Biomedical subjects

Sheng Zhong

Publications and source records attributed to Sheng Zhong.

23 records · Page 2Linked to original sources

PubMed2003

Hepatitis B virus reactivation in breast cancer patients receiving cytotoxic chemotherapy: a prospective study.

Breast cancer is a rapidly increasing problem in many developing countries, and cytotoxic chemotherapy is now an integral part of its management. In several developing countries, the carriage of hepatitis B virus (HBV) in cancer patients may be as high as 12%, and such patients are at risk of developing fatal HBV reactivation during chemotherapy. HBV reactivation is well recognized in patients with hematological malignancies, but limited data are available on patients with other, more common, cancers, such as breast cancer. Recent data have suggested that increased viral replication, an indication of HBV reactivation, may precede clinical hepatitis. In the absence of serial HBV DNA monitoring, HBV reactivation during chemotherapy may have been underestimated. In this prospective study, breast cancer patients who were hepatitis B surface antigen (HBsAg) seropositive were followed up during chemotherapy. The main objectives were to determine the incidence of HBV reactivation in breast cancer patients undergoing conventional chemotherapy; to investigate whether "serial HBV DNA monitoring" improves the accuracy of diagnosing HBV reactivation when compared with previous schema that only measured HBV DNA at the time of clinical hepatitis ("conventional monitoring"); and to assess the clinical consequences as a result of developing the condition. The secondary objective was to identify risk factors associated with this condition. Over an 18-month period, 41 patients were studied. Ten developed HBV reactivation by conventional monitoring criteria, but with serial HBV DNA monitoring, seven additional patients were diagnosed when increased HBV DNA levels were detected before, but not concomitant with, clinical hepatitis. Thus, a total of 17 patients (41%) developed HBV reactivation. Premature termination of chemotherapy or delay in treatment schedules occurred in 71% of the patients who developed viral reactivation, as compared with 33% in those who did not develop the condition (P = 0.019). No risk factors associated with the development of HBV reactivation could be identified. Serial monitoring of HBV DNA, in addition to liver function, increases the sensitivity of diagnosing of HBV reactivation, and helps explain some cases that would otherwise be labeled as "cryptogenic hepatitis," for which concomitant HBV DNA measured at the time of hepatitis was undetectable. The present study highlights the importance of monitoring HBsAg-seropositive patients who are receiving chemotherapy for common solid tumors such as breast cancer.

Adult↗

PubMed2003

[Study on the mitochondrion DNA mutation in tumor tissues of gynecologic oncology patients].

OBJECTIVE: To investigate the mitochondrion DNA (mtDNA) mutation in tumor tissues of gynecologic oncology patients and their relationship to tumorigenesis and tumor development. METHODS: The samples of tumor tissue and their proximal normal tissue of 32 gynecological malignant tumor patients as well as 8 gynecological benign tumor patients were taken. The malignants were 5 squamous cervical carcinomas, 10 endometrial carcinomas and 17 epithelial ovarian cancers (EOC). The benign tumors were 4 ovarian epithelial tumors and 4 uterine myomas. Polymerase chain reaction-single strain conformation polymorphism (PCR-SSCP) and DNA sequencing were done to examine mtDNA mutation. RESULTS: The mtDNA mutation rate and polymorphism rate were 68.8% and 56.3% respectively in 32 cases of malignants. The mtDNA mutation rate and polymorphism rate were 2/8 and 4/8 respectively in 8 cases of benigns. The difference between malignants and benigns was significant (P < 0.05). The hot point of mtDNA mutation were located in Cytb gene region. The characteristic mtDNA mutation is multigene and multisites mutation. The mojarity (63.6%) of patients involved in 2 more gene mutation. CONCLUSIONS: There is high frequent mtDNA coding area mutation in gynecological malignant tumors, indicating that mtDNA coding region mutation is closely related to gynecological malignants development and progression. It may be an important extra nuclear molecular genetic alteration in mechanisms of tumorigenesis.

DNA, Mitochondrial↗

PubMed2002

Pathways involved in synchronization of sympathetic nerve discharge to lung inflation.

