Diversity of a Xylella fastidiosa population isolated from Citrus sinensis affected by Citrus variegated chlorosis in Brazil

Diversity of a population of Xylella fastidiosa isolated from sweet orange plants showing citrus variegated chlorosis (CVC) symptoms was assessed by PCR-based techniques. Thirty-seven strains were isolated throughout the 1997 year in the orange belt of Sao Paulo State, Brazil. Strains isolated from coffee, grape, oleander and plum were also included as outgroup reference strains. PCR amplification of the spacer sequence between the 16-23S rDNA yielded one fragment of 1.2 kb. Digestion with restriction enzymes, DdeI, HinfI or Sau3AI generated identical RFLP patterns for citrus and coffee strains, which could be distinguished from the strains isolated from the other hosts. Eight RAPD primers were also used and the results showed similarity from 80 to 100% within the CVC population. Three prevalent haplotypes comprising 24 CVC strains showed a high level of similarity (95%). Strains from the other hosts clustered apart from CVC strains, forming distinct groups.21459359

A phase I trial of the dual farnesyltransferase and geranylgeranyltransferase inhibitor L-778,123 and radiotherapy for locally advanced pancreatic cancer.

PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed