RESUMO
A randomized, two-way, crossover, bioequivalence study in 32 fasting, healthy, male volunteers was conducted to compare two brands of clopidogrel 75 mg tablets, Thrombo (EIPICO, Egypt) as test and Plavix (Sanofi Pharma/Bristol-Myers Squibb, Paris, France) as reference. The study was performed in a Pharmaceutical Research Unit (PRU) using HPLC/ MS-MS. Arithmetic means for clopidogrel test versus reference formulation, respectively were for Cmax (4.39 +/- 2.58 vs. 4.30 +/- 2.65) ng/ml, AUC0-t (11.98 +/- 9.82 vs. 12.01 +/- 9.46) ng.h/ml, AUC0- yen (12.43 +/- 9.94 vs. 12.49 +/- 9.58) ng.h/ml, t1/2 (6.06 +/- 3.87 vs. 5.87 +/- 2.47) h and the medians for tmax (1 h vs. 0.75 h). Arithmetic means for clopidogrel carboxylic acid metabolite were Cmax (3.75 +/- 1.19 vs. 3.51 +/- 0.97) microg/ml AUC0-t (9.18 +/- 2.36 vs. 9.17 +/- 2.06) microg.h/ml, AUC0- yen (9.72 +/- 2.4 vs. 9.80 +/- 2.21) microg.h/ml , and t1/2 (6.43 +/- 3.52 vs. 6.33 +/- 1.71) h for test versus reference formulation respectively and there was no difference in the medians for tmax (0.75 h). The parametric 90% confidence intervals for the mean of the difference between log-transformed values were within the accepted range for bioequivalence of 80 - 125% as proposed by the US-FDA , namely for clopidogrel (90.66% - 109.66%), (90.63% - 109.73%), and (93.19% - 115.37%) for AUC0-t, AUC0- yen, and Cmax, respectively and also for clopidogrel carboxylic acid metabolite (94.90 - 104.19) , (94.04 - 103.86) and (96.47 - 114.79) for AUC0-t , AUC0- yen, and Cmax, respectively. Thus there was no significant difference between these values and therefore the two products can be considered bioequivalent.
Assuntos
Inibidores da Agregação Plaquetária/farmacocinética , Ticlopidina/análogos & derivados , Administração Oral , Adulto , Clopidogrel , Humanos , Masculino , Inibidores da Agregação Plaquetária/administração & dosagem , Comprimidos , Equivalência Terapêutica , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Ticlopidina/farmacocinéticaRESUMO
OBJECTIVES: This study was undertaken to evaluate the diagnostic efficacy of telomerase in urine, and bladder wash and also the matrix metalloproteinase-9 (MMP-9) in urine, compared with voided urine cytology (VUC) and bladder wash cytology (BWC) for the detection of bladder cancer cells. MATERIAL AND METHODS: A total of 110 subjects provided a single preoperative voided morning urine sample for telomerase, matrix metalloproteinase-9 (MMP-9) and cytology. Bladder wash samples were obtained for telomerase and cytology. Cystoscopy was done for all patients as the reference standard for the identification of bladder cancer. Biopsy of any suspicious lesion was performed for histopathological examination. Of 110 cases 73 were histologically diagnosed as bladder cancer, whereas the remaining 16 had benign urological disorders. A group of 21 healthy volunteers were also enrolled in this study. RESULTS: The optimal threshold values for telomerase activity in urine, bladder wash and MMP-9 were calculated by receiver-operator characteristics (ROC) curves as 0.05, 0.088 and 0.51 (ng/ml), respectively. The levels and the positivity rates of the 2 parameters were significantly higher in the malignant group compared to either the benign group or normal controls. Of the entire group, telomerase activity in urine, bladder wash, and MMP-9 were positive in 92%, 87% and 61%, respectively in bladder cancer patients with positive cytology. Moreover, these positive rates for them were significantly higher in bilharzial bladder cancer cases (88%, 89%, 69%, respectively) compared to non-bilharzial cases (50%, 62.5%, 50%). The overall sensitivity and specificity were 83% and 88.6%, 86.3% and 78.3% for telomerase activity in urine, and in bladder wash, respectively; 66.6% and 80% for MMP-9 and 58.5% and 100% for voided urine cytology and 64.4% and 100% for bladder wash cytology. Combined sensitivity of VUC with the 2 biomarkers together was higher than either combined sensitivity of VUC with one of the biomarkers or than that of the biomarker alone. CONCLUSIONS: Our data indicate that urinary telomerase and MMP-9 had superior sensitivities over VUC. The combined use of markers increased the sensitivity of cytology from 58.46% to 95%. The higher sensitivities of markers in bilharzial bladder cancer than non-bilharzial type highlight their clinical utility in screening patients with urinary bilharziasis.
