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The Comparative Role of BAMLET and 5-Fluorouracil in Colorectal Cancer Cells by Targeting WNT/& Beta; -Catenin Pathway BAMLET与5-氟尿嘧啶靶向WNT/& β在结直肠癌细胞中的作用比较连环蛋白通路
IF 0.7 Q4 ONCOLOGY Pub Date : 2022-09-20 DOI: 10.5812/ijcm-123140
Marziyeh Babazadeh, Mozhdeh Zamani, P. Mehrbod, P. Mokarram
Background: Aberrant activation of the WNT/β-catenin signaling pathway is involved in various types of cancers, particularly colorectal cancer (CRC), which is a prevalent malignancy. Targeting the Wnt signaling pathway has gained a reputation as an attractive therapeutic strategy, mainly because of its potential for regulating cell proliferation, migration, differentiation, angiogenesis, and apoptosis. Objectives: The aim of the current research was to investigate the effects of 5-Fluorouracil (5-FU) and bovine alpha-lactalbumin made lethal to tumor cells (BAMLET), a complex of oleic acid with bovine α-lactalbumin protein, on colon cancer cells focusing on the Wnt signaling pathway. Methods: For this purpose, HT-29 and HCT116 cells were treated with 5-FU and BAMLET, and the expression levels of Wnt signaling-related proteins (β-catenin and E-cadherin) and VEGF as angiogenesis regulators were evaluated by quantitative real-time polymerase chain reaction (RT-qPCR) and Western Blot analysis. Results: Bovine alpha-lactalbumin made lethal to tumor cells (BAMLET) treatment down-regulated the expression of β-catenin and up-regulated the expression of E-cadherin significantly compared to the 5-FU (P < 0.0001). The reduced mRNA levels of VEGF in treated cells revealed the effectiveness of 5-FU and BAMLET on angiogenesis. Conclusions: Bovine alpha-lactalbumin made lethal to tumor cells (BAMLET) can be considered for targeting the Wnt signaling pathway and angiogenesis. It is amenable to further investigation in the development of CRC treatment.
背景:WNT/β-catenin信号通路的异常激活涉及多种类型的癌症,特别是结直肠癌(CRC),这是一种常见的恶性肿瘤。靶向Wnt信号通路作为一种有吸引力的治疗策略已经获得了声誉,主要是因为它具有调节细胞增殖、迁移、分化、血管生成和凋亡的潜力。目的:本研究旨在探讨5-氟尿嘧啶(5-FU)和牛α-乳清蛋白(BAMLET)(油酸与牛α-乳清蛋白的复合物)对结肠癌细胞Wnt信号通路的影响。方法:为此,采用5-FU和BAMLET处理HT-29和HCT116细胞,采用实时荧光定量pcr (RT-qPCR)和Western Blot分析Wnt信号相关蛋白(β-catenin和E-cadherin)和VEGF作为血管生成调节因子的表达水平。结果:与5-FU相比,BAMLET能显著下调β-catenin的表达,上调E-cadherin的表达(P < 0.0001)。处理细胞中VEGF mRNA水平的降低表明5-FU和BAMLET对血管生成的作用。结论:牛α -乳白蛋白(BAMLET)可考虑靶向Wnt信号通路和血管生成。在结直肠癌治疗的发展中,这是值得进一步研究的。
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引用次数: 1
Isolation and Characterization of a Discrete Genetically Homogeneous Viral Subpopulation of Mumps Virus RS-12 Strain with Superior Oncolytic Potency Compared to Its Progenitor Virus 与前代病毒相比,具有更强溶瘤能力的腮腺炎病毒RS-12株的分离和鉴定
IF 0.7 Q4 ONCOLOGY Pub Date : 2022-09-19 DOI: 10.5812/ijcm-122781
B. Alirezaie, A. Foroughi, A. Mohammadi
Background: Oncolytic virotherapy can serve as a novel therapeutic strategy in oncology. In this study, we aimed to evaluate the oncolytic activity of the mumps virus RS-12 strain after its adaptation to cancer cells via serial passaging. Methods: To adapt the RS-12 strain-based vaccine to cancer cells, it was passaged eight times in the HT1080 cell line and was isolated via two terminal endpoint dilutions. The genetic homogeneity of isolated cancer cell-adapted RS-12 variant was confirmed by direct sequencing of regions, encompassing four known heterogeneous genomic positions. The in vitro cytotoxic effects of viruses was assessed in two different cancer cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis-inducing effects of the cancer cell-adapted variant and its parental virus on cancer cells were quantified by flow cytometry. Results: According to the chromatograms, the RS-12 strain vaccine seed exhibited two peaks at the genomic nucleotide positions 1591, 2417, 3774, and 12977. On the contrary, cancer cell-adapted RS-12, isolated by terminal endpoint serial dilutions, contained no viral subpopulations in these positions. A significant improvement was observed in the oncolytic potency of our cancer cell-adapted variant compared to its parental virus vaccine seed in vitro. Besides, the variant efficiently induced apoptosis in the human fibrosarcoma and adenocarcinoma cell lines. Conclusions: Considering the increased oncolytic potency and apoptosis-inducing capacity of this variant in cancer cells, it can be a promising option for future experiments.
