Marker Assisted Foreground Selection for Identification of Striga Resistant Backcross Lines in Sorghum bicolor

Striga is a major constraint to sorghum production causing high yield loss due to increasing infestation. Locally-adapted cultivars with resistant genes/QTLs could be an effective control strategy for Striga. Marker-Assisted Foreground Selection was used to select backcross lines possessing Striga resistance QTLs from N13. Marker polymorphism was conducted for the donor parent N13 and 10 recurrent parents using 10 Simple Sequence Repeat (SSR) markers. Recurrent parents with SSR alleles, polymorphic to the donor parent allele were selected. F1 lines were developed by making a cross between the selected recurrent parent and the donor. The F1 were confirmed for heterozygosity using SSR markers. Selected heterozygote F1s were backcrossed to their recurrent parent to develop backcross populations (BC1F1 and BC2F1). BC1F1 and BC2F1 populations were genotyped using SSR markers flanking the Striga resistant QTLs in N13. Forty two DANYANA-N13 BC2F1 lines (with 4 QTLs in 3 lines, 3 QTLs in 10 lines and other 28 lines having 1 to 2 QTLs) were selected for the presence of N13 QTLs. Forty three SAMSORG39-N13 BC2F1 lines (with 3 QTLs in 2 lines while 41 lines had 1 to 2 QTLs) were also selected for the presence of N13 QTLs. Although, selected lines will be genotyped for the recovery of recurrent parent background and evaluated to identify elite genotypes for possible release as varieties, the successful introgression of Striga resistance QTLs using Marker Assisted Selection suggests that in developing superior sorghum varieties, breeders could make use of molecular marker technologies to speed up breeding programmes

Genetic diversity assessment of sorghum (Sorghum bicolor (L.) Moench) accessions using single nucleotide polymorphism markers

Sorghum (Sorghum bicolor (L.) Moench) is an important resource to the national economy and it is essential to assess the genetic diversity in existing sorghum germplasm for better conservation, utilization and crop improvement. The aim of this study was to evaluate the level of genetic diversity within and among sorghum germplasms collected from diverse institutes in Nigeria and Mali using Single Nucleotide Polymorphic markers. Genetic diversity among the germplasm was low with an average polymorphism information content value of 0.24. Analysis of Molecular Variation revealed 6%variation amonggermplasmand 94%withingermplasms.Dendrogramrevealed threegroupsof clusteringwhich indicatevariationswithinthegermplasms. Privatealleles identified inthesorghum accessions from National Center for Genetic Resources and Biotechnology, Ibadan, Nigeria and International Crop Research Institute for the Semi-Arid Tropics, Kano, Nigeria shows their prospect for sorghum improvement and discovery of new agronomic traits. The presence of private alleles and genetic variation within the germplasms indicates that the accessions are valuable resources for future breeding programs

Impact of concomitant administration of gastric acid-suppressive agents and pazopanib on outcomes in soft-tissue sarcoma patients treated within the EORTC 62043/62072 trials

Purpose: Pazopanib is active in soft-tissue sarcoma (STS). Because pazopanib absorption is pH-dependent, coadministration with gastric acid-suppressive (GAS) agents such as proton pump inhibitors could affect exposure of pazopanib, and thereby its therapeutic effects.Experimental Design: The EORTC 62043 and 62072 were single-arm phase II and placebo-controlled phase III studies, respectively, of pazopanib in advanced STS. We first compared the outcome of patients treated with pazopanib with or without GAS agents for ≥80% of treatment duration, and subsequently using various thresholds. The impact of concomitant GAS therapy was assessed on progression-free survival (PFS) and overall survival (OS) using multivariate Cox models, exploring and comparing also the potential effect on placebo-treated patients.Results: Of 333 eligible patients, 59 (17.7%) received concomitant GAS therapy for >80% of pazopanib treatment duration. Median PFS was shorter in GAS therapy users versus nonusers: 2.8 vs. 4.6 months, respectively [HR, 1.49; 95% confidence interval (CI), 1.11-1.99; P = 0.01]. Concomitant administration of GAS therapy was also associated with a shorter median OS: 8.0 vs. 12.6 months (HR, 1.81; 95% CI, 1.31-2.49; P < 0.01). The longer the overlapping use of GAS agents and pazopanib, the worse the outcome with pazopanib. These effects were not observed in placebo-treated patients (HR, 0.82; 95% CI, 0.51-1.34; P = 0.43 for PFS and HR, 0.84; 95% CI, 0.48-1.48; P = 0.54 for OS).Conclusions: Coadministration of long-term GAS therapy with pazopanib was associated with significantly shortened PFS and OS. Withdrawal of GAS agents must be considered whenever possible. Therapeutic drug monitoring of pazopanib plasma concentrations may be helpful for patients on pazopanib and GAS therapy

