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A Jalil

Publications and source records attributed to A Jalil.

At least 19 recordsLinked to original sources

Imatinib enhances human melanoma cell susceptibility to TRAIL-induced cell death: Relationship to Bcl-2 family and caspase activation.

In order to define genetic determinants of primary and metastatic melanoma cell susceptibility to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), we have applied oligonucleotide microarrays to TRAIL-sensitive primary T1 cells and TRAIL-resistant metastatic G1 cells treated or not with TRAIL. T1 and G1 cells are isogenic melanoma cell subclones. We examined 22 000 spots, 4.2% of which displayed differential expression in G1 and T1 cells. Cell susceptibility to TRAIL-mediated apoptosis was found to be correlated with gene expression signatures in this model. Some of the differentially expressed genes were identified as involved in ATP-binding and signaling pathways, based on previously published data. Further analysis provided evidences that c-kit was overexpressed in G1 cells while it was absent in T1 cells. The c-kit inhibitor, imatinib, did not restore TRAIL sensitivity, excluding a role for c-kit in TRAIL resistance in G1 cells. Surprisingly, imatinib inhibited cell proliferation and TRAIL-mediated apoptosis in melanoma cells. We investigated the possible involvement of several molecules, including c-ABL, platelet-derived growth factor receptor (PDGFR), cellular FADD-like interleukin-1 alpha-converting enzyme-like inhibitory protein (c-FLIP)(L/S), Fas-associated DD kinase, p53, p21(WAF1), proteins of B-cell leukemia/lymphoma 2 (Bcl-2) family and cytochrome c. Imatinib did not modulate the expression or activation of its own targets, such as c-ABL, PDGFRalpha and PDGFRbeta, but it did affect the expression of c-FLIP(L), BCL2-associated X protein (Bax) and Bcl-2. Moreover, c-FLIP(L) knockdown sensitized T1 cells to TRAIL-mediated apoptosis, with a sensitivity similar to that of cells previously treated with imatinib. More notably, we found that the resistance to TRAIL in G1 cells was correlated with constitutive c-FLIP(L) recruitment to the DISC and the inhibition of caspase 8, 3 and 9 processing. Moreover, c-FLIP(L) knockdown partly restored TRAIL sensitivity in G1 cells, indicating that the expression level of c-FLIP(L) and its interaction with TRAIL receptor2 play a crucial role in determining TRAIL resistance in metastatic melanoma cells. Our results also show that imatinib enhances TRAIL-induced cell death independently of BH3-interacting domain death agonist translocation, in a process involving the Bax:Bcl-X(L) ratio, Bax:Bcl-X(L)/Bcl-2 translocation, cytochrome c release and caspase activation. Our data indicate that imatinib sensitizes T1 cells by directly downregulating c-FLIP(L), with the use of an alternative pathway for antitumor activity, because PDGFRalpha is not activated in T1 cells and these cells do not express c-kit, c-ABL or PDGFRbeta. Caspase cascade activation and mitochondria also play a key role in the imatinib-mediated sensitization of melanoma cells to the proapoptotic action of TRAIL.

Antineoplastic Agents↗

The sensitivity of renal cell carcinoma cells to interferon alpha correlates with p53-induction and involves Bax.

Interferon alpha (IFN-alpha) is an approved treatment in metastatic renal cell carcinoma (RCC). The underlying mechanisms are far from being clear, but are presumed to be a combination of stimulation of cell-mediated cytotoxicity, direct antiproliferative activity and antiangiogenic effects. Recently, the role of p53 in the cellular response to IFN-alpha has been proposed in other tumor models (hepatoblastoma). We therefore studied the expression of p53 during IFN-alpha treatment using two freshly established RCC cell lines RCC5 and RCC7. While IFN-alpha treatment significantly enhanced the expression of p53 in RCC7, no changes were observed in RCC5. Cell viability under IFN-alpha remained unchanged in both cell lines. Following gamma-irradiation, a p53-activating stimulus, an enhanced cell death was observed in IFN-alpha-treated RCC7 but not in RCC5. We further demonstrate that there were no changes in Bcl-2- and Bax-expression, two target genes regulated by p53. However, intracellular staining revealed that cell death induced by IFN-alpha and gamma-irradiation was preceded by a shift of Bax to the mitochondria in RCC7. Our results suggest a role of p53 and its downstream target Bax, in the control of RCC sensitivity to IFN-alpha.

