Nilotinib is used for treating patients with imatinib-sensitive or -resistant chronic myeloid leukemia (CML); however, nilotinib-resistant cases have been observed in recent years. In addition, a considerable number of patients receiving nilotinib developed diabetes. Metformin is a front-line drug for the treatment of type 2 diabetes, and several studies have shown that diabetes patients treated with metformin have reduced incidence of cancer. This study aimed to define the effect of metformin on CML cells to determine whether metformin overcomes nilotinib resistance, and to identify novel targets for the treatment of nilotinib resistance. Methods: We observed the effects of metformin and nilotinib on K562 and KU812 human CML cell lines. Nilotinib-resistant CML cell lines were generated by exposing cells to gradually increasing doses of nilotinib. Then, we investigated the driving force that makes resistance to nilotinib and the effect of metformin on the driving force. Results: Sub-toxic doses of metformin enhanced nilotinib efficacy by reducing Bcl-xL expression, which induces apoptosis in CML cells. Next, we generated nilotinib-resistant K562 and KU812 cell lines that overexpressed the c-Jun N-terminal kinase (JNK) gene. JNK silencing by a JNK inhibitor restored sensitivity to nilotinib. Furthermore, metformin was effective in decreasing phosphorylated JNK levels, restoring nilotinib sensitivity. Combined treatment with nilotinib and metformin was more effective than combined treatment with nilotinib and a JNK inhibitor in terms of cell proliferation inhibition. Conclusions: This study suggested that combination therapy with metformin and nilotinib may have clinical benefits of enhancing antileukemia efficacy and overcoming resistance to nilotinib.

PURPOSE: The aim of this study was to evaluate the ossification and maturation of the midpalatal suture in young Koreans using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: The study sample consisted of 40 patients with ages from 8.2 to 23.6 years who visited the Department of Orthodontics, Chung-Ang University Dental Hospital. CBCT images were taken for diagnosis. From the CBCT image, morphological stages and Hounsfield units (HU) of midpalatal suture were obtained to evaluate the midpalatal suture maturation. Spearman's correlation coefficients were calculated to analyze relationships between chronological age, morphological stage, and HU. RESULT: There was a wide variation in the morphology of the midpalatal suture in each age group. It showed a modest relationship between the chronological age and the degree of morphological stages. Also there was a modest relationship between the chronological age and HU. In contrast, there was a significant relationship between morphological stages and HU of midpalatal suture (P < 0.01). CONCLUSION: CBCT images can be used for the evaluation of midpalatal suture maturation. For the estimation of the prognosis of rapid maxillary expansion, CBCT may be reliable for the assessment of the maturation of the midpalatal suture.
Cone-Beam Computed Tomography ; Diagnosis ; Humans ; Orthodontics ; Palatal Expansion Technique ; Prognosis ; Sutures

The publication of this article unfortunately contained several mistakes.
Humans ; Orthognathic Surgery ; Publications ; Snoring

BACKGROUND: Two-jaw surgery including mandibular and maxillary backward movement procedures are commonly performed to correct class III malocclusion. Bimaxillary surgery can reposition the maxillofacial bone together with soft tissue, such as the soft palate and the tongue base. We analyzed changes of pharyngeal airway narrowing to ascertain clinical correlations with the prevalence of snoring after two-jaw surgery. METHODS: A prospective clinical study was designed including a survey on snoring and three-dimensional (3D) computed tomography (CT) in class III malocclusion subjects before and after bimaxillary surgery. We conducted an analysis on changes of the posterior pharyngeal space find out clinical correlations with the prevalence of snoring. RESULTS: Among 67 subjects, 12 subjects complained about snoring 5 weeks after the surgical correction, and examining the 12 subjects after 6 months, 6 patients complained about the snoring. The current findings demonstrated the attenuation of the largest transverse width (LTW), anteroposterior length (APL), and cross-sectional area (CSA) following bimaxillary surgery given to class III malocclusion patients, particularly at the retropalatal level. The average distance of maxillary posterior movements were measured to be relatively higher (horizontal distance 3.9 mm, vertical distance 2.6 mm) in case of new snorers. CONCLUSIONS: This study found that bimaxillary surgery could lead to the narrowing of upper airway at the retropalatal or retroglossal level as well as triggering snoring in subjects with class III malocclusion. Based on the current clinical findings, we also found that upper airway narrowing at retropalatal level may contribute to increasing the probability of snoring and that polysonography may need to be performed before orthognathic surgery in subjects with class III malocclusion.
Clinical Study ; Humans ; Malocclusion ; Orthognathic Surgery* ; Palate, Soft ; Prevalence ; Prospective Studies ; Sleep Apnea, Obstructive ; Snoring* ; Tongue

