Objectives: Peroxisomal trans-2-enoyl-CoA reductase (PECR) encodes proteins related to fatty acid metabolism and synthesis. It has been confirmed that PECR has decreased expression in colon cancer and breast cancer, while the role of PECR in liver cancer is unknown. We aimed to study the role and mechanism of PECR in the genesis and development of liver cancer.Methods: In this study, the expression of PECR was queried in the Cancer Genome Atlas Database and Western Blotting and RT-PCR experiments were carried out in paired liver cancer tissues to detect the expression of PECR. Functional tests were evaluated by cell count kit-8 (CCK-8), Flow cytometry, wound healing assay, Transwell, migration. In vivo study, we constructed a nude mouse tumorigenic model to observe the effect of PECR on the proliferation of liver cancer. And the tumor body of the mouse was taken out for histochemistry (IHC). Multiple Cox regression was used to analyze the correlation between PECR and Clinicopathology.Results: We confirmed that the overexpression of PECR inhibited the proliferation, migration and invasion of hepatocellular carcinoma and promoted the apoptosis of hepatocellular carcinoma. The low expression group of PECR promoted the proliferation and metastasis of liver cancer. In vivo, overexpression of PECR inhibits the proliferation of mouse tumors. In addition, the mechanism study shows that PECR may indirectly affect the proliferation of hepatocellular carcinoma cells through ERK pathway.Conclusion: In general, PECR may be a new diagnostic marker and a potential therapeutic target for hepato-cellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common types of cancer, which is associated with a poor prognosis. It is necessary to identify novel prognostic biomarkers and therapeutic targets to improve the survival of patients with HCC. In the present study, a seven-gene signature associated with HCC progression was identified using weighted gene co-expression network analysis and least absolute shrinkage and selection operator, and its prognostic prediction value was confirmed in The Cancer Genome Atlas-liver HCC and International Cancer Genome Consortium liver cancer-RIKEN, Japan cohorts. Subsequently, a rarely reported gene, epoxide hydrolase 2 (EPHX2), was selected for further validation. Downregulation of EPHX2 in HCC was revealed using multiple expression datasets. Furthermore, reduced expression of EPHX2 was confirmed in HCC tissue samples and cell lines using reverse transcription-quantitative polymerase chain reaction and western blotting. Additionally, Kaplan-Meier survival curves indicated that patients with higher EPHX2 expression exhibited better prognosis, and clinicopathological analysis also revealed elevated EPHX2 levels in patients with early-stage HCC. Notably, EPHX2 was identified as an independent prognostic biomarker for overall survival of patients with HCC. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis and gene set enrichment analysis were performed to elucidate the functions of EPHX2. The results suggested that EPHX2 expression was closely associated with metabolic reprogramming. Finally, the prognostic value of EPHX2 was evaluated using HCC tissue microarrays. In conclusion, downregulation of EPHX2 was significantly associated with the development of HCC; therefore, EPHX2 may be considered a putative therapeutic candidate for the targeted treatment of HCC.
Metabolic syndrome has been previously identified as a risk factor for breast cancer and is increasingly a public health concern. This study aims to investigate the prevalence of metabolic syndrome and its components among primary breast cancer and control population. The clinical data of metabolic syndrome and its components in the breast cancer (605 cases) and control population (3212 cases), from Breast Cancer Center and Physical Examination Center of Chongqing, China, from July 2015 to February 2017, were collected for comparative analysis. This study was prospectively registered in Chinese Clinical Trial Registry (http://www.chictr.org.cn/, number: ChiCTR-OOB-15007543). The prevalence of metabolic syndrome in breast cancer (32.6%) was obviously higher than that in control population (18.2%) (p<0.001; OR: 2.173, 95%CI: 1.793 to 2.633). With age stratification, the prevalence of metabolic syndrome in breast cancer group aged below 60 years (24.9%, p<0.001; OR: 2.216, 95%CI: 1.744 to 2.816) and equal/above 60 years (58.3%, p<0.001; OR: 2.291, 95%CI: 1.580 to 3.322) were also statistically higher than those (13.0% & 37.9%) in control population, respectively. Breast cancer women were more likely to have preobese (BMI 25.0-29.9) or obesity (BMI ≥30.0), broader waist circumference, lower HDL-C level, higher systolic and/or diastolic blood pressure and higher fasting blood glucose level compared to the control population, corresponding prevalence were 31.7%vs.19.4%, 76.0%vs.29.6%, 37.4%vs.30.4%, 34.2%/27.3%vs.27.6%/14.2% and 25.0%vs.20.1%, respectively (p<0.01). In summary, there is high prevalence of metabolic syndrome and its components in Chinese breast cancer women, and metabolic syndrome is closely related with breast cancer. Therefore, screening and prevention strategy of metabolic syndrome should be carried out in the management of breast cancer.
1临床资料55岁,女性,因"右乳包块7d"入院。体检:右乳外上象限扪及一约3.5 cm×3.0 cm肿块,质中、无压痛、边界欠清、活动度差。乳腺彩超:右乳外上象限探及一大小约32 mm×27 mm异常回声,边界不清,外形不规则。钼靶示:右乳外上毛刺状肿块,约36 mm×33 mm,其内伴较多不规则微小钙化灶。既往有糖尿病病史。入院完善相关检查和积极术前准备后,行右乳腺癌改良根治术,术后重庆医科大学病理检测中心诊断:右乳浸润性导管癌,腋窝淋巴结见癌转移(1/11),原发灶免疫组
Breast cancer is one of the most common malignant tumors in females.Recent years,surgery,chemotherapy as well as other systemic therapy had greatly improved the prognosis of the patients.However,damage of ovarian function by chemotherapy lowered life quality,especially for young females.At present,there are several methods to protect the ovarian function of female patients undergoing chemotherapy,such as administration of a gonadotropin-releasing hormone (GnRH) analogs,ovarian cryopreservation,unfertilized ova cryopreservation,embryo cryopreservation,inhibitors of apoptosis,etc.Each method has its advantage,disadvantage and indications.Issues related to ovarian protection are reviewed here.
七年长学制医学教育是为了适应医疗卫生现代化建设的要求的一种培养方式,承担着培养高层次医学人才的任务.将探讨如何在临床阶段将七年制医学生培养成为符合卫生事业发展需求的具有胜任临床工作能力,同时有创新意识、科研素质和科研能力的医疗卫生骨干人才.
We performed a case-control study to investigate the prevalence and clinicopathological features of breast cancer patients with hepatitis B virus (HBV) infection in China. The clinical data for 2,796 female patients with newly diagnosed, primary breast cancer were evaluated. A total of 234 breast cancer patients with HBV infection (the case group; positive for hepatitis B surface antigen [HBsAg]) and 444 breast cancer patients without HBV infection (the control group; negative for HBsAg, hepatitis B surface antibody, hepatitis B envelope antigen, hepatitis B envelope antibody, and hepatitis B core antibody) were selected for study. Analysis of the clinicopathological features revealed that the metastatic axillary lymph node ratio was lower in the case group than the control group, as was the proportion of patients with pathological T stage ≥T2. No differences in the expression levels of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, p53, or Ki67 were observed between the case and control groups. These data indicate that the rate of HBV infection is high among female breast cancer patients in China, and that HBsAg-positive breast cancer patients were generally diagnosed at an earlier stage and had fewer lymph node metastases.
