Gene therapy of cancer based on interleukin 12

Tumor formation and growth depends mainly on the inability of the organism to elicit a potent immune response, and on the formation of new blood vessels that enable tumor nutrition. Interleukin-12 (IL-12) therapy can target both processes. And IL-12-based gene therapy may restrict IL-12 production to the relevant site in order to obtain enhanced antitumor activity and reduced toxicity. In the clinical setting, IL-12 gene transfer can be used either to improve the pharmacokinetic/pharmacodynamic profile of the cytokine, to transduce dendritic cells or to enhance the efficiency of antitumor vaccination. It can also synergize with other procedures involving the simultaneous transfer of other transgenes or non-gene based strategies. The strong anti-tumoral power shown in many different animal models has not been found in early clinical trials in which cancer patients were treated by peritumoral injections of autologous fibroblasts producing IL-12, intratumoral injections of an adenoviral vector encoding human IL-12 genes, or intratumoral injection of autologous dendritic cells transduced ex vivo with this same adenoviral vector. However, these trials have set the proof-of-concept that local production of IL-12 inside a tumor can stimulate tumor infiltration by effector immune cells and that in some cases it is followed by tumor regression. From the many questions that arise after these disappointing results the most relevant concerns the duration and intensity of transgene expression and the capability to monitor this topics in vivo. New vectors that might achieve regulated, long-term production of this cytokine might have better results and merit clinical testing.     

Lymphocyte subsets in Heymann nephritis

Altered ratios of T lymphocyte subsets have recently been reported in some forms of glomerulonephritis, including membranous glomerulonephritis. Heymann nephritis is a model of membranous glomerulonephritis that can be induced in susceptible strains of rat by a single subcutaneous injection of renal tubular antigen in Freund's complete adjuvant. Monoclonal antibodies were used to identify cytotoxic/suppressor and helper/inducer T cells in the blood, spleen, peripheral lymph nodes, and, where relevant, the lymph node draining the antigen injection site in susceptible and nonsusceptible rat strains before and after immunization with renal tubular antigen. A marked interstrain variation in the proportions of T lymphocyte subsets was found, but this did not segregate strains that are susceptible to Heymann nephritis induction from those that are resistant. Neither the development of Heymann nephritis in susceptible strains or immunization of resistant strains with renal tubular antigen was associated with any specific alteration in the T lymphocyte subpopulations.     

前列腺增生症趋于年轻化的探讨

目的:探讨不同年龄组前列腺增生症的检出率及原因,以达到早发现,早预防,早治疗的目的.方法:应用Acuson 128xp超声显像仪诊断前列腺增生症.结果:前列腺增生症检出率:35岁～39岁纽1053例,检出8例(0.76%);40岁～44岁组1550例,检出30例(1.68%);45岁～49岁组2855例,检出486例(17.0%);50岁～54岁组2784例,检出715例(25.7%);55岁～59岁2924例,检出1231例(37.5%);60岁～64岁组2450例,检出1521例(62.1%);65岁～69岁组1241例,检出826例(66.6%);70岁～74岁组1118例,检出711例(63.6%);≥75岁组588例,检出293例(49.8%).结论:前列腺增生症并非老年人特有疾病,似有年轻化趋势.     

Lack of STK11 gene expression in homozygous twins with Peutz-Jeghers syndrome

Clinical features of Peutz-Jeghers syndrome (PJS), an autosomal dominant disorder, include clusters of melanotic spots on the lips and limbs, polyposis of the gastrointestinal (GI) tract, and propensity to develop neoplasms of the GI tract, ovaries, testes, and other sites. We report twin sisters with PJS who were found to be homozygous, based on analyses of 9 DNA markers containing short tandem repeats (STR). Aberrant expression of a putative tumor suppressor gene, STK11, which encodes a serine threonine kinase, has been suggested as the etiologic factor in PJS. In both of the twin sisters with PJS, mRNA analyses by RT-PCR demonstrated a complete lack of STK11 gene expression. These results provide direct evidence that STK11 gene expression is abnormal in PJS. Detecting abnormal expression of the STK11 gene may serve as a molecular approach to the diagnosis of PJS and may facilitate genotype-phenotype correlations in PJS patients.     

