Eun-Ji Choi

Trends in Participation Rates for the National Cancer Screening Program in Korea, 2002-2012

Purpose The National Cancer Screening Program (NCSP) in Korea supports cancer screening for stomach, liver, colorectal, breast, and cervical cancer. This study was conducted to assess trends in participation rates among Korean men and women invited to undergo screening via the NCSP as part of an effort to guide future implementation of the program in Korea. Materials and Methods Data from the NCSP for 2002 to 2012 were used to calculate annual participation rates with 95% confidence intervals (CI) by sex, insurance status, and age group for stomach, liver, colorectal, breast, and cervical cancer screening. Results In 2012, participation rates for stomach, liver, colorectal, breast, and cervical cancer screening were 47.3%, 25.0%, 39.5%, 51.9%, and 40.9%, respectively. The participation rates increased annually by 4.3% (95% CI, 4.0 to 4.6) for stomach cancer, 3.3% (95% CI, 2.5 to 4.1) for liver cancer, 4.1% (95% CI, 3.2 to 5.0) for colorectal cancer, 4.6% (95% CI, 4.1 to 5.0) for breast cancer, and 0.9% (95% CI, –0.7 to 2.5) for cervical cancer from 2002 to 2012. Conclusion Participant rates for the NCSP for the five above-mentioned cancers increased annually from 2002 to 2012.

Mouse adaptation of influenza B virus increases replication in the upper respiratory tract and results in droplet transmissibility in ferrets

To investigate the molecular changes that allow influenza B viruses to adapt to new mammalian hosts, influenza B/Florida/04/2006 was serially passaged in BALB/c mice until highly virulent. The viral factors underlying this transition were then investigated in mice and ferrets. Five viruses, including the wild-type virus (P0), three intermediate viruses (P5, P9, and P12), and a lethal mouse-adapted virus (P17 (MA)), harbored one to five amino acid substitutions in the hemagglutinin, M, NP, and PA segments suggesting that these mutations enhance virulence. The P17 (MA) virus replicated significantly more efficiently than the P0 virus both in vitro and in vivo (Pu2009<u20090.0001), and was highly virulent (MLD50: 105.25TCID50) while the P0, P5, and P9 viruses did not kill any infected mice (MLD50u2009>u2009106.0TCID50). Furthermore, the P17 (MA) virus grew to greater titers in the ferret upper respiratory tract compared with the P0 and intermediate viruses, and only the P17 (MA) virus was transmissible between ferrets via both direct and aerosol contact. To our knowledge, this is the first study to demonstrate ferret-to-ferret transmission of influenza B virus and to delineate factors that may affect its transmission.

Suppressor of Cytokine Signaling 2 Negatively Regulates NK Cell Differentiation by Inhibiting JAK2 Activity

Suppressor of cytokine signaling (SOCS) proteins are negative regulators of cytokine responses. Although recent reports have shown regulatory roles for SOCS proteins in innate and adaptive immunity, their roles in natural killer (NK) cell development are largely unknown. Here, we show that SOCS2 is involved in NK cell development. SOCS2−/− mice showed a high frequency of NK cells in the bone marrow and spleen. Knockdown of SOCS2 was associated with enhanced differentiation of NK cells in vitro, and the transplantation of hematopoietic stem cells (HSCs) into congenic mice resulted in enhanced differentiation in SOCS2−/− HSCs. We found that SOCS2 could inhibit Janus kinase 2 (JAK2) activity and JAK2-STAT5 signaling pathways via direct interaction with JAK2. Furthermore, SOCS2−/− mice showed a reduction in lung metastases and an increase in survival following melanoma challenge. Overall, our findings suggest that SOCS2 negatively regulates the development of NK cells by inhibiting JAK2 activity via direct interaction.

Responses to Overdiagnosis in Thyroid Cancer Screening among Korean Women.

Purpose Communicating the harms and benefits of thyroid screening is necessary to help individuals decide on whether or not to undergo thyroid cancer screening. This study was conducted to assess changes in thyroid cancer screening intention in response to receiving information about overdiagnosis and to determine factors with the greatest influence thereon. Materials and Methods Data were acquired from subjects included in the 2013 Korean National Cancer Screening Survey (KNCSS), a nationwide, population-based, cross-sectional survey. Of the 4,100 respondents in the 2013 KNCSS, women were randomly subsampled and an additional face-to-face interview was conducted. Finally, a total of 586 female subjects were included in this study. Intention to undergo thyroid cancer screening was assessed before and after receiving information on overdiagnosis. Results Prior awareness of overdiagnosis in thyroid cancer screening was 27.8%. The majority of subjects intended to undergo thyroid cancer screening before and after receiving information on overdiagnosis (87% and 74%, respectively). Only a small number of subjects changed their intention to undergo thyroid cancer screening from positive to negative after receiving information on overdiagnosis. Women of higher education level and Medical Aid Program recipients reported being significantly more likely to change their intention to undergo thyroid cancer screening afterreceiving information on overdiagnosis,whilewomen with stronger beliefs on the efficacy of cancer screening were less likely to change their intention. Conclusion Women in Korea appeared to be less concerned about overdiagnosis when deciding whether or not to undergo thyroid cancer screening.

