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Biomedical subjects

James Spicer

Publications and source records attributed to James Spicer.

8 recordsLinked to original sources
PubMed2006

Targeting novel and established therapies for non-small cell lung cancer.

The prognosis in advanced non-small cell cancer (NSCLC) remains poor despite the introduction of several new cytotoxic drugs in the past decade. New approaches are required, and an improved understanding of lung cancer biology is identifying molecular mechanisms that are potential targets for novel therapies. Antagonists of signalling via the erbB and VEGFR families of transmembrane receptors have promising activity in NSCLC, and survival benefit has already been demonstrated for both erlotinib and bevacizumab. Although some patients enjoy dramatic and sustained responses to some of the new targeted drugs, overall response rates in unselected NSCLC patient groups are modest. This reflects the molecular heterogeneity of the disease; further clinical progress will require improved patient selection for treatment with both novel agents and established chemotherapy drugs. Here, we review recent advances in NSCLC biology likely to provide insight into such selection strategies.

Antibodies, Monoclonal↗
PubMed2006

The value of metals bioavailability and speciation information for ecological risk assessment in arid soils.

When evaluating the risk chemicals may pose to mammals and birds in ecological risk assessments (ERAs), it is common practice to conservatively assume that all (100%) of a chemical in an environmental medium is bioavailable to receptors. This assumption often leads to overestimating ecological risk and may ultimately result in costly and unnecessary risk management actions. While effects of bioavailability and speciation of metals such as arsenic (As) and lead (Pb) have been considered in human health risk assessment, these effects are rarely taken into consideration when assessing risks to mammals and birds. An ERA was conducted at the former Col-Tex refinery site in Colorado City, Texas, USA, to characterize risks to select wildlife species from exposure to chromium (Cr) and Pb found in soils. The focus on these metals was based on results of a screening-level ERA that found that Cr and Pb were posing ecological risks at the site. Soils were analyzed for total Cr and Pb, trivalent Cr (CrIII), hexavalent Cr (CrVI), organic Pb, and the bioavailability and speciation of Pb. Results for Pb and Cr indicated that >94% of the Cr was present as the less toxic and immobile Cr(III) and that >99% of the Pb in soils was present as inorganic Pb. Lead bioaccessibility measured by in vitro testing ranged from 8% to 77.8%, depending on location of individual soil samples. Results demonstrated that Pb and Cr bioavailability and speciation information can raise soil cleanup concentrations while being protective of ecological receptors. The costs of performing the ERA were de minimus compared to the reduction in remediation costs at the site. The refined hazard estimates allowed informed decision making in the management and segregation of soils, allowing for effective risk management at the site.

Animals↗
PubMed2005

Combination therapy versus single agent chemotherapy in non-small cell lung cancer.

There is proven evidence of improved symptom control with platinum-based chemotherapy in the palliation of non-small cell lung cancer, and small but definite improvements in progression-free and overall survival when compared with best supportive care. The newer chemotherapy agents vinorelbine, gemcitabine, docetaxel and paclitaxel all have single agent activity, and in combination with cisplatin these provide superior quality of life and/or survival compared with the single agents, albeit with some increase in haematological toxicity. Doublet chemotherapy consisting of a new agent combined with platinum, cisplatin by preference where tolerated, has become the standard of care for advanced disease. The use of a functional assessment of fitness, rather than chronological age alone, is appropriate in the treatment of elderly patients. Although in this group there is evidence that doublets are superior to single agents, treatment should be undertaken with caution. In the second line setting where patients are unlikely to tolerate combination therapy, single agents have proven superiority over best supportive care. Patients with poor performance status (PS2) without comorbidity may tolerate combination therapy, but currently available evidence is insufficient to allow a definitive recommendation for combination or single-agent chemotherapy.

Antineoplastic Agents↗
PubMed2005

Technology evaluation: nimotuzumab, the Center of Molecular Immunology/YM BioSciences/Oncoscience.

A joint venture between YM BioSciences (formerly York Medical) and The Center of Molecular Immunology is collaborating with Oncoscience in Europe for the development of a humanized monoclonal antibody, nimotuzumab, for the potential treatment (TheraCIM and RadioTheraCIM) and diagnosis (DiaCIM) of cancers of epithelial origin, such as breast, lung, head and neck, and pancreatic cancer. The antibody is currently undergoing phase II clinical trials.

Animals↗
PubMed2004

LKB1 kinase: master and commander of metabolism and polarity.

LKB1, the product of a tumour suppressor gene, is a serine/threonine kinase that coordinates disparate cellular processes. Recent data have revealed novel functions for LKB1, providing new insight into the regulation of cell polarity and energy-generating metabolism.

AMP-Activated Protein Kinase Kinases↗
PubMed2004

Technology evaluation: pertuzumab, Roche/Genentech/Chugai.

Genentech, Roche and Chugai are developing pertuzumab, a next-generation trastuzumab-like molecule (an anti-HER/neu monoclonal antibody), for the potential treatment of cancer. Pertuzumab is currently undergoing phase II clinical trials.

Animals↗
PubMed2003

Regulation of the Wnt signalling component PAR1A by the Peutz-Jeghers syndrome kinase LKB1.

Loss-of-function mutations in the LKB1 (STK11) serine-threonine kinase gene cause Peutz-Jeghers syndrome, which is associated with inherited susceptibility to colorectal and other cancers. No downstream targets of LKB1 kinase activity have been identified. Here we show that LKB1 can direct the phosphorylation of the serine-threonine kinase PAR1A. The amino-acid residues phosphorylated as a result of LKB1 activity have been identified and phosphorylation at these residues is required for PAR1A kinase activity. PAR1A has previously been implicated as a positive regulator of the Wnt-betacatenin signalling pathway. We show here that LKB1 can modify transcription driven by the Wnt-regulated TCF response element, implicating LKB1 in a pathway known to play a key role in human colorectal tumorigenesis.

AMP-Activated Protein Kinase Kinases↗