Survivin and aven: two distinct antiapoptotic signals in acute leukemias.

BACKGROUND: Antiapoptotic signals are important in the development, progression and prognosis of malignant tumors. The aim of this study was to determine the two distinct antiapoptotic signals-survivin and aven-in acute leukemias and compare them with clinical and hematological findings and response to therapy. Real-time quantitative PCR was used and survivin and aven were detected at the messenger (m)RNA level. PATIENTS AND METHODS: Sixty-five patients with acute leukemia [37 with acute myeloblastic leukemia (AML) and 28 with acute lymphoblastic leukemia (ALL)] were used as the study group and 10 healthy subjects were used as the control group. RESULTS: Survivin was between 0.0 and 0.829 copy number/cell (median 0.0721, mean 0.5424301909 +/- 0.139799488589) and aven was between 0.0 and 0.853 copy number/cell (median 0.0124, mean 0.070335542 +/- 0.1524685709). We found an important association between survivin and aven (P = 0.000). Both survivin and aven were higher in the study group than in the controls (P = 0.001 and 0.035, respectively). When we compared survivin and aven with other clinical and hematological parameters, there was an important association between survivin and extramedullary involvement (P = 0.033), survivin and alkaline phosphatase (P = 0.06), white blood cell (WBC) count and lactate dehydrogenase (LDH) (P = 0.000), WBC count and uric acid (P = 0.074), hemoglobin level and LDH (P = 0.072), LDH and uric acid (P = 0.057), CD7 expression and survivin (P = 0.097), and CD34 expression and aven (P = 0.058). Response to therapy was evaluated according to the survivin and aven levels. Survivin level was lower in refractory patients as compared with complete responders (P = 0.085). Aven level was higher in patients with relapse as compared with non-relapse patients (P = 0.04). There was no important association between survivin or aven and performance status, lymphadenopathy or organomegaly. CONCLUSIONS: Both survivin and aven are important antiapoptotic signals in acute leukemias, and the association between extramedullary involvement, CD7 expression and CD34 expression, which are important poor prognostic indicators in acute leukemias, suggests that survivin and/or aven may be novel prognostic indicators in acute leukemias. Further studies with a higher number of patients will be more informative.     

Cancer Patterns in the Middle East Special Report from the Middle East Cancer Society

To update its cancer statistics, the newly established Middle East Cancer Society examined the cancer frequency patterns in Egypt and the Gaza Strip. The results revealed differing overall patterns. For men the highest frequencies were found for lymphoma, bladder cancer and cancers of the oral cavity and pharynx in Egypt, and for lung cancer, leukaemia and lymphoma in Gaza. For women, breast cancer had the highest frequency in both areas, followed by cancers of the oral cavity and pharynx in Egypt, and leukaemia and lymphoma in Gaza. The distribution of cancer occurrence by organ system also varied. In the light of the different ethnicities, lifestyles, socioeconomic levels and carcinogenic exposure among the countries of the Middle East, this kind of comparison can provide the background for more sophisticated approaches for discerning risk factors in cancer. We believe that further cooperation among participating countries will overcome the present limitations in data collection, registration and access.     

The comparison of dual phase Tc-99m MIBI and Tc-99m MDP scintimammography in the evaluation of breast masses: Preliminary report

The aim of this prospective study was to determine the diagnostic value of Tc-99m MDP scintimammography (SMG) for the detection of breast cancer in patients with breast masses and to compare the results with Tc-99m MIBI scintimammography. Twenty patients, categorized as suspicious, positive or benign for breast cancer according to the mammographic findings were included in the study. Dual phase Tc-99m MIBI and Tc-99m MDP SMG were performed in the prone lateral position within 5 days of each other. Although early and late Tc-99m MIBI SMG showed equal (90.4%) sensitivity, the specificity of late Tc-99m MIBI (87.5%) was found superior to early (62.5%) imaging. The overall sensitivity and specificity of early Tc-99m MDP SMG were 71.4% and 62.5%, respectively. Although late Tc-99m MDP imaging showed 100% specificity, its sensitivity was only 23.8%. In the patients with palpable masses, both early Tc-99m MDP and Tc-99m MIBI showed equal sensitivity (100%), but the sensitivity of early Tc-99m MIBI (37.5%) was found slightly higher than Tc-99m MDP (25.0%) for nonpalpable breast lesions. The sensitivity of Tc-99m MIBI and Tc-99m MDP SMG in detecting metastatic axillary involvement was 66.6% and 50%, respectively. High sensitivity and specificity together with its low cost, easy availability and the possibility of detecting bone metastases seems to make Tc-99m MDP a contributive agent in the evaluation of breast lesions as an alternative to Tc-99m MIBI.     

Long-term outcome of patients with spinal myxopapillary ependymoma: treatment results from the MD Anderson Cancer Center and institutions from the Rare Cancer Network

Background

Spinal myxopapillary ependymomas (MPEs) are slowly growing ependymal gliomas with preferential manifestation in young adults. The aim of this study was to assess the outcome of patients with MPE treated with surgery, radiotherapy (RT), and/or chemotherapy.

Methods

The medical records of 183 MPE patients (male: 59%) treated at the MD Anderson Cancer Center and 11 institutions from the Rare Cancer Network were retrospectively reviewed. Mean patient'' age at diagnosis was 35.5 ± 15.8 years. Ninety-seven (53.0%) patients underwent surgery without RT, and 86 (47.0%) were treated with surgery and/or RT. Median RT dose was 50.4 Gy. Median follow-up was 83.9 months.

Results

Fifteen (8.2%) patients died, 7 of unrelated cause. The estimated 10-year overall survival was 92.4% (95% CI: 87.7–97.1). Treatment failure was observed in 58 (31.7%) patients. Local failure, distant spinal relapse, and brain failure were observed in 49 (26.8%), 17 (9.3%), and 11 (6.0%) patients, respectively. The estimated 10-year progression-free survival was 61.2% (95% CI: 52.8–69.6). Age (<36 vs ≥36 y), treatment modality (surgery alone vs surgery and RT), and extent of surgery were prognostic factors for local control and progression-free survival on univariate and multivariate analysis.

Conclusions

In this series, treatment failure of MPE occurred in approximately one third of patients. The observed recurrence pattern of primary spinal MPE was mainly local, but a substantial number of patients failed nonlocally. Younger patients and those not treated initially with adjuvant RT or not undergoing gross total resection were significantly more likely to present with tumor recurrence/progression.     

Fermeture percutanée des communications interventriculaires congénitales par la prothèse Amplatzer Duct OccluderII: données préliminaire d’une étude Tunisienne monocentrique

Introduction . Percutaneous closure of congenital ventricular septal defects (VSDs) represents a promising alternative to surgery with lower rate of complications and shorter hospital stay. Its main limitation is the choice of the appropriate device for each type of defect. Aim. To report the experience of the service of cardiology (Sahloul hospital, Sousse, Tunisia) in percutaneous closure of congenital VSDs with Amplatzer Duct Occluder