促红细胞生成素对实验性肾性贫血的作用

促红细胞生成素(erythropoietin,EPO)是由肾细胞分泌的一种糖蛋白激素。从人胚肾细胞中诱导,经生物化学方法分离、提纯得到此品。本试验用5/6肾切除的方法造成大鼠慢性肾衰性(CRF)贫血,研究不同剂量EPO对CRF贫血的作用。结果表明EPO有显著的促进红细胞生成,改善CRF贫血状态,使其接近或达到正常水平,最佳剂量为1000 U/kg,并可预防实验性贫血,对正常鼠未见明显作用。     

Modulation of novel DNA adducts during human uterine cervix cancer progression

Progressive accumulation of DNA lesions leads to genetic mutations that are central to the process of tumorigenesis. Human cervix provides an ideal system to determine progressive accumulation of DNA adducts in the target tissue because of its accessibility during routine diagnostic checkups. Uterine cervix samples from various pathologies, i.e. normal (n=13), inflammation (n=9), dysplasia (n=5) and different stages of invasive cancer (n=47), were analyzed for DNA adduct burden by modified 32P-postlabeling/TLC systems. Six subgroups of adducts were detected in the following descending order of polarities: P-1, P-2, PL-1, PL-2, L-1 and L-2 (P, polar; L, lipophilic; PL, between polar and lipophilic). No qualitative differences were observed in adduct profiles in the various cervix pathologies analyzed. However, significant quantitative differences were found. Previously known lipophilic adducts increased significantly from normal to cancer (144+/-61 to 503+/-51 adducts/10(9) nucleotides). Interestingly, the newly discovered polar adducts were present at 61- to 527-fold higher levels than lipophilic adducts. Of all the polar adducts, the known mutagenic lesion, 8-oxodeoxyguanosine, predominated in all cervix conditions. Notably, this lesion was elevated 27-fold in inflammation compared with normal cervix (51,058+/-9,863 versus 1,886+/-507 adducts/10(9) nucleotides). The P-1, PL-1, PL-2 and L-1 adducts were elevated 3- to 13-fold in inflammation compared with normal cervix, and were also higher in dysplasia and cancer. Our data suggest that inflammation may be involved in directing the course of disease progression by accumulating higher levels of DNA lesions. The data further suggest the biomarker potential of the newly detected array of DNA adducts.     

Five-year Long-term Outcomes of Stereotactic Body Radiation Therapy for Operable Versus Medically Inoperable Stage I Non–small-cell Lung Cancer: Analysis by Operability,Fractionation Regimen,Tumor Size,and Tumor Location

Background

Stereotactic body radiation therapy (SBRT) is standard for medically inoperable stage I non–small-cell lung cancer (NSCLC) and is emerging as a surgical alternative in operable patients. However, limited long-term outcomes data exist, particularly according to operability. We hypothesized long-term local control (LC) and cancer-specific survival (CSS) would not differ by fractionation schedule, tumor size or location, or operability status, but overall survival (OS) would be higher for operable patients.

Duane—minus (Duane sine retraction and Duane sine limitation): possible incomplete forms of Duane retraction syndrome

PurposeTo report ocular motility patterns that mimic, but do not fulfil the full clinical picture of Duane retraction syndrome (DRS) and to describe their clinical features and surgical management.MethodsThis is a retrospective case series study conducted on patients with DRS, mimicking non-comitant exotropia or esotropia and a face turn. Patients were included only if they lacked either globe retraction on adduction (sine retraction) or limitation of adduction or abduction on ductions (sine limitation not >0.5). Any overshoots or pattern strabismus was recorded. The ocular motility and alignment, details of surgery and their surgical outcomes were analysed.ResultsTwenty-one patients were identified; 13 in the sine retraction and 8 in the sine limitation group. All patients presented with a compensatory face turn. Overshoots were present in 10 (77%) and 7 patients (88%) in the sine retraction and sine limitation groups, respectively. Forced duction test showed tightness of the ipsilateral medial and the ipsilateral lateral rectus muscle in esotropic (n = 3) and exotropic patients (n = 18), respectively. Orthotropia was achieved in 82% of patients following ipsilateral medial or lateral rectus muscle recession.ConclusionsThere is a subset of patients who present with motility pattern similar to DRS but lack its complete diagnostic criteria. The presence of a face turn, overshoots on adduction or an ipsilateral tightness of the affected muscle should make one consider DRS sine retraction/sine limitation. The patients in our study responded well to lines of management similar to those of DRS.Subject terms: Ocular motility disorders, Eye abnormalities     

A region of deletion on chromosome 22q13 is common to human breast and colorectal cancers

Chromosomal allelic losses have varying frequency in breast cancer, with key regions including chromosomes 1, 3p, 7q, 9p, 16q, 17, and 22q. Recently, we have been able to map a new target region of allelic loss on chromosome 22q involved in colorectal cancer. The aim of the current investigation was to determine whether this target region may also be involved in human breast carcinogenesis. Thirty-six pairs of matched normal and tumor specimens from breast cancer patients, as well as eight breast cancer-derived cell lines, were genotyped using 17 microsatellite markers spanning chromosome 22q. Allelic deletion was found in 19 of 36 tumors (53%), and the pattern observed in those cases with partial losses was consistent with a region flanked by D22S1171 and D22S928. This interval overlaps that identified in colorectal cancer and comprises nearly 1.1 Mb. This study provides evidence of a common region of deletion on chromosome 22q13 involved in both breast and colorectal cancers and underscores the existence of putative tumor suppressor gene(s) at this location.     

