Comparison of treatment outcomes between first-line chemotherapy with or without bevacizumab for advanced ovarian,fallopian tube,and primary peritoneal cancer (Tohoku gynecologic cancer unit: TGCU-RS001 study)

International Journal of Clinical Oncology - Outcomes with and without bevacizumab as first-line chemotherapy in Japanese-only ovarian cancer patients have not been reported. In this study, we...     

Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing metastatic breast cancer: multicenter phase II and pharmacokinetic study in Japan

Tolerability and response rate to weekly combination chemotherapy with trastuzumab and vinorelbine in Japanese women with HER2-overexpressing breast cancer not previously receiving either therapy were assessed. Tumor response was evaluated every 4 weeks and adverse events were graded. A total of 23 patients from six participating centers in Japan were enrolled. Median dose intensity of vinorelbine was 16.9 mg/m2/week and response rate was 73% (complete response+partial response); complete response=9%, partial response=64%, and progressive disease=5%. Time to progression was 361 days, with 75.0% of liver metastases and 60% of lung metastases responding to this treatment. The most common adverse events were leukocytopenia and neutropenia (96%); however, hematologic toxicity associated with vinorelbine was manageable by adjusting the dose. No pharmacokinetic differences for vinorelbine were found between single administration and combination with trastuzumab. This combination therapy produced high response rates and good tolerability, indicating a promising role in first-line chemotherapy for HER2-overexpressing metastatic breast cancer in Japan.     

Osteopontin deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice

Rheumatoid arthritis is one of the most critical diseases that impair the quality of life of patients, but its pathogenesis has not yet been fully understood. Osteopontin (OPN) is an extracellular matrix protein containing Arg-Gly-Asp (RGD) sequence, which interacts with alpha(v)beta3 integrins, promotes cell attachment, and cell migration and is expressed in both synovial cells and chondrocytes in rheumatoid arthritis; however, its functional relationship to arthritis has not been known. Therefore, we investigated the roles of OPN in the pathogenesis of inflammatory process in a rheumatoid arthritis model induced by a mixture of anti-type II collagen mAbs and lipopolysaccharide (mAbs/LPS). mAbs/LPS injection induced OPN expression in synovia as well as cartilage, and this expression was associated with joint swelling, destruction of the surface structures of the joint based on scanning electron microscopy, and loss of toluidine blue-positive proteoglycan content in the articular cartilage in wild-type mice. In contrast, OPN deficiency prevented the mice from such surface destruction, loss of proteoglycan in the articular joint cartilage, and swelling of the joints even when the mice were subjected to mAbs/LPS injection. Furthermore, mAbs/LPS injection in wild-type mice enhanced the levels of CD31-positive vessels in synovia and terminal deoxynucleotidyltransferase-mediated UTP end labeling-positive chondrocytes in the articular cartilage, whereas such angiogenesis as well as chondrocyte apoptosis was suppressed significantly in OPN-deficient mice. These results indicated that OPN plays a critical role in the destruction of joint cartilage in the rheumatoid arthritis model in mice via promotion of angiogenesis and induction of chondrocyte apoptosis.     

Efficacy of Dextromethorphan and Cyclosporine A for Acute Encephalopathy

Acute encephalopathy with biphasic seizures and late reduced diffusion was recently established clinicoradiologically as an encephalopathy syndrome. The outcome of this encephalopathy is characterized by a low mortality rate and high incidence of neurologic sequelae. Although the exact pathogenesis of this encephalopathy is uncertain, excitotoxic injury with delayed neuronal death is proposed. On the basis of this hypothesis, we tried a combination therapy of N-methyl-D-aspartate receptor antagonist, dextromethorphan, and apoptosis inhibitor, cyclosporine A, in four patients with acute encephalopathy with biphasic seizures and late reduced diffusion. All patients recovered except for hyperactivity in one patient. Furthermore, an additional four patients with near-miss encephalopathy, who showed mild disturbance of consciousness at 24 hours after prolonged febrile seizures associated with exanthem subitum, recovered without secondary seizures by the early administration of dextromethorphan. The combination regimen of dextromethorphan and cyclosporine A could be effective for the treatment and prevention of acute encephalopathy with biphasic seizures and late reduced diffusion.     