In urethane-anesthetized cats, we tested the hypothesis that sympathetic nerve discharge (SND) is synchronized to lung inflation, in part, over a vagal afferent pathway that bypasses the central respiratory oscillator. For this purpose, partial coherence analysis was used to mathematically remove the portion of the relationship between intratracheal pressure (ITP; index of lung inflation) and inferior cardiac SND that was common to that between ITP and phrenic nerve activity (PNA; index of central respiratory cycle). ITP-SND partial coherence (PNA-related component removed) at the frequency of breathing should be significantly different from zero if a bypass pathway exists. This was found to be the case in paralyzed, artificially ventilated cats when lung inflation and rhythmic PNA were coupled in various ratios (e.g. 1:1, 3:1) and in spontaneously breathing cats. As expected, surgical vagotomy eliminated ITP-SND coherence in artificially ventilated cats. These findings support the view that a portion of the relationship between ITP and SND is independent of the influences of pulmonary stretch receptors on central respiratory networks.

Afferent Pathways↗

PubMed2002

Frequent detection of the replicative form of TT virus DNA in peripheral blood mononuclear cells and bone marrow cells in cancer patients.

The TT virus (TTV), a member of a family of human viruses related to the circoviridae viruses, was associated initially with acute and chronic liver diseases. TTV consists of a single-stranded, circular DNA genome of 3.8 kilobases (kb) and at least three open reading frames (ORFs). The objective of the present study was to determine whether or not TTV replicated in peripheral blood mononuclear cells (PBMCs) and bone marrow cells (BMCs). DNA was extracted from the PBMCs or BMCs of 153 cancer patients and from the PBMCs of 50 healthy blood donors (the controls). By using a single round of polymerase chain reaction (PCR), TTV was detected in 98.6% (141 of 143) of the PBMCs and in 90% (9 of 10) of the BMCs from cancer patients. TTV DNA was detected in significantly fewer control subjects at 86% (43 of 50; P < 0.05). Strand-specific PCR (SSPCR) targeting the ORF2 of the common genotypes of TTV was developed specifically to detect TTV positive or negative strand DNA and to examine TTV replication. TTV positive strand DNA, which may be an intermediate of viral replication, was detected in 55.3% (78 of 141) of the TTV-infected PBMCs of the cancer patients and in 7% (3 of 43) of the controls (P < 0.001). The replicative form of TTV was also detectable in 55.6% (5 of 9) of the TTV-infected BMCs. The existence of double-strand (positive and negative strands) TTV DNA in PBMCs and BMCs of the cancer patients was also supported by the finding that TTV DNA extracted from these cells was resistant to S1 nuclease. Using in situ hybridization, TTV DNA was also demonstrated to be present in the nucleus of PBMCs. It is concluded that replicative intermediate forms of TTV DNA are present in both PBMCs and BMCs, indicating that blood cells may be a site of TTV replication.

Bone Marrow Cells↗

PubMed2002

Silencing of GSTP1 gene by CpG island DNA hypermethylation in HBV-associated hepatocellular carcinomas.

PURPOSE AND EXPERIMENTAL DESIGN: Glutathione S-transferases, enzymes that defend cells against damage mediated by oxidant and electrophilic carcinogens, may be critical determinants of cancer pathogenesis. In this report, we assess the role of epigenetic silencing of the GSTP1 gene, a gene encoding the pi-class glutathione S-transferase, in the pathogenesis of hepatitis B virus (HBV)-associated hepatocellular carcinomas (HCC). The cell lines Hep3B, HepG2, and a cohort of 43 HBV-associated HCC tissue specimens and corresponding nontumor tissues were subjected to analysis for GSTP1 epigenetic alteration and expression. GSTP1 "CpG" island DNA hypermethylation in the liver cell lines, and the tissue specimens were determined by methylation-specific PCR and correlated with expression of the gene using reverse-transcription PCR, immunoblotting, and immunohistochemistry. RESULTS: GSTP1 CpG island DNA hypermethylation was detected in 28 of 43 (65.1%) HCC tissues and 4 of 40 (10%) corresponding nontumor tissues. GSTP1 protein was absent in those cases showing hypermethylation of the gene. Similarly, DNA from Hep3B and HepG2 cell lines displayed complete GSTP1 hypermethylation in the CpG island, and they failed to express GSTP1 mRNA and the corresponding protein product. Treatment of the cell lines with the DNA methyltransferase inhibitor 5-aza-deoxycytidine reversed the hypermethylation, and restored GSTP1 mRNA and polypeptide expression. CONCLUSIONS: These data indicate that epigenetic silencing of GSTP1 gene expression by CpG island DNA hypermethylation is common in human HBV-associated HCC. In addition, somatic GSTP1 inactivation via CpG island hypermethylation may contribute to the pathogenesis of this malignancy.

Adult↗