Genetic manipulation of LKB1 elicits lethal metastatic prostate cancer

Gene dosage is a key defining factor to understand cancer pathogenesis and progression, which requires the development of experimental models that aid better deconstruction of the disease. Here, we model an aggressive form of prostate cancer and show the unconventional association of LKB1 dosage to prostate tumorigenesis. Whereas loss of Lkbl alone in the murine prostate epithelium was inconsequential for tumorigenesis, its combination with an oncogenic insult, illustrated by Pten heterozygosity, elicited lethal metastatic prostate cancer. Despite the low frequency of LKB1 deletion in patients, this event was significantly enriched in lung metastasis. Modeling the role of LKB1 in cellular systems revealed that the residual activity retained in a reported kinase-dead form, LKB1(K781), was sufficient to hamper tumor aggressiveness and metastatic dissemination. Our data suggest that prostate cells can function normally with low activity of LKB1, whereas its complete absence influences prostate cancer pathogenesis and dissemination

Randomized pharmacokinetic study comparing subcutaneous and intravenous palonosetron in cancer patients treated with platinum based chemotherapy

BACKGROUND: Palonosetron is a potent second generation 5- hydroxytryptamine-3 selective antagonist which can be administered by either intravenous (IV) or oral routes, but subcutaneous (SC) administration of palonosetron has never been studied, even though it could have useful clinical applications. In this study, we evaluate the bioavailability of SC palonosetron. PATIENTS AND METHODS: Patients treated with platinum-based chemotherapy were randomized to receive SC or IV palonosetron, followed by the alternative route in a crossover manner, during the first two cycles of chemotherapy. Blood samples were collected at baseline and 10, 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8, 12 and 24 h after palonosetron administration. Urine was collected during 12 hours following palonosetron. We compared pharmacokinetic parameters including AUC0-24h, t1/2, and Cmax observed with each route of administration by analysis of variance (ANOVA). RESULTS: From October 2009 to July 2010, 25 evaluable patients were included. AUC0-24h for IV and SC palonosetron were respectively 14.1 and 12.7 ng × h/ml (p = 0.160). Bioavalability of SC palonosetron was 118% (95% IC: 69-168). Cmax was lower with SC than with IV route and was reached 15 minutes following SC administration. CONCLUSIONS: Palonosetron bioavailability was similar when administered by either SC or IV route. This new route of administration might be specially useful for outpatient management of emesis and for administration of oral chemotherapy

Combined drying of Nopal pads (Opuntia ficus‐indica): optimization of osmotic dehydration as a pretreatment before hot air drying

The aim of this work was to optimize the osmotic dehydration (OD) as a pretreatment before hot air drying (HAD) in Nopal pads. A Box–Behnken experimental design was used to optimize the OD conditions with respect to physicochemical and chromatic parameters, and mechanical properties of Nopal pads. Factors studied were: Three concentrations of sucrose (30, 40, and 50°Brix), calcium lactate (1, 2, and3%), and immersion time (1.5, 2.5, and 3.5 hr). Results showed that sucrose concentration and immersion time were the variables with higher influence. Quality properties mentioned before and the final mineral content of the dried samples (at 60°C for 48 hr) were analyzed. The combined drying (OD + HAD) reduced the moisture content in the range of 23% to 30% compared to HAD alone. It was found that the optimization of OD allowed preserving the quality properties, being a good alternative to give an added value for dried Nopal padsFil: Rodriguez, Anabel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Tecnología de Alimentos; Argentina.Centro de Investigación y Desarrollo en Criotecnología de Alimentos; Argentina. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Sancho, Ana Maria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Tecnología de Alimentos; Argentina.Fil: Barrio, Yanina Ximena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Argentina de la Empresa. Facultad de Ingeniería y Ciencias. Departamento de Biotecnología y Tecnología Alimentaria ; Argentina.Fil: Rosito, Pablo. Universidad Argentina de la Empresa. Facultad de Ingeniería y Ciencias. Departamento de Biotecnología y Tecnología Alimentaria ; Argentina.Fil: Gozzi, Marta Sofía. Universidad Argentina de la Empresa. Instituto de Tecnología; Argentina

Assessment of Epidermal Growth Factor Receptor and K-Ras Mutation Status in Cytological Stained Smears of Non-Small Cell Lung Cancer Patients: Correlation with Clinical Outcomes

