RESUMEN
Angiogenesis plays an important role in the pathogenesis of rheumatoid arthritis (RA). This study assesses basic fibroblast growth factor (bFGF) as an angiogenic factor and soluble E-selectin (sE-sel) as an angiogenic mediator in RA patients and correlates their levels in serum and synovial fluid (SF) with disease activity, functional status and joint derangement. Thirty RA patients and 15 osteoarthritis (OA) patients were clinically, radiologically and laboratory investigated. bFGF, sE-sel, interleukin -1 beta (IL-1beta) and IL-6 in serum of patients and 15 healthy subjects and in SF tapped from knee joints of 9 RA and 9 OA patients were measured by ELISA. Both serum bFGF and sE-sel were significantly elevated in RA compared to OA patients and controls. These levels correlated positively with functional class stages of the disease. SF levels of bFGF and sE-sel showed significant increase in RA than OA patients. Both levels showed positive correlation with each other and with disease functional stages. A positive correlation was also found between SF bFGF with grades of joint derangement assessed radiologically. No significant correlations were observed between bFGF or sE-sel and clinical parameters of disease activity or other biochemical markers. In conclusion, serum and SF b-FGF and sE-sel may be considered as makers of functional status of RA patients. SF bFGF seems to reflect progressive joint derangement.
Asunto(s)
Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Selectina E/sangre , Factor 2 de Crecimiento de Fibroblastos/sangre , Líquido Sinovial/química , Adulto , Progresión de la Enfermedad , Egipto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/sangre , Valores de Referencia , Índice de Severidad de la EnfermedadRESUMEN
Based on the assumption that an accelerated proliferation process prevails in tumour cell residues after surgery, the possibility that treatment acceleration would offer a therapeutic advantage in postoperative radiotherapy of locally advanced head and neck cancer was investigated. The value of T(pot) in predicting the treatment outcome and in selecting patients for accelerated fractionation was tested. Seventy patients with (T2/N1-N2) or (T3-4/any N) squamous cell carcinoma of the oral cavity, larynx and hypopharynx who underwent radical surgery, were randomized to either (a) accelerated hyperfractionation: 46.2 Gy per 12 days, 1.4 Gy per fraction, three fractions per day with 6 h interfraction interval, treating 6 days per week or (b) Conventional fractionation: 60 Gy per 6 weeks, 2 Gy per fraction, treating 5 days per week. The 3-year locoregional control rate was significantly better in the accelerated hyperfractionation (88 +/- 4%) than in the CF (57+/- 9%) group, P=0.01 (and this was confirmed by multivariate analysis), but the difference in survival (60 +/- 10% vs 46 +/- 9%) was not significant (P=0.29). The favourable influence of a short treatment time was further substantiated by demonstrating the importance of the gap between surgery and radiotherapy and the overall treatment time between surgery and end of radiotherapy. Early mucositis progressed more rapidly and was more severe in the accelerated hyperfractionation group; reflecting a faster rate of dose accumulation. Xerostomia was experienced by all patients with a tendency to be more severe after accelerated hyperfractionation. Fibrosis and oedema also tended to be more frequent after accelerated hyperfractionation and probably represent consequential reactions. T(pot) showed a correlation with disease-free survival in a univariate analysis but did not prove to be an independent factor. Moreover, the use of the minimum and corrected P-values did not identify a significant cut-off. Compared to conventional fractionation, accelerated hyperfractionation did not seem to offer a survival advantage in fast tumours though a better local control rate was noted. This limits the use of T(pot) as a guide for selecting patients for accelerated hyperfractionation. For slowly growing tumours, tumour control and survival probabilities were not significantly different in the conventional fractionation and accelerated hyperfractionation groups. A rapid tumour growth was associated with a higher risk of distant metastases (P=0.01). In conclusion, tumour cell repopulation seems to be an important determinant of postoperative radiotherapy of locally advanced head and neck cancer despite lack of a definite association between T(pot) and treatment outcome. In fast growing tumours accelerated hyperfractionation provided an improved local control but without a survival advantage. To gain a full benefit from treatment acceleration, the surgery-radiotherapy gap and the overall treatment time should not exceed 6 and 10 weeks respectively.
Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/radioterapia , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Terapia Combinada , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Femenino , Fibrosis/etiología , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Cuidados Posoperatorios , Traumatismos por Radiación/etiología , Dosificación Radioterapéutica , Xerostomía/etiologíaRESUMEN
Cell proliferation in carcinoma in the bilharzial bladder was studied in 92 patients in terms of the in vitro labeling index (LI), cell density (CD) and labeled cell density (LCD) using the in vitro 3H-Tdr technique. Cell proliferation was much greater in high than in low grade tumors and in deep than in superficial parts of the tumor, but was much less dependent on cell type; transitional cell cancer had the highest activity followed by squamous cell and adenocarcinoma. The probability of local recurrence after cystectomy decreased markedly when the LI exceeded 5.0%. The influence of the following three pre-operative radiotherapy regimens was studied: split-course (SC): the initial course consisted of 20 Gy in 10 treatments with a similar course was given after one week, hyper-fractionation using 17 treatments 0.6 Gy each on two successive days, this 2-day course of 20 Gy was repeated after one week, and concentrated irradiation consisting of two treatments, 6.0 Gy each with a gap of one week. Cystectomy was performed 14-20 days after treatment in all groups. Preoperative irradiation was generally associated with an increased probability of local control. The unfavorable influence of a high pretreatment LI was not noted after pre-operative irradiation. The CD was also reduced in proportion to the pretreatment LI. It is proposed that the response to irradiation was proportional to the initial proliferation activity and hence the prognostic significance of tumor grade and pretreatment LI was masked. Postirradiation tumor volume reduction was a strong predictor of treatment outcome. Concentrated irradiation was the least efficient pre-operative irradiation regimen and was associated with the least tumor volume reduction.
Asunto(s)
Carcinoma/etiología , Esquistosomiasis/complicaciones , Enfermedades de la Vejiga Urinaria/complicaciones , Neoplasias de la Vejiga Urinaria/etiología , Carcinoma/patología , Carcinoma/radioterapia , Carcinoma/cirugía , División Celular/efectos de la radiación , Terapia Combinada , Humanos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/radioterapia , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
Penetration studies of MIS after intravesical administration showed adequate concentrations with a gradient across the tumor. After instillation of 2.5 g in 50 ml water the concentration in the deep parts of the tumor amounted to about 100 microgram per ml. This corresponds to a SER for hypoxic cell of the order of 1.7. A more uniform tissue distribution of the drug was noted 3.5 hours after an oral dose of 3 g/meter square. The concentration in the deep parts of the tumor and perivesical tissue was of the order of 100 micrograms/g. The concentration in these regions are relevant to preoperative irradiation which aims at sterilizing the deep infiltrating margins. The intravesical use with or without oral augmentation is suitable for use in association with concentrated preoperative radiotherapy regimens. The topical use of MIS in such regimens markedly reduces the risk of neurotoxicity. The tissue concentration resulting from the two routes proved to be additive. The higher concentration in lymph nodes after the oral route the greater concentration and prolonged contact after combined administration may have therapeutic merits.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Transicionales/metabolismo , Misonidazol/administración & dosificación , Nitroimidazoles/administración & dosificación , Neoplasias de la Vejiga Urinaria/metabolismo , Vejiga Urinaria/metabolismo , Administración Oral , Administración Tópica , Humanos , Cinética , Misonidazol/metabolismo , Membrana Mucosa/metabolismo , Neoplasias de la Vejiga Urinaria/radioterapiaRESUMEN
Measurement of intercapillary distances suggests the presence of significant cell hypoxia in Bilharzial bladder cancer. This tumor seems to be capable of reoxygenation in view of the existence of a correlation between prognosis and immediate tumor shrinkage after irradiation. Two programs are presented: 1) Use of misonidazole with concentrated preoperative irradiation where the reoxygenation properties are not used fully. A prospective randomized study is presented whereby cystectomy alone is compared with cystectomy plus preoperative irradiation (6.5 Gy X 2F/1 week) with or without misonidazole. the drug is given either orally (in two doses 3 g/m2 each given 3.5 hours prior to each fraction; blood levels: 90-110 micrograms/ml) or intravesically. The intravesical administration is designed in the light of penetration studies and seems to have the advantage of the complete lack of systemic drug toxicity. Twenty-eight patients were included in this study and no drug toxicity was recorded. A second preoperative irradiation study is presented whereby cystectomy alone is compared with cystectomy plus preoperative irradiation (4.0 Gy X 5F) with or without misonidazole in individual doses of 2 g/m2. 2) Two radical radiotherapy regimes are presented. One protocol involves a split course (SC) protracted regime making full use of spontaneous reoxygenation. The drug is given in 0.5 g/m2 daily doses (total dose 14 g/m2 spread over 61 days, blood level: 15-20 micrograms/ml). A second protocol involves hyperfractionation stimulating continuous low-dose-rate irradiation. Higher blood levels are attained (60-80 micrograms/ml) after daily doses of 2 g/m2 (total dose: 14 g/m2 spread over 35 days). In a phase II study using SC technic, reversible grade 1 peripheral neuropathy was encountered in 5 of 22 patients. Complete tumor regression 3 months after irradiation was achieved in 18 of 22 patients with 3T tumors. No neuropathy was encountered in four patients subjected to the HF regimen who also showed complete tumor regression.