Oncotype DX 21基因检测在ER阳性早期乳腺癌中的应用

在诸多评估雌激素受体(estrogen receptor,ER)阳性早期乳腺癌复发风险的多基因工具中,Oncotype DX 21基因检测因其独特的疗效预测作用而被广泛应用于淋巴结阴性患者.多项回顾性研究已证明其在淋巴结阳性人群同样具有预后预测价值,但前瞻性临床试验证据仍不充分.该检测能协同其他重要临床病理因素,影响乳腺癌患者的辅助治疗方案,且具较高的成本效益.该研究就21基因检测对早期乳腺癌患者的预后预测价值、独特优势、辅助治疗决策影响、成本效果和现存争议进行综述.     

ER阳性、HER2阴性、淋巴结阴性早期浸润性乳腺导管癌X线征象与Oncotype DX21基因检测结果间的相关性分析

背景与目的：Oncotype DX21基因检测具有预后预测和辅助治疗决策的价值,但通过有创手术获取的检测样本无法完全表征肿瘤的整体情况,而乳腺X线摄影是一项无创、经济、操作简单的常规检查项目。若能找到影像标志物,则可以实现以非侵入方式获取相关基因表达量方面的信息,同样达到预测预后和复发风险概率的目的。探究雌激素受体（estrogen receptor,ER）阳性、人表皮生长因子受体2（human epidermal growth factor receptor 2,HER2）阴性、淋巴结阴性的早期浸润性乳腺导管癌患者的X线影像特征与Oncotype DX21基因检测结果间的相关性。方法：回顾性收集了282例于2017年9月—2019年6月在复旦大学附属肿瘤医院进行过乳腺X线检查以及Oncotype DX21基因检测的ER阳性、HER2阴性、淋巴结阴性的早期浸润性乳腺导管癌患者资料。采用单因素和多因素有序logistic回归分析X线征象与Oncotype DX21基因检测复发风险评分（recurrence score,RS）分级的相关性,采用单因素方差分析X线征象与RS分值的相关性。结果：单因素和多因素有序logistic回归分析结果一致表明,肿块边缘和钙化形态与RS分级显著相关（P<0.05）。进一步检验发现边缘模糊肿块的平均RS值为33.6,与边缘清楚（18.4）、毛刺（24.9）、小分叶（27.3）、遮蔽（23.1）间存在差异。不定形钙化和点状钙化的RS均值间差异有统计学意义。结论：乳腺X线影像中的钙化形态和肿块边缘特征具有成为Oncotype DX21基因检测的影像标志物的潜力,为临床医师对患者进行个体化治疗方案的决策提供强有力的帮助。     

苏州地区乳腺癌患者BRCA1和BRCA2基因突变的分析

目的 探讨中国苏州地区乳腺癌患者乳腺癌易感基因1(BRCA1)和乳腺癌易感基因2(BRCA2)基因的突变位点及携带情况，并对携带致病突变基因患者的家系成员进行基因筛查和风险管理。方法 收集2018年7月至2021年10月确诊的85例乳腺癌患者，其中早发性乳腺癌40例，家族性乳腺癌36例，三阴性乳腺癌35例。采用高通量测序技术，对患者外周血中BRCA1和BRCA2基因的外显子及其部分内含子序列进行检测，将检测到的致病突变与ClinVar数据库进行对照，确定是否为新发现的致病突变。通过对家系先证者进行遗传咨询和肿瘤易感基因检测，进一步对携带致病基因患者的健康家系成员进行BRCA基因突变筛查。结果 85例乳腺癌患者中BRCA1和BRCA2的总致病突变率为21.2%(18/85),其中BRCA1致病突变率为11.8%(10/85), BRCA2致病突变率为9.4%(8/85)。在18例致病性突变患者中发现3个新发位点，分别为BRCA1基因c.1559dupA,BRCA2基因c.8939-8941delinsT和BRCA2基因c.3677-3678insATGAAAT。进一步对携带BRCA1/B...     

28基因检测在亚洲早期乳腺癌中的研究进展

乳腺癌是全球女性中最常见且死亡率最高的恶性肿瘤之一.随着分子生物学技术的发展,乳腺癌的诊疗模式也逐渐向精准化、个体化方向发展.目前临床应用较广泛的多基因检测包括Oncotype DX?、MammaPrint?等;然而这些检测技术均起源于欧美人群,在亚洲乳腺癌患者中的应用有限,对预后的评判价值有待考量.而28基因检测是第...     