背景:溶瘤病毒治疗可作为一种新的肿瘤治疗策略。在本研究中,我们旨在通过序列传代评价腮腺炎病毒RS-12株在适应癌细胞后的溶瘤活性。方法:为使RS-12疫苗适应于癌细胞,在HT1080细胞系中传代8次,经2次终点稀释分离。分离的癌细胞适应RS-12变异的遗传同质性通过区域的直接测序得到证实,包括四个已知的异质性基因组位置。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)测定法,对病毒在两种不同癌细胞系中的体外细胞毒作用进行了评估。用流式细胞术定量测定了癌细胞适应变异及其亲本病毒对癌细胞的诱导凋亡作用。结果:RS-12株疫苗种子在基因组核苷酸位置1591、2417、3774和12977处出现两个峰。相反,通过末端序列稀释分离的癌细胞适应RS-12在这些位置不含病毒亚群。与亲本病毒疫苗种子相比,我们的癌细胞适应变体在体外的溶瘤效力有显著改善。此外,该突变体还能有效诱导人纤维肉瘤和腺癌细胞的凋亡。结论:考虑到该变异在癌细胞中的溶瘤能力和诱导凋亡能力增强,它可能是未来实验的一个有希望的选择。
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引用次数: 0
Graft-Versus-Host Disease Associated Post-operative Complications After Pelvic Reconstructive Surgery: A Case Report 盆腔重建术后移植物抗宿主病相关并发症1例报告
IF 0.7 Q4 ONCOLOGY Pub Date : 2022-09-19 DOI: 10.5812/ijcm-11594
Christopher P. Chung, A. Nademanee, Grace Wakabayashi, M. Sadeghi
Introduction: Graft-versus-host disease (GVHD) can occur after allogeneic bone marrow transplantation (BMT) and can affect the skin, gastrointestinal tract, lungs, liver, and vulvovaginal areas. Case Presentation: This case report described a 65-year-old multiparous patient with myelodysplastic syndrome who underwent a matched unrelated donor transplant approximately 3 years before her surgery. After her BMT she developed GVHD. She underwent anterior and posterior repair and uterosacral ligament suspension for stage III post-hysterectomy vaginal vault prolapse. Her postoperative course was complicated by mental status changes, abnormal liver function tests, and increasing abdominal distention. All her post-operative symptoms were resolved with conservative management. Conclusions: This case presentation highlights the potential atypical post-operative course of BMT patients with GVHD. The management of patients with GVHD relies heavily on the early involvement of hematologists.
