RESUMO
BACKGROUND: It would be helpful for the decision-making process of patients with metastatic bone disease to understand which patients are at risk for worse quality of life (QOL), pain, anxiety, and depression. Normative data, and where these stand compared with general population scores, can be useful to compare and interpret results of similar patients or patient groups, but to our knowledge, there are no such robust data. QUESTIONS/PURPOSES: We wished (1) to assess what factors are independently associated with QOL, pain interference, anxiety, and depression in patients with metastatic bone disease, and (2) to compare these outcomes with general US population values. METHODS: Between November 2011 and February 2015, 859 patients with metastatic bone disease presented to our orthopaedic oncology clinic; 202 (24%) were included as they completed the EuroQOL-5 Dimension (EQ-5DTM), PROMIS® Pain Interference, PROMIS® Anxiety, and PROMIS® Depression questionnaires as part of a quality improvement program. We did not record reasons for not responding and found no differences between survey respondents and nonrespondents in terms of age (63 versus 64 years; p = 0.916), gender (51% men versus 47% men; p = 0.228), and race (91% white versus 88% white; p = 0.306), but survey responders were more likely to be married or living with a partner (72%, versus 62%; p = 0.001). We assessed risk factors for QOL, pain interference, anxiety, and depression using multivariable linear regression analysis. We used the one-sample signed rank test to assess whether scores differed from US population averages drawn from earlier large epidemiologic studies. RESULTS: Younger age (ß regression coefficient [ß], < 0.01; 95% CI, 0.00-0.01; p = 0.041), smoking (ß, -0.12; 95% CI, -0.22 to -0.01; p = 0.026), pathologic fracture (ß, -0.10; 95% CI, -0.18 to -0.02; p = 0.012), and being unemployed (ß, -0.09; 95% CI, -0.17 to -0.02; p = 0.017) were associated with worse QOL. Current smoking status was associated with more pain interference (ß, 6.0; 95% CI, 1.6-11; p = 0.008). Poor-prognosis cancers (ß, 3.8; 95% CI, 0.37-7.2; p = 0.030), and pathologic fracture (ß, 6.3; 95% CI, 2.5-7.2; p = 0.001) were associated with more anxiety. Being single (ß, 5.9; 95% CI, 0.83-11; p = 0.023), and pathologic fracture (ß, 4.4; 95% CI, 0.8-8.0; p = 0.017) were associated with depression. QOL scores (0.68 versus 0.85; p < 0.001), pain interference scores (65 versus 50; p < 0.001), and anxiety scores (53 versus 50; p = 0.011) were worse for patients with bone metastases compared with general US population values, whereas depression scores were comparable (48 versus 50; p = 0.171). CONCLUSIONS: Impending pathologic fractures should be treated promptly to prevent deterioration in QOL, anxiety, and depression. Our normative data can be used to compare and interpret results of similar patients or patient groups. Future studies could focus on specific cancers metastasizing to the bone, to further understand which patients are at risk for worse patient-reported outcomes. LEVEL OF EVIDENCE: Level III, prognostic study.
Assuntos
Ansiedade/psicologia , Neoplasias Ósseas/psicologia , Neoplasias Ósseas/secundário , Dor do Câncer/psicologia , Depressão/psicologia , Qualidade de Vida/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/complicações , Neoplasias Ósseas/complicações , Dor do Câncer/complicações , Depressão/complicações , Avaliação da Deficiência , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The major limitation to the success of chemotherapy in osteosarcoma is the development of multidrug resistance (MDR). Preventing the emergence of MDR during chemotherapy treatment has been a high priority of clinical and investigational oncology, but it remains an elusive goal. The NSC23925 has recently been identified as a novel and potent MDR reversal agent. However, whether NSC23925 can prevent the development of MDR in cancer is unknown. Therefore, this study aims to evaluate the effects of NSC23925 on prevention of the development of MDR in osteosarcoma. METHODS: Human osteosarcoma cell lines U-2OS and Saos were exposed to increasing concentrations of paclitaxel alone or in combination with NSC23925 for 6 months. Cell sublines selected at different time points were evaluated for their drug sensitivity, drug transporter P-glycoprotein (Pgp) expression and activity. RESULTS: We observed that tumour cells selected with increasing concentrations of paclitaxel alone developed MDR with resistance to paclitaxel and other Pgp substrates, whereas cells cultured with paclitaxel-NSC23925 did not develop MDR and cells remained sensitive to chemotherapeutic agents. Paclitaxel-resistant cells showed high expression and activity of the Pgp, whereas paclitaxel-NSC23925-treated cells did not express Pgp. No changes in IC50 and Pgp expression and activity were observed in cells grown with the NSC23925 alone. CONCLUSIONS: Our findings suggest that NSC23925 may prevent the development of MDR by specifically preventing the overexpression of Pgp. Given the significant incidence of MDR in osteosarcoma and the lack of effective agents for prevention of MDR, NSC23925 and derivatives hold the potential to improve the outcome of cancer patients with poor prognosis due to drug resistance.