Activation of Cellular Immunity in Herpes Simplex Virus Type 1‐Infected Mice by the Oral Administration of Aqueous Extract of Moringa oleifera Lam. Leaves

Moringa oleifera Lam. is used as a nutritive vegetable and spice. Its ethanol extract has been previously shown to be significantly effective in alleviating herpetic skin lesions in mice. In this study, we evaluated the alleviation by the aqueous extract (AqMOL) and assessed the mode of its anti‐herpetic action in a murine cutaneous herpes simplex virus type 1 (HSV‐1) infection model. AqMOL (300 mg/kg) was administered orally to HSV‐1‐infected mice three times daily on days 0 to 5 after infection. AqMOL significantly limited the development of herpetic skin lesions and reduced virus titers in the brain on day 4 without toxicity. Delayed‐type hypersensitivity (DTH) reaction to inactivated HSV‐1 antigen was significantly stronger in infected mice administered AqMOL and AqMOL augmented interferon (IFN)‐γ production by HSV‐1 antigen from splenocytes of HSV‐1‐infected mice at 4 days post‐infection. AqMOL administration was effective in elevating the ratio of CD11b⁺ and CD49b⁺ subpopulations of splenocytes in infected mice. As DTH is a major host defense mechanism for intradermal HSV infection, augmentation of the DTH response by AqMOL may contribute to their efficacies against HSV‐1 infection. These results provided an important insights into the mechanism by which AqMOL activates cellular immunity. Copyright © 2016 John Wiley & Sons, Ltd.     

Risk assessment in the patients with uterine cervical cancer harboring intermediate risk factors after radical hysterectomy: a multicenter,retrospective analysis by the Japanese Gynecologic Oncology Group

International Journal of Clinical Oncology - Adjuvant therapy is usually considered for surgically treated patients with uterine cervical cancer harboring intermediate risk (IR) factors such as...     

Neoechinulin a imparts resistance to acute nitrosative stress in PC12 cells: a potential link of an elevated cellular reserve capacity for pyridine nucleotide redox turnover with cytoprotection

Treatment of PC12 cells with fungus-derived alkaloid neoechinulin A for more than 12?h renders the cells resistant to subsequent superoxide (O??)/nitric oxide (NO) insults derived from 3-morpholinosydnonimine (SIN-1). However, the underlying mechanism(s) remains largely unclear. To elucidate the mechanism(s), we assessed the specificity of the cytoprotection afforded by neoechinulin A treatment using other cytocidal stressors and also clarified the resulting cellular alterations, focusing on the antioxidant and metabolic enzymes systems. Neoechinulin A treatment for more than 12?h endowed PC12 cells with significant resistance to transient NO toxicity, but not persistent NO toxicity, bolus H?O? toxicity, or oxidative insult from the redox cycling quinone menadione. Cellular antioxidant system profiling revealed no substantial potentiation of the activity of any antioxidant enzyme in lysate from the neoechinulin A-treated cells excluding glutathione (GSH) content, which was significantly decreased (>50%), resulting in a proportional compromise in the thiol-reducing activity of the intact cells. In addition, no differences were observed in the activity for any nicotinamide adenine dinucleotide (phosphate) reduced form (NAD(P)H)-generating enzyme, steady-state NAD(P)H/nicotinamide adenine dinucleotide (phosphate) oxidized form (NAD(P)?) ratios, or the levels of total NAD(P)H. Nevertheless, the neoechinulin A-treated intact cells exhibited increased NAD(P)H redox turnover when driven by extracellular tetrazolium. The structurally inactive analog preechinulin failed to protect cells against NO toxicity or induce these alterations, suggesting their link with the cytoprotective mechanism. These results suggest that neoechinulin A, despite disabling the GSH defense system, confers cytoprotection against nitrosative stresses by elevating the cellular reserve capacity for NAD(P)H generation, which could offset crippling of energy-supplying systems due to nitrosative stress.     

Antimicrobial activity of Gel-entrapped catechins toward oral microorganisms

The oral cavity contains almost half of the commensal bacterial population present in the human body. An increase in the number of these microorganisms may result in systemic diseases such as infective endocarditis and aspiration pneumonia as well as oral infections. It is essential to control the total numbers of these microorganisms in order to suppress disease onset. Thus, we examined the antimicrobial activity of a newly developed gel-entrapped catechin (GEC) preparation against oral microorganisms. The minimum inhibitory concentration (MIC) of GEC was determined based on the relationship between a modified agar diffusion method and a broth microdilution method. GEC inhibited the growth of the Actinomyces, periodontopathic bacteria and Candida strains tested, but did not inhibit the growth of the oral streptococci that are important in the normal oral flora. Commercially available moisture gels containing antimicrobial components showed antimicrobial activity against all of the tested strains. After a series of washes and after a 24-h incubation, GEC retained the antimicrobial activity of the catechins. Catalase prevented GEC-induced growth inhibition of Actinomyces naeslundii and Streptococcus mutans suggesting that hydrogen peroxide may be involved in the antimicrobial activity of catechins. These results suggest that GEC may be useful for controlling oral microorganism populations and reducing the accumulation of dental plaque, thereby helping to prevent periodontal disease and oral candidiasis.