Potential impact of hormonal male contraception: cross-cultural implications for development of novel preparations

The prospect of a hormonal male contraceptive is no longer distant. Data on the potential impact of this improvement in contraceptive provision, however, is limited, particularly between different cultures. We have therefore carried out a multi-centre study to assess men's attitudes to proposed novel hormonal methods. Questionnaire-based structured interviews were administered to men in Edinburgh, Cape Town, Shanghai and Hong Kong. Approximately 450 men were interviewed in Edinburgh, Shanghai and Hong Kong, and a slightly larger group (n = 493) in Cape Town to give samples (n > 150) of black, coloured and white men. Knowledge of existing male and female methods of contraception was high in all centres and groups. The majority of men welcomed a new hormonal method of contraception, 44-83% stating that they would use a male contraceptive pill. Overall, a pill was more acceptable than an injectable form (most popularly given at 3-6 month intervals); long-acting implants were least so except in Shanghai. Familiarity with comparable female methods appeared to influence acceptability, for both oral and injectable methods. Hong Kong was the only centre where a male method (condom) was currently the most commonly used; men there appeared to rate the convenience of condoms highly while being least likely to think that they provided effective protection against pregnancy compared to other centres, and were least enthusiastic about novel male methods. The acceptability of potential male hormonal methods of contraception was high in some groups but showed wide variability, determining factors including cultural background and current contraceptive usage. These results suggest that the emerging emphasis that men should have greater involvement in family planning will be substantiated when appropriate contraceptive methods become available.     

18例恶性苗勒混合瘤临床病理分析

目的：探讨女性生殖系统恶性苗勒混合瘤（MMMT）的临床与病理特征。方法：对18例女性生殖系统MMMT进行光镜观察及免疫组化染色，结合临床资料进行分析，对9例进行了术后随访。结果：各部位MMMT的形态特征相似，均含有上皮及间叶两种组织成分，相互间有穿插和移行变化，组织成分形态多样，免疫组化有助于判断。恶性度与异型性、核分裂数及出血坏死程度有关。预后与临床分期有关。化疗有效。结论：MMMT的诊断主要依据组织形态学，预后与临床分期有关。     

DNA prime followed by protein boost enhances neutralization and Th1 type immunity against FMDV

Prime-boost strategy has been exhibited its potency to enhance immune responses, which would be important to the success to develop a vaccine against the foot-and-mouth disease virus (FMDV). An eukaryotic expression construct encoding the FMDV capsid VP1 protein with a recombinant VP1 protein or a commercial FMDV vaccine were tested in the prime-boost strategy in mice and cattle trials. The levels of induced specific antibodies, T cell proliferations, and DTH activities were significantly higher in the prime-boost groups than in those vaccinated with DNA, protein or FMDV vaccine alone. More importantly, the levels of neutralizing antibodies in the former groups were significantly higher than others and could last for at least four months in cattle trials. This study suggests that the prime-boost strategy significantly improves the effective immunity and may provide a longer protection against FMDV infection.     

支气管肺炎患儿治疗前后血清IGF-Ⅱ和CRP测定的临床意义

目的：探讨了支气管肺炎患儿血清中胰岛素样生长因子-Ⅱ（IGF-Ⅱ）和C反应蛋白（CRP）水平的变化及意义。方法：分别应用放免法和免疫法测定了33例支气管肺炎患儿血清中IGF-Ⅱ和CRP，并与35名正常儿作比较。结果：在治疗前血清IGF-Ⅱ和CRP水平非常显著地高于正常儿组（P〈0．01-0．001），经治疗后一周则与正常儿组比较无显著性差异（P〉0．05）。结论：测定支气管肺炎患儿血清中IGF-Ⅱ和CRP水平对疾病的治疗和预后有十分重要的临床价值。