Assuntos
Neoplasias Ósseas/tratamento farmacológico , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Osteossarcoma/tratamento farmacológico , Piperidinas/farmacologia , Quinolinas/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese , Antineoplásicos Fitogênicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Linhagem Celular Tumoral , Sinergismo Farmacológico , Humanos , Paclitaxel/farmacologiaRESUMO
HYPOTHESIS: This study assessed, if there was a difference in surgical decision making for metastatic humeral lesions based on; orthopaedic subspecialty, tumor characteristics. STUDY TYPE: Cross sectional survey study. MATERIALS AND METHODS: Twenty-four case scenarios were created by combining: tumor type, life expectancy, fracture type, and anatomical location. Participants were asked for every case: what treatment would you recommend? Participants were 78 (48%) orthopaedic oncologists and 83 (52%) orthopaedic surgeons that were not regularly involved in the treatment of bone tumors. RESULTS: There was a difference between orthopaedic oncologists and other subspecialty surgeons in recommendation for specific treatments: intramedullary nailing was less often recommended by orthopaedic oncologists (53%, 95%CI: 47-59) compared to other surgeons (62%, 95%CI: 57-67) (p=0.023); while endoprosthetic reconstruction (orthopaedic oncologists: 8.8% [95%CI: 6.6-11], other surgeons: 3.6%[95%CI: 2.3-4.8], p<0.001) and plate-screw fixation (orthopaedic oncologists: 19%[95%CI: 14-25], other surgeons: 9.5%[95%CI: 5.9-13], p=0.003) were more often recommended by orthopaedic oncologists. There was no difference in recommendation for nonoperative management. There were differences in recommendation for specific treatments based on tumor type, life expectancy, and anatomical location, but not fracture type. DISCUSSION: Subspecialty training and patient and tumor characteristics influence the decision for operative management and the decision for a specific implant in metastatic humeral fractures. LEVEL OF EVIDENCE: Level 3.
Assuntos
Neoplasias Ósseas/cirurgia , Fraturas Espontâneas/cirurgia , Fraturas do Úmero/cirurgia , Ortopedia , Padrões de Prática Médica , Oncologia Cirúrgica , Neoplasias Ósseas/complicações , Neoplasias Ósseas/secundário , Placas Ósseas , Parafusos Ósseos , Estudos Transversais , Feminino , Fixação Intramedular de Fraturas , Fraturas Espontâneas/etiologia , Humanos , Fraturas do Úmero/etiologia , Masculino , Próteses e Implantes , Inquéritos e QuestionáriosRESUMO
PURPOSE: The scapula is a relatively common site for chondrosarcoma to develop in contrary to the clavicle, which is rarely affected by these tumors. The aim of this study is to determine the functional and oncological outcome for patients treated operatively for scapular or clavicular chondrosarcoma. METHODS: In this single-center retrospective study, we included a sample of 20 patients that received the diagnosis of a primary chondrosarcoma of the scapula or clavicle. Of the surviving patients, the functional function was assessed using the DASH and the PROMIS Physical Function-Upper Extremity. Patients were longitudinally tracked for their oncological outcome. RESULTS: All patients were followed for at least 2 years or until death. The mean age of the cohort was 47 years. Eighteen patients suffered from a chondrosarcoma of the scapula, and in 2 patients, the tumor was located in the clavicle. Metastasis, local recurrence and a higher tumor grade were all associated with a decreased overall survival. For the patients with a chondrosarcoma of the scapula, the average DASH score was 16 ± 16 and the mean PROMIS Physical Function-Upper Extremity score was 48 ± 10. Patients with both an intact rotator cuff and glenoid had a better physical function. CONCLUSIONS: Upper extremity function after (partial) scapulectomy varied depending on whether the glenoid was spared and whether a functioning shoulder abductor remained. When the resection spared these structures, then excellent functional outcomes were reported. Oncologic outcomes depended upon the grade of the tumor and whether local recurrence and metastases occurred.