Carcinoma, Renal Cell↗

[Management of phyllodes tumors of the breast at the National institute of oncology of Rabat, Morocco].

OBJECTIVES: Phyllodes tumors of the breast (PTB) are rare fibro epithelial tumors. Their terminology, histological classification and their treatment are exposed to controversy. The aim of our work is to underline the epidemiological, clinical, histological, therapeutical, prognostic and evolutive features of these tumours through a retrospective study and a review of the literature. PATIENTS AND METHODS: We reviewed at the National Institute of Oncology of Rabat, Morocco, between 1985 and 1998, all the files of patients with histological certainty of PTB, doubtful PTB were excluded. We collected epidemiological, clinical, histological, therapeutical, prognostic and evolutive features of these tumours. STATISTICS: quantitative parameters were represented by mean +/- S.D. and qualitative parameters by percentage or effective. RESULTS: We studied nine cases of PTB, which represented 0.09% of all primitive tumors of the breast treated at our institution during the study period. All our patients were female. Mean age was 37.3 +/- 10.07 years. Two of our patients (22.2%) had a history of fibroadenoma and 44.4% were nulliparous. Mean delay before consulting was 60.7 +/- 17.56 months and the median tumour size was 13 +/- 7.47 cm. Pathological findings were six benign or borderline phyllodes tumours (66.7%) and three cystosarcomas phyllodes (33.3%). The treatment consisted in simple mastectomy in seven cases (77.8%) and tumorectomy in two cases (22.2%). All the surgical margins were clear. Two of the three cystosarcomas phyllodes received adjuvant external bean radiation therapy 50 Gy on the thoracic chest wall. After a median outcome of 3 +/- 2 years ranging from 3 to 74 months, we did not note any relapse or metastasis. DISCUSSION AND CONCLUSION: In our series, PTB happened exclusively in females. History of fibroadenoma within 22.2% of the patients suggests the hypothesis of a filiation between these two entities. Their distinctive features were young age in diagnosis, long delay before consulting, important tumor size, predominant benign and borderline histological types, treatment mainly surgical and good local and distant control.

Adult↗

[Breast angiosarcomas: three case reports].

Angiosarcoma is a rare type of breast cancer, it has the worst prognosis of all breast malignancies. We report three cases of breast angiosarcoma observed at the National Oncology Institute and the Maternity of Orangers. A preoperative diagnosis was evoked in one case only, after a local recurrence in the second one and histological in the last one. Mastectomy is the reference treatment. The development is distinguished by general metastasis. Based on review of literature, we analysed the different aspects of this disease.

Adult↗

[Kidney cancer: report of 47 cases].

The authors report a series of 47 cases observed over a 15-years period in the department of carcinological at the national oncological institute of Rabat. Patients consisted of 16 mean and 21 women (57%), with a mean age of 49 years old (range 29 to 70 years). The clinical features were polymorph, firstly loin pain (81%), hematuria is the next (25%). A lumbar mass (10%). The diagnosis was established by ultra-sonography and CT-scan in all the patients. The mean tumour diameter was 10 cm (5-17 cm), it were located in down pole in 53%. The surgical procedure consisted of radical nephrectomy and regional or hailer lymph node dissection in 46 patients. The post operative course was marked by one death due to pulmonary metastases. The mean follow-up was (2 to 15 years). Asynchronies metastases occurred in 6 patients after a mean interval (9 to 36 months). The overall 5 year survival was 100% PT1, 78% PT2, 34% PT3.

Adult↗

[Post-radiotherapy ureterovaginal fistula. 12 case reports].

The authors report a series of 12 cases of ureterovaginal fistulas observed over 15 years period. Our patients had a mean age of 38 years (range 27 to 44 years old). Eighty four percent of ureterovaginal fistulas were due to radiotherapy and clopohysterectomy. Sixteen percent of ureterovaginal fistulas were due to brachy and radiotherapy. The clinical features were dominated by urine leak via the vagina with persistent micturition. Intravenous urography confirmed the diagnosis and revealed ureterohydronephrosis. Various therapeutic methods were used, in 7 patients treatment consisted of end-to-end anastomosis. We have used ureterovesical reimplantation in 3 cases and double J sent in 2 cases. The course was favourable in 84%.

Adult↗

[Association of ovarian juvenile granulosa cell tumor with Maffucci's syndrome].

