Apurinic/apyrimidinic endonuclease 1 is associated with poor prognosis after curative resection followed by adjuvant chemotherapy in patients with stage III colon cancer

Purpose@#Apurinic/apyrimidinic endonuclease 1 (APE1) is a key enzyme involved in the base excision repair pathway. It also has redox activity and maintains various transcription factors in an active reduced state. APE1 may be associated with chemoresistance. In the present study, we first investigated the expression level of APE1 protein and its correlation with oncologic outcomes of oxaliplatin-based chemotherapy in patients with stage III colon cancer. Further, we investigated the effects of human APE1 siRNA on the sensitivity of oxaliplatin in SNU-C2A colon cancer cells. @*Methods@#Tissue specimens from tumor and normal colon of 33 patients with stage III colon cancer were obtained from 2006 to 2009. The patients received at least eight cycles of oxaliplatin-based chemotherapy. APE1 expression was analyzed by immunohistochemistry and Western blotting using a cultured SNU-C2A cell line. Cell viability and apoptosis were determined by Cell Counting Kit-8 and caspase-3 cleavage using Western blotting. @*Results@#All the colon cancer tissues showed APE1 staining in the nucleus, whereas all the normal colon tissues were negative for APE1 staining in the cytoplasm. The group with a higher expression of APE1 demonstrated poorer prognosis than the group with low expression (P=0.026 for overall survival and P=0.021 for disease-free survival). Treatment with oxaliplatin resulted in a dose-dependent increase in APE1 expression in SNU-C2A cells. APE1 siRNA significantly enhanced oxaliplatin-induced growth inhibition, and also increased oxaliplatin-induced apoptosis in SNU-C2A cells. @*Conclusion@#APE1 could be considered a prognostic factor in colon cancer patients treated with oxaliplatin-based chemotherapy.

HLA-A*24:02/B*51:01 haplotype and lamotrigine-induced cutaneous adverse drug reactions in Koreans

Antiepileptic drugs (AEDs) have been known to induce cutaneous adverse drug reaction (cADR), ranging from a mild maculopapular eruption (MPE) to potentially life-threatening cADRs such as Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Despite studies examining mechanisms associated with human leukocyte antigen (HLA), the association between lamotrigine (LTG)-induced cADR and HLA alleles still has room to investigate. We investigated HLA-A,-B, and -C alleles in LTG-induced cADR. The medical records of four patients with LTG-induced cADR were retrospectively reviewed. All patients were treated with LTG for epilepsy. All recovered from cADR after stopping LTG treatment and receiving intensive care. HLA-A, -B, and -C genotyping was performed in all four patients using a PCR-sequence-based typing (SBT) method. Two patients had SJS, and the other two had MPE due to LTG. The range of latency to cADR after the initial LTG dose was 19–42 days. Two patients experienced cross-reactivity with other aromatic or new AEDs. Expression of the HLA-A*24:02/B*51:01 haplotype was detected in three (75%) patients with LTG-induced cADR. The other patient carried homozygous HLA-B*58:01 alleles. The results suggest that Korean individuals with the HLA-A*24:02/B*51:01 haplotype may be susceptible to LTG-induced cADR. Further investigations are necessary to confirm these findings.

Brief introduction to current pharmacogenomics research tools

There is increasing interest in the application of personalized therapy to healthcare to increase the effectiveness of and reduce the adverse reactions to treatment. Pharmacogenomics is a core element in personalized therapy and pharmacogenomic research is a growing field. Understanding pharmacogenomic research tools enables better design, conduct, and analysis of pharmacogenomic studies, as well as interpretation of pharmacogenomic results. This review provides a general and brief introduction to pharmacogenomics research tools, including genotyping technology, web-based genome browsers, and software for haplotype analysis.

Genetic polymorphisms of CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 in Vietnamese-Koreans

The Vietnamese-Koreans, especially offspring between a Vietnamese mother and a Korean father constituted the highest proportion (64.2%) of total Kosian population according to a census in 2014. To evaluate genetic characteristics in the Vietnamese-Koreans, a total of 25 alleles from CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 were genotyped using SNaPshot method with DNA samples of 127 Vietnamese-Koreans. The previous reports on the CYPs of Korean and Vietnamese populations were also analyzed for the comparative studies for the frequencies of CYP alleles. The statistical significances in allele and genotype frequencies among the ethnics were analyzed by Chi-square or Fisher's exact probability test. Although most of variants analyzed in 5 CYPs did not reach the statistically significant difference between the Vietnamese-Koreans and Vietnamese, some alleles were only found in Vietnamese-Koreans. Compared with Korean population, frequencies of CYP2D6*1 and CYP2D6*10B were statistically different from Vietnamese-Koreans (p<0.05). This is the first report to describe the CYP genotype profiles of Vietnamese-Koreans, which may provide important insight for the genotype based prediction of CYP activities of this admixture of Korean and Vietnamese.

