原发性肺癌患者的血液流变学研究

观察了原发性肺癌患者血液流变学的变化,采用血液比粘度计检测正常组(42例),肺癌组(58例),慢性阻塞性肺病(COPD)组(76例)患者的血沉降率、血球压积、全血比粘度、血浆比粘度及全血还原比粘度。结果:1 COPD组血球压积、低及中切变率时全血比粘度较正常组、肺癌组显著升高(P<0.05).2 肺癌组血沉降率较正常组、COPD组显著升高(P<0.05).3 肺癌组的血球压积、低及中切变率时的全血比粘度较正常组无显著性差异(P>0.05).4 3组高切变率时全血比粘度、全血还原比粘度与血浆比粘度无显著性差异(P>0.05).5正常组与COPD组血沉降率无显著性差异(P>0.05)。结论:肺癌患者血沉降率增高提示其红细胞聚集力增强,而其血粘度无明显改变,可能与红细胞压积无明显改变有关。COPD患者血球压积、血粘度明显增高,可能与长期缺氧有关。     

Wheezing in Chinese schoolchildren: disease severity distribution and management practices, a community-based study in Hong Kong and Guangzhou

BACKGROUND: Asthma is a common chronic disease and information on its management practices at the community level is helpful in identifying problems and improving asthma care. OBJECTIVE: To assess the severity status and management of the asthma symptom of wheeze of children at the community level in Hong Kong (HK) and Guangzhou (GZ). METHODS: Cross-sectional study of children aged 10 years using the International Study of Asthma and Allergic disease in Childhood (ISAAC Phase II protocol). Asthma management and lung function were assessed in 178 (98 from HK and 80 from GZ) randomly selected children with wheeze over the past 12 months. RESULTS: Eighty-three percent, 11%, 6% and 0% of children suffered from intermittent, mild persistent, moderate persistent and severe persistent asthma, respectively, according to the frequency of their symptoms. Addition of spirometric parameter only changed the asthma severity classification in 2.8% of children. Medications were used by 30.6% and 71.3% of children for wheeze in HK and GZ, respectively. In HK, inhaled beta(2)-agonist (73.3% among the drug users) was the commonest medication used followed by inhaled corticosteroid (ICS) (23.3%). In GZ, inhaled beta(2)-agonist was used by 75.4% of children, but use of ICS (26.3%), oral beta(2)-agonist (26.3%), oral theophylline (45.6%), oral ketotifen (36.8%) and oral steroid (35.1%) were also common. ICS was only used by 11.4% of children with persistent asthma. Ten percent and 18.7% of children in HK and GZ, respectively, had emergency department visits, while 16.3% and 11.6% of children in HK and GZ, respectively, had missed school secondary to asthma over the past 1 year. CONCLUSIONS: Most children in the community had intermittent asthma and addition of lung function to symptoms did not significantly affect classification of asthma severity. Significant morbidity was seen even in this group of children with mostly intermittent and mild persistent asthma.     

On the role of additive hormone monotherapy with tamoxifen,medroxyprogesterone acetate and aminoglutethimide,in advanced breast cancer

Summary We analyzed the results of clinical studies on the therapeutic efficacy of hormone monotherapy with tamoxifen, medroxyprogesterone acetate, and aminoglutethimide in metastatic breast cancer, which were published between 1971 and 1986 and involved altogether 7000 patients. The overall response rates in patients treated with these hormonal single agents at various dose levels ranged from 31%–42%. When only estrogen receptor-positive patients were considered, the response rates lay between 41% and 54% in groups which were treated with the antiestrogenic agents tamoxifen or aminoglutethimide. The duration of remission was 12 months for tamoxifen- and aminoglutethimide-treated women, whereas medroxy-progesterone acetate effected remissions lasting from 6–16 months. The overall mean survival from start of therapy in tamoxifen- and aminoglutethimide-treated groups was 20 months, whereas information concerning this therapeutic parameter was available only in a minority of medroxyprogesterone acetate-treated groups. With respect to the response by site of metastatic lesions, all three agents caused a significantly higher degree of remissions in the soft tissue as compared to visceral disease.Abbreviations AG Aminoglutethimide - MPA Medroxyprogesterone acetate - TAM Tamoxifen     