Donor-Derived Natural Killer Cell Infusion after Human Leukocyte Antigen–Haploidentical Hematopoietic Cell Transplantation in Patients with Refractory Acute Leukemia

The optimum method of donor natural killer cell infusion (DNKI) after allogeneic hematopoietic cell transplantation (HCT) remains unclear. Fifty-one patients (age range, 19 years to 67 years) with refractory acute leukemia underwent HLA-haploidentical HCT and underwent DNKI on days 6, 9, 13, and 20 of HCT. Median DNKI doses were .5, .5, 1.0, and 2.0u2009×u2009108/kg cells, respectively. During DNKI, 33 of the 45 evaluated patients (73%) developed fever (>38.3°C) along with weight gain (median, 13%; range, 2% to 31%) and/or hyperbilirubinemia (median, 6.2u2009mg/dL; range, 1.0 mg/dL to 35.1u2009mg/dL); the toxicity was reversible in 90% of patients. After transplantation, we observed cumulative incidences of neutrophil engraftment (≥500/µL), grade 2 to 4 acute graft-versus-host disease (GVHD), chronic GVHD, and nonrelapse mortality of 84%, 28%, 30%, and 16%, respectively. The leukemia complete remission rate was 57% at 1 month after HCT and 3-year cumulative incidence of leukemia progression was 75%. When analyzed together with our historical cohort of 40 patients with refractory acute leukemia who underwent haploidentical HCT and DNKI on days 14 and 21 only, higher expression of NKp30 (>90%) on donor NK cells was an independent predictor of higher complete remission (hazard ratio, 5.59) and less leukemia progression (hazard ratio, .57). Additional DNKI on days 6 and 9 was not associated with less leukemia progression (75% versus 55%).

Macrophage migration inhibitory factor interacts with thioredoxin-interacting protein and induces NF-κB activity

The nuclear factor kappa B (NF-κB) pathway is pivotal in controlling survival and apoptosis of cancer cells. Macrophage migration inhibitory factor (MIF), a cytokine that regulates the immune response and tumorigenesis under inflammatory conditions, is upregulated in various tumors. However, the intracellular functions of MIF are unclear. In this study, we found that MIF directly interacted with thioredoxin-interacting protein (TXNIP), a tumor suppressor and known inhibitor of NF-κB activity, and MIF significantly induced NF-κB activation. MIF competed with TXNIP for NF-κB activation, and the intracellular MIF induced NF-κB target genes, including c-IAP2, Bcl-xL, ICAM-1, MMP2 and uPA, by inhibiting the interactions between TXNIP and HDACs or p65. Furthermore, we identified the interaction motifs between MIF and TXNIP via site-directed mutagenesis of their cysteine (Cys) residues. Cys57 and Cys81 of MIF and Cys36 and Cys120 of TXNIP were responsible for the interaction. MIF reversed the TXNIP-induced suppression of cell proliferation and migration. Overall, we suggest that MIF induces NF-κB activity by counter acting the inhibitory effect of TXNIP on the NF-κB pathway via direct interaction with TXNIP. These findings reveal a novel intracellular function of MIF in the progression of cancer.

Reduced-Intensity Conditioning with Busulfan, Fludarabine, and Antithymocyte Globulin for Hematopoietic Cell Transplantation from Unrelated or Haploidentical Family Donors in Patients with Acute Myeloid Leukemia in Remission

To investigate the role of antithymocyte globulin (ATG)-containing reduced-intensity conditioning (RIC) in hematopoietic cell transplantation (HCT) from unrelated (UD) or haploidentical family donors (HFD), we conducted a phase 2 trial of 237 patients (age range, 16 to 69 years) with acute myeloid leukemia (AML) in remission. Patients undergoing UD-HCT (nu2009=u200993) or HFD-HCT (nu2009=u200959) received RIC comprising busulfan, fludarabine, and ATG, 9u2009mg/kg, whereas those undergoing HCT from matched sibling donors (MSD, nu2009=u200985) received myeloablative busulfan and cyclophosphamide conditioning or aforementioned RIC with ATG, 4.5u2009mg/kg. For graft-versus-host disease (GVHD) prophylaxis, cyclosporine and methotrexate were administered. The median follow-up period was 44.7 months after HCT for 161 survivors. For UD-HCT versus HFD-HCT, there were no significant differences in leukemia recurrence, nonrelapse mortality, relapse-free survival, grades 2 to 4 acute GVHD, and moderate-to-severe chronic GVHD. Furthermore, when the outcomes of UD-HCT and HFD-HCT were combined and compared with those of MSD-HCT, there were no significant differences in leukemia recurrence (3-year cumulative incidence, 30% versus 29%), nonrelapse mortality (3-year cumulative incidence, 7% versus 8%), relapse-free survival (3-year estimate, 63% versus 63%), and grades 2 to 4 acute GVHD (120-day cumulative incidence, 16% versus 13%). Moderate-to-severe chronic GVHD, however, occurred less frequently in UD/HFD-HCT (2-year cumulative incidence, 22% versus 40%; Pu2009=u2009.006). The addition of ATG to conditioning regimen was a significant predictor for less chronic GVHD (subdistribution hazard ratio, .59). In AML in remission, UD/HFD-HCT after ATG-containing RIC achieved leukemia control equivalent to that of MSD-HCT. Despite HLA disparity in UD/HFD-HCT, chronic GVHD occurred less frequently after ATG-containing RIC, suggesting a strong GVHD-modulating effect of ATG.

