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Biomedical subjects

Y Lu

Publications and source records attributed to Y Lu.

At least 793 records · Page 44Linked to original sources

[Detection of c-myc translocation in human lung cancer cells by fluorescence in situ hybridization (FISH)].

c-myc gene amplification has been found in lung cancer, however, it can not explain all cases of lung cancer with c-myc gene overexpression. Gene translocation is one of the ways by which oncogene is activated. But the old methods for detecting gene mutations are not so effective for the detection of gene translocation, especially in solid tumors. Fluorescence in situ hybridization (FISH) can be used to detect gene translocation more efficiently. Using FISH, we discovered c-myc gene translocation in a lung adenocarcinoma cell line GLC-82 and SV40T-transformed human bronchial epithelial cells. In GLC-82, c-myc gene translocated to the short arm of a C group marker chromosome. In the SV40T-transformed epithelial cells, c-myc gene translocated to 14q32, which was the same as that found in Burkitt's lymphomas. Translocation was related to oncogene activation. c-myc translocation may play an important role in the carcinogenesis of lung cancer.

Adenocarcinoma↗

An amino-terminal polypeptide fragment of the influenza virus NS1 protein possesses specific RNA-binding activity and largely helical backbone structure.

The NS1 protein of influenza A virus has the unique property of binding to three apparently different RNAs: poly A; a stem-bulge in U6 small nuclear RNA; and double-stranded RNA. One of our major goals is to determine how the NS1 protein recognizes and binds to its several RNA targets. As the first step for conducting structural studies, we have succeeded in identifying a fragment of the NS1 protein that possesses all the RNA-binding activities of the full-length protein. The RNA-binding fragment consists of the 73 amino-terminal amino acids of the protein. We have developed procedures for obtaining large amounts of the polypeptide in pure form. This has enabled us to establish the RNA-binding properties of this polypeptide and to demonstrate that it retains the ability to dimerize exhibited by the full-length protein. In addition, far-UV CD spectroscopy indicates that this RNA-binding polypeptide is largely (approximately 80%) helical, suggesting that the mode of dimerization of the NS1 protein and of its interaction with RNA is mediated, at least in part, by helices.

Amino Acid Sequence↗

Quantitative detection of amplification of proto-oncogenes in breast cancer.

In the present study, dot-blot hybridization, serial dilution analysis and densitometric scanning were used to detect amplification of proto-oncogenes including c-erbB2, c-myc, int-2 and c-Ha-ras in 101 paraffin-embedded breast cancers. Expression of c-erbB2 was also examined by immunohistochemistry. Amplification of c-erbB2, c-myc and int-2 genes was found in 34.7%, 17.8% and 11.9% of breast cancers respectively. However amplification of c-Ha-ras was not detected in all cases. In 11.9% of cases co-amplification of two or more oncogenes was observed. Positive immunostaining of c-erbB2 was seen in 23.8% of the cases and it was significantly associated, but not always corresponding to the amplification of the gene. There was no difference between primary and metastatic breast cancer in the alterations of proto-oncogenes examined in this study, which suggested that the amplification and overexpression of these proto-oncogenes occurred prior to and maintained in the process of metastasis of breast cancer. Statistical analysis showed that high-scale of immunopositive staining of c-erbB2 and high-fold co-amplification of proto-oncogenes were significantly correlated with large size of the tumour and the number of involved lymph nodes. Our results indicate that the alterations of multiple oncogenes are involved in the development of breast cancer and some of them may have prognostic importance for breast cancer patients.

Breast Neoplasms↗

[Multiple gene alterations involved in the processor of human gastric carcinogenesis].

