Sweet cherry phytochemicals: Identification and characterization by HPLC-DAD/ESI-MS in six sweet-cherry cultivars grown in Valle del Jerte (Spain)

Individual anthocyanin pigments and phenolic compounds were isolated, identified and quantified in six different sweet-cherry cultivars (Prunus avium L.) grown in Valle del Jerte area (Spain). An extractive-chromatographic method has been optimized for one-step extraction and simultaneous determination of all the studied components by HPLC/DAD-MS. The highest levels of phytochemicals were found in the autochthonous sweet-cherry cultivars that belong to the Protected Designation of Origin (POD) Cereza del Jerte. Van cultivar showed the lowest level of anthocyanin pigments and phenolic compounds. The most abundant anthocyanin pigment in all the studied cultivars was cyanidin-3-rutinoside (105 mg/100 g fresh weight (fwt) in Pico Negro sweet-cherry cultivar). The most abundant phenolic compound was the flavanol p-coumaroylquinic acid (130 mg/100 g fwt in Pico Negro sweet-cherry cultivar). In addition, chemical attributes (antioxidant activity, soluble solid content and pH) were also evaluated.     

Intraductal Delivery of Adenoviruses Targets Pancreatic Tumors in Transgenic Ela-myc Mice and Orthotopic Xenografts

Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route.We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTK^T plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TK^T oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p<0.0001) when combined with GCV. Of notice, both AduPARTK^T and ICOVIR15-TK^T antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration.In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors.     

Evaluation of tumor response after locoregional therapies in hepatocellular carcinoma

BACKGROUND:

Evaluation of response to treatment is a key aspect in cancer therapy. Response Evaluation Criteria in Solid Tumors (RECIST) are used in most oncology trials, but those criteria evaluate only unidimensional tumor measurements and disregard the extent of necrosis, which is the target of all effective locoregional therapies. Therefore, the European Association for the Study of the Liver (EASL) guidelines recommended that assessment of tumor response should incorporate the reduction in viable tumor burden. The current report provides an assessment of the agreement/concordance between both RECIST and the EASL guidelines for the evaluation of response to therapy.

METHODS:

The authors evaluated a cohort of 55 patients within prospective studies, including 24 patients with hepatocellular carcinoma who underwent transarterial chemoembolization (TACE) with drug eluting beads (DEB‐TACE) and 31 patients who underwent percutaneous ablation (percutaneous ethanol injection [PEI]/radiofrequency [RF]). Triphasic helical computed tomography scans were performed at baseline, at 1 month, and at 3 months after procedure, and 2 independent radiologists evaluated tumor response.

RESULTS:

Evaluating response according to RECIST criteria, no patients achieved a complete response (CR), 21.8% of patients achieved a partial response (PR) (none in the PEI/RF group), 47.3% of patients had stable disease (SD), and 30.9% of patients had progressive disease (PD). When response was evaluated according to the EASL guidelines, 54.5% of patients achieved a CR, 27.3% of patients achieved a PR, 3.6% of patients had SD, and 14.5% had PD. The κ coefficient was 0.193 (95% confidence interval, 0.0893‐0.2967; P < .0001).

CONCLUSIONS:

RECIST missed all CRs and underestimated the extent of partial tumor response because of tissue necrosis, wrongly assessing the therapeutic efficacy of locoregional therapies. This evaluation should incorporate the reduction in viable tumor burden as recognized by nonenhanced areas on dynamic imaging studies. Cancer, 2009. © 2008 American Cancer Society.     

Natural history of hepatocellular carcinoma in Spain. Five year's experience in 249 cases

In this study we attempted to define the clinical pattern and prognosis of hepatocellular carcinoma (HCC) patients in Spain. Two hundred and forty-nine patients were included in the study. One hundred and eighty-seven were male and 62 female, with their mean age being 62.5 +/- 0.6 years. The majority of patients (92.8%) had an underlying cirrhosis. In most of the patients, the disease appeared as decompensated liver disease. Only 18.5% of the HCC cases were asymptomatic. Only 8.2% of the cases were HBsAg positive. alpha-Fetoprotein reached diagnostic values in only 37.2% of the patients. Surgical treatment was successfully performed in 14 patients: one underwent orthotopic liver transplantation and the 13 others complete tumor resection. Chemotherapy was administered to 38 subjects, while percutaneous ethanol injection was applied in seven cases. Patients receiving only symptomatic treatment, comprised 76.7%. Survival was related to tumor size and liver function. While the median survival of the whole series was 3.3 +/- 0.4 months, it was 14.5 +/- 2.2 months in patients with preserved liver function and small tumors. These results reflect that in Spain HCC patients are diagnosed at a moderately advanced phase. Since early diagnosis is the only way to increase the proportion of patients suitable for curative treatment, early detection plans are mandatory in the population at risk.     

Histamine‐N‐methyl transferase polymorphism and risk for multiple sclerosis

Background: Histamine N‐methyltransferase (HNMT) is the main metabolizing enzyme of histamine (a mediator of inflammation implicated in the pathogenesis of multiple sclerosis‐MS) in the CNS. We have investigated the possible association between a single nucleotide polymorphism of the HNMT (chromosome 2q22.1), that causes the amino acid substitution Thr105Ile (decreasing enzyme activity) and the risk for MS. Methods: We studied the frequency of the HNMT genotypes and allelic variants in 228 MS patients and 295 healthy controls using a PCR‐RLFP method. Results: The frequencies of the HNMT genotypes and allelic variants did not differ significantly between MS patients and controls, and were unrelated with the age of onset of MS, gender, and course of MS. Conclusion: The HNMT polymorphism is not related with the risk for MS.