Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.467
Filtrar
2.
J Biol Regul Homeost Agents ; 34(5): 1699-1708, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33148374

RESUMO

Osteosarcoma is the most prevailing malignant bone tumor among adolescents. Punicalagin, a polyphenolic compound extracted from pomegranate, possesses many functions such as anti-oxidation, anti-bacterial, anti-virus, and immunosuppression, which can counter the aggressiveness of a variety of cancers such cervical, ovarian and prostate. This study aimed to investigate the inhibitory effect of punicalagin on the proliferation and metastasis of osteosarcoma cells and its potential regulatory mechanisms. Osteosarcoma cell lines (HOS cells, U2OS cells and MG63 cells) were treated with different doses of punicalagin, and the effects on osteosarcoma cell activity were examined in vitro using cell counting kit-8 (CCK-8), colony formation and apoptosis assays. The mobility, migration and invasion abilities of osteosarcoma cells were detected by wound healing and Transwell assays. NF-κB activity was explored by the NF-κB p65 luciferase reporter assay. Western blot was used to investigate the expressions of downstream proteins. We found that punicalagin inhibited the viability of osteosarcoma cells in vitro in dose-dependent and time-dependent manners and promoted apoptosis. In addition, punicalagin could significantly impede the mobility, migration and invasion abilities of osteosarcoma cells. In terms of mechanism, punicalagin down-regulated the expressions of p65, survivin, XIAP, CIAP2 and other proteins, and suppressed the proliferation and metastasis of osteosarcoma cells by repressing NF-κB signaling pathway. In conclusion, it is concluded that punicalagin restrains the growth and metastasis of osteosarcoma by obstructing the NF-κB signal transduction pathway.


Assuntos
Neoplasias Ósseas/patologia , Taninos Hidrolisáveis/uso terapêutico , NF-kappa B/antagonistas & inibidores , Osteossarcoma/patologia , Transdução de Sinais/efeitos dos fármacos , Apoptose , Neoplasias Ósseas/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , NF-kappa B/genética , Osteossarcoma/tratamento farmacológico
3.
Crit Rev Oncol Hematol ; 155: 103108, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33038694

RESUMO

Soft tissue sarcomas in elderly patients beyond the age of 65 years account for almost 50 % of the sarcomas of the total patient population in this rare tumor entity. Distinct clinical and biological characteristics of the different sarcoma subtypes have to be taken into account in the various age groups. Old age should not per se be a contraindication to chemotherapy administration or to undergo surgery; however, particular aspects regarding safety, comorbidities, toxicity, and quality of life have to be considered. The use of a geriatric assessment and especially the use of predictive tools for estimating the expected toxicity may be helpful in this challenging situation. On the other side, osteosarcomas in the elderly patient population represent an extreme rarity. The adequate primary surgical care of these patients seems crucial in terms of prognosis as the addition of chemotherapy does not significantly improve patients' overall survival.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Sarcoma , Neoplasias de Tecidos Moles , Idoso , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/epidemiologia , Humanos , Osteossarcoma/diagnóstico , Osteossarcoma/tratamento farmacológico , Qualidade de Vida , Sarcoma/diagnóstico , Sarcoma/tratamento farmacológico , Sarcoma/epidemiologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/tratamento farmacológico
4.
Nat Commun ; 11(1): 5023, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024108

RESUMO

Chondrosarcomas, malignant cartilaginous neoplasms, are capable of transitioning to highly aggressive, metastatic, and treatment-refractory states, resulting in significant patient mortality. Here, we aim to uncover the transcriptional program directing such tumor progression in chondrosarcomas. We conduct weighted correlation network analysis to extract a characteristic gene module underlying chondrosarcoma malignancy. Hypoxia-inducible factor-2α (HIF-2α, encoded by EPAS1) is identified as an upstream regulator that governs the malignancy gene module. HIF-2α is upregulated in high-grade chondrosarcoma biopsies and EPAS1 gene amplification is associated with poor prognosis in chondrosarcoma patients. Using tumor xenograft mouse models, we demonstrate that HIF-2α confers chondrosarcomas the capacities required for tumor growth, local invasion, and metastasis. Meanwhile, pharmacological inhibition of HIF-2α, in conjunction with the chemotherapy agents, synergistically enhances chondrosarcoma cell apoptosis and abolishes malignant signatures of chondrosarcoma in mice. We expect that our insights into the pathogenesis of chondrosarcoma will provide guidelines for the development of molecular targeted therapeutics for chondrosarcoma.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Condrossarcoma/tratamento farmacológico , Condrossarcoma/patologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Benzimidazóis/administração & dosagem , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Condrossarcoma/genética , Cisplatino/administração & dosagem , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Isocitrato Desidrogenase/genética , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Zhonghua Zhong Liu Za Zhi ; 42(8): 692-696, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867464