家族性与散发性乳腺癌BRCA1与FANCD2基因相关性的研究

目的:探讨乳腺癌组织BRCA1与FANCD2基因表达,明确BRCA1基因与FANCD2基因之间的相关性.方法:选取104例乳腺癌手术标本,其中家族性乳腺癌52例,散发性乳腺癌52例.采用SP免疫组化法检测BRCA1和FANCD2在家族和散发性乳腺癌组织中的表达.结果:在家族性乳腺癌组织中,BRCA1蛋白阳性表达37例(71.2％),FANCD2蛋白阳性表达18例(34.6％),两组差异有统计学意义,P＜0.05.在散发性乳腺癌组织中,BRCA1蛋白阳性表达19例(36.5％),FANCD2蛋白阳性表达27例(51.9％),两组差异无统计学意义.结论:BRCA1和FANCD2基因表达与乳腺癌的发生和发展存在一定相关性,FANCONI/BRCA 通路的抑制,可能是乳腺癌,尤其是家族性乳腺癌发生发展以及形成的原因之一.     

家族性乳腺癌患者及家系成员乳腺癌易感基因携带情况调查

目的 乳腺癌易感基因1(breast cancer susceptibility gene 1,BRCA1)和BRCA2基因已经证实与家族性乳腺癌密切相关.本研究旨在分析中国汉族家族性乳腺癌患者及家系成员BRCA1和BRCA2突变特征及携带情况.方法 收集2013 12-02-2015-06-08军事医学科学院附属医院确诊的中国汉族家族性乳腺癌患者55例及家系成员48名,共计103例样本.柚取外周静脉血提取DNA,应用聚合酶链反应(polymerase chain reaction,PCR) DNA直接测序方法检测BRCA1和BRCA2基因全编码外显子序列.结果 55例家族性乳腺癌患者中发现5个BRCA基因致病性突变位点,1个突变位点乳腺癌信息库中见报道(BRCA1:4730insG),4个为新发现突变位点(BRCA1:1937insC,4538insAG;BRCA2:1382delA,2820delA).家族性乳腺癌患者BRCA1/2突变率为9.09％(BRCA1,5.45％;BRCA2,3.64％),其中三阴性乳腺癌患者突变率为22.22％(x2 =1.99,P=0.20),早发性乳腺癌患者(≤35岁)突变率为20.00％,x2=0.79,P=0.39.48例家系成员检测到3个新发现突变位点(BRCA1:1370insA,3459insA;BRCA2:6502insT),总突变率为6.25％.结论 中国汉族家族性乳腺癌患者BRCA基因突变率显著低于国外,应重点关注有家族史的三阴性乳腺癌患者和早发性乳腺癌患者;家系成员中发现BRCA基因致病性突变,家系成员突变率和发病风险有待进一步研究,应引起重视.     

BRCA1和BRCA2基因与乳腺癌相关的研究进展

BRCA1和BRCA2基因是与乳腺癌尤其是遗传性乳腺癌发生发展密切相关的抑癌基因.研究表明,部分乳腺癌患者存在BRCA1和BRCA2基凶突变,而且出现这两个基因突变的乳腺癌表现出不同的病理学特点.通过检测乳腺癌患者BRCA1和BRCA2基因的突变情况,将有助于对乳腺癌患者预后的早期评估.     

中国BRCA1/2突变阳性和突变阴性乳腺癌病理学特征的比较性研究

背景与目的：BRCA1和BRCA2是两个最主要的遗传性乳腺癌相关基因,本研究旨在发现中国BRCA1/2突变阳性乳腺癌的病理学特征。方法：本研究入组了2012—2016年间287例接受过BRCA1/2基因突变检测的乳腺癌,对其中BRCA1/2突变阳性和突变阴性患者的组织病理学和免疫组织化学检测结果进行了比较性研究。结果：在287例乳腺癌中,66例为BRCA1突变阳性,47例为BRCA2突变阳性,174例为BRCA1/2突变阴性。BRCA1突变的乳腺癌表现为更高的组织学分级（P＜0.001）,更高比例的三阴性乳腺癌（72.7%,P＜0.001）。BRCA1突变阳性和BRCA2突变阳性的乳腺癌中人表皮生长因子受体2（human epidermal growth factor receptor 2,HER2）的阳性表达率较BRCA1/2突变阴性的乳腺癌更低（P＜0.001）。BRCA1突变阳性乳腺癌基底标志物细胞角蛋白5/6（cytokeratin 5/6,CK5/6）和表皮生长因子受体（epidermal growth factor receptor,EGFR）的阳性率为50%,明显高于其他两组（P＜0.001）,雄激素受体（androgen receptor,AR）的阳性率也更低（P＜0.05）。结论：中国BRCA1突变阳性乳腺癌更多为三阴性乳腺癌,具有CK5/6和EGFR的阳性率更高等特点,并且BRCA1和BRCA2突变阳性乳腺癌中HER2受体阳性率也更低。     

353例遗传性高危乳腺癌患者BRCA1、BRCA2、PALB2基因胚系突变的分布情况研究

摘 要：［目的］通过对女性乳腺癌患者进行胚系基因检测,评估BRCA1、BRCA2、PALB2基因胚系致病/可能致病性突变在高危乳腺癌患者中的分布情况。［方法］ 收集2016年12月1日至2022年4月30日中山大学附属第一医院收治的女性乳腺癌患者,对已进行胚系多基因检测的353例具有遗传性高危因素的女性乳腺癌患者,对她们的检测结果进行分析,评估BRCA1、BRCA2和PALB2基因胚系致病/可能致病性突变患者的病理和临床特征等情况。［结果］ 353例患者中,胚系BRCA1、BRCA2和PALB2致病/可能致病突变者共59例,突变率为16.71%,年轻患者较其他年龄患者的BRCA1突变率更高（P=0.039）,相比其他分子分型,三阴性乳腺癌患者的BRCA1突变（P＜0.001）和3个基因的总突变率（P=0.007）都明显更高。和没有肿瘤家族史的患者相比,有肿瘤家族史的患者并没有体现出明显的高突变率。具有2个或2个以上危险因素的患者的基因突变率要明显高于只有1个高危因素的患者（P=0.048）。［结论］ PALB2基因胚系致病/可能致病突变在高危乳腺癌患者中的发生比例较高,其重要性并不亚于BRCA1/2基因,建议将PALB2基因纳入常规乳腺癌胚系基因检测范围,且对具有遗传性高危因素的乳腺癌患者进行包括胚系BRCA1、BRCA2和PALB2基因的常规检测。     

分子标志预测乳腺癌治疗疗效

21世纪将是肿瘤个体化治疗的时代,2008年美国年度10大医学突破中之一是关于Oncotype DX基因扫描能够确定乳腺癌复发的风险,并作为选择化疗药物的依据,更有针对性选择治疗方案。用生物标志物来预测肿瘤治疗疗效,可以避免患者选择无效的细胞毒药物或昂贵治疗。在近年来的ASCO、St．Gallen和NCCN指南中,一些预测性的标志物已经被重点推荐。     

Dermatomycosis in Goats in India

Summary: In an extensive survey involving 2176 goats 1.56% of goats manifested clinical lesions of ringworm infection. Animals below the age of 6 months were affected most (4.20%). The incidence of infection was higher during the winter months. T. verrucosum, T. mentagrophytes and M. gypseum were isolated from the skin scrapings of 12, 4, and 2 goats respectively. It is suggested that the infected animals could be a source of disease to human population in which the zoophilic dermatophyte invasion is characterized by severe inflammatory lesions of the skin. The zoonotic importance of different dermatophytes is stressed.
Zusammenfassung: In einer ausgedehnten Untersuchung an 2176 Ziegen wurden bei 1,56% klinische Zeichen einer Hautmykose festgestellt. Tiere, die jühger als 6 Monate alt waren, zeigten mit 4,20% am häfigsten Krankheitssymptome. In den Wintermonaten war die Erkrankungshäufigkeit am gröBten. T. vermcosum, T. mentagrophytes and M. gypseum wurden jeweils von 12,4 bzw. 2 Ziegen isoliert. Die inflzierten Tiere köinnen eine Infektionsquelle für die menschliche Bevölkerung darstellen und dort Mykosen mit stark entzündlichen Veränderungen auslösen. Die Bedeutung verschiedener Dermatophyten als Erreger von Zoonosen wird hervorgehoben.     