Assuntos
Biomarcadores Tumorais/análise , Metaloproteinase 9 da Matriz/urina , Telomerase/urina , Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Idoso , Biópsia por Agulha , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Metaloproteinase 9 da Matriz/análise , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Probabilidade , Prognóstico , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Telomerase/análise , Irrigação Terapêutica , Urinálise , Bexiga Urinária/química , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/urinaRESUMO
OBJECTIVES: In an attempt to find a more sensitive and specific non-invasive diagnostic assay for the detection of bladder cancer cells, the authors assayed the exfoliated cells from patient's voided urine and bladder washing fluids for the presence of telomerase, an enzyme that maintains a cell's chromosomal length, metalloproteinase-9 (MMP-9), which has been associated with tumor cell invasion and metastasis. Their results were compared with both voided urine cytology (VUC) and bladder wash cytology (BWC) for the detection of bladder cancer cells. MATERIALS AND METHODS: The authors used preoperative voided morning urine samples from 110 subjects for telomerase, matrix metalloproteinase-9 (MMP-9) and cytology. Bladder wash samples were obtained for telomerase and cytology. Of 110 cases 73 were histologically diagnosed as bladder cancer, whereas the remaining 16 had benign urological disorders. A group of 21 healthy volunteers were also enrolled in this study. Cystoscopy was done for all patients as the reference standard for the identification of bladder cancer. Biopsy of any suspicious lesion was performed for histopathological examination. RESULTS: Receiver-operator characteristics (ROC) curves were used to determine the optimal threshold values for telomerase activity in urine, bladder wash and MMP-9 [0.05, 0.088 and 0.51 (ng/ml), respectively]. The levels and the positivity rates of telomerase activity and MMP-9 were significantly higher in the malignant group compared to either the benign group or normal controls. Bladder cancer patients with positive cytology revealed positive telomerase activity in urine, bladder wash, and MMP-9 in 92%, 87% and 61%, respectively. Also, these positive rates were significantly higher in bilharzial bladder cancer cases (88%, 89%, 69%, respectively) compared to non-bilharzial cases (50%, 62.5%, 50%). The overall sensitivity and specificity were 83% and 88.6%, 86.3% and 78.3% for telomerase activity in urine, and in bladder wash, respectively. 66.6% and 80% for MMP-9, 58.5% and 100% for voided urine cytology and 64.4% and 100% for bladder wash cytology. Combined sensitivity of VUC with the 2 biomarkers together was higher than either combined sensitivity of VUC with one of the biomarkers or than that of the biomarker alone. CONCLUSION: Urinary telomerase and MMP-9 had superior sensitivities over VUC; moreover, combined use of these markers increased the sensitivity of cytology from 58.46% to 95%. The higher sensitivities of markers in bilharzial bladder cancer than non-bilharzial type highlight their clinical utility in screening patients with urinary bilharziasis.
