p53 Protein expression in tumours from head and neck subsites,larynx and hypopharynx,and differences in relationship to survival

The present study involves an immunohistochemical analysis of p53 protein expression in head and neck tumours located at two separate subsites, the larynx and hypopharynx. It attempts to relate differences in expression to differences in the behaviour of these tumours. Detection of the p53 protein was performed using immunohistochemistry on 32 specimens of hypopharyngeal squamous cell carcinoma and 35 specimens of laryngeal squamous cell carcinoma. p53 overexpression was found in 66% of the hypopharyngeal tumours and in 51% of the laryngeal specimens analysed. Some differences between the two tumour types were noted in the pattern staining. p53 staining in those with hypopharyngeal tumours was associated with a statistically significant increased survival. For laryngeal carcinoma the converse was true but did not reach statistical significance. Differences in the behaviour of different head and neck tumour types may be reflected in differences in expression of the p53 protein. While p53 protein expression does not appear to be a useful prognostic indicator in laryngeal carcinoma it might be a useful prognostic indicator in tumours of the hypopharynx. Moreover, it may help predict those tumours which are radioresistant, thus suggesting other modes of treatment for these tumours. Of particular importance is the molecular basis for the observed differences in survival associated with p53 expression in the two tumour sites. This is under further investigation.     

Growth and survival of B-chronic lymphocytic leukaemia cells

Although chronic lymphocytic leukaemia of B-cell type (B-CLL) is the most common form of leukaemia in the Western world, several questions about the biology of B-CLL remain to be clarified. To obtain a conceptual model for B-CLL, defined as a relentless accumulation of resting B-CLL cells, it is particularly relevant to ask which cell type is the normal counterpart of B-CLL; what is the site of proliferation; which signals are involved in the recruitment and induction of proliferation and which signals contribute to the survival of the B-CLL cells? The significance of the studies on B-CLL cellsin vitro for the interpretation of thein vivo situation may be questioned since they oversimplify the multiple and complex cellular interactions that occurin vivo. However, thein vitro studies have been instrumental in elucidating signals that may regulate growth, differentiation and survival of B-CLL cells. This knowledge, herein reviewed, can be used to put forward a hypothesis on B-CLL cell regulationin vivo.     

Influence of intratumoral basic fibroblast growth factor concentration on survival in ovarian cancer patients

Since basic fibroblast growth factor (bFGF) is considered as a potent mitogen that stimulates the growth of ovarian cancer cells, we evaluated the role of bFGF as a prognostic marker in patients with epithelial ovarian cancer. bFGF was quantified from the tumor cytoplasm of 76 patients with FIGO stage I–III ovarian cancer by a human FGF basic immunoassay (R&D Systems). After a mean follow-up period of 42 months, 50 patients were found to be free of tumor while 26 patients had died of the disease. The median bFGF concentration was 352.9 pg/mg (range 27.4–26 600 pg/mg). After dichotomization cytoplasmic expression of bFGF was found to be low in 44 tumors (≤500 pg/mg) and high in 32 tumors (>500 pg/mg). The probability of overall survival was 38.8 and 58.5% in the low bFGF and high bFGF groups, respectively (log-rank P=0.0066). In multivariate analysis, residual tumor after initial surgery and bFGF, but not histologic grade or stage of the disease, independently influenced the overall survival probability. Furthermore, tumors with high cytoplasmic expression of bFGF revealed a much greater stromal content. Therefore, we hypothesize that bFGF may induce a fibroblastic response which causes tumors with a high bFGF to be less aggressive than those with less stromal tissue.     

Primary metastatic (stage IV) Ewing tumor: Survival analysis of 171 patients from the EICESS studies

Background: In the multicenter European Intergroup Cooperative Ewing's Sarcoma Studies, localized Ewing tumors of bone were treated by combination chemotherapy with surgery and/or radiotherapy. Patients with primary metastases (pm-pts) were treated in high risk protocols.Patients and methods: One hundred seventy-seven pm-pts were registered from January 1990 to December 1995, 171 were evaluable for survival analyses. Thirty-six pm-pts received myeloablative megatherapy with stem cell rescue following conventional treatment. Bilateral whole lung irradiation (WLI) was administered in 57 pm-pts with pulmonary involvement. Event-free survival (EFS) rates were estimated by Kaplan–Meier analysis. Prognostic factors were identified by log-rank statistics, Cox procedures and logistic regression.Results: Eighty-nine deaths were recorded by 1 February 1997, EFS four years after diagnosis for all 171 pm-pts was 0.27. EFS for isolated lung metastases was 0.34, for bone/bone marrow (BM) metastases, 0.28, and for combined lung plus bone/BM metastases, 0.14 (P < 0.005). WLI improved outcome in case of isolated pulmonary involvement (0.40 vs. 0.19, P < 0.05). In pm-pts with combined pulmonary/skeletal metastases, intensification by megatherapy and/or WLI improved EFS from 0.00 to 0.27 (P = 0.0001).Conclusions: EFS four years after diagnosis in patients with disseminated Ewing tumors is 0.27. Whole lung irradiation and megatherapy improve outcome in subgroups of patients with disseminated Ewing disease.     

Squamous cell carcinomas of the head and neck in Norway, 1953-92: an epidemiologic study of a low-risk population

Trends in incidence, five-year relative survival, and mortality among patients in Norway with squamous cell carcinoma of the oral sites, oro-/hypopharynx, and larynx were studied for the period 1953-92. Throughout the first part of the study period, age-adjusted incidence rates (AAIR) of oral cancer remained stable in both genders. Since the end of the 1960s, AAIRs increased by 13 percent per five-year period in males and 12 percent in females. The figures suggest increased male incidence rates of oral cancer in younger age groups. During the same period, AAIRs of cancers of the oro-/hypopharynx in males increased by 19 percent per five-year period. The AAIRs of laryngeal cancer increased steadily from 1953-92 among both males and females by 17 percent and 21 percent per five-year period, respectively. For all sites, changes in AAIRs for males were greater in rural than in urban areas. No improvement in detection of disease at a localized stage was observed for either gender. There are indications of improvements in the five-year relative survival rates for oral and pharyngeal cancer in both genders. For all sites, relative survival was better in younger than in older patients. Only in the case of pharyngeal cancer in males was an increase in disease-specific mortality rates positive for a time trend.     

Survival rates for primary malignant brain tumours in Europe

In the framework of EUROCARE, a concerted action between 45 population-based cancer registries, in 17 European countries, survival of patients with primary malignant brain tumours was investigated. Survival analysis was carried out on 16 268 patients diagnosed between 1985 and 1989 and followed-up for at least 5 years. The mean European age-standardised 5-year relative survival was 17% in men and 20% in women, with minimal intercountry variations, except for markedly lower rates in Scotland, Estonia and Poland. The age-specific analysis showed a relatively uniform survival in patients aged more than 65 years at diagnosis, but there were more marked intercountry differences in younger patients. In the 15–44 year age group (25% of the total study population) 5-year relative survival ranged between 55% (Finland and Sweden) and 27% (Poland). Generally, survival decreased with increasing age at diagnosis. The analysis of a temporal trend in survival was carried out on a subset of registries with available data from 1978–1989. Overall, there was an increase in survival over the considered study period, mostly confined to 1-year survival, suggesting that it was mostly related to improved diagnostic techniques. The most important survival increase occurred in the younger patients, both for 1- and 5-year survival, suggesting that younger patients have less biologically aggressive tumours, benefiting from the combined effect of diagnostic accuracy and effective therapies. The most marked survival increase was seen in England and Denmark, countries with low survival rates at the beginning of the study period, whereas in Finland and Germany, where survival was relatively high to begin with, no important temporal trend was seen.     

新型的治疗阿尔茨海默氏症药物(1-二甲基磷酰基-2,2,2-三氯)-乙基-1-醇烟酸酯对体外神经细胞的作用

目的：观察本实验室合成的一种治疗阿尔茨海默氏症(AD)的药物(1-二甲基磷酰基-2，2，2-三氯)-乙基-1-醇烟酸酯(NMF)，对体外培养的皮层神经细胞活性的影响以及对海人藻酸(KA)所致的神经损伤的保护作用。方法：采用体外培养皮层神经元的方法，解剖分离15d胚胎小鼠皮层神经细胞，接种于96孔板，48h后加药并培养72h，以MTT法观察NMF对小鼠皮层神经细胞活性的影响；同时将接种于24孔板的细胞预先给予NMF，d3时加或不加KA处理后，以台盼蓝染色鉴别并计数死、活细胞，可得出细胞的存活率。结果：NMF明显促进胎鼠皮层神经元活性，其中NMF 1、0．1、10 nmol·L~(-1)促进神经元活性增殖率分别高达34．7％、37．4％、36．7％。NMF明显促进正常胎鼠皮层神经元存活率，与对照组比较，10、1nmol·L~(-1)NMF对皮层神经元的存活率分别提高39．3％、73．5％。NMF能显著对抗KA所致的神经元损伤，与KA损伤组相比，NMF0．1、10、1nmol·L~(-1)对损伤皮层神经元的保护率分别为77．30％、80．10％、84．15％。结论：NMF明显促进胎鼠皮层神经元的活性、提高正常皮层神经元的存活率，并能有效地保护KA所致的神经元损伤，提示NMF是一种很有潜力的治疗AD的药物。     

