In this study, we examined the possibility that MPTP and 6-hydroxydopamine (6-OHDA) act on distinct cell death pathways in a murine dopaminergic neuronal cell line, MN9D. First, we found that cells treated with 6-OHDA accompanied ultrastructural changes typical of apoptosis, whereas MPP+ treatment induced necrotic manifestations. Proteolytic cleavage of poly-(ADP-ribose)polymerase by caspase was induced by 6-OHDA, whereas it remained uncleaved up to 32 h after MPP+ treatment and subsequently disappeared. Accordingly, 6-OHDA- but not MPP(+)-induced cell death was significantly attenuated in the presence of a broad-spectrum caspase inhibitor, N-benzyloxy-carbonyl-Val-Ala-Asp-fluomethylketone (Z-VAD-fmk). As measured by fluorometric probes, the level of reactive oxygen species (ROS) significantly increased after 6-OHDA treatment. In contrast, the level of dihydroethidium-sensitive ROS following MPP+ treatment remained unchanged while a slight increase in dichlorofluorescin-sentive ROS was temporarily observed. As demonstrated by immunoblot analysis, the level of superoxide dismutase was down-regulated following 6-OHDA treatment, whereas it remained unchanged after MPP+ treatment. Cotreatment of cells with antioxidants such as N-acetylcysteine or Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP, cell-permeable superoxide dismutase mimetic) rescued 6-OHDA- but not MPP(+)-induced cell death, whereas inclusion of catalase or N(G)-nitro-L-arginine had no effect in both cases. In addition, 6-OHDA induced ROS-mediated c-Jun N-terminal kinase (JNK) activation that was attenuated in the presence of N-acetylcysteine or MnTBAP but not catalase or Z-VAD-fmk. In contrast, MPP+ has little effect on JNK activity, indicating that ROS and/or ROS-induced cell death signaling pathway seems to play an essential role in 6-OHDA-mediated apoptosis but not in MPP(+)-induced necrosis in a mesencephalon-derived, dopaminergic neuronal cell line.

Neuropathic cancer pain (NCP) is caused by nerve damage attributable to the cancer per se, and/or treatments including chemotherapy, radiotherapy, and surgery; the prevalence is reported to be as high as 40%. The etiologies of NCP include direct nerve invasion or nerve compression by the cancer, neural toxicity, chemotherapy, and radiotherapy. NCP is subdivided into plexopathy, radiculopathy, and peripheral neuropathies, among several other categories. The clinical characteristics of NCP differ from those of nociceptive pain in terms of both the hypersensitivity symptoms (burning, tingling, and an electrical sensation) and the hyposensitivity symptoms (numbness and muscle weakness). Recovery requires several months to years, even after recovery from injury. Management is complex; NCP does not usually respond to opioids, although treatments may feature both opioids and adjuvant drugs including antidepressants, anticonvulsants, and anti-arrhythmic agents, all of which improve the quality-of-life. This review addresses the pathophysiology, clinical characteristics and management of NCP, and factors rendering pain control difficult.

Background: Capecitabine plus oxaliplatin (XELOX) has shown modest activity and tolerable toxicity in a phase II trial for biliary tract cancers (BTCs). Meanwhile, gemcitabine plus oxaliplatin (GEMOX) has been the reference arm in recent phase II and III trials for BTCs. We aimed to investigate the efficacy of XELOX versus GEMOX as first-line therapy for advanced BCTs. Patients and methods:In this open-label, randomized, phase III, noninferiority trial, we randomly selected patients with metastatic BCTs to receive GEMOX (gemcitabine 1000 mg/m 2 on days 1 and 8, and oxaliplatin 100 mg/m 2 on day 1) or XELOX (capecitabine 1000 mg/m 2 , twice daily, on days 1-14 and oxaliplatin 130 mg/m 2 on day 1) as first-line treatment, given every 3 weeks, totaling eight cycles. The primary end point was to prove the noninferiority of XELOX to GEMOX in terms of 6-month progression-free survival (PFS) rate.Results: In total, 114 patients randomly received GEMOX and 108 randomly received XELOX. The median PFS was 5.3 months for the GEMOX group and 5.8 months for the XELOX group. The 6-month PFS rate was 44.5% for the GEMOX group and 46.7% for the XELOX group. The 95% confidence interval of the 6-month PFS rate difference between both groups was À12% to 16%, meeting the criteria for noninferiority of XELOX to GEMOX. There was no difference in objective response (P¼0.171) and median overall survival (P¼0.131) between both groups. The most common grade three to four adverse events were neutropenia and thrombocytopenia. No patient died of treatment-related causes. The XELOX group had significantly lower frequencies of hospital visits than the GEMOX group (P<0.001). Conclusion:XELOX showed significant noninferiority to GEMOX in terms of 6-month PFS rate. Thus, XELOX could be an alternative first-line treatment of BCTs.Trial Registration: This study was registered in ClinicalTrials.gov (number NCT01470443).

We conducted a prospective study to assess the prevalence and clinical characteristics of anemia and to define the risk factors for anemia in older Koreans. From October 2002 to November 2002, 1,254 subjects over the age of 60 years were selected from a crosssectional study. All subjects underwent a complete medical history taking and laboratory testing, which included; a complete blood cell count, reticulocyte, liver and renal function tests, lipid profiles, and iron profiles. The median age was 70 years old (range, 60-95 years). The mean levels of hemoglobin (mean ± SD) were 14.5 ± 1.4 g/dL in men and 13.0 ± 1.1 g/dL in women, and the overall prevalence of anemia was 13.6% (171/1,254): 9.9% (27/273) in men and 14.7% (144/981) in women. We found that the prevalence of anemia differed significantly between those of age 60-69 and 70-79 years (P < 0.0001), those of age 60-69 and ‡80 (P < 0.0001), and those of age 70-79 and ‡80 (P = 0.0474). Hemoglobin levels were significantly lower in subjects ‡80 years old. By logistic regression testing, female sex, old age, lower albumin level, higher creatinine level, and lower body mass index were identified as independent risk factors of anemia in elderly Koreans. In conclusion, the overall prevalence of anemia in our study group was 13.6% (171/1,254), and this increased with age. Am.

Cordyceps is a genus of ascomycete fungi that has been used for traditional herbal remedies. It contains various bioactive ingredients including cordycepin. Cordycepin, also known as 3-deoxyadenosine, is a major compound and has been suggested to have anticancer potential. The treatment of various cancer cells with cordycepin in effectively induces cell death and retards their cancerous properties. However, the underlying mechanism is not fully understood. Recent evidence has shed light on the molecular pathways involving cysteine-aspartic proteases (caspases), mitogen-activated protein kinases (MAPKs), and glycogen synthase kinase 3 beta (GSK-3β). Furthermore, the pathways are mediated by putative receptors, such as adenosine receptors (ADORAs), death receptors (DRs), and the epidermal growth factor receptor (EGFR). This review provides the molecular mechanisms by which cordycepin functions as a singular or combinational anticancer therapeutic agent.