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Justin Stebbing

Publications and source records attributed to Justin Stebbing.

At least 37 records · Page 2Linked to original sources
PubMed2006

Chemotherapy for advanced cholangiocarcinoma: what is standard treatment?

Cholangiocarcinoma is a relatively uncommon malignancy, that presents late in the vast majority of cases. Overall survival rates are extremely poor and treatment options remain limited in patients with inoperable, recurrent or metastatic disease. Systemic chemotherapy has historically had little impact on the natural history of this disease, owing to both the absence of agents with substantial activity and the overall morbidity of treatment in this patient population. Response rates with 5-fluorouracil have been 10% at best, with a median survival of 6 months. However, there has been interest in the use of newer cytotoxic drugs and combination regimens in advanced cholangiocarcinoma, and Phase II trials have reported much improved results. This review examines this data and assesses whether a new standard of care for advanced cholangiocarcinoma can be found.

Bile Duct Neoplasms↗
PubMed2006

Recent advances in the systemic management of colorectal cancer.

Colorectal cancer represents one of the most prevalent malignancies. There have been considerable improvements in the management of the disease in the last decade, including advances in surgery. In terms of systemic management, 5-fluorouracil, usually with leucovorin, has remained the mainstay of chemotherapy for colorectal cancer in both the adjuvant and metastatic settings. In the late 1990s, irinotecan and oxaliplatin reached the clinical arena, and the introduction of these agents has led to significant improvements in outcomes. More recently, several biopharmaceuticals, including the monoclonal antibodies bevacuzimab and cetuximab, have shown promise in clinical studies. These novel agents are now being incorporated into treatment schedules for colorectal cancer. This review assesses recent improvements in the systemic management of large bowel cancer and highlights future challenges.

Antibodies, Monoclonal↗
PubMed2006

Clots and cancer.

Explore the source record for details and available documents.

Anticoagulants↗
PubMed2005

A prognostic index for systemic AIDS-related non-Hodgkin lymphoma treated in the era of highly active antiretroviral therapy.

BACKGROUND: The established International Prognostic Index for lymphomas has not included patients with systemic AIDS-related non-Hodgkin lymphoma. OBJECTIVE: To establish the most appropriate prognostic index for use in patients with systemic AIDS-related non-Hodgkin lymphoma. DESIGN: A prospective study involving univariate and multivariable analyses of patients with AIDS-related non-Hodgkin lymphoma whose data were used to examine standard and new criteria for survival after diagnosis. SETTING: The Chelsea and Westminster cohort of HIV-1-infected persons. PATIENTS: 9621 HIV-positive patients, 111 in whom AIDS-related non-Hodgkin lymphoma was treated after 1996, in the era of highly active antiretroviral therapy (HAART). INTERVENTION: Cox proportional hazards regression analysis to determine the prognostic significance of multiple clinicopathologic variables. RESULTS: Survival of patients with AIDS-related non-Hodgkin lymphoma has increased in the HAART era (log-rank chi-square, 9.23; P = 0.002). Univariate analyses using the established International Prognostic Index factors of age, tumor stage, lactate dehydrogenase level, Eastern Cooperative Oncology Group performance status, and number of extranodal sites were confirmed to be significant variables. Regression modeling for patients in whom disease was diagnosed after 1996 revealed only 2 independent predictors of death: International Prognostic Index risk group and CD4 cell count. These predictors yielded 4 internally validated risk strata with predicted 1-year survival rates of 82%, 47%, 20%, and 15% (P < 0.001). Prognostic risk scores in the highest quartile yielded a likelihood ratio for death of 7.90 (hazard ratio, 1.0), whereas a prognostic score less than 1.0 yielded a likelihood ratio of 0.23 (hazard ratio, 0.15 [95% CI, 0.06 to 0.33]). LIMITATIONS: The sample was small, and different HAART regimens were used. CONCLUSIONS: For patients with AIDS-related non-Hodgkin lymphoma that was diagnosed in the era of HAART, application of the International Prognostic Index remains useful. The addition of CD4 cell count provides further independent prognostic information. Patients who present with AIDS-related non-Hodgkin lymphoma and a low CD4 cell count have a poor prognosis; this information can be used to guide therapeutic options.