Assuntos
Biomarcadores Tumorais/urina , Metaloproteinase 9 da Matriz/urina , Telomerase/urina , Neoplasias da Bexiga Urinária/enzimologia , Adenocarcinoma/enzimologia , Adenocarcinoma/patologia , Adenocarcinoma/urina , Adulto , Idoso , Carcinoma de Células de Transição/enzimologia , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/urina , Humanos , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/urinaRESUMO
BACKGROUND: Several molecular genetic alterations in breast cancer, including aneuploidy, altered apoptosis, aberrant expression of p53, HER-2/neu and Bcl-2, have been associated with poor prognosis in breast cancer patients. To determine the importance of molecular-genetic factors relative to more traditional surgical-pathological prognostic factors, multivariate analysis was performed. PATIENTS AND METHODS: Ninety-four fresh tissue samples of primary breast carcinoma were studied with flow cytometry for DNA ploidy. On the same specimens, steroid hormone receptors (ER and PR) were measured in the cytosol fraction using Abbott ELISA assays. HER-2/neu was determined in the membrane fraction and mutant p53 protein in the nuclear fraction, both, by Oncogene Science ELIZA procedures. Bcl-2 and apoptosis (cell death) were measured in cell lysates by Oncogene Science & Boehringer Mannheim ELISA assays. In addition, information regarding surgical-pathological features of the tumor was obtained. Multivariate analysis using an unconditional logistic regression model was done to identify variables predictive of poor prognosis. RESULTS: Using univariate analysis, histological grade, tumor stage, lymph node status, HER-2/neu and mutant p53 were predictive of poor short-term prognosis. By multivariate analysis, tumor stage, lymph node status and HER-2/neu were independent factors. Grade subgroup analysis versus time of relapse, illustrated a predictive value of Bcl-2 in only low-grade tumors while apoptosis was significant in high-grade type. CONCLUSION: Among a panel of molecular-genetic factors investigated, HER-2/neu was the most strongly predictive of poor short-term prognosis in breast cancer. Patients with HER-2/neu-positive tumors can benefit from Herceptin therapy.
Assuntos
Neoplasias da Mama/genética , Mutação , Proteínas Proto-Oncogênicas c-bcl-2/genética , Receptor ErbB-2/genética , Proteína Supressora de Tumor p53/genética , Adulto , Apoptose , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , DNA de Neoplasias/análise , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas c-bcl-2/análise , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Taxa de Sobrevida , Fatores de Tempo , Proteína Supressora de Tumor p53/análiseRESUMO
PURPOSE: We evaluate the diagnostic efficacy of nuclear matrix protein-22 (NMP22, Matritech, Newton, Massachusetts), fibronectin and urinary bladder cancer antigen (UBC, IDL Biotech, Borlange, Sweden) compared with voided urine cytology in the detection of bladder cancer. MATERIALS AND METHODS: A total of 168 patients provided a single voided urine sample for NMP22, fibronectin an ideal monoclonal for urinary bladder cancer and cytology before cystoscopy. Cystoscopy was done for all patients as the reference standard for identification of bladder cancer. Biopsy of any suspicious lesion was performed for histopathological examination. Of the 168 cases 100 were histologically diagnosed as bladder cancer, whereas the remaining 68 had benign urological disorders. A group of 47 healthy volunteers were also enrolled in this study. Voided urine was evaluated by NMP22, fibronectin and UBC, and their values were expressed relative to mg. creatinine. RESULTS: The optimal threshold values for NMP22, fibronectin and UBC were calculated by receiver operator characteristics curves as 27 units per mg. creatinine, 198 mg./mg. creatinine and 13 ng./mg. creatinine, respectively. The levels and positive rates of the 3 parameters were significantly higher in the malignant group compared to either the benign group or normal controls. Of the entire group NMP22, fibronectin and UBC were positive in 93.2%, 91% and 68.2%, respectively in bladder cancer cases with positive cytology. Moreover, these positive rates were significantly higher in bilharzial bladder cancer cases (58.8%, 67.5%, 58.8%, respectively) compared to nonbilharzial cases (35.6%, 36.3%, 31.1%). Overall sensitivity and specificity were 85% and 91.3% for NMP22, 83% and 82.6% for fibronectin, 67% and 80.8% for UBC and 44% and 100% for voided urine cytology. Combined sensitivity of voided urine cytology with the 3 biomarkers together was higher than either combined sensitivity of voided urine cytology with 1 of the biomarkers or than that of the biomarker alone. CONCLUSIONS: Our data indicate that NMP22 and fibronectin had superior sensitivities compared to UBC and voided urine cytology, while NMP22 and voided urine cytology had the highest specificities. The combined use of markers increased the sensitivity of cytology from 44% to 95.3%. The higher sensitivities of markers in bilharzial than nonbilharzial bladder cancer highlight their clinical use in screening patients with urinary bilharziasis.