Assuntos
Neoplasias Ósseas/cirurgia , Condrossarcoma/cirurgia , Clavícula/cirurgia , Escápula/cirurgia , Adulto , Idoso , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/mortalidade , Condrossarcoma/diagnóstico , Condrossarcoma/mortalidade , Feminino , Seguimentos , Humanos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
AIMS: The aim of the study was to compare measures of the quality of life (QOL) after resection of a chordoma of the mobile spine with the national averages in the United States and to assess which factors influenced the QOL, symptoms of anxiety and depression, and coping with pain post-operatively in these patients. PATIENTS AND METHODS: A total of 48 consecutive patients who underwent resection of a primary or recurrent chordoma of the mobile spine between 2000 and 2015 were included. A total of 34 patients completed a survey at least 12 months post-operatively. The primary outcome was the EuroQol-5 Dimensions (EQ-5D-3L) questionnaire. Secondary outcomes were the Patient-Reported Outcome Measurement Information System (PROMIS) anxiety, depression and pain interference questionnaires. Data which were recorded included the indication for surgery, the region of the tumour, the number of levels resected, the status of the surgical margins, re-operations, complications, neurological deficit, length of stay in hospital and rate of re-admission. RESULTS: The median EQ-5D-3L score was 0.71 (interquartile range (IQR) 0.44 to 0.79) which is worse than the national average in the United States of 0.85 (p < 0.001). Anxiety (median: 55 (IQR 49 to 61), p = 0.031) and pain (median: 61 (IQR 56 to 68), p < 0.001) were also worse than the national average in the United States (50), while depression was not (median: 52 (IQR 38 to 57), p = 0.513). Patients who underwent a primary resection had better QOL and less anxiety, depression and pain compared with those who underwent resection for recurrent or residual disease. The one- and five-year probabilities were 0.96 and 0.74 for survival, 0.07 and 0.25 for tumour recurrence, and 0.02 and 0.16 for developing distant metastasis. A total of 25 local complications occurred in 20 patients (42%), and there were 50 systemic and other complications in 25 patients (52%) within 90 days. CONCLUSION: These patient reported outcomes and oncological and surgical outcomes can be used when counselling patients and to aid decision-making when planning surgery. Cite this article: Bone Joint J 2017;99-B:979-86.
Assuntos
Cordoma/psicologia , Cordoma/cirurgia , Qualidade de Vida , Neoplasias da Medula Espinal/psicologia , Neoplasias da Medula Espinal/cirurgia , Idoso , Ansiedade/psicologia , Cordoma/patologia , Depressão/psicologia , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dor Pós-Operatória/psicologia , Medidas de Resultados Relatados pelo Paciente , Doses de Radiação , Neoplasias da Medula Espinal/patologia , Inquéritos e Questionários , Tomografia Computadorizada por Raios X , Estados UnidosRESUMO
AIMS: Instability of the hip is the most common mode of failure after reconstruction with a proximal femoral arthroplasty (PFA) using an endoprosthesis after excision of a tumour. Small studies report improved stability with capsular repair of the hip and other techniques, but these have not been investigated in a large series of patients. The aim of this study was to evaluate variables associated with the patient and the operation that affect post-operative stability. We hypothesised an association between capsular repair and stability. PATIENTS AND METHODS: In a retrospective cohort study, we identified 527 adult patients who were treated with a PFA for tumours. Our data included demographics, the pathological diagnosis, the amount of resection of the abductor muscles, the techniques of reconstruction and the characteristics of the implant. We used regression analysis to compare patients with and without post-operative instability. RESULTS: A total of 20 patients out of 527 (4%) had instability which presented at a mean of 35 days (3 to 131) post-operatively. Capsular repair was not associated with a reduced rate of instability. Bivariate analysis showed that a posterolateral surgical approach (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.02 to 0.86) and the type of implant (p = 0.046) had a significant association with reduced instability; age > 60 years predicted instability (OR 3.17, 95% CI 1.00 to 9.98). Multivariate analysis showed age > 60 years (OR 5.09, 95% CI 1.23 to 21.07), female gender (OR 1.73, 95% CI 1.04 to 2.89), a malignant primary bone tumour (OR 2.04, 95% CI 1.06 to 3.95), and benign condition (OR 5.56, 95% CI 1.35 to 22.90), but not metastatic disease or soft-tissue tumours, predicted instability, while a posterolateral approach (OR 0.09, 95% CI 0.01 to 0.53) was protective against instability. No instability occurred when a synthetic graft was used in 70 patients. CONCLUSION: Stability of the hip after PFA is influenced by variables associated with the patient, the pathology, the surgical technique and the implant. We did not find an association between capsular repair and improved stability. Extension of the tumour often dictates surgical technique; however, our results indicate that PFA using a posterolateral approach with a hemiarthroplasty and synthetic augment for soft-tissue repair confers the lowest risk of instability. Patients who are elderly, female, or with a primary benign or malignant bone tumour should be counselled about an increased risk of instability. Cite this article: Bone Joint J 2017;99-B:531-7.
