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C L Wu

Publications and source records attributed to C L Wu.

133 records · Page 8Linked to original sources

Immunization with TGF-beta antisense oligonucleotide-modified autologous tumor vaccine enhances the antitumor immunity of MBT-2 tumor-bearing mice through upregulation of MHC class I and Fas expressions.

The major purpose of this study was to define if the immunosuppressive effect of a transforming growth factor-beta (TGF-beta)-producing autologous tumor vaccine can be abrogated and rendered immunogenic by suppressing its TGF-beta secretion with antisense strategy. In this study, using a TGF-beta antisense gene modified MBT-2 tumor cell line [MBT-2/TGF-beta(-)#3] which we established by ourselves, we first demonstrated that the amounts of TGF-beta produced by irradiated (IR) and non-irradiated MBT-2/TGF-beta(-) #3 were both significantly decreased when detected after in vitro culture for 48 hours. The result of flow cytometry analysis reveals that decreased production of TGF-beta led to the increased expressions of MHC class I molecule and Fas on the surface of MBT-2 tumor cells. This finding may in part explain why the splenocytes obtained from day 17 tumor bearing mice (D17TBM) immunized with IRMBT-2/TGF-beta(-)#3 on day 26 expressed a higher in vitro cytotoxic activity against MBT-2 tumor cells and hence ensured a better survival of D17TBM when they were rechallenged with a two-fold higher amount of wild-type MBT-2 tumor cells, 48 hours after surgical removal of the primary tumor. Our result implies that decreasing the amount of TGF-beta secreted from the autologous tumor vaccine by antisense strategy may significantly improve its immunogenicity through up-regulation of both MHC class I and Fas expressions. Therefore, this could provide an alternative approach for future active immunotherapy.

Animals↗

Helicobacter pylori infection in recurrent abdominal pain in children--a prospective study.

A total of 40 children was recruited to assess the role of Helicobacter pylori infection in children with recurrent abdominal pain syndrome. Among 40 children, seven (17.5%) cases were confirmed to have H. pylori infection. All H. pylori-positive patients had active chronic gastritis histologic findings (p < 0.0001); however, the majority of the H. pylori-negative patients had minimal to mild gastritis histologic findings (p = 0.001). Grossly, chronic gastritis picture was present in all children infected with H. pylori and antral nodular gastropathy present in 43%. 71% of H. pylori-positive patients had elevated anti-H. pylori IgG titer; however, 15% in H. pylori-negative patients (p = 0.006). Serum H. pylori assay had a sensitivity of 71% and specificity of 85%; however, sensitivity and specificity of rapid urease test were 86% and 100% respectively. Antral nodularity is a specific, peculiar endoscopic finding of children infected with H. pylori (p = 0.004). Although the present study suggests that H. pylori-related chronic gastritis may play an etiological role in a subgroup of children with RAP syndrome, but the routine screening of H. pylori infection in children with RAP is not recommended, since no compelling data support the significant association between H. pylori infection and RAP syndrome.

Abdominal Pain↗

[Self-assessment and physicians' assessment of sexual maturation in adolescents' in Taipei].

The characteristics of puberty included the change of physiology, psychology and behavior, the inter-relationship within three was emphasized. The study of the sexual development is difficult to be achieved, only adolescents' self-assessment can overcome this obstacle. Four-hundred and twelve male and ninety female junior high school students grade three were enrolled from Taipei middle schools by probability proportionate to size method. The criteria of Tanner sexual staging were explained to the target population orally and pictorially. The orchidometer was demonstrated as well. Judging self-development were then asked for. School children were later examined by physician of same sex. The study included pubic hair, testis, penis and breast. The agreement between adolescents' rating and physicians' rating was high in penis and breast, low in male's testis and female's pubic hair. The correlation coefficient between two ranged from 0.25 to 0.52. Although the foreign reports revealed that adolescents can assess their own sexual development reliably. It is not so in our study. Perhaps more efforts in discussion on development performed immediately would help.

Adolescent↗

Oral anticoagulant prophylaxis and epidural catheter removal.

BACKGROUND AND OBJECTIVES: The use of regional anesthesia in patients receiving anticoagulants is controversial. The purpose of this review is to document the incidence of neurologic complications with insertion and removal of an epidural catheter in patients receiving oral anticoagulants and antiplatelet medication. METHODS: A retrospective review was made of the charts of 459 patients who underwent hip pinning or hip or knee replacement under regional anesthesia and received postoperative epidural analgesia and warfarin thromboembolism prophylaxis. The number of patients receiving preoperative antiplatelet therapy and warfarin, as well as baseline coagulation parameters, was documented. For patients who had postoperative epidural analgesia, the prothrombin time on the day of epidural catheter removal was obtained. Neurologic complications during the hospital stay were noted. RESULTS: Spinal anesthesia was administered to 47 patients and epidural anesthesia and postoperative analgesia to 412. Before surgery, antiplatelet therapy was given to 270 and warfarin to 180 patients, with some patients receiving both. The mean +/- SD preoperative prothrombin and partial thromboplastin times were 10.8 +/- 1.2 seconds (normal, 9.6-11.1 seconds) and 27.5 +/- 3.5 seconds (normal, 24.6-33.2 seconds), respectively. Blood on needle or catheter insertion was noted in 21 patients, all of whom were taking antiplatelet medication and/or warfarin. Epidural catheters remained postoperatively for a mean of 43.6 +/- 12.5 hours (range 5-118 hours). The mean prothrombin time on the day of epidural catheter removal was 14.1 +/- 3.2 seconds. Four postoperative peripheral neuropathies were detected. There was no clinical evidence of spinal hematoma in any patient. CONCLUSIONS: Epidural catheter placement and removal in patients taking oral anticoagulants appears to be safe. Careful monitoring of the patient for evidence of spinal hematoma after epidural catheter removal is recommended.

