RESUMO
A retrospective case review was carried out to report the outcomes in a contemporary case series of Ewing's sarcoma originating in the hand. We identified five patients treated since 1995. All five had wide surgical excision, one by ray amputation. All were treated with chemotherapy. Four patients also received radiation therapy, two to treat metastases and two as an adjunct to local excision. There were no local recurrences. Two patients developed metastases. Both died of their disease. Neither of these two patients had received local postoperative radiation therapy; one did not receive chemotherapy before definitive surgery. The other three patients were alive and free of disease at last follow-up, 4 to 12 years after initial presentation.
Assuntos
Neoplasias Ósseas/cirurgia , Falanges dos Dedos da Mão/cirurgia , Metacarpo/cirurgia , Sarcoma de Ewing/cirurgia , Adolescente , Adulto , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/radioterapia , Transplante Ósseo , Quimioterapia Adjuvante , Criança , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Radioterapia Adjuvante , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/radioterapia , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/radioterapia , Neoplasias de Tecidos Moles/cirurgia , Adulto JovemRESUMO
Laboratory bioassays consisting of sediments spiked with three concentrations (30, 130, and 260 microg g-1 As dry wt) of arsenic (As+3) were used to assess morphologic responses and growth in Chironomus tentans larvae. Chironomid larvae were raised in contaminated sediments from egg stage to emergence, and mouthpart abnormalities, larval length, and larval head width were used as end points to determine differences between metal-spiked and control specimens. C. tentans exhibited significantly higher mouthpart deformity proportions, smaller body sizes, smaller head widths, and slower development than control larvae. Our results demonstrate a dose-response relationship between As and mentum deformities in C. tentans. However, the proportion of deformed larvae did not increase with time in the treatment tanks. Results demonstrate that As induces mouthpart abnormalities at various concentrations. This research provides more support for the use of chironomid abnormalities as a tool for the assessment of heavy-metal pollution in aquatic systems.
Assuntos
Anormalidades Induzidas por Medicamentos , Arsênio/toxicidade , Chironomidae/efeitos dos fármacos , Crescimento/efeitos dos fármacos , Animais , Chironomidae/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Larva/efeitos dos fármacosRESUMO
Diabetes, which causes enhanced oxidative stress, is a multifactorial disease that leads to deleterious effects in many organ systems within the body. Ubiquinones (coenzyme Q(9) and Q(10)) are amphipathic molecular components of the electron transport chain that function also as endogenous antioxidants and attenuate the diabetes-induced decreases in antioxidant defense mechanisms. Insulin-like growth factor 1 (IGF-1) is considered to be an "essential surviving factor", the level and function of which are compromised in diabetes. This study investigated the impact of IGF-1 supplementation on ubiquinone levels in a rat model of type I diabetes. Adult male Sprague-Dawley rats were divided into four groups: control, control plus IGF-1, diabetic and diabetic plus IGF-1. Diabetic animals received a single intravenous injection of streptozotocin (STZ, 55 mg/kg). IGF-1 supplementation groups received a daily intraperitoneal dose of 3 mg IGF-1 per kilogram body weight for 7 weeks. Coenzyme Q(9) and Q(10) levels were assessed by ultraviolet detection on high pressure liquid chromatography. STZ caused a significant reduction in body weight and an elevation in blood glucose level, which were not prevented by IGF-1 supplementation. In addition Q(9) and Q(10) levels in diabetic liver were significantly elevated. IGF-1 supplementation prevented liver alterations in Q(10) but not Q(9) levels. Q(9) and Q(10) levels in diabetic kidney were significantly depressed, and these deleterious effects were abolished by IGF-1 treatment. These data suggest that IGF-1 antagonizes the diabetes-induced alterations in endogenous antioxidants including coenzyme Q(10), and hence may have a therapeutic role in diabetes.
