PURPOSE: Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells. MATERIALS AND METHODS: The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis. RESULTS: AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines. CONCLUSION: Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.
Apoptosis ; Autophagy ; Blotting, Western ; Cell Cycle ; Cell Death ; Cell Line ; Cell Proliferation ; Cell Survival ; DNA Damage ; Fluorescent Antibody Technique ; Humans ; Phosphotransferases ; Protein Isoforms ; Stomach Neoplasms

BACKGROUND/AIMS: Fecal microbiota transplantation (FMT) is a highly effective therapy for refractory and recurrent Clostridium difficile infection (CDI). Despite its excellent efficacy and recent widespread use, FMT has not been widely used in South Korea thus far. We describe our experience with FMT to treat refractory/recurrent CDI. METHODS: We conducted a chart review of patients who underwent FMT for refractory/recurrent CDI at Inha University Hospital, between March 2014 and June 2016. The demographic information, treatment data, and adverse events were reviewed. FMT was administered via colonoscopy and/or duodenoscopy. All stool donors were rigorously screened to prevent infectious disease transmission. RESULTS: FMT was performed in nine patients with refractory/recurrent CDI. All patients were dramatically cured. Bowel movement was normalized within one week after FMT. There were no procedure-related adverse events, except aspiration pneumonia in one patient. During the follow-up period (mean 11.4 months), recurrence of CDI was observed in one patient at one month after FMT due to antibiotics. CONCLUSIONS: FMT is a safe, well-tolerated and highly effective treatment for refractory/recurrent CDI. Although there are many barriers to using FMT, we expect that FMT will be widely used to treat refractory/recurrent CDI in South Korea.
Anti-Bacterial Agents ; Clostridium difficile* ; Clostridium* ; Colonoscopy ; Disease Transmission, Infectious ; Duodenoscopy ; Fecal Microbiota Transplantation* ; Follow-Up Studies ; Gastrointestinal Microbiome ; Humans ; Korea ; Pneumonia, Aspiration ; Recurrence ; Tissue Donors

PURPOSE: Although procalcitonin (PCT) level is useful for the diagnosis of neonatal sepsis, PCT reliability is inconsistent because of the varied conditions encountered in neonatal intensive care units. This study aimed to investigate PCT levels and factors influencing increased PCT levelin newborns without bacterial infection during the first week of life. METHODS: In newborns hospitalized between March 2013 and October 2015, PCT levels were measured on the first, third, and seventh days after birth. Newborns with proven bacterial (blood culture positive for bacteria) or suspicious infection (presence of C-reactive protein expression or leukocytosis/leukopenia) were excluded. Various neonatal conditions were analyzed to identify the factors influencing increased PCT level. RESULTS: Among 292 newborns with a gestational age of 35.2±3.0 weeks and a birth weight of 2,428±643 g, preterm newborns (n=212) had higher PCT levels than term newborns (n=80). Of the newborns, 7.9% had increased PCT level (23 of 292) on the firstday; 28.3% (81 of 286), on the third day; and 3.3% (7 of 121), on the seventh day after birth. The increased PCT level was significantly associated with prenatal disuse of antibiotics (P=0.004) and surfactant administration (P<0.001) on the first day after birth, postnatal use of antibiotics (P=0.001) and ventilator application (P=0.001) on the third day after birth, and very low birth weight (P=0.042) on the seventh day after birth. CONCLUSION: In newborns without bacterial infection, increased PCT level was significantly associated with lower gestational age and respiratory difficulty during the first week of life. Further studies are needed for clinical applications.
Anti-Bacterial Agents ; Bacterial Infections ; Birth Weight ; C-Reactive Protein ; Diagnosis ; Dyspnea ; Gestational Age ; Humans ; Infant, Newborn* ; Infant, Very Low Birth Weight ; Intensive Care Units, Neonatal ; Parturition ; Premature Birth ; Sepsis ; Ventilators, Mechanical