Assuntos
Artroplastia de Quadril/métodos , Neoplasias Femorais/cirurgia , Luxação do Quadril/etiologia , Prótese de Quadril , Instabilidade Articular/etiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Criança , Pré-Escolar , Feminino , Neoplasias Femorais/secundário , Seguimentos , Humanos , Cápsula Articular/cirurgia , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Adulto JovemRESUMO
ET-743 (Yondelis(TM), Trabectedin) isolated from the tunicate Ecteinascidia turbinata, is being tested in phase II clinical trials in Europe and the United States of America (USA). Studies with different solid tumours have shown antitumour activity in advanced, pre-treated sarcomas as well as in drug-resistant breast and ovarian cancer. The primary mechanism of action for ET-743 has not been fully elucidated and different models have been suggested to explain its molecular mechanism of action. ET-743 binds tightly to the minor groove of DNA and previous data have suggested that ET-743 acts by interfering with RNA transcription. To further investigate the mechanism of in vitro drug resistance, we evaluated the gene expression profile in ovarian and chondrosarcoma cell lines selected for resistance to ET-743. We found 70 genes whose expression was modulated in both drug-resistant cell lines when compared with their respective parental drug-sensitive cell lines. This pattern of gene expression seems to be selective for ET-743-resistant cells, since ovarian cancer cells resistant to paclitaxel did not share the same gene expression changes. Data presented in this study reveal different molecular pathways that could be involved in the cellular mechanism of ET-743 resistance.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Condrossarcoma/tratamento farmacológico , Dioxóis/uso terapêutico , Isoquinolinas/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Antineoplásicos , Antineoplásicos Alquilantes/farmacocinética , Linhagem Celular Tumoral , Condrossarcoma/genética , Dioxóis/farmacocinética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Isoquinolinas/farmacocinética , Neoplasias Ovarianas/genética , RNA Neoplásico/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Tetra-Hidroisoquinolinas , TrabectedinaRESUMO
The cell cycle progression and viability of stimulated and intact lymphocytes from 20 subjects with acquired immune deficiency syndrome (AIDS) was determined by flow cytometry. As compared to controls, 62% less AIDS lymphocytes, cultured for 72 hr in the presence of lectins (Con-A, PHA, PWM), had entered the proliferative phases of the cell cycle, while the respective value for periodic-acid (H5IO6)-stimulated cells was 34%. The helper-suppressor ratios and natural kill cell percentages of the unstimulated and PHA-activated AIDS lymphocytes increased approximately 3-fold after 72 hr in culture. The natural killer (NK) cell fraction of the PHA-stimulated and unstimulated AIDS cultures comprised approximately 20% as compared to 10% in controls. However, no changes in the percentages of T-lymphocytes were detected in the AIDS cell cultures. Throughout the culture period, viability of the unstimulated AIDS lymphocytes exceeded 90%, whereas in stimulated cultures it fluctuated within the 65-90% range. It is concluded that the liability of AIDS lymphocytes to mitogens is probably a direct consequence of the human immunodeficiency virus (HIV) infection.
Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Antígenos de Superfície/análise , Ativação Linfocitária , Linfócitos T/imunologia , Ciclo Celular/efeitos dos fármacos , Humanos , Interleucina-2/biossíntese , Masculino , Fenótipo , Fito-Hemaglutininas/farmacologia , Linfócitos T/classificaçãoRESUMO
Cultures of HUT 102 lymphoblasts, comprised of near-diploid and hyperdiploid cells (11 and 22 pg of DNA/nucleus), were irradiated for 2 h by long wave ultraviolet light (UV-A) (2.1 mW/cm2), reacted for the same time in the dark with suprapharmacologic concentrations of 8-methoxypsoralen (8-MOP) (15 micrograms/ml) and exposed to 8-MOP and UV-A (PUVA) under identical conditions. Flow cytometric determinations of cellular DNA content and IdUrd incorporation indicated that UV-A irradiated cells incorporated IdUrd at the control levels and that the number of cells in S and G2 + M phases of the cell cycle likewise were identical to controls. The dark reaction of HUT 102 cells with 8-MOP has, however, resulted in a transient increase of IdUrd incorporation, but it has not affected cellular proliferation rates. On the other hand, no IdUrd incorporation was detected after PUVA. The analysis of the DNA content of intact and PUVA-exposed cultures showed that the number of near-diploid S-phase cells was greater 24 h after PUVA, whereas the number of hyperdiploid cells in all phases of the cell cycle had decreased. Under stated conditions the viability of HUT 102 cells and their cell cycle disturbances by PUVA are determined in part by the amount of DNA in target lymphoblasts.
