Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma. Michaelson MD,McKay RR,Werner L,Atkins MB,Van Allen EM,Olivier KM,Song J,Signoretti S,McDermott DF,Choueiri TK.Cancer. 2015 Oct 1;121(19):3435-43. [Epub 2015 Jun 8]. doi: 10.1002/cncr.29503.

Background

Sarcomatoid renal cell carcinoma (RCC) is associated with an aggressive biology and a poor prognosis. Poor-risk RCC is defined by clinical prognostic factors and demonstrates similarly aggressive behavior. No standard treatment exists for patients with sarcomatoid RCC, and treatment options for patients with poor-risk disease are of limited benefit. The objective of this study was to investigate the efficacy of antiangiogenic therapy in combination with cytotoxic chemotherapy in clinically aggressive RCC.

Radiation dose to the neurovascular bundles or penile bulb does not predict erectile dysfunction after prostate brachytherapy

PURPOSE: To examine the relationship between calculated doses to the neurovascular bundles (NVBs) and the penile bulb (PB) and the development of erectile dysfunction (ED) after low-dose-rate prostate brachytherapy (LDRPB) alone. METHODS AND MATERIALS: Between September 1997 and June 1999, 84 men were treated with LDRPB alone. Inclusion criteria for this study were (1) no ED according to a self-administered questionnaire before PB, (2) treatment with PB alone (125I; 144 Gy), (3) postimplant CT scan of the prostate 1 month after PB, and (4) minimum of 24 months of continuous follow-up. Fifty men met all inclusion criteria. ED was assessed by a self-administered questionnaire completed before and at each follow-up visit after LDRPB. Radiation doses to the NVB and PB were calculated on the basis of axial postimplant CT images. Multiple variables (patient-related and dosimetric quantifiers) that may predict for the development of ED were examined by univariate analysis. RESULTS: Thirty of the 50 men (60%) were potent at last follow-up. The only patient-related variable that predicted for the development of ED was patient age (<65 vs. >65 years; p=0.03). The calculated mean maximum doses to the NVB and PB were 684 Gy (range, 195-1277 Gy) and 498 Gy (range, 44-971 Gy), respectively. The mean calculated doses to 50% of the NVB and PB were 158 Gy (range, 76-240 Gy) and 43 Gy (range, 19-101 Gy), respectively. The calculated mean maximum, mean minimum, and mean doses to 50% of the NVB or PB did not differ between those men who developed ED and those men who did not develop ED. None of the dosimetric variables examined predicted the development of ED after LDRPB. CONCLUSIONS: In our experience, higher calculated doses to the NVB or PB are not associated with ED after LDRPB.     

Comparative evaluation of gustatory function between postmenopausal women and age‐matched men

Oral Diseases (2010) 16 , 469–475 Objective: The aim of the study was to compare the gustatory function between postmenopausal women and age‐matched men. Subjects and methods: During a period of 4 months, 30 postmenopausal women and 30 age‐matched men were prospectively evaluated for gustatory function. Each subject was given a symptoms questionnaire for self‐assessment of taste function. Then, whole mouth taste test was performed in which the quality identification and intensity ratings of taste solutions were measured. Results: Regarding correct quality identification, the results were statistically non‐significant (P > 0.05). As far as the intensity judgments are concerned, significant difference exists between postmenopausal women and age‐matched men. Intensity of taste perception for sucrose was significantly lower in postmenopausal women than intensity of taste perception for other tastes (P < 0.05). One of the noticeable findings is that 15 (50%) postmenopausal women reported a change in dietary habits; all expressed liking for sweeter food. Conclusion: Postmenopausal women appeared to have a reduced perception of sucrose, which can alter eating habits, such as intake of more sweet foods, whereas no significant difference is observed in taste perception of NaCl, citric acid and quinine hydrochloride between postmenopausal women and age‐matched men. Fifteen (50%) postmenopausal women stated fondness for sweet taste.     

Cannabidiol inhibits synaptic transmission in rat hippocampal cultures and slices via multiple receptor pathways

BACKGROUND AND PURPOSE

Cannabidiol (CBD) has emerged as an interesting compound with therapeutic potential in several CNS disorders. However, whether it can modulate synaptic activity in the CNS remains unclear. Here, we have investigated whether CBD modulates synaptic transmission in rat hippocampal cultures and acute slices.

EXPERIMENTAL APPROACH

The effect of CBD on synaptic transmission was examined in rat hippocampal cultures and acute slices using whole cell patch clamp and standard extracellular recordings respectively.

KEY RESULTS

Cannabidiol decreased synaptic activity in hippocampal cultures in a concentration-dependent and Pertussis toxin-sensitive manner. The effects of CBD in culture were significantly reduced in the presence of the cannabinoid receptor (CB₁) inverse agonist, {"type":"entrez-nucleotide","attrs":{"text":"LY320135","term_id":"1257555575","term_text":"LY320135"}}LY320135 but were unaffected by the 5-HT_1A receptor antagonist, WAY100135. In hippocampal slices, CBD inhibited basal synaptic transmission, an effect that was abolished by the proposed CB₁ receptor antagonist, AM251, in addition to {"type":"entrez-nucleotide","attrs":{"text":"LY320135","term_id":"1257555575","term_text":"LY320135"}}LY320135 and WAY100135.

CONCLUSIONS AND IMPLICATIONS

Cannabidiol reduces synaptic transmission in hippocampal in vitro preparations and we propose a role for both 5-HT_1A and CB₁ receptors in these CBD-mediated effects. These data offer some mechanistic insights into the effects of CBD and emphasize that further investigations into the actions of CBD in the CNS are required in order to elucidate the full therapeutic potential of CBD.