The activity of letrozole in patients with advanced or recurrent endometrial cancer and correlation with biological markers – a study of the National Cancer Institute of Canada Clinical Trials Group

A multicenter phase II trial was conducted to define the activity of letrozole in postmenopausal women with recurrent or advanced endometrial carcinoma, who had no more than one prior line of progestins and never had chemotherapy (except adjuvant). Archival paraffin-embedded tumor samples were retrieved to determine the expression level of estrogen (ER) and progesterone receptor (PgR), p53, HER-2, bcl-2 and PTEN protein, and phosphorylation status of protein kinase B (PKB/Akt). Thirty-two eligible patients were treated with letrozole at 2.5 mg daily continuously, of whom 10 (31%) had prior progestins. Of the 28 patients evaluated for response, one complete and two partial responses were noted; overall response was 9.4% (95% confidence interval 2-25%). Eleven patients had stable disease for a median duration of 6.7 months (range 3.7-19.3 months). Amongst 22 patients who had tumor blocks available, the proportion showing positive expression of the following markers includes: PgR (86%), ER (86%), PTEN (82%), phosphorylated PKB/Akt (59%), bcl-2 (45%), p53 (32%), and HER-2 (0%). None of these markers correlated with response to letrozole or disease progression. In conclusion, letrozole is well tolerated but has little overall activity in this cohort of women with endometrial cancer.     

人细胞色素p450IA1基因cDNA的克隆和鉴定

在用３－甲基胆蒽诱导培养人羊膜ＦＬ细胞２４ｈ后，抽提细胞总ＲＮＡ并直接合成ｃＤＮＡ第一链。利用人工合成的一对寡核苷酸引物，采用ＰＣＲ技术特异性地扩增Ｃｙｔ ｐ５０ＩＡ１ ｃＤＮＡ。３０个循环后琼脂糖凝胶电泳显示１．５Ｋｂ大小片段，长度与预计相符。Ｓｏｕｔｈｅｒｎ杂交结果证实此片段确为Ｃｙｔ ｐ４５０ＩＡ１ ｃＤＮＡ。将此片段克隆至质粒ｐＧＥＭ－３Ｚ并进行部份序列分析。结果显示克隆片段包含Ｃｙｔ ｐ     

Ganglioglioma: A clinicopathological study of 10 cases

The clinical, radiological, and pathological features in 10 cases of ganglioglioma are described. The clinical data were derived from the patients' medical records, including a review of the age, sex, details of the presenting symptoms, radiological imagings, surgical intervention, and the clinical outcome. Age ranged from 1 to 66 years (mean 29); there were five males and five females. The tumors were located in the fronto-medial, bifrontal, temporal, temporo-basal, temporo-parieto-occipital, and parietal lobes; the 3rd ventricle; the cervicothoracic spinal cord; and the conus medullaris. The presenting symptoms were focal seizures, headaches, hemiparesis, paraparesis, and tetraparesis. In four patients, gross total resection was achieved and in the remaining six patients only subtotal resection was possible. Tumor recurrence occurred in three patients, 1 year, 14 months, and 2 years after the first operation. The histopathologic appearance of gangliogliomas showed a broad variation of the neuronal, glial, and stromal component. Studying proliferation characteristics, labeling for Ki-67 ranged from 0 to 13.7% (mean 4.1) and for PCNA from 0 to 32.1% (mean 20.4). Due to their favorable prognosis, early recognition and correct diagnosis are important in order to avoid progressive neurological deficits and unnecessary aggressive therapy. The application of immunohistochemistry for both neuronal (synaptophysin, NSE, NFP) and astrocytic (GFAP) cell markers, as well as proliferation markers, are recommended in the diagnostic setting for gangliogliomas. The treatment of choice is total surgical resection. The role of radio- and chemotherapy is still controversial.     

人精液中ABH血型物质分泌强度的研究

本文采用中和试验、沉降反应和解离试验对１３５例已知血型人精液中ＡＢＨ血型物质的分泌强度进行了检验，并将其分为强、中、弱三型。这对区别个人血型物质含量及性犯罪的法医学鉴定均有重要意义。并证明了ＡＢ型人精液中Ａ、Ｂ血型物质含量不均等现象，并且绝大多数人Ｂ型物质高于Ａ型物质。     

Suggestive linkage to chromosome 19 in a large Cuban family with late‐onset Parkinson's disease

The identification of disease genes using family‐based approaches has provided important insights into the pathogenesis of Parkinson's disease (PD) demonstrating the importance of genetic studies on monogenic forms of the disease. We studied a large Cuban family with typical, late‐onset PD and probable autosomal dominant inheritance. Mean age at onset was 61.2 years (±12.53, 45–76). Other phenotypes such as essential tremor and atypical parkinsonism were observed in this family. We carried out a genome‐wide scan and linkage analyses. The genetic data were analyzed using a conservative model in which only patients with clinically definite or likely PD were considered affected, other phenotypes were regarded as “unknown.” Multipoint analyses yielded a maximum LOD of 2.26 between markers D19S221 and D19S840. Haplotype analysis showed a region on chromosome 19 shared by six of seven PD patients. The essential tremor phenotype and the atypical parkinsonism do not segregate with this haplotype, suggesting a different etiology. Our findings suggest the presence of a novel locus for PD on chromosome 19p13.3–q12. We propose that an oligogenic model with moderate contribution of two or three genes rather than a “pure” monogenic model might explain better the wide range in age at onset, the reduced penetrance and the phenotypical variability observed in PD families. © 2003 Movement Disorder Society     

Polymorphism p53 codon-72 and invasive cervical cancer: a meta-analysis.

OBJECTIVES: Although some studies have reported that the arginine isoform on codon 72 of p53 increases the susceptibility to invasive cervical cancer, such data remain controversial. The objective of this study was to quantitatively summarize the evidence for such a relationship. METHODS: Our data sources consisted of a MEDLINE search of the literature published before December 2002, bibliography review, and expert consultation. Thirty-seven studies met the inclusion criteria. Information on sample size, study design, Hardy-Weinberg equilibrium, and method of genotype determination was abstracted by two reviewers using a standardized protocol. The overall odds ratio (OR) of the p53 gene on invasive cervical cancer was estimated using the Mantel-Haenzel method. RESULTS: The overall OR (95% confidence interval) for cervical cancer among those with the homozygous mutant (Arg/Arg) was 1.2 (1.1-1.3, P=0.001) compared with those with the heterozygous mutant (Arg/Pro). By a cellular type of cervical cancer, the overall OR among those with Arg/Arg was statistically significant in adenocarcinomas (1.7, 1.1-2.6, P=0.024), but not in squamous cell carcinomas (1.1, 0.9-1.2, P=0.960), compared with Pro/Pro. Compared with Arg/Pro, the OR among those with Arg/Arg was statistically significant in HPV types 16 (1,5, 1.2-2.0, P=0.002). CONCLUSIONS: Overall, the p53 gene was associated with increased risk for invasive cervical cancer. However, the risk varied by country, cellular, and HPV type.     

Human T cells that have been conditioned by the proteolytic activity of the major dust mite allergen Der p 1 trigger enhanced immunoglobulin E synthesis by B cells

BACKGROUND: We have previously demonstrated that the proteolytic activity of Der p 1 selectively cleaves human CD25, the 55 kDa alpha subunit of the IL-2 receptor. As a result of cleavage of surface CD25, peripheral blood T cells produce less IFN-gamma and more IL-4, thereby leading to progressive polarization of the T cells towards a Th2 cytokine profile. Therefore, these observations underline the potential role of the proteolytic activity of Der p 1 in creating a microenvironment conducive for IgE synthesis. OBJECTIVE: To study the effect of T cells that have been conditioned by the proteolytic activity of Der p 1 on IgE synthesis by B cells. METHODS: We have examined this concept in experiments whereby T cells that have been exposed to either proteolytically active or inactive Der p 1 were cocultured with autologous B cells and IgE antibody synthesis was monitored. RESULTS: Here we demonstrate for the first time that coculturing T cells that have been in contact with proteolytically active Der p 1 with autologous B cells leads to augmentation of IgE antibody responses. CONCLUSIONS: The proteolytic activity of Der p 1 conditions human T cells, which then become empowered to trigger enhanced IgE synthesis by B cells.     

Anaplastic ganglioglioma with sarcomatous component: An immunohistochemical study and molecular analysis of p53 tumor suppressor gene

The present case report describes a case of ganglioglioma with a distinct sarcomatous component in the left temporal lobe of a 59‐year‐old Japanese man. Neoplastic neuroglial tissue contained both benign and anaplastic glial components with a MIB‐1 labeling index of 0.1% and 12.0%, respectively. Sarcomatous tissue adjacent to the anaplastic glial tissue was dominated by pleomorphic fibroblastic cells with a MIB‐1 labeling index of 10.8%. They were immunoreactive for smooth muscle actin, type IV collagen, and alpha 1 antitrypsin, but not for desmin and CD34. Interestingly, some of the sarcomatous cells were double‐positive for smooth muscle actin and GFAP. The p53 protein had accumulated in the anaplastic astrocytes and sarcomatous cells, but direct DNA sequencing of PCR products failed to detect any mutation in the p53 gene (from exon 4 to exon 10).     

Isochromosome 18q in a girl with holoprosencephaly,DiGeorge anomaly,and streak ovaries

We report on the clinical and pathologic findings in a girl with isochromosome 18q (46, XX,i(18q)) who had combined manifestations of monosomy 18p and trisomy 18q. Major congenital anomalies included premaxillary agenesis, alobar holoprosenphaly, double Outlet right ventricle, DiGeorge anomaly and streak ovaries. The clinical spectrum in i(18q) is very broad. © 1993 Wiley-Liss, Inc.