Assuntos
Diabetes Mellitus Experimental/sangue , Fator de Crescimento Insulin-Like I/farmacologia , Ubiquinona/análogos & derivados , Ubiquinona/metabolismo , Animais , Coenzimas , Diabetes Mellitus Tipo 1/sangue , Suplementos Nutricionais , Modelos Animais de Doenças , Fator de Crescimento Insulin-Like I/administração & dosagem , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Valores de ReferênciaRESUMO
Diabetes and hypertension both produce myocardial dysfunction that accelerates cardiovascular morbidity and mortality. Coexistence of the two often results in a more severe cardiomyopathy than either process alone. The purpose of this study was to characterize the contractile function of diabetic hypertensive cardiomyopathy at the single myocyte level. Adult spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were made diabetic with a single injection (55 mg/kg) of streptozotocin (STZ). Contractile properties of ventricular myocytes were evaluated, including peak shortening (PS), time-to-peak shortening (TPS), time-to-90% relengthening (TR90) and maximal velocities of shortening/relengthening (+/-dL/d t). The experimental animals exhibited enlarged heart size, elevated blood glucose and systolic blood pressure. PS was unchanged (SHR), enhanced (WKY-STZ) or depressed (SHR-STZ) compared to control (WKY). Myocytes from all experimental groups displayed prolonged TPS and TR90 compared to the WKY group, although only those from the hypertensive groups (SHR, SHR-STZ) were associated with reduced +/-dL/d t. Additionally, myocytes from the WKY-STZ but not the SHR or the SHR-STZ groups exhibited impaired responsiveness to increased extracellular Ca2+. Myocytes from the SHR-STZ group displayed a leftward shift of the stimulus frequency-peak shortening response curve compared to the WKY group. These results confirmed observations at the multicellular levels that combination of diabetes and hypertension results in a greater impairment of cardiac contractile function than is seen with either disease alone.
Assuntos
Cardiomiopatias/fisiopatologia , Diabetes Mellitus Experimental/complicações , Hipertensão/complicações , Contração Miocárdica/fisiologia , Animais , Cálcio/metabolismo , Cardiomiopatias/etiologia , Cardiomiopatias/patologia , Estimulação Elétrica , Coração/fisiopatologia , Ventrículos do Coração , Humanos , Técnicas In Vitro , Masculino , Miocárdio/patologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
We studied the effect of ovariectomy (OVX) on cardiac contraction in myocytes maintained under a 'diabetes-simulated high-glucose' environment. Female rats were ovariectomized or sham operated (SHAM) and kept for 6 weeks. Isolated myocytes were maintained in a diabetes-simulated high [glucose] medium (HG; 25.5 mM) for 24 h before mechanical properties were measured. Contractile indices analyzed included peak shortening (PS), time to PS (TPS), time to 90% relengthening (TR90), maximal velocity of shortening and relengthening (+/- dL/dt), intracellular Ca2+ fura-2 fluorescence intensity and decay rate (tau). Nitric oxide synthase (NOS) activity was also evaluated. OVX myocytes displayed a longer TR(90), slower +/- dL/dt, lower fluorescence intensity and higher tau (slower decay rate) when compared to SHAM myocytes. In the SHAM group, HG exerted diabetes-like contractile dysfunctions, including depressed PS, prolonged TR90, reduced fluorescence intensity, higher tau and enhanced NOS activity when compared to myocytes maintained in low [glucose] medium (5.5 mM). Interestingly, the HG- induced mechanical alterations were significantly exaggerated (TPS, TR90 and tau), reversed (PS and NOS) or lost (+/- dL/dt and fluorescence intensity) in the OVX group. These data suggest that ovarian hormones play a role in the regulation of cardiac contractile function, and may have potentially protective effects against diabetes-associated cardiac dysfunction.
Assuntos
Diabetes Mellitus Experimental/patologia , Ventrículos do Coração/citologia , Contração Miocárdica/fisiologia , Ovariectomia , Ovário/fisiologia , Animais , Cálcio/metabolismo , Feminino , Fluorescência , Glucose/administração & dosagem , Técnicas In Vitro , Ratos , Ratos Sprague-DawleyRESUMO
Dietary copper deficiency leads to cardiac hypertrophy, cardiac fibrosis, derangement of myofibrils, and impaired cardiac contractile and electrophysiological function. The purpose of this study was to determine whether impaired cardiac function from copper deficiency is due to depressed contractile function at the single myocyte level. Male Sprague-Dawley rats were fed diets that were either copper adequate (5.59-6.05 microg copper/g body wt; n = 11) or copper deficient (0.29-0.34 microg copper/g body wt; n = 11) for 5 wk. Ventricular myocytes were dispersed and mechanical properties were evaluated using the SoftEdge video-based edge-detection system. Intracellular Ca2+ transients were examined using fura 2-acetoxymethyl ester. Myocytes were electrically stimulated to contract at 0.5 Hz. Properties evaluated included peak shortening (PS), time to peak shortening (TPS), time to 90% relengthening (TR90), and maximal velocities of shortening and relengthening (+/-dL/dt). Myocytes from the copper-deficient rat hearts exhibited significantly enhanced PS values associated with shortened TR90 measurements compared with those from copper-adequate rat hearts. The +/-dL/dt values were enhanced and the intracellular Ca2+ transient decay rate was depressed in myocytes from copper-deficient rats. These data indicate that impaired cardiac contractile function that is seen in copper-deficient whole hearts might not be due to depressed cardiac contractile function at the single cell level but rather to other mechanisms such as cardiac fibrosis.
