Evaluation of a multiplex PCR for detection of serotypes K1, K2 and K5 in Klebsiella sp. and comparison of isolates within these serotypes.

A multiplex PCR using targets within the serotype-specific region of the capsular polysaccharide synthesis gene cluster of serotypes K1, K2 and K5 was evaluated using the 77 reference serotype strains of Klebsiella, and a panel of clinical isolates subjected previously to conventional serotyping. The PCR was highly specific for these serotypes, which are those most associated with virulence in humans and horses. PCR confirmed that isolates of the K5 serotype had cross-reacted with antiserum for other serotypes, particularly for K7.

Does patient position influence Doppler signal quality from the USCOM ultrasonic cardiac output monitor?

Background: The USCOM1A continuous wave cardiac output monitor (USCOM Pty Ltd., Sydney, NSW, Australia) is a novel Doppler-based device used to measure cardiac output noninvasively. The proper alignment of the transducer, and hence the ultrasound beam to the aortic or pulmonary outflow tracts, is essential to acquire accurate measurements and often much time is spent on transducer and/or patient positioning.

Phase I study of MGCD0103 given as a three-times-per-week oral dose in patients with advanced solid tumors.

Purpose: MGCD0103 is a novel isotype-selective inhibitor of human histone deaceylases (HDACs) with the potential to regulate aberrant gene expression and restore normal growth control in malignancies.

Patients And Methods: A phase I trial of MGCD0103, given as a three-times-per-week oral dose for 2 of every 3 weeks, was performed in patients with advanced solid tumors. Primary end points were safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD) assessments of HDAC activity, and histone acetylation status in peripheral WBCs.

Molecular-targeted therapies in the treatment of squamous cell carcinomas of the head and neck.

Purpose Of Review: The present study reviews recent developments of molecular-targeted therapies in the treatment of recurrent and/or metastatic head and neck squamous cell carcinoma. It also highlights ongoing research regarding predictive markers of sensitivity or resistance to anti-epidermal growth factor receptor agents and discusses some promising novel targets in head and neck squamous cell carcinoma, as well as clinical trial design challenges.

Recent Findings: Phase III randomized studies have brought the proof that cetuximab, an anti-epidermal growth factor receptor agent, is able to improve survival, either in combination with radiation therapy or in first-line treatment for recurrent and/or metastatic head and neck squamous cell carcinoma.

Clinical trials and biomarker development with molecularly targeted agents and radiotherapy.

Introduction: The conventional paradigm of drug development used for cytotoxic chemotherapeutic agents may not represent the most effective method of assessing the safety and biological activity of molecularly targeted agents, given that the latter may offer improved therapeutic indices with less toxic effects on normal tissues.

Objectives: With the number of novel therapeutics in oncology entering the investigative arena, there is a need to expedite the drug development process by allowing for optimal selection of agents with the greatest likelihood of having clinical benefit over those of lower potential utility.

Discussion: The high throughput techniques now available in genomic, proteomic and metabolomic profiling should allow for more effective preclinical investigation with the identification of biomarkers or indicators of treatment response, leading to increased clinical efficacy with appropriate patient selection.

Neuroendocrine tumors of the gastrointestinal tract: a decade of experience at the Princess Margaret Hospital.

Objectives: Neuroendocrine tumors (NETs) are uncommon malignancies with variable natural history and often indolent biological behavior. Over the past decade, novel treatment approaches have been developed. The purpose of this study was to review the experience at the Princess Margaret Hospital in treating patients with NET over the past decade.

How carbapenem-resistant Acinetobacter spp. established in a newly constructed hospital.

Annually increasing rates of carbapenem-resistant Acinetobacter spp. were observed in a Taiwan hospital since its establishment in November 1998 to March 2005. Increasing consumption of carbapenems was also noticed.

Improving the quality of abstract reporting for phase I cancer trials.

Purpose: Conference abstracts of phase I trials (P1T) communicate important anticancer drug development information. Our objectives were to determine elements essential for good P1T abstract reporting, to assess the quality of P1T abstracts submitted to American Society of Clinical Oncology (ASCO) meetings, and to propose reporting guidelines.

Experimental Design: A survey of developmental therapeutics experts established elements of P1T reporting quality, and a scoring system was generated.

Nomograms to predict serious adverse events in phase II clinical trials of molecularly targeted agents.

Purpose: A tool that quantifies the risk of treatment-related toxicity based on individual patient characteristics can augment the informed consent process and safety monitoring in the setting of phase II cancer treatment trials of molecularly targeted agents (MTAs).

Methods: A regression model was constructed to predict the risk of a serious adverse event (SAE) with an MTA and presented as a nomogram. Estimation of risk can be performed by integrating risk estimates from the nomogram and from a reference or average patient.

A phase I study of OGX-011, a 2'-methoxyethyl phosphorothioate antisense to clusterin, in combination with docetaxel in patients with advanced cancer.

Purpose: Clusterin is a cytoprotective chaperone protein that promotes cell survival and confers broad-spectrum treatment resistance. OGX-011 is a 2'-methoxyethyl-modified phosphorothioate antisense oligonucleotide that is complementary to clusterin mRNA, has a prolonged tissue half life, enhances drug efficacy in xenograft models, and reduces clusterin expression in humans with a biologically effective dose of 640 mg. The objective of this study was to determine a recommended phase II dose of OGX-011 in combination with docetaxel.

Phase II study of ispinesib in recurrent or metastatic squamous cell carcinoma of the head and neck.