Assuntos
Antígenos de Neoplasias/urina , Biomarcadores Tumorais/urina , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células de Transição/diagnóstico , Proteínas de Ligação a DNA/urina , Fibronectinas/urina , Fatores de Transcrição/urina , Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Idoso , Biópsia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/urina , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/urina , Cistoscopia , Diagnóstico Diferencial , Fatores de Ligação de DNA Eritroide Específicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Fatores de Risco , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/urinaRESUMO
There are a wide variety of tumor markers now available that proved to be of value in the management of cancer patients. Of these markers, tissue polypeptide antigen (TPA) and tissue polypeptide specific antigen (TPS) are well known in the field of bladder cancer. TPA was found to be a mixture of cytokeratins 8, 18 and 19 and recent investigations proved that TPS is keratin 18. The aim of the present study was to assess the clinical value of urinary cytokeratin 19 (CYFRA21-1) in the differential diagnosis between bladder cancer and benign urinary tract diseases represented by bilharziasis. Two hundreds and seventy individuals were included in the present study: 186 with bladder cancer representing the different stages and grades, 44 with urinary tract bilharziasis and 40 normal healthy controls. CYFRA21-1 was evaluated in 24-hour urine samples by ELISA using the automatic set supplied by Boehringer Manheim, Manheim, Germany (ES 300). Results of this study revealed significant elevation of CYFRA21-1 in bladder cancer followed by bilharziasis. 82.3% (153/186) of bladder cancer patients and 11.4% (5/44) of bilharzial patients exhibited CYFRA21-1 levels above the upper limit of the control group (3 micrograms/24-hr). CYFRA21-1 was more sensitive in advanced than early stages of bladder cancer and in patients with positive than those with negative lymph nodes, but association of tumor with bilharziasis did not markedly affect its level.
Assuntos
Antígenos de Neoplasias/urina , Biomarcadores Tumorais/urina , Queratinas/urina , Esquistossomose Urinária/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/urina , Adulto , Idoso , Carcinoma/diagnóstico , Carcinoma/patologia , Carcinoma/urina , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/urina , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/urina , Diagnóstico Diferencial , Egito , Feminino , Humanos , Queratina-19 , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/patologia , Leiomiossarcoma/urina , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valores de Referência , Reprodutibilidade dos Testes , Esquistossomose Urinária/urina , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/patologiaRESUMO
Recent studies demonstrated the role of antioxidants in preventing organ damage caused by free radicals. The present study was conducted to find out the modulatory effect of some antioxidants on lipid patterns in experimentally-induced liver damage. Rats chronically intoxicated with carbon tetrachloride (CCl4) were used as a model of liver injury terminating with fibrosis or cirrhosis. One hundred and sixty six albino rats were classified into five groups: one served as a control group; the second was subjected to oral administration of CCl4 (200 microL/100 g body weight) twice a week; the other three groups, in addition to CCl4, received oral doses of silymarin (30 mg/kg), vitamin E (200 IU/kg) and vitamin C (50 mg/kg) respectively. At the end of the experiment, the animals were killed, blood was collected and liver was taken for histopathological examination. Liver function tests, disturbed by CCl4 were significantly modulated by antioxidants, and histopathological examination showed that antioxidants ameliorated the necrotic and fibrotic changes caused by CCl4. Treatment with antioxidants was also shown to modulate the toxic effect of CCl4 on the lipid profile and malondialdehyde content. Administration of antioxidants could play an important role in prophylaxis against lipid peroxidation and consequently liver fibrosis caused by free radicals.
Assuntos
Antioxidantes/farmacologia , Metabolismo dos Lipídeos , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/fisiopatologia , Animais , Intoxicação por Tetracloreto de Carbono/metabolismo , Intoxicação por Tetracloreto de Carbono/patologia , Intoxicação por Tetracloreto de Carbono/fisiopatologia , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/patologia , Testes de Função Hepática , Masculino , Necrose , RatosRESUMO
Sonolysis of aqueous solutions produces H. and HO. that lead to Co-C bond cleavage in methylcob-(III)alamin (CH3-CblIII) and 2-[4-[4'-[bis(2-chloroethyl)amino]phenyl]butyroxy]ethylcob (III)alamin (Chl-HE-CblIII). Under anaerobic conditions, H. reduces CH3-CblIII to the unstable 19 e-CH3-CblII that dissociates to the alkane and CblII. Under aerobic conditions, O2 scavenges H. and Co-C bond cleavage occurs via a HO.-mediated process along with modification of the corrin ring by HO.. When H. and HO. are scavenged, there is no evidence of Co-C bond cleavage. This suggests no direct sonolysis of the Co-C bond occurs, in spite of the fact that the Co-C bond is 80 kcal/mol weaker than the H-OH bond. A bioconjugate of cob(III)alamin and the alkylating agent chlorambucil has been synthesized to give 2-[4-[4'-[bis(2-chloroethyl)amino]phenyl]butyroxy]ethylcob(I II)alamin. The chlorambucil-cobalamin complex also undergoes Co-C bond cleavage in a manner similar to that of methylcob-(III)alamin. Sonorelease of an active alkylating agent from the bioconjugate may provide a new method for the selective release of anticancer drugs and thus potentially reduce systemic toxicity.
