anthracycline- and taxane-based regimens have been extensively studied in clinical trials and consequently are widely used. In this study aimed to research the complete response (pCR) rates in different regimens for neoadjuvant setting and determine associated clinical and biological factors. Methods: This study included 63 patients diagnosed with breast carcinoma among 95 patients that had been treated with neoadjuvant chemotherapy between 2007 and 2010. TNM staging system was used for staging. The histologic response to neoadjuvant chemotherapy was characterized as a pCR when there was no evidence of residual invasive tumor in the breast or axillary lymph nodes. Biologic subclassification using estrogen receptor (ER), progesterone receptor (PR), HER2 were performed. Luminal A was defined as ER+, PR+, HER2-; Luminal B tumor was defined as ER+, PR-, HER2-; ER+, PR-, HER2+; ER-, PR+, HER2-; ER+, PR+, HER2+; HER2 like tumor ER-, PR+, HER2+; and triple negative tumor ER, PR, HER2 negative. Results: Patients median age was 54.14 (min-max: 30-75). Thirty-two patients (50.8%) were premenapousal and 31 (49.2%) were postmenapousal. Staging was performed postoperatively based on the pathology report and appropriated imaging modalities The TNM (tumor, lymph node, metastasis) system was used for clinical and pathological staging. Fifty-seven (90.5%) were invasive ductal carcinomas, 6 (9.5%) were other subtypes. Thirty nine (61.9%) were grade II and 24 (38.1%) were grade III. Seven (11.1%) patients were stage II and 56 (88.9) patients were stage III. The patients were classified for ER, PR receptor and HER2 positivity. Seventeen patients had complete response to chemotherapy. Forty patients (63.5%) were treated with dose dense regimen (cyclophosphamide 600 mg/m2 and doxorubicine 60 mg/m every two weeks than paclitaxel 175 mg/m2 every two weeks with filgrastim support) 40 patients (48%) were treated anthracycline and taxane containing regimens. Thirteen patients (76%) from 17 patients with pCR were treated with the dose dense regimen but without statistical significance (p=0.06). pCR was higher in HER2(-), ER(-), grade III, premenopausal patients. Conclusion: pCR rate was higher in the group that treated with dose dense regimen, which should thus be the selected regimen in neoadjuvant setting. Some other factors can predict pCR in Turkish patients, like grade, menopausal status, triple negativity, percentage of ER positivity, and HER2 expression.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6397-6403
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• 2014

Background: Aberrant promoter hypermethylation has been recognized in human breast carcinogenesis as a frequent molecular alteration associated with the loss of expression of a number of key regulatory genes and may serve as a biomarker. The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir. Materials and Methods: Methylation specific PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive ductal carcinomas (IDCs) paired with the corresponding normal tissue samples. Immunohistochemistry was used to study the expression of E-cadherin, ER and PR. Results: CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of our samples. Loss of E-cadherin expression was significantly associated with the CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79). Hypermethylation of CDH1 was significantly associated with age at diagnosis (p=0.030), tumor size (p=0.008), tumor grade (p=0.024) and rate of node positivity or metastasis (p=0.043). Conclusions: Our preliminary findings suggest that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression. We found significant differences in tumor-related CDH1 gene methylation patterns relevant to tumor grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which could be extended in future to provide diagnostic and prognostic information.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.6013-6017
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• 2013

Background: To evaluate the clinicopathologic and demographic characteristics of triple-negative breast cancer (TNBC) patients and to determine differences from non-triple-negative cases. Materials and Methods: A detailed review of the medical records of 882 breast cancer (BC) patients was conducted to obtain information regarding age, menopausal status, height and weight at the time of diagnosis, presence of diabetes or hypertension, and pathologic characteristics of the tumor (tumor size, lymph node status, histologic grade, ER status, PR status, HER2 status, p53 mutation). Body mass index (BMI) was calculated and a value of ${\geq}30$ was considered as indicative of obesity. Results: 14.9% (n=132) of the patients had TNBC. There was no difference among the patients in terms of median age, comorbid conditions and menopausal status. The proportion of medullary, tubular and mucinous carcinomas was significantly higher (15.9%) in the triple-negative (TN) group, while invasive lobular histology was more frequent (8.2%) among non-triple negative (NTN) cases (p<0.001). Grade 3 (G3) tumors were more frequent in the triple-negative group (p<0.001). The rate of p53 mutation was 44.3% in TN tumors versus 28.2% in the NTN group (p<0.001). The two groups were similar in terms of LN metastasis. In the NTN group, the rate of patients with BMI ${\geq}30$ was 53% among postmenopausal patients, while it was 36% among premenopausal women, and the difference was statistically significant (p<0.001). No significant difference was observed in terms of BMI between postmenopausal and premenopausal patients in the TN group (p=0.08). Conclusions: TNBC rates and clinicopathologic characteristics of the Turkish patient population were consistent with the data from Europe and America. However, no relationship between obesity and TNBC was observed in our study. The association between TNBC and obesity needs to be evaluated in a larger patient population.

• Imaging Science in Dentistry
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• 제35권3호
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• pp.179-183
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• 2005

Metastatic tumors to the jaw bones are uncommon. The most common metastatic tumors to the jaw bones are the breast, lung and kidney. In the jaw bones, the common location of the lesions is the mandible, and the posterior area of the mandible is more commonly affected. The radiographic appearance is quite variable. In this report, a very rare case of metastatic gastric adenocarcinoma to the mandible is presented. The patient had undergone a gastrectomy 3 years ago.

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2011년도 추계학술발표회
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• pp.274-275
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• 2011

• Journal of Chest Surgery
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• 제18권1호
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• pp.86-91
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• 1985

A clinical analysis was performed on 11 cases of metastatic lung cancer experienced at Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital during the 15 year period from 1970 to 1984. Of the 1lpatients of metastatic lung cancer, 4 patients were male and 7 patients were female and the age ranged from 27 years to 60 years old with the average of 38.8 years old. The sites of primary tumor were uterus and ovary in 5 patients, breast in 2, sarcoma in 2, rectum in 1 and testis in l.\ulcorner Tumor free intervals in each patients were as followed; unrecognition of primary site in 2 patients, simultaneous discovery of primary tumor and metastasis in 3, 14 months in 1, 4 years in 4 and 5 years in Twelve thoracotomies were performed in 11 patients and performed procedures were as followed; pneumonectomy in 1 patient, lobectomy in 7, wedge resection in 2, decortication and wedge resection in 1 and biopsy only in 1. Of the 11 patients, 4 patients died within one year after operation, 2 patients died within 2 years and 2 patients are alive over 5 years after operations. Other 3 patients are alive 2 months, 4 months and 9 months after operation at present.