The authors report a rare case of the ovarian juvenile granulosa cell tumor associated with Maffucci's syndrome (enchondromathosis + hemangiomas), no heriditary mesodermal dysplasia. Sarcomatous changes of chondromas are encountered most frequently; however other various typed neoplasma have been reported: ovarian juvenile granulosa cell tumor may occur not infrequently in female patients with Maffucci's syndrome in the first or second decades. Sarcomatous changes of choromas established prognosis of the Maffucci's syndrome.

Adolescent↗

Artificial neural networks for blur identification and restoration of nonlinearly degraded images.

In this paper, an image restoration algorithm is proposed to identify noncausal blur function. Image degradation processes include both linear and nonlinear phenomena. A neural network model combining an adaptive auto-associative network with a random Gaussian process is proposed to restore the blurred image and blur function simultaneously. The noisy and blurred images are modeled as continuous associative networks, whereas auto-associative part determines the image model coefficients and the hetero-associative part determines the blur function of the system. The self-organization like structure provides the potential solution of the blind image restoration problem. The estimation and restoration are implemented by using an iterative gradient based algorithm to minimize the error function.

Algorithms↗

Arsenic in drinking water and pregnancy outcomes.

We studied a group of women of reproductive age (15-49 years) who were chronically exposed to arsenic through drinking water to identify the pregnancy outcomes in terms of live birth, stillbirth, spontaneous abortion, and preterm birth. We compared pregnancy outcomes of exposed respondents with pregnancy outcomes of women of reproductive age (15-49 years) who were not exposed to arsenic-contaminated water. In a cross-sectional study, we matched the women in both exposed and nonexposed groups for age, socioeconomic status, education, and age at marriage. The total sample size was 192, with 96 women in each group (i.e., exposed and nonexposed). Of the respondents in the exposed group, 98% had been drinking water containing [Greater and equal to] 0.10 mg/L arsenic and 43.8% had been drinking arsenic-contaminated water for 5-10 years. Skin manifestation due to chronic arsenic exposure was present in 22.9% of the respondents. Adverse pregnancy outcomes in terms of spontaneous abortion, stillbirth, and preterm birth rates were significantly higher in the exposed group than those in the nonexposed group (p = 0.008, p = 0.046, and p = 0.018, respectively).

Abortion, Spontaneous↗

Decreased production of local immunoglobulin A to Pneumocystis carinii in bronchoalveolar lavage fluid from human immunodeficiency virus-positive patients.

An enzyme-linked immunosorbent assay and a Western blot analysis were developed to study the antibody response to Pneumocystis carinii in serum and bronchoalveolar lavage fluid from 27 human immunodeficiency virus 27 (HIV)-infected patients with P. carinii pneumonia (Pcp), 32 patients without Pcp, and 51 HIV-negative controls. Urea was used for the correct dilution of epithelial lining fluid, and albumin was used to evaluate transudation from plasma for the assessment of local production of antibodies to P. carinii. By contrast with those of immunoglobulin G (IgG), IgA responses to P. carinii were increased in serum from HIV-positive patients compared to negative controls. Local production of antibodies to P. carinii, especially IgA, was decreased in patients with Pcp. In a study of 10 patients of each group, IgG and IgA responses to gp116 from P. carinii were lower in patients with Pcp than in other groups. These results suggest that, in addition to alveolar macrophages, local antibodies may play a role in host defense against P. carinii.

Animals↗

[Bone metastasis revealing a primary prostate cancer].

Spiculated reactive periosteal bone is usually found in cases of primary malignant bone tumors; rarely in secondary bone lesions. The authors report a case of bone tumor of the clavicle in a 62 year-old patient with "sunburst " periosteal reaction on radiographs. The metastatic nature of this lesion from an unknown prostate carcinoma was confirmed by immunohistochemical studies of the clavicle biopsy. Tumorectomy was performed and the patient's status is stable with a follow-up of 10 months.

Biopsy↗

A rare case of angiosarcoma of the breast in a man: case report.

This is a case report of a 57-year-old man who had primary angiosarcoma of the left breast. Five months after detecting a mass in his breast, he underwent mastectomy with biopsy of the ipsilateral axillary lymph nodes. Three years later, he is still alive without any recurrence. Angiosarcoma of the female breast is rare and exceptional in males. It is a condition with a poor prognosis and there are as yet no established chemotherapeutic regimens.