Assuntos
Vitamina B 12/química , Hidrólise , Espectroscopia de Ressonância Magnética , Espectrofotometria Ultravioleta , Vitamina B 12/análogos & derivadosRESUMO
Squamous cell carcinoma (SCC) antigen levels were measured by immunoparticle assay (IMx) in the sera of 32 patients with gynecologic malignancies, 15 with benign diseases of the genital system and 14 normal healthy controls. At a cut-off value of 4.8 ng/ml (100% specificity), the rate of SCC antigen elevation was 100% in vulvar and vaginal cancer (n = 5), 90% in ovarian cancer (n = 10), 60.0% in endometrial cancer (n = 10) and 57.2% in cervical cancer (n = 7). The benign disease's group had 80.0% false positivity at the same cut-off value. Serum SCC-A was found to correlate directly with the clinical stage of disease. A sensitivity of 73.3% was obtained at stage I which gives SCC-A a role in screening the high risk population for gynecological cancer. Concerning the histopathologic type of tumor, serum SCCA was highly sensitive in SCC tumors, in ovarian serous cystadenocarcinoma and in patients with recurrent ovarian cancer.
Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Neoplasias dos Genitais Femininos/sangue , Serpinas , Adolescente , Adulto , Idoso , Feminino , Neoplasias dos Genitais Femininos/patologia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sensibilidade e EspecificidadeRESUMO
Amplification of erbB-1 and c-erbB-2 genes has been shown in human breast cancer. Expression of these protooncogenes results in production of epidermal growth factor receptor (EGFR) and c-erbB-2. Both are transmembrane receptors with tyrosine kinase activity. Recent data have indicated that the external domain of c-erbB-2 is shed into the culture supernatant of certain breast cancer cell lines and sera of breast cancer patients. A body of literature has shown that the overexpression of these receptors in malignant tissue and c-erbB-2 when shed into serum is associated with bad prognosis. In the present work, tissue EGFR and c-erbB-2 were determined in the membrane fractions of histopathologically verified malignant and normal tissues from the same breast of 94 patients. These values were also determined in 48 tissue specimens of benign mastopathies. Serum c-erbB-2 was quantified in breast cancer patients (n = 105), patients with benign breast disease (n = 48) and 30 apparently healthy women as controls. Patients were followed up by determination of serum c-erbB-2 for one year and clinically for three years to detect any distant metastasis or recurrence. The levels of tissue and serum c-erbB-2 and Estrogen receptors were significantly higher in the carcinomas and sera of breast cancer patients than benign breast diseases or normal controls. Follow-up, although short, of pre-operative serum c-erbB-2 showed a prognostic value (P = 0.007) better than that of tumor size (P = 0.04), EGFR (P = 0.18), nodal involvement (P = 0.25) and tissue c-erbB-2 (P = 0.85). The shedding of soluble fragments of c-erbB-2 into the serum seems to be a characteristic of the potentially malignant cell. The EGFR mean level, however, was significantly lower in malignant tissues than benign and normal ones. A new definition of EGFR status was developed. Accordingly, the recurrence of the disease was more frequent among patients with negative EGFR. The present work did not reveal any correlation between tissue, serum c-erbB-2 or EGFR on one hand and age, menopausal status, stage, histological type and grade of carcinomas and nodal involvement on the other hand. The present work showed an inverse correlation between estrogen receptor level and level of EGFR in malignant tissues.