PURPOSE: Although procalcitonin (PCT) level is useful for the diagnosis of neonatal sepsis, PCT reliability is inconsistent because of the varied conditions encountered in neonatal intensive care units. This study aimed to investigate PCT levels and factors influencing increased PCT levelin newborns without bacterial infection during the first week of life. METHODS: In newborns hospitalized between March 2013 and October 2015, PCT levels were measured on the first, third, and seventh days after birth. Newborns with proven bacterial (blood culture positive for bacteria) or suspicious infection (presence of C-reactive protein expression or leukocytosis/leukopenia) were excluded. Various neonatal conditions were analyzed to identify the factors influencing increased PCT level. RESULTS: Among 292 newborns with a gestational age of 35.2±3.0 weeks and a birth weight of 2,428±643 g, preterm newborns (n=212) had higher PCT levels than term newborns (n=80). Of the newborns, 7.9% had increased PCT level (23 of 292) on the firstday; 28.3% (81 of 286), on the third day; and 3.3% (7 of 121), on the seventh day after birth. The increased PCT level was significantly associated with prenatal disuse of antibiotics (P=0.004) and surfactant administration (P<0.001) on the first day after birth, postnatal use of antibiotics (P=0.001) and ventilator application (P=0.001) on the third day after birth, and very low birth weight (P=0.042) on the seventh day after birth. CONCLUSION: In newborns without bacterial infection, increased PCT level was significantly associated with lower gestational age and respiratory difficulty during the first week of life. Further studies are needed for clinical applications.
Anti-Bacterial Agents ; Bacterial Infections ; Birth Weight ; C-Reactive Protein ; Diagnosis ; Dyspnea ; Gestational Age ; Humans ; Infant, Newborn* ; Infant, Very Low Birth Weight ; Intensive Care Units, Neonatal ; Parturition ; Premature Birth ; Sepsis ; Ventilators, Mechanical

The posaconazole tablet formulation was developed to have improved bioavailability compared to the oral suspension. Here, we compared posaconazole plasma concentration (PPC) with the posaconazole oral suspension versus the tablet in Korean patients undergoing remission induction chemotherapy for hematologic malignancies. PPC was measured at 3, 8, and 15 days of treatment with the oral suspension (174 patients) or the tablet (40 patients). At all time-points, mean PPC was significantly higher with the tablet compared to the oral suspension. Our findings suggest that posaconazole tablets generate an optimal PPC earlier and in more patients than the oral suspension among Korean patients.
Antifungal Agents ; Biological Availability ; Dosage Forms ; Drug Therapy ; Hematologic Neoplasms* ; Humans ; Plasma* ; Remission Induction ; Tablets

BACKGROUND: Bendamustine may be a potential treatment option for patients with myeloma, but little is known about the utility of bendamustine as a salvage treatment, especially in Asian patients. METHODS: We performed a multicenter retrospective study of patients with relapsed or refractory myeloma who received bendamustine and prednisone. RESULTS: The records of 65 heavily pre-treated patients, who had undergone bortezomib and lenalidomide treatment (median number of previous treatments: 5), were analyzed. The median time from diagnosis to bendamustine treatment was 3.8 years, and the median patient age was 63 years (range, 38‒77 yr). The responses to the last treatment before bendamustine were refractory disease (N=52, 80%) or disease progression from partial response (N=13, 20%). Twenty-three patients responded to the treatment, with an overall response rate of 35% (23/65), and the median number of bendamustine treatment cycles was two (range, 1‒5 cycles). The median overall survival after bendamustine treatment was 5.5 months and the overall survival rate in responders to bendamustine was significantly better than that in non-responders (P=0.036). CONCLUSION: Bendamustine may be a potential salvage treatment to extend survival in a select group of heavily pre-treated patients with relapsed or refractory myeloma.
Asian Continental Ancestry Group ; Bendamustine Hydrochloride* ; Bortezomib ; Diagnosis ; Disease Progression ; Humans ; Multiple Myeloma* ; Prednisone ; Retrospective Studies* ; Salvage Therapy ; Survival Rate

X-linked agammaglobulinemia (XLA) is a hereditary humoral immunodeficiency that results from Bruton’s tyrosine kinase (BTK) gene mutations. These mutations cause defects in B-cell development, resulting in the virtual absence of these lymphocytes from the peripheral circulation. Consequently, this absence leads to a profound deficiency of lg all isotypes, and an increased susceptibility to encapsulated bacterial infections. A 15-month-old Korean boy presented with recurrent sinusitis and otitis media after 6 months of age, and had a family history of 2 maternal uncles with XLA. Laboratory tests revealed a profound deficiency of Ig isotypes, and a decreased count of CD19⁺ B cells in the peripheral circulation. Based on his family history and our laboratory test results, he was diagnosed with XLA. We performed BTK gene analysis of peripheral blood samples obtained from family members to confirm the diagnosis. Mutational analysis revealed a novel hemizygous frameshift mutation (c.82delC, p.Arg28Alafs*5), in the BTK gene. His mother and maternal grandmother were heterozygous carriers of this mutation and his two maternal uncles were hemizygous at the same position. After XLA diagnosis, intravenous immunoglobulin (400 mg/kg, monthly) treatment was initiated; recurrent sinusitis and otitis media were subsequently brought under control. To our knowledge, this is the first reported case of a Korean pedigree with a novel mutation in the BTK gene.
Agammaglobulinemia* ; B-Lymphocytes ; Bacterial Infections ; Diagnosis ; Frameshift Mutation ; Grandparents ; Humans ; Immunoglobulins ; Infant ; Lymphocytes ; Male ; Mothers ; Otitis Media ; Pedigree ; Protein-Tyrosine Kinases ; Sinusitis

