Renal cell carcinoma (RCC) is the most frequent upper urinary tract cancer in humans and accounts for 80-85% of malignant renal tumors. Eker rat represents a unique animal model to study RCC since these rats develop spontaneous renal tumors and leiomyoma, which may be due to tuberous sclerosis 2 (TSC2) mutation resulting in the activation of the mammalian target of rapamycin (mTOR) pathway. This study examines the role of a lycopene-rich diet in the development of RCC in the TSC2 mutant Eker rat model. Ten-week old female Eker rats (n = 90) were assigned in equal numbers to receive 0,100 or 200 mg/kg of lycopene as part of their daily diet. After 18 months the rats were sacrificed and the kidneys were removed. Immunohistochemical staining with antibodies against mTOR, phospho-S6 and EGFR were performed, as well as hematoxylin-eosin staining for histologic examination of the tumors. Tumors were counted and measured in individual kidneys. Presence of tumor decreased from 94% in control animals to 65% in the experimental group, but the difference was not statistically significant (P< 0.12). However, mean numbers of renal carcinomas were statistically significantly decreased in the lycopene-treated rats (P< 0.008) when compared to untreated controls. In the lycopene group, tumor numbers decreased (P< 0.002) and the numbers tended to decrease linearly (P< 0.003) as supplemental lycopene increased from 0 to 200. Control rats fed only basal diet had a greater length of tumors (23.98 mm) than rats fed lycopene supplement groups (12.90 mm and 11.07 mm) (P<0.05). Moreover tumor length decreased (P<0.02) and tumor length tended to decrease linearly (P<0.03) as supplemental lycopene increased from 0 to 200 mg/kg. All tumors showed strong staining with antibodies against mTOR, phospho-S6 and EGFR. In conclusion, dietary supplementation with lycopene attenuates the development of renal cell cancers in the predisposed TSC2 mutant Eker rat model. These results suggest that lycopene may play a role in the prevention of RCC.
procarbazine, spironolactone, sunitinib, tacrolimus, thalidomide and topotecan) compounding oral information was found. No information was obtained for 12 API (20.3%) (bexarotene, bosutinib, cabozantinib, fingolimod, fludarabine, ixazomib, lenalidomide, nilotinib, pazopanib, pomalidomide, regorafenib and vinorelbine) for which avoiding their handling and seeking other therapeutic alternative was advised. For the remaining 79.7% of API, priority was given to the recommendation of the lowest dust inhalation risk handling alternative. Conclusion and relevance Safe handling alternatives were found for most of the analysed oral HD in the sample, with potential to minimise workers' handling risk and ensure safety measures in hospital units.
BackgroundThere is only limited information about the sequential use of abiraterone acetate (AA) and enzalutamide (ENZ) in metastatic castration-resistant prostate cancer (mCRPC) patients. Patients who receive AA or ENZ as first-line therapy and subsequently become resistant have only a response rate of 15% to 30% to the alternative agent as second-line treatment. That finding clearly shows that cross-resistance occurs between ENZ and AA.PurposeTo evaluate the effectiveness of ENZ after failure of AA in patients with mCRPC.Material and methodsRetrospective study including all patients with mCRPC having sequential therapy with AA and ENZ from May 2012 to October 2017. Posttreatment changes in prostate-specific antigen (PSA) and differences in the median duration treatment (MDT) with AA and ENZ were used to determine the effectiveness of ENZ. A PSA reduction <30% and/or a MDT-ENZ/MDT-AA ratio <0.3 was considered as ineffective.ResultsThe study included 16 mCRPC patients treated sequentially with AA and ENZ. Only three patients had undergone prior docetaxel therapy. MDT-AA was 15 months (range: 3–38). During AA therapy 10 (67%) achieved a>50% decline in PSA, 12 (80%) a>30% and three (20%) did not achieve any decline in PSA. Subsequent MDT-ENZ was 4 months (range: 1–12), showing a MDT ratio of 0.27. Three patients did not have PSA levels after taking enzalutamide. None of the CRPC patients who were or not initially AA-sensitive showed a>30% PSA decline while taking ENZ. The medium PSA decline after abiraterone and enzalutamide were 37% and 17.8% respectively. Of the 15 patients, 7 (46.6%) were primarily ENZ-resistant and showed a rising PSA as the best response. Median time to progression was 7 months (range: 2–12) for five of 15 patients with at least one declining PSA value while taking enzalutamide (33.3%).ConclusionAlthough the number of patients included in this study is small, ENZ therapy after AA failure shows a low activity in terms of PSA response and/or medium duration of treatment. Results would be compatible with qualifying the use of ENZ after failure to AA as ineffective. Further properly designed studies to this aim are needed.Reference and/or Acknowledgements1. J Clin Oncol2014;32:125.No conflict of interest