RESUMO

Objective: To evaluate the efficacy and safety of polyethylene glycol liposome doxorubicin (PLD) in the treatment of osteosarcoma. Methods: This study was a single-center retrospective clinical study. Two hundreds and seventy-six classical osteosarcoma treated in Beijing Jishuitan Hospital from 2015 to 2016 were enrolled. There were 213 patients who received combined chemotherapy of high dose methotrexate, ifosfamide, cisplatin and doxorubicin (ADM) were classified in ADM group. Other 63 patients received the same types, doses and cycles of chemotherapy drugs except ADM replaced by PLD were identified as PLD group. Clinical and imaging evaluation and surgical treatment were performed after neoadjuvant chemotherapy. Tumor necrosis rate was examined according to Huvos method. The efficacy of neoadjuvant chemotherapy was evaluated based on 90% necrosis rate. The recurrence, metastasis and survival were followed up regularly after operation. The adverse reactions of hematology, hepatorenal toxicity, gastrointestinal reaction and cardiotoxicity were evaluated. Results: There were no significant differences between PLD group and ADM group in age, sex, location, stage and surgical margin (all P>0.05). There were no significant differences in clinical symptoms and imaging evaluation between PLD group and ADM group after preoperative chemotherapy (all P>0.05). The tumor necrosis rate was detected in 134 cases. Among 27 cases of PLD group, tumor necrosis rates more than 90% were 11 cases, while among 107 cases of ADM group, tumor necrosis rates more than 90% were 45 cases. No significant difference of tumor necrosis rate between this two group was observed (P=0.901). The recurrence rates of PLD group and ADM group were 7.8% (4/51) and 7.3% (12/164), the metastasis rates were 19.6% (10/51) and 16.5% (27/164), the median progression free survival (PFS) were 42 and 37 months, respectively, without significant differences (all P>0.05). The incidence of granulocytopenia and decrease degree of granulocytes in PLD group were significantly lower than those in ADM group (P<0.001). There were no significant differences in the incidences of thrombocytopenia, anemia, gastrointestinal reaction, liver function damage and stomatitis between two groups (all P>0.05). Conclusions: PLD and ADM have similar chemotherapeutic effects in osteosarcoma. The incidences of adverse reactions of PLD are lower, especially the hematological toxicity represented by granulocytopenia is significantly reduced. PLD has a better application prospect.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/terapia , Lipossomos/uso terapêutico , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/patologia , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Extremidades , Humanos , Ifosfamida/administração & dosagem , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Osteossarcoma/patologia , Polietilenoglicóis , Prognóstico , Estudos Retrospectivos
6.
Oncology (Williston Park) ; 34(8): 317-319, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32785928

RESUMO

A 78-year-old man had a medical history of hypertension, atrial fibrillation, chronic kidney disease, and metastatic castration-resistant prostate cancer (CRPC). He had progressed to first-line therapy for CRPC with abiraterone plus androgen-deprivation therapy (ADT) and as second-line therapy he was being treated with docetaxel, with biochemical progression in his last prostate specific antigen measurement. He was admitted to the hospital on April 2020, in the middle of the coronavirus disease 2019 (COVID-19) pandemic, because of painful bone lesions and deterioration of renal function.