EGFR and K-ras mutation status was determined from tumor DNA extracted from cytological samples from non-small cell lung cancer patients, with results comparable with those from biopsy samples. Clinical outcomes of patients harboring mutations and their response to tyrosine kinase inhibitor therapy are also discussed

Randomized pharmacokinetic study comparing subcutaneous and intravenous palonosetron in cancer patients treated with platinum based chemotherapy

BACKGROUND: Palonosetron is a potent second generation 5- hydroxytryptamine-3 selective antagonist which can be administered by either intravenous (IV) or oral routes, but subcutaneous (SC) administration of palonosetron has never been studied, even though it could have useful clinical applications. In this study, we evaluate the bioavailability of SC palonosetron. PATIENTS AND METHODS: Patients treated with platinum-based chemotherapy were randomized to receive SC or IV palonosetron, followed by the alternative route in a crossover manner, during the first two cycles of chemotherapy. Blood samples were collected at baseline and 10, 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8, 12 and 24 h after palonosetron administration. Urine was collected during 12 hours following palonosetron. We compared pharmacokinetic parameters including AUC0-24h, t1/2, and Cmax observed with each route of administration by analysis of variance (ANOVA). RESULTS: From October 2009 to July 2010, 25 evaluable patients were included. AUC0-24h for IV and SC palonosetron were respectively 14.1 and 12.7 ng × h/ml (p = 0.160). Bioavalability of SC palonosetron was 118% (95% IC: 69-168). Cmax was lower with SC than with IV route and was reached 15 minutes following SC administration. CONCLUSIONS: Palonosetron bioavailability was similar when administered by either SC or IV route. This new route of administration might be specially useful for outpatient management of emesis and for administration of oral chemotherapy

Randomized Pharmacokinetic Study Comparing Subcutaneous and Intravenous Palonosetron in Cancer Patients Treated with Platinum Based Chemotherapy

<div><p>Background</p><p>Palonosetron is a potent second generation 5- hydroxytryptamine-3 selective antagonist which can be administered by either intravenous (IV) or oral routes, but subcutaneous (SC) administration of palonosetron has never been studied, even though it could have useful clinical applications. In this study, we evaluate the bioavailability of SC palonosetron.</p><p>Patients and Methods</p><p>Patients treated with platinum-based chemotherapy were randomized to receive SC or IV palonosetron, followed by the alternative route in a crossover manner, during the first two cycles of chemotherapy. Blood samples were collected at baseline and 10, 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8, 12 and 24 h after palonosetron administration. Urine was collected during 12 hours following palonosetron. We compared pharmacokinetic parameters including AUC_0–24h, t_1/2, and C_max observed with each route of administration by analysis of variance (ANOVA).</p><p>Results</p><p>From October 2009 to July 2010, 25 evaluable patients were included. AUC0–24h for IV and SC palonosetron were respectively 14.1 and 12.7 ng × h/ml (p = 0.160). Bioavalability of SC palonosetron was 118% (95% IC: 69–168). C_max was lower with SC than with IV route and was reached 15 minutes following SC administration.</p><p>Conclusions</p><p>Palonosetron bioavailability was similar when administered by either SC or IV route. This new route of administration might be specially useful for outpatient management of emesis and for administration of oral chemotherapy.</p><p><i>Trial Registration</i></p><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT01046240?term=NCT01046240&rank=1" target="_blank">NCT01046240</a></p></div

Palonosetron mean plasma levels (±SD) following administration of a single 250 µg dose IV or SC (first two hours).

<p>Palonosetron mean plasma levels (±SD) following administration of a single 250 µg dose IV or SC (first two hours).</p

Palonosetron mean plasma levels (±SD) following a single 250 µg dose IV or SC (first 24 h, semilogarithmic graph).

<p>Palonosetron mean plasma levels (±SD) following a single 250 µg dose IV or SC (first 24 h, semilogarithmic graph).</p

Pharmacokinetic characteristics of subcutaneous and intravenous palonosetron, compared by Student's t test for paired samples and Wilcoxon's test.

<p>IV: intravenous. SC: subcutaneous. AUC_0–24h: area under the plasma drug concentration-time curve between 0 to 24 hours. n.s.s: non statistically significant. C_max: maximum concentration. t_max: time to maximum concentration. k_e: elimination constant t_1/2: half life. C: concentration. A_e: amount of palonosetron eliminated by urine.</p><p>*: Wilcoxon's test.</p>1<p>: Median and range.</p

Patient characteristics.

<p>Patient characteristics.</p