Assuntos
Divisão Celular , Linfócitos/citologia , Metoxaleno/farmacologia , Raios Ultravioleta , Divisão Celular/efeitos dos fármacos , Divisão Celular/efeitos da radiação , Sobrevivência Celular , DNA/metabolismo , Citometria de Fluxo , Humanos , Linfócitos/metabolismo , Células Tumorais CultivadasRESUMO
Ultrastructural alterations of the plasma membrane in HUT 102 lymphoblasts were assessed after a 2-h interaction with a suprapharmacologic (15 micrograms/ml) concentration of 8-MOP, 2-h irradiation with UVA (2.1 mW/cm2), and the exposure of the HUT 102 cells to PUVA under the same conditions. The dark reaction of HUT cells with 8-MOP resulted in the disappearance of microvilli, the emergence of plasma-membrane-associated spherical bodies, formation of lamellar fungiform membrane evaginations, and, in approximately 1% of the cells, formation of uropods and cell capping. Except for uropod formation and cell capping, UVA has induced the same plasma-membrane alterations, and was more deleterious to structural cytoplasmic integrity than 8-MOP. Morphologic changes of the plasma membrane in PUVA-exposed cells tended to replicate structural alterations elicited independently during the dark reaction by suprapharmacologic 8-MOP concentrations. Partial retention of microvilli by cells after PUVA was the sole exception. In light of all available evidence we conclude that psoralen during the dark reactions interacts with plasma membrane lipids by as yet undisclosed mechanisms and that in addition to lipids, membrane proteins are also the primary target of the initial interaction of HUT 102 cells with psoralen during PUVA treatment.
Assuntos
Ficusina/farmacologia , Furocumarinas/farmacologia , Linfócitos/efeitos dos fármacos , Terapia PUVA , Células-Tronco/efeitos dos fármacos , Raios Ultravioleta , Membrana Celular/efeitos dos fármacos , Membrana Celular/efeitos da radiação , Membrana Celular/ultraestrutura , Escuridão , Luz , Linfócitos/efeitos da radiação , Linfócitos/ultraestrutura , Metoxaleno/farmacologia , Microscopia Eletrônica , Células-Tronco/efeitos da radiação , Células-Tronco/ultraestrutura , Células Tumorais CultivadasRESUMO
Thyroid function, including growth, is TSH dependent, and most metabolic functions of TSH are thought to be mediated by cAMP. Recently, it has been suggested by several groups that growth may be an exception and that it may not be related to cAMP action. In addition, evidence has accrued indicating that the thyroid-stimulating antibody (TSAb) of Graves' disease, the metabolic actions of which are also cAMP mediated, may not be the goitrogenic agent in that syndrome. To evaluate these concepts, we used functioning rat thyroid cells (FRTL5) in monolayer culture and, as indices of growth, the incorporation of [3H]thymidine ([3H]Tdr) into DNA, the concentration of DNA measured directly, and the percentage of cells in S phase, as assessed by flow cytometry, all studied over 72 h of incubation. TSH, forskolin, and cholera toxin enhanced growth by each criterion and increased the concentration of cAMP in parallel; the effect on cAMP occurred rapidly and was maximal well in advance of influences on growth. In all instances, measures of growth promotion were minimal at 24 h and maximal at 48 h, except for [3H]Tdr incorporation, which was greater at 72 h than at 48 h. 3-Isobutyl-1-methylxanthine (IBMX) and (Bu)2 cAMP were also tested. Both enhanced all indices of growth and were as effective as TSH. Maximal responses to TSH were obtained at 100-200 microU/ml, maximal responses to both IBMX and (Bu)2cAMP occurred at 5 X 10(-4) M, and all three stimulators increased the DNA concentration and [3H]Tdr uptake and induced S phase in at least 20% of all cells in culture. The peak effect on DNA and S phase was consistently at 48 h. Epidermal growth factor (EGF) was shown to increase [3H]Tdr incorporation in a nondose-dependent fashion (10(-10) to 5 X 10(-9) M gave approximately 250% of control) over 1, 2, 3, 5, and 7 days, with no increase in DNA and a slight decrement in the concentration of cAMP. A laboratory standard TSAb-immunoglobulin G was shown to parallel TSH in both increasing cAMP (over 2 h of incubation) and growth stimulation (over 72 h). The data are entirely consistent with the view that TSH-stimulated thyroid growth is mediated by cAMP and that the established action of TSAb on adenylate cyclase is sufficient to explain goiter as well as hyperthyroidism in Graves' disease.