Hyperthermia can cause severe complications such as rhabdomyolysis, which can induce acute kidney injury. Normal thermoregulation can be disturbed by high fever, and maintenance of a normal body temperature by external cooling can reduce oxygen consumption, and increase vascular tone. Several studies have been conducted to determine the effectiveness of external cooling in treat rhabdomyolysis or renal failure. We report a case of rhabdomyolysis leading to multiple organ dysfunction, including renal failure. The use of an external cooling device achieved fever control and successfully treated rhabdomyolysis and renal failure.
Acute Kidney Injury* ; Body Temperature ; Body Temperature Regulation ; Fever ; Oxygen Consumption ; Renal Insufficiency ; Rhabdomyolysis*

OBJECTIVE: The purpose of this study was to determine the incidence and risk factors of infections associated with implantable venous access ports (IVAPs). MATERIALS AND METHODS: From August 2003 through November 2011, 1747 IVAPs were placed in our interventional radiology suite. One hundred forty four IVAPs were inserted in patients with hematologic malignancy and 1603 IVAPs in patients with solid tumors. Among them, 40 ports (23 women and 17 men; mean age, 57.1 years; range, 13-83) were removed to treat port-related infections. We evaluated the incidence of port-related infection, patient characteristics, bacteriologic data, and patient progress. Univariable analyses (t test, chi-square test, and Fisher's exact test) and multiple logistic regression analyses were used to determine the risk factors for IVAP related infection. RESULTS: Overall, 40 (2.3%) of 1747 ports were removed for symptoms of infection with an incidence rate of 0.067 events/1000 catheter-days. According to the univariable study, the incidences of infection were seemingly higher in the patients who received the procedure during inpatient treatment (p = 0.016), the patients with hematologic malignancy (p = 0.041), and the patients receiving palliative chemotherapy (p = 0.022). From the multiple binary logistic regression, the adjusted odds ratios of infection in patients with hematologic malignancies and those receiving palliative chemotherapy were 7.769 (p = 0.001) and 4.863 (p = 0.003), respectively. Microorganisms were isolated from 26 (65%) blood samples, and two of the most causative organisms were found to be Staphylococcus (n = 10) and Candida species (n = 7). CONCLUSION: The underlying hematologic malignancy and the state of receiving palliative chemotherapy were the independent risk factors of IVAP-related infection.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Catheter-Related Infections/*epidemiology/microbiology ; Catheters, Indwelling/*adverse effects ; Female ; Hematologic Neoplasms/drug therapy ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasms/drug therapy ; Palliative Care/statistics & numerical data ; Retrospective Studies ; Risk Factors ; Vascular Access Devices/*adverse effects ; Young Adult

Melatonin affects diverse physiological functions through its receptor and plays an important role in the central nervous system. In the present study, we compared immunoreactivity patterns of arylalkylamine N-acetyltransferase (AANAT), an enzyme essential for melatonin synthesis, and melatonin receptor type 1B (MT2) in the spinal cord of young adult (2~3 years) and aged (10~12 years) beagle dogs using immunohistochemistry and Western blotting. AANAT-specific immunoreactivity was observed in the nuclei of spinal neurons, and was significantly increased in aged dog spinal neurons compared to young adult spinal neurons. MT2-specific immunoreactivity was found in the cytoplasm of spinal neurons, and was predominantly increased in the margin of the neuron cytoplasm in aged spinal cord compared to that in the young adult dogs. These increased levels of AANAT and MT2 immunoreactivity in aged spinal cord might be a feature of normal aging and associated with a feedback mechanism that compensates for decreased production of melatonin during aging.
Age Factors ; Aging/physiology ; Animals ; Arylalkylamine N-Acetyltransferase/*analysis/immunology/physiology ; Blotting, Western ; Dogs ; Fluorescent Antibody Technique ; Male ; Receptor, Melatonin, MT2/*analysis/immunology/physiology ; Spinal Cord/*chemistry/immunology/physiology

Standard endocrine therapy and chemotherapy can induce long-term remission in breast cancer patients; however, breast cancer can recur at any site. Pulmonary nodules with lymphadenopathy in advanced cancer patients are likely to be assumed as metastases. A 44-year-old woman with a history of breast cancer was presented to our institution with abnormal findings on 18-fluorodeoxyglucose positron emission tomography imaging, which suggested lung metastasis. She had previously been diagnosed with breast cancer (T1N2M0, Stage IIIa, intraductal carcinoma, triple negative cancer). Histological analysis of the mediastinal lymph node biopsy demonstrated sarcoidosis, showing a chronic, non-caseating, granulomatous inflammation. Our case highlights the need for non-malignant diagnoses in those with prior malignancies, and the need for histological evaluations in the event of first recurrence following potentially curative therapy.
Adult ; Biopsy ; Breast Neoplasms* ; Carcinoma, Intraductal, Noninfiltrating ; Diagnosis ; Drug Therapy ; Female ; Humans ; Inflammation ; Lung ; Lymph Nodes ; Lymphatic Diseases ; Neoplasm Metastasis* ; Positron-Emission Tomography ; Recurrence ; Sarcoidosis ; Sarcoidosis, Pulmonary*