Clinical outcomes of hematopoietic stem cell transplantation from HLA-matched parental donor in childhood acute leukemia / 소아과

PURPOSE: In this study, we retrospectively analyzed the clinical outcomes of patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) grafted from HLA-matched parents. METHODS: Seven children with acute leukemia (4 acute lymphoblastic leukemia, 3 acute myeloid leukemia) in first complete remission received allogeneic HSCT from their respective parents at the St. Marys Hospital between April, 1999 and October, 2005. The median age of patients at transplantation was 5 years (range, 1-11 years; 2 male, 5 female) and the median age of donors was 35 years (range, 30-41 years; 5 male, 2 female). We investigated the clinical outcomes such as engraftment, acute and chronic graft-versus-host disease (GVHD), transplant-related morbidity and mortality, relapse and survival. RESULTS: Median time from transplantation to last follow-up was 69.5 months (range, 18.8-96.5 months). All patients were successfully engrafted, with a median time of 11 days (range, 10-16 days) and 26 days (range, 13-39 days) for neutrophil and platelet recovery, respectively. Grade II acute GVHD occurred in 3, and grade III acute GVHD in 1 of 7 recipients. Extensive chronic GVHD developed in 2, and limited chronic GVHD in 1 of 7 recipients. Death from transplant-related complications occurred in 1, and relapse occurred in 1 of 7 recipients. Estimated 5-year overall survival was 83+/-15%. CONCLUSION: The clinical outcomes of recipients who underwent HSCT from HLA-matched parents were comparable to those of patients who received HSCT grafted from HLA-matched sibling donors in childhood leukemia. HLA typing of parents, as well as siblings will increase the likelihood of finding an HLA-matched family donor for patients who need HSCT.

Transarterial Embolization of an Aortoesophageal Fistula Secondary to Placement of a Palliative Esophageal Stent: A Case Report

An aortoesophageal fistula is a rare condition caused by descending aortic diseases such as an aneurysm, foreign body ingestion, esophageal malignancy, and ulcers. An aortoesophageal fistula as a complication of esophageal stent placement is extremely rare and only one case has been reported previously worldwide, to the best of our knowledge. We report a case of an aortoesophageal fistula in a 64-year-old man who previously underwent palliative esophageal stent placement due to local tumor recurrence after a total gastrectomy of advanced gastric cancer in the cardia. The fistula was occluded by glue embolization.

Stroke Associated With Protein C and S deficiency in Neonate: Report of two Cases

Recently, cases of stroke with inherited disorders of blood coagulation have been reported in children. Deficiency of protein C or S predisposing to a hypercoagulable state has been associated with cerebrovascular disease. We describe here two cases of cerebral infarction in neonates presenting with respiratory distress and seizure respectively. One had decreased protein C and the other was found to have decreased protein C and S. One case had asphyxia as an additional risk factor for stroke. No specific therapy was administered in both cases. They are currently being observed in the outpatient clinic without specific events.

Effect of Potent Aromatase Inhibitor (Letrozole) on Bone Maturation and Predicted Adult Height in Boys with Early Puberty / 대한소아내분비학회지

PURPOSE: We evaluated the effect of potent aromatase inhibitor (Letrozole) on the rate of bone maturation and an increase in predicted adult height (PAH) in boys with early puberty. METHODS: Nine boys, aged 10.9-12.9 years, with early puberty were studied. The boys were treated with the aromatase inhibitor, letrozole, 2.5 mg/day for 1 year. The main outcome parameters were the change in bone age and predicted adult height. Also, serum LH, FSH, testosterone and estradiol concentrations were measured and sexual maturation before and after 12 months of treatment were evaluated. RESULTS: PAH significantly increased by 3.3 cm (P<0.05) and PAH standard deviation score significantly increased by 0.6 (P<0.05). Bone age before therapy advanced by 0.72+/-0.93 year, but bone age after therapy decreased by 0.07+/-0.90 year compared to chronological age (P<0.01). Whereas, sexual maturation of the subjects progressed normally. CONCLUSION: These results suggest that treatment with the potent aromatase inhibitor, letrozole, delays bone maturation and improves PAH in boys with early puberty.

Incidence and Clinical Characteristics of Diabetes Mellitus in Aplastic Anemia Patients Treated with Multiple Transfusions / 대한소아내분비학회지

PURPOSE: We investigated the epidemiological and clinical characteristics of diabetes mellitus developed in aplastic anemia patients who have had many blood transfusions. METHODS: We retrospectively reviewed medical records of 170 patients with aplastic anemia who were diagnosed before 15 years of age in Department of Pediatrics, The Catholic University of Korea from 1987 to 2001. We obtained their medical history, family history of diabetes mellitus, clinical onset of diabetes mellitus and the successive history, and coexistence of other disorders. RESULTS: Diabetes mellitus was diagnosed in 8 of 107 patients (7.5%) with severe aplastic anemia in childhood. The mean age of diagnosis of diabetes mellitus was 18.5+/-5.2 years, and the mean duration from the start of blood transfusion to the diagnosis of diabetes mellitus was 7.7+/-2.9 years. Duration of multiple blood transfusions was a major risk factor for the development of diabetes mellitus in severe aplastic anemia patients. There was a wide range of symptoms at clinical onset of diabetes mellitus from asymptomatic hyperglycemia to diabetic ketoacidosis. Incidence of other complications, such as hepatic impairment (88%) and cardiac dysfunction (75%), was high in patients who developed diabetes mellitus. CONCLUSION: Severe aplastic anemia patients treated with prolonged, multiple transfusions have a significant risk of developing insulin-deficient diabetes mellitus. These patients are at risk for other complications, such as hepatic, cardiac, or thyroid disorders. Early prevention of iron overload and screening for transfusion-related complications are very important in these patients.