Numerous studies have demonstrated a relationship between the extracellular matrix protein BIGH3 and variations in the malignant properties of different cancer cell types, including osteosarcoma cells. BIGH3 protein c...Numerous studies have demonstrated a relationship between the extracellular matrix protein BIGH3 and variations in the malignant properties of different cancer cell types, including osteosarcoma cells. BIGH3 protein can suppress and promote tumor growth, even on the same cancer cell type, indicating that contextual cues regulate BIGH3-mediated divergent outcomes. We employed a multicellular tumor spheroid model to study the effects of BIGH3 with respect to physical and molecular features of three-dimensional tumor growth. The results demonstrated that exogenous recombinant BIGH3 blocked the development of multicellular large tumor spheroids so that only small spheroids formed. The effect was dependent on the BIGH3 concentration in the growth medium and the time of incubation of BIGH3 with the osteosarcoma cells in the spheroid model. TGF-β1 signaling induced multicellular tumor spheroids to synthesize a greater quantity of BIGH3 relative to non-treated spheroids. The TGF-β1-mediated increase in BIGH3 protein antagonized the development of multicellular large spheroids. Anti-BIGH3 antibody, and an inhibitor of TGF-β1 signaling, blocked the antagonistic effect induced through TGF-β1 stimulation and BIGH3 protein expression, resulting in the formation of multicellular large spheroids. Immunohistochemistry detected BIGH3 at cell bodies within the spheroid stroma, suggesting osteosarcoma cell-surface proteins bind BIGH3. Flow cytometry demonstrates that osteosarcoma cells interact with soluble BIGH3, and solid-phase cell adhesion assays show that osteosarcoma adhesion to BIGH3 substratum is mediated by integrin α4β1. However, anti-α4 antibody did not attenuate the BIGH3-mediated antagonism toward formation of multicellular large spheroids. We conclude that TGFβ1 and BIGH3 suppress the development of large osteosarcoma tumors.展开更多
A 61-year-old female with past medical history of maculopapular rash reaction to ciprofloxacin and amoxicillin being treated for diverticulitis develops the same rash with administration of piperacillin/tazobactam and...A 61-year-old female with past medical history of maculopapular rash reaction to ciprofloxacin and amoxicillin being treated for diverticulitis develops the same rash with administration of piperacillin/tazobactam and aztreonam. A diffuse maculopapular rash developed after the administration of piperacillin. It resolved with discontinuation of the drug and the patient was switched to aztreonam and a very similar rash developed subsequently. In a review of the literature, there are no documented cases of a patient with an allergy to both aztreonam and piperacillin/tazobactam despite in vivo cross-reactivity. Unfortunately, there are no standardized allergy tests for aztreonam or piperacillin. This case, however, does offer the possibility that aztreonam may not always be the right alternative to persons with beta-lactam antibiotic allergies.展开更多
文摘Numerous studies have demonstrated a relationship between the extracellular matrix protein BIGH3 and variations in the malignant properties of different cancer cell types, including osteosarcoma cells. BIGH3 protein can suppress and promote tumor growth, even on the same cancer cell type, indicating that contextual cues regulate BIGH3-mediated divergent outcomes. We employed a multicellular tumor spheroid model to study the effects of BIGH3 with respect to physical and molecular features of three-dimensional tumor growth. The results demonstrated that exogenous recombinant BIGH3 blocked the development of multicellular large tumor spheroids so that only small spheroids formed. The effect was dependent on the BIGH3 concentration in the growth medium and the time of incubation of BIGH3 with the osteosarcoma cells in the spheroid model. TGF-β1 signaling induced multicellular tumor spheroids to synthesize a greater quantity of BIGH3 relative to non-treated spheroids. The TGF-β1-mediated increase in BIGH3 protein antagonized the development of multicellular large spheroids. Anti-BIGH3 antibody, and an inhibitor of TGF-β1 signaling, blocked the antagonistic effect induced through TGF-β1 stimulation and BIGH3 protein expression, resulting in the formation of multicellular large spheroids. Immunohistochemistry detected BIGH3 at cell bodies within the spheroid stroma, suggesting osteosarcoma cell-surface proteins bind BIGH3. Flow cytometry demonstrates that osteosarcoma cells interact with soluble BIGH3, and solid-phase cell adhesion assays show that osteosarcoma adhesion to BIGH3 substratum is mediated by integrin α4β1. However, anti-α4 antibody did not attenuate the BIGH3-mediated antagonism toward formation of multicellular large spheroids. We conclude that TGFβ1 and BIGH3 suppress the development of large osteosarcoma tumors.
文摘A 61-year-old female with past medical history of maculopapular rash reaction to ciprofloxacin and amoxicillin being treated for diverticulitis develops the same rash with administration of piperacillin/tazobactam and aztreonam. A diffuse maculopapular rash developed after the administration of piperacillin. It resolved with discontinuation of the drug and the patient was switched to aztreonam and a very similar rash developed subsequently. In a review of the literature, there are no documented cases of a patient with an allergy to both aztreonam and piperacillin/tazobactam despite in vivo cross-reactivity. Unfortunately, there are no standardized allergy tests for aztreonam or piperacillin. This case, however, does offer the possibility that aztreonam may not always be the right alternative to persons with beta-lactam antibiotic allergies.
