Time dependent expression of cytokines in Mycobacterium bovis infected cattle lymph nodes.

Advancements in the current diagnostic and vaccination protocols employed against bovine tuberculosis rely heavily upon a sound knowledge of the bovine immunological response. Central to this is the importance of timing in the cellular immune profile and how this dynamic process evolves post-Mycobacterium bovis challenge. In the present study, we quantitatively analysed mRNA expression of interferon gamma (IFN-γ), tumour necrosis factor alpha (TNF-α) and interleukins (IL) 4 and 10 within select thoracic lymph nodes of cattle infected with M. bovis for 5, 12 and 19 weeks as compared to non-infected bovine tissues. The M. bovis infected lymph nodes displayed significantly higher expression levels of IFN-γ and TNF-α as compared to the non-infected lymph node tissues. This, in conjunction with undetectable levels of IL4, suggests a pro-inflammatory cytokine response. However a significant increase was also detected in IL10 mRNA which is consistent with a described aspect of T(H)1 type T cells in Leishmania infection, a 'self-limiting' process in which cells produced both IFN-γ and IL10 with the aim of controlling the heightened immunopathological responses. This was further reflected when comparing the cytokine profiles of the individual lymph node types, as those displaying a higher IFN-γ/IL10 ratio also had a greater level of gross pathology. This data highlights the important role of IL10 in the bovine response to M. bovis infection and supports its involvement as an immunological marker of disease progression.

Epidermal growth factor receptor-directed therapy in esophageal cancer.

Esophageal adenocarcinoma (EAC) is one of the fastest growing malignancies in the US. The long-term survival of patients with this cancer remains poor; only 25% of patients undergoing surgical excision are alive after 5 years. Multimodal programs that incorporate radiotherapy, chemotherapy and surgery for localized tumors may result in a modest survival advantage. However, significant strides in this disease can result from the inclusion of targeted therapies. The epidermal growth factor receptor (EGFR) family represents one such target and is receiving increasing attention due to the advent of specific inhibitors. Studies conducted by us and others have shown that the overexpression of EGFR family signaling intermediates is common in Barrett's esophagus and EAC. In the latter case, EGFR expression may have prognostic significance. EGFR inhibitors, including oral tyrosine kinase inhibitors and monoclonal antibodies, result in a synergistic antitumor effect with chemotherapeutic agents or with radiotherapy. Therefore, several ongoing studies include EGFR-directed therapy either alone or in combination with chemoradiotherapy for this disease. Our study of gefitinib, oxaliplatin and radiotherapy suggested that gefitinib can be safely incorporated into an oxaliplatin-based chemoradiation program for esophageal cancer, although the clinical activity of this combination is modest. Herein, we review the current literature on this subject.