Assuntos
Cobre/deficiência , Coração/fisiologia , Contração Miocárdica/fisiologia , Miocárdio/citologia , Animais , Separação Celular , Células Cultivadas , Ventrículos do Coração/citologia , Masculino , Ratos , Ratos Sprague-Dawley , Função VentricularRESUMO
Patients with long-standing, severe, erosive rheumatoid arthritis who have extra-articular manifestations and have undergone joint replacement surgery are at increased risk for serious infection and premature mortality. New therapies, including cytokine antagonists, hold great promise for improving the course of rheumatoid arthritis. However, they have powerful anti-inflammatory effects that may mask symptoms of serious infection. We report a case of fatal pneumococcal sepsis occurring in a 37-year-old woman with rheumatoid arthritis treated with the tumor necrosis factor antagonist etanercept and suggest management strategies for early detection and management of this complication.
Assuntos
Antirreumáticos/efeitos adversos , Artrite Infecciosa/induzido quimicamente , Artrite Reumatoide/tratamento farmacológico , Bacteriemia/induzido quimicamente , Fasciite Necrosante/induzido quimicamente , Imunoglobulina G/efeitos adversos , Infecções Pneumocócicas/induzido quimicamente , Streptococcus pneumoniae , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anti-Inflamatórios/uso terapêutico , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/tratamento farmacológico , Artrite Reumatoide/imunologia , Artrite Reumatoide/cirurgia , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Quimioterapia Combinada , Etanercepte , Fasciite Necrosante/diagnóstico , Fasciite Necrosante/tratamento farmacológico , Evolução Fatal , Feminino , Humanos , Infecções Pneumocócicas/diagnóstico , Infecções Pneumocócicas/tratamento farmacológico , Prednisona/uso terapêutico , Receptores do Fator de Necrose Tumoral , Índice de Gravidade de DoençaRESUMO
The radiographic features of Ewing's sarcoma of the bones of the hands and feet are reviewed utilizing cases obtained from the Mayo Clinic patient files and the consultation files of Drs. D.C. Dahlin and K.K. Unni. This series consists of a total of 43 cases of pathologically proven Ewing's sarcoma involving the small bones of the hands and feet. The classic radiographic features of Ewing's sarcoma in the long bones, including lytic, permeative destruction, aggressive periosteal reaction, cortical violation, and a soft tissue mass, are also seen in the bones of the hands and feet, with similar frequency. These classic features are most commonly present in lesions affecting the short tubular bones. Lesions affecting the tarsal bones more often demonstrate atypical radiographic features. These atypical radiographic appearances may play a role in the reported delay in diagnosis of Ewing's sarcoma within the tarsal bones.
Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Doenças do Pé/diagnóstico por imagem , Mãos , Metacarpo , Ossos do Metatarso , Sarcoma de Ewing/diagnóstico por imagem , Ossos do Tarso , Adulto , Feminino , Humanos , Masculino , RadiografiaRESUMO
Fetal alcohol syndrome (FAS) is often associated with cardiac hypertrophy and impaired ventricular function in a manner similar to postnatal chronic alcohol ingestion. Chronic alcoholism has been shown to lead to hypomagnesemia, and dietary Mg2+ supplementation was shown to ameliorate ethanol- induced cardiovascular dysfunction such as hypertension. However, the role of gestational Mg2+ supplementation on FAS-related cardiac dysfunction is unknown. This study was conducted to examine the influence of gestational dietary Mg2+ supplementation on prenatal ethanol exposure-induced cardiac contractile response at the ventricular myocyte level. Timed-pregnancy female rats were fed from gestation day 2 with liquid diets containing 0.13 g/L Mg2+ supplemented with ethanol (36%) or additional Mg2+ (0.52 g/L), or both. The pups were maintained on standard rat chow through adulthood, and ventricular myocytes were isolated and stimulated to contract at 0.5 Hz. Mechanical properties were evaluated using an IonOptix soft-edge system, and intracellular Ca2+ transients were measured as changes in fura-2 fluorescence intensity (Delta FFI). Offspring from all groups displayed similar growth curves. Myocytes from the ethanol group exhibited reduced cell length, enhanced peak shortening (PS), and shortened time to 90% relengthening (TR90) associated with a normal Delta FFI and time to PS (TPS). Mg2+ reverted the prenatal ethanol-induced alteration in PS and maximal velocity of relengthening. However, it shortened TPS and TR90, and altered the Delta FFI, as well as Ca2+ decay rate by itself. Additionally, myocytes from the ethanol group exhibited impaired responsiveness to increased extracellular Ca2+ or stimulating frequency, which were restored by gestational Mg2+ supplementation. These data suggest that although gestational Mg2+ supplementation may be beneficial to certain cardiac contractile dysfunctions in offspring of alcoholic mothers, caution must be taken, as Mg2+ supplementation affects cell mechanics itself.
Assuntos
Animais Recém-Nascidos/fisiologia , Depressores do Sistema Nervoso Central/toxicidade , Etanol/toxicidade , Magnésio/farmacologia , Contração Miocárdica/efeitos dos fármacos , Envelhecimento/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Depressores do Sistema Nervoso Central/sangue , Dieta , Estimulação Elétrica , Etanol/sangue , Feminino , Ventrículos do Coração/efeitos dos fármacos , Magnésio/sangue , Gravidez , Efeitos Tardios da Exposição Pré-Natal , RatosRESUMO
Obesity is commonly associated with impaired myocardial contractile function. However, a direct link between these 2 states has not yet been established. There has been an indication that leptin, the product of the human obesity gene, may play a role in obesity-related metabolic and cardiovascular dysfunctions. The purpose of this study was to determine whether leptin exerts any direct cardiac contractile action that may contribute to altered myocardial function. Ventricular myocytes were isolated from adult male Sprague-Dawley rats. Contractile responses were evaluated by use of video-based edge detection. Contractile properties analyzed in cells electrically stimulated at 0.5 Hz included peak shortening, time to 90% peak shortening, time to 90% relengthening, and fluorescence intensity change. Leptin exhibited a dose-dependent inhibition in myocyte shortening and intracellular Ca(2+) change, with maximal inhibitions of 22.4% and 26.2%, respectively. Pretreatment with the NO synthase inhibitor N:(omega)-nitro-L-arginine methyl ester (L-NAME, 100 micromol/L) blocked leptin-induced inhibition of both peak shortening and fluorescence intensity change. Leptin also stimulated NO synthase activity in a time- and concentration-dependent manner, as reflected in the dose-related increase in NO accumulation in these cells. Addition of an NO donor (S-nitroso-N-acetyl-penicillamine [SNAP]) to the medium mimicked the effects of leptin administration. In summary, this study demonstrated a direct action of leptin on cardiomyocyte contraction, possibly through an increased NO production. These data suggest that leptin may play a role in obesity-related cardiac contractile dysfunction.