Assuntos
Neoplasias da Mama/química , Receptores ErbB/análise , Receptor ErbB-2/análise , Adulto , Idoso , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , PrognósticoRESUMO
This study included 34 normal healthy controls, 35 patients with urinary tract bilharziasis and 93 bladder cancer patients (62 were operable cases and 31 non-operable). Serum tumor necrosis factor alpha (TNF-alpha) was determined using the enzyme immunoassay reagents supplied by Medgenix Diagnostics, Belgium. Cytosol Cathepsin-D was estimated using the immunoradiometric assay supplied by CIS BIO International, France. The results revealed that at 100% and 90% specificities, cytosol Cathepsin-D had 35.7% and 59.5% sensitivity in bladder cancer patients. Serum TNF-alpha showed sensitivity of 17.0% and 55.0% at 100% and 90% specificities in operable bladder cancer patients and 48.0% and 77.0% in non-operable cases respectively. Cytosol cathepsin D and TNF-alpha did not show prognostic values like positive correlation with tumor stages, grades or association of tumors with bilharzial ova or lymph node involvement.
Assuntos
Biomarcadores Tumorais/análise , Catepsina D/análise , Fator de Necrose Tumoral alfa/análise , Neoplasias da Bexiga Urinária/química , Adulto , Idoso , Citosol/enzimologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquistossomose/metabolismo , Sensibilidade e EspecificidadeRESUMO
The predictive potential of Epidermal Growth Factor Receptor (EGFR) is still a matter of debate. EGFR was quantified biochemically using an enzyme immunoassays malignant and normal tissues from the same breast (n = 94) as well as benign mastopathies (n = 40). The mean level of EGFR in malignant tissues showed a significant decrease from the control and benign ones with a weak positive correlation existing between EGFR level in malignant and control tissue of the same breast. Statistically, no cut-off line could be drawn between malignant and non malignant tumors due to the large overlap in their values. On the contrary to reports on EGFR, when the patients were classified according to the relative changes in EGFR from malignant and adjacent tissue, patients with a relative EGFR decrease (negative EGFR) in malignant tissue showed the poorer prognosis in short term follow up. Mean EGFR values in malignant or normal tissue, or the difference between them, did not show any significant correlation with the age of the patients, menstrual status, clinical stage, type and grade of the carcinoma and lymph node involvement. The present work showed also an inverse correlation between EGFR and Estrogen Receptor (ER) level in the malignant tissues.
Assuntos
Neoplasias da Mama/química , Receptores ErbB/análise , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Receptores de Estrogênio/análiseRESUMO
The effect of Granulocyte-Macrophage, Colony Stimulating Factor (GM-CSF) and Interleukin-6 (IL-6) on leukotriene production by CML white blood cells induced by calcium ionophore (A23187) was investigated and the leukotrienes formed were identified and quantified using high performance liquid chromatography (HPLC). The in vivo levels of IL-6 and LTB4 were determined by enzyme immunoassay reagents, while GM-CSF was measured by enzyme amplified sensitivity immunoassay. Although GM-CSF or IL-6 alone did not stimulate the synthesis of 5-lipoxygenase product, preincubation of the white blood cells of CML with GM-CSF or IL-6 for 30 minutes at 37 degrees C enhanced the ionophore A23187 induced leukotrienes synthesis, thus the CML white blood cell suspension primed with GM-CSF or IL-6 produced 26.6 +/- 2.8 and 18.9 +/- 1.3 pmol LTC4/10(6) cells respectively, and 30.2 +/- 3.6 and 25.5 +/- 2.5 Pmol LTB4/10(6) cells. In contrast minute amount of leukotrienes were produced by the control cells. In vivo levels of GM-CSF, IL-6 and LTB4 were investigated in CML and normal healthy donors, elevated chemotactic B4 was found in plasma from CML (267 +/- 70.4) while the mean value in normal healthy donors was (127 +/- 13.6) pg/ml. The plasma level of GM-CSF was 32.4 +/- 15.7 pg/ml and 10.5 +/- 3.1 pg/ml respectively in CML and normal healthy donors, while the mean value of GM-CSF and IL-6 in normal healthy donors were 6.7 +/- 2.2 and 4.9 +/- 2.4 pg/ml respectively. No significant correlation was observed between the level of LTB4 and the level of GM-CSF or IL-6 in CML.
Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Interleucina-6/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucócitos/metabolismo , Leucotrienos/biossíntese , Calcimicina/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Humanos , Interleucina-6/sangueRESUMO
There is significant research in the role of interleukins in lung disease, as the cytokines are important mediators in the host response to mycobacterium tuberculosis infection. Plasma from patients with pulmonary tuberculosis (TB) and healthy controls were investigated for their content of granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-6 (IL-6) and leukotriene B4 (LTB4). LTB4 and IL-6 were measured by enzyme immunoassay after lipid extraction in the case of LTB4 while GM-CSF was measured by enzyme amplified sensitive immunoassay. Significantly elevated concentrations of IL-6 were found in far-advanced lesions of pulmonary tuberculosis patients, P < 0.05. However, nonsignificant increases of IL-6 were obtained in moderate lesions and minimal lesions compared to normal healthy subjects. Marked elevations of LTB4 were found in TB patients, the highest values being shown in patients with far-advanced lesions followed by moderately advanced and minimal lesions in relation to the mean value for normal healthy controls, P < 0.001 for all groups. 93% of the tuberculosis patients showed a higher level of LTB4 above the upper limit of the control group. In contrast there was no significant increase of GM-CSF in any of the TB subgroups. These results suggest that LTB4 and the interleukins may play a role in the pathogenesis of mycobacterium tuberculosis infection.
Assuntos
Interleucina-6/sangue , Leucotrieno B4/sangue , Leucotrieno C4/sangue , Tuberculose/sangue , Adolescente , Adulto , Cromatografia Líquida de Alta Pressão , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , HumanosRESUMO
This study demonstrates the changing levels of leukotrieneB4 (LTB4) and leukotrieneC4 (LTC4) generated by human white blood cells primed with different human interleukins IL-3, IL-5, IL-6, IL-8 and with human hematopoietic growth factor granulocyte-macrophage colony stimulating factor (GM-CSF). Preincubation of white blood cells at 37 degrees C for 30 min with different human interleukins significantly increased leukotriene production in white blood cells preincubated with diluent control while IL-3 was without priming effects. Addition of exogenous arachidonic acid to non primed white blood cells increased the production of leukotrienes in response to the calcium ionophore (A23187). The enhancement of the leukotrienes production by white blood cells stimulated by A23187 was only observed when the cells stimulated for periods of 2 min or less. The results reveal that GM-CSF, IL-4, IL-6 and IL-8 belong to particular set of cytokines with potent modulating effect on inducing inflammatory mediators released by white blood cells, while IL-3 was ineffctive.
RESUMO
UGP (Urinary gonadotropin peptide) also know as urinary gonadotropin fragment (UGF) or the beta-core of hCG (c beta hCG), was identified as a peptide with a molecular weight of 10.5 kD, having the same amino acid sequence as the core section of the beta-subunit of human chorionic gonadotropin. UGP has been found in normal pregnancy urine as well as in the urine of patients with gestational trophoblastic and non-trophoblastic malignancies. The aim of the present work was to investigate the clinical value of UGP in Egyptian patients with urogenital disorders. The study included 793 cases (462 males and 331 females) classified into 5 groups: 277 with bladder cancer, 121 with benign urinary tract disorders, 27 with different gynecological malignancies, 53 with benign gynecological disease and 315 apparently healthy individuals as a control group. The normal females included 88 premenopausal and 71 postmenopausal women. UGP was determined in 24- hour urine samples from all cases, and in morning urine samples from 151 subjects by ELISA technique using the reagents supplied by Ciba Corning Diagnostics, CA, USA (Triton UGP - EIA). The results of this study revealed significant elevation of UGP in cancer patients when compared to either normal controls or patients with benign diseases. Females in the control and benign diseases groups expressed higher UGP values than males and UGP in postmenopausal women was significantly elevated when compared to premenopausal control females. A a tumor marker, UGP was more sensitive and more specific in bladder than in gynecological cancer. A significant correlation (r = 0.934) was obtained between UGP levels in 24-hr and morning urine samples.
