Biomedical subjects

Rajesh V Lalla

Publications and source records attributed to Rajesh V Lalla.

8 recordsLinked to original sources

PubMed2006

Amifostine in the management of radiation-induced and chemo-induced mucositis.

INTRODUCTION: Mucositis is a significant complication of cancer therapy, with important clinical and economic implications. In June 2005, the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) conducted an evidence-based update review of the literature on mucositis. The goal of this literature review is to update previously published guidelines for the management of mucositis. RESULTS: This article reports the findings of the subgroup charged with reviewing the literature related to amifostine.

Amifostine↗

PubMed2006

Anti-inflammatory agents in the management of alimentary mucositis.

BACKGROUND: Alimentary mucositis is a significant complication of cancer therapy, with important clinical and economic implications. MATERIALS AND METHODS: In June 2005, the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology conducted an evidence-based review of the literature on alimentary mucositis. The goal of this literature review was to update previously published guidelines for the management of mucositis. RESULTS: This article reports the findings of the subgroup charged with reviewing the literature related to anti-inflammatory interventions. Considerable preclinical and clinical evidence suggests that the use of anti-inflammatory agents may be a promising approach to reduce the severity of mucositis. However, there was not enough evidence to support any new guidelines advocating the use of any specific anti-inflammatory intervention. CONCLUSION: Thus, there is a need for well-designed clinical trials evaluating the use of anti-inflammatory agents in the management of mucositis.

Allopurinol↗

PubMed2005

Oral mucositis.

Oral mucositis refers to erythematous, erosive, and ulcerative lesions of the oral mucosa seen in two patient populations: (1) head and neck cancer patients undergoing radiation therapy to fields involving the oral cavity, and (2) patients receiving high-dose chemotherapy for cancer. Oral mucositis is a significant and dose-limiting toxicity of cancer therapy, with important clinical and economic implications. This article reviews the current knowledge on the pathogenesis, clinical presentation, diagnosis, and management of oral mucositis.

Humans↗

PubMed2005

Velafermin (CuraGen).

CuraGen is developing velafermin (CG-53135), human fibroblast growth factor-20 administered intravenously, for the potential treatment and prevention of oral mucositis (OM). By December 2004, phase II trials for the prevention of OM in cancer patients undergoing bone marrow transplant had been initiated, and in September 2005 CuraGen indicated that results from this study will be reported during the first quarter of 2006.

Animals↗

PubMed2003

Expression of vascular endothelial growth factor receptors on tumor cells in head and neck squamous cell carcinoma.

BACKGROUND: Angiogenesis is essential for the growth of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Angiogenesis is regulated by angiogenic factors such as vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) 1, 2, and 3 known to be located on vascular endothelial cells (VECs). We hypothesize that VEGFRs are also expressed on HNSCC tumor cells in vitro and in vivo and likely control tumor function in vivo. DESIGN: Immunohistochemical analysis for VEGFR-1 (n = 13), VEGFR-2 (n = 21), and VEGFR-3 (n = 16) was performed on human HNSCC tumor samples. Specimens were analyzed for receptor expression and staining intensity. A cultured oral SCC cell line (SCC-25) and a pharyngeal SCC cell line (FADU) were also studied for receptor expression. RESULTS: The HNSCC tumor cells expressed VEGFR-1, VEGFR-2, and VEGFR-3 in all specimens evaluated. Staining for all 3 receptors was also found on tumor-associated macrophages and fibroblasts, except that VEGFR-2 was not present on fibroblasts. Staining intensity for VEGFR-1 and VEGFR-2 was significantly higher in tumor cells and macrophages than in VECs stained for the same receptor. Both cultured HNSCC cell lines demonstrated expression of all 3 receptors. CONCLUSIONS: This represents the first report of all 3 VEGFRs being expressed by HNSCC cells. These findings indicate that VEGF may be an autocrine regulator of tumor cell activity in addition to its known angiogenic effects on VECs. The presence of VEGFRs on tumor-associated macrophages and fibroblasts contributes to the complexity of the VEGF/VEGFR system in human cancer.

