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Biomedical subjects

Karen Roberts

Publications and source records attributed to Karen Roberts.

15 recordsLinked to original sources
PubMed2006

Phase I study of 131I-chimeric(ch) TNT-1/B monoclonal antibody for the treatment of advanced colon cancer.

PURPOSE: The primary aim of this study was to evaluate the biodistribution and toxicity of 131I-chimeric(ch) TNT-1/B monoclonal antibody (MAB), which binds to intracellular antigens of necrotic regions within tumors, in patients with advanced colon or colorectal cancer. The rationale for targeting areas of tumor necrosis is the observation that necrotic lesions are more abundant in cancer lesions than in surrounding tissues. PATIENTS AND METHODS: Cohorts of patients with advanced colon or colorectal cancer were administered a one-time 30-60-minute intravenous (i.v.) infusion of 131I-chTNT-1/B at doses ranging from 12.95 to 66.23 MBq/kg (0.35-1.79 mCi/kg). RESULTS: The dose-limiting toxicity, experienced at 66.23 MBq/kg (1.79 mCi/kg) 131I-chTNT-1/B MAB, was myelosuppression. Two (2) patients at the 66.23-MBq/kg (1.79 mCi/kg) dose level had both grade 3 thrombocytopenia and grade 3 neutropenia that persisted for at least 2 weeks but were reversible. The maximum tolerated dose was 58.09 MBq/kg (1.57 mCi/kg) 131I-chTNT-1/B MAB. Of the 21 patients, one developed a moderate human antichimeric antibody (HACA) response and 6 developed low HACA responses. CONCLUSIONS: The infusion of 131I-chTNT-1/B MAB was well tolerated, without significant nonhematological toxicity. No patient obtained a complete or partial response, based on tumor cross-product response criteria. Tumor localization was seen in patients with dose levels at, and exceeding, 50.23 MBq/kg (1.36 mCi/kg) 131I-chTNT-1/B MAB.

Adult↗
PubMed2006

(131)I-chTNT-1/B mAb: tumour necrosis therapy for malignant astrocytic glioma.

Treatment of malignant glioma is therapeutically challenging. Despite improvements in neurosurgery, radiotherapy and chemotherapy, few patients diagnosed with anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) (WHO grades 3 and 4, respectively) will live beyond 2 years. Poor survival is due to the highly invasive nature and protected location of these tumours. Most malignant gliomas cannot be completely resected or irradiated due to their ability to infiltrate diffusely into normal brain tissue. Brain tissue is protected from the systemic circulation via the blood-brain barrier (BBB), which impedes entry of water-soluble chemotherapeutic agents into the tumour at therapeutic concentrations. (131)I-chTNT-1/B mAb (Cotara) employs an innovative strategy to treat the invasive portion of the tumour and the core lesion. (131)I-chTNT-1/B mAb is a genetically engineered, radiolabelled, chimeric monoclonal antibody specific for a universal intracellular antigen (i.e., DNA/histone H1 complex) exposed in the necrotic core of malignant gliomas. This antigen provides an abundant, insoluble, non-diffusible anchor for the mAb. Once localised to necrotic regions of the tumour, (131)I-chTNT-1/B mAb delivers a cytotoxic dose of (131)I radiation to the core lesion. (131)I-chTNT-1/B mAb is delivered via convection-enhanced delivery in order to maximise coverage to the tumour and the invasive front of the glial tumour. The clinical experience to date with (131)I-chTNT-1/B mAb is presented.

Adolescent↗
PubMed2005

Angels?

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Attitude of Health Personnel↗
PubMed2004

More evidence of the need for an ergonomic standard.

BACKGROUND: In 1999, the Occupational Safety and Health Administration (OSHA) proposed regulations designed to reduce work related inquiries by limiting worker exposure to "ergonomic risk factors." Congress subsequently overturned the regulations. We provide additional evidence on earnings losses attributable to musculoskeletal disorders (MSDs), and thus on the need for an ergonomic standard. METHODS: Regression techniques are used to analyze data from a survey of injured workers that has been matched to employer-reported earnings data covering pre- and post-injury periods, and to workers' compensation claims records. RESULTS: MSDs lead to large and persistent earnings losses. Cost estimates used by OSHA to justify the 1999 EPS are corroborated. Losses are greatest among workers who file workers compensation claims, but nonclaimants also have losses. CONCLUSIONS: Earnings losses and lost productivity associated with work-related MSDs are substantial and an ergonomic standard could be cost effective.

Cost of Illness↗
PubMed2004

The Brn-2 transcription factor links activated BRAF to melanoma proliferation.

Malignant melanoma, an aggressive and increasingly common cancer, is characterized by a strikingly high rate (70%) of mutations in BRAF, a key component of the mitogen-activated protein (MAP) kinase signaling pathway. How signaling events downstream from BRAF affect the underlying program of gene expression is poorly understood. We show that the Brn-2 POU domain transcription factor is highly expressed in melanoma cell lines but not in melanocytes or melanoblasts and that overexpression of Brn-2 in melanocytes results in increased proliferation. Expression of Brn-2 is strongly upregulated by Ras and MAP kinase signaling. Importantly, the Brn-2 promoter is stimulated by kinase-activating BRAF mutants and endogenous Brn-2 expression is inhibited by RNA interference-mediated downregulation of BRAF. Moreover, silent interfering RNA-mediated depletion of Brn-2 in melanoma cells expressing activated BRAF leads to decreased proliferation. The results suggest that the high levels of Brn-2 expression observed in melanomas link BRAF signaling to increased proliferation.

Animals↗
PubMed2003

Expectations and perceptions of graduates' performance at the start and at the end of their graduate year.

This descriptive study reports on the expectations and perceptions of graduate performance by graduates themselves, their preceptors, and their clinical nurse consultants (CNCs) at the commencement of employment as a beginning level registered nurse, and near the end of graduates' twelve months of professional employment. Findings indicate that graduates expected to be functioning at a higher level of performance at the beginning of their graduate year than did the preceptors and CNCs. There was little agreement between the three groups regarding the rating of their expectations of graduates' nursing performance. When agreement between pairs of groups was examined, preceptors and CNCs agreed most, followed by graduates and preceptors, and graduates and CNCs. When perceptions of graduates' performance were compared near the end of the graduates' employment period, graduates rated their own nursing performance higher than preceptors and CNCs. Once again there was little agreement among the three groups. Overall, graduates and preceptors agreed most. On the basis of these results the question is begged, on what basis is the decision taken to terminate preceptorship support for graduates?

Attitude↗
PubMedDate not supplied

Here comes trouble.

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Humans↗