Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group

Our objective was to determine whether oral etoposide and cisplatin combination (EoP) is superior to paclitaxel in the treatment of advanced breast cancer (ABC) patients pretreated with anthracyclines. From December 1997 to August 2003, 201 patients were randomised, 100 to EoP and 101 to paclitaxel arms. Four patients in each arm were ineligible. The doses of etoposide and cisplatin were 50 mg p.o. twice a day for 7 days and 70 mg m−2 intravenously (i.v.) on day 1, respectively, and it was 175 mg m−2 on day 1 for paclitaxel. Both treatments were repeated every 3 weeks. A median of four cycles of study treatment was given in both arms. The response rate obtained in the EoP arm was significantly higher (36.3 vs 22.2%; P=0.038). Median response duration was longer for the EoP arm (7 vs 4 months) (P=0.132). Also, time to progression was significantly in favour of the EoP arm (5.5 vs 3.9 months; P=0.003). Median overall survival was again significantly longer in the EoP arm (14 vs 9.5 months; P=0.039). Toxicity profile of both groups was similar. Two patients in each arm were lost due to febrile neutropenia. The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines

Using RNA-Seq for gene identification, polymorphism detection and transcript profiling in two alfalfa genotypes with divergent cell wall composition in stems

<p>Abstract</p> <p>Background</p> <p>Alfalfa, [<it>Medicago sativa </it>(L.) sativa], a widely-grown perennial forage has potential for development as a cellulosic ethanol feedstock. However, the genomics of alfalfa, a non-model species, is still in its infancy. The recent advent of RNA-Seq, a massively parallel sequencing method for transcriptome analysis, provides an opportunity to expand the identification of alfalfa genes and polymorphisms, and conduct in-depth transcript profiling.</p> <p>Results</p> <p>Cell walls in stems of alfalfa genotype 708 have higher cellulose and lower lignin concentrations compared to cell walls in stems of genotype 773. Using the Illumina GA-II platform, a total of 198,861,304 expression sequence tags (ESTs, 76 bp in length) were generated from cDNA libraries derived from elongating stem (ES) and post-elongation stem (PES) internodes of 708 and 773. In addition, 341,984 ESTs were generated from ES and PES internodes of genotype 773 using the GS FLX Titanium platform. The first alfalfa (<it>Medicago sativa</it>) gene index (MSGI 1.0) was assembled using the Sanger ESTs available from GenBank, the GS FLX Titanium EST sequences, and the <it>de novo </it>assembled Illumina sequences. MSGI 1.0 contains 124,025 unique sequences including 22,729 tentative consensus sequences (TCs), 22,315 singletons and 78,981 pseudo-singletons. We identified a total of 1,294 simple sequence repeats (SSR) among the sequences in MSGI 1.0. In addition, a total of 10,826 single nucleotide polymorphisms (SNPs) were predicted between the two genotypes. Out of 55 SNPs randomly selected for experimental validation, 47 (85%) were polymorphic between the two genotypes. We also identified numerous allelic variations within each genotype. Digital gene expression analysis identified numerous candidate genes that may play a role in stem development as well as candidate genes that may contribute to the differences in cell wall composition in stems of the two genotypes.</p> <p>Conclusions</p> <p>Our results demonstrate that RNA-Seq can be successfully used for gene identification, polymorphism detection and transcript profiling in alfalfa, a non-model, allogamous, autotetraploid species. The alfalfa gene index assembled in this study, and the SNPs, SSRs and candidate genes identified can be used to improve alfalfa as a forage crop and cellulosic feedstock.</p

Aberrant nocturnal cortisol and disease progression in women with breast cancer

PURPOSE: While a relationship between disruption of circadian rhythms and the progression of cancer has been hypothesized in field and epidemiologic studies, it has never unequivocally demonstrated. We determined the circadian rhythm of cortisol and sleep in women with advanced breast cancer (ABC) under the conditions necessary to allow for the precise measurement of these variables. METHODS: Women with ABC (n=97) and age-matched controls (n=24) took part in a 24-hour intensive physiological monitoring study involving polysomnographic sleep measures and high density plasma sampling. Sleep was scored using both standard clinical metrics and power spectral analysis. Three-harmonic regression analysis and functional data analysis were used to assess the 24-hour and sleep-associated patterns of plasma cortisol, respectively. RESULTS: The circadian pattern of plasma cortisol as described by its timing, timing relative to sleep, or amplitude was indistinguishable between women with ABC and age-matched controls (p's>0.11, t-tests). There was, however, an aberrant spike of cortisol during the sleep of a subset of women, during which there was an 8-fold increase in the amount of objectively-measured wake time (p<0.004, Wilcoxon Signed-Rank). This cortisol aberration was associated with cancer progression such that the larger the aberration, the shorter the disease-free interval (time from initial diagnosis to metastasis; r=−0.30, p=0.004; linear regression). The same aberrant spike was present in a similar percent of women without ABC and associated with concomitant sleep disruption. CONCLUSIONS: A greater understanding of this sleep-related cortisol abnormality, possibly a vulnerability trait, is likely important in our understanding of individual variation in the progression of cancer

One-step Bone Marrow-derived Cell Transplantation in Talar Osteochondral Lesions

The ideal treatment of osteochondral lesions is debatable. Although autologous chondrocyte implantation provides pain relief, the need for two operations and high costs has prompted a search for alternatives. Bone marrow-derived cells may represent the future in osteochondral repair. Using a device to concentrate bone marrow-derived cells and collagen powder or hyaluronic acid membrane as scaffolds for cell support and platelet gel, a one-step arthroscopic technique was developed for cartilage repair. We performed an in vitro preclinical study to verify the capability of bone marrow-derived cells to differentiate into chondrogenic and osteogenic lineages and to be supported onto scaffolds. In a prospective clinical study, we investigated the ability of this technique to repair talar osteochondral lesions in 48 patients. Minimum followup was 24 months (mean, 29 months; range, 24–35 months). Clinical results were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) score and the influence of scaffold type, lesion area, previous surgeries, and lesion depth was considered. MRI and histologic evaluation were performed. The AOFAS score improved from 64.4 ± 14.5 to 91.4 ± 7.7. Histologic evaluation showed regenerated tissue in various degrees of remodeling although none showed entirely hyaline cartilage. These data suggest the one-step technique is an alternative for cartilage repair, permitting improved functional scores and overcoming the drawbacks of previous techniques

The Development of New Radionuclide Generator Systems for Nuclear Medicine Applications

Radioisotope generator systems have traditionally played a central role in nuclear medicine in providing radioisotopes for both research and clinical applications. In this paper, the development of several tungsten-188/rhenium-188 prototype generators which provide rhenium-188 for radioimmunotherapy (RAIT) is discussed. The authors have recently demonstrated that carrier-free iridium-194 can be obtained from the activated carbon system from decay of reactor-produced osmium-194 for potential RAIT applications. Instrumentation advances such as the new generation of high-count-rate (fast) gamma camera systems for first-pass technology require the availability of generator-produced ultra short-lived radioisotopes for radionuclide angiography (RNA). The activated carbon generator is an efficient system to obtain ultra short-lived iridium-191 m from osmium-191 for RNA. In addition, the growing number of PET centers has stimulated research in generators which provide positron-emitting radioisotopes. Copper-62, obtained from the zinc-62 generator, is currently used for PET evaluation of organ perfusion. The availability of the parent radioisotopes, the fabrication and use of these generators, and the practical factors for use of these systems in the radiopharmacy are discussed. 74 refs., 6 figs., 5 tabs