Receptors for Dolichos biflorus agglutinin: New cell surface markers on a spontaneous leukemia

$\text{Dolichos biflorus}$ agglutinin (DBA), which is specific for terminal α-N-acetylgalactosamine, bound to a spontaneous leukemia cell of $\text{GRS}\text{A}$ mice, but not to lymphoid cells of the host. The DBA receptors were isolated from the leukemia cell labeled with [³H]-galactose after detergent solubilization and affinity chromatography on DBA-agarose. The major component of the receptors migrated as a glycoprotein of apparent molecular weight 100,000 upon SDS gel electrophoresis. Alkaline treatment degraded the glycoproteins, releasing oligosaccharides of molecular weight around 1,000.     

Diagnostic accuracy of fine-needle aspiration cytology in histological grade 1 breast carcinomas: are we good enough?

Background: Fine-needle aspiration cytology (FNAC) of both palpable and non-palpable breast carcinomas has a high accuracy and sensitivity in dedicated centres. It is generally thought that low-grade carcinomas have a distinctly lower sensitivity due to discrete cellular atypia that may be difficult to appreciate. Grade 1 carcinomas make up about 45% of screening-detected breast carcinomas and about 20% of symptomatic breast cancers. The aim of this study was to evaluate the diagnostic sensitivity of grade 1 carcinomas and identify the critical features in the cytological diagnostic work-up of these tumours. Methods: There were FNAC smears from 494 histologically confirmed grade 1 carcinomas diagnosed during 1996–2004. The cytological diagnoses were compared with the histology. Results: A definitive malignant diagnosis (absolute sensitivity) was given in 382 cases (77.3%). Equivocal or suspicious diagnoses were given in 75 (15.2%), benign or probably benign (false negative) in 24 (4.8%). Thirteen cases (2.6%) were unsatisfactory. Complete sensitivity was 92.7%. Invasive ductal carcinomas comprised 81.3% of all cases; absolute sensitivity for these was 80.9%. Invasive lobular and tubular carcinomas comprised 7.3% and 5.9% of cases, respectively; absolute sensitivity for these diagnosis was 50.0% and 57.1%, respectively, significantly lower than for other subtypes (P ≤ 0.0001) whereas the difference for complete sensitivity was less but still significant (P = 0.017). Absolute and complete sensitivities were lower for tumours less than 1 cm size compared with more than 1 cm (P ≤ 0.00001). Conclusion: Preoperative FNAC diagnosis of grade 1 breast carcinoma has a high sensitivity, especially in ductal carcinomas. Invasive lobular and tubular carcinomas were less likely to receive a definite preoperative diagnosis. The main reason for not reaching a definitive malignant diagnosis was sampling error due to small tumours less than 1 cm in diameter, irrespective of tumour subtype.     

F10蛋白及mRNA在部分正常组织及癌组织中的表达

目的:了解F10基因在部分正常组织及肿瘤组织中的表达情况。方法:利用原位杂交和免疫组化方法对F10在部分正常组织和肿瘤组织中的mRNA和蛋白表达情况进行分析。结果:F10基因不仅在腺癌组织中表达呈阳性,在鳞癌组织中表现出较腺癌更强的强阳性,并且在正常组织中也有一定的表达。结论:F10是一个在多种组织普遍表达的细胞内蛋白,其功能可能与物质转运相关。     

Autophagy inhibition radiosensitizes in vitro,yet reduces radioresponses in vivo due to deficient immunogenic signalling

Clinical oncology heavily relies on the use of radiotherapy, which often leads to merely transient responses that are followed by local or distant relapse. The molecular mechanisms explaining radioresistance are largely elusive. Here, we identified a dual role of autophagy in the response of cancer cells to ionizing radiation. On one hand, we observed that the depletion of essential autophagy-relevant gene products, such as ATG5 and Beclin 1, increased the sensitivity of human or mouse cancer cell lines to irradiation, both in vitro (where autophagy inhibition increased radiation-induced cell death and decreased clonogenic survival) and in vivo, after transplantation of the cell lines into immunodeficient mice (where autophagy inhibition potentiated the tumour growth-inhibitory effect of radiotherapy). On the other hand, when tumour proficient or deficient for autophagy were implanted in immunocompetent mice, it turned out that defective autophagy reduced the efficacy of radiotherapy. Indeed, radiotherapy elicited an anti-cancer immune response that was dependent on autophagy-induced ATP release from stressed or dying tumour cells and was characterized by dense lymphocyte infiltration of the tumour bed. Intratumoural injection of an ecto-ATPase inhibitor restored the immune infiltration of autophagy-deficient tumours post radiotherapy and improved the growth-inhibitory effect of ionizing irradiation. Altogether, our results reveal that beyond its cytoprotective function, autophagy confers immunogenic properties to tumours, hence amplifying the efficacy of radiotherapy in an immunocompetent context. This has far-reaching implications for the development of pharmacological radiosensitizers.     