移植物抗宿主病(GVHD)可在同种异体骨髓移植(BMT)后发生,可影响皮肤、胃肠道、肺、肝脏和外阴阴道区域。病例介绍:本病例报告描述了一名65岁的多胎骨髓增生异常综合征患者,她在手术前大约3年接受了匹配的非亲属供体移植。BMT后,她患上了GVHD。她接受了子宫切除术后第三期阴道穹窿脱垂的前后修复和子宫骶韧带悬吊。术后出现精神状态改变、肝功能异常、腹胀加重等并发症。经保守治疗,术后症状全部消失。结论:本病例报告强调了BMT合并GVHD患者的潜在非典型术后病程。GVHD患者的管理在很大程度上依赖于血液学家的早期参与。
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引用次数: 0
The Association of rs5745687 Polymorphism Located at HGF Gene with Risk of Gastric and Breast Cancer in the Helicobacter Positive Patients of Isfahan Population Isfahan人群幽门螺杆菌阳性患者HGF基因rs5745687多态性与胃癌和乳腺癌风险的关系
IF 0.7 Q4 ONCOLOGY Pub Date : 2022-09-18 DOI: 10.5812/ijcm-118832
Mehrnoush Azadeh Jouneghani, F. Keshavarzi, Nahid Haghnazari, S. Amini, Z. Hooshmandi
Background: Hepatocyte growth factor (HGF) protein regulates cell growth, motility, and morphogenesis in a variety of cells and tissues by binding to the HGF receptor. The rs5745687 SNPs in the introns of the HGF gene could affect the splicing and expression of HGF mRNA. Objectives: In this study, the genotype frequency of rs5745687 in breast cancer (BC) and gastric cancer (GC) (positive helicobacter) patients has been investigated and compared with the healthy controls in the Isfahan population. Methods: Firstly, initial bioinformatics studies were done. Then, according to the results, bioinformatics High-Resolution Melt (HRM) and Real-Time PCR were recruited to determine genotypes rs5745678 for 432 participants in the case-control analysis (84 GC with 126 healthy control samples, as well as 111 BC cases with 111 normal controls). The conditional logistic regression model was used to measure odds ratios (OR) and 95% confidence intervals (CI) to produce these cancers based on genotype frequency. Results: The homozygote genotype of the mutant (G) allele of rs5745678 has a significant association with the lower risk of gastric cancer (P-value < 0.0001) and this allele can increase the risk of GC in a co-dominant model (OR: 5.541, P-value < 0.0001). Also, the rs5745678 SNP had a significant association with the clinicopathological features (age, smoking, H. Pylori infection) in GC patients. Conclusions: The presence of a single G allele in rs5745678 heterozygote (AG/AA) and co-dominant (AG/AA+GG) models could significantly impact GC pathogenicity in different ways. There was no significant correlation between the rs5745678 polymorphism and BC (P-value: 0.671) in the studied sample size.
背景:肝细胞生长因子(HGF)蛋白通过与HGF受体结合调节多种细胞和组织中的细胞生长、运动和形态发生。HGF基因内含子中的rs5745687 snp可以影响HGF mRNA的剪接和表达。目的:本研究调查了Isfahan人群中乳腺癌(BC)和胃癌(GC)(幽门螺杆菌阳性)患者rs5745687基因型频率,并与健康对照进行了比较。方法:首先进行初步的生物信息学研究。然后,根据结果,利用生物信息学高分辨率熔融(HRM)和实时荧光定量PCR (Real-Time PCR)对432名参与者进行病例对照分析(84例GC与126例健康对照,111例BC与111例正常对照),确定rs5745678基因型。使用条件逻辑回归模型来测量基于基因型频率产生这些癌症的优势比(OR)和95%置信区间(CI)。结果:rs5745678突变(G)等位基因的纯合子基因型与较低的胃癌风险显著相关(p值< 0.0001),该等位基因在共显性模型中可增加胃癌风险(OR: 5.541, p值< 0.0001)。rs5745678 SNP与GC患者的临床病理特征(年龄、吸烟、幽门螺杆菌感染)有显著相关性。结论:rs5745678杂合子(AG/AA)和共显性(AG/AA+GG)模型中单个G等位基因的存在可通过不同方式显著影响胃癌的致病性。rs5745678多态性与BC在研究样本量上无显著相关(p值为0.671)。
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引用次数: 0
Parametric Models for Survival Analysis of Childhood Cancer Patients' Data 儿童癌症患者数据生存分析的参数化模型
IF 0.7 Q4 ONCOLOGY Pub Date : 2022-09-18 DOI: 10.5812/ijcm-127430
Aliasghar Keramatinia, Maryam Mohseny, Esmat Davoudi Monfared, Fatemeh Sadat Hosseini-Baharanchi, Fateme Shahabi, Nilofar Safavi Naeini, Sima Kianpour Rad, Mojgan Sheikhpour, Seyed Ehsan Beladian- Behbhan, Ayad Bahadorimonfared, Mandana Aphsharpad, A. Movafagh