Antiretroviral Therapy, Highly Active↗
PubMed2005

Hepatitis C infection is not associated with systemic HIV-associated non-Hodgkin's lymphoma: a cohort study.

Immunosuppression induced by the human immunodeficiency virus (HIV) increases the risk of developing non-Hodgkin's lymphoma (NHL). As the hepatitis C virus (HCV) has been implicated in the development of B cell lymphomas, we compared the incidence of systemic NHL during HIV infection compared to HIV and HCV co-infection. Of 5,832 individuals studied during the era of highly active anti-retroviral therapy (HAART), 102 patients were diagnosed with systemic NHL. The incidence of systemic NHL was 6.9 of 10(4) patient years during HIV infection compared to 7.1 of 10(4) patient years during HIV alone (p = 0.9). In this immunocompromised patient population, there was no association between HCV infection and an increased risk of lymphoma.

Cohort Studies↗
PubMed2005

Hepatitis C virus infection in HIV type 1-infected individuals does not accelerate a decrease in the CD4+ cell count but does increase the likelihood of AIDS-defining events.

Human immunodeficiency virus type 1 (HIV-1) appears to adversely affect hepatitis C, but whether hepatitis C virus (HCV) has a reciprocal effect on HIV-1 infection remains a point of controversy. In a multivariate analysis of a cohort of 5832 individuals, we found that individuals coinfected with HCV and HIV-1 (prevalence of coinfection, 5.8%) had a CD4+ cell count that decreased at a rate similar to that for individuals infected with HIV-1 alone. However, coinfection was associated with a statistically significant increased likelihood of onset of an acquired immunodeficiency syndromedefining illness or developing a CD4+ cell count of <200 cells/mm3, compared with infection with HIV-1 alone (hazard ratio, 1.52; 95% confidence interval, 1.072.17). Patients who were naive to highly active antiretroviral therapy were significantly less likely to progress to either end point, because of their higher CD4+ cell counts. In conclusion, there was an increased number of adverse events in coinfected individuals, compared with individuals infected with HIV-1 alone.

Adult↗
PubMed2005

Adherence to trizivir and tenofovir as a simplified salvage regimen is associated with suppression of viraemia and a decreased cholesterol.

BACKGROUND: Treatment failure during highly active antiretroviral therapy (HAART) is ultimately common and associated with the development of resistance mutations. Trizivir (zidovudine/lamivudine/abacavir) and tenofovir disoproxil fumarate may improve adherence and enhance virological suppression in individuals who have failed previous regimens. METHODS: Individuals were identified who had failed previous HAART and who were then prescribed trizivir and tenofovir. Viral load and genotypic information were obtained to assess virological response. RESULTS: One hundred and twenty-two individuals were identified from a database containing 5883 patients. In a last observation carried forward intention to treat analysis, 34% of individuals achieved an undetectable viral load of <50 copies/mL at 1 year. Of those who were able to remain on treatment for 1 year, 65% achieved undetectability. We observed no effect regarding previous regimens on viral outcome. Accumulation of TAMs (thymidine analogue mutations) was associated with a decrease in the number of patients achieving an undetectable viral load (with <2 TAMs present 38% of patients developed undetectable viral loads, > or =1;2 TAMs 17% undetectable; P = 0.03). Using the mean cell volume as a measure of compliance, those with higher values were more likely to achieve a viral load <50 copies/mL (P = 0.04). A beneficial effect on cholesterol was noted regardless of virological outcome. CONCLUSIONS: In compliant heavily pre-treated individuals with less than 2 TAMs, salvage therapy with trizivir and tenofovir is associated with suppression of viraemia and an improved lipid profile.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Conservation of unique cell-surface CD antigen mosaics in HIV-1-infected individuals.