Assuntos
AMP Cíclico/farmacologia , Glândula Tireoide/citologia , 1-Metil-3-Isobutilxantina/farmacologia , Animais , Bucladesina/farmacologia , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Colforsina/farmacologia , DNA/biossíntese , Fator de Crescimento Epidérmico/farmacologia , Imunoglobulina G/fisiologia , Imunoglobulinas Estimuladoras da Glândula Tireoide , Ratos , Tireotropina/farmacologiaRESUMO
A functioning rat thyroid cell line (FRTL5) was used to study interactions of thyrotropin (TSH) and various cytokines on expression of class I and II major histocompatibility complex (MHC) antigens and on growth stimulation. Only gamma-interferon (gamma-IFN) affected MHC antigen expression, i.e., to enhance class I, that was constitutive, and to induce class II. A concomitant, but probably not directly related, effect of gamma-IFN was to diminish growth stimulation, as effected by TSH and other activators of adenylate cyclase and measured by DNA increase and enhanced incorporation of [3H]thymidine into DNA. Stimulation of growth by tetradecanoylphorbol ester was also decreased by gamma-IFN. These effects of gamma-IFN were mimicked to some degree by tumor necrosis factor but there was major synergism between the two cytokines. Enhanced accumulation of cAMP by TSH and other agents was not diminished in these experiments. Flow cytometry analysis showed that inhibition of growth stimulation involved blocking of the passage of cells from the G0/1 phase to the S phase. The data may have relevance to goiter size in autoimmune thyroid disease.
Assuntos
Crescimento/efeitos dos fármacos , Antígenos de Histocompatibilidade Classe II/imunologia , Interferon gama/farmacologia , Glândula Tireoide/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Animais , Células Cultivadas , Indutores de Interferon/farmacologia , Ratos , Glândula Tireoide/citologia , Tireotropina/antagonistas & inibidoresRESUMO
The dark reaction of 8-methoxypsoralen (8-MOP) with cultured rat osteoblasts did not cause significant changes in cellular replication rates or in the synthesis of RNA and proteins. Microscopic examination, however, revealed that the dark reaction resulted in massive accumulation of perinuclear lipids and in the statistically significant enhancement of alkaline phosphatase activity. A sharp, and statistically significant, upsurge of lipid synthesis in osteoblasts preceded microscopically detectable accumulation of lipids and occurred only during the initial, but not during the subsequent stages of the dark reaction. These results suggest that in the course of the dark reaction the plasma membrane of osteoblasts is a target of psoralen.
Assuntos
Metoxaleno/farmacologia , Osteoblastos/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Divisão Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Células Cultivadas , Escuridão , Cinética , Metabolismo dos Lipídeos , Osteoblastos/citologia , Osteoblastos/metabolismo , RatosRESUMO
Nitroxyldisulfonate [Fremy's salt; (KSO3)2NO.] and bisulfite (NaHSO3) have abolished periodic acid (H5IO6)-induced blastogenesis of human peripheral blood lymphocytes (HPBL), but only inhibited the blastogenic response of H5IO6-oxidized rat and mouse lymphocytes, as determined by the rates of nucleic acids synthesis, BrdUrd incorporation and by cell numbers in S + G2 + M phases of the cell cycle. The viability of the intact human, rat and mouse lymphocytes remained essentially unimpaired by 30 min pulses of 1 mM Fremy's salt or bisulfite. The marked inhibition of periodic acid-induced blastogenesis, exerted by Fremy's salt and by bisulfite, was attributed to the effect of the corresponding carbonyl addition derivatives formed in situ of the oxidized cell membranes. Consequently, it is concluded that Fremy's salt like bisulfite possibly forms addition derivatives with membrane carbonyls of viable target cells.