Background: The rate of childhood cancer death has dropped steadily over the past 50 years. The pediatric cancer risk has remained under investigation. Objectives: This study aims at investigating the associated factors with the survival of pediatric patients with retinoblastoma, sarcoma, brain tumor, and leukemia cancer. Methods: The cohort study of 1879 children with retinoblastoma, sarcoma, brain tumor, and leukemia aged < 1, 1 - 5, 6 - 10, 11 - 15, and > 15 years in Mahak Hospital and Rehabilitation Complex from 2007 to 2016 were enrolled in the study. Median survival time was reported for each cancer. Parametric survival models including Gompertz, Weibull, lognormal, and log‑logistic models were fitted. Then, the model with almost minimum Akaike information criterion (AIC) was chosen. The hazard ratio (HR) and the analysis were performed by R3.5.1. Results: Totally, 270 (14.37%) patients with Retinoblastoma, 667 (35.5%) with leukemia, 625 (33.26%) with a Brain tumor, and 317 (16.87%) with Sarcoma were included in this study; 815 (43.37%) patients were female. Gompertz's model was chosen to fit the data due to the minimum AIC. The associated factors with the survival of childhood cancers were as follows: age < 1 year, parental relation, loco-regional relapse and chemotherapy alone (HR: 7.63, 1.56, 4.61, 1.12) in leukemia, other nationalities, metastasis or metastasis and loco-regional relapse and chemotherapy alone (HR = 3.74, 5.75, 2.12) in retinoblastoma, loco-regional relapse and metastasis (HR = 2.40, 3.71) in brain tumor, other ages except for 5 - 10 years, parental relation, chemotherapy alone, and metastasis (HR = 33.3, 1.80, 3.57, 3.8) in sarcoma. Conclusions: Age, parental familial relationships, combination therapy, and metastasis of primary cancer were the risk factors for survival of children with 4 common cancers of leukemia, retinoblastoma, brain tumors, and sarcoma, using the Gompertz model.
背景:儿童癌症死亡率在过去50年中稳步下降。儿童癌症风险仍在调查中。目的:本研究旨在探讨影响儿童视网膜母细胞瘤、肉瘤、脑肿瘤和白血病患者生存的相关因素。方法:选取2007 - 2016年Mahak医院及康复中心1879例年龄< 1、1 - 5、6 - 10、11 - 15和> 15岁的视网膜母细胞瘤、肉瘤、脑肿瘤和白血病患儿为研究对象。报告了每种癌症的中位生存时间。参数生存模型包括Gompertz、Weibull、对数正态和对数logistic模型。然后,选择具有几乎最小赤池信息准则(Akaike information criterion, AIC)的模型。风险比(HR)和分析采用R3.5.1。结果:共纳入视网膜母细胞瘤270例(14.37%),白血病667例(35.5%),脑肿瘤625例(33.26%),肉瘤317例(16.87%);女性815例(43.37%)。由于AIC最小,选用Gompertz模型拟合数据。影响儿童肿瘤生存的相关因素有:年龄< 1岁、父母关系、局部-区域复发和单独化疗(HR:白血病(7.63,1.56,4.61,1.12),其他民族,视网膜母细胞瘤(HR = 3.74, 5.75, 2.12),脑肿瘤(HR = 2.40, 3.71),肉瘤(HR = 33.3, 1.80, 3.57, 3.8),其他年龄(5 - 10岁除外),父母关系,单纯化疗,转移(HR = 33.3, 1.80, 3.57, 3.8)。结论:采用Gompertz模型,年龄、父母家庭关系、联合治疗和原发肿瘤转移是影响白血病、视网膜母细胞瘤、脑肿瘤和肉瘤4种常见癌症患儿生存的危险因素。
{"title":"Parametric Models for Survival Analysis of Childhood Cancer Patients' Data","authors":"Aliasghar Keramatinia, Maryam Mohseny, Esmat Davoudi Monfared, Fatemeh Sadat Hosseini-Baharanchi, Fateme Shahabi, Nilofar Safavi Naeini, Sima Kianpour Rad, Mojgan Sheikhpour, Seyed Ehsan Beladian- Behbhan, Ayad Bahadorimonfared, Mandana Aphsharpad, A. Movafagh","doi":"10.5812/ijcm-127430","DOIUrl":"https://doi.org/10.5812/ijcm-127430","url":null,"abstract":"Background: The rate of childhood cancer death has dropped steadily over the past 50 years. The pediatric cancer risk has remained under investigation. Objectives: This study aims at investigating the associated factors with the survival of pediatric patients with retinoblastoma, sarcoma, brain tumor, and leukemia cancer. Methods: The cohort study of 1879 children with retinoblastoma, sarcoma, brain tumor, and