Neoadjuvant chemotherapy remains an inseparable part of systemic therapy for hormone receptor positive (HR+) advanced breast cancer. However, efficacy of neoadjuvant chemotherapy in this subtype of patients is inferior to its hormone receptor negative counterpart. Several preclinical and clinical studies have suggested that it was growth rate rather than hormone receptor status that determined sensitivity to chemotherapy. In addition, estrogen was proved to recruit more HR+ breast cancer cells into actively dividing phase according to various studies. For premenopausal females, sexual hormone like estradiol fluctuates with menstrual cycle. When menstruation occurs, women have the lowest level of estradiol, which is resemble to pharmaceutical effect of endocrine therapy. If chemotherapy is given to females during menstruation, it’s almost equal to concurrent use of chemotherapy and endocrine therapy, which is not recommended by guideline. Accordingly, chemotherapy would attain best efficacy applied at the peak of estradiol, because more tumor cells being in actively dividing phase recruited by comparatively high level of estradiol would help cytotoxic agents function better given that majority of chemotherapeutic drugs are cellular phase dependent. We name this rhythmic mode of chemotherapy for premenopausal HR+breast cancer females, giving chemotherapy to patients when estradiol rises and avoiding prescription at menstruation, tidal chemotherapy. It’s postulated that tidal chemotherapy would improve efficacy of neoadjuvant chemotherapy for premenopausal HR+breast cancer females, achieve more pathologic complete response and in the long run improve prognosis.
BACKGROUND:Triple negative breast cancer (TNBC) is not sensitive to RAS/RAF/ERK signaling pathway (ERK pathway) targeting therapy, due to the absence of excessive activation of ERK pathway. However, the kinase cascades might be activated after chemotherapy in TNBC. Here we aimed to predict whether ERK pathway targeting therapy could be used as an adjuvant therapy in TNBC.METHODS:Within online GEO datasets (GSE43816 and GSE54326), gene set enrichment analysis (GSEA) was performed to detect molecular changes in epirubicin treated TNBC samples and cells, ERK pathway components and regulation genes changes were included.RESULTS:In epirubicin treated TNBC samples and cells, we found ERK pathway components (eg. MAPK13, MAP3K1, MAPK12, MAPK11 and MAPKAPK3) were obviously enriched, also, expression of ERK pathway positive regulation genes significantly increased (P<0.05) and negative regulation genes decreased (P<0.05) in epirubicin resistant cells. Moreover, phosphorylated ERK levels were significantly elevated in MDA-MB-231 cells after epirubicin treatment.CONCLUSION:ERK signaling pathway was more activated in epirubicin treated TNBC, possibly contributing to the epirubicin resistance in TNBC, it implicated that ERK pathway could be used as an novel candidate for targeting therapy in refractory and relapse TNBC.
代谢综合征(metabolic syndrome,MS)是以肥胖和胰岛素抵抗为中心的多种代谢性危险因素在个体内集结的状态,主要组分包括肥胖、高血糖、高胰岛素血症、血脂异常和高血压等.研究表明代谢综合征不仅是心血管病的危险因素,还与乳腺癌的发生和预后相关.本文综述代谢综合征与乳腺癌患病风险的关系及其致乳腺癌的可能机制,为乳腺癌的预防、治疗及预后提供新的策略.
In metastatic breast cancer (MBC), hormone receptor positive (HR+), human epidermal growth factor negative (HER2−) subtype accounts for the majority. With various new modalities available to prolong life span in this group of patients, the effect is distant from optimum. Prevalent strategy of treating postmenopausal HR+ HER2− MBC is application of chemotherapy (CT) after progression of disease on endocrine therapy (ET) of several lines. Generally, ET targets HR+ ingredients and CT works better with HR− tumor cells. HR+ MBC, though hormone-sensitive, has HR− portion which reacts poorly to ET. Thus, sequential use of ET and CT neglects its insensitive part and gives rise to drug resistance, while alleviation of tumor burden is the top priority in metastatic setting. Chemohormonal therapy (i.e. concomitant use of ET and chemotherapy) complements for the shortcoming of current therapy strategy targeting both HR+ and HR− ingredients theoretically. Fulvestrant, a pure estrogen receptor antagonist and down-regulator, could be a promising agent using concurrently with CT based on chemosensitizing character shown in preclinical and pilot clinical studies. It is hypothesized in this article that chemohormonal therapy with concurrent fulvestrant and CT would be a promising strategy in postmenopausal HR+ HER2− MBC patients. Proof of this hypothesis would help control evolvement of tumor burden and acquirement of drug resistance over a short period of time.