A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer

Background: Serum interleukin (IL)-6 levels correlate with disease outcomes in renal cell carcinoma (RCC) patients. Siltuximab, a chimeric, murine-human mAb against IL-6, was evaluated in a three-part phase I/II study in patients with progressive metastatic RCC. Methods: In part 1, 11 patients received 1, 3, 6, or 12 mg kg–1 at weeks 1, 4 and q2w × 2 thereafter; in part 2, 37 patients randomly received 3 or 6 mg kg–1 q3w × 4; in part 3, 20 low-risk patients received 6 mg kg–1 q2w × 6. Modified WHO response criteria were assessed at weeks 7, 11, the 6-week follow-up, and when clinically indicated. Results: Siltuximab was well tolerated overall, with no maximum tolerated dose or immune response observed. In all, 5 out of 11, 17 out of 37, and 9 out of 20 patients in parts 1, 2, and 3, respectively, received extended treatment beyond 4–6 initial infusions. In part 2, stable disease (SD) (greater than or equal to11weeks) or better was achieved by 11 out of 17 (65%) 3 mg kg–1 treated patients (one partial response (PR) ~8 months, 10 SD) and 10 out of 20 (50%) 6 mg kg–1 treated patients (10 SD). In part 3, documented complete or PR was not observed, but 13 out of 20 (65%) patients achieved SD. Conclusion: Siltuximab stabilised disease in >50% of progressive metastatic RCC patients. One PR was observed. Given the favourable safety profile of siltuximab and poor correlation of tumour shrinkage with clinical benefit demonstrated for other non-cytotoxic therapies, further evaluation of dose-escalation strategies and/or combination therapy may be considered for patients with RCC

First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)—a systematic review and individual patient data meta-analysis

Evidence for prognosis and treatment of elderly patient with primary central nervous system is limited. High-dose methotrexate should be applied whenever possible, especially combination with oral alkylating agents is a promising approach. Further combinations with other intravenous drugs do not seem to improve outcome. More prospective trials designed for elderly PCNSL patients are warrante

A phase I/II study of 4 monthly courses of high-dose cyclophosphamide and thiotepa for metastatic breast cancer patients

This pilot phase I/II study intended to determine the maximum tolerated dose of cyclophosphamide and thiotepa administered on four consecutive courses with peripheral blood progenitor cell and granulocyte-colony stimulating factor support, as first-line therapy for hormone-refractory metastatic breast cancer patients. Twenty-eight patients were entered in the study. After two courses of epirubicin (120 mg m−2) and cyclophosphamide (2 g m−2) followed by granulocyte-colony stimulating factor injection and leukaphereses, patients received four cycles of cyclophosphamide and thiotepa. Each cycle was followed by peripheral blood progenitor cell and granulocyte-colony stimulating factor supports, then repeated every 28 to 35 days. Six escalating dose levels of cyclophosphamide and thiotepa were planned, beginning at cyclophosphamide 1.5 g m−2 and thiotepa 200 mg m−2. At least three patients were enrolled for each dose level. Eighteen patients completed the study. The maximum tolerated dose was 3000 mg m−2 cyclophosphamide and 400 mg m−2 thiotepa per course. Haematological toxicity was manageable on an outpatient basis and did not increase significantly with dose escalation. Dose-limiting toxicity was chemotherapy-induced immuno-suppression, which resulted in one toxic death and two life-threatening infections. Median times to treatment failure and survival were 11 and 26 months, respectively. Three patients were alive, free of disease 30 months after completion of the study. Such therapy allows for high-dose intensity and high cumulative doses on a short period of time with manageable toxicity

Incidence and prognostic value of tumour cells detected by RT–PCR in peripheral blood stem cell collections from patients with Ewing tumour

To retrospectively evaluate the incidence of tumour cell contamination of peripheral blood stem cell (PBSC) collections and to correlate these data with the clinical outcome after high-dose chemotherapy (HDCT) with stem cell rescue in patients with a high-risk Ewing tumour. Peripheral blood stem cell collections obtained from 171 patients were analysed. Tumour contamination was assessed by reverse transcriptase–polymerase chain reaction (RT–PCR). The files of 88 patients who underwent HDCT followed by PBSC reinfusion were reviewed in detail, and their outcome compared to the PBSC RT–PCR results. Seven of 88 PBSC collections (8%) contained tumour cells as detected by RT–PCR. Peripheral blood stem cells were collected after a median of five cycles of chemotherapy. No clinical factor predictive of tumour cell contamination of PBSC harvest could be identified. Event-free survival (EFS) and overall survival (OS) of the whole study population were 45.3 % and 51.8 % at 3 years from the date of the graft, respectively. Forty-five patients relapsed with a median time of 15 months after graft, only four of whom had tumour cell contamination of the PBSC harvest. Tumour cell contamination of PBSC collection is rare and does not seem to be associated with a significantly poorer EFS or OS in this high-risk population

On Component Forces in Physics: A Pragmatic View

Do component forces exist? I argue that the answer lies in the affirmative, on historical and operational grounds