Kinase GSK3β functions as a suppressor in colorectal carcinoma through the FTO-mediated MZF1/c-Myc axis

Colorectal carcinoma (CRC) poses heavy burden to human health and has an increasing incidence. Currently, the existing biomarkers for CRC bring about restrained clinical benefits. GSK3β is reported to be a novel therapeutic target for this disease but with undefined molecular mechanisms. Thus, we aimed to investigate the regulatory effect of GSK3β on CRC progression via FTO/MZF1/c-Myc axis. Firstly, the expression patterns of GSK3β, FTO, MZF1 and c-Myc were determined after sample collection. Lowly expressed GSK3β but highly expressed FTO, MZF1 and c-Myc were found in CRC. After transfection of different overexpressed and interference plasmids, the underlying mechanisms concerning GSK3β in CRC cell functions were analysed. Additionally, the effect of GSK3β on FTO protein stability was assessed followed by detection of MZF1 m6A modification and MZF1-FTO interaction. Mechanistically, GSK3β mediated ubiquitination of demethylase FTO to reduce FTO expression. Besides, GSK3β inhibited MZF1 expression by mediating FTO-regulated m6A modification of MZF1 and then decreased the proto-oncogene c-Myc expression, thus hampering CRC cell proliferation. We also carried out in vivo experiment to verify the regulatory effect of GSK3β on CRC via FTO-mediated MZF1/c-Myc axis. It was found that GSK3β inhibited CRC growth in vivo which was reversed by overexpressing c-Myc. Taken together, our findings indicate that GSK3β suppresses the progression of CRC through FTO-regulated MZF1/c-Myc axis, shedding light onto a new possible pathway by which GSK3β regulates CRC.     

Intraductal mammary carcinoma and benign ovarian teratoma in a rhesus monkey

A benign ovarian teratoma and an intraductal mammary carcinoma were found in an adult rhesus monkey that had been used in reproductive studies and received human luteinizing hormone, follicle-stimulating hormone, and human chorionic gonadotropin.     

从国际非专利名称纵观全球生物药发展

生物药(bio-therapeutics)是指采用生物技术制备的、临床上用于疾病治疗的大分子生物制品,具有结构复杂、异质性高等特点,科学严谨的生物药通用名命名,是区分生物药物质基础的主要依据,也是药品生命周期管理的重要基础。世界卫生组织(World Health Organization,WHO)协调建立的国际非专利名称(International Nonproprietary Names,INN)是全球药物命名的标准化体系。从INN的起源,以及生物药INN的类别、发生与发展为主线,以较为详实的数据统计和分析,呈现了全球生物药的衍化进程,从不同的角度纵览生物药技术发展历程,对生物药的研发设计、技术标准及监管策略的考量均具有一定的参考意义。     

TIPE1‐mediated autophagy suppression promotes nasopharyngeal carcinoma cell proliferation via the AMPK/mTOR signalling pathway

Recent studies have shown that tumour necrosis factor‐α–induced protein 8 like‐1(TIPE1) plays distinct roles in different cancers. TIPE1 inhibits tumour proliferation and metastasis in a variety of tumours but acts as an oncogene in cervical cancer. The role of TIPE1 in nasopharyngeal carcinoma (NPC) remains unknown. Interestingly, TIPE1 expression was remarkably increased in NPC tissue samples compared to adjacent normal nasopharyngeal epithelial tissue samples in our study. TIPE1 expression was positively correlated with that of the proliferation marker Ki67 and negatively correlated with patient lifespan. In vitro, TIPE1 inhibited autophagy and induced cell proliferation in TIPE1‐overexpressing CNE‐1 and CNE‐2Z cells. In addition, knocking down TIPE1 expression promoted autophagy and decreased proliferation, whereas overexpressing TIPE1 increased the levels of pmTOR, pS6 and P62 and decreased the level of pAMPK and the LC3B. Furthermore, the decrease in autophagy was remarkably rescued in TIPE1‐overexpressing CNE‐1 and CNE‐2Z cells treated with the AMPK activator AICAR. In addition, TIPE1 promoted tumour growth in BALB/c nude mice. Taken together, results indicate that TIPE1 promotes NPC progression by inhibiting autophagy and inducing cell proliferation via the AMPK/mTOR signalling pathway. Thus, TIPE1 could potentially be used as a valuable diagnostic and prognostic biomarker for NPC.