registers compiled and updated on the AIFA (Italian Drugs Agency) web monitoring platform. Patient data such as age, sex, smoking, diabetes, hypertension and adherence were extracted and processed using Microsoft Access. In the same way, lipid ratios were calculated, and factors and percentage cardiovascular risk at 10 years were calculated using the Framingham Heart Study algorithm. Results Average age was 63 years and 68% were men. About 60% of 120 patients had arterial hypertension and 22% had diabetes mellitus. Concomitant therapy with statins (evolocumab-alirocumab) was present in 42% and 56% of patients, respectively, while intolerance was found in 52% and 47% of cases, respectively. Adherence to therapy was 100%. LDL and triglyceride concentrations decreased (LDL À60%) while HDL values remained constant over the study period. The percentage risk of a 10 year cardiovascular event was reduced from about 35% to 15% in 6 months and remained stable at 12 months. Conclusion and relevance The results confirmed a reduction in LDL cholesterol levels. These drugs represent treatment for patients subject to therapeutic failure. Alirocumab and evolocumab are innovative drugs with high costs. Their use should be limited to patient categories who have no real feedback with conventional drugs used in hypercholesterolaemia.
BackgroundAlthough clinical trials show low virological failures rates (<10%) for initial combination regimens of antiretroviral therapy (ART), we have observed a considerable percentage of naïve patients switching to another combination regimen.PurposeTo evaluate the switch rate among naïve patients who begin ART and to determine the reasons that led to a change in the ART regimen.Material and methodsWe conducted a retrospective observational study that included naïve HIV positive persons who initiated ART between January 2015 and January 2016 and attended the pharmaceutical care office. The main variable was persistence with treatment. Secondary variables were: demographics (age, gender); virological response (viral load), pharmacotherapeutics (initial combination regimen, new combination regimen) and reason for switching to another combination (virological failure, documented toxicity, prevention of long term toxicity, avoiding serious drug–drug interactions, simplification). Persistence rates were obtained through dispensing records of the pharmacy programme. The remaining variables were obtained from microbiology reports and the medical history of each patient.Results31 patients with an average age of 40±11 years were included. Most patients were men (90.3%). Median viral load was 23.300 (elite controller 481.000) copies/mL. The proportion of patients coinfected with hepatitis C virus was 16.1%. In all cases patients received triple therapy. More than half of patients (67.7%) began treatment with a combination regimen based on two nucleos(t)ide analogues plus an integrase inhibitor and the preferred regimen was tenofovir, emtricitabine, elvitegravir and cobicistat (58.1%). Non-nucleoside rilpivirine was used as a third drug in 25.8% of cases. Almost half of the patients switched to another treatment (48.4%). No virological failure occurred in any patient. The most common reason for changing to another regimen was documented toxicity (6). Other reasons were prevention of long term toxicity (4), simplification (4) and avoidance of serious drug–drug interactions (1).ConclusionThis study showed that a high proportion of ART regimens in naïve HIV patients were changed, even though these regimens achieved undetectable viral load. The main reason for switching was based on safety, either documented or potential toxicity. These data might help in designing pharmacist intervention programmes to improve the efficacy and safety of ART.No conflict of interest
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