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Biomedical subjects

C W Xu

Publications and source records attributed to C W Xu.

At least 19 recordsLinked to original sources

Familial aggregation of lung cancer in a high incidence area in China.

To investigate whether lung cancer clusters in families in a high incidence county of China, an analysis was conducted using data on domestic fuel history and tobacco use for family members of 740 deceased lung cancer probands and 740 controls (probands' spouses). Lung cancer prevalence was compared among first-degree relatives of probands and of controls, taking into account various factors using logistic regression and generalised estimating equations. First-degree relatives of probands, compared with those of controls, showed an excess risk of lung cancer (odds ratio (OR)=2.05, 95% confidence interval (CI): 1.68-2.53). Overall, female relatives of probands had a greater risk than did their male counterparts, and the risk was 2.90-fold for parents of probands as compared with parents of spouses. Female relatives of probands had 2.67-fold greater risk than female controls. Lung cancer risk was particularly marked among mothers (OR=3.78, 95% CI: 2.03-7.12). Having two or more affected relatives was associated with a 2.69-5.40-fold risk increase. The risk elevation was also found for other cancers overall. Results confirm previous findings of a genetic predisposition to lung cancer, and also imply that lung cancer may share a genetic background with other cancers.

Adult↗

EDAG regulates the proliferation and differentiation of hematopoietic cells and resists cell apoptosis through the activation of nuclear factor-kappa B.

Erythroid differentiation-associated gene (EDAG) is considered to be a human hematopoiesis-specific gene. Here, we reported that downregulation of EDAG protein in K562 cells resulted in inhibition of growth and colony formation, and enhancement of sensitivity to erythroid differentiation induced by hemin. Overexpression of EDAG in HL-60 cells significantly blocked the expression of the monocyte/macrophage differentiation marker CD11b after pentahydroxytiglia myristate acetate induction. Moreover, overexpression of EDAG in pro-B Ba/F3 cells prolonged survival and increased the expression of c-Myc, Bcl-2 and Bcl-xL in the absence of interleukin-3 (IL-3). Furthermore, we showed that EDAG enhanced the transcriptional activity of nuclear factor-kappa B (NF-kappa B), and high DNA-binding activity of NF-kappa B was sustained in Ba/F3 EDAG cells after IL-3 was withdrawn. Inhibition of NF-kappa B activity resulted in promoting Ba/F3 EDAG cells death. These results suggest that EDAG regulates the proliferation and differentiation of hematopoietic cells and resists cell apoptosis through the activation of NF-kappa B.

Apoptosis↗

Plastid-expressed 5-enolpyruvylshikimate-3-phosphate synthase genes provide high level glyphosate tolerance in tobacco.

Plastid transformation (transplastomic) technology has several potential advantages for biotechnological applications including the use of unmodified prokaryotic genes for engineering, potential high-level gene expression and gene containment due to maternal inheritance in most crop plants. However, the efficacy of a plastid-encoded trait may change depending on plastid number and tissue type. We report a feasibility study in tobacco plastids to achieve high-level herbicide resistance in both vegetative tissues and reproductive organs. We chose to test glyphosate resistance via over-expression in plastids of tolerant forms of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). Immunological, enzymatic and whole-plant assays were used to prove the efficacy of three different prokaryotic (Achromobacter, Agrobacterium and Bacillus) EPSPS genes. Using the Agrobacterium strain CP4 EPSPS as a model we identified translational control sequences that direct a 10,000-fold range of protein accumulation (to >10% total soluble protein in leaves). Plastid-expressed EPSPS could provide very high levels of glyphosate resistance, although levels of resistance in vegetative and reproductive tissues differed depending on EPSPS accumulation levels, and correlated to the plastid abundance in these tissues. Paradoxically, higher levels of plastid-expressed EPSPS protein accumulation were apparently required for efficacy than from a similar nuclear-encoded gene. Nevertheless, the demonstration of high-level glyphosate tolerance in vegetative and reproductive organs using transplastomic technology provides a necessary step for transfer of this technology to other crop species.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗

[Genetic analysis of gelatinization temperature in rice via microsatellite(SSR) markers].

