Hyaluronic acid (HA), a ligand of CD44, accumulates in some types of tumors and is responsible for tumor progression. The nuclear factor erythroid 2-like 2 (NRF2) regulates cytoprotective genes and drug transporters, which promotes therapy resistance in tumors. Previously, we showed that high levels of CD44 are associated with NRF2 activation in cancer stem like-cells. Herein, we demonstrate that HA production was increased in doxorubicin-resistant breast cancer MCF7 cells (MCF7-DR) via the upregulation of HA synthase-2 (HAS2). HA incubation increased NRF2, aldo-keto reductase 1C1 (AKR1C1), and multidrug resistance gene 1 (MDR1) levels. Silencing of HAS2 or CD44 suppressed NRF2 signaling in MCF7-DR, which was accompanied by increased doxorubicin sensitivity. The treatment with a HAS2 inhibitor, 4-methylumbelliferone (4-MU), decreased NRF2, AKR1C1, and MDR1 levels in MCF7-DR. Subsequently, 4-MU treatment inhibited sphere formation and doxorubicin resistance in MCF7-DR. The Cancer Genome Atlas (TCGA) data analysis across 32 types of tumors indicates the amplification of HAS2 gene is a common genetic alteration and is negatively correlated with the overall survival rate. In addition, high HAS2 mRNA levels are associated with increased NRF2 signaling and poor clinical outcome in breast cancer patients. Collectively, these indicate that HAS2 elevation contributes to chemoresistance and sphere formation capacity of drug-resistant MCF7 cells by activating CD44/ NRF2 signaling, suggesting a potential benefit of HAS2 inhibition.

Leptomeningeal metastasis (LMM), also referred to as leptomeningeal carcinomatosis, results from diffuse infiltration of the leptomeninges by malignant cells originating from extra-meningeal primary tumors. It occurs in approximately 5%-10% of patients with solid tumor. Among solid tumors, the most common types leading to infiltration of the leptomeninges are breast cancer, lung cancer, and melanoma. Patients with LMM may present various signs and symptoms. Herein, we report a rare case with initial presentation of isolated chest wall pain. Computed tomography of the chest with contrast revealed a 2.5-cm nodule over the left upper lung. Biopsy confirmed the diagnosis of adenocarcinoma. Later, cerebrospinal fluid cytology exam also confirmed leptomeningeal seeding. It is rare for leptomeningeal carcinomatosis patients to present with chest wall pain. Therefore, a high index of suspicion is mandatory for accurate and prompt diagnosis.
Adenocarcinoma ; Biopsy ; Breast Neoplasms ; Cerebrospinal Fluid ; Chest Pain ; Diagnosis ; Humans ; Lung ; Lung Neoplasms ; Melanoma ; Meningeal Carcinomatosis* ; Neoplasm Metastasis ; Thoracic Wall* ; Thorax

BACKGROUND: In Korea, the number of liver transplantation (LT) center is still changing. Many more centers are performing liver transplantations than that during the past decades. But several centers have stopped liver transplantation, while some centers have newly started performing liver transplantation. We present our initial experience in a newly built center as an example for any center that is considering performing LT. METHODS: A total of 33 consecutive adult LTs that were performed from June 2006 to October 2009 were analyzed by comparing the first 11 living donor liver transplants (LDLTs) performed with the help of an outside experienced team (group 2) with the second 11 LDLTs (group 3) and the 11 deceased donor liver transplantations (DDLTs) cases (group 1) that were independently performed in our center. RESULTS: There was no operative mortality for the donors and there were two operative mortalities for the recipients. During a mean follow-up of 27.1 months (range: 2 days~61 months), there were two cases of late mortality for the recipients. There were no re-operations and no major complications for the donors. The warm ischemic time was significantly longer in group 1 than that in groups 2 and 3. Otherwise, there was no significant difference in the operative outcomes among the three groups. CONCLUSIONS: Thorough preparation and the valuable assistance of an experienced liver transplantation team at the beginning can facilitate a more rapid learning curve and bring about good outcomes even in a small, newly established institution.
Adult ; Follow-Up Studies ; Humans ; Korea ; Learning Curve ; Liver ; Liver Transplantation ; Living Donors ; Tissue Donors ; Transplants ; Treatment Outcome ; Warm Ischemia

OBJECTIVE: To investigate the effect on pain reduction and strengthening of the whole body vibration (WBV) in chronic knee osteoarthritis (OA). METHODS: Patients were randomly divided into two groups: the study group (WBV with home based exercise) and control group (home based exercise only). They performed exercise and training for 8 weeks. Eleven patients in each group completed the study. Pain intensity was measured with the Numeric Rating Scale (NRS), functional scales were measured with Korean Western Ontario McMaster score (KWOMAC) and Lysholm Scoring Scale (LSS), quadriceps strength was measured with isokinetic torque and isometric torque and dynamic balance was measured with the Biodex Stability System. These measurements were performed before training, at 1 month after training and at 2 months after training. RESULTS: NRS was significantly decreased in each group, and change of pain intensity was significantly larger in the study group than in the control group after treatment. Functional improvements in KWOMAC and LSS were found in both groups, but no significant differences between the groups after treatment. Dynamic balance, isokinetic strength of right quadriceps and isometric strengths of both quadriceps muscles improved in both groups, but no significant differences between the groups after treatment. Isokinetic strength of left quadriceps did not improve in both groups after treatment. CONCLUSION: In chronic knee OA patients, WBV reduced pain intensity and increased strength of the right quadriceps and dynamic balance performance. In comparison with the home based exercise program, WBV was superior only in pain reduction and similarly effective in strengthening of the quadriceps muscle and balance improvement.
Humans ; Knee ; Muscle Strength ; Ontario ; Osteoarthritis ; Osteoarthritis, Knee ; Quadriceps Muscle ; Torque ; Vibration ; Weights and Measures

