RESUMO
BACKGROUND: Osteosarcoma, a malignant tumor characterized by bone or osteoid formation, is the second most common primary bone neoplasm. Clinical symptoms include local and surrounding pain, unrelieved by rest or anesthesia. Osteosarcoma has a poor chemotherapeutic response with prognosis dependent on complete tumor excision. Therefore, for inoperable osteosarcoma new therapeutic strategies are needed. The present study aimed to develop murine models of cranial and vertebral osteosarcoma that facilitate simple clinical monitoring and real-time imaging to evaluate the outcome of photodynamic therapy based on a previously developed photosensitizer. METHODS: Balb/c nude mice were divided into two groups: the cranial and vertebral osteosarcoma groups. Each group was further subdivided into the photodynamic therapy-treated and untreated groups. Images were obtained by scintigraphy with 99mTc-MIBI and radiography. Tumor growth, necrotic area, osteoid matrix area, and inflammatory infiltration were analyzed. RESULTS: Cranial and vertebral tumors could be macroscopically observed and measured. Radiographic and scintigraphic images showed tumor cells present at the inoculation sites. After photodynamic therapy, scintigraphy showed lower tumoral radiopharmaceutical uptake, which correlated histologically with increased necrosis. Osteoid matrix volume increased, and tumor size decreased in all photodynamic therapy-treated animals. CONCLUSION: Cranial and vertebral osteosarcoma models in athymic mice are feasible and facilitate in vivo monitoring for the development of new therapies. Photodynamic therapy is a potential antitumoral treatment for surgically inoperable osteosarcoma.
Assuntos
Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Animais , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Osteossarcoma/patologia , Cintilografia , Crânio/patologia , Coluna Vertebral/patologiaRESUMO
BACKGROUND: Molecular investigation of breast tumors has permitted better understanding about interaction of genes and pathways involved in tumor progression. OBJECTIVE: The aim of this study was to evaluate the association between genes belonging to the pathway of apoptosis with tumor response to photodynamic therapy. STUDY DESIGN/MATERIALS AND METHODS: The mammary tumors were induced in twenty-four Spraguey-Dawley female rats by oral gavage of 7,12-dimethylbenz(a)anthracene (8mg/Kg body weight). Animals were divided into three groups: G1 (normal tissue), G2 (tumors without treatment), G3 (animals euthanized 48h after treatment). The photosensitizer used was a chlorin, 5,15-bis-(2-bromo-5-hydroxyphenyl) chlorin in the dose of 8mg/kg for each animal. Light source of diode laser at a wavelength of 660nm, fluence rate of 100mW/cm, and light dose of 100J/cm was delivery to lesions for treatment. A sample from each animal was investigated by quantitative real time PCR using Rat Apoptosis RT(2) Profiler™ PCR Array platform. RESULTS: Pro-apoptotic BAK1, CARD6, CASP8, CIDEA, CIDEB, DAPK1, TNF, TNFRSF10B, FASLG, LOC687813, and TP73 genes showed increased expression, and CD40 anti-apoptotic gene showed decreased expression in the group who underwent PDT (G3) in relation to G2. CONCLUSION: The results indicated that these genes are involved more directly with cellular apoptosis induced by PDT using the Chlorin photosensitizer.