Phase II Study of Ifosfamide+Doxorubicin in Patients With Advanced Synovial Sarcomas (E1793): A Trial of the Eastern Cooperative Oncology Group

Purpose Because we had observed in the synovial sarcoma subgroup of a broad phase III advanced soft tissue sarcoma study a significantly greater objective regression rate from ifosfamide+doxorubicin (88%) than from doxorubicin alone (20%) (P = 0.02), the Eastern Cooperative Oncology Group (ECOG) decided to further assess this two drug combination in a subsequent Phase II study

Detecting Cancer Gene Networks Characterized by Recurrent Genomic Alterations in a Population

High resolution, system-wide characterizations have demonstrated the capacity to identify genomic regions that undergo genomic aberrations. Such research efforts often aim at associating these regions with disease etiology and outcome. Identifying the corresponding biologic processes that are responsible for disease and its outcome remains challenging. Using novel analytic methods that utilize the structure of biologic networks, we are able to identify the specific networks that are highly significantly, nonrandomly altered by regions of copy number amplification observed in a systems-wide analysis. We demonstrate this method in breast cancer, where the state of a subset of the pathways identified through these regions is shown to be highly associated with disease survival and recurrence

Phase II Trial of Dolastatin-10, a Novel Anti-Tubulin Agent, in Metastatic Soft Tissue Sarcomas

Patients:Soft tissue sarcomas are uncommon malignancies with few therapeutic options for recurrent or metastatic disease. Dolastatin-10 (Dol-10) is a pentapeptide anti-microtubule agent that binds to tubulin sites distinct from vinca alkaloids. Based on the novel mechanism of action, limited activity of other anti-microtubular agents, and anti-neoplastic activity in pre-clinical screening of Dol-10, this multi-institutional phase II study was conducted to determine the objective response rate of Dol-10 in recurrent or metastatic soft tissue sarcomas that had not been treated with chemotherapy outside of the adjuvant setting

Phase II study of IfosfamideþDoxorubicin in patients with advanced synovial sarcomas (E1793): a trial of the Eastern Cooperative Oncology Group

Abstract Purpose Because we had observed in the synovial sarcoma subgroup of a broad phase III advanced soft tissue sarcoma study a significantly greater objective regression rate from ifosfamideþdoxorubicin (88%) than from doxorubicin alone (20%) ( P ¼ 0.02), the Eastern Cooperative Oncology Group (ECOG) decided to further assess this two drug combination in a subsequent Phase II study. Patients Between 1994 and 1999, twelve adult patients with advanced synovial sarcomas were enrolled to receive, as their initial chemotherapy, ifosfamide 7.5 gm/m 2 plus doxorubicin 60 mg/m 2 , given intravenously over two consecutive days every 3 weeks. Methods Each day for 2 days doxorubicin 30 mg/m 2 was infused over 5 min through a running i.v., followed by ifosfamide 3750 mg/m 2 over 4 h. Continuous i.v. fluid was infused at 300 mL /h for 3 h on day 1, before chemotherapy was begun; then the infusion was continued at 100 mL /h for a total of 3 days. Mesna 750 mg/m 2 was given 15 min before ifosfamide and at 4 and 8 h after ifosfamide on days 1 and 2 of each treatment cycle. Filgrastim (G-CSF) 5 mg/kg was given subcutaneously each day for 14 days beginning on day 3 of each treatment cycle to limit the severity of neutropenia. Results Five of our 12 patients (42%) experienced partial regression of their advanced synovial sarcomas; however, this first stage result was borderline for proceeding to the second planned stage of accrual and our case accrual was quite poor. Thus, the study was closed after stage one accrual. Our patients received a median of four cycles of chemotherapy (range: 1 to 6). All patients experienced at least grade 3 neutropenia (grade 4 in nine of them), and one patient died of treatment-related sepsis following the initial cycle of chemotherapy. Median survival was 11 months

Customisation of the Exome Data Analysis Pipeline Using a Combinatorial Approach

The advent of next generation sequencing (NGS) technologies have revolutionised the way biologists produce, analyse and interpret data. Although NGS platforms provide a cost-effective way to discover genome-wide variants from a single experiment, variants discovered by NGS need follow up validation due to the high error rates associated with various sequencing chemistries. Recently, whole exome sequencing has been proposed as an affordable option compared to whole genome runs but it still requires follow up validation of all the novel exomic variants. Customarily, a consensus approach is used to overcome the systematic errors inherent to the sequencing technology, alignment and post alignment variant detection algorithms. However, the aforementioned approach warrants the use of multiple sequencing chemistry, multiple alignment tools, multiple variant callers which may not be viable in terms of time and money for individual investigators with limited informatics know-how. Biologists often lack the requisite training to deal with the huge amount of data produced by NGS runs and face difficulty in choosing from the list of freely available analytical tools for NGS data analysis. Hence, there is a need to customise the NGS data analysis pipeline to preferentially retain true variants by minimising the incidence of false positives and make the choice of right analytical tools easier. To this end, we have sampled different freely available tools used at the alignment and post alignment stage suggesting the use of the most suitable combination determined by a simple framework of pre-existing metrics to create significant datasets

Mammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic bottleneck

Human infection with avian influenza A(H7N9) virus is associated mainly with the exposure to infected poultry. The factors that allow interspecies transmission but limit human-to-human transmission are unknown. Here we show that A/Anhui/1/2013(H7N9) influenza virus infection of chickens (natural hosts) is asymptomatic and that it generates a high genetic diversity. In contrast, diversity is tightly restricted in infected ferrets, limiting further adaptation to a fully transmissible form. Airborne transmission in ferrets is accompanied by the mutations in PB1, NP and NA genes that reduce viral polymerase and neuraminidase activity. Therefore, while A(H7N9) virus can infect mammals, further adaptation appears to incur a fitness cost. Our results reveal that a tight genetic bottleneck during avian-to-mammalian transmission is a limiting factor in A(H7N9) influenza virus adaptation to mammals. This previously unrecognized biological mechanism limiting species jumps provides a measure of adaptive potential and may serve as a risk assessment tool for pandemic preparedness.published_or_final_versio

Bartonella quintana coinfection with Mycobacterium avium complex and CMV in an AIDS patient: case presentation

BACKGROUND: As a greater number of HIV-infected patients survive despite profound immunodepression due to medical progress, we face complex infection with multiple agents in AIDS-patients. CASE PRESENTATION: We report the case of an AIDS patient with a primary clinical presentation suggestive of bacillary angiomatosis. We also found in cutaneous lesions Mycobacterium avium complex and cytomegalovirus. CONCLUSION: This clinical case illustrates the possibility of multiple coinfections in AIDS patients and the need to be exhaustive in evaluating infectious diseases in severely immunocompromised patients