The investigation of molecular evidence of gastric carcinoma will be contributable to the prevention, gene diagnosis and therapy of human gastric neoplasms. To determine the specific genetic change in human gastric cancer (HGC) and precancerous lesions, we analysized FISH, PCR/SSCP, IHC and DNA sequencing by using multiple probes to detect the gene abnormalities (mutation, deletion, amplification or overexpression of genes) of 67 fresh tumors, 63 endoscopic biopsies including 30 dysplasia (DYS) and 33 intestinal metaplasia (IM, and 4 tumor cell lines from HGC patients. Multiple genetic abnormalities including hypomethylation of H-ras gene, amplification and overexpression of met and erbB2, deletion of APC, mts1/p16, p53 and nm23 gene and point mutation of p53 gene were noted in HGC and precancerous lesion of human gastric mucosa. Among these changes, p53 gene was the highest frequence genetic alteration in 39/67 (54-58%) of gastric carcinoma. These results indicate that overexpression of met and H-ras occurs at early stage in progression of neoplasia, amplification of met, erbB2 and akt2 gene occurs at progressing stage of tumorigenesis, deletion of p53, APC, mts1/p16 and nm23 occurs at advanced stage in the progression of cancer. The abnormalities should be associated with malignant phenotypes: poor differentiation, vascular invasion, lymph nodes metastasis, and low survival time. We detected p53 gene mutation in both cancer and precancerous lesions of IM and DYS. These results suggest that p53 may be a susceptible gene and alteration of p53 gene plays an important role in the development of HGC.

Gastric Mucosa↗

[Expression of ras and erbB2 in benign and malignant lesions of the stomach].

The expression of P185erbB2 and P21ras was examined immunohistochemically in normal mucosa, intestinal metaplasia, dysplasia, intestinal type and diffuse type carcinoma of the stomach. The positive rates of P185 and P21 in the intestinal type carcinoma were significantly higher than those of the diffuse type. The results suggest that the two types of gastric carcinoma differ not only in histo-morphology but also in molecular mechanism. P21 immunopositivity is unlikely a specific marker of malignancy in gastric mucosa because of no significant difference of immunoreactivity among intestinal metaplasia, dysplasia, and carcinoma of the stomach. The positive staining of cell membrane for P185 was observed specifically in intestinal type carcinoma, but was absent in all other lesions. So it appears to be a useful marker of malignant change in the gastric mucosa. Overexpression of erbB2 gene in gastric carcinoma was demonstrated both at the mRNA level by in situ hybridization and at the protein level by immunohistochemical staining.

Gastric Mucosa↗

[Fine stereo structure for natural organic molecules, a preliminary study. II. Melting point influenced by structure factors].

Crystal structures of two compounds from Tripterygium wilfordii Hook f. have been determined by X-ray diffraction method. Structure factors influencing melting point of solid state have been analysed. Crystal class (or space group), recrystallization solvent, force between molecules and fine changes of molecular structures will all cause melting point changes of crystal substance.

Crystallography, X-Ray↗

[Determination of diazepam concentration in maternal and fetal serum after intravenous administration during active phase of labor and its effects on neonates].

OBJECTIVE: To investigate the effects of diazepam on the neonates administered intravenously during the active phase in labour. METHODS: Sixty normal term parturients during the active phase of labour with the cervical dilatation to 3-5 cm were randomly divided into two groups, study group (n = 30) and control group (n = 30). In study group 10mg diazepam was administered intravenously. The concentrations of diazepam and demethyldiazepam in maternal and cord serum were measured by high performance liquid chromatography and neonatal arterial blood gas and Apgar scoring were determined immediately after birth. RESULTS: At delivery, the mean level of diazepam in umbilical cord serum was 947 +/- 314 micrograms/L, markedly higher than that of maternal serum which was 488 +/- 300 micrograms/L, while the mean levels of demethyldiazepam were not significantly different in maternal and fetal serum. There was no marked difference between the two groups in fetal arterial blood gas and acidbase status. However, the rates of respiratory depression and muscle tone inhibition in the neonates of study groups (63.3% and 26.7% respectively) were significantly higher than those in the control group (30% and 3.3% respectively) (P < 0.05, P < 0.01). CONCLUSIONS: Use of diazepam in pregnant women during active phase of labour may cause depression of neonatal respiration.

Adult↗

Induction of osteogenesis by bovine platelet transforming growth factor-beta (TGF-beta) in adult mouse femur.

