ACT UP 25: HIV/AIDS,Archival Queers,and Mnemonic World Making

Audre Lorde's speech, “The Transformation of Silence into Language and Action, “sheds light on the margins of rhetoric in the sense of the public speech because she examines factors that may cause some people to remain silent while enabling others to speak and act. “Margins” refers both to the parameters employed for defining a practice and the relative place or value of varied activities exemplifying the practice. Lorde interweaves her commentary on the silence surrounding breast cancer with insights about silence drawn from her experiences as a member of several subordinated communities, especially as they relate to the misuse of power to silence those who are different. Her speech comments on silencing and power, sexism, verbal abuse, violence and sexualized aggression, shame, the taboo, and hostile social environments. Paradoxically, Lorde's speech is as much about the possibilities of rhetoric as its limits.     

纳米氧化锌对人肺腺癌细胞A549的毒性

探讨纳米氧化锌（ZnO）对体外培养的人肺腺癌细胞A549的生物学效应。使用原子力显微镜（AFM）、透射电镜（TEM）和X射线衍射仪（XRD）研究纳米ZnO颗粒物的理化性质。然后,使用0mmol/L、0.1mmol/L、0.5mmol/L、1mmol/L、5mmol/L、10mmol/L的纳米ZnO处理体外培养的人肺腺癌A549细胞,MTT 法测定细胞生长活性。并且测定1mmol/L 纳米ZnO染毒24h后细胞培养液上清中,乳酸脱氢酶（LDH）和胞内的超氧化物歧化酶（SOD）、过氧化氢酶（CAT）的活性以及丙二醛（MDA）的含量。使用透射电镜和流式细胞仪检测细胞凋亡的情况。荧光染色检测细胞产生活性氧（ROS）的生成。实验所用的ZnO纳米颗粒为长75 nm、直径20nm的针状纤锌矿晶体。细胞实验结果表明,纳米ZnO颗粒对A549细胞的生长活性具有明显的抑制作用,存在剂量－效应关系。培养液上清中LDH活性显著升高（P < 0.05）,胞内CAT活性显著下降、MDA含量显著升高（P < 0.01）,但SOD活性下降不明显。荧光染色检测发现染毒后A549细胞出现细胞凋亡,而且细胞内ROS的生成与纳米ZnO存在剂量－效应关系。结论是纳米氧化锌诱导人肺腺癌A549细胞产生活性氧,引发细胞凋亡,并产生细胞毒性。     

Blood glutathione levels in head and neck malignancies

Blood glutathione was estimated in fifty patients of head and neck cancer in the age group of 18–76 years and the results were compared with a group of normal healthy controls. Mean blood glutathione level was found to be significantly lowered in patients than the controls. Irrespective of the site, TNM classification, histopathology, and character of lesion, fall in blood glutathione was nearly same in all the patients. The mean level was significantly increased after radiotherapy when compared with the levels before radiotherapy. The decreased levels of GSH in-patients with head and neck cancer, observed in the present study, may be due to its increased utilization by the cells. The results suggest that patients with head and neck cancer have increased oxidative stress.     

Effect of Vitamin B<Subscript>12</Subscript> and Folate on Homocysteine levels in colorectal cancer

Folate and cobalamin (Vitamin B₁₂) are two essential micronutrients involved in one-carbon metabolism, which affects heart disease, neural tube defects and cancer. Methylenetetrahydrofolate reductase, the key enzyme involved in one carbon metabolism produces methyl tetrahydrofolate from methylene tetrahydrofolate, which in turn donates methyl group to homocysteine to generate methionine. There exist two common low function polymorphic variants of the methylenetetrahydrofolate reductase gene involving nucleotides 677 C→T and 1298 A→C, which are associated with hyperhomocysteinemia. These polymorphisms are also linked with increased risk for certain cancers such as breast cancer and at the same time providing a protective effect on colorectal cancer. In this case control study, we have evaluated levels of folic acid, vitamin B₁₂ and homocysteine in patients with colorectal cancer. Folate and homocysteine levels did not differ significantly between the two groups; however an increasing trend was noticed with increase in homocysteine levels. Vitamin B₁₂ levels were increased in cases compared to control group.     