Assuntos
Anticoagulantes/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Infecções por Coronavirus/terapia , Cuidados Paliativos , Pneumonia Viral/terapia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Insuficiência Respiratória/terapia , Idoso , Antagonistas de Androgênios/uso terapêutico , Androstenos/uso terapêutico , Antineoplásicos/uso terapêutico , Betacoronavirus , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/complicações , Neoplasias Ósseas/secundário , Dor do Câncer/complicações , Dor do Câncer/terapia , Infecções por Coronavirus/complicações , Progressão da Doença , Docetaxel/uso terapêutico , Combinação de Medicamentos , Definição da Elegibilidade , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Unidades de Terapia Intensiva/provisão & distribução , Lopinavir/uso terapêutico , Masculino , Oxigenoterapia , Pandemias , Pneumonia Viral/complicações , Neoplasias de Próstata Resistentes à Castração/complicações , Neoplasias de Próstata Resistentes à Castração/patologia , Insuficiência Renal , Insuficiência Respiratória/etiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ritonavir/uso terapêutico , Índice de Gravidade de Doença , Ácido Zoledrônico/uso terapêutico
7.
PLoS One ; 15(7): e0236315, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32706791

RESUMO

The natural product nobiletin is a small molecule, widely studied with regard to its therapeutic effects, including in cancer cell lines and tumors. Recently, nobiletin has also been shown to affect circadian rhythms via their enhancement, resulting in protection against metabolic syndrome. We hypothesized that nobiletin's anti-oncogenic effects, such as prevention of cell migration and formation of anchorage independent colonies, are correspondingly accompanied by modulation of circadian rhythms. Concurrently, we wished to determine whether the circadian and anti-oncogenic effects of nobiletin differed across cancer cell lines. In this study, we assessed nobiletin's circadian and therapeutic characteristics to ascertain whether these effects depend on cell line, which here also varied in terms of baseline circadian rhythmicity. Three cell culture models where nobiletin's effects on cell proliferation and migration have been studied previously were evaluated: U2OS (bone osteosarcoma), which possesses robust circadian rhythms; MCF7 (breast adenocarcinoma), which has weak circadian rhythms; and MDA-MB-231 (breast adenocarcinoma), which is arrhythmic. We found that circadian, migration, and proliferative effects following nobiletin treatment were subtle in the U2OS and MCF7 cells. On the other hand, changes were clear in MDA-MB-231s, where nobiletin rescued rhythmicity and substantially reduced oncogenic features, specifically two-dimensional cell motility and anchorage-independent growth. Based on these results and those previously described, we posit that the effects of nobiletin are indeed cell-type dependent, and that a positive correlation may exist between nobiletin's circadian and therapeutic effects.


Assuntos
Antineoplásicos Fitogênicos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Flavonas , Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Flavonas/farmacologia , Flavonas/uso terapêutico , Humanos , Osteossarcoma/tratamento farmacológico
8.
Medicine (Baltimore) ; 99(27): e20808, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629666

RESUMO

RATIONALE: Palbociclib (PAL) is a first-in-class selective inhibitor of the cyclin-dependent kinases 4 (CDK4) and CDK6 and is indicated for the treatment of hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) in combination with fulvestrant (FUL) in postmenopausal women. Antrodia cinnamomea (AC), a well-known Chinese folk medicine in Taiwan, possesses numerous biological capabilities, most notably an anti-tumor effect. However, the clinical use of AC as complementary medicine combined with adjuvant therapy is unexplored. In this case report, we evaluated AC combined with PAL plus FUL to reduce the tumor burden in an MBC patient. PATIENT CONCERNS: A Slovenian woman diagnosed with relapsed bone metastases of breast cancer (BC) was unable to undergo surgery and refused radiation therapy due to fear of side effects; she also feared the side effects of adjuvants. However, she was eager to live with a high quality of life. DIAGNOSIS: Stage IV, HR-positive/HER2-negative BC with relapse of bone metastases. INTERVENTIONS: After diagnosis of relapse of bone metastases, she received adjuvant with PAL plus FUL. Additionally, she chose to take AC orally (10 g/d). OUTCOMES: The pain was mostly relieved, and the side effects of adjuvant therapy reduced. Magnetic resonance imaging revealed reduction of tumor size at the fifth month of adjuvant therapy plus AC. After 14 months of adjuvant therapy plus AC, the tumors at the thoracic vertebrae T1 and T3 were found to have shrunk from 35.2 and 12.0 mm to 28.1 and 9.9 mm, respectively. Remarkably, no further metastases were observed. LESSONS: According to the circulating tumor cells (CTCs) test data, AC had better anti-tumor efficacy on active tumor cells than PAL plus FUL. Thus, AC could be an effective complementary medicine for adjuvant therapy in patients with HR-positive/HER2-negative MBC. Interestingly, continued elevation of carcinoma antigen 15-3 and lactate dehydrogenase levels but decreasing levels of alkaline phosphatase were observed, which may be indicative of the potent efficacy of treatment resulting in massive tumor cell death. The CTCs test may be a sensitive approach to monitor the progression of BC and subsequently evaluate the efficiency of therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antrodia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Feminino , Fulvestranto/uso terapêutico , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Piridinas/uso terapêutico , Qualidade de Vida , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo
9.
Neoplasma ; 67(4): 724-734, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32726125