Ispinesib (SB-715992) inhibits the mitotic kinesin spindle protein (KSP), a novel target for anticancer therapy. A phase II study was conducted to examine the efficacy of ispinesib in recurrent or metastatic head and neck squamous cell carcinoma (RMHNSC). Patients with up to one prior line of chemotherapy for RMHNSC were treated with ispinesib 18 mg/m2 IV over 1 hour every 21 days.

Correlation of changes between 2-year disease-free survival and 5-year overall survival in adjuvant breast cancer trials from 1966 to 2006.

Background: Although disease-free survival (DFS) is accepted as a valid end point in adjuvant breast cancer trials, improvement in 2-year DFS has never been formally established as an adequate correlate for 5-year overall survival (OS). We set out to ascertain if changes in 2-year DFS can be used to accurately predict 5-year OS changes.

Design: We conducted a systematic Medline search (1966-2006) for randomized adjuvant breast cancer trials of >100 patients per arm with 2-year DFS and 5-year OS data.

Methicillin-resistant Staphylococcus aureus carriage, infection and transmission in dialysis patients, healthcare workers and their family members.

Background: Carriage and subsequent infection with methicillin resistant S. aureus (MRSA) and its transmission between hospital and community settings have not been studied in dialysis patients and their contacts.

Methods: Surveillance for nasal MRSA carriage and infection among dialysis patients, healthcare workers (HCWs) and their family members in a dialysis centre was prospectively undertaken during three time periods within 1 year.

Prognostic significance of mesenteric tumor nodules in patients with stage III colorectal cancer.

Background: Tumor nodules are occasionally found in adjacent mesentery of colorectal cancer specimens and are felt to reflect a worse prognosis. The clinical significance of mesenteric tumor nodules was investigated.

Methods: A review of 786 patients with stage III colorectal cancer referred between 1995 and 1999 was undertaken.

The influence of mentorship on research productivity in oncology.

Background: This study evaluates the impact of mentors in research productivity in oncology.

Methods: Two electronic surveys were sent out to 1009 oncologists who attended educational workshops between 1996 and 2004.

Results: Response rate was 41.

Molecular targeted therapy of head and neck cancer: review and clinical development challenges.

Recently, new targets have been identified in head and neck squamous cell carcinomas (HNSCC) as playing key roles in tumour proliferation and metastases. The first target that has led to the approval of a molecularly based therapy in HNSCC has been the epidermal growth factor receptor (EGFR). Indeed, cetuximab, a monoclonal antibody directed against EGFR, has recently been approved in combination with radiation therapy in patients with locally advanced HNSCC, and in patients with platinum-refractory recurrent or metastatic (R/M) HNSCC.

Surrogate end points for median overall survival in metastatic colorectal cancer: literature-based analysis from 39 randomized controlled trials of first-line chemotherapy.

Purpose: Our aims were to determine the correlations between progression-free survival (PFS), time to progression (TTP), and response rate (RR) with overall survival (OS) in the first-line treatment of metastatic colorectal cancer (MCRC), and to identify a potential surrogate for OS.

Methods: Randomized trials of first-line chemotherapy in MCRC were identified, and statistical analyses were undertaken to evaluate the correlations between the end points.

Results: Thirty-nine randomized controlled trials were identified containing a total of 87 treatment arms.

Phase II study of lapatinib in recurrent or metastatic epidermal growth factor receptor and/or erbB2 expressing adenoid cystic carcinoma and non adenoid cystic carcinoma malignant tumors of the salivary glands.

Purpose: Expression of erbB2 and/or epidermal growth factor receptor (EGFR) is associated with biologic aggressiveness and poor prognosis in malignant salivary gland tumors (MSGTs). This phase II study was conducted to determine the antitumor activity of lapatinib, a dual inhibitor of EGFR and erbB2 tyrosine kinase activity, in MSGTs.

Patients And Methods: Patients with progressive, recurrent, or metastatic adenoid cystic carcinoma (ACC) immunohistochemically expressing at least 1+ EGFR and/or 2+ erbB2 were treated with lapatinib 1,500 mg daily, in a two-stage cohort.

Phase II trial of sorafenib in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or nasopharyngeal carcinoma.

Purpose: To determine the efficacy and safety of single-agent sorafenib in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) and nasopharyngeal carcinoma (NPC).

Patients And Methods: In this single-arm phase II trial, oral continuous sorafenib was administered in 28-day cycles. Patients had View Article and Find Full Text PDF

Phase I targeted combination trial of sorafenib and erlotinib in patients with advanced solid tumors.

Purpose: Sorafenib and erlotinib are potent, orally administered receptor tyrosine kinase inhibitors with antiproliferative and antiangiogenic activities. Given their inhibitory target profile and efficacy as single agents, the combination of these drugs is of considerable interest in solid malignancies. This study aimed to determine the recommended phase II dose of this targeted combination, their toxicity profile, pharmacokinetic interaction, and preliminary clinical activities.

Molecularly targeted oncology therapeutics and prolongation of the QT interval.

Investigation and utilization of molecularly targeted agents has induced a number of drug adverse effects that are not typically associated with conventional chemotherapy. QT interval prolongation, a cardiac toxicity that increases the risk of fatal arrhythmia, is associated with several novel oncology therapies. Classes of molecularly targeted agents with described QT effects include histone deacetylase inhibitors, multitargeted tyrosine kinase inhibitors, vascular disruption agents, farnesyl protein transferase inhibitors, Src/Abl kinase inhibitors, and protein kinase C inhibitors.