Rice gelatinization temperature is an important character contributing to cooking quality. Here the inheritance of gelatinization temperature (GT), which was represented by alkali spreading value (ASV), was reported. Two parents, Balilla (japonica variety) and Nantehao (indica variety), which were significantly different on GT-ASV, were selected to construct a backcross population Balilla/Nantehao//Balilla containing 142 individuals. And ASV was investigated in the population, a continuous distribution with two obvious peaks was observed. It indicated that GT-ASV was controlled by one major gene, also modified by some minor genes. In order to map the major and minor genes and estimate the effects of genes. A total of 119 SSR markers were employed to construct a linkage map; further a genome-wide detection was carried out by interval mapping method. The results showed that 6 QTLs were detected, of which, qASV6-1 located on chromosome 6 was a major gene with 87.6% variance explained, and alleles from parent Nantehao could decrease the value. It shoud be the same locus as the alkali degeneration gene (alk). The other QTLs (qASV2, qASV3, qASV6-2, qASV9, and qASV11) all belong to minor genes, which were located on chromosome 2,3,6,9 and 11, respectively. In two parents, they carried the positive and negative alleles simultaneously. These results will be helpful for rice quality breeding and improvement.

Chromosome Mapping↗

[Quantitative analysis for inheritance of quality characters in indica hybrid rice].

Nine quality characters of 3 sterile lines, 10 restorers and their 30 indica hybrid rice by NC II genetic design were studied. The results showed as follows: (1) No genetic segregation occurred in F2 grains in grain length, grain width, grain weight, brown rice% and head rice%, which indicated these traits are completely controlled by maternal plant genotypes. (2) Significant genetic segregation occurred in F2 grains in chalkiness score, amylose content, gelatinization temperature and gel consistency, which indicated the genetic expression of these traits is mainly controlled by endosperm genotypes. (3) The quality characters have relatively high heritabilities except brown rice % and chalkiness score. The genetic variation of quality characters was mainly caused by additive effect except grain weight.

Hybridization, Genetic↗

LCK-phosphorylated human killer cell-inhibitory receptors recruit and activate phosphatidylinositol 3-kinase.

HLA-specific killer cell inhibitory receptors (KIR) are thought to impede natural killer (NK) and T cell activation programs through recruitment of the SH2 domain-containing tyrosine phosphatases, SHP-1 and SHP-2, to their cytoplasmic tails (CYT). To identify other SH2 domain-containing proteins that bind KIR CYT, we used the recently described yeast two-bait interaction trap and a modified version of this system, both of which permit tyrosine phosphorylation of bait proteins. Using these systems, we show that KIR CYT, once phosphorylated by the src-family tyrosine kinase LCK, additionally bind the p85alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase. Furthermore, we show that in an NK cell line, NK3.3, cross-linking of KIR results in recruitment of p85alpha to KIR and activation of PI 3-kinase lipid kinase activity. One consequence of KIR coupling to PI 3-kinase is downstream activation of the antiapoptotic protein kinase AKT. Therefore, in addition to providing negative signals, KIR may also contribute positive signals for NK and T cell growth and/or survival.

Cell Line↗

Cells that register logical relationships among proteins.

Two-hybrid methods have augmented the classical genetic techniques biologists use to assign function to genes. Here, we describe construction of a two-bait interaction trap that uses yeast cells to register more complex protein relationships than those detected in existing two-hybrid systems. We show that such cells can identify bridge or connecting proteins and peptide aptamers that discriminate between closely related allelic variants. The protein relationships detected by these cells are analogous to classical genetic relationships, but lend themselves to systematic application to the products of entire genomes and combinatorial libraries. We show that, by performing logical operations on the phenotypic outputs of these complex cells and existing two-hybrid cells, we can make inferences about the topology and order of protein interactions. Finally, we show that cells that register such relationships can perform logical operations on protein inputs. Thus these cells will be useful for analysis of gene and allele function, and may also define a path for construction of biological computational devices.

Alleles↗

Nucleus-encoded histone H1-like proteins are associated with kinetoplast DNA in the trypanosomatid Crithidia fasciculata.