Assuntos
Ventrículos do Coração/metabolismo , Leptina/metabolismo , Contração Miocárdica/fisiologia , Miocárdio/metabolismo , Óxido Nítrico/metabolismo , Animais , Cálcio/metabolismo , Tamanho Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Ventrículos do Coração/citologia , Ventrículos do Coração/efeitos dos fármacos , Líquido Intracelular/metabolismo , Leptina/farmacologia , Masculino , Contração Miocárdica/efeitos dos fármacos , Miocárdio/citologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
To investigate outcome and evaluate prognostic factors in primary fibrosarcoma of bone, all patients at the authors' institution who had surgical treatment for primary fibrosarcoma of bone from 1910 to 1995 were studied. Medical records, surgical reports, radiographs, and histologic slides of 92 patients (51 males, 41 females; mean age, 38 years; range, 8-84 years) were reviewed. The most common tumor locations were the femur (28 patients), tibia (21 patients), and pelvis (14 patients). Sixty-one tumors (66%) were Enneking Stage IIB. Twenty-nine patients (31.5%) had adjuvant therapy: 16 had radiation, nine had chemotherapy alone, and four had radiation and chemotherapy. Amputation or disarticulation was performed in 61 patients (66%), wide excision was performed in 13 (14%), marginal excision was performed in 15 (16%), and intralesional excision was performed in three (3.3%). Local recurrence occurred in 14 patients (15%) at a median time of 7 months (range, 3-21 months). Metastases developed in 58 of the 85 patients (68%) with Stage I or II tumors at presentation, at a median of 9 months (range, 1-51 months). Survivorship analysis showed that the overall probability of survival was 33.4% at 5 years after surgery. Multivariate analysis showed that the main prognostic risk factors affecting overall survival included age older than 40 years, tumor location in the axial skeleton, and high-grade tumor (Grade 3 or 4). With the high incidence of systemic failure after surgical treatment, perioperative adjuvant treatment modalities should be considered.
Assuntos
Neoplasias Ósseas/cirurgia , Fibrossarcoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Osso e Ossos/cirurgia , Criança , Intervalo Livre de Doença , Feminino , Fibrossarcoma/diagnóstico por imagem , Fibrossarcoma/mortalidade , Fibrossarcoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radiografia , Análise de Sobrevida , Resultado do TratamentoRESUMO
The benign vascular tumors of bone represent a diverse group of tumors that can present with a broad spectrum of clinical signs and symptoms. They can also present a significant diagnostic challenge due to their widely variable radiographic imaging and histologic features. Some of the tumors manifest as clearly benign lesions with tissue-specific diagnostic imaging features, while others have non-specific imaging features that may simulate malignant neoplasm. This article will provide a review of the nomenclature and the characteristic radiographic and pathologic features of the benign vascular lesions of bone. The information will aid in improving our diagnostic accuracy and enhance our understanding of the biologic potential of this diverse group of osseous lesions.
Assuntos
Angiomatose/diagnóstico , Neoplasias Ósseas/diagnóstico , Hemangioma/diagnóstico , Biópsia , Doenças Ósseas/diagnóstico , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Diagnóstico Diferencial , Hemangioendotelioma Epitelioide/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Osteólise Essencial/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
The myxoid variant of adrenocortical carcinoma is a rare neoplasm described previously in only two case reports. Because of the rarity of these lesions, the presence of myxoid changes in adrenal cortical neoplasms usually raises the possibility of malignancy. We studied the histopathologic features of 14 cases of myxoid adrenocortical neoplasms, including six adenomas and eight carcinomas. All patients with adenomas with sufficient follow-up (n = 5) were alive with no recurrence of their tumors or evidence of metastatic disease. Four patients with carcinomas died of their disease, two were alive with metastatic disease, and one was alive with no evidence of recurrence or metastatic disease. Histologically, the 14 tumors varied in their myxoid composition, ranging from 10% to 95%. The myxoid foci stained positively with Alcian blue and were usually negative with periodic acid-Schiff and mucicarmine stains. As a group, the immunophenotype of the lesions was typical of other adrenal cortical neoplasms, with positive immunostaining for vimentin, synaptophysin, and alpha-inhibin. One tumor was focally positive for keratin. Myxoid adrenal cortical neoplasms should be included in the differential diagnosis of myxoid retroperitoneal neoplasms. Myxoid changes in adrenal cortical neoplasms may be present in both adenomas and carcinomas, and the usual clinical and histopathologic features for adrenocortical neoplasms should be used to diagnose these neoplasms.
Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Adenoma Adrenocortical/patologia , Adolescente , Neoplasias do Córtex Suprarrenal/ultraestrutura , Adenoma Adrenocortical/ultraestrutura , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
It is well established that cardiomyopathy is a consistent feature of diabetes and that alcohol consumption increases the risk of cardiovascular disease among diabetic subjects. Acetaldehyde (ACA), the main ethanol metabolite, is considered to play a role in the ethanol-induced cardiac dysfunction. It has been reported recently that the negative inotropic effect of ACA was more potent in the diabetic myocardium. To determine whether the disparate ACA-induced myocardial depression in diabetes is due to intrinsic alterations at the cellular level, mechanical properties in response to ACA were evaluated in ventricular myocytes from both normal and streptozotocin-induced diabetic rat hearts. Myocytes were electrically stimulated to contract at 0.5 Hz and contractile properties analyzed included peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)) and maximal velocities of shortening and relengthening (+/-dL/dt). Ca(2+) transients were measured as fura-2 fluorescence intensity (DeltaFFI) changes. ACA (0. 1-30 mM) disproportionately depressed PS in a dose-dependent manner, in myocytes from diabetic hearts compared to normal hearts. Interestingly, the degree of inhibition in DeltaFFI was similar in both groups. Neither the duration nor maximal velocities of shortening and relengthening were affected by ACA in either group. These results are the first to suggest that enhanced ACA-induced myocardial depression in diabetes is due to disparate intrinsic actions on individual myocytes. The mechanism underlying the alteration of ACA-induced myocardial depression may be due, in part, to depressed Ca(2+) responsiveness in diabetic hearts.
Assuntos
Acetaldeído/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Coração/efeitos dos fármacos , Contração Miocárdica/fisiologia , Animais , Cálcio/metabolismo , Células Cultivadas , Estimulação Elétrica , Coração/fisiologia , Coração/fisiopatologia , Ventrículos do Coração , Cinética , Masculino , Contração Miocárdica/efeitos dos fármacos , Miocárdio/citologia , Miocárdio/metabolismo , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley , Valores de ReferênciaRESUMO
Several retrospective studies have suggested p53 gene mutation as an adverse prognostic indicator in breast cancer patients, based on a selective growth advantage of p53 mutant cancer cells and their presumed resistance to current adjuvant therapy regimens. A cohort of 90 Caucasian midwestern breast cancer patients was analyzed prospectively (60 months of follow-up) with a rigorous mutation detection methodology. The presence of a p53 gene mutation was the single most adverse prognostic indicator for recurrence (p = 0.0032) and death (p = 0.0001), and was associated with poor response to both adjuvant (p = 0.0001) and palliative (p = 0.006) therapy. Analysis of the p53 gene with appropriate mutation detection methodology markedly improves the prediction of early recurrence, treatment failure, and death in breast cancer patients.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Genes p53 , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Estudos de Coortes , Seguimentos , Humanos , Imuno-Histoquímica , Mutação , Prognóstico , Estudos ProspectivosRESUMO
PURPOSE: The purpose of this study was to determine whether the presence of HER-2/neu gene amplification and/or overexpression in benign breast disease was associated with an increased risk of subsequent breast cancer. PATIENTS AND METHODS: We conducted a nested case-control study of a cohort of women who were diagnosed with benign breast disease at the Mayo Clinic and who were subsequently observed for the development of breast cancer. Patients who developed breast cancer formed the case group, and a matched sample from the remaining cohort served as controls. Benign tissue samples from 137 cases and 156 controls and malignant tissues from 99 cases provided DNA or tissue for evaluation of HER-2/neu amplification and protein overexpression. RESULTS: Among the controls, seven benign tissues (4.5%) demonstrated low-level HER-2/neu amplification, whereas 13 benign (9.5%) and 18 malignant (18%) tissue specimens from cases exhibited amplification. HER-2/neu amplification in benign breast biopsies was associated with an increased risk of breast cancer (odds ratio ¿OR = 2.2; 95% confidence interval ¿CI, 0.9 to 5.8); this association approached statistical significance. The risks for breast cancer associated with benign breast histopathologic diagnoses were OR = 1.1 (95% CI, 0.6 to 1.9) for lesions exhibiting proliferation without atypia and OR = 1.5 (95% CI, 0.4 to 5.6) for the diagnosis of atypical ductal hyperplasia. For women having both HER-2/neu amplification and a proliferative histopathologic diagnosis (either typical or atypical), the risk of breast cancer was more than seven-fold (OR = 7.2; 95% CI, 0.9 to 60.8). Overexpression of the HER-2/neu protein product, defined as membrane staining in 10% or more of epithelial cells, was found in 30% of the breast tumors but was not detected in any of the benign breast tissues. Case patients who had HER-2/neu gene amplification in their malignant tumor were more likely to have had HER-2/neu amplification in their prior benign biopsy (P =.06, Fisher's exact test). CONCLUSION: Women with benign breast biopsies demonstrating both HER-2/neu amplification and a proliferative histopathologic diagnosis may be at substantially increased risk for subsequent breast cancer.