Evaluation of immunohistochemistry and enzyme linked immunosorbent assay for HER-2/neu expression in breast carcinoma

HER-2 is overexpressed in approximately 20–30% of invasive Breast Cancer. ECD of the HER-2 protein is frequently cleaved and released into the circulation, where it can be detected by ELISA in up to 45% of patients with metastatic breast cancer. The objective of our study was to compare the current methods for the detection of HER-2 protein. Tissue HER-2 levels were studied in 100 breast cancer patients by IHC and compared with serum HER-2 levels by ELISA. IHC frequency was 29%. Serum HER-2 ECD was positive in 42% of patients. A statistically significant correlation was observed. HER-2 detected by IHC correlates significantly with serum HER-2 levels detected by ELISA. Thus, ELISA is a reliable and economical tool to assess the HER-2 status in tumors, when breast tissue sample is not available.     

SRB显色法用于抗癌药物敏感性试验的研究

采用ＳＲＢ显色法对９６孔培养板中短期培养的人大肠癌细胞株Ｃｏｌｏ２０５、人骨肉瘤细胞株ＯＳ７３２,人舌癌细胞株Ｔｃａ８１１３经５－ＦＵ,顺铂,蟾酥等药物处理后的活性进行了研究。结果表明,ＳＲＢ法对这些细胞株的体外抗癌药物敏感试验结果稳定,该法与其它细胞毒试验相比有一定优点,值得推广应用。     

A proof of concept for neutralizing antibody-guided vaccine design against SARS-CoV-2

Mutations and transient conformational movements of the receptor binding domain (RBD) that make neutralizing epitopes momentarily unavailable present immune escape routes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To mitigate viral escape, we developed a cocktail of neutralizing antibodies (NAbs) targeting epitopes located on different domains of spike (S) protein. Screening of a library of monoclonal antibodies generated from peripheral blood mononuclear cells of COVID-19 convalescent patients yielded potent NAbs, targeting the N-terminal domain (NTD) and RBD domain of S, effective at nM concentrations. Remarkably, a combination of RBD-targeting NAbs and NTD-binding NAbs, FC05, enhanced the neutralization potency in cell-based assays and an animal model. Results of competitive surface plasmon resonance assays and cryo-electron microscopy (cryo-EM) structures of antigen-binding fragments bound to S unveil determinants of immunogenicity. Combinations of immunogens, identified in the NTD and RBD of S, when immunized in rabbits and macaques, elicited potent protective immune responses against SARS-CoV-2. More importantly, two immunizations of this combination of NTD and RBD immunogens provided complete protection in macaques against a SARS-CoV-2 challenge, without observable antibody-dependent enhancement of infection. These results provide a proof of concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD.     

Hyperinsulinemia and Hypoadiponectinemia are Associated with Increased Risk for Occurrence of Ovarian Cancer in Non-diabetic Women of North Indian Population

Ovarian cancer has been emerged as a most common and lethal gynecological malignancy in India. High serum insulin and low adiponectin have been associated with increased risk of ovarian cancer. But their role in development of ovarian cancer is conflicting and little evidence is available. We aimed to evaluate blood levels of insulin and adiponectin in epithelial ovarian cancer (EOC) patients and their association with the risk to develop EOC. The study included following three groups; Group 1: fifty cases of cytohistopathologically confirmed cases of EOC, Group 2: fifty age matched cases of benign ovarian conditions and Group 3: fifty ages matched healthy controls with no evidence of any benign or malignant ovarian pathology as ruled out by clinical examination and relevant investigations. Cytohistopathologically confirmed and newly diagnosed cases of EOC and benign ovarian cancer were included in this study. The median value of fasting serum insulin was significantly high (15.0 µlU/ml, P = 0.02) and adiponectin were significantly low (5.1 µg/ml, P < 0.001) in ovarian cancer patients compared to benign ovarian tumors and healthy controls group. A significant increase risk of ovarian cancer was found in high tertile (≥ 18.7 µlU/ml) of serum insulin level (OR = 2.7; 95% CI = 1.00–6.67, P = 0.04) and lower tertile (≤ 5.45 µg/ml) of adiponectin level (OR = 3.2; 95% CI = 1.10–9.71, P = 0.03). High serum insulin level and low adiponectin levels were significantly associated with increased risk for development of ovarian cancer.