Kinetoplast DNA (kDNA), the mitochondrial DNA of trypanosomatids, consists of thousands of minicircles and 20 to 30 maxicircles catenated into a single large network and exists in the cell as a highly organized compact disc structure. To investigate the role of kinetoplast-associated proteins in organizing and condensing kDNA networks into this disc structure, we have cloned three genes encoding kinetoplast-associated proteins. The KAP2, KAP3, and KAP4 genes encode proteins p18, p17, and p16, respectively. These proteins are small basic proteins rich in lysine and alanine residues and contain 9-amino-acid cleavable presequences. Proteins p17 and p18 are closely related to each other, with 48% identical residues and carboxyl tails containing almost exclusively lysine, alanine, and serine or threonine residues. These proteins have been expressed as Met-His6-tagged recombinant proteins and purified by metal chelate chromatography. Each of the recombinant proteins is capable of compacting kDNA networks in vitro and was shown to bind preferentially to a specific fragment of minicircle DNA. Expression of each of these proteins in an Escherichia coli mutant lacking the HU protein rescued a defect in chromosome condensation and segregation in the mutant cells and restored a near-normal morphological appearance. Proteins p16, p17, and p18 have been localized within the cell by immunofluorescence methods and appear to be present throughout the kDNA. Electron-microscopic immunolocalization of p16 shows that p16 is present both within the kDNA disc and in the mitochondrial matrix at opposite edges of the kDNA disc. Our results suggest that nucleus-encoded H1-like proteins may be involved in the organization and segregation of kDNA networks in trypanosomatids.

Animals↗

[Effects of 8 antitumor drugs against the growth of human lung adenocarcinoma (LAX-83) transplanted under the kidney capsule of nude mice].

Nude mice, inoculated with LAX 83 in bilateral subrenal capsules, were used in experimental therapy with 8 antitumor drugs. Treatment was initiated 2 d after tumor inoculation. All the drugs were ip to the nude mice daily for 7 d. At the daily doses VCR 0.4, MMC 2, CCNU 16, cis-DDP 2, AdM 2.5, 5-Fu 30, CTX 40 and MTX 2-6 mg/kg, the inhibition of the tumor growth were 100, 95.8, 91.3, 79.2, 65.2, 60.7, 62.3 and 0%, respectively. The results indicated that the effects of the drugs on nude mice inoculated with LAX-83 in subrenal capsule not only exhibited a good correlation to those in sc, but also shortened the period of experiment from 22 to 11 d. Furthermore, when LAX-83 was inoculated into the subrenal capsule of Swiss +/+ mice, the tumor tissues degenerated and disintegrated 2 d after the inoculation and replaced by inflammatory granuloma tissues 6 d later.

Adenocarcinoma↗

Lung cancer and indoor air pollution in Xuan Wei, China.

In Xuan Wei County, Yunnan Province, lung cancer mortality is among China's highest and, especially in females, is more closely associated with indoor burning of "smoky" coal, as opposed to wood or "smokeless" coal, than with tobacco smoking. Indoor air samples were collected during the burning of all three fuels. In contrast to wood and smokeless coal emissions, smoky coal emission has high concentrations of submicron particles containing mutagenic organics, especially in aromatic and polar fractions. These studies suggested an etiologic link between domestic smoky coal burning and lung cancer in Xuan Wei.

China↗

Multiple primary lung cancers.

From November 1957 to June 1984 at Shanghai Chest Hospital, 30 cases of multiple primary lung cancers were confirmed, based on clinical characteristics, diagnostic process, histologic type, treatment, and prognosis. Out of 3,815 cases of resected primary lung cancer, the incidence of multiple primary lung cancers was 0.8 percent. There were ten synchronous cases and 20 metachronous cases. Seventeen cases were unilateral, and 13 cases were bilateral, of which only one case was synchronous, and the remaining 12 cases were postoperative resection of an opposite lesion. Among the ten synchronous cases, four cases of multiple primary lung cancers were definitely diagnosed before surgery by chest x-ray films or fiberoptic bronchoscopy. Among the 20 metachronous cases, 11 cases were definitely diagnosed before surgery as the second primary lesion by chest x-ray films taken during periodic follow-ups after the initial resection, while nine cases were proven by thoracotomy. All of the 15 cases definitely diagnosed before surgery as multiple primary lung cancers were according to our criteria. Histologically, adenocarcinoma was relatively scarce, at a rate of 13 percent (4/30); but epidermoid carcinoma was predominant, at a rate of 87 percent (26/30), of which 11 cases were accompanied by adenocarcinoma or large-cell undifferentiated carcinoma. The average postoperative survival in the ten synchronous cases was 29 months and in the 20 metachronous cases was 26.2 months, counting from the time of the second operation. The criteria of clinicopathologic findings, early diagnostic procedure, and surgery for multiple primary lung cancers were also discussed.