RESUMO

Acquisition of drug resistance is an enormous obstacle for osteosarcoma (OS) treatment. Copious microRNAs (miRNAs) have been reported to participate in chemoresistance. However, the role and molecular basis of miR-375 in cisplatin (Cis/DDP) sensitivity in OS remain unclear. Expression of miR-375 and autophagy-related 2B (ATG2B) in OS was examined by reverse-transcription qPCR (RT-qPCR) and western blot assay. The value of 50% growth inhibitory concentration (IC50) for DDP was determined by Cell Counting Kit (CCK)-8 assay. Cell autophagy was measured with cell proliferation, apoptotic rate, acridine orange-positive cells, and LC3-II/LC3-I ratio determined by MTT assay, flow cytometry, and western blot assay. The candidate target of miR-375 was predicted using TargetScan and was further validated by luciferase reporter and western blot analyses. Mice xenograft model was established to further investigate the tumorigenesis of U2OS/DDP in vivo. In the study, miR-375 was downregulated in DDP-resistant OS tissues and cell lines U2OS and MG63. Elevated miR-375 or reduced ATG2B decreased cell proliferation, acridine orange-positive cells and LC3-II/LC3-I ratio, and increased apoptosis rate in U2OS/DDP and MG63/DDP cells, as accompanied with lower IC50 value for DDP. ATG2B was identified to be a target of miR-375. Re-expression of ATG2B abolished miR-375-mediated effects on cell autophagy. Moreover, the reintroduction of miR-375 slowed down tumor growth of U2OD/DDP cells in vivo. In conclusion, miR-375 suppressed cells autophagy and tumor growth in DDP-resistant U2OS/DDP and MG63/DDP cells by targeting ATG2B, providing a potential target for the treatment of DDP-resistant OS.


Assuntos
Autofagia , Neoplasias Ósseas , MicroRNAs , Osteossarcoma , Animais , Apoptose , Proteínas Relacionadas à Autofagia/genética , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Carcinogênese , Linhagem Celular Tumoral , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , MicroRNAs/genética , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Proteínas de Transporte Vesicular
10.
Br J Radiol ; 93(1115): 20200257, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32706980

RESUMO

OBJECTIVE: To evaluate the multiparametric MRI in predicting chemotherapy response in pathologically proven cases of osteosarcoma and Ewing's sarcoma. Correlation between the tumor size changes and internal breakdown using RECIST 1.1, modified RECIST, quantitative apparent diffusion coefficient (ADC) and tumor volume as well as dynamic contrast-enhanced MRI (DCE-MRI). METHODS: The study included 104 patients pathologically proved osteosarcoma (53) and Ewing`s sarcoma (51) underwent MRI examinations; before and after chemotherapy. All patients were assessed using the RECIST 1.1 criteria, m-RECIST, quantitative ADC, and tumor volume evaluation. 21 patients underwent DCE-MRI curve type with quantitative parameters. Correlation between the different evaluations was carried out. Results were correlated with the post-operative pathology in 42 patients who underwent surgery and for statistical evaluation, Those patients were classified into responders (≥90% necrosis) and non-responders (<90% necrosis). RESULTS: The initial mean ADC of 104 patients of osteosarcoma and Ewing's sarcoma (0.90 ± 0.29) and (0.71 ± 0.16) respectively, differed significantly from that after treatment (1.62 ± 0.46) and (1.6 ± 0.39) respectively with (p<0.001).ADC variations (ADC%) in the non-progressive group were higher than those of the progressive group (128.3 ± 63.49 vs 36.34 ± 78.7) % with (p<0.001).ADC values and ADC variations were inversely correlated with morphologic changes, regardless of the effectiveness of chemotherapy expressed as changes in tumor size based on (RECIST 1.1, RECIST, and 3D volume). Linear regression analysis revealed a Pearson correlation coefficient of r=-0.427, -0.498 and -0.408, respectively with (p<0.001).An increase in the ADC value was not always associated with a reduction in tumor volume. The disease control rate (defined as the percentage of CR+PR+SD patients) was 89.4% and 93.9% according to RECIST 1.1 and m-RECIST respectively.42 out of the 104 patients had postsurgical histological evaluation as regards the chemotherapeutic response divided into two groups. ADC values showed a statistically significant difference between Group A and Group B being more evident with minimum ADC% (p<0.001). CONCLUSION: Quantitative diffusion-weighted imaging with ADC mapping and ADC % after chemotherapy allows a detailed analysis of the treatment response in osteosarcoma and Ewing's sarcoma. The therapeutic response can be underestimated using RECIST 1.1, so the modified RECIST should be also considered. ADVANCES IN KNOWLEDGE: Quantitative ADC especially ADC% provided an accurate non-invasive tool in the assessment of post-therapeutic cases of osteosarcoma and Ewing's sarcoma.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Imagem de Difusão por Ressonância Magnética , Imageamento por Ressonância Magnética Multiparamétrica , Osteossarcoma/tratamento farmacológico , Sarcoma de Ewing/tratamento farmacológico , Adolescente , Adulto , Área Sob a Curva , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Criança , Pré-Escolar , Meios de Contraste , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Estudos Prospectivos , Curva ROC , Critérios de Avaliação de Resposta em Tumores Sólidos , Sarcoma de Ewing/diagnóstico por imagem , Sarcoma de Ewing/patologia , Sarcoma de Ewing/cirurgia , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Adulto Jovem
11.
Bone Joint J ; 102-B(6): 795-803, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32475245