1临床资料<br> 病例1女,49岁,确诊右乳腺癌后行右乳腺癌改良根治术,术后行CEF(吡柔比星75 mg/m2,环磷酰胺600 mg/m2,氟尿嘧啶500 mg/m2,第1~3天静脉点滴)方案化疗(21 d方案,共6疗程)。既往体健,否认糖尿病、高血压等病史。首次入院体重68 kg,身高160 cm,口服葡萄糖耐量( oral glucose toler-ance test , OGTT )及胰岛素释放试验( insulin releasing test , IRT)检查:空腹血糖6.4 mmol/L,餐后30min 12.2 mmol/L,餐后60min 13.3 mmol/L,餐后120min 10.6 mmol/L;空腹胰岛素5.6μU/ml,餐后30min胰岛素53.4μU/ml,餐后60min 70.1μU/ml,餐后120min 54.5μU/ml。 CEF方案化疗第6疗程前(第5疗程结束后3周),入院体重69 kg,身高160 cm,OGTT检查:空腹血糖6.0 mmol/L,餐后30min 11.9 mmol/L,餐后60min 9.4 mmol/L,餐后120min 7.3 mmol/L;空腹胰岛素4.6μU/ml,餐后30min胰岛素63.0μU/ml,餐后60min 63.9μU/ml,餐后120min 50.6μU/ml。患者首次入院时确诊为糖尿病前期,由入院的普通饮食改为糖尿病饮食,输注葡萄糖注射液时添加胰岛素拮抗。最后一疗程化疗前复查OGTT及IRT示糖耐量转为正常。患者出院后,继续注意饮食和体重控制,适当的运动,门诊定期随访。
Fundamental Operations in Surgery is an essential part of surgery teaching, as well as a bridge between basic theoretic study and clinical practice. The construction and development of the bilingual textbook of Fundamental Operations in Surgery is important and will be introduced in this article.
1临床资料<br> 女性,54岁,因“体检发现右乳成簇细小钙化4d”入院。体检:双乳、双腋窝、甲状腺及双颈侧区未见明显异常。乳腺钼靶示:右乳外上见较多成簇细小钙化。乳腺彩超:双乳腺增生。甲状腺彩超:甲状腺右叶可见一异常回声,大小约11 mm ×6 mm,边界可见,形态较规则,以低回声为主,内回声不均质,其内见较多团状及粗大强回声伴声影,加彩后其内见条状血流信号;进一步行甲状腺超声造影检查提示甲状腺癌不能除外。完善术前准备后行右乳钼靶导丝定位下钙化灶切除活检+甲状腺手术,术中冰冻病理检查示:右乳腺组织增生活跃,原位癌不能除外,需待术后石蜡病检确诊;右甲状腺微小乳头状癌,遂行双侧甲状腺全切+中央组淋巴结清扫。术后重庆医科大学病理检测中心诊断:右甲状腺微小乳头状癌;右乳原位癌(导管内癌)。补行右乳单纯乳房切除术。患者术后恢复可,顺利出院,长期口服左旋甲状腺素片(优甲乐,150μg, qd),门诊定期随访。
Fundamental Operations in Surgery is an essential part of surgery teaching, as well as a bridge between basic theoretic study and clinical practice. The author adds teaching contents of gastrostomy to the chapter of repairment of gastric perforation (gastrorrhaphy) properly without extending teaching time and experimental equipments. Through it students can master gastrostomy and get a better view of the removement of ifstula vividly, which gained agreeable teaching effects.