Assuntos
Doenças Mamárias/genética , Neoplasias da Mama/genética , Amplificação de Genes , Receptor ErbB-2/genética , Adulto , Doenças Mamárias/patologia , Neoplasias da Mama/etiologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Receptor ErbB-2/biossíntese , Medição de RiscoRESUMO
The malignant vascular tumors of bone represent an uncommon diverse group of tumors with widely variable clinical and radiographic presentations. Although the radiographic imaging features of the lytic osseous lesions typically seen with this group of tumors are relatively nonspecific, the propensity to develop multifocal disease in an anatomic region is a feature that can be helpful in suggesting the diagnosis of a vascular tumor. The differential diagnosis varies according to the age of the patient and presence of solitary or multifocal disease. The histologic features are variable and range from tumors with vasoformative features to those that mimic mesenchymal neoplasm or metastatic carcinoma. Familiarity with the radiographic and pathologic spectrum of disease is essential for making an accurate diagnosis in this diverse group of neoplasms. This paper will provide a review of the nomenclature for the malignant vascular tumors of bone and discuss the radiographic and pathologic differential diagnosis.
Assuntos
Neoplasias Ósseas/diagnóstico , Osso e Ossos/irrigação sanguínea , Diagnóstico por Imagem , Neoplasias Vasculares/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Osso e Ossos/patologia , Criança , Pré-Escolar , Feminino , Hemangioendotelioma/diagnóstico , Hemangiossarcoma/diagnóstico , Humanos , Lactente , Masculino , Pessoa de Meia-IdadeRESUMO
Clear cell sarcoma is a rare soft tissue neoplasm, accounting for less than 1% of soft tissue sarcomas. We are presenting a case of a clear cell sarcoma of bone which, to our - knowledge, is the only report of a , primary clear cell sarcoma of bone.
Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Costelas , Sarcoma de Células Claras/diagnóstico por imagem , Adolescente , Neoplasias Ósseas/terapia , Humanos , Masculino , Radiografia , Costelas/lesões , Sarcoma de Células Claras/secundário , Sarcoma de Células Claras/terapia , Neoplasias de Tecidos Moles/secundárioRESUMO
BACKGROUND: Metaplastic breast cancer is a rare disease with little information available to guide therapy. The goals of this study were to describe the patient characteristics, systemic therapies and clinical outcomes of all patients with primary metaplastic breast cancer treated at Mayo Clinic between 1976 and 1997. PATIENTS AND METHODS: Patients were identified through the medical index of Mayo Clinic. Clinical information was abstracted from the medical record of each patient. A literature search using MEDLINE and CANCERLIT for the years 1966-1997 was performed to identify all previously reported case series in the English language containing 10 or more patients. RESULTS: Twenty-seven patients were identified with a median age at diagnosis of 59 years (range 39-90 years). The median tumor size was 3.4 cm (range 0.5-7.0 cm). One patient had metastatic disease at presentation. Twenty-three patients had information available on nodal status, estrogen receptor (ER) and progesterone receptor (PR) status. Twenty patients (87%) were node-negative and three patients (13%) were both ER and PR positive. Disease-free survival (DFS) and overall survival (OS) were assessed for those who presented with local-regional disease. The three-year DFS was 40% (95% CI: 23%-73%) and the three-year OS was 71% (95% CI: 51%-97%). In univariate analysis, those patients 60 years of age or older at diagnosis were found to have an increased DFS (P = 0.011). Among those with prior estrogen use, both DFS (P = 0.022) and OS (P = 0.003) were decreased. Thirteen patients (50%) developed metastases with a median DFS time of 2.4 years. Ten different chemotherapy regimens were utilized for metastatic disease and one partial response was observed. There were no responses to tamoxifen in four patients with metastatic disease. Median survival after the development of metastases was eight months. CONCLUSIONS: Despite presenting more commonly as node-negative disease, DFS and OS in metaplastic breast cancer is decreased compared to typical adenocarcinomas. Systemic therapy also appears to be less effective. Patients with metaplastic breast cancer, particularly those with metastatic disease could be appropriate candidates for innovative therapeutic regimens.