Functional estrogen receptor signal transduction pathway activity and antihormonal therapy response in low-grade ovarian carcinoma

Background

Advanced low-grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. However, only a subgroup of patients respond to AHT, and this response cannot be adequately predicted by currently used immunohistochemistry (IHC). A possible explanation is that IHC only takes the ligand, but not the activity, of the whole signal transduction pathway (STP) into account. Therefore, in this study, the authors assessed whether functional STP activity can be an alternative tool to predict response to AHT in LGOC.

Methods

Tumor tissue samples were obtained from patients with primary or recurrent LGOC who subsequently received AHT. Histoscores of ER and progesterone receptor (PR) were determined. In addition, STP activity of the ER STP and of six other STPs known to play a role in ovarian cancer was assessed and compared with the STP activity of healthy postmenopausal fallopian tube epithelium.

Results

Patients who had normal ER STP activity had a progression-free survival (PFS) of 16.1 months. This was significantly shorter in patients who had low and very high ER STP activity, with a median PFS of 6.0 and 2.1 months, respectively (p < .001). Unlike ER histoscores, PR histoscores were strongly correlated to the ER STP activity and thus to PFS.

Conclusions

Aberrant low and very high functional ER STP activity and low PR histoscores in patients with LGOC indicate decreased response to AHT. ER IHC is not representative of functional ER STP activity and is not related to PFS.     

Female reproductive and hormonal factors and lung cancer mortality among never-smokers: A prospective cohort study of 287 408 Chinese women

There is growing, but inconsistent evidence suggesting oestrogen may play a key role in lung cancer development, especially among never-smoking women for whom lung cancer risk factors remain largely elusive. Using the China Kadoorie Biobank, a large-scale prospective cohort with 302 510 women aged 30 to 79 years recruited from 10 regions in China during 2004 to 2008, we assessed the risk of lung cancer death among self-reported never-smoking women who were cancer-free at baseline, in relation to age at menarche, age at menopause, time since menopause, prior use of oral contraceptives (OCP), number of livebirths, breastfeeding and age at first livebirth. Women were followed up to December 31, 2016 with linkage to mortality data. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression, adjusting for key confounders including several socio-demographic, environmental and lifestyle factors. Among 287 408 never-smoking women, 814 died from lung cancer with a median follow-up of 10.3 years. Women who had used OCP within 15 years prior to baseline had a significantly higher hazard of lung cancer death compared with never-users: HR = 1.85 (95% CI: 1.14-3.00) and risk increased by 6% with each additional year of use: HR = 1.06 (1.01-1.10). Among parous women, the hazard of lung cancer death increased by 13% with each single livebirth: HR = 1.13 (1.05-1.23); and among post-menopausal women, the risk increased by 2% with each year since menopause: HR = 1.02 (1.01-1.04). These results suggest that reproductive factors which were proxies for lower endogenous oestrogen level, for example, longer duration of OCP use, could play a role in lung cancer development.     

Andexanet alfa after 4-factor PCC administration for intracranial hemorrhage: a case series

Journal of Thrombosis and Thrombolysis - The ongoing controversy regarding optimal reversal agent for factor Xa-inhibitors is mainly due to lack of comparative data of andexanet alfa (AA) to...     

血液透析发生结核感染的影响因素分析

目的分析维持性血液透析患者发生结核感染的影响因素及临床特点。方法回顾性调查2018年5月-2019年8月北京清华长庚医院肾内科收治的长期规律血液透析患者共150例,收集患者的年龄、性别、合并疾病、血常规、生化、透析充分性等检验结果和影像学资料,归纳分析血液透析患者发生结核感染的影响因素。结果150例血液透析患者,男性91人,女性59人,平均年龄(62.7±14.2)岁,发生结核感染者共11例(7.33%),其中肺外结核比例高(54.5%),以浆膜腔积液为主要表现(54.5%),血红蛋白(94.7±11.6)g/L、血清白蛋白(34.6±2.0)g/L、血肌酐(593.6±221.4)umol/L低于无结核感染者,差异具有统计学意义(P<0.05);血小板(228.7±103.5)×10⁹/L高于无结核感染者,差异具有统计学意义(P<0.05)。两组患者年龄、透析充分性、淋巴细胞、血糖、血脂、血钙、血磷、全段甲状旁腺激素无统计学差异。结论血红蛋白<110g/L、白蛋白<35g/L是MHD患者发生结核感染的高危因素,MHD患者发生结核感染以肺外结核为主,临床表现具有隐匿性和不典型性,临床工作应提高警惕避免漏诊。     

Trends in radiation dose for low grade gliomas across the United States

Journal of Neuro-Oncology - Adjuvant radiation is often used in patients with low grade gliomas with high-risk characteristics with a recommended dose of 45–54&nbsp;Gy. We used the...