(A) study on the reconsideration for the ability of the new drug development in Korean pharmaceutical industry.

국제보건학과/석사ope

급성골수성 백혈병세포에서 transforming growth factor-β(TGF-β)를 통한 vitamin D₃의 세포증식억제 효과에 관한 연구

학위논문(석사)--서울대학교 대학원 :의학과 내과학전공,1997.Maste

Prognostic significance of microvascular invasion in tumor stage for hepatocellular carcinoma

Background: The presence of microvascular invasion (McVI) in hepatocellular carcinoma (HCC) has been proposed as a cause of recurrence and poor survival, although this has not been officially emphasized in staging systems. Thus, we conducted a retrospective study to investigate the prognostic importance of McVI in tumor staging in patients with HCC who underwent hepatic resection. Methods: A retrospective analysis was performed of patients who underwent hepatic resection for HCC at our center from 1994 to 2012. Patients with HCC were classified into four groups based on the presence of McVI and extent of gross vascular invasion (VI). Results: The 5-year overall and recurrence-free survival rates of 676 patients were 63.3 and 42.6%, respectively. There was no difference in tumor recurrence or survival rate between patients with HCC and McVI without gross VI and those with gross VI confined to segmental/sectional branches. Multivariate analysis revealed that the extent of VI based on the presence of McVI and gross VI was independently associated with tumor recurrence and overall survival. Conclusions: McVI was revealed to be an important risk factor similar to gross VI confined to a segmental/sectional branch in patients with HCC who underwent hepatic resection. This finding should be considered when estimating the stage for prognosis

Treatment outcome and prognostic factors of Korean patients with chronic lymphocytic leukemia: a multicenter retrospective study

Background/Aims: Compared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL. Methods: We retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012. Results: Compared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (>= 100 x 103/mu L), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (>= 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS ( p < 0.001 and p = 0.010, respectively). Conclusions: Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL

Controlling Aging Restoration of Cellular Senescence

Senescence is defined as an irreversible cell-cycle arrest and is the main driving-force of aging and age-related diseases. Recently, the reversal of senescence has been suggested as a promising target for rejuvenating organism or alleviating age-related pathologies. Cell physiology is regulated by complex signal pathways in which various kinase are involved. We hypothesized that aged altered cell physiology could be restored by modulating kinase activity, and performed high-throughput screening (HTS) with kinase inhibitor library to find compounds that can reverse senescence. From the chemical screening for agents that dismantle the cell cycle arrest of senescent cells and ameliorate aged-related phenotypic changes such as elevated SA-b-gal activity and reactive oxygen species concentration, Ataxia telangiectasia mutated (ATM) inhibitor as well as rho-associated, coiled-coil-containing protein kinase (ROCK) inhibitors were identified as effective agents. Since the role of ATM or ROCK in senescence remains elusive, the identification of novel interacting partners with these kinases would provide clues toward revealing its function in senescence and furthermore deciphering mode of action in reverting senescence by the kinase inhibitors. A yeast two-hybrid screen and further analysis confirmed that a subunit of vascular ATPase complex and a protein belonging to Rho family of GTPase are a novel substrate for ATM and ROCK, respectively. Attenuation of the aged-related kinase activation by the screened inhibitors reduced phosphorylation of the substrate protein, which induced functional recovery of lysosomes or mitochondria where the substrate is located. Our data revealed a novel mechanism in which reversal of senescence is controlled by the recovered lysosomal-mitochondrial axis upon adjustment of kinase activity

The 2020 revision of the guidelines for the management of myeloproliferative neoplasms

In 2016, the World Health Organization revised the diagnostic criteria for myeloproliferative neoplasms (MPNs) based on the discovery of disease-driving genetic aberrations and extensive analysis of the clinical characteristics of patients with MPNs. Recent studies have suggested that additional somatic mutations have a clinical impact on the prognosis of patients harboring these genetic abnormalities. Treatment strategies have also advanced with the introduction of JAK inhibitors, one of which has been approved for the treatment of patients with myelofibrosis and those with hydroxyurea-resistant or intolerant polycythemia vera. Recently developed drugs aim to elicit hematologic responses, as well as symptomatic and molecular responses, and the response criteria were refined accordingly. Based on these changes, we have revised the guidelines and present the diagnosis, treatment, and risk stratification of MPNs encountered in Korea