Comparison of idarubicin and daunorubicin regarding intracellular uptake, induction of apoptosis, and resistance

Anthracycline antibiotics are widely used as anticancer agents. Idarubicin (4-demethoxydaunorubicin; Ida), a semisynthetic derivative of daunorubicin (Dnr) is more potent than the parent compound in vitro and in vivo. The equitoxic dose of Ida in patients is about one-fourth of that of Dnr. We compared these drugs regarding cytotoxicity, apoptosis induction, and resistance mechanisms in human leukaemic cell lines. Cytotoxicity was studied by means of the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay and drug-induced apoptosis by means of the Annexin V-fluorescein isothiocyanate method at similar intracellular concentrations (extracellular concentrations of 0.35 microM for Ida and 1 microM for Dnr). Ida was at least twice as potent as Dnr in MOLT-4, HL60, CEM, and K562 cell lines. It took 8 h for Ida to induce approximately 20% apoptosis, but at least 22 h for Dnr to reach 20% apoptosis at identical intracellular concentration. Ida induces a faster and higher apoptosis rate compared with Dnr. The human chronic myelogenous leukaemia cell line (K562) was selected for resistance to Dnr and Ida with and without verapamil (Ver). Continuous incubation with Dnr, but not with Ida, led to an increased mdr1 gene expression as assessed by real-time PCR. The development of mdr1 gene expression in Dnr-resistant cells could be reversed by the presence of Ver. Ver also reversed the cytotoxicity to Dnr, but not to Ida, in K562/Dnr cells. The results show that Ida is more effective than Dnr in inducing apoptosis and that there are differences in resistance mechanisms between the drugs.     

Leptin and leptin receptor polymorphisms are associated with increased risk and poor prognosis of breast carcinoma

Background  

Leptin (LEP) has been consistently associated with angiogenesis and tumor growth. Leptin exerts its physiological action through its specific receptor (LEPR). We have investigated whether genetic variations in LEP and LEPR have implications for susceptibility to and prognosis in breast carcinoma.     

Possible correlation between urinary muramidase (E.C.3.2.1.27) and oesophageal cancer

The diagnostic value of determination of low-mass enzymes in urine is very important, especially for early detection of some diseases. There are several investigations about lysozyme (muramidase, E.C.3.2. 1.27) and its correlation with some malignancies, but until now nothing has been reported about the lysozyme, and oesophageal cancer. This study was undertaken for determination of lysozyme concentration in urine of 32 oesophageal cancer patients to evaluate if this enzyme activity changes in oesophageal cancer used for detection of this cancer especially in its early stage. We used high performance liquid chromatography (HPLC) for determination of urinary muramidase after Sep-pac pre-purification of the samples. The mean results of lysozymuria in patients in comparison with the mean of enzyme activity in normal controls were statistically high (12.14+/-0.403 vs. 2.04+/-0.134, P相似文献   

Binaural sensitivity to temporal fine structure and lateralization ability in children with suspected (central) auditory processing disorder

Objective

Previous studies have shown that a subgroup of children with suspected (central) auditory processing disorder (SusCAPD) have insufficient ability to use binaural cues to benefit from spatial processing. Thus, they experience considerable listening difficulties in challenging auditory environments, such as classrooms. Some researchers have also indicated the probable role of binaural temporal fine structure (TFS) in the perceptual segregation of target signal from noise and hence in speech perception in noise. Therefore, in the present study, in order to further investigate the underlying reason for listening problems against background noise in this group of children, their performance was measured using binaural TFS sensitivity test (TFS-LF) as well as behavioral auditory lateralization in noise test, both of which are based on binaural temporal cues processing.

Metastatic breast cancer 49 years after initial treatment

Very late metastases after cancer therapy are not common. We report an exceptionnal case of breast carcinoma associated with pregnancy that reocurred in the form of brain metastasis 49 years after initial treatment.     

Intestinal T cell lymphoma in coeliac disease. A case report

Primary intestinal T-cell lymphomas account for about 5% of all primary gastrointestinal lymphomas and are mostly associated with coeliac disease. Intestinal lymphomas are usually discovered during the 4th to 5th decade and constitute an exceptional complication of coeliac disease. This lymphoma is generally a high grade pleomorphic cell lymphoma with large cells. Our case concerned a 30 year old woman with a history of coeliac disease who developed a gastro-enteromesenteric lymphoma. Anatomopathological and immunohistochemical analysis showed an enteropathy associated T-cell lymphoma. We suggest that patients with coeliac disease unresponsive to a gluten free diet or with deteriorating clinical condition be investigated for complications such as enteropathy associated T-cell lymphoma. It is also important to avoid this complication by detecting asymptomatic form of coeliac disease that needs a gluten-free diet.     

Maternal and foetal prognostic during severe toxemia

Severe gravidic toxemia gives heavy maternal and foetal morbidity and mortality. The purpose of our study is to loosen the factors of bad maternal and foetal prognostic. It's a retrospective study about 100 cases of severe and complicated gravidic toxemia repertorieted in the maternity of Military Hospital of Tunis. Maternal morbidity is dominated by the complications of hypertension and a blood disorders. We raised 4 cases of eclampsia, 9 cases of retro placental hematome and 5 cases of HELLP syndrome. We don't deplore any maternal death. Perinatal mortality is 28.8%. The rate of delay intra-uterine growth was 43.8% and the prematurity 65.9%. More toxemia appears early during pregnancy more maternal and foetal prognostic is compromised.     

Preoperative concurrent chemotherapy and radiation therapy in cervix cancer: preliminary results

This is a retrospective study of patients treated for cervix cancer staged IB2, IIA or IIB with bulky tumor (> 4cm). Treatment was concurrent radiotherapy (45Gy with 1,8Gy daily fraction) and chemotherapy (5 cycles of Platinum 40mg/m2/week). All patients underwent Brachytherapy (15Gy on the reference isodose according to Paris system) followed by surgery (radical abdominal hysterectomy and bilateral pelvic lymphadenectomy: Piver 3) Between October 1999 and December 2002, forty five patients were treated in this protocol. Median age was 46 years (21- 68). Histology was squamous cell carcinoma in 93% and glandular carcinoma in 7%. Average external radiation dose was 44Gy (20-50). Ninety three percent of patients had at least 3 cycles of chemotherapy and 46,5% received the planned 5 cycles. On the operative specimens, there was 62,5% complete response and only 7 pelvic node involvement (17,5%). Four postoperative complications were noted (one vascular injury, one urinary fistula, one phlebitis and one lymph collection). Preoperative combined radiotherapy and chemotherapy in the early bulky stages of uterine cervix cancer is well tolerated and "gives" a high rate of sterilisation. There was no increase in surgical morbidity.     

Emphysematous pyelonephritis. Two cases

The emphysematous pyelonephritis is a rare and severe renal infection characterized by the presence of gas in renal parenchyma and its perirenal spaces. We report two cases of emphysematous pyelonephritis in two diabetic women (53 and 50 years old respectively). In the first case, the treatment was based on nephrectomy because of the presence of a septic shock and three risk factors, which are acute renal failure, hematuria and thrombopenia. In the second case, the treatment was only medical. The evolution was favorable in the two cases. We insist in this article that this diagnosis should be considered in every female diabetic patient having severe acute pyelonephritis resistant to a well-conducted medical treatment.