Adult↗

[Multiple primary lung cancer].

From November 1957 to June 1984, 30 patients with multiple primary lung cancer were diagnosed, basing on clinical features, diagnostic means, histologic type, treatment and prognosis. Out of 3,815 cases of resected primary lung cancer, the incidence of multiple primary cancer was 0.8%. There were 10 synchronous and 20 metachronous cases. There were 17 unilateral, only 1 simultaneous bilateral and 12 contralateral after resection of cancer in the opposite lung. Four of the 10 synchronous cases were definitely diagnosed preoperatively. Among the 20 metachronous cases, 9 were definitely diagnosed as a second primary lesion and the other 11 were proved by thoracotomy. Pathologically, 19 had identical types (15 squamous cell and 4 adenocarcinoma) but 11 had double types (9 squamous cell + adenocarcinoma, 2 squamous cell + anaplastic). The average survival of these 30 patients was 27.1 months, that in the synchronous group was 29 months and that in the metachronous group was 26.2 months. The 5 year survival rate of the synchronous cases was 35%, that of the metachronous cases was 42%. The clinicopathological criteria of multiple primary lung cancer, early diagnostic and operative procedure are also discussed.

Adenocarcinoma↗

[Chemotherapy combined with selective resection in small cell lung cancer--analysis of 239 patients].

From 1957 to 1976, 143 patients with small cell lung cancer (SCLC) were treated with surgical resection followed by chemotherapy. The 5 year survival rates were 38.7%, 8.7% and 3.5% in stages I, II and III. The prognostic factors were clinical stage and chemotherapy. 4 stage I and 1 stage II patients without chemotherapy have survived for more than 5 years. It seems to suggest that SCLC in stage I be indicated for surgery. 4 stage III have survived for more than 5 years, all of whom had received postoperative chemotherapy for more than 4 courses. From 1980 to 1982, 96 patients with SCLC were treated, 37 of whom by chemotherapy combined with surgery. 11/37 patients were alive for more than 2 years, 7 for more than 3 years and 4 for more than 4 years. In the preoperative chemotherapy followed by selective resection plus postoperative chemotherapy group (13 patients), the mean survival time was 22.7 months, but in the postoperative chemotherapy group (24 patients), it was 11.0 months. It indicates that full-dose chemotherapy before and after operation may be superior to the postoperative chemotherapy alone.

Antineoplastic Combined Chemotherapy Protocols↗

[CMC chemotherapy regimen combined with surgery of small cell lung cancer (SCLC)].

From Dec. 1982 to Oct. 1984, 35 patients with SCLC proved by pathology or cytology, were treated by cyclophosphamide + methotrexate + CCNU (CMC) regimen combined with surgery in our hospital. All the patients received chemotherapy for more than 2 courses and the overall response rate was 85.7%, complete remission (CR) rate was 14.3%. Toxic reactions were tolerable to the patients. Treatment result was better in SCLC with localized than extensive disease. Operation was done for 9 out of 21 patients with localized lesions which had responded to chemotherapy. Of them, 1 died of postoperative complication, 2 were lost in follow-up and the rest 6 were disease-free for 8-32 months with a median survival time of 19 months. The 1 year survival rate was 75%. The results indicate that in limited disease of SCLC, successful chemotherapy combined with surgery can prolong the survival time. For patients with an limited disease which has given a CR, surgical resection should be strived for.

Adult↗

Establishment and characterization of human malignant pleural mesothelioma cell line SMC-1.

A cell line (SMC-1) has been established from the resected tissue of a patient with malignant pleural mesothelioma which has been pathologically confirmed to be the mixed type. The cell line is characterized by the pleomorphy and multilayered growth of the cells with the population-doubling time of approximately 32 h, the highest mitotic index of 46--50% and the modal chromosome number of 69-70. Transplantation of the cells into the animals can produce tumors bearing histological resemblance to the original material. The cultured cells, xenografted tumor cells and the cells from the host specimen show similar histochemical expressions. These data meet the requirements of a human malignant pleural mesothelioma cell line. The establishment of this cell line will serve as a useful tool in clinical research of diagnosis and treatment of this devastating disease.

Adult↗