p185neu expression in human lung adenocarcinomas predicts shortened survival

p185neu is the protein product of the HER2/neu protooncogene. This protein has characteristics of a tyrosine kinase growth factor receptor and is postulated to be important in human carcinogenesis. To define the significance of the expression of this protein in human non-small cell lung cancer, 55 tumors from patients with squamous cell carcinoma (16), adenocarcinoma (29), or large cell carcinoma (10) of the lung were examined for p185neu using immunohistological methods. Five of 16 squamous cell carcinomas and 10 of 29 adenocarcinomas were found to overexpress p185neu relative to levels of expression seen in uninvolved bronchiolar epithelium. For the adenocarcinomas, p185neu expression was associated with older age (66.6 +/- 10.1 versus 57.5 +/- 10.8 years) (P = 0.04) and shortened survival (83.7 +/- 94.1 versus 188.5 +/- 120 weeks) (P = 0.01). In this group, using Cox's multivariate survival analysis, p185neu expression was found to be a significant determinant of survival (P = 0.04) even after accounting for the effect of tumor stage. For the squamous cell carcinomas, p185neu expression was not correlated with any of our clinicopathological parameters. Our findings indicate that non-small cell lung cancers which express p185neu do so at levels higher than that found in normal bronchiolar epithelium, and expression in adenocarcinomas of the lung is independently associated with diminished survival intervals.     

Postnatal changes of nicotinic acetylcholine receptor 2, α3, α4, α7 and β2 subunits genes expression in rat brain

Postnatal changes of nicotinic acetylcholine receptor (nAChR) α2, α3, α4, α7 and β2 subunits mRNAs were investigated in rat brain using ribonuclease protection assay. Multiple developmental patterns were observed: (1) transient expression during the first few postnatal weeks; α2 in the hippocampus and brain stem, α3 in the striatum, cerebellum and cortex, α4 in the hippocampus, striatum and cerebellum, α7 in the cerebellum and β2 in the striatum. (2) Constant expression across development; α2 and α3 in the thalamus, α4 in the cortex, thalamus and brain stem, α7 in the thalamus and brain stem and β2 in all brain regions except striatum. (3) Non-detection across development; α2 in the cortex, striatum and cerebellum. (4) Increase with age; α7 in the cortex and hippocampus. (5) Bell-shaped development; α7 in the striatum. Postnatal changes of nAChR isoforms in different brain regions of rat were investigated by receptor binding assays. The developmental patterns of [³H]epibatidine and (−)-[³H]nicotine binding sites were similar to each other in each brain region, but different from that of [³H]α-bungarotoxin binding sites. No obvious correlation was observed between the developmental patterns of [³H]α-bungarotoxin, [³H]epibatidine and (−)-[³H]nicotine binding sites and corresponding subunits mRNAs. These results indicate that multiple mechanisms are involved in changes of gene expression of nAChRs subunits in the brain of developing rats.     

Insulin-like growth factors and insulin-like growth factor binding proteins in cerebrospinal fluid and serum of patients with dementia of the Alzheimer type

Summary After acid gelchromatography cerebrospinal fluid and serum levels of immunoreactive insulin-like growth factor 1 and 2 (IGF-1 and IGF-2) were determined in patients with dementia of the Alzheimer type (AD) and in healthy subjects. The AD CSF levels of immunoreactive IGF-1 did not differ from the subjects but the levels of immunoreactive IGF-2 was significantly elevated in both serum and CSF in the AD patient group. Additionally immunoreactive IGF-1 in AD serum was found to be significantly elevated. To characterize the CSF IGF binding protein activity (IGFBP), ligand blotting was performed on whole CSF from AD patients and subjects. The results demonstrate two major forms of IGFBP in CSF with approximate molecular weights of 33 KDa and 30 KDa. The two IGFBP forms are suggested to represent IGFBP-2 and IGFBP-6. A highly significant increase in both the IGFBPs was observed in the CSF of the AD patients compared to the healthy subjects.     

金属硫蛋白对大鼠肝脏线粒体氧自由基损伤的保护作用

目的：研究金属硫蛋白（ＭＴ）对氧自由基损伤线粒体的保护作用以探讨其细胞保护机制。方法：采用ＦｅＳＯ４／抗坏血酸自由基发生系统直接损伤线粒体，测定Ｃａ（２＋）－Ｍｇ（２＋）－ＡＴＰａｓｅ活性和Ｃａ（２＋）摄入的变化。结果：ＭＴ能够直接拮抗氧自由基对线粒体Ｃａ（２＋）－Ｍｇ（２＋）－ＡＴＰａｓｅ活性和Ｃａ（２＋）摄入的抑制作用（Ｐ＜０．０１）。结论：ＭＴ对氧自由基损伤线粒体有明显保护作用，ＭＴ对细胞器线粒体的保护作用可能是细胞保护机制之一。     

EGFR expression as an ancillary tool for diagnosing lung cancer in cytology specimens.

Lung cancer evolves in a multistep process, and its early detection portends a better prognosis. Bronchial washings/brushings and fine-needle aspirations are often used as early screening and cytological diagnosis of lung cancer. In some cases, it is difficult to differentiate morphologically malignant from reactive cells. Epidermal growth factor receptor (EGFR) is a transmembrane receptor overexpressed in high percentage lung cancers, and contributes to tumor growth. Assessing EGFR expression levels by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) may provide critical information of tumor marker abnormalities, assist in the cytological diagnosis, and stratify patients for EGFR inhibitor therapy. Fifty patients with bronchial washings/brushings or fine-needle aspiration specimens, and corresponding histologically confirmed lung biopsies, were studied for EGFR expression with FISH and IHC. Copy numbers of the EGFR gene locus were analyzed with those of chromosome 7 by FISH. EGFR and FISH results were compared to our FISH data with combined EGFR, c-myc, 5p15.2, and chromosome 6 probes in selected cases. Cell blocks, if available, and tissue biopsy sections were used for EGFR IHC. The intensity of IHC was scored, and quantified. Only balanced aneuploidy of EGFR was identified by FISH. Gene amplification was not detected. The chromosomal abnormalities of EGFR were often accompanied by other chromosomal aneuploidies demonstrated in c-myc (8q24), 5p15.2 or 6p, indicating a general genomic instability. About half of the specimens with confirmed malignancy showed EGFR balanced aneuploidy by FISH, and gene copy number was not coupled with protein expression in many cases. The benign or reactive cytology specimens confirmed by biopsies had high specificity by FISH (96%) and IHC (88%). FISH and IHC analysis of EGFR, possibly along with other tumor markers, may be a useful ancillary tool to classify difficult cytology cases and inform clinicians arranging targeted chemotherapy.     

Dosimetry of combined intracavitary and external irradiation of carcinoma of the uterine cervix.

Dose distribution around intracavitary applicators (Stockholm technique) has been investigated. The gradient of dose around the combination of intrauterine and vaginal applicators used is steep. The position of the uterus with and without the radium applicators inserted varies. Together with the steep dose gradient this implies that external irradiation following intracavitary treatment involves a risk for overdosage to tissues in the vicinity of the uterus and underdosage to the parametrium.