Chang Woo Nam

Mitotic checkpoint gene MAD1 in hepatocellular carcinoma is associated with tumor recurrence after surgical resection

Underlying mechanism of mitotic checkpoint gene mitosis arrest deficiency 1 (MAD1) in human hepatocellular carcinoma (HCC) is rarely known.

Gemcitabine Therapy in Patients with Advanced Pancreatic Cancer

Background: Advanced, unresectable pancreatic cancer is an extremely aggressive disease. The 5-year survival rate for pancreatic cancer is only less than 5%. Current therapeutic options for patients with locally advanced or metastatic disease are limited. This analysis is a retrospective evaluation of the efficacy and toxicity of gemcitabine regimen as first-line chemotherapy in patients with advanced pancreatic cancer. Methods: Seventeen chemotherapy-naïve patients with advanced or recurred pancreatic cancer were consecutively treated. Gemcitabine was diluted in normal saline and administered intravenously over 1 hour. Gemcitabine 1,000 mg/m2 was administered once weekly for 3 out of every 4 weeks. Results: The median age of patients was 55 years (range 44–82 years). Based on RECIST criteria, there were 5 cases of stable disease (45%) and 6 cases of progressive disease (55%) among the 11 assessable patients. The median survival time was 189 days (range, 84 to 409 days), the 1 year survival rate was 18% in all 17 patients. Grade 3–4 toxic side effect was leucopenia only (29%) and was easily managed without infection. Conclusion: Gemcitabine is well tolerated, but has no objective response in advanced pancreatic cancer.

Fixed Dose Rate Infusion of Gemcitabine with Oral Doxifluridine and Leucovorin for Advanced Unresectable Pancreatic Cancer: A Phase II Study

The standard beneficial chemotherapy proven for patients with advanced pancreatic cancer is a regimen containing gemcitabine. In the pregemcitabine era, 5-fluorouracil (5-FU) was the standard agent. Oral 5-FU can be added to gemcitabine to improve the efficacy of chemotherapy and to provide better patient convenience. The possibility to improve efficacy of gemcitabine by fixed dose rate infusion (FDRI) was proposed in addition to combining it with 5-FU. We tried a new chemotherapy combining FDRI of gemcitabine with doxifluridine and leucovorin. Eligibility criteria were pathologically proven, chemotherapy-naïve, and metastatic or nonoperable advanced pancreatic cancer. Gemcitabine 1,000 mg/m2 was infused over 100 min (days 1, 8 and 15). Doxifluridine 200 mg/m2 t.i.d. and leucovorin 15 mg b.i.d. were given orally (days 1–21). Chemotherapy was repeated every 28 days until a patient had received 6 cycles or progression was found. Twenty-nine patients were enrolled from October 2002 to December 2004. A total of 78 cycles were given at a mean of 2.7 cycles per patient. Response could be evaluated in 26 patients. Responses were partial remission in 4/26 patients (15.4%), stable disease in 8/26 (30.8%) and progression in 14/26 (53.8%). All patients progressed except for 2 in partial remission and 2 in stable disease. Toxicities could be assessed in 23 patients. Maximal hematological toxicities greater than grade 2 were leucopenia in 3 patients (11.5%), neutropenia in 2 (7.7%), anemia in 2 (7.7%), thrombocytopenia in 1 (3.8%) and febrile neutropenia in 3 (11.5%). Maximal nonhematological grade 3 or 4 toxicities were asthenia in 1 patient (3.8%), anorexia in 1 (3.8%), vomiting in 1 (3.8%), diarrhea in 2 (7.7%), allergic reaction in 1 (3.8%), hand-foot syndrome in 1 (3.8%) and hyperbilirubinemia in 1 (3.8%). All 29 patients were dead on last follow-up. Median progression-free survival was 3.91 months in 26 evaluable patients and median overall survival was 5.59 months in all patients. Combination chemotherapy including FDRI of gemcitabine seems minimally active for patients with advanced, nonoperable pancreatic cancer. Further research to improve effectiveness of chemotherapy for advanced pancreatic cancer is mandatory.

Analysis op alloimmuno T cell activation in 4-IBB KO mice

BB, a member of the TNF receptor superfamily, functions mainly as a costimulatory molecule in T cells. Since signaling through 4-1BB provides T cells with costimulation independently of CD28, it has been postulated that 4-1BB plays an important role in allograft rejection. In this study, we demon- strated the critical role of 4-1BB in heart allograft rejection using 4-1BB-deficient mice. When 4-1BB- deficient C57BL/6 mice received MHC-mis- matched cardiac transplant of Balb/c origin, there was a markedly-delayed graft rejection as com- pared with the wild type. The delayed graft rejec- tion in the mutant mice correlated with less severe lymphocytic infiltration and vasculitis in the donor hearts. The cardiac grafts were harvested on days 1,3, 5, and 7, and the transcription level of various T cell cytokines and antigens were analyzed by RT- PCR. Furthermore, T cells of 4-1BB-deficient mice showed lower proliferation and cytokine produc- tion when challenged with allostimulatory den- dritic cells. We found that the mRNA levels of FasL and T cell activation cytokines such as IL-2, IFN-y, iNOS were decreased in 4-1BB-/- mice compared to wild type mice. Whereas, transcription of B7-2 antigen, CD28 related costimulatory molecule, was increased in 4-1BB/- mice. These findings have a clinical implication that the blockade of 4-BB sig- naling may prolong the survival of solid organ transplants.