leukemia aged < 1, 1 - 5, 6 - 10, 11 - 15, and > 15 years in Mahak Hospital and Rehabilitation Complex from 2007 to 2016 were enrolled in the study. Median survival time was reported for each cancer. Parametric survival models including Gompertz, Weibull, lognormal, and log‑logistic models were fitted. Then, the model with almost minimum Akaike information criterion (AIC) was chosen. The hazard ratio (HR) and the analysis were performed by R3.5.1. Results: Totally, 270 (14.37%) patients with Retinoblastoma, 667 (35.5%) with leukemia, 625 (33.26%) with a Brain tumor, and 317 (16.87%) with Sarcoma were included in this study; 815 (43.37%) patients were female. Gompertz's model was chosen to fit the data due to the minimum AIC. The associated factors with the survival of childhood cancers were as follows: age < 1 year, parental relation, loco-regional relapse and chemotherapy alone (HR: 7.63, 1.56, 4.61, 1.12) in leukemia, other nationalities, metastasis or metastasis and loco-regional relapse and chemotherapy alone (HR = 3.74, 5.75, 2.12) in retinoblastoma, loco-regional relapse and metastasis (HR = 2.40, 3.71) in brain tumor, other ages except for 5 - 10 years, parental relation, chemotherapy alone, and metastasis (HR = 33.3, 1.80, 3.57, 3.8) in sarcoma. Conclusions: Age, parental familial relationships, combination therapy, and metastasis of primary cancer were the risk factors for survival of children with 4 common cancers of leukemia, retinoblastoma, brain tumors, and sarcoma, using the Gompertz model.","PeriodicalId":44764,"journal":{"name":"International Journal of Cancer Management","volume":"15 1","pages":""},"PeriodicalIF":0.7,"publicationDate":"2022-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75001266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prevalence of DNA Mismatch Repair Deficiency in Endometrial Cancer Using Immunohistochemistry 应用免疫组织化学研究子宫内膜癌中DNA错配修复缺陷的患病率
IF 0.7 Q4 ONCOLOGY Pub Date : 2022-09-13 DOI: 10.5812/ijcm-119065
B. Mehdizadeh, M. Gharib, A. Jafarian, M. Afzalaghaee, F. Homaee Shandiz, Amirhosein Irajpour
Background: Endometrial cancer (EC) is known as the most common malignancy of the female reproductive system, suggested to be associated with hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome (LS). Objectives: Therefore, the aim of the present study was to screen for LS in patients with EC using immunohistochemistry (IHC). Methods: In this retrospective cross-sectional study, the patients with EC, referred to Qaem Hospital, Mashhad, Iran, from 2015 - 2019, were enrolled. Paraffin-embedded tissue blocks were then examined via IHC for the expression of four mismatch repair (MMR) proteins, including MLH1, MSH2, MSH6, and PMS2. The demographic and tumor-related data were also extracted from medical records and pathology reports. The data were consequently analyzed at the significance level of P < 0.05. Results: A total number of 100 patients with EC were evaluated using IHC, and 12 (12%) cases were found suspected. As well, no significant relationship was observed between LS and age, tumor site, tumor histology, tumor size, tumor grade, tumor-infiltrating lymphocytes (TILs), and a family/personal history of malignancies. Conclusions: The prevalence of LS based on the IHC expression of the MMR proteins (MLH1, MSH2, MSH6, and PMS2) was 12% in the patients with EC. There was also no significant relationship between the cases suspected and the demographic and tumor-related data.
