Glycolysis markers including glucose transporter 1 (GLUT1), monocarboxylate transporter 4 (MCT4), hexokinase 2 (HK2), pyruvate kinase M2 (PKM2) and glucose transporter 4 (GLUT4) play vital roles in head and neck squamous cell carcinoma (HNSCC). However, their prognostic value in HNSCC is still controversial. In this meta-analysis, we searched the PubMed, Web of Science and Cochrane Library databases and included thirty-seven studies (3272 patients) that met the inclusion criteria. Higher expression levels of the glycolysis markers in tumor tissues correlated with poorer overall survival (OS; P less then 0.001), disease-free survival (DFS; P = 0.03) and recurrence-free survival (RFS; P less then 0.001) of HNSCC patients. Subgroup and sensitivity analyses demonstrated that higher expression levels of GLUT1 (P less then 0.001), MCT4 (P = 0.002), HK2 (P = 0.002) and PKM2 (P less then 0.001) correlated with poorer OS among HNSCC patients. Higher expression of MCT4 (P less then 0.001) and PKM2 (P = 0.008) predicted poorer DFS among HNSCC patients. However, GLUT4 expression levels did not associate with clinical outcomes in HNSCC patients. These results demonstrate that glycolysis markers, such as GLUT1, MCT4, HK2 and PKM2, are potential prognostic predictors and therapeutic targets in HNSCC.

To determine the safety of hypofractionated imaging-guided (IG) volumetric-modulated arc radiotherapy (IG-VMAT; 70 Gy/28 fractions over 5.5 weeks) versus conventionally fractionated regimen (IG-VMAT; 80 Gy/40 fractions over 8 weeks) in Chinese patients with localized prostate cancer.

In this randomized non-comparative phase II trial, 92 patients with localized prostate cancer were assigned to receive either hypofractionated IG-VMAT (HFRT; 70 Gy/2.5Gy/28f) or conventionally fractionated IG-VMAT (CFRT; 80 Gy/2Gy/40f). Primary endpoint was grade 2 or higher late gastrointestinal (GI) and genitourinary (GU) toxicity at 2 years. The GI/GU toxicity and biochemical relapse-free survival (bRFS) were compared between the two treatment groups.

Median follow-up was 26 months. The incidence of grade 2 or higher late GI/GU toxicity was low in both groups; the 5-year cumulative incidence of Radiation Therapy Oncology Group grade 2 or higher GI/GU toxicity at 2 years was 7.6% with HFRT versus 10.3% with CFRT (

= 0.707). Biochemical control was not significantly different between the two groups; the 2-year bRFS was 94.6% for HFRT versus 95.0% for CFRT (

= 0.704).

Hypofractionated IG-VMAT appears to be equivalent to conventionally fractionated IG-VMAT in terms of toxicity in Chinese patients with localized prostate cancer.

Hypofractionated IG-VMAT appears to be equivalent to conventionally fractionated IG-VMAT in terms of toxicity in Chinese patients with localized prostate cancer.As an antagonist of voltage-gated potassium (Kv) channels, 4-aminopyridine (4-AP) is used as symptomatic therapy in several neurologic disorders. The improvement of visual function and motor skills and relieve of fatigue in patients with MS have been attributed to 4-AP. Its prolonged release formulation (fampridine) has been approved for the symptomatic treatment of walking disability in MS. The beneficial effects were explained by the blockade of axonal Kv channels, thereby enhancing conduction along demyelinated axons. However, an increasing body of evidence suggests that 4-AP may have additional properties beyond the symptomatic mode of action. In this review, we summarize preclinical and clinical data on possible neuroprotective features of 4-AP.

Therapies targeting B cells have been used in the clinic for multiple sclerosis (MS). In patients with relapsing MS, anti-CD20 therapy often suppresses relapse activity; yet, their effect on disease progression has been disappointing. Most anti-CD20 therapeutic antibodies are type I, but within the unique microenvironment of the brain, type II antibodies may be more beneficial, as type II antibodies exhibit reduced complement-dependent cytotoxicity and they have an increased capacity to induce direct cell death that is independent of the host immune response.

We compared the effect of type I with type II anti-CD20 therapy in a new rodent model of secondary progressive MS (SPMS), which recapitulates the principal histopathologic features of MS including meningeal B-cell aggregates. Nanvuranlat Focal MS-like lesions were induced by injecting heat-killed

into the piriform cortex of MOG-immunized mice. Groups of mice were treated with anti-CD20 antibodies (type I [rituxumab, 10 mg/kg] or type II [GA101, 10 mg/kg]) 4 weeks after lesion initiation, and outcomes were evaluated by immunohistochemistry.

Anti-CD20 therapy decreased the extent of glial activation, significantly decreased the number of B and T lymphocytes in the lesion, and resulted in disruption of the meningeal aggregates. Moreover, at the given dose, the type II anti-CD20 therapy was more efficacious than the type I and also protected against neuronal death.

These results indicate that anti-CD20 may be an effective therapy for SPMS with B-cell aggregates and that the elimination of CD20

B cells alone is sufficient to cause disruption of aggregates in the brain.

These results indicate that anti-CD20 may be an effective therapy for SPMS with B-cell aggregates and that the elimination of CD20+ B cells alone is sufficient to cause disruption of aggregates in the brain.Given the high frequency of urinary tract infections (UTIs) and their recurrence, there is keen interest in developing effective UTI vaccines. Currently, most vaccine studies, including those in humans, involve parenteral vaccination aimed at evoking and sustaining elevated levels of systemic antibody directed at the uropathogens. In view of recent reports of aberrant Th2-biased bladder immune responses to infection, we hypothesized that immunizing mice intravesically with antigens from uropathogenic Escherichia coli (UPEC) combined with a Th1-skewing adjuvant could correct this defect and promote protection against UTIs. Here we report that compared with mice immunized subcutaneously with this vaccine combination, intravesically immunized mice were markedly more protected from UTIs because of their distinctive ability to recruit Th1 cells into the bladder. This mode of vaccination was effective even in mice that experienced multiple UTIs and displayed pronounced aberrant bladder immune responses. Thus, intravesical vaccination with one or more UPEC antigens to induce bladder Th1 responses represents a superior strategy to combat UTIs, especially in UTI-prone subjects.