Trends in zygomycosis in children

Zygomycosis, or mucormycosis, is associated with significant morbidity and mortality in both children and adults. Studies in adults have shown an increase in the incidence of zygomycosis, particularly among haemtopoietic stem cell transplant (HSCT) recipients and patients with haematologic malignancies. There is a paucity of data on the epidemiology of zygomycosis in children. We performed a retrospective analysis to describe trends in zygomycosis between 1 January 2003 and 31 December 2010. We used the Pediatric Health Information System (PHIS) database to identify paediatric patients who were diagnosed with zygomycosis during the study period. Administrative data on diagnoses, demographics, underlying conditions and clinical experiences were collected. Summary statistics were calculated and tests for trend were conducted. We identified 156 unique patients with zygomycosis. The prevalence of zygomycosis did not significantly increase over time (P=0.284). The most common underlying condition was malignancy (58%) and over half received intensive care. Voriconazole utilisation among all hospitalised children significantly increased during the period (P=0.010). Our study demonstrates that the incidence of zygomycosis is not significantly increasing. During the time period there was a significant increase in the use of voriconazole among children.     

Increased apoptosis in cancer cells in vitro and in vivo by ceramides in transferrin-modified liposomes

Lysosomes are a promising therapeutic target for induction apoptosis in cancer cells due to lysosomal membrane permeabilization (LMP) leading to leakage of hydrolytic enzymes, especially the cathepsins, into the cytoplasm. We hypothesized that with the modification of the ceramide-loaded liposomes with transferrin (Tf), we would achieve both tumor targeting and increased delivery of lysosome-destabilizing agents, such as ceramides to lysosomes, to initiate LMP-induced apoptosis. We prepared Tf-modified (TL) and plain (PL) liposomes and loaded with short (C6)- or long (C16) N-acyl chain ceramides. Uptake, intracellular localization of liposomes, stability of the lysosomal membrane and release of cathepsin D were investigated on Hela cells by fluorescence microscopy and flow cytometry. Apoptosis was evaluated by binding of fluorescently-labeled Annexin V. Antitumor and pro-apoptotic effects of C6Cer-loaded Tf-liposomes were demonstrated in vivo in an A2780-ovarian carcinoma xenograft mouse model. TL were internalized specifically via the TfR-dependent endocytic pathway and localized within the endosome-lysosomal compartment. Ceramide-loaded Tf-liposomes significantly increased apoptosis compared with ceramide-free and ceramide-loaded non-modified liposomes. The treatment of cancer cells with TL led to increased LMP and cytoplasmic relocation of the intralysosomal cathepsin D. A strong antitumor and pro-apoptotic effect of C6Cer-loaded TL was also demonstrated in vivo in an A2780-ovarian carcinoma xenograft mouse model. The lysosomal accumulation of ceramides delivered by Tf-liposomes initiates the permeabilization of the lysosomal membranes required for the release of lysosomal cathepsins into the cytoplasm and initiation of the cancer cell apoptosis both in vitro and in vivo.     

Ringworm in animals in a farm in Assiut

Bericht über das Auftreten von Hautmykosen bei Tieren auf der Farm der Landwirtschaftlichen Fakultät der Universität Assiut. Von 70 Kälbern waren 42 pilzkrank, davon 22 durch T. mentagrophytes, 20 durch T. verrucosum. Von 180 Kühen waren 8 pilzbefalien, sämtlich durch T. mentagrophytes. Von 2 kranken Bullen wurde T. verrucosum isoliert. Auch die 3 Pferde und 2 Maultiere der Farm waren pilzinfiziert; Erreger war in diesen Fällen T. equinum. Auch ein Kalb war von T. equinum befallen. Die gleiche Pilzart wurde ferner von 3 Tierpflegern isoliert, die Pilzherde am Hals und an den Armen aufwiesen.     

Survey of changes in dietary preferences in cancer patients in China

Objective The aim of this study was to investigate the changes in dietary preferences in cancer patients in China and to determine the need for encouraging the adherence to a sensible diet among such patients.Methods A total of 468 cancer patients were interviewed using a self-designed questionnaire focusing on changes in the intake of specific foods. Data were analyzed using SPSS 16.0. Results Most patients completely avoided roosters and carp(73.1%), condiments(51.9%), and meat of aquatic species(40.4%). All other types of the specific foods were completely avoided by different subpopulations of the patients.Conclusion In addition to focusing on disease treatment, medical professionals need to help cancer patients overcome barriers associated with the customs of avoiding specific foods encompassed by the term ”fawu” and provide them with dietary guidance in order to prevent negative nutritional effects.     