Administration, Oral↗

Modulation of the immunostimulating effect of autologous tumor vaccine by anti-TGF-beta antibody and interferon-alpha on murine MBT-2 bladder cancer.

UNLABELLED: Our aims were to: a) elucidate whether MBT-2 cells, lethally irradiated or nonirradiated, express TGF-beta 1 mRNA and secrete TGF-beta 1 protein, and b) to investigate whether the adverse effects from IRMBT-2-secreting TGF-beta 1 in the tumor vaccine can be abrogated by exogenous addition of monoclonal anti-TGF-beta 1 antibody and/or IFN-alpha. MATERIALS AND METHODS: using the Northern hybridization analysis and the two-antibody sandwich ELISA, we demonstrate that both irradiated IRMBT-2 and nonirradiated MBT-2 cells secrete TGF-beta 1. The effect of anti-TGF-beta and/or IFN-alpha were studied by an in vitro splenocyte proliferation assay and in vivo tumor rechallenge study on day 17-TBM. RESULTS: Both IRMBT-2 and splenocytes from day 17-TBM secrete TGF-beta 1 which can express suppression of the proliferation of the splenocytes from day 17-TBM. This suppression can be partially reversed by the simultaneous addition of both anti-TGF-beta and IFN-alpha, either alone being insufficient. The result of the in vivo tumor rechallenge study on day 17-TBM reveals that a lower tumor outgrowth incidence can be obtained in groups of mice treated with postoperative vaccination with anti-TGF-beta modified tumor vaccine with or without an additional administration of IFN-alpha. CONCLUSION: Apart from TGF-beta, MBT-2 cells, both irradiated and nonirradiated, may also secrete other suppressive factors that adversely downregulate the immune response of TBM which can not then be adequately reversed by IFN-alpha.

Animals↗

Antisense oligonucleotide specific for transforming growth factor-beta 1 inhibit both in vitro and in vivo growth of MBT-2 murine bladder cancer.

INTRODUCTION AND OBJECTIVES: TGF-beta is a potent immunosuppressive cytokine produced by many tumor cells. Secretion of TGF-beta by malignant cells may be a mechanism by which tumor cells escape destruction by tumor-specific T lymphocytes. In this study, we used a TGF-beta producing C3H/He-MBT-2 murine bladder tumor model to investigate the feasibility of antisense oligonucleotide (ODN) gene therapy strategy to block the production of TGF-beta from tumor cells and evaluate its influence on both in vitro tumor growth and in vivo tumor formation. MATERIALS AND METHODS: Using a plasmid, pRUFCD, we constructed a recombinant plasmid pRUFCD/TGF-beta 1(-) containing antisense TGF-beta ODN and then transfected in into MBT-2 cells by electroporation. Three transfectant clones were successfully obtained by their resistance to 5-fluorouracil and cytosine. RESULTS: The secretion of TGF-beta from the three obtained TGF-beta antisense-blocked MBT-2 cell clones, as assessed by ELISA, were all decreased. Moreover, they all exhibited smaller colony size in the in vitro anchorage-independent soft agar colony forming assay. Tumor growths in mice injected with these three clones were all inhibited compared with those injected with parental tumor cells. CONCLUSION: This study demonstrates that after reducing the secretion of TGF-beta 1 on tumor cells by TGF-beta 1 antisense, ODN can inhibit their in vitro growth and in vivo tumor formation suggesting that this approach can be a potentially useful strategy to abolish the adverse immunosuppression effect of TGF-beta 1 producing autologous tumor vaccine and therefore to enhance host antitumor immune response.

Animals↗

Modulating the antitumor immunity of MBT-2 murine bladder tumor bearing mice by postoperative administration of interferon-alpha.

This study was conducted mainly to investigate the effect of interferon-alpha (IFN-alpha) on the antitumor immunity of a tumor bearing host (TBH) when postoperatively administrated with or without lethally irradiated autologous tumor cells. Using the C3H/He-MBT-2 murine bladder tumor model, a status of postoperative residual tumor was mimicked by rechallenging tumor cells 24 hours after resecting the day-17 tumor. Using immunohistochemical analysis we demonstrated that after treating with lethally irradiated MBT-2 tumor cells (IRMBT-2) + IL-2 cells of CD4+, CD8+, CD44+ and CD11b+ phenotypes prominently infiltrate the subcutaneous local injection sites. In contrast, only scanty immune responding cells could be seen locally if treated with IRMBT-2 + IFN-alpha 2b, albeit in the presence of interleukin-2 (IL-2). However, the spleens of D17TBM treated with IRMBT-2 + IFN-alpha 2b contained the highest percentage of CD44+ memory T cells and cells of the CD11b+ phenotype; moreover, their natural killer (NK), lymphokine activated killer (LAK) and cytotoxic T lymphocytes (CTL) activities were significantly augmented. The results of in vivo tumor rechallenge revealed that administration of IFN-alpha, either alone or combined with IRMBT-2, could both effectively suppress the outgrowth of perioperative rechallenged tumor cells as well as prolong the survival of TBH. We conclude that despite the presence of autologous tumor vaccine, postoperative administration of IFN-alpha can further enhance the antitumor immunity of TBH and therefore can be an effective adjuvant therapy to improve the therapeutic results of surgery on a tumor bearing host.

Animals↗