Carcinoma, Squamous Cell↗

PubMed2003

Identification of a region of the fibrin molecule involved in upregulation of interleukin-8 expression from human oral squamous cell carcinoma cells.

A number of studies have implicated the fibrin-coagulation-fibrinolysis system in human tumour progression. Interleukin-8 (IL-8) mediates most of the angiogenic activity induced by human oral squamous cell carcinoma (OSCC) cells. We have recently demonstrated that: (1) fibrin is present in association with IL-8 expressing human OSCC cells in vivo and (2) in situ fibrin polymerisation induces a specific, dose and time-dependent upregulation of IL-8 expression from human OSCC cells in vitro. Our present studies extend this observation by demonstrating that in addition to fibrin formed in situ, both fibrin-derived liquid expressates (soluble fibrin) and preformed fibrin clots induced an over eight-fold stimulation of IL-8 expression from human OSCC cells as compared to media controls. IL-8 upregulation by soluble fibrin was dose-dependent. A monoclonal antibody against the N terminal region of the beta chain of human fibrin (Bbeta15-42) inhibited 67% of soluble fibrin-induced IL-8 expression from human OSCC cells. A peptide (GHRP), representing the sequence at the N terminus of this region, induced a dose-dependent stimulation of IL-8 expression, further confirming the role of this region. These studies directly support our hypothesis that fibrin induces protumourigenic factor expression from tumour cells, thus promoting tumour progression. Future studies to further characterise the role of the Bbeta15-42 region in tumour cell activation may lead to the design of peptide antagonists with important therapeutic potential.

Aged↗

PubMed2003

Association of fibrin and interleukin 8 in human oral squamous cell carcinoma.

OBJECTIVE: We have recently demonstrated that fibrin induces a specific, dose- and time-dependent upregulation of the angiogenic factor interleukin 8 (IL-8) from human oral squamous cell carcinoma (OSCC) cells in vitro. In this study we begin to test the hypothesis that fibrin induces IL-8 expression from tumor cells in vivo by studying their in vivo association in OSCC. STUDY DESIGN: The presence of fibrin(ogen) was initially evaluated in 20 archival human OSCCs by means of immunohistochemistry with a polyclonal antibody. The presence of fibrin and IL-8 was then studied in 19 sections from 8 different patients' head and neck tumors (including 6 OSCCs) by means of immunohistochemistry with a monoclonal antibody against fibrin. These 8 tumors had been treated with inhibitors of new fibrin formation and degradation immediately after surgical removal. RESULTS: Fibrin staining was found in 100% of the tumor sections tested. IL-8 staining was found in the cytoplasm of tumor cells in 100% of the studied tumors, including areas adjacent to fibrin. CONCLUSIONS: These data demonstrate an in vivo association between fibrin and IL-8 in OSCC. These studies support our hypothesis that fibrin induces expression of protumorigenic factors such as IL-8 from tumor cells in vivo.

Antibodies↗

PubMedDate not supplied

Treatment of mucositis, including new medications.

Mucositis is a clinically important and sometimes dose-limiting complication of cancer therapy. Mucositis lesions can be painful, affect nutrition and quality of life, lead to sepsis, and have significant economic impact. Recent modeling of the toxicity has been based on the continuum of clinical signs and symptoms of mucositis involving the alimentary tract, including both oral and gastrointestinal sites. The pathogenesis of oral and gastrointestinal mucositis is multifactorial and complex. In recent years, there has been a substantial increase in both basic and clinical research related to mucosal injury in cancer patients. Since most of this research has been directed to oral mucositis, the present review principally addresses this component of the toxicity. Morbidity, economic impact, pathogenesis and clinical course of mucositis are discussed. In addition, several agents in clinical development for mucositis are discussed in the context of the current pathobiologic model as well as the recently updated evidence-based clinical management guidelines.

Evidence-Based Medicine↗