Purpose Clinical evidence demonstrating the effectiveness of systemic therapy for advanced salivary duct carcinoma (SDC) is lacking because of the disease’s rarity. We assessed the efficacy and toxicity of trastuzumab plus docetaxel in patients with locally advanced and/or recurrent or metastatic human epidermal growth factor receptor 2–positive SDC. Patients and Methods This was a single-center, single-arm, open-label, phase II study in Japan. The patients received trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks. Docetaxel 70 mg/m2 was administrated every 3 weeks. The primary end point was the overall response rate; the secondary end points included the clinical benefit rate, progression-free survival, overall survival, and toxicity. This study is registered with the University Hospital Medical Information Network Clinical Trials Registry (Identification No. UMIN000009437). Results Fifty-seven eligible patients with SDC were enrolled. The overall response rate was 70.2% (95% CI, 56.6% to 81.6%), and the clinical benefit rate was 84.2% (95% CI, 72.1% to 92.5%). Median progression-free and overall survival times were 8.9 months (95% CI, 7.8 to 9.9 months) and 39.7 months (95% CI, not reached), respectively. The most frequent adverse event was anemia (52 patients [91%]), followed by a decreased WBC count (51 patients [89%]) and neutropenia (50 patients [88%]). The most frequently observed grade 4 adverse event was a decreased neutrophil count (34 patients [60%]). Grade 3 febrile neutropenia was reported in eight patients (14%). No grade 2 or greater adverse events of heart failure or left ventricular ejection fraction decline to less than 50% occurred. Conclusion Our data show encouraging efficacy of trastuzumab plus docetaxel therapy in patients with human epidermal growth factor receptor 2–positive SDC, with a manageable toxicity profile.

OBJECTIVE-Mesenchymal stem cells (MSCs) have been reported to secrete various cytokines that exhibit angiogenic and neurosupportive effects. This study was conducted to investigate the effects of MSC transplantation on diabetic polyneuropathy (DPN) in rats.RESEARCH DESIGN AND METHODS-MSCs were isolated from bone marrow of adult rats and transplanted into hind limb skeletal muscles of rats with an 8-week duration of streptozotocin (STZ)-induced diabetes or age-matched normal rats by unilateral intramuscular injection. Four weeks after transplantation, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) productions in transplanted sites, current perception threshold, nerve conduction velocity (NCV), sciatic nerve blood flow (SNBF), capillary number-to-muscle fiber ratio in soleus muscles, and sural nerve morphometry were evaluated.RESULTS-VEGF and bFGF mRNA expression were significantly increased in MSC-injected thigh muscles of STZ-induced diabetic rats. Furthermore, colocalization of MSCs with VEGF and bFGF in the transplanted sites was confirmed. STZ-induced diabetic rats showed hypoalgesia, delayed NCV, decreased SNBF, and decreased capillary number-to-muscle fiber ratio in soleus muscles, which were all ameliorated by MSC transplantation. Sural nerve morphometry showed decreased axonal circularity in STZ-induced diabetic rats, which was normalized by MSC transplantation. D iabetic polyneuropathy (DPN) is the most common complication of diabetes. It is estimated that ϳ20 -30% of diabetic patients are affected by symptomatic DPN (1). Generally, DPN develops symmetrically in a length-dependent fashion, with dying back or dropout of the longest nerve fibers; both myelinated and unmyelinated, large and small are affected. Diabetic patients suffer from various symptoms of DPN, such as spontaneous pain, hyperalgesia, and diminished sensation (2). It has been shown that tight glycemic control is effective in slowing the progression of DPN but cannot completely prevent it (3). Therefore, additional therapeutic strategies are required. CONCLUSIONS-TheseNeural cell degeneration and decreased nerve blood flow (NBF) have been recognized as pathophysiologically characteristic features of DPN (4). Therefore, therapeutic agents that could act as both neurotrophic and angiogenic factors would be useful for the treatment of DPN even at an advanced stage. We previously demonstrated that local administration of basic fibroblast growth factor (bFGF) by intramusclar injection with crosslinked gelatin hydrogel improved the impaired nerve functions of streptozotocin (STZ)-induced diabetic rats, including amelioration of decreased NBF, hypoalgesia, and the delayed motor nerve conduction velocity (MNCV) on the treated side of sciatictibial nerves and that these effects were maintained for at least 30 days (5). Schratzberger et al. (6) showed that vascular endothelial growth factor (VEGF) gene transfer significantly increased the NCV and NBF as well as the vascular densities in muscle and peripheral nerv...

BackgroundThere is no standard first-line chemotherapy for recurrent/metastatic (RM) or unresectable locally advanced (LA) salivary gland carcinoma (SGC).Patients and methodsWe conducted a single institution, open-label, single arm, phase II trial of combined androgen blockade (CAB) for androgen receptor (AR)-positive SGC. Leuprorelin acetate was administered subcutaneously at a dose of 3.75 mg every 4 weeks. Bicalutamide was administered orally at a daily dose of 80 mg. Patients were treated until progressive disease or unacceptable toxicities.ResultsThirty-six eligible patients were enrolled. Thirty-three patients had RM disease and three patients had LA disease. The pathological diagnoses were salivary duct carcinoma (34 patients, 94%) and adenocarcinoma, NOS (two patients, 6%). The best overall response rate was 41.7% [n = 15, 95% confidence interval (CI), 25.5%–59.2%], the clinical benefit rate was 75.0% (n = 27, 95% CI, 57.8%–87.9%). The median progression-free survival was 8.8 months (95% CI, 6.3–12.3 months) and the median overall survival was 30.5 months (95% CI, 16.8 months to not reached). Additional analyses between treatment outcomes and clinicopathological factors or biomarkers including AR positivity, human epidermal growth factor receptor 2 status, and its complex downstream signaling pathway gene mutations showed no statistically significant differences. Elevated grade 3 liver transaminases and increased serum creatinine were reported in two patients, respectively. Discontinuation of leuprorelin acetate or bicalutamide due to adverse event occurred in one patient.ConclusionThis study suggests that CAB has equivalent efficacy and less toxicity for patients with AR-positive RM or unresectable LA SGC compared with conventional chemotherapy, which warrants further study.Clinical Trial RegistrationUMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703

Polycyclic aromatic compounds can be synthesized from 2-benzylic- or 2-allylbenzaldehydes using a catalytic amount of In(III) or Re(I) complexes. By using this method, polycyclic aza-aromatic compounds can also be prepared efficiently. In these reactions, only water is formed as a side product.

Treatment of phenol derivatives with terminal alkenes in the presence of a catalytic amount of a rhenium complex, Re(2)(CO)(10), gave monoalkylated phenol derivatives in good to excellent yields. This reaction proceeds at the ortho- or para-position of phenols regioselectively.