• Title/Summary/Keyword: Molecular subtype

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Male Breast Cancer: 20 Years Experience of a Tertiary Hospital from the Middle Black Sea Region of Turkey

  • Serarslan, Alparslan;Gursel, Bilge;Okumus, Nilgun Ozbek;Meydan, Deniz;Sullu, Yurdanur;Gonullu, Guzin
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6673-6679
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    • 2015
  • Background: Male breast cancer is a rare neoplasm, and its treatments are based on those of female breast cancer. This study aimed to analyze 20 years of male breast cancer clinical characteristics and treatment results from the Middle Black Sea Region of Turkey. Materials and Methods: A retrospective analysis of 16 male breast cancer patients treated in our tertiary hospital between 1994 and 2014 was performed. Epidemiologic data, tumor characteristics, and treatments were recorded and compared with 466 female breast cancer ((premenopausal; n = 230) + (postmenopausal n = 236)) patients. The 5-year disease-free and overall survival rates were calculated. Results: Male breast cancer constituted 0.1% of all malignant neoplasms in both sexes, 0.2% of all malignant neoplasms in males, and 0.7% of all breast cancers. The mean patient age in this study was $59.8{\pm}9.5$ (39-74) years. The mean time between first symptom and diagnosis was $32.4{\pm}5.3$ (3-60) months. Histology revealed infiltrative ductal carcinoma in 81.3% of patients. The most common detected molecular subtype was luminal A, in 12 (75%) patients. Estrogen receptor rate (93.8%) in male breast cancer patients was significantly higher than that in female breast cancer (70.8% in all females, p = 0.003; 68.2% in postmenopausal females, p = 0.002) patients. Most of the tumors (56.3%) were grade 2. Tumor stage was T4 in 50% of males. The majority (56.3%) of the patients were stage III at diagnosis. Surgery, chemotherapy, radiotherapy and endocrine-therapy were applied to 62.5%, 62.5%, 81.2% and 73.3%, respectively. Loco-regional failure did not occur in any of the cases. All recurrences were metastastic. The 5-year disease-free and overall survival rates in male breast cancer patients were 58% and 68%, respectively. Conclusions: Tumors found in male breast cancer patients were similar in size to tumors found in females, but they advanced to T4 stage more rapidly because of the lack of breast parenchymal tissues. The rate of estrogen receptor expression tended to be higher in male breast cancer patients than in female breast cancer patients. Metastasis is the most important problem in initially non-metastatic male breast cancer patients.

Gallbladder Cancer: a Subtype of Biliary Tract Cancer Which is a Current Challenge in China

  • Qu, Kai;Liu, Si-Nan;Chang, Hu-Lin;Liu, Chang;Xu, Xin-Sen;Wang, Rui-Tao;Zhou, Lei;Tian, Feng;Wei, Ji-Chao;Tai, Ming-Hui;Meng, Fan-Di
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1317-1320
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    • 2012
  • Biliary tract cancers, broadly described as malignancies that arise from the biliary tract epithelia, are usually divided into two major clinical phenotypes: cholangiocarcinoma and gallbladder cancer, differing in etiopathogenesis, risk factors, and perhaps molecular and genetic signatures. Atypical symptoms and lack of tumor biomarkers make it difficult to diagnose in early stages. At the time of presentation, few patients are candidates for potentially curative surgical resection. We here assessed and compared features of a total of 150 cases divided into extra- and intrahepatic cholangiocarcinomas and gallbladder cancers (GBC). Althought there were no significant differences in serum tumour marker levels, GBC patients had the poorest prognosis. Furthermore, gallbladder cancer respond poorly to chemotherapy or radiation therapy and approximately half of untreated patients died within 10 months. Therefore, treatment for patients with gallbladder cancer is still in challenge. Outcomes and survival of these patients had improved little over the past three decades - a period in which new successful treatments have greatly contributed to the prolonged patient survival for many other cancers.

Benefit of Post-mastectomy Radiotherapy of the Supra-/infraclavicular Lymphatic Drainage Area in Breast Cancer Patients

