ABSTRACT: Pro-inflammatory cytokines like TNF-α activate sphingosine kinase (SK). Therefore, inhibition of SK is a potential molecular target for the treatment of rheumatoid arthritis.
The primary goal of this study was to assess the efficacy of ABC249640 (a selective SK-2 inhibitor) in two models of rodent arthritis. A secondary goal was to evaluate the pharmacological profile of ABC294640, when given in combination with methotrexate.
The efficacy of ABC294640 was determined by paw diameter/volume measurements, histological evaluations, and micro-CT analyses.
ABC294640 attenuated both collagen-induced arthritis in mice, as well as adjuvant-induced arthritis in rats. With the adjuvant arthritis model, the prophylactic efficacy profile of ABC294640 was similar to indomethacin. Of note, ABC294640 reduced the bone and cartilage degradation, associated with adjuvant-induced arthritis. Rats treated with a suboptimal dose of MTX (50 μg/kg/day) in combination with ABC249640 (100 mg/kg/day) had better anti-arthritis effects in the adjuvant model, than treatment with either agent alone.
Our results suggest that ABC249640 is an orally available drug candidate with a good pre-clinical efficacy profile for the prevention and/or treatment of RA.
Inflammopharmacology 10/2010; 19(2):75-87.
ABSTRACT: Crystal-storing histiocytosis (CSH) is a rare process most often occurring in conjunction with an underlying hematopoietic neoplasm, usually multiple myeloma or low-grade B-cell lymphoma. We report the first case of pulmonary CSH diagnosed by fine-needle aspiration biopsy. A patient with a history of urothelial carcinoma developed a lung nodule, which was evaluated by fine-needle aspiration biopsy. Cytologic examination revealed macrophages with abundant cytoplasmic crystals diagnostic of CSH. Based on this cytologic interpretation, additional clinical laboratory evaluation was pursued and revealed a previously unknown monoclonal serum protein. CSH must be differentiated from other non-neoplastic and neoplastic lesions and when diagnosed, should trigger a search for an underlying lymphoproliferative disorder.
Diagnostic Cytopathology 10/2009; 38(4):274-8. · 1.16 Impact Factor
ABSTRACT: Well-differentiated thyroid cancer typically presents as a thyroid mass. Common sites of metastases upon presentation include cervical lymph nodes, lung, and bone. Well-differentiated thyroid cancer with clinically apparent kidney metastases is rare, with fewer than 20 cases reported in the literature. In the vast majority of these cases, the patients had known thyroid neoplasms at the time the renal metastases were identified. We report a case of papillary thyroid carcinoma that presented with abdominal pain in a 25-year-old woman with no previous history of thyroid disease.
This study is a case report.
The patient underwent radical nephrectomy for a right renal mass, which was diagnosed as papillary thyroid carcinoma follicular variant. During subsequent evaluation, metastatic disease was also identified in the patient's lungs. The patient was treated with total thyroidectomy and iodine 131.
Papillary cancer, which ordinarily behaves in an indolent manner, can have unusual presentation, including disseminated metastasis on presentation. Renal metastases are extremely rare.
American Journal of Otolaryngology 26(2):142-5. · 0.87 Impact Factor