Cancer mortality-to-incidence ratio as an indicator of cancer management outcomes in Organization for Economic Cooperation and Development countries

OBJECTIVES Assessing long-term success and efficiency is an essential part of evaluating cancer control programs. The mortality-to-incidence ratio (MIR) can serve as an insightful indicator of cancer management outcomes for individual nations. By calculating MIRs for the top five cancers in Organization for Economic Cooperation and Development (OECD) countries, the current study attempted to characterize the outcomes of national cancer management policies according to the health system ranking of each country. METHODS The MIRs for the five most burdensome cancers globally (lung, colorectal, prostate, stomach, and breast) were calculated for all 34 OECD countries using 2012 GLOBOCAN incidence and mortality statistics. Health system rankings reported by the World Health Organization in 2000 were updated with relevant information when possible. A linear regression model was created, using MIRs as the dependent variable and health system rankings as the independent variable. RESULTS The linear relationships between MIRs and health system rankings for the five cancers were significant, with coefficients of determination ranging from 49 to 75% when outliers were excluded. A clear outlier, Korea reported lower-than-predicted MIRs for stomach and colorectal cancer, reflecting its strong national cancer control policies, especially cancer screening. CONCLUSIONS The MIR was found to be a practical measure for evaluating the long-term success of cancer surveillance and the efficacy of cancer control programs, especially cancer screening. Extending the use of MIRs to evaluate other cancers may also prove useful.

Comparison of anthracyclines used for induction chemotherapy in patients with FLT3 -ITD-mutated acute myeloid leukemia

This retrospective analysis compared anthracyclines (as part of an induction regimen) in 128 newly diagnosed FLT3-ITD-mutated AML patients. Induction regimens comprised high-dose daunorubicin (HD-DN; 90u202fmg/m2/du202f×u202f3d; nu202f=u202f44), standard-dose daunorubicin (SD-DN; 45u202fmg/m2/du202f×u202f3d; nu202f=u202f51), or idarubicin (IDA; 12u202fmg/m2/du202f×u202f3d; nu202f=u202f33) in combination with cytarabine (100-200u202fmg/m2/du202f×u202f7d). Fifty-three patients showing persistent leukemia on interim bone marrow examination received a second course of induction chemotherapy comprising 2u202fdays of daunorubicin (45u202fmg/m2/d) or IDA (8 or 12u202fmg/m2/d) in addition to 5u202fdays of cytarabine. Complete remission (CR) rates were 77.3%, 56.9%, and 69.7% for HD-DN, SD-DN, and IDA, respectively (Pu202f=u202f0.101; HD-DN vs. SD-DN, Pu202f=u202f0.036; HD-DN vs. IDA, Pu202f=u202f0.453; IDA vs. SD-DN, Pu202f=u202f0.237). The HD-DN showed higher overall survival (OS) and event-free survival (EFS) than SD-DN and IDA: the differences between HD-DN and SD-DN (Pu202f=u202f0.009 for OS and Pu202f=u202f0.010 for EFS) were statistically significant. Results of in vitro studies using FLT3-ITD-mutated cell lines supported these findings. In conclusion, HD-DN improved the CR rate, OS, and EFS of FLT3-ITD-mutated AML patients. HD-DN also tended to yield better outcomes than IDA, though the difference was not significant. The superiority of HD-DN over IDA should be confirmed in future studies.

Associations of perceived risk and cancer worry for colorectal cancer with screening behaviour

We investigated the associations of perceived risk and cancer worry with colorectal cancer screening by the faecal occult blood test, colonoscopy or both. This study was based on the 2013 Korean National Cancer Screening Survey, including 2154 randomly selected, cancer-free and over 50-year-old adults. Individuals with higher cancer worry were 1.53 times more likely to undergo colorectal cancer screening, influenced by emotional reaction; individuals with greater perceived risk were 1.61 times more, affected by subjective awareness. However, cancer worry was only associated with the faecal occult blood test. Better understanding of cancer worry and perceived risk on screening behaviours may help to increase colorectal cancer screening rates.