Assuntos
Ativação Linfocitária/efeitos dos fármacos , Compostos Nitrosos/farmacologia , Ácido Periódico/antagonistas & inibidores , Sulfitos/farmacologia , Animais , Concanavalina A/farmacologia , DNA/biossíntese , Feminino , Citometria de Fluxo , Imunofluorescência , Radicais Livres , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Oxirredução , Ratos , Ratos Endogâmicos , Especificidade da Espécie , Baço/metabolismoRESUMO
Osteoid osteoma, a benign bone tumor, has traditionally been treated with operative excision. A recently developed method for percutaneous ablation of the tumor has been proposed as an alternative to operative treatment. The relative outcomes of the two approaches to treatment have not previously been compared, to our knowledge. The rates of recurrence and of persistent symptoms were compared in a consecutive series of eighty-seven patients who were managed with operative excision and thirty-eight patients who were managed with percutaneous ablation with radiofrequency. Patients who had a spinal lesion were excluded. The minimum duration of follow-up was two years. There was a recurrence, defined as the need for subsequent intervention, after operative treatment in six (9 per cent) of sixty-eight patients who had been managed for a primary lesion and in two of nineteen who had been managed for a recurrent lesion. The average length of the hospital stay was 4.7 days for the patients who had a primary lesion and 5.1 days for those who had a recurrent lesion. There was a recurrence after percutaneous treatment in four (12 per cent) of thirty-three patients who had been managed for a primary lesion and in none of five who had been managed for a recurrent lesion. The average length of the hospital stay was 0.2 day for these thirty-eight patients. With the numbers available, we could detect no significant difference between the two treatments with regard to the rate of recurrence. The rate of persistent symptoms (that is, symptoms that did not necessitate additional treatment) was greater than the rate of recurrence. According to responses to a questionnaire, eight (30 per cent) of twenty-seven patients had persistent symptoms after operative treatment and six (23 per cent) of twenty-six patients had persistent symptoms after percutaneous treatment with radiofrequency. Two patients had complications after operative excision, necessitating a total of five additional operations. There were no complications associated with the percutaneous method. The results of the present study suggest that percutaneous ablation with radiofrequency is essentially equivalent to operative excision for the treatment of an osteoid osteoma in an extremity. The percutaneous method is preferred for the treatment of extraspinal osteoid osteoma because it generally does not necessitate hospitalization, it has not been associated with complications, and it is associated with a rapid convalescence.
Assuntos
Neoplasias Ósseas/cirurgia , Ablação por Cateter/métodos , Recidiva Local de Neoplasia/etiologia , Osteoma Osteoide/cirurgia , Osteotomia/métodos , Adulto , Neoplasias Ósseas/complicações , Neoplasias Ósseas/diagnóstico por imagem , Pré-Escolar , Feminino , Seguimentos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Osteoma Osteoide/complicações , Osteoma Osteoide/diagnóstico por imagem , Osteotomia/efeitos adversos , Radiografia , Reoperação/estatística & dados numéricos , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Blastogenic and cytotoxic effects of hexavalent chromium were evaluated by direct, 2 and 20 min oxidation of lymphocytes by 10.0 to 0.0005 mM CrO3 at 0 degrees C. Oxidized cells exhibited concentration-dependent cytotoxicity and the inhibition of tritiated thymidine incorporation rates. When lymphocytes were oxidized first by 1.0 mM periodic acid (H5IO6) and thereafter by 1.0 mM CrO3, the viability and [3H]-TdR incorporation rates of sequentially oxidized cells were identical to the corresponding indicators of lymphocytes oxidized only by CrO3. The reversal of the oxidation sequence restored [3H]-TdR incorporation to control levels and increased cell survival. It is therefore concluded that direct interaction of hexavalent CrO3 with plasma membrane of lymphocytes results in concentration-dependent cytotoxicity and the inhibition of [3H]-TdR incorporation, but it does not induce blastogenesis.
Assuntos
Cromatos/farmacologia , Ativação Linfocitária , Linfócitos/metabolismo , Animais , Células Cultivadas , Camundongos , Oxirredução , Ácido Periódico/farmacologiaRESUMO
STUDY DESIGN: This was a blind, prospective study of the effect of sera from patients with spinal cord and head injuries on osteoblast proliferation. OBJECTIVES: The authors studied whether a humoral factor that stimulates the formation of heterotopic bone is released into the circulation after a neural injury. BACKGROUND DATA: Other authors have shown that a humoral osteoinductive factor may be released after head and spinal cord injuries. METHODS: Serum was obtained at certain times throughout the first 12 weeks post-injury and from control subjects. It was incubated with osteoblasts harvested from fetal rats, as well as with fibroblast controls. RESULTS: There was a significant rise in serum mitogenic activity after injury in both groups. When patients that developed heterotopic ossification were compared to other patients and controls, no significant differences were seen. CONCLUSIONS: This in vitro study fails to support a humoral mechanism for heterotopic ossification after spinal cord or brain injuries.