RESUMO

AIMS: To assess the correlation between the histological response to preoperative chemotherapy and event-free survival (EFS) or overall survival (OS) in patients with high-grade localized osteosarcoma. METHODS: Out of 625 patients aged ≤ 40 years treated for primary high-grade osteosarcoma between 1997 and 2016, 232 patients without clinically detectable metastases at the time of diagnosis and treated with preoperative high-dose methotrexate, adriamycin and cisplatin (MAP) chemotherapy and surgery were included. Associations of chemotherapy-induced necrosis in the resected specimen and EFS or OS were assessed using Cox model and the Pearson's correlation coefficients (r). Time-dependent receiver operating characteristic analysis was applied to determine the optimal cut-off value of chemotherapy-induced necrosis for EFS and OS. RESULTS: OS was 74% (95% confidence interval (CI) 67 to 79) at five years. Median chemotherapy-induced necrosis was 85% (interquartile range (IQR) 50% to 97%). In multivariate Cox model, chemotherapy-induced necrosis was significantly associated with EFS and OS (hazard ratio (HR) = 0.99 (95% CI 0.98 to 0.99); p < 0.001 and HR = 0.98 (95% CI 0.97 to 0.99); p < 0.001, respectively). Positive correlation was observed between chemotherapy-induced necrosis and five-year EFS and five-year OS (r = 0.91; p < 0.001, and r = 0.85; p < 0.001, respectively). The optimal cut-off value of chemotherapy-induced necrosis for five-year EFS and five-year OS was 85% and 72%, respectively. CONCLUSION: Chemotherapy-induced necrosis in the resected specimen showed positive correlation with EFS and OS in patients with high-grade localized osteosarcoma after MAP chemotherapy. In our analysis, optimal cut-off values of MAP chemotherapy-induced necrosis in EFS and OS were lower than the commonly used 90%, suggesting the need for re-evaluation of the optimal cut-off value through larger, international collaborative research. Cite this article: Bone Joint J 2020;102-B(6):795-803.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/cirurgia , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Metotrexato/administração & dosagem , Osteossarcoma/tratamento farmacológico , Osteossarcoma/cirurgia , Adolescente , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Criança , Correlação de Dados , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Necrose/induzido quimicamente , Terapia Neoadjuvante , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Período Pré-Operatório , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
12.
DNA Cell Biol ; 39(7): 1172-1180, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32584170

RESUMO

Osteosarcoma is one of the most common primary malignant tumors of the bone and tends to develop in teenage years. Although multitreatments for the diagnosis and therapy of osteosarcoma have been developed, there are still needs of new methods to prevent and treat the osteosarcoma. Here, we performed bioinformatic analysis to screen for the key genes, molecules, and pathways involved in osteosarcoma survival. Four microarray data sets (GSE99671, GSE87624, GSE65071, and GSE28423), which include data from human bone and osteosarcoma samples, were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed mRNAs and miRNAs were identified. Kyoto Encyclopedia of Genes and Genomes enriched pathways, miRNA-mRNA target, gene/disease relationship, and overall survival was elucidated using related websites and software according to bioinformatic analysis protocols. We found three critical genes miR-29c, blood vessel epicardial substance (BVES), and proteasome 20S subunit beta 2 (PSMB2) through the GEO database and predicting miRNA-mRNA target. Among these genes, BVES and PSMB2 presented a high expression level in osteosarcoma based on GSE99671 and GSE87624 data sets, while miR-29c showed a low expression level in osteosarcoma based on GSE65071 and GSE28423 data sets. Furthermore, we found that the high expression level of miR-29c and BVES associated with better prognosis, while highly expressed PSMB2 associated with poor prognosis. The abnormally expressed mRNAs and miRNAs, which were identified by integrated bioinformatic analysis, provided insights into the molecular mechanisms of osteosarcoma. Notably, we found three critical genes that could be used as novel therapeutic targets for preventing or diagnosing osteosarcoma. Finally, PSMB2 may be the target of miR-29c.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Biologia Computacional , Terapia de Alvo Molecular , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Neoplasias Ósseas/diagnóstico , Bases de Dados Genéticas , Ontologia Genética , Humanos , Osteossarcoma/diagnóstico , Prognóstico , Transcriptoma
13.
Medicine (Baltimore) ; 99(24): e20396, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541460

RESUMO

RATIONALE: Patients with, or who develop, metastatic breast cancer have a 5-year relative survival of about 25%. Endocrine therapy clearly improves outcomes in patients with estrogen receptor-positive breast cancer. In the metastatic setting, the primary goal of treatment is to maintain long-term disease control with good quality of life. Rarely, exceptional responders achieve durable disease control, and potential cures cannot be ruled out. PATIENT CONCERNS: We report the case of a 39-year-old woman with primary breast cancer and associated synchronous bone metastases, who experienced a disease response of 12 years with hormonal therapy as maintenance after first line chemotherapy, with a good toxicity profile. DIAGNOSIS: The patient was diagnosed with estrogen receptor + human epidermal growth factor receptor 2 (HER2)- metastatic breast cancer with synchronous bone metastases. INTERVENTIONS: This patient was treated with chemotherapy for 6 cycles as a first-line therapy following by endocrine treatment given as a maintenance therapy. OUTCOMES: Our patient experienced a progression-free survival >12 years with an exceptionally good quality of life. LESSONS: Our anecdotal experience highlights the existence of exceptional responders among patients with hormone receptor-positive metastatic breast cancer, who achieve clinical remission and durable disease control with endocrine therapy. Being able to identify these patients could help in the selection of the best treatment option among the many available.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Adulto , Antineoplásicos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Feminino , Humanos , Intervalo Livre de Progressão , Qualidade de Vida , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Resultado do Tratamento
14.
Adv Exp Med Biol ; 1257: 45-53, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483729

RESUMO

Although trace amounts of radioactivity are routinely used to detect osteosarcoma, the use of larger therapeutic amounts of radiation is often an unrecognized opportunity to treat metastatic osteosarcoma. This chapter will review a number of approaches to use ionizing radiation in the form of injectable radiopharmaceuticals. Since bone metastases are a common pattern of metastatic spread of cancer in general, a number of bone-seeking radiopharmaceuticals have been developed and FDA approved for treatment of bone metastases. Although osteosarcoma, a bone-forming cancer, would seem ideally suited to be treated with bone seekers, patterns of relapse involving non-ossifying metastases remain a major problem to be overcome. Thus, this review will not only describe experience using a number of bone-seeking radiopharmaceuticals such as 153-samarium-EDTMP, 153-samarium-DOTMP, and 223-radium against osteosarcoma, but also approaches to identify patients who may benefit as well as some means to the improve overall efficacy including combination therapy with routine agents and using nuclear imaging to develop best strategy for use. These include imaging with not only 99mTc-MDP standard bone scans, but also 99mTc-MDP bone scans with SPECT CT, bone-specific sodium fluoride PET-CT (Na18F), and 18FDG-PET-CT. Accurate knowledge of oligometastatic active disease can facilitate more effective use of combination therapy, including radiosensitizers and local control measures, for example, stereotactic body radiotherapy (SBRT) and/or cryoablation to reduce disease burden as well as manage and prevent micrometastatic disease from growing and metastasizing. Finally, a new tumor-specific radiopharmaceutical, CLR 131, may also provide another radiopharmaceutical to treat both osteoblastic and non-ossifying areas of osteosarcoma.


Assuntos
Antineoplásicos , Neoplasias Ósseas , Osteossarcoma , Compostos Radiofarmacêuticos , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Humanos , Recidiva Local de Neoplasia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/radioterapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/uso terapêutico
15.
Adv Exp Med Biol ; 1257: 55-66, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483730

RESUMO

In this chapter, we will review studies of HER2 in osteosarcoma and discuss the controversies that have existed in this field. Our present understanding of HER2 in the context of osteosarcoma is that it is expressed on a subset of patient samples, but that expression is not prognostic. We will review the two trials that have been conducted in osteosarcoma which have targeted HER2. Use of an antibody, trastuzumab, did not suggest activity, but a smaller study using HER2-targeted CAR T cells suggested activity may be present. A trial of an antibody-drug conjugate targeting HER2 for recurrent osteosarcoma is under consideration. Trials targeting other surface proteins for the treatment of osteosarcoma have occurred or are in development. Indeed, this leads us to discuss in a broader fashion therapeutic approaches to targeting surface proteins. It is hoped that some of these approaches will lead to new effective therapies for patients with osteosarcoma.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Receptor ErbB-2 , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia , Osteossarcoma/tratamento farmacológico , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêutico
16.
Adv Exp Med Biol ; 1257: 67-73, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483731

RESUMO

Inhalation therapy remains a suitable approach to treat lung diseases including cancer. This approach has been used to deliver various therapies including chemotherapy. The rationale for using the inhalation route vs. the systemic route has been the fewer side effects encountered when drugs are administered via inhalation. Furthermore, this approach overcomes one of the major limitations of systemic chemotherapy that results from inability of the drug to reach high concentrations in the lungs. Local delivery overcomes this limitation and spares exposure of vital organs to the drug, resulting in a more effective delivery system.Pulmonary metastasis of osteosarcoma (OS) remains a major cause of death and is very difficult to treat. Using various OS mouse models, we demonstrated that aerosol chemotherapy causes regression of pulmonary metastases and improves survival of mice with OS. In these studies, we used gemcitabine, a nucleoside analog that is effective against various solid tumors. An initial phase I study done in Europe in patients with primary lung cancer demonstrated aerosol gemcitabine therapy to be feasible and safe. In this chapter, we describe different chemotherapeutic agents delivered by inhalation to treat lung diseases with an emphasis on an ongoing study of aerosolized gemcitabine for patients with solid tumors and lung metastases developed at the MD Anderson Cancer Center that uses a convenient approach to track patient lung health with the ultimate goal of implementing this therapy at home.


Assuntos
Antineoplásicos , Neoplasias Ósseas , Neoplasias Pulmonares , Osteossarcoma , Administração por Inalação , Animais , Antineoplásicos/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Modelos Animais de Doenças , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Camundongos , Osteossarcoma/tratamento farmacológico
17.
Adv Exp Med Biol ; 1257: 75-83, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483732

RESUMO

The prognosis for metastatic osteosarcoma (OS) is poor and has not changed in several decades. Therapeutic paradigms that target and exploit novel molecular pathways are desperately needed. Recent preclinical data suggests that modulation of the Fas/FasL pathway may offer benefit in the treatment of refractory osteosarcoma. Fas and FasL are complimentary receptor-ligand proteins. Fas is expressed in multiple tissues, whereas FasL is restricted to privilege organs, such as the lung. Fas expression has been shown to inversely correlate with the metastatic potential of OS cells; tumor cells which express high levels of Fas have decreased metastatic potential and the ones that reach the lung undergo cell death upon interaction with constitutive FasL in the lung. Agents such as gemcitabine and the HDAC inhibitor, entinostat/Syndax 275, have been shown to upregulate Fas expression on OS cells, potentially leading to decreased OS pulmonary metastasis and improved outcome. Clinical trials are in development to evaluate this combination as a potential treatment option for patients with refractory OS.


Assuntos
Benzamidas , Neoplasias Ósseas , Osteossarcoma , Piridinas , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/enzimologia , Proteína Ligante Fas/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/enzimologia , Piridinas/farmacologia , Piridinas/uso terapêutico
18.
Adv Exp Med Biol ; 1257: 85-94, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483733

RESUMO

Osteosarcoma relapses not only herald a very poor prognosis but also opportunities to treat this genetically diverse complex cancer in new ways. This review will attempt to show that the field is a rapidly evolving one in which not only cytotoxic agents but also local control strategies and the immune system can be harnessed to improve the prognosis of relapsed patients. The molecular heterogeneity and the difficulty of effectively treating most common patterns of relapse with surgery and/or radiation (lung and/or bone metastases) have been responsible for a wide variety of approaches to learning whether agents are active against osteosarcoma. This chapter will highlight past, current, and potential future approaches to provide more effective systemic therapy for the problem of recurrent metastases of osteosarcoma. These include single-agent trials with a wide variety of agents, radiopharmaceuticals, and immune therapies. Finally, how such efforts are integrated into more effective local control strategies is also discussed.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/cirurgia , Ensaios Clínicos como Assunto , Humanos , Recidiva Local de Neoplasia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/radioterapia , Osteossarcoma/cirurgia
19.
Adv Exp Med Biol ; 1257: 133-139, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483736

RESUMO

The recruitment of autologous macrophages to attack osteosarcoma represents a novel immunotherapy approach to the treatment of osteosarcoma. Muramyl tripeptide-phosphatidyl ethanolamine encapsulated in liposomes (L-MTP-PE) was derived as a compound with the ability to stimulate macrophages to destroy autologous osteosarcoma tumor cells. Preclinical studies including studies in dogs with spontaneously arising osteosarcoma showed the ability of L-MTP-PE to control microscopic metastatic disease in osteosarcoma. A pivotal clinical trial led to the approval of L-MTP-PE for the treatment of newly diagnosed osteosarcoma in over 40 countries.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Acetilmuramil-Alanil-Isoglutamina , Animais , Neoplasias Ósseas/tratamento farmacológico , Ensaios Clínicos como Assunto , Cães , Humanos , Fatores Imunológicos/administração & dosagem , Lipossomos/administração & dosagem , Lipossomos/química , Osteossarcoma/tratamento farmacológico , Fosfatidiletanolaminas/administração & dosagem
20.
Life Sci ; 256: 118011, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32592723

RESUMO

Melatonin is recognized as an anti-angiogenic agent, but its function in the tumor microenvironment especially in osteosarcoma remains uncertain. Among the selected miRNAs, miR-205, miR-424, miR-140, miR-106, and miR-519 were upregulated by melatonin in osteosarcoma cells. The functional role of miR-424-5p in osteosarcoma was further analyzed using miR-424-5p mimic/inhibitor. VEGFA mRNA and protein expression were altered by miR-424-5p mimic/inhibitor transfection with and without melatonin treatment and it was further identified that the VEGFA 3'UTR is directly targeted by miR-424-5p using the luciferase reporter gene system. The conditioned medium from SaOS2 and MG63 cells treated with melatonin and/or transfected with miR-424-5p mimic/inhibitor was exposed to endothelial cells, and cell proliferation and migration was analyzed. MG-63 and SaOS2 cells are also transfected with miR-424-5p inhibitors and positioned on CAM vascular bed to study the angiogenic activity at both morphological and molecular level under melatonin treatment. Our observations demonstrate for the first time that, melatonin upregulated the expression of miR-424-5p in osteosarcoma inhibiting VEGFA. Furthermore, it suppresses tumor angiogenesis, modulating surrounding endothelial cell proliferation and migration as well as the morphology of blood vessels, and angiogenic growth factors. These findings suggest that melatonin could play a pivotal role in tumor suppression via miR-424-5p/VEGFA axis.


Assuntos
Inibidores da Angiogênese/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Melatonina/farmacologia , Osteossarcoma/tratamento farmacológico , Animais , Neoplasias Ósseas/irrigação sanguínea , Linhagem Celular Tumoral , Galinhas , Gema de Ovo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , MicroRNAs/genética , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Osteossarcoma/irrigação sanguínea , RNA Mensageiro/genética , Transdução de Sinais/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA