• Annals of Surgical Treatment and Research
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• 제95권5호
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• pp.240-248
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• 2018

Purpose: This study aimed to validate the synergistic effect of ABT-737 on docetaxel using MDA-MB-231, a triple negative breast cancer (TNBC) cell line overexpressing B-cell lymphoma-2 (Bcl-2). Methods: Western blot analysis was performed to assess expression levels of Bcl-2 family proteins and caspase-related molecules. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle distribution was determined by flow cytometry analysis. Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (z-VAD-fmk) was used for pretreatment to assess the role of caspases. Results: Cell viability of MDA-MB-231 after combination treatment with ABT-737 and docetaxel was significantly lower than that after docetaxel or ABT-737 monotherapy based on MTT assay (both P < 0.001), with a combination index of 0.41. The proportion of sub-G1 population after combination treatment was significantly higher than that after docetaxel or ABT-737 monotherapy (P = 0.001, P = 0.003, respectively). Pretreatment with z-VAD-fmk completely restored cell viability of MDA-MB-231 from apoptotic cell death induced by combination therapy (P = 0.001). Although pro-caspase-8 or Bid did not show significant change in expression level, pro-casepase-9 showed significantly decreased expression after combination treatment. Cleaved caspase-3 showed increased expression while poly (ADP-ribose) polymerase cleavage was induced after combination treatment. However, hypoxia-inducible factor 1-alpha and aldehyde dehydrogenase 1 totally lost their expression after combination treatment. Conclusion: Combination of ABT-737 with docetaxel elicits synergistic therapeutic effect on MDA-MB-231, a TNBC cell line overexpressing Bcl-2, mainly by activating the intrinsic pathway of apoptosis. Therefore, adjunct of ABT-737 to docetaxel might be a new therapeutic option to overcome docetaxel resistance of TNBCs overexpressing Bcl-2.

• 대한골대사학회지
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• 제25권4호
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• pp.251-266
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• 2018

Background: The causal networks among genes that are commonly expressed in osteoblasts and during bone metastasis (BM) of breast cancer (BC) are not well understood. Here, we developed a machine learning method to obtain a plausible causal network of genes that are commonly expressed during BM and in osteoblasts in BC. Methods: We selected BC genes that are commonly expressed during BM and in osteoblasts from the Gene Expression Omnibus database. Bayesian Network Inference with Java Objects (Banjo) was used to obtain the Bayesian network. Genes registered as BC related genes were included as candidate genes in the implementation of Banjo. Next, we obtained the Bayesian structure and assessed the prediction rate for BM, conditional independence among nodes, and causality among nodes. Furthermore, we reported the maximum relative risks (RRs) of combined gene expression of the genes in the model. Results: We mechanistically identified 33 significantly related and plausibly involved genes in the development of BC BM. Further model evaluations showed that 16 genes were enough for a model to be statistically significant in terms of maximum likelihood of the causal Bayesian networks (CBNs) and for correct prediction of BM of BC. Maximum RRs of combined gene expression patterns showed that the expression levels of UBIAD1, HEBP1, BTNL8, TSPO, PSAT1, and ZFP36L2 significantly affected development of BM from BC. Conclusions: The CBN structure can be used as a reasonable inference network for accurately predicting BM in BC.

• Genomics & Informatics
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• 제20권2호
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• pp.18.1-18.7
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• 2022

According to long-term projections, by 2030, the world's population is predicted to reach 7.5 billion individuals, and there will be roughly 27 million new cancer cases diagnosed. The global burden of breast cancer (BC) is expected to rise. According to the Ministry of Health-Iraqi Cancer Registry, cancer is the second largest cause of death after cardiovascular disease. This study investigated the interleukin-18 (IL18) single-nucleotide polymorphisms (SNPs) -607C/A rs1946518 and -137G/C rs187238 using the sequence-specific amplification-polymerase chain reaction approach. Regarding the position -607C/A, there was a highly significant difference between the observed and expected frequencies in patients and controls (χ² = 3.16 and χ² = 16.5), respectively. The AA and CA genotypes were associated with significantly increased BC risk (odds ratio [OR], 3.68; p = 0.004 and OR, 2.83; p = 0.04, respectively). Women with the A allele had a 5.03-fold increased susceptibility to BC. The C allele may be a protective allele against BC (OR, 0.19). Although position -137G/C showed no significant differences in the CC genotype distribution (p = 0.18), the frequency of the CC genotype was significantly higher in patients than in controls. In contrast, patients had a significantly higher frequency of GC genotypes than controls (p = 0.04), which was associated with an increased risk of developing BC (OR, 2.63). The G allele frequency was significantly lower in patients than in controls (55.0% vs. 76.2%, respectively). This SNP may be considered a common genotype in the Iraqi population, with the wild-type G allele having a protective function (OR, 0.19) and the mutant C allele having an environmental effect (OR, 2.63).

• Genomics & Informatics
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• 제20권4호
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• pp.42.1-42.11
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• 2022

Breast cancer (BC) is a significant threat to female health, with both modifiable and non-modifiable risk factors. It is essential to monitor patients regularly and to raise population awareness. Increasing research also suggests that E-selectin (SELE) may increase tumor angiogenesis and the development of cancer. This study investigated SELE single-nucleotide polymorphisms (SNPs) in the following positions: rs5367T/C, rs5368C/T, rs5362T/G, and rs5362T/C. Using polymerase chain reaction, significant differences in allele and genotype frequencies were found between BC patients and controls. Position rs5368 was associated with an increased risk of BC for the CT and TT genotypes, with odds ratios (ORs) of 16.3 and 6.90 (Fisher probability = 0.0001, p = 0.005). Women with the T allele had a 19.3-fold higher incidence of BC, while allele C may be a protective allele against BC (OR, 0.05). Heterozygous genotypes at rs5367, rs5362, and rs5362 were significantly more common in BC patients, with ORs of 5.70, 4.50, and 3.80, respectively. These SNPs may be associated with the risk of BC, because the frequency of mutant alleles was significantly higher in patients (OR: 4.26, 3.83, and 4.30, respectively) than in controls (OR: 0.23, 0.30, and 0.20, respectively). These SNPs may be considered a common genotype in the Iraqi population, with the wild-type allele having a protective fraction and the mutant allele having an environmental fraction. The results also revealed a 2-fold increase in gene expression in BC patients compared to controls, with a significant effect (p = 0.017). This study's findings confirm the importance of SELE polymorphisms in cancer risk prediction.

• 대한영상의학회지
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• 제82권1호
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• pp.2-11
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• 2021

국가암검진사업에서 매년 400만 명 이상의 여성이 유방촬영술을 이용한 유방암 검진을 받고 있다. 2000년 디지털 유방촬영술의 도입 이후, 선행 연구들에 의하면 디지털 유방촬영술은 치밀유방을 가진 여성에서 제한적으로 기존의 필름 방식 또는 computed radiography (이하 CR)보다 높은 진단 정확도를 보고하였다. 최근 국가암검진사업에서 수행된 자료를 분석한 결과에 따르면 디지털 유방촬영술의 진단 정확도가 필름 또는 CR 방식에 비해서 치밀유방을 가진 여성뿐만 아니라 모든 연령대의 여성에서 검진 횟수와 상관없이 보다 정확하였다. 우리나라는 OECD 국가 중에서도 높은 유방촬영기기 보급률에도 불구하고 현재 디지털 유방촬영기기의 보급은 전체 유방촬영기기 중, 35% 정도 수준으로 더디기만 하다. 디지털 유방촬영기기로의 신속한 전환을 위하여 수가제도의 개선, 유방 영상 판독 교육 지원 등 관련 법과 제도의 정비가 필요할 것이다. 아울러 국가암검진사업에서 보다 많은 여성이 디지털 유방촬영기기를 이용한 유방암 검진을 받을 수 있도록 장비 보급의 지역 간 격차 해소를 위해 노력해야 할 것이다.

• Korean Journal of Radiology
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• 제25권4호
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• pp.343-350
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• 2024

Objective: Artificial intelligence-based computer-aided diagnosis (AI-CAD) is increasingly used in mammography. While the continuous scores of AI-CAD have been related to malignancy risk, the understanding of how to interpret and apply these scores remains limited. We investigated the positive predictive values (PPVs) of the abnormality scores generated by a deep learning-based commercial AI-CAD system and analyzed them in relation to clinical and radiological findings. Materials and Methods: From March 2020 to May 2022, 656 breasts from 599 women (mean age 52.6 ± 11.5 years, including 0.6% [4/599] high-risk women) who underwent mammography and received positive AI-CAD results (Lunit Insight MMG, abnormality score ≥ 10) were retrospectively included in this study. Univariable and multivariable analyses were performed to evaluate the associations between the AI-CAD abnormality scores and clinical and radiological factors. The breasts were subdivided according to the abnormality scores into groups 1 (10-49), 2 (50-69), 3 (70-89), and 4 (90-100) using the optimal binning method. The PPVs were calculated for all breasts and subgroups. Results: Diagnostic indications and positive imaging findings by radiologists were associated with higher abnormality scores in the multivariable regression analysis. The overall PPV of AI-CAD was 32.5% (213/656) for all breasts, including 213 breast cancers, 129 breasts with benign biopsy results, and 314 breasts with benign outcomes in the follow-up or diagnostic studies. In the screening mammography subgroup, the PPVs were 18.6% (58/312) overall and 5.1% (12/235), 29.0% (9/31), 57.9% (11/19), and 96.3% (26/27) for score groups 1, 2, 3, and 4, respectively. The PPVs were significantly higher in women with diagnostic indications (45.1% [155/344]), palpability (51.9% [149/287]), fatty breasts (61.2% [60/98]), and certain imaging findings (masses with or without calcifications and distortion). Conclusion: PPV increased with increasing AI-CAD abnormality scores. The PPVs of AI-CAD satisfied the acceptable PPV range according to Breast Imaging-Reporting and Data System for screening mammography and were higher for diagnostic mammography.

• Korean Journal of Radiology
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• 제21권4호
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• pp.442-449
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• 2020

Objective: To compare the diagnostic performance of contrast-enhanced spectral mammography (CESM) versus ultrasonography (US) in symptomatic patients with dense breasts, while using histology as the gold standard. Materials and Methods: After obtaining approval from the local ethics board, this prospective study collected data from patients with symptomatic breasts who underwent CESM and US examinations from May 1, 2017 to September 30, 2017. We then selected those with dense breasts and pathological results as our sample population. Both CESM and US results were classified by a radiologist through the Breast Imaging Reporting and Data System, and the results were compared with their corresponding histological results. The chi-square test was conducted to compare the diagnostic performance of CESM and US, and the receiver operating characteristic curves for the two imaging modalities were obtained. Results: A total of 131 lesions from 115 patients with dense breasts were included in this study. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 93.8%, 88.1%, 88.2%, 93.7%, and 90.8% for CESM, and 90.6%, 82.1%, 82.9%, 90.2%, and 86.3% for US, respectively. The p values for sensitivity, specificity, PPV, NPV, and accuracy were 0.687, 0.388, 0.370, 0.702, and 0.238, respectively. The area under the curve of CESM (0.917) was comparable with that of US (0.884); however, the differences between CESM and US were not statistically significant (p = 0.225). Eight false-positive cases and 4 false-negative cases for breast cancer were found in CESM, while 12 false-positive cases and 6 false-negative cases were found in US. Conclusion: The diagnostic performances of CESM and US are comparable in symptomatic women with dense breasts; however, the routine use of additional US imaging is questionable for lesions that can be detected by CESM.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1719-1722
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• 2012

The Wiskott-Aldrich Syndrome Protein family Verprolin - homologous proteins (WAVEs), encoded by a metastasis promoter gene, play considerable roles in adhesion of immune cells, cell proliferation, migration and destruction of foreign agents by reactive oxygen species. These diverse functions have lead to the hypothesis that WAVE proteins have multi-functional roles in regulating cancer invasiveness, metastasis, development of tumor vasculature and angiogenesis. Differentials in expression of WAVE proteins are associated with a number of neoplasms include colorectal cancer, hepatocellular cancer, lung squamous cell carcinoma, human breast adenocarcinoma and prostate cancer. In this review we attempt to unify our knowledge regarding WAVE proteins, focusing on their potentials as diagnostic markers and molecular targets for cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.4965-4972
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• 2013

This study aimed to discuss the consumption of alcohol as a risk factor for major cancers. We performed a search in the PubMed database, using the following inclusion criteria: meta-analysis published in English in the last 10 years that addressed the relationship between alcohol and the risk of developing cancer. The results indicate that moderate to heavy consumption of alcohol increases the risk of developing cancer of the oral cavity and pharynx, esophagus, stomach, larynx, colorectum, central nervous system, pancreas, breast and prostate. This review did not find any association between alcohol consumption and an increased risk of cancers of the lung, bladder, endometrium and ovary. It was also observed that alcohol consumption may be inversely related to thyroid cancer. Our systematic review has confirmed consumption of alcohol as a risk factor for the development of several types of cancer.