Inhibition of autophagy by chloroquine makes chemotherapy in nasopharyngeal carcinoma more efficient

Objectives

A combination of platinum-based chemotherapy and radiotherapy is the standard treatment for nasopharyngeal carcinoma (NPC). However, the efficacy of chemotherapy has reached a plateau. Many autophagy studies suggest that autophagy can either promote or suppress to cancer progression. Thus, a role of autophagy in the acquisition of chemoradioresistance has recently been a notable event. Therefore, we examined the relationship between autophagy and chemotherapy in NPC.

Effects of visible-light irradiation on vitreous structure in the presence of a photosensitizer

Sensitized photo-induced changes of vitreous structure were investigated using both in vivo and in vitro model systems. In the former, rabbit eyes were injected with the photosensitizer riboflavin, and in the latter, calf vitreous samples were treated with riboflavin or Methylene Blue prior to irradiation with white light. The active species of oxygen, i.e. singlet oxygen, superoxide anion, hydroxyl radical and hydrogen peroxide, generated by the photodynamic action of the sensitizer, caused significant liquefaction of the calf vitreous in vitro. There was little liquefaction of the rabbit vitreous in vivo, suggesting the presence of a protective mechanism in vivo. hyaluronidase induced significantly greater liquefaction in vitro than either Methylene Blue or riboflavin. This study suggests that loss of gel vitreous structure can result from extensive depolymerization of hyaluronidase by hyaluronidase and less drastic conformation and molecular weight changes in the photosensitized reactions. Although light-induced liquefaction was less marked than enzyme-induced liquefaction, the mechanism of the former is more pertinent to age-related vitreous synchysis.     

Phase IIb study of pembrolizumab combined with S‐1 + oxaliplatin or S‐1 + cisplatin as first‐line chemotherapy for gastric cancer

The KEYNOTE‐659 study evaluated the efficacy and safety of first‐line pembrolizumab plus S‐1 and oxaliplatin (SOX) (cohort 1) or S‐1 and cisplatin (SP) (cohort 2) for advanced gastric/gastroesophageal junction (G/GEJ) cancer in Japan. Herein, we update the results of cohort 1 and describe the results of cohort 2. This open‐label phase IIb study enrolled patients with advanced programmed death‐ligand 1 (PD‐L1)‐positive (combined positive score ≥ 1) human epidermal growth factor receptor 2 (HER2)‐negative G/GEJ adenocarcinoma. The primary end‐point was the objective response rate (ORR). Other end‐points were duration of response (DOR), disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and safety. One hundred patients were enrolled. In cohorts 1 and 2, median follow‐up time was 16.9 and 17.1 months; ORR (central review), 72.2% and 80.4%; DOR, 10.6 and 9.5 months; DCR (central review), 96.3% and 97.8%; median PFS (central review), 9.4 and 8.3 months; and median OS, 16.9 and 17.1 months, respectively. Treatment‐related adverse events (TRAEs) occurred in all patients, including peripheral sensory neuropathy (94.4%, cohort 1), decreased neutrophil count (82.6%, cohort 2), nausea (59.3% and 60.9% in cohorts 1 and 2), and decreased appetite (61.1% and 60.9% in cohorts 1 and 2). Grade 3 or higher TRAEs were reported by 59.3% (cohort 1) and 78.3% (cohort 2), including decreased platelet count (14.8%, cohort 1) and decreased neutrophil count (52.2%, cohort 2). Pembrolizumab in combination with SOX or SP showed favorable efficacy and safety in patients with PD‐L1‐positive, HER2‐negative G/GEJ adenocarcinoma.     

Comparison of biochemical markers and cervical length for predicting preterm delivery

AIM: To examine the clinical utility of several prognostic factors for predicting preterm delivery. METHODS: One hundred and nineteen patients with a singleton pregnancy admitted to our hospital because of symptoms of preterm labor were included in this study. Maternal serum C-reactive protein (CRP), transvaginal sonographic measurement of cervical length (CL), granulocyte elastase (EL) in cervical secretions, fetal fibronectin (fFN), alpha-fetoprotein (AFP), and insulin-like growth factor binding protein-1 (IGFBP-1) in vaginal secretions were examined on admission. EL, fFN, AFP, and IGFBP-1 were measured by bed-side test kits. Correlation between each factor and the duration of pregnancy (from admission to delivery) was investigated. RESULTS: A significant correlation was found between the duration of pregnancy and CRP (r= -0.37, P<0.001), but not CL. The duration was significantly shorter in the fFN-positive group than in the negative group (P=0.0015). However, no significant difference was observed between the positive group and the negative group for each of CL, EL, AFP and IGFBP-1. CONCLUSION: Association between the duration of the pregnancy and two biochemical markers (CRP and fFN) was confirmed. As they can be examined quickly and easily, they are quite useful for estimating prognosis of preterm labor.     

Seizure Deterioration with Increased Levetiracetam Blood Concentration during the Postpartum Period in Refractory Temporal Lobe Epilepsy

We evaluated a 39-year-old pregnant woman with right temporal lobe epilepsy. During the second trimester, seizure deterioration was responsive to an increased daily dose of levetiracetam (LEV). However, immediately after delivery, new non-habitual seizures emerged along with a sharply increased LEV concentration. The frequency of habitual seizures also slightly increased. The non-habitual seizures completely disappeared, and the frequency of the habitual seizures improved to the baseline level after the LEV dosage was reduced. Thus, a paradoxical effect of an increased LEV blood concentration was assumed to be a potential cause of these events. Peripartum pharmacokinetic fluctuations in LEV levels should be monitored carefully.     

Biopsy-proven Streptococcus suis-associated Infectious Glomerulonephritis

A 64-year-old Japanese man who worked at a butcher shop was hospitalized for a fever, headache, and deafness. We diagnosed him with sepsis and meningitis caused by Streptococcus suis infection. The patient''s renal function declined rapidly, and hemodialysis was performed temporarily. A renal biopsy was performed, and the renal function tended to improve with antimicrobial therapy. This case seemed rather similar to one of staphylococcal-associated nephritis in that it showed mesangial proliferative nephritis with immunoglobulin A deposition, even though the nephritis was caused by streptococci. Similarly, intramembranous electron-dense deposits were characteristic findings. We present new findings of an in vivo renal biopsy in a case of S. suis-associated glomerulonephritis.