Cluster of differentiation (CD) antigens are expressed on cells of myeloid and lymphoid lineages. As most disease processes involve immune system activation or suppression, these antigens offer unique opportunities for monitoring host responses. Immunophenotyping using limited numbers of CD antigens enables differentiation states of immune system cells to be determined. Extended phenotyping involving parallel measurement of multiple CD antigens may help identify expression pattern signatures associated with specific disease states. To explore this possibility we have made a CD monoclonal antibody array and scanner, enabling the parallel immunophenotyping of leukocyte cell suspensions in a single and rapid analysis. To demonstrate this approach, we used the specific example of patients infected with human immunodeficiency virus type-1 (HIV-1). An invariant HIV-induced CD antigen signature has been defined that is both robust and independent of clinical outcome, composed of a unique profile of CD antigen expression levels that are both increased and decreased relative to internal controls. The results indicate that HIV-induced changes in CD antigen expression are disease specific and independent of outcome. Their invariant nature indicates an irreversible component to retroviral infection and suggests the utility of CD antigen expression patterns in other disease settings.

Antibodies, Monoclonal↗
PubMed2005

Expression of the common heat-shock protein receptor CD91 is increased on monocytes of exposed yet HIV-1-seronegative subjects.

The significantly higher surface expression of the surface heat-shock protein receptor CD91 on monocytes of human immunodeficiency virus type-1 (HIV-1)-infected, long-term nonprogressors suggests that HIV-1 antigen uptake and cross-presentation mediated by CD91 may contribute to host anti-HIV-1 defenses and play a role in protection against HIV-1 infection. To investigate this further, we performed phenotypic analysis to compare CD91 surface expression on CD14(+) monocytes derived from a cohort of HIV-1-exposed seronegative (ESN) subjects, their seropositive (SP) partners, and healthy HIV-1-unexposed seronegative (USN) subjects. The median fluorescent intensity (MFI) of CD91 on CD14(+) monocytes was significantly higher in ESN compared with SP (P = 0.028) or USN (P = 0.007), as well as in SP compared with USN subjects (P = 0.018). CD91 MFI was not normalized in SP subjects on highly active antiretroviral therapy (HAART) despite sustainable, undetectable plasma viraemia. Data in three SP subjects experiencing viral rebounds following interruption of HAART showed low CD91 MFI comparable with levels in USN subjects. There was a significant positive correlation between CD91 MFI and CD8(+) T cell counts in HAART-naïve SP subjects (r = 0.7, P = 0.015). Increased surface expression of CD91 on CD14(+) monocytes is associated with the apparent HIV-1 resistance that is observed in ESN subjects.

Adult↗
PubMed2005

The potential significance of adaptive evolution and dimerization in chimpanzee intercellular cell adhesion molecules (ICAMs).

Cell adhesion molecules are involved in a diverse array of cellular processes. Recent data suggests that human immunodeficiency virus (HIV-1) co-opts their functions, in particular the properties of the intercellular cell adhesion molecules (ICAMs), to enhance viral infection and transmission. To investigate mechanisms that may underlie the non-progression that occurs in immunodeficiency virus-infected chimpanzees, we amplified the protein coding regions of multiple non-human primate ICAMs 1-5 and two ICAM ligands, leukocyte function-associated antigen-1 (LFA-1) and macrophage antigen 1 (Mac-1). We then employed a phylogenetic tree-based approach to comparative genomics, in order to screen for the presence of adaptive changes. Strong Darwinian positive selection in chimpanzee ICAMs 1, 2 and 3 was observed, most markedly in domains that are critical for the integrity and maintenance of ICAM-1 dimerization. As binding of ligands, including the attachment of virions, is influenced by the state of ICAM 1 dimerization, chimpanzee ICAMs may have evolved to modulate their own dimerization. In concert with previous evidence suggesting an ancient retroviral pandemic as a prominent selective force in chimpanzee evolution, adaptation of chimpanzee ICAMs may have effected a mechanism that explains the lack of immunosuppression observed following HIV-1 or simian immunodeficiency virus (SIVcpz) infection.

Amino Acid Sequence↗