背景:子宫内膜癌(EC)是女性生殖系统最常见的恶性肿瘤,与遗传性非息肉病性结直肠癌(HNPCC)或Lynch综合征(LS)有关。目的:因此,本研究的目的是使用免疫组织化学(IHC)筛查EC患者的LS。方法:在这项回顾性横断面研究中,纳入2015 - 2019年在伊朗马什哈德Qaem医院转诊的EC患者。石蜡包埋组织块通过免疫组化检测四种错配修复(MMR)蛋白的表达,包括MLH1、MSH2、MSH6和PMS2。人口统计学和肿瘤相关数据也从医疗记录和病理报告中提取。结果以P < 0.05的显著性水平进行分析。结果:共对100例EC患者进行免疫组化评估,发现疑似12例(12%)。此外,LS与年龄、肿瘤部位、肿瘤组织学、肿瘤大小、肿瘤分级、肿瘤浸润淋巴细胞(til)和恶性肿瘤家族史/个人病史之间无显著关系。结论:基于MMR蛋白(MLH1、MSH2、MSH6和PMS2)在EC患者中IHC表达的LS患病率为12%。疑似病例与人口统计学和肿瘤相关数据之间也没有显著关系。
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引用次数: 0
Evaluation of TP53 and HER-2/neu Genes Expression Levels in Gestational Trophoblastic Diseases Cases and Determining Their Predictive Value in Diagnosis of Malignancy and Disease Progression 妊娠滋养细胞疾病病例中TP53和HER-2/neu基因表达水平的评估及其在恶性肿瘤和疾病进展诊断中的预测价值
IF 0.7 Q4 ONCOLOGY Pub Date : 2022-09-12 DOI: 10.5812/ijcm-119264
Fatemeh Hadi, N. Kazemi, M. Hosseini, A. Ebrahimi
Background: Gestational trophoblastic disease (GTD) is a general term that includes several types of pathologically different diseases, which range from hydatidiform mole to choriocarcinoma. Early differentiation of these types is important to determine treatment strategy and prognosis. Objectives: Genetic markers such as TP53 and HER-2/neu expression are recently shown to have diagnostic and prognostic values. The aim of this study was to evaluate its significance. Methods: We enrolled 62 patients diagnosed with GTD referred to Imam Hossein Hospital in Tehran, Iran between 2012 and 2017. Endometrial pathologic specimens were stained, using the immunohistochemistry (IHC) method for the expression of TP53 and HER-2/neu genes. Expression levels determined by IHC were compared between final pathologic diagnoses, using one-way ANOVA test (analysis of variances), which detects significant differences between the means of 3 or more independent groups. Results: Out of 62 participants, 32 and 24 cases were diagnosed as partial and complete hydatidiform mole, respectively. Four cases had invasive hydatidiform mole and only 2 cases were diagnosed as choriocarcinoma. Analysis using ANOVA demonstrated that expression levels of both TP53 and HER-2/neu genes are significantly higher among patients with invasive form and choriocarcinoma compared with non-invasive hydatidiform mole (P < 0.05 for both genes). The receiver operating characteristic (ROC) curve for each gene showed that more than 55% positive staining for the TP53 gene can differentiate non-invasive hydatidiform mole from invasive form and choriocarcinoma with 100% sensitivity, and 92.9% specificity. Conclusions: TP53 expression might serve as a potential diagnostic aid to differentiate benign and malignant GTDs and a future target for adjusting treatment based on the expression levels.