  • He, Zhen-Yu;Wu, San-Gang;Zhou, Juan;Sun, Jia-Yuan;Li, Feng-Yan;Lin, Qin;Guo, Ling;Lin, Huan-Xin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.14
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    • pp.5557-5563
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    • 2014
  • Background: This study investigated the survival benefit of radiotherapy (RT) of the supra- and infraclavicular lymphatic drainage area in Chinese women with T1-2N1M0 breast cancer receiving mastectomy. Methods: A total of 593 cases were retrospectively reviewed from 1998 to 2007. The relationship between supra- or infraclavicular fossa relapse (SCFR) and post-operative RT at the supra-/infraclavicular lymphatic drainage area was evaluated. Results: The majority of patients (532/593; 89. 8%) received no RT while 61 patients received RT. The median follow-up was 85 months. Among patients without RT, 54 (10. 2%) developed recurrence in the chest wall or ipsilateral SCFR. However, none of the 61 patients who underwent RT demonstrated SCFR. One patient who received RT (1. 6%) experienced recurrence in the chest wall. Univariate analysis revealed that age and molecular subtype (both P < 0. 05) were two prognostic factors related to supraclavicular and infraclavicular fossa relapse-free survival (SFRFS). Multivariate analysis revealed that only Her-2 positive status (P = 0. 011) was an independent predictor of SFRFS. RT had no influence on distant metastasis (P = 0. 328) or overall survival (P = 0. 541). SCFR significantly affected probability of distant metastasis (P < 0. 001) and overall survival (P < 0. 001). Conclusion: Although RT was not significantly associated with SFRFS, postoperative RT was significantly associated with a lower locoregional (i. e., supraclavicular/infraclavicular and chest wall) recurrence rate. SCFR significantly influenced distant metastasis-free survival, which significantly influenced the overall survival of T1-2N1M0 breast cancer patients after mastectomy. Thus, prophylactic RT is recommended in T1-2N1M0 breast cancer patients, especially those who have Her-2 positive lesions.

Prediction of Axillary Lymph Node Metastasis in Early Breast Cancer Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging and Diffusion-Weighted Imaging

  • Jeong, Eun Ha;Choi, Eun Jung;Choi, Hyemi;Park, Eun Hae;Song, Ji Soo
    • Investigative Magnetic Resonance Imaging
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    • v.23 no.2
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    • pp.125-135
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    • 2019
  • Purpose: The purpose of this study was to evaluate dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI), and diffusion-weighted imaging (DWI) variables, for axillary lymph node (ALN) metastasis in the early stage of breast cancer. Materials and Methods: January 2011-April 2015, 787 patients with early stage of breast cancer were retrospectively reviewed. Only cases of invasive ductal carcinoma, were included in the patient population. Among them, 240 patients who underwent 3.0-T DCE-MRI, including DWI with b value 0 and $800s/mm^2$ were enrolled. MRI variables (adjacent vessel sign, whole-breast vascularity, initial enhancement pattern, quantitative kinetic parameters, signal enhancement ratio (SER), tumor apparent diffusion coefficient (ADC), peritumoral ADC, and peritumor-tumor ADC ratio) clinico-pathologic variables (age, T stage, multifocality, extensive intraductal carcinoma component (EIC), estrogen receptor, progesterone receptor, HER-2 status, Ki-67, molecular subtype, histologic grade, and nuclear grade) were compared between patients with axillary lymph node metastasis and those with no lymph node metastasis. Multivariate regression analysis was performed, to determine independent variables associated with ALN metastasis, and the area under the receiver operating characteristic curve (AUC), for predicting ALN metastasis was analyzed, for those variables. Results: On breast MRI, moderate or prominent ipsilateral whole-breast vascularity (moderate, odds ratio [OR] 3.45, 95% confidence interval [CI] 1.28-9.51 vs. prominent, OR = 15.59, 95% CI 2.52-96.46), SER (OR = 1.68, 95% CI 1.09-2.59), and peritumor-tumor ADC ratio (OR = 6.77, 95% CI 2.41-18.99), were independently associated with ALN metastasis. Among clinico-pathologic variables, HER-2 positivity was independently associated, with ALN metastasis (OR = 23.71, 95% CI 10.50-53.54). The AUC for combining selected MRI variables and clinico-pathologic variables, was higher than that of clinico-pathologic variables (P < 0.05). Conclusion: SER, moderate or prominent increased whole breast vascularity, and peritumor-tumor ADC ratio on breast MRI, are valuable in predicting ALN metastasis, in patients with early stage of breast cancer.

Visualization of the binding between gintonin, a Panax ginseng-derived LPA receptor ligand, and the LPA receptor subtypes and transactivation of the EGF receptor

