αE‐catenin is a candidate tumor suppressor for the development of E‐cadherin‐expressing lobular‐type breast cancer

Although mutational inactivation of E‐cadherin (CDH1) is the main driver of invasive lobular breast cancer (ILC), approximately 10–15% of all ILCs retain membrane‐localized E‐cadherin despite the presence of an apparent non‐cohesive and invasive lobular growth pattern. Given that ILC is dependent on constitutive actomyosin contraction for tumor development and progression, we used a combination of cell systems and in vivo experiments to investigate the consequences of α‐catenin (CTNNA1) loss in the regulation of anchorage independence of non‐invasive breast carcinoma. We found that inactivating somatic CTNNA1 mutations in human breast cancer correlated with lobular and mixed ducto‐lobular phenotypes. Further, inducible loss of α‐catenin in mouse and human E‐cadherin‐expressing breast cancer cells led to atypical localization of E‐cadherin, a rounded cell morphology, and anoikis resistance. Pharmacological inhibition experiments subsequently revealed that, similar to E‐cadherin‐mutant ILC, anoikis resistance induced by α‐catenin loss was dependent on Rho/Rock‐dependent actomyosin contractility. Finally, using a transplantation‐based conditional mouse model, we demonstrate that inducible inactivation of α‐catenin instigates acquisition of lobular features and invasive behavior. We therefore suggest that α‐catenin represents a bona fide tumor suppressor for the development of lobular‐type breast cancer and as such provides an alternative event to E‐cadherin inactivation, adherens junction (AJ) dysfunction, and subsequent constitutive actomyosin contraction. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

An accidental gallbladder schwannoma misdiagnosis as malignant cancer

<正>To the Editor: Schwannomas are mainly benign neurogenic tumors originating from the Schwann cells in peripheral nerves sheaths and occur in patients at any age and in every location [ 1, 2 ]. The most common occurring sites of schwannomas are the head, neck and extremities [3]. In the abdominal cavity, the most frequently involved sites are the retroperitoneum and stomach [4].     

Serum hepatitis B surface antigen correlates with fibrosis and necroinflammation: A multicentre perspective in China

The kinetics of serum hepatitis B surface antigen (HBsAg) during the natural history of hepatitis B virus (HBV) infection has been studied, but the factors affecting them remain unclear. We aimed to investigate the factors affecting HBsAg titres, using data from multicentre, large‐sized clinical trials in China. The baseline data of 1795 patients in 3 multicentre trials were studied, and the patients were classified into 3 groups: hepatitis B early antigen (HBeAg)‐positive chronic HBV infection (n = 588), HBeAg‐positive chronic hepatitis B (n = 596), and HBeAg‐negative chronic hepatitis B (n = 611). HBsAg titres in the different phases were compared, and multiple linear progression analyses were performed to investigate the implicated factors. HBsAg titres varied significantly in different phases (P = .000), with the highest (4.60 log10 IU/mL [10%‐90% confidence interval: 3.52 log10 IU/mL‐4.99 log10 IU/mL]) in patients with HBeAg‐positive chronic HBV infection. In all phases, age and HBV DNA were correlated with serum HBsAg level. In HBeAg‐positive chronic hepatitis B patients, a negative correlation between HBsAg titres and fibrosis stage was observed. Alanine amonitransferase or necroinflammatory activity was also correlated with HBsAg titres in HBeAg‐negative chronic hepatitis B patients. In conclusion, decreased HBsAg titres may be associated with advancing fibrosis in HBeAg‐positive chronic hepatitis B patients or increased necroinflammation in those with HBeAg‐negative chronic hepatitis B. Our findings may help clinicians better understand the kinetics of HBsAg and provide useful insights into the management of this disease.     

乌拉尔甘草中新香豆素的化学研究

甘草是一味重要的传统中药,为临床广泛使用。多年来国内外学者对其化学成分的研究颇为重视。近来,用不同溶剂对甘草进行分步提取,以酶和受体生物学指标进行监测,发现乌拉尔甘草(Glycyrrhiza uralensis Fisch)的二氯甲烷提取物对安定受体,胆囊收缩素受体以及二氢还原酶具有明显的抑制作用。为了寻找其中的有效成分,我们对该部分进行了化     

Development after prenatal exposure to cocaine, heroin and methadone

In Amsterdam a longitudinal, prospective and multidisciplinary study on the development of infants of drug-dependent mothers (IDDM) was started in 1983: 35 IDDM and 35 reference infants were originally enrolled. The drug-dependent women had used combinations of methadone, heroin, cocaine and other drugs during pregnancy. Of the IDDM, 80% had to be treated pharmaceutically for neonatal abstinence symptoms (NAS). Physical, neurological, cognitive and the socio–emotional development of the children were studied regularly from birth until 5.5 years of age. Differences between the reference group and the IDDM were found most clearly in cognitive development. The IDDM also had more behavioural problems at some of the ages studied. No group differences were seen in motor development. So far the results of the study show that IDDM and their caregivers need extra support in order to improve early communication and the children's cognitive development.