Socioeconomic factors in cancer in Sweden

It is well known that certain cancers have shown clustering in socioeconomic groups, but limited data are available on recent results and time trends in such clustering. We determined standardized incidence ratios (SIR) for cancer, adjusted for age, period, region, parity and age at first childbirth among men and women in 6 socioeconomic groups based on the Swedish Family-Cancer Database. Persons had to be identified with the same socioeconomic status in the census of years 1960 and 1970, or of years 1960, 1970 and 1980; the comparison group was all people according to the same censuses. Cancers were followed from years 1970 to 1998 or from 1980 to 1998. Both increased and decreased SIRs were found, and a consistent pattern emerged, although the overall SIRs for cancer did not differ much, the lowest being for farmers (0.85) and the highest for professional men (1.07) and women (1.11). At individual sites, manual workers were at risk of tobacco-, alcohol- and occupation- and human papilloma virus-related cancers and at a decreased risk at most other cancers. Manual workers and farmers showed an excess of stomach cancer; professionals had an excess of melanoma and squamous cell skin cancer. Male and female SIRs correlated highly for manual and blue-collar workers and for professionals. The overall population-attributable fraction for selected sites was 16.7% for men and 10.9% for women and it was highest, over 50%, for lung cancer in both genders.     

Advances in cancer epidemiology in Japan

Epidemiologists in Japan have been performing calculations to estimate nationwide cancer incidence rates as well as 5‐year survival rates using population‐based cancer registry data. There have been remarkable changes in cancer incidence and/or mortality in cancers of the lung, liver and stomach, which were thought to be attributed to the changing impact of exposure to cigarette smoking, chronic hepatitis C virus infection and Helicobacter pylori infection, respectively. In systematic reviews providing evidence in risk/protective factors for cancer sites using case–control and cohort studies of the Japanese population, there were associations between cancer sites (esophagus, stomach, colo‐rectum, liver, pancreas, lung and breast) and various lifestyle factors. In the past 10 years, a hospital‐based case–control study at Aichi Cancer Center provided valuable evidence of gene‐environment interaction on the development of cancer [i.e., the effects of aldehyde dehydrogenase‐2 (ALDH2) polymorphism and heavy alcohol drinking on esophageal cancer, ALDH2 polymorphism and smoking on lung cancer, methylenetetrahydrofolate reductase polymorphism and heavy alcohol drinking on pancreatic cancer]. The database with stored DNA was also used and identified seven loci containing significant but low‐penetrance polymorphisms associated with the development of breast cancer. These findings together with established risk factors are likely to be useful to predict personalized breast cancer risk in East Asian women. In 2005, the Japan Multi‐Institution Collaborative Cohort (J‐MICC) study was launched to elucidate gene‐environment interactions as well as to confirm preclinical diagnostic biomarkers of cancer. J‐MICC, which has recruited 92,000 healthy individuals by the end of 2012, will follow the individuals until 2025.     

整合素在急性白血病中的研究进展

急性白血病是一种早期造血干/祖细咆的恶性克隆性疾病.微小残留病和耐药被认为是其复发和难治的根源.近来,越来越多的证据显示白血病细胞通过与骨髓微环境中的基质细胞或细胞外基质相互作用促进其存活,并增强其对常规化疗药物的耐药.整合素是介导细胞与细胞外基质（细胞与非细胞成分）粘连的最主要黏附分子,在细胞增殖、存活等生物学过程中发挥关键作用,但作用机制尚不完全清楚.现就目前揭示的整合素及肿瘤微环境在急性白血病发生、发展中的作用进行综述.     

Foreign bodies in ENT in a teaching hospital in Eastern India

Objective

To evaluate the nature, common sites, modes of presentation of various foreign bodies (FB) in Ear, Nose and Throat (ENT).

Materials and methods

Observational retrospective study carried out at Vivekananda Institute of Medical Sciences, Ramakrishna Mission Seva Pratishthan. The study period was between Jan 2006 to Jan 2007. The information obtained from the hospital record books.

Results

Four hundred and eighty-two patients presented in the Department of Otorhinolaryngology of Vivekananda Institute of Medical Sciences, in the study period with FB in their ENT. Out of 482 pts, the commonest location of FB was to be in throat with 302 pts (62%) followed by ear with 119 pts (25%) and nose 61 pts (13%). Amongst the FB in throat the commonest was fish bone and the commonest site being tonsils. Artificial denture accounted for a significant number of 13 (4.3%). External auditory canal was the commonest site of FB lodgment in ear found in 118 patients (99.16%). Nasal FB were found in 61 patients; more common in pediatric age group (98.36%).

Conclusion

From this study we have found that FB lodgement is a very common complaint with which patients come to otolaryngologist. The commonest site of FB lodgement is in the throat. Most of the FB could be removed in emergency room (ER) with or without Local Anesthesia.