  • Choi, Sun-Hye;Lee, Ra Mi;Cho, Han-Sung;Hwang, Sung Hee;Hwang, Hong-Ik;Rhim, Hyewhon;Kim, Hyoung-Chun;Kim, Do-Geun;Cho, Ik-Hyun;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • v.46 no.3
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    • pp.348-356
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    • 2022
  • Background: Gintonin is a ginseng-derived exogenous G-protein-coupled lysophosphatidic acid (LPA) receptor ligand. Gintonin exerts its neuronal and non-neuronal in vitro and in vivo effects through LPA receptor subtypes. However, it is unknown whether gintonin can bind to the plasma membrane of cells and can transactivate the epidermal growth factor (EGF) receptor. In the present study, we examined whether gintonin-biotin conjugates directly bound to LPA receptors and transactivated the EGF receptor. Methods: We designed gintonin-biotin conjugates through gintonin biotinylation and examined whether gintonin-biotin conjugate binding sites co-localized with the LPA receptor subtype binding sites. We further examined whether gintonin-biotin transactivated the EGF receptor via LPA receptor regulation via phosphor-EGF and cell migration assays. Results: Gintonin-biotin conjugates elicit [Ca2+]i transient similar to that observed with unbiotinylated gintonin in cultured PC3 cells, suggesting that biotinylation does not affect physiological activity of gintonin. We proved that gintonin-biotin conjugate binding sites co-localized with the LPA1/6 receptor binding sites. Gintonin-biotin binding to the LPA1 receptor transactivates the epidermal growth factor (EGF) receptor through phosphorylation, while the LPA1/3 receptor antagonist, Ki16425, blocked phosphorylation of the EGF receptor. Additionally, an EGF receptor inhibitor AG1478 blocked gintonin-biotin conjugate-mediated cell migration. Conclusions: We observed the binding between ginseng-derived gintonin and the plasma membrane target proteins corresponding to the LPA1/6 receptor subtypes. Moreover, gintonin transactivated EGF receptors via LPA receptor regulation. Our results suggest that gintonin directly binds to the LPA receptor subtypes and transactivates the EGF receptor. It may explain the molecular basis of ginseng physiology/pharmacology in biological systems.

DNA Mutation Pattern of gyrA and gyrB Genes according to the SCCmec Subtype of Quinolone-resistant Staphylococcus aureus Isolates from Blood Culture (혈액배양에서 분리된 Fluoroquinolone계 약제 내성 황색포도알균의 SCCmec 아형에 따른 gyrA와 gyrB 유전자에서의 DNA 돌연변이 양상)

  • Inwon HWANG;Sang-Ha KIM;Taewon JUNG;Young-Kwon KIM;Sunghyun KIM
    • Korean Journal of Clinical Laboratory Science
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    • v.56 no.2
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    • pp.115-124
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    • 2024
  • The emergence and spread of Staphylococcus aureus, which is resistant to quinolone antibacterial agents, has made it difficult to treat infectious diseases. Accordingly, this study examined the molecular epidemiological characteristics of quinolone-resistant S. aureus (QRSA) to obtain helpful data for treatment. Mutations in mecA and SCCmec typing, gyrA, and gyrB genes were investigated for QRSA strains isolated from the blood culture specimens at a general hospital in Daejeon Metropolitan City. The ciprofloxacin-resistant strains in SCCmec typing were II (44 strains, 73%), IVa (five strains, 8%), III, and V (one strain, 2%); the non-typeable strains (11 strains, 18%), and levofloxacin (LVX) and moxifloxacin (MXF) strains were II (44 strains, 73%), IVa (five strains, 8%), III, and V (one strain, 2%); the non-typeable strains were 10 (17%). In both gyrA and gyrB regions, there were 58 mutations, or 96.7%. In LVX, there were 56 mutations or 93.3%, and in MXF, there were 57 mutations or 95%. Twelve mutations, six mutations each in gyrA and gyrB, were identified for the QRSA strain. The resistance rate for the quinolone antibiotics of QRSA studied was approximately 98%, and 12 mutations, six each in gyrA and gyrB, were identified in the QRSA strain. Therefore, the rational use of antibiotics needs to be improved.

The Study for the Relationship of Weight Loss with Plasma Leptin and TNF-α Level in Patients with Chronic Bronchitis and Emphysema (만성기관지염과 폐기종 환자에서 체중감소와 혈중 Leptin 및 TNF-α와의 관계에 대한 연구)

  • Pack, Jong Hae;Park, Ji Young;Park, Hye Jeong;Baek, Suk Hwan;Shin, Kyeong Cheol;Chung, Jin Hong;Lee, Kwan Ho
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.2
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    • pp.199-209
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    • 2003
  • Background : Unexplained weight loss, which commonly occurs in patients with chronic obstructive pulmonary disease(COPD), is important because weight loss is an independent risk factor of mortality and morbidity in these patients. Leptin is known to play an important role in regulating body weight. In addition, the tumor necrosis factor($TNF-{\alpha}$) might also play a potential role in the weight loss experienced in chronic wasting disease. The aim of this study was to determine the influence of plasma leptin and the circulating $TNF-{\alpha}$ system to the difference in the body compositions in patients with COPD. Methods : Spirometry, body composition analysis and the plasma concentrations of leptin, $TNF-{\alpha}$ and a soluble TNF receptor (STNF-R55, -R75) were measured in 31 patients with chronic bronchitis and 10 patients with emphysema. The COPD subtype was classified by the transfer coefficient of carbon monoxide, DLco/VA. Results : The circulating levels of leptin were significantly lower in those patients with emphysema($108.5{\pm}39.37pg/ml$) than those with chronic bronchitis($180.9{\pm}57.7pg/ml$). The circulating levels of sTNF-R55 were significantly higher in the emphysema patients($920.4{\pm}116.4pg/ml$) than in those with chronic bronchitis($803.2{\pm}80.8pg/ml$). There was no relationship between the circulating leptin levels and the activated TNF system in patients with chronic bronchitis and emphysema. However, the circulating leptin levels correlated well with the BMI and fat mass in both patient groups. Conclusion : These results suggest that the weight loss noted in emphysema patients may be associated with the activation of the $TNF-{\alpha}$ system rather than the plasma leptin level.