背景:妊娠滋养细胞疾病(GTD)是一个总称,包括几种不同病理类型的疾病,范围从葡萄胎到绒毛膜癌。这些类型的早期鉴别对于确定治疗策略和预后很重要。目的:遗传标记如TP53和HER-2/neu表达最近被证明具有诊断和预后价值。本研究的目的是评价其意义。方法:我们纳入了2012年至2017年在伊朗德黑兰伊玛目侯赛因医院转诊的62例诊断为GTD的患者。对子宫内膜病理标本进行免疫组化(IHC)染色,检测TP53和HER-2/neu基因的表达。将IHC检测的表达水平与最终病理诊断进行比较,采用单因素方差分析(one-way ANOVA test,方差分析),发现3个或更多独立组的平均值之间存在显著差异。结果:62例患者中,32例诊断为部分葡萄胎,24例诊断为完全葡萄胎。4例有浸润性葡萄胎,2例诊断为绒毛膜癌。方差分析显示,侵袭性绒毛膜癌和绒毛膜癌患者中TP53和HER-2/neu基因的表达水平明显高于非侵袭性葡萄胎癌患者(两种基因均P < 0.05)。各基因的受试者工作特征(ROC)曲线显示,TP53基因55%以上阳性染色可区分非侵袭性葡萄胎、侵袭性葡萄胎和绒毛膜癌,敏感性为100%,特异性为92.9%。结论:TP53表达可作为鉴别GTDs良恶性的潜在诊断手段,并可作为未来根据表达水平调整治疗的靶点。
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引用次数: 0
The Expression Pattern of Non-apoptotic Cell Death Pathway in Osteosarcoma: Necroptosis and Autophagy as Backup Mechanisms for Therapeutics Strategy 骨肉瘤非凋亡细胞死亡通路的表达模式:坏死和自噬作为治疗策略的备份机制
IF 0.7 Q4 ONCOLOGY Pub Date : 2022-09-12 DOI: 10.5812/ijcm-117962
Marzieh Neykhonji, Shima Nazem, H. Ghaedi, A. Mirzaei, Masoumeh Tavakoli-Yaraki, Z. Shahsavari
Background: Among the primary bone tumors, osteosarcoma accounts for a malignant tumor with a high rate of progression and poor prognosis. Despite the achievement of combined therapy regimens in improving patients’ overall survival, patients with osteosarcoma confront the chemoresistance obstacle. Objectives: This study aimed at determining the expression pattern of autophagy and necroptosis pathways mediators in osteosarcoma tumors. Methods: The expression level of autophagy main mediators such as autophagy-associated protein 5 (ATG5), Beclin 1 (BECN1), and microtubule-associated protein 1A/1B-light chain 3 (LC3), necroptosis biomarkers such as receptor-interacting protein kinases (RIPK1 and RIPK3), and mixed lineage kinase domain-like (MLKL) were evaluated in 80 bone tissues including 60 bone tumors (40 malignant tumors and 20 benign tumors) and 20 margin tissues, using real-time PCR. The correlations of gene expression levels with the patient’s clinical and pathological features were considered. Results: Based on our data, ATG5, BECN1 and LC3 expression were down-regulated in osteosarcoma tumors compared to margin tissues. Also, malignant osteosarcoma tumors showed a significant decrease in the expression level of RIPK1 and MLKL as necroptosis regulators, which revealed a correlation with tumor malignancy. In addition, the higher expression levels of BECN1, LC3, RIPK1, and MLKL were observed in tumor tissues of patients under the chemotherapy regimen, indicating the relevance of autophagy and necroptosis pathways with the patient’s response to therapy. Conclusions: Reduction in the expression level of autophagy and necroptosis mediators in high-grade osteosarcoma tumors indicates the possible impact of these pathways on the rate of proliferation and growth of osteosarcoma tumor cells and can emphasize the importance of cell death alternative pathways for treatment when apoptosis machinery is mutated and cause chemoresistance.