Assuntos
Biomarcadores Tumorais/urina , Gonadotropina Coriônica Humana Subunidade beta/urina , Doenças Urogenitais Femininas/diagnóstico , Doenças Urogenitais Masculinas , Fragmentos de Peptídeos/urina , Neoplasias Urogenitais/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Adenocarcinoma is the commonest primary malignancy encountered in the endometrium. Adenomatous hyperplasia represents an important precancerous endometrial lesion. In this study, different techniques have been applied in a trial to early detect endometrial carcinoma and to distinguish between hyperplasia with minimal and high risk of progression to endometrial adenocarcinoma. Eighty women were included in this study and classified into 4 groups: 10 with adenocarcinoma, 28 with simple hyperplasia, 12 with hyperplasia with atypia and 30 normal healthy women. All individuals were subjected to Doppler endovaginal ultrasonography (EVS) for endometrial thickness and uterine artery resistance index (RI). Endometrial biopsy was taken for histopathological examination and DNA analysis. 24-hr urine was collected for the estimation of UGP by ELISA using reagents supplied by Ciba Corning Diagnostica, Alameda, CA, USA (Triton UGP-EIA). On referring to histopathological findings, no single parameter was seen to be specific and sensitive enough to differentiate between benign and malignant endometrial lesions. Doppler endovaginal ultrasonography could detect 76% of endometrial abnormalities. DNA ploidy and UGP showed equal sensitivity rate (60%) in endometrial carcinoma but DNA ploidy was more specific than UGP (0% and 10% false positivity in benign endometrial diseases respectively.
Assuntos
Adenocarcinoma/diagnóstico , Gonadotropina Coriônica Humana Subunidade beta/urina , Hiperplasia Endometrial/diagnóstico , Neoplasias do Endométrio/diagnóstico , Fragmentos de Peptídeos/urina , Hemorragia Uterina/diagnóstico , Adulto , Idoso , DNA de Neoplasias/análise , Feminino , Humanos , Pessoa de Meia-Idade , Ultrassonografia , Hemorragia Uterina/diagnóstico por imagem , Hemorragia Uterina/patologiaRESUMO
Urinary gonadotropin peptide (UGP) levels were determined in urine samples from 450 Egyptian subjects to determine its relative level of expression in benign and malignant urological disease, and normal individuals. The mean UGP level in patients with bladder cancer was 44-fold higher than in patients with benign disease, and 81-fold higher than in normal individuals. At specificities of 95% and 100%, overall sensitivities of 73% and 60%, respectively, were observed for the detection of malignant disease. Mean UGP levels in patients with bladder cancer were significantly correlated with the stage and grade of malignant disease but did not vary significantly when stratified according to histological type of disease, nodal involvement or bilharzial association. UGP could be a potentially useful marker for the differentiation of benign from malignant urological disease.
Assuntos
Biomarcadores Tumorais/urina , Gonadotropina Coriônica Humana Subunidade beta/urina , Fragmentos de Peptídeos/urina , Neoplasias da Bexiga Urinária/urina , Doenças Urológicas/urina , Adulto , Idoso , Diagnóstico Diferencial , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Doenças Urológicas/diagnósticoRESUMO
In a study of 34 normal healthy controls, 35 patients with urinary tract bilharziasis and 93 bladder cancer patients (62 of them are operable cases and 31 are non-operable ones), serum tumor necrosis factor alpha (TNF-alpha) and cytosolic Cathepsin-D were estimated. Though both potential markers were elevated in bladder cancer patients, neither Cathepsin-D nor TNF-alpha showed associations of prognostic value since there were no positive correlations with tumor stages, grades or association of tumors with bilharzial ova or lymph node involvement.
Assuntos
Biomarcadores Tumorais/metabolismo , Catepsina D/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Citosol/enzimologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquistossomose Urinária/metabolismo , Sensibilidade e Especificidade , Bexiga Urinária/enzimologiaRESUMO
Some environmental factors and diseases have been demonstrated to affect trace-element homeostasis. Ninety individuals were included in the present study (30 with bronchogenic carcinoma, 30 with some nonmalignant lung diseases, and 30 normal healthy controls). Serum copper, zinc, and iron levels were determined by the atomic absorption spectrophotometry. Results of this study revealed that serum copper was markedly elevated in benign lung diseases followed by bronchial carcinoma. Serum zinc was significantly reduced, whereas serum iron was not significantly decreased in both benign and malignant lung diseases compared to normal healthy controls. As to the sensitivity of the studied elements in lung disorders, neither serum copper nor serum iron can be used to detect benign or malignant diseases. Serum zinc and copper/zinc ratios showed reasonable values for prediction of pulmonary diseases but cannot be recommended as tumor markers in lung cancer.