Kinetics and Mechanism of Degradation of a Cyclic Hexapeptide (Somatostatin Analogue) in Aqueous Solution

A highly active cyclic hexapeptide analogue of somatostatin, Cyclo(N-Me-L-Ala-L-Tyr-D-Trp-L-Lys-L-Val-L-Phe), L-363,586, was found to improve the control of postprandial hyperglycemia in diabetic animals when given in combination with insulin. The compound is reported to be relatively stable in blood, nasal cavity, and intestinal lumen but undergoes rapid degradation in aqueous solution. The objective of this study was to elucidate the degradation mechanisms based on the kinetic data and the structure of the degradation products. Both pH and temperature had a profound influence on the instability of the peptide in aqueous solution. The data indicated that the peptide was most stable at a pH of about 4.7. The pH-rate profile exhibited specific acid catalysis at a pH less than 3.0 and base catalysis above pH 10.5. The kinetic pK _a was determined to be 9.7. This pK _a could be attributed to the tyrosine residue. The mechanisms of degradation under acidic and alkaline conditions appear to be different. Identification of the fragments obtained using mass spectrometry and amino acid sequencing suggest that the cyclic compound was cleaved to yield a linear fragment, which underwent further cleavage at both peptide linkages alpha to the trypto-phanyl residue. The indole group of that residue is probably the potential nucleophile attacking the adjacent carbonyls. A rate equation for the degradation of the hexapeptide has been proposed.     

甘草叶中甘草宁P-3′-甲醚的分离和鉴定

Two flavonoids were isolated from the leaves of Glycyrrhiza uralensis Fisch (Licorice, Leguminosae). On the basis of physico-chemical properties and spectroscopy (UV, ¹HNMR and MS), a new compound was elucidated as 3,5,7,4′-tetrahydroxy-3′-methoxy- 6-isoprenyl flavone (gancaonin P-3′-methylether) and another known compound was identified as 8-C-prenyleriodictyol.     

Telomerase inhibition by siRNA causes senescence and apoptosis in Barrett's adenocarcinoma cells: mechanism and therapeutic potential

Background  

In cancer cells, telomerase induction helps maintain telomere length and thereby bypasses senescence and provides enhanced replicative potential. Chemical inhibitors of telomerase have been shown to reactivate telomere shortening and cause replicative senescence and apoptotic cell death of tumor cells while having little or no effect on normal diploid cells.     

Co-treatment with vorinostat synergistically enhances activity of Aurora kinase inhibitor against human breast cancer cells

Aurora kinases (AKs) regulate multiple components of mitotic cell division in eukaryotic cells. Aurora A is frequently amplified or overexpressed in breast cancer cells leading to aberrant chromosome segregation, genomic instability, and activation of oncogenic pathways. In the present studies, we determined the effects of treatment with the pan-AK inhibitor MK-0457 and/or the pan-histone deacetylase inhibitor vorinostat against human breast cancer cells that were either ER-, PR-, and HER2- (MDA-MB-468 and MDA-MB-231) or exhibited Aurora A amplification (BT-474 and MDA-MB-231 cells). Treatment with MK-0457 depleted p-AKs levels and their activity, as well as induced G2/M accumulation, DNA endoreduplication, multipolar mitotic spindles, and apoptosis of the breast cancer cells. Similar apoptotic effects were observed with treatment with the Aurora A-specific inhibitor, MLN8237. Treatment with vorinostat induced hsp90 acetylation and inhibited its chaperone association with AKs, leading to depletion of AKs and Survivin. Exposure of the siRNA to AK A also induced apoptosis, which was augmented by co-treatment with MK-0457 and vorinostat. Co-treatment with vorinostat enhanced MK-0457-mediated inhibition of the activities of Aurora A and Aurora B, leading to synergistic in vitro activity against human breast cancer cells. Co-treatment with MK-0457 and vorinostat also caused greater tumor growth inhibition and superior survival of mice bearing MDA-MB-231 xenografts. These pre-clinical findings indicate that combined treatment with a pan-AK inhibitor or an Aurora A-specific inhibitor and vorinostat represents a novel therapeutic strategy for the treatment of Aurora A-amplified and/or triple negative breast cancers.