Cerebral hemorrhage is one of the most common causes of dysphagia. In many cases, dysphagia gets better once the acute phase has passed. Structural lesions such as thyromegaly, cervical hyperostosis, congenital web, Zenker's diverticulum, neoplasm, radiation fibrosis, and retropharyngeal abscess must be considered as other causes of dysphagia as well. Retropharyngeal abscess seldom occur in adults and if it does so, a search for a prior dental procedure, trauma, head and neck infection is needed. The symptoms may include neck pain, dysphagia, sore throat, and in rare cases, dyspnea accompanied by stridor. We present a case and discuss a patient who had dysphagia and neck pain after a cerebral hemorrhage. Testing revealed a retropharyngeal abscess. The symptoms were successfully treated after the administration of antibiotics.
Adult ; Anti-Bacterial Agents ; Cerebral Hemorrhage ; Craniocerebral Trauma ; Deglutition Disorders ; Dyspnea ; Humans ; Hyperostosis ; Neck ; Neck Pain ; Pharyngitis ; Radiation Pneumonitis ; Respiratory Sounds ; Retropharyngeal Abscess ; Subarachnoid Hemorrhage ; Zenker Diverticulum

Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disease characterized by spiking fever, arthralgia, skin rashes, and hyperferritinemia. The rash is usually salmon-colored, non-itchy, accompanied by fever, and disappears with an improvement of fever. However, in some cases, the rash persisted regardless of fever. Here, we present a case of AOSD with an atypical persistent rash that showed histological findings resembling those of neutrophilic urticarial dermatosis. The patient was a 60-year-old woman with high fever, arthralgia, and a persistent flagellated skin rash. Despite systemic steroid treatment, the patient developed a serious complication: macrophage activation syndrome. Since this case presented with an atypical persistent rash with histological resemblance to neutrophilic urticarial dermatosis, we report its contribution to the further study of AOSD.

OBJECTIVE: Hepatic dysfunction frequently occurs in patients with hematologic malignancies and aplastic anemia who receive intensive chemotherapy or bone marrow transplantation (BMT). The role of laparoscopic liver biopsy in patients with hematologic disorders is very important to determine the etiological factors and to make treatment decisions. The aim of the present study was to evaluate the possible causes of liver disease in patients with abnormal liver function tests. METHODS: Laparoscopy guided liver biopsy was performed in 38 subjects who were receiving intensive cytotoxic therapy with BMT or without BMT. Two to three pieces of liver tissues were obtained in each patients using Vim-Silverman needle with electrocoagulation on biopsy site. Platelet transfusions were given if platelet count was less than 50,000/mm3. 39 biopsies were obtained in 38 patients. RESULTS: At the time of liver biopsy, platelet count was 170,000+/-138000/mm3 (range: 42,000 - 798,000/mm3). No procedure-related complications were observed. Biopsy findings after BMT (n=16) revealed graft versus host disease (GVHD) (n=9), drug induced hepatitis (n=6), veno-occlusive disease (n=2), viral hepatitis (n=1), and nonspecific reactive hepatitis (n=1). 3 patients of GVHD associated with other liver diseases such as drug-induced hepatitis, veno-occlusive disease and chronic active hepatitis B. The authors compared histologic diagnosis with laparoscopic findings. Laparoscopic findings of the liver surface were classified by Shimada's code number system. 5 patients who were biopsed before BMT showed cholestasis and fatty changes and it was possible to be treated with allogenic BMT. Histologic diagnosis in patients without BMT (n=18) showed viral hepatitis (n=6), drug induced hepatitis (n=5), non-specific reactive hepatitis (n=1), and others (n=6). In 12 cases (31%) laparoscopic liver biopsy led to a change in medical management. CONCLUSION: Laparascopic liver biopsy has been proven to be an effective means of assessing the cause of liver dysfunction in patients with hematologic disorders. The diagnosis obtained at laparoscopic liver biopsy could be changed the therapeutic plan in 12 of 39 (31%) patients.
Anemia, Aplastic ; Biopsy* ; Bone Marrow Transplantation ; Cholestasis ; Diagnosis ; Drug Therapy ; Drug-Induced Liver Injury ; Electrocoagulation ; Graft vs Host Disease ; Hematologic Neoplasms ; Hepatitis ; Hepatitis, Chronic ; Humans ; Laparoscopy ; Liver Diseases ; Liver Function Tests ; Liver* ; Needles ; Platelet Count ; Platelet Transfusion

Purpose: Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies. Materials and Methods: In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing. Results: By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores. Conclusion Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.

Purpose: Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies. Materials and Methods: In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing. Results: By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores. Conclusion Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.