TGF-beta has been shown to be one of the most important regulators in chondrogenesis and osteogenesis. Daily subperiosteal injection of TGF-beta, which was extracted and purified from bovine platelets, into adult mouse femur resulted in proliferation and differentiation of the mesenchymal cells, chondrogenesis, and endochondral osteogenesis. After cessation of the injection, the endochondral ossification occurred widely, resulting in replacement of the cartilage with new bone. These phenomena demonstrate that exogenous TGF-beta stimulates mesenchymal proliferation and differentiation that occur in early fracture healing and suggest the possibility of clinical application of TGF-beta for fracture repair and bone transplantation.

Animals↗

[Detection of T-antigen in colorectal adenocarcinoma and polyps].

Galactose oxidase method was employed to detect the beta-D-Gal (1-->3) -D-Gal NAc residue of T-antigen present in the large intestinal mucus of 156 subjects. The positive rates of the test were 84.4%, 29.1%, and 7.2% in the mucus samples obtained from 32 patients with colorectal adenocarcinomas, 55 with polyps and 69 controls respectively. Chi-square test demonstrated that there were significant differences between the group of carcinoma and control (P < 0.001) as well as between also polyp and control (P < 0.01). The test had a high sensitivity (84.4%) and specificity (92.8%) in the diagnosis of colorectal cancer and may be used as a practical mass screening test for colorectal neoplasms.

Adenocarcinoma↗

[Anti-metastasis gene nm23 expression in buccal cancer studied by immunohistochemistry stain].

The nm23 gene has been proposed as a candidate metastasis-suppressor gene. In this study we used immunohistochemistry stain for polyclone antibody nm23 in 62 cases of buccal carcinoma. The results showed that both the epithelium of mucosa and the duct epithelium of minor salivary gland nearby the tumor were strong positive. The stains on tumor cells were various. 31.0% (9/29) of the cases with lymph-node metastasis were positive while 57.6% (19/33) of those with no lymph-node metastasis positive (P = 0.044). Histologically, 59.4% (19/32) of the cases were positive in Grade I, while 37.5% (6/16) positive in Grade II and 21.4% (3/14) in Grade III (P = 0.048). The positive rate increased with the patients survival time from less than 3 years to 3-5 years and more than 5 years correspondingly, but there was no statistical significance (P = 0.126). The results suggested that the expression of nm23 might be one of the factors influencing the lymph-node metastasis and prognosis of buccal cancer.

Carcinoma, Squamous Cell↗

Expression of p53 gene in oral squamous cell carcinoma and its relation with clinical and pathological parameters and prognosis of patients.

One hundred and eleven cases of oral squamous cell carcinoma (OSCC) were examined for overexpression of p53 protein by using immunohistochemical technique. Association between p53 protein overexpression and clinical and pathological parameters as well as prognosis of patients were also analyzed. p53 protein overexpression was commonly observed (69.4%) in OSCC and may be used as a marker of carcinogenesis of OSCC. The level of p53 protein overexpression is correlated with the lower three and five-year survival rate of OSCC. The presence or absence of p53 overexpression was not correlated with sex, age, site of tumor, size of tumor, degree of differentiation, node status, and clinical stage in OSCC. Single factor COX proportional hazards regression model analysis indicated that there was no significant association between p53 overexpression and prognosis of OSCC. Multivariable COX model analysis failed to establish effective life function or risk rate function. These showed that all the parameters analyzed in this study as well as p53 overexpression were not significant and effective risk factors of prognosis for patients with OSCC.

Carcinoma, Squamous Cell↗

[Effect of streptomycin placing in the fenestra of semicircular canals on the function and morphology of the normal and hydropic ears in guinea pigs].