Calreticulin binding and other biological activities of survival peptide Y-P30 including effects of systemic treatment of rats

Neuron survival-promoting peptide Y-P30, purified from oxidatively stressed neural cell lines, inhibits the appearance of microglia and rescues neurons 1 week after direct application to lesions of the rat cerebral cortex (7). Y-P30 affinity matrices treated with solubilized membranes from a variety of cell lines including human neuroblastoma SY5Y, mouse hippocampal cells HN 33.1, and human promonocytes HL-60, as well as with cerebral cortex tissue from both humans and rats, showed highly specific binding to calreticulin, a ubiquitous calcium binding protein that may be critical for integrin function. Treatment of cultures with 0.1 nM Y-P30 stabilized all these cell types whether differentiated or not, while 1 microM peptide also inhibited the morphological differentiation of the HL-60 cells into macrophages. Western analysis of the medium of SY5Y cell cultures suggested Y-P30-stimulated release of calreticulin, a result consistent with its other biological activities. Likewise, single dose systemic application of Y-P30 in unoperated rats and in rats with cerebral cortex lesions produced significant reductions in cerebral cortex membrane-associated calreticulin. Both direct and intravenous treatment with peptide also reduced cortical neuron atrophy 4 days after these lesions but only direct application consistently inhibited the appearance of ED-1(+) monocyte derivatives. We suggest that in vitro and in vivo mechanisms of Y-P30 effects are similar and involve the targeting of calreticulin. The results also suggest that some of these activities are apparent in the cerebral cortex after systemic application of this peptide.     

Primary clinical analysis of medical disorders in Chinese women with endometrial carcinoma

The objectives of this study were to survey the prevalence of medical disorders in Chinese women with endometrial carcinoma and evaluate their potential impact on the clinical treatment and prognosis. Three hundred and seven women with endometrial carcinoma, from July 1, 1971 to October 31, 2001, were analyzed retrospectively. One hundred and forty-six of them (47.6%) were found to have associated medical disorders. The most common medical disorders were hypertension (33.9%), diabetes mellitus (9.8%), and coronary heart disease (9.4%). As many as 38.4% of the women had two or more medical disorders. The patients with medical disorders were on average elder than those without any medical disorders (P < 0.01). Radiotherapy and chemotherapy were administered more commonly in the group with medical disorders than in the one without (P < 0.01). The rate of surgical procedures was significantly lower in the group with medical disorders than in the group without (P < 0.01). However, the extent of surgical interventions was similar in both groups (P > 0.05). The occurrence of medical disorders was independent of the tumor stage, grade, and histological types (P > 0.05). In addition, follow-up data showed that the 3-year and 5-year survivals were not influenced by the medical disorders (P > 0.05). The results thus suggest that Chinese women with endometrial carcinoma have frequently concurrent medical disorders. Selection of treatment strategies can be influenced by these associated medical disorders, but the overall survival is little changed.     

Vascular endothelial growth factor expression in oligodendrogliomas: a correlative study with Sainte-Anne malignancy grade, growth fraction and patient survival

Microangiogenesis is a delayed but crucial event in the malignant progression of oligodendrogliomas. Accord-ingly, in the new Sainte-Anne grading system of oligodendrogliomas, endothelial hyperplasia and contrast enhancement, both being indicators of microangiogenesis, are key criteria for the distinction of grade A from grade B tumours. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor: a strong correlation between VEGF expression, Sainte-Anne malignancy grade and patient outcome might thus be expected. In order to assess this hypothesis, VEGF immunostaining was performed in a series of 34 oligodendrogliomas that included 11 grade B and 23 grade A, of which nine became grade B during the study period (mean clinical and imaging follow-up: 41 months). VEGF expression correlated strongly with Sainte-Anne tumour grade (P < 0.001), and inversely with patient survival (P < 0.001) and recurrence-free survival (P = 0.002). One hundred per cent of grade B but only 17% of grade A were VEGF-positive. By contrast, the MIB-1 labelling index did not correlate with VEGF expression, total survival or recurrence-free survival. In accordance with the grading system, this study showed that, in oligodendrogliomas, VEGF expression and microangiogenesis are progression-related phenomena that confer on these tumours a growth advantage by presumably reducing hypoxia-induced apoptotic cell death. These findings might have important implications in the future for the indication and timing of anti-angiogenic therapies.