Treatment with aflatoxin B1 for immortalization of human fibroblasts from Li-Fraumeni patients

Immortalization of normal human fibroblasts is a very rare event. Multiple genes such as p53 and cellular senescence genes are possibly involved in immortalization of human fibroblasts, suggesting that multiple treatments with carcinogens are required for the immortalization. We describe here the procedure for immortalization of human fibroblasts (MDAH 087) from Li-Fraumeni cancer syndrome with a germ-line p53 mutation. The cells were subjected to multiple treatments with aflatoxin B₁ (AFB₁) in the presence of exogenous metabolic activation with rat liver post-mitochondrial supernatant (PMS), and 3 of 9 MDAH 087 cell cultures treated 1–3 times with 0.1–1 µg/ml AFB₁ became immortal, defined as continuous growth for over 300 population doublings after the first treatment. However, cultures of human fibroblasts from a normal embryo treated under the same conditions failed to escape senescence. The results indicate that the model of human fibroblasts with a mutated p53 allele exposed to AFB₁ is potentially useful for studying mechanisms of chemically induced immortalization.     

Expression of p53 protein in infiltrating and in-situ breast carcinomas.

Five antibodies directed against the whole or part of p53 protein have been used to detect the protein immunohistochemically in 70 infiltrating breast carcinomas and 10 ductal carcinomas in situ. Mutations are known to occur in different conserved domains, and the antibodies employed spanned the expected sites. p53 protein was identified in 53 per cent of infiltrating carcinomas using the antibodies PAb 240, PAb 1801, C19, and JG8. The antibody PAb 421 detected the protein in 31.5 per cent; all positive with the other antibodies. Well-differentiated oestrogen receptor-positive tumours had a low incidence of p53 detection. Variation in the percentage of reactivity was seen between carcinomas and in some cases between different antibodies in the same cancer. Those carcinomas with a high percentage of positive cells with all antibodies were more likely to have metastasized to nodes, be at an advanced stage, and be oestrogen receptor-negative/epidermal growth factor receptor-positive. There was no significant correlation with c-erbB-2 protein expression or retinoblastoma protein loss. p53 protein was detected in a high proportion of cells in three of the six comedo ductal carcinomas in situ studied but either not at all or at a lower level in tumours of the cribriform type. p53 mutations are common in breast carcinomas, but heterogeneity within individual tumours is frequent. Marked expression of p53 appears to relate to tumour progression.     

The use of luteinizing hormone releasing hormone agonists and antagonists in gynaecological cancers

The use of agonistic analogues of luteinizing hormone releasinghormone (LHRH) is an established therapy for hormone-dependentmetastatic pre-menopausal breast cancer. Their mechanism ofaction in this disease is the suppression of ovarian oestrogenproduction (medical castration). In the treatment of post-menopausalmetastatic breast cancer, LHRH agonists alsohave some effect,although minor, probably through a suppression of ovarian androgenproduction. Convincing evidence has been accumulated that LHRHanalogues can directly inhibit the proliferation of breast cancercells in vitro. The clinical impact of these findings, however,is still controversial. Experimental data and several pilotclinical trals suggest that in epithelial ovarian cancer andsex-cord-stromal tumours of the ovary, LHRH agonists might haveantitumour activity through the suppression of gonadotrophinsecretion (selective medical hypophysectomy). Phase III clinicaltrials, evaluating this hypothesis, are in progress. Directantiproliferative effects of LHRH analogues on epithelial ovariancancer cells have been demonstrated in vitro. In endometrialcnacer, experimental and early clinical results support theconcept of a direct antiproliferative activity of LHRH analogues.Recently, potent antagonistic analogues of LHRH, devoid of relevantside-effects have become available for clinical testing. Thesenew antagonists might be superior to agonistic LHRH analogueswith respect to the rapidity and efficacy of selective medicalhypophysectomy and medical castration. Modern LHRH antagonistsmight also permit a better exploitation of direct antitumoureffects. A further therapeutic improvement in gynaecologicaloncology might result from a combination of LHRH agonists orantagonists with other peptide hormone anlogues such as agonistsof somatostatin or antagonists of bombesin/gatrin releasingpeptide which have antitumour activity. Since 50% of breastcancers and 80% of epithelial ovarian cancers and endometrialcancers have high affinity binding sites for LHRH, cytotoxicLHRH analogues might provide a targeted chemotherapy, whichwould be more efficacious and less toxic than conventional regimens.     

