Biomedical subjects

Beicheng Sun

Publications and source records attributed to Beicheng Sun.

9 recordsLinked to original sources

PubMed2006

Late onset of severe graft-versus-host disease following liver transplantation.

Graft versus host disease (GVHD) is an uncommon but lethal complication following liver transplantation that results from the engraftment of T lymphocytes associated with the liver graft. It usually occurs 2 to 6 weeks after the procedure. We herein report a case of late onset of severe GVHD 4 months after cadaveric liver transplantation for hepatocellular carcinoma in a 54-year-old woman, which was characterized by refractory diarrhea and abdominal pain. Moreover we discuss risk factors of GVHD including the recipient age and cytomegalovirus (CMV) infection.

Abdominal Pain↗

PubMed2006

Tumorigenic study on hepatocytes coexpressing SV40 with Ras.

A model of neoplastic transformation by the combination of SV40 large T antigen (LT), SV40 small T antigen (ST), oncogenic Ras, and human telomerase reverse trasncriptase subunit (hTERT) has become established and replicated in primary human fibroblasts, however, there is no report on human hepatocytes. Here we use cell transplantation model, and show that transplantation of human hepatocytes of HL-7702 and HL-7703 expressing Ha-RasV12 and SV40 LT into subrenal capsule of immunodeficient mice results in fully malignant tumors, in contrast to conventional subcutaneous injections where tumors fail to develop. In GM-847 cell study, we have found that hTERT is not required for tumorigenic growth in subrenal capsule transplantation, however, it is required in subcutaneous injection assay. These results demonstrate that Human hepatocytes can be transformed under kidney capsule by coexpressing SV40 LT and Ha-RasV12, neither hTERT nor protein phosphatase 2A (PP2A) inhibition are required for malignant transformation, a gene which increases cell survival in the subcutaneous injection model is not required for tumorigenic growth in subrenal capsule.

Animals↗

PubMed2005

Immortal ALT+ human cells do not require telomerase reverse transcriptase for malignant transformation.

Many human cancer cells lack telomerase activity but nevertheless maintain telomeres via a process termed "alternative lengthening of telomeres" (ALT). Despite being immortal and having a telomere maintenance mechanism, ALT+ human fibroblasts require telomerase reverse transcriptase (hTERT) for tumor formation in immunodeficient mice when tested by s.c. injection. Here we show that three ALT+ human SV40-immortalized fibroblast cell lines require only oncogenic RasV12G to be converted to a fully tumorigenic state. When cells were implanted beneath the kidney capsule of immunodeficient mice, they invaded the kidney and neighboring organs and metastasized to the lungs. Ras(V12G)-expressing ALT+ cells remained completely telomerase negative. Introduction of hTERT conferred strong telomerase activity but did not appreciably change the malignant properties of the cells. However, when cells were tested by s.c. injection, RasV12G-transduced ALT+ cells did not form tumors, and in this site, hTERT was required for tumorigenicity. These data show that when the s.c. injection method is used as an assay for tumorigenicity, hTERT may be artifactually scored as an oncogene; the subrenal capsule assay shows that ALT, as a telomere maintenance mechanism, is equivalent to hTERT in neoplastic transformation of human cells by oncogenes.

Animals↗

PubMed2005

The minimal set of genetic alterations required for conversion of primary human fibroblasts to cancer cells in the subrenal capsule assay.

Based on previous studies, a minimal set of genetic alterations that is required to convert normal human fibroblasts into cancer cells has been defined. Essential roles for telomere maintenance and alterations in phosphatase 2A activity were inferred from experiments in which tumorigenicity was tested by injecting cells under the skin of immunodeficient mice. However, in the present experiments, the combination of SV40 large T antigen and activated Ras, without hTERT or SV40 small t antigen, was sufficient to convert nine different primary human fibroblast cell strains to a fully malignant state. The malignant behavior of the cells was demonstrated by growth of the cells into invasive tumors when the cells were injected beneath the kidney capsule of immunodeficient mice. Lung metastases and circulating tumor cells were also detected. These tumors were not immortal; cells entered crisis, from which they could be rescued by expression of hTERT. However, the same cell populations were not tumorigenic when they were injected under the skin. In this site, tumorigenicity required the expression of hTERT and SV40 small t antigen as well as SV40 large T antigen and Ras. The cellular pathways targeted by SV40 large T antigen (p53 and pRb) and those targeted by activated Ras represent a minimal set of genetic alterations required for the conversion of normal human fibroblasts into cancer cells.

Animals↗

PubMed2004

Progressive loss of malignant behavior in telomerase-negative tumorigenic adrenocortical cells and restoration of tumorigenicity by human telomerase reverse transcriptase.

