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Abstract: Esophageal cancer (EC) and gastric cancer (GC) constitute a major cause of cancer deaths worldwide. Recent improvements in both surgical techniques and adjuvant/neoadjuvant chemotherapy, radiotherapy or both have increased the survival of patients with loco-regional disease. However, most patients with GC or EC have advanced disease either at diagnosis or during the follow-up, and despite recent advances, these patients still do poorly. Understanding of the molecular pathways that characterize cell growth, cell cycle, apoptosis, angiogenesis and invasion has provided novel targets in cancer therapy. In this review we describe the current status of targeted therapies in the treatment of EC and GC, including EGFR inhibitors, antiangiogenic agents, cell cycle inhibitors, apoptosis promoters and matrix metalloproteinases inhibitors. The emerging data from the clinical development of these compounds has provided novel opportunities in the treatment of EC and GC that will probably translate into clinical benefit for patients with these common malignancies. [Copyright &y& Elsevier]

[Display omitted] • Adolescent THC treatment potentiated cocaine actions in motor cortex. • Adolescent THC potentiated cocaine actions dorsomedial hypothalamus (in females). • Sex-specific cocaine effects on the Islands of Calleja and orbitofrontal cortex. • Lasting, sex-dependent effects of THC alone on somatosensory and piriform cortices. It has been suggested that cannabis consumption during adolescence may be an initial step to cocaine use in adulthood. Indeed, previous preclinical data show that adolescent exposure to cannabinoids (both natural and synthetic) potentiates cocaine self-administration in rats. Here we aimed at gaining a deeper understanding of the cellular activation patterns induced by cocaine as revealed by Fos imaging and how these patterns may change due to adolescent exposure to THC. Male and female Wistar rats were administered every other day THC (3 mg/kg i.p.) or vehicle from postnatal day 28–44. At adulthood (PND90) they were given an injection of cocaine (20 mg/kg i.p.) or saline and sacrificed 90 min later. Cocaine-induced Fos activation was measured by immunohistochemistry as an index of cellular activation. We found that cocaine-induced activation in the motor cortex was stronger in THC-exposed rats. Moreover, there was significant sex-dependent interaction between cocaine and adolescent THC exposure in the dorsal hypothalamus, suggesting that cocaine induced a more robust cellular activation in THC-exposed females but not in THC-treated males. Other THC- and cocaine-induced effects were also evident. These results add to the previous literature suggesting that the behavioral, cellular, molecular, and brain-activating actions of cocaine are modulated by early experience with cannabinoids and provide additional knowledge that may explain the enhanced actions of cocaine in rats exposed to cannabinoids during their adolescence. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cisplatin-based combination chemotherapy is the mainstay of treatment for locally advanced or metastatic urothelial carcinoma. However, standard dose schedule of cisplatin cannot be used in patients with impaired renal function. We evaluated the safety and efficacy of gemcitabine and a split dose administration of cisplatin in patients with renal dysfunction. Patients and methods: Patients with locally advanced or metastatic urothelial carcinoma with creatinine clearance between 35 and 59ml/min received gemcitabine 2500mg/m2 and cisplatin 35mg/m2 on day 1 and day 15 for an every 28day schedule. Results: Between March 2004 and November 2009, 38 patients were treated. Median creatinine clearance was 49ml/min. Median number of cycles per patient was 3 (1–7). There were 15 partial responses (39%) and 12 patients had stable disease (31%). Median progression free survival and overall survival were 3.5 and 8.5months (mo), respectively. Grade 3–4 haematological toxicities were: neutropenia 9%, anaemia 6% and thrombocytopenia 16%. No patient developed renal toxicity. Conclusions: Biweekly gemcitabine and cisplatin is an active and feasible regimen in this subset of patients and could be an option for unfit patients. However, results seem not to be superior to those obtained with carboplatin based regimens in this population of patients. [Copyright &y& Elsevier]