The effect of streptomycin placed in the fenestra of lateral semicircular canal (LSC) on the function and morphology of the normal and artificial hydropic inner ears in guinea pigs was studied in order to explore the method and possibility of treating Meniere's disease by using aminoglycosides. After placing the drug in the fenestra of LSC, no change in AP threshold of ECochG in normal ears but an increase of that in hydropic ears were found caloric induced nystagmus in both groups were disappeared. Under light microscope, severe damage of vestibular epithelium of three canal cristae and utricular macula was noted, while no insult of cochlear hair cells was found in normal ears. More severe damage of vestibular epithelium with part of them degenerated and atrophied and lesions of cochlear hair cells in basal turns and part of second turns occurred in hydropic ears. These demonstrated that the ototoxicity of streptomycin was higher in hydropic ears than in normal ears. In order to destroy vestibular function and preserve cochlear function, further study for adequate dosage of streptomycin and correct route of administration is needed.

Animals↗

Antibody-induced epidermal growth factor receptor dimerization mediates inhibition of autocrine proliferation of A431 squamous carcinoma cells.

We previously reported that anti-epidermal growth factor (EGF) receptor monoclonal antibody (mAb) 225 can block receptor activation and inhibit proliferation of tumor cells bearing EGF receptors. To further explore the mechanism of mAb-mediated growth inhibition, we compared the capacities of bivalent 225 mAb and 225 F(ab')2, and monovalent 225 Fab' fragment to block ligand binding to EGF receptors, inhibit activation of receptor tyrosine kinase by exogenous and endogenous ligand, produce receptor dimerization, down-regulate receptors, and inhibit proliferation of cultured A431 squamous carcinoma cells. Unlike 225 mAb and 225 F(ab')2, 225 Fab' fragment was a poor inhibitor of A431 cell proliferation. The weak antiproliferative capacity of 225 Fab' was not due to depletion of active fragment from cultures. When cells were exposed to exogenous EGF, monovalent 225 Fab' remaining in conditioned culture medium could act as well as the bivalent forms of mAb to block binding and tyrosine kinase activation by exogenous EGF. However, unlike the bivalent forms, 225 Fab' fragment was unable to induce receptor dimerization and down-regulation, and it lacked the capacity to block autocrine activation of EGF receptors by endogenous ligand. These deficiencies were corrected by addition of rabbit anti-mouse IgG antibody, which also enabled 225 Fab' fragment to inhibit cell proliferation. We conclude that in A431 cells, inhibition of autocrine-stimulated proliferation by anti-EGF receptor mAbs requires antibody bivalency, which provides the capacity to produce EGF receptor dimerization accompanied by receptor down-regulation. These properties may explain the greater efficacy of bivalent mAb and F(ab')2, compared with monovalent Fab' fragment, in inhibiting proliferation of a variety of malignant and nonmalignant cultured cell lines.

Antibodies, Monoclonal↗

Effects of denervation upon receptor cell survival and basal cell proliferation in tuberous electroreceptor organs of a weakly electric fish.

Weakly electric fish generate electric fields for the purposes of electrolocation and communication. These fields are detected by specialized receptor organs: the tuberous organs. In the present study we investigated the effects of denervation upon receptor cell survival and progenitor (basal) cell proliferation rate. The left, infraorbital, anterior lateral line nerve of brown ghosts (Apteronotus leptorhynchus) was sectioned, and the proximal stump was dipped in ricin to prevent regrowth. In groups of four, the animals were given two daily injections of the cell proliferation marker bromodeoxyuridine (BrdU) for 2 days at 1, 2, 3, or 4 weeks following denervation. At the completion of the BrdU injection schedule, a piece of cheek skin, rostroventral to the eye, was removed from the left (denervated) and the right (intact) sides and processed for light microscopy or immunocytochemistry. Our results show: (1) there is progressive receptor cell death and tuberous organ degeneration following denervation; (2) basal cell proliferation increases steadily with time after denervation and tuberous organ degeneration; and (3) despite denervation, some proliferating basal cells differentiate into receptor cells, but these new receptor cells eventually die. These results suggest that innervation is essential for tuberous electroreceptor cell survival and that the rate at which basal cells proliferate is regulated by receptor cell health, locally released factors, or both.

Animals↗