Replicative senescence/crisis is thought to act as a tumor suppressor mechanism. Although recent data indicate that normal human cells cannot be converted into cancer cells without telomerase, the original concept of senescence as a tumor suppressor mechanism is that senescence/crisis would act to limit the growth of telomerase-negative tumors. We show here that this concept is valid when oncogene-expressing human and bovine cells are introduced into immunodeficient mice using tissue reconstruction techniques, as opposed to conventional subcutaneous injection. Primary human and bovine adrenocortical cells were transduced with retroviruses encoding Ha-Ras(G12V) and SV40 large T antigen and transplanted in immunodeficient mice using tissue reconstruction techniques. Transduced cells were fully malignant (invasive and metastatic) in this model. They had negligible telomerase activity both before transplantation and when recovered from tumors. When serially transplanted, tumors showed progressively slower growth, decreased invasion and metastasis, shortened telomeres, and morphological features of crisis. Whereas telomerase was not essential for malignant behavior, expression of human telomerase reverse transcriptase enabled cells from serially transplanted tumors that had ceased growth to reacquire tumorigenicity. Moreover, telomerase-negative oncogene-expressing cells were tumorigenic only when transplanted using tissue reconstruction techniques; human telomerase reverse transcriptase was required for cells to form tumors when cells were injected subcutaneously. This work provides a new model to study crisis in an in vivo setting and its effects on malignancy; despite having invasive and metastatic properties, cells are eventually driven into crisis by proliferation in the absence of a telomere maintenance mechanism.

Adrenal Cortex↗

PubMed2004

Telomerase is not required for experimental tumorigenesis of human and bovine adrenocortical cells.

Telomerase has often been thought to be essential for tumorigenesis of human cells. Adrenocortical cancers, like other cancers, typically have telomerase activity. We reinvestigated the requirement for telomerase in the conversion of normal human and bovine adrenocortical cells to cancer cells. When primary adrenocortical cells were transduced with retroviruses encoding SV40 large T antigen and Ha-RasG12V and immediately transplanted into immunodeficient mice they produced invasive and metastatic tumors. Cells had negligible telomerase activity before transplantation and after recovery from tumors. However, these tumors were not immortal and cells entered crisis, limiting further growth of the tumor as well as invasion and metastasis. Infection of these tumor cells with a retrovirus encoding hTERT restored growth in culture and restored the malignant properties of the cells in immunodeficient animals. These experiments differ from previous studies in which telomerase was found to be essential for tumorigenicity: 1) we used tissue reconstruction techniques for introduction of cells into host animals and 2) we infected primary cells with retroviruses and immediately transplanted them without drug selection.

Adrenal Cortex↗

PubMed2003

Using cell transplantation to investigate genes involved in aging.

Cell transplantation provides a way to study genes that may be important in human tissue aging. Studies on gene action in human cells are usually restricted to cell culture investigations and clinical observations. Differences in human and rodent cellular biology, particularly with respect to telomere dynamics, show the need for new systems for investigating aging that use human cells or cells of other large, long-lived mammals, such as bovine cells. The system we describe uses human and bovine adrenocortical cells transplanted into scid (severe combined immunodeficiency) mice. They form a vascularized tissue structure that can replace the essential functions of the animals' own adrenal glands. The cells may be genetically modified before introduction into the animal. Using hTERT (telomerase reverse transcriptase) and oncoproteins, we show the potential for investigating gene action in genetically modified tissues created by cell transplantation.

Adrenal Cortex↗

PubMed2002

[Application of microsurgical technique to hepatic artery reconstruction in liver transplantation].

OBJECTIVE: To explore the value of the microsurgical technique in the reconstruction of hepatic artery. METHODS: From September 2000 to June 2001, we performed liver transplantation for 11 patients including living related liver transplantation (4) and 7 orthotopic liver transplantation (7). Arterial reconstruction was performed under an operating microscope. RESULTS: No patients developed hepatic arterial thrombosis and serious complication, nor death for multiple organ failure. CONCLUSION: Microsurgical technique in reconstruction of the hepatic artery can improve surgical outcome, not only in orthotopic liver transplantation but also in living related liver transplantation.

Adolescent↗

PubMed2002

[Multimodal approach to clinical liver transplantation].

OBJECTIVE: To sum up the clinical experience of liver transplantation. METHOD: A retrospective study was made in 11 patients receiving living donor liver transplantation (LDLT)/and 14 patients having orthotopic liver transplantation (OLT), including one time operation of reduced size liver retransplantation and one time operation of cadaveric liver retransplantation. RESULTS: The voluntary donors were a sister and 10 mothers of recipients. The location of graft included 3 patients of segment II, III, part of IV (not including intermediate hepatic veins), 6 patients of segment II, III, IV (including intermediate hepatic veins), and 2 patients of V, VI, VII, VIII (not including intermediate hepatic veins). The weight range of graft was 270 - 620 g. Twenty-four recipients achieved a long-term survival and retained normal liver function during the follow-up. Only 1 patient died from serious rejection on the 72nd day postoperatively. Ten patients with hepatitis B cirrhosis were treated with lamivudine and anti-HBVIg, and HBV-DNA in serum was negative during the follow-up for 4 approximately 21 months. Copperoxidase, ceruloplasmin and main indexes of liver function became normal in all patients with Wilson's Disease. Postoperative complications included abdominal hemorrhage (2 patients), acute respiratory distress syndrome (5), acute rejection (4), and acute renal function failure (2). CONCLUSIONS: The wise solution to improve the result of liver transplantation and optimize liver resources is the "multimodal approach", by which all kinds of techniques for liver transplantation including CLT, LDLT and RSLT should well developed.

Adolescent↗