Paraffin wax-embedded material as a source of DNA for the detection of somatic genetic changes

Loss of genetic material, corresponding to chromosomal deletions, has been detected in a wide range of tumours and may indicate the position of a tumour suppressor gene. In order to identify the position of such a gene more precisely, many tumour samples must be studied until a minimum consensus deletion is characterized. This process is particularly necessary for lung tumours in which the deletion in chromosome 3, seen with such high frequencies in all histological subtypes, is almost always large. We have recently described the use of the polymerase chain reaction (PCR) for restriction fragment length polymorphism (RFLP) analysis of DNA isolated from small bronchial biopsies of lung tumours. In this study we adapted this technique to allow genotyping of DNA isolated from paraffin wax-embedded material (PWEM) microdissected from glass slides. We have investigated 12 lung tumours at polymorphic loci on chromosome 3 and showed allelic loss in all samples. In adapting PCR–RFLP analysis for DNA isolated from PWEM, we have concentrated on those approaches which might be adaptable to routine clinical practice. Somatic genetic changes are now being identified in many tumour types, and this information is expected to be of diagnostic and prognostic significance.     

直肠癌转移与癌组织微血管密度的关系

目的:分析直肠癌组织的微血管密度(MVD)变化及其对癌转移的临床诊断价值。方法:采用免疫组织化学法,对72例手术切除直肠癌组织标本进行微血管标记;在光学显微镜下测定其MVD。将所有患者的临床及追踪随访资料与其手术标本的MVD数据进行统计分析。结果:有转移直肠癌组织的MVD高于无转移者(106.12±32.18vs84.26±27.13),差异有非常显著性意义。结论:直肠癌组织的MVD增加对诊断癌转移有一定的临床价值。     

Biological properties and gene expression associated with metastatic potential of human osteosarcoma

Lung metastasis has a great influence on the prognosis of patients with osteosarcoma. We previously established two high-metastatic sublines, M112 and M132, from the HuO9 human osteosarcoma cell line by in vivo selection. In this study, we newly isolated a high-metastatic subline, H3, and three low-metastatic sublines, L6, L12 and L13, from HuO9 by the dilution plating method. Three high-metastatic sublines produced more than 200 metastatic nodules in the lung, while three low-metastatic sublines produced no or few nodules after injection of 2 × 10⁶ cells into the tail vein of nude mice. There were significant differences in the motility and invasiveness between high- and low-metastatic sublines, whereas the growth rates in vitro and the tumorigenicity in vivo showed no correlation with their metastatic abilities. Early adherence to culture plates was significantly lower in two of three low-metastatic sublines, which occupied smaller surface areas on the culture plates than other sublines did. Comparison of the expression of 637 cancer-related genes by cDNA microarray revealed that seven genes were differentially expressed between high- and low-metastatic sublines. Among them, five genes (AXL, TGFA, COLL7A1, WNT5A, and MKK6) were associated with adherence, motility, and/or invasiveness. These results suggest that the differences in motility/invasiveness and adhesive abilities are key determinants of lung metastasis in osteosarcoma. This revised version was published online in July 2006 with corrections to the Cover Date.     

Haplotype analysis of the BRCA2 9254delATCAT recurrent mutation in breast/ovarian cancer families from Spain

A frame-shift 9254del5 mutation was independently identified in 12 families, eleven of them with Spanish ancestors, in a BRCA2 screening performed in 841 breast and/or ovarian cancer families and in 339 women with breast cancer diagnosed before the age of 40 at different centers in France and Spain. We sought to analyze in detail the haplotype and founder effects of the 9254del5 and to estimate the time of origin of the mutation. Eight polymorphic microsatellite markers and two BRCA2 polymorphisms were used for the haplotype analyses. The markers were located flanking the BRCA2 gene spanning a region of 6.1 cM. Our results suggest that these families shared a common ancestry with BRCA2 9254del5, which is a founder mutation originating in the Northeast Spanish, with an estimated age of 92 (95% CI 56-141) generations.