背景:骨肉瘤是原发性骨肿瘤中进展率高、预后差的一种恶性肿瘤。尽管联合治疗方案在提高患者总体生存率方面取得了成就,但骨肉瘤患者面临化疗耐药障碍。目的:本研究旨在确定骨肉瘤肿瘤中自噬和坏死凋亡通路介质的表达模式。方法:采用实时荧光定量PCR技术检测自噬相关蛋白5 (ATG5)、Beclin 1 (BECN1)、微管相关蛋白1A/ 1b -轻链3 (LC3)等自噬主要介质、受体相互作用蛋白激酶(RIPK1、RIPK3)、混合谱系激酶结构域样(MLKL)等坏死坏死生物标志物在60例骨肿瘤(40例恶性肿瘤和20例良性肿瘤)和20例边缘组织中的表达水平。考虑基因表达水平与患者临床和病理特征的相关性。结果:根据我们的数据,与边缘组织相比,ATG5、BECN1和LC3在骨肉瘤肿瘤中的表达下调。恶性骨肉瘤肿瘤中坏死下垂调节因子RIPK1和MLKL的表达水平显著降低,与肿瘤恶性相关。此外,化疗方案下患者的肿瘤组织中BECN1、LC3、RIPK1、MLKL的表达水平较高,表明自噬和坏死下垂途径与患者对治疗的反应相关。结论:高级别骨肉瘤肿瘤中自噬和坏死坏死介质表达水平的降低表明这些途径可能影响骨肉瘤肿瘤细胞的增殖和生长速度,并可以强调细胞死亡替代途径在凋亡机制发生突变并引起化疗耐药时的重要性。
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引用次数: 0
Investigation of the Global Trend of Thyroid Cancer Incidence and Its Relationship with the Prevalence of Type 2 Diabetes: An Application of Longitudinal Random Effects Regression Model 甲状腺癌全球发病率趋势及其与2型糖尿病患病率关系的研究:纵向随机效应回归模型的应用
IF 0.7 Q4 ONCOLOGY Pub Date : 2022-09-11 DOI: 10.5812/ijcm-120720
Maryam Rezaei Gazaki, Mohsen Askari Shahi, R. Malboosbaf, S. Jambarsang
Background: In recent years, the incidence of thyroid cancer has been increasing. On the other hand, those with insulin resistance often have higher thyroid volume and a risk of developing thyroid nodules. Objectives: The objective of this study was to investigate the global trend of thyroid cancer and its relationship with the prevalence of type 2 diabetes. Methods: The information in the present study is related to the prevalence of type 2 diabetes and the incidence of thyroid cancer in all countries of the world, which was extracted from the Global Burden of Disease site during 1990 - 2019. In order to investigate the relationship between the prevalence of type 2 diabetes and the incidence of thyroid cancer, a longitudinal random effects regression model was used with both random effects of intercept and the slope of the regression line. Results: The results showed that the risk of developing thyroid cancer associated with diabetes was 0.00024 (95% CI 0.00023 - 0.00025), 24 persons per 100000. This significance level was also evaluated separately in men and women, so that the relative risk in men was estimated to be 0.00018 (95% CI 0.00017 - 0.00019) and in women equal to 0.00033 (95% CI 0.00031 - 0.00035). Conclusions: Findings showed that type 2 diabetes can be a risk factor for thyroid cancer. So that this effect can be considered on both men and women and is more intense in women than men.
背景:近年来,甲状腺癌的发病率呈上升趋势。另一方面,那些有胰岛素抵抗的人往往有更高的甲状腺体积和发展甲状腺结节的风险。目的:本研究的目的是调查甲状腺癌的全球趋势及其与2型糖尿病患病率的关系。方法:本研究的数据来源于1990 - 2019年全球疾病负担网站(Global Burden of Disease site),与世界各国2型糖尿病患病率和甲状腺癌发病率相关。为了探讨2型糖尿病患病率与甲状腺癌发病率之间的关系,采用纵向随机效应回归模型,随机效应为截距和回归线斜率。结果:结果显示,患甲状腺癌合并糖尿病的风险为0.00024 (95% CI 0.00023 - 0.00025),每10万人24人。该显著性水平在男性和女性中也分别进行了评估,因此男性的相对风险估计为0.00018 (95% CI 0.00017 - 0.00019),女性的相对风险为0.00033 (95% CI 0.00031 - 0.00035)。结论:研究结果表明,2型糖尿病可能是甲状腺癌的危险因素。因此,这种影响对男性和女性都有影响,而且女性比男性更强烈。
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引用次数: 0
Pregnancy in Breast Cancer Survivors; Is It Safe? 乳腺癌幸存者怀孕安全吗?
IF 0.7 Q4 ONCOLOGY Pub Date : 2022-09-11 DOI: 10.5812/ijcm-128858
A. Akbari, Mansoureh Baniasadi
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引用次数: 0
期刊
International Journal of Cancer Management
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