Breast Neoplasms, Male↗

Catecholamine metabolism inhibitors and receptor blockades only partially suppress cardiac hypertrophy of juvenile visceral steatosis mice with systemic carnitine deficiency.

To clarify the mechanism of cardiac hypertrophy in carnitine-deficient JVS mice, we studied the possible role of catecholamine metabolism. Cardiac hypertrophy occurs 2 weeks after birth. The turnover of norepinephrine in the ventricles of JVS mice at 2 weeks was 3 times that of control, but it was not different from control at 5 days when the heart weight was not changed. To evaluate the accelerated norepinephrine turnover, we examined the effects of catecholamine metabolism inhibitors (alpha-methyltyrosine and 6-hydroxydopamine) and catecholamine receptor blockades (propranolol, prazosin and yohimbine) on the ratio of heart weight to body weight (HW/BW) and on the augmented expression of atrial natriuretic peptide (ANP) and the down-regulated carnitine deficiency-associated gene expressed in ventricle (CDV-1). The HW/BW ratio in JVS mice treated with catecholamine metabolism inhibitors and receptor blockades was significantly lower than in JVS mice without treatment, but still higher than in controls treated with each drug and in JVS mice treated with carnitine. The HW/BW ratio of JVS mice with propranolol was not significantly different from that of JVS mice treated with catecholamine metabolism inhibitors and was significantly lower than that of JVS mice treated with prazosin and yohimbine. Northern blot analysis showed that the altered expression of ANP and CDV-1 was not corrected in the ventricles of JVS mice treated with any of the drugs except carnitine. These results suggest that the catecholamine metabolism accelerated in JVS mice ventricles at 2 weeks is not the major cause of cardiac hypertrophy, but probably promotes cardiac hypertrophy mainly through the beta-adrenergic signaling pathway. The aberrant gene expression of ANP and CDV-1 found in JVS mice seems to be independent of catecholamine metabolism, and mediated primarily by the systemic carnitine deficiency.

Adrenergic Antagonists↗

Allogeneic peripheral blood stem cell transplantation for hypereosinophilic syndrome with severe cardiac dysfunction.

A 42-year-old male underwent an HLA-matched sibling PBSC transplant for hypereosinophilic syndrome (HES) diagnosed in August 1995. Prior to transplant he experienced progressive cardiac and pulmonary dysfunction with red cell and platelet transfusion dependence despite therapy with hydroxyurea, steroids and interferon. He received busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) as conditioning and standard GVHD prophylaxis with cyclosporin A and methotrexate. At day +336 he was transfusion independent without GVHD. Prompt reduction of the eosinophil count (<500/microl) and rapid improvement of cardiac function were documented, demonstrating the reversibility of organ dysfunction. Allogeneic PBSCT is an effective therapeutic option for patients with HES who fail conventional therapy.

Adult↗

Humoral immune response within the lung in HIV-1 infection.

In order to study the humoral immune defences in the respiratory tract during HIV-1 infection, we measured the levels, local productions and anti-HIV and antibacterial activities of IgG and IgA in the bronchoalveolar lavage fluid (BALF) and serum of 61 adult patients with severe HIV infection and of 56 HIV- controls. Albumin was used as the serum transudation factor. The increase of immunoglobulin levels in the serum of HIV-infected patients was confirmed. The IgG level was also increased in epithelial lining fluid (ELF), whereas the total IgA level was unchanged and secretory IgA (SIgA) level was decreased. The ELF/serum immunoglobulin ratios suggested that the IgG present in ELF resulted mainly from transudation, in contrast to SIgA, which was synthesized locally in controls but greatly diminished in HIV-infected patients. IgG to HIV-1 could be detected in BALF of all the patients, but IgA to HIV-1 only in 30% of patients. BAL IgG reacted more consistently and with a broader array of HIV-1 antigens than did IgA. BAL IgA, when present in samples, reacted primarily with viral envelope antigens. Because IgA specificities to some HIV-1 antigens were detected more intensively by BAL than by serum immunoglobulins, we conclude that the mucosal immune response is distinct from that in serum. IgG antibody activity to Streptococcus pneumoniae was decreased in HIV-infected patients' sera, and IgA antibody activities to S. pneumoniae and to Pseudomonas aeruginosa were decreased in ELF in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