The drug inducing tubulointerstitial nephritis is a crucial cause of acute kidney injury. Use of herbal plants in disease treatment is generally practiced in Korea. Although there are a small number of case reports, tubulointerstitial nephritis caused by taking Atractylodes macrocephala Koidzumi in human has never been reported. A 62-year-old man visited our hospital with symptoms of systemic edema accompanied by reduced urine volume and dyspnea after taking herbal plant 1 week ago. Chest radiographs showed both sided pleural effusion. Blood test results showed elevation of serum blood urea nitrogen and creatinine level and urine test results showed hematuria and proteinuria. Renal biopsy result showed evidence of tubulointerstitial nephritis by tubulitis and inflammatory cell expansion in the interstitium was observed. The patient's renal function recovered after administration of active renal replacement treatment and conservative therapy such as supplementation of fluid and electrolytes, and there was no disease recurrence for 1 year. Therefore, this case proved that Atractylodes macrocephala Koidzumi could cause acute kidney injury by the drug induced tubulointerstitial nephritis in human.
Acute Kidney Injury* ; Atractylodes* ; Biopsy ; Blood Urea Nitrogen ; Creatinine ; Dyspnea ; Edema ; Electrolytes ; Hematologic Tests ; Hematuria ; Herbal Medicine ; Humans ; Korea ; Middle Aged ; Nephritis ; Nephritis, Interstitial ; Plants ; Pleural Effusion ; Proteinuria ; Radiography, Thoracic ; Recurrence ; Renal Dialysis

Multiple myeloma (MM) is the third most common hematologic malignancy in Korea. Historically, the incidence of MM in Korea has been lower than that in Western populations, although there is growing evidence that the incidence of MM in Asian populations, including Korea, is increasing rapidly. Despite advances in the management of MM, patients will ultimately relapse or become refractory to their current treatment, and alternative therapeutic options are required in the relapsed/refractory setting. In Korea, although lenalidomide/dexamethasone is indicated for the treatment of relapsed or refractory MM (RRMM) in patients who have received at least one prior therapy, lenalidomide is reimbursable specifically only in patients with RRMM who have failed bortezomib-based treatment. Based on evidence from pivotal multinational clinical trials as well as recent studies in Asia, including Korea, lenalidomide/dexamethasone is an effective treatment option for patients with RRMM, regardless of age or disease status. Adverse events associated with lenalidomide/dexamethasone, including hematologic toxicity, venous thromboembolism, fatigue, rash, infection, and muscle cramps, are largely predictable and preventable/manageable with appropriate patient monitoring and/or the use of standard supportive medication and dose adjustment/interruption. Lenalidomide/dexamethasone provides an optimal response when used at first relapse, and treatment should be continued long term until disease progression. With appropriate modification of the lenalidomide starting dose, lenalidomide/dexamethasone is effective in patients with renal impairment and/or cytopenia. This review presents updated evidence from the published clinical literature and provides recommendations from an expert panel of Korean physicians regarding the use of lenalidomide/dexamethasone in patients with RRMM.
Asia ; Asian Continental Ancestry Group ; Disease Progression ; Exanthema ; Fatigue ; Hematologic Neoplasms ; Humans ; Incidence ; Korea ; Monitoring, Physiologic ; Multiple Myeloma* ; Muscle Cramp ; Recurrence ; Venous Thromboembolism

Congenital factor VII deficiency is a rare hemorrhagic disorder, and invasive procedures are likely to cause excessive bleeding in these patients. Endoscopic submucosal dissection (ESD) has been accepted as a curative treatment modality for gastric adenoma, early gastric cancer (EGC) and any other mucosal and submucosal tumors. The most important complications of ESD are bleeding and perforation. The use of antiplatelet agents or coagulopathies are risk factors for these complications. There are only few reports of successful ESD with coagulation disorders. We report a case of a 70-year-old female patient who was diagnosed with a gastric adenoma and factor VII deficiency. The patient was successfully treated with ESD. Before ESD, recombinant Coagulation factor VIIa was injected, and the procedure was performed successfully without any complications. In conclusion, ESD can be performed successfully in patients with factor VII deficiency, when recombinant human factor VIIa is administered properly.
Adenoma* ; Aged ; Endoscopy ; Factor VII Deficiency* ; Factor VIIa ; Female ; Hemorrhage ; Hemorrhagic Disorders ; Humans ; Platelet Aggregation Inhibitors ; Risk Factors ; Stomach Neoplasms