Association between MIR149 SNPs and Intrafamilial Phenotypic Variations of Charcot-Marie-Tooth Disease Type 1A (샤르코-마리-투스병 1A형(CMT1A)의 가족내 표현형적 이질성과 MIR149 SNP에 대한 연관성 연구)

  • Choi, Yu Jin;Lee, Ah Jin;Nam, Soo Hyun;Choi, Byung-Ok;Chung, Ki Wha
    • Journal of Life Science
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    • v.29 no.7
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    • pp.800-808
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    • 2019
  • Charcot-Marie-Tooth disease (CMT) is a group of rare peripheral neuropathies characterized by progressive muscle weakness and atrophy and areflexia in the upper and lower extremities. The most common subtype of CMT is CMT1A, which is caused by a tandem duplication of the PMP22 gene in the 17p12 region. Patients with CMT1A show a loose genotype-phenotype correlation, which suggests the existence of secondary genetic or association factors. Recently, polymorphisms of rs71428439 (n.83A>G) and rs2292832 (n.86T>C) in the MIR149 have been reported to be associated with late onset and mild phenotypic CMT1A severity. The aim of this study was to examine the intrafamilial heterogeneities of clinical phenotypes according to the genotypes of these two SNPs in MIR149. For this study, we selected 6 large CMT1A families who showed a wide range of phenotypic variation. This study suggested that both SNPs were related to the onset age and severity in the dominant model. In particular, the AG+GG (n.83A>G) and TC+CC genotypes (n.86T>C) were associated to late onset and mild symptoms. Motor nerve conduction velocity (MNCV) was not related to the MIR149 genotypes. These results were consistent with the previous studies. Therefore, we suggest that the rs71428439 and rs2292832 variants in MIR149 may serve as genetic modifiers of CMT1A intrafamilial phenotypic heterogeneity, as they have a role in the unrelated patients. This is the first study to show an association using large families with variable clinical CMT1A phenotypes. The results will be helpful in the molecular diagnosis and treatment of patients with CMT1A.

Digital Breast Tomosynthesis as a Breast Cancer Screening Tool for Women with Gynecologic Cancer (부인암을 가진 여성에서 유방암의 선별검사로서의 디지털 유방단층 촬영술)

  • Da-hoon Kim;Jin Chung;Eun-Suk Cha;Jee Eun Lee;Jeoung Hyun Kim
    • Journal of the Korean Society of Radiology
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    • v.81 no.4
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    • pp.886-898
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    • 2020
  • Purpose The purpose of our study was to evaluate digital breast tomosynthesis as a breast cancer screening modality for women with gynecologic cancer. Materials and Methods This retrospective study included patients with underlying gynecologic malignancies who underwent screening digital breast tomosynthesis for breast cancer. The cancer detection rate, recall rate, sensitivity, specificity, and positive predictive value (PPV) were calculated. PPV1 was defined as the percentage of all positive screening exams that have a tissue diagnosis of cancer within a year. PPV2 was defined as the percentage of all diagnostic exams (and Breast Imaging Reporting and Data System category 4, 5 from screening setting) with a recommendation for tissue diagnosis that have cancer within a year. PPV3 was defined as the percentage of all known biopsies actually performed that resulted in a tissue diagnosis of cancer within the year. For each case of screen-detected cancer, we analyzed the age, type of underlying gynecologic malignancy, breast density, imaging features, final Breast Imaging Reporting and Data System assessment, histologic type, T and N stages, molecular subtype, and Ki-67 index. Results Among 508 patients, 7 with breast cancer were identified after a positive result. The cancer detection rate was 13.8 per 1000 screening exams, and the recall rate was 17.9%. The sensitivity was 100%, and the specificity was 83.2%. The false negative rate was 0 per 1000 exams. The PPV1, PPV2, and PPV3 were 7.7, 31.8, and 31.8, respectively. Conclusion Digital breast tomosynthesis may be a promising breast cancer screening modality for women with gynecologic cancer, based on the high cancer detection rate, high sensitivity, high PPV, and high detection rate of early-stage cancer observed in our study.