Assuntos
Lesões Encefálicas/sangue , Glicoproteínas/sangue , Substâncias de Crescimento/sangue , Ossificação Heterotópica/etiologia , Osteoblastos/citologia , Traumatismos da Medula Espinal/sangue , Adulto , Animais , Lesões Encefálicas/complicações , Células Cultivadas , Feminino , Fibroblastos/citologia , Glicoproteínas/isolamento & purificação , Substâncias de Crescimento/isolamento & purificação , Humanos , Técnicas In Vitro , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Mitose , Ratos , Traumatismos da Medula Espinal/complicaçõesRESUMO
The turnover of 32P-labeled phospholipids in HUT 102 lymphoblasts was determined after a 2 h interaction of lymphoblasts with 8-methoxypsoralen (8-MOP) (15 micrograms ml-1), longwave UV light (UVA) irradiation and PUVA (8-MOP and UVA). In parallel experiments, micellar suspensions of lyso-phosphatidylcholine (PtdC), dipalmitoyl-PtdC and dilinoleoyl-PtdC, treated in a similar manner, served for the correlative assessments of cellular lipid changes. The dark reaction, UVA irradiation and PUVA all depressed total phospholipid levels in HUT 102 cells, although only PUVA induced a statistically significant decline. Thin layer chromatography (TLC) analysis revealed that neither UVA nor 8-MOP alone triggered any significant changes in the cellular content of phosphatidylinositol (PtdI), phosphatidylinositol 4-monophosphate (PtdIP) and phosphatidylinositol 4,5-bisphosphate (PtdIP2), whereas the lyso-PtdC and PtdI content of lymphoblasts showed a two-fold increase after PUVA. The TLC analysis of lyso-PtdC and micelles of dipalmitoyl-PtdC did not reveal any detectable changes after the dark reaction with 8-MOP, UVA irradiation and PUVA. In contrast, the derivatives of dark and UVA mediated reactions of 8-MOP with dilinoleoyl-PtdC were detected by TLC. These results suggest that the formation of 8-MOP derivatives of cellular phospholipids effected by PUVA, modulates the turnover of phosphoinositides and the rate of cellular proliferation.
Assuntos
Metoxaleno/farmacologia , Fosfatidilcolinas/metabolismo , Fosfolipídeos/metabolismo , Raios Ultravioleta , Linhagem Celular , Cromatografia em Camada Fina , Humanos , Linfoma de Células T , Fosfatidilcolinas/isolamento & purificação , Fosfatidilinositóis/isolamento & purificação , Fosfatidilinositóis/metabolismo , Fosfolipídeos/isolamento & purificação , Radioisótopos de Fósforo , Neoplasias CutâneasRESUMO
Serum calcitonin was determined by RIA in 59 healthy subjects (Group 1), 49 randomly selected patients with treated or untreated thyroid disorders (Group 2), and in 12 kindred of a pheochromocytoma index case (Group 3). Although most subjects in Group 2 had normal calcitonin levels, there were significant (p less than 0.001) differences between all three groups. Of the five patients in Group 2 with high serum calcitonin, one had medullary cancer of the thyroid, one had multiple endocrine neoplasia, one had acromegaly, and two remained undiagnosed. Increased serum calcitonin levels were also found in seven of 12 normotensive relatives of a patient with pheochromocytoma. It is therefore concluded that high serum calcitonin levels in patients with thyroid disorders strongly suggest the presence of C-cell neoplasia or medullary cancer of the thyroid.
Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Calcitonina/sangue , Feocromocitoma/genética , Doenças da Glândula Tireoide/sangue , Adolescente , Neoplasias das Glândulas Suprarrenais/sangue , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Feocromocitoma/sangue , Radioimunoensaio , Valores de Referência , Neoplasias da Glândula Tireoide/sangueRESUMO
This article discusses opinions for reconstruction of bony defects created by tumor resections. The literature is reviewed, and the results of different reconstruction methods from the Massachusetts General and Children's Hospitals' database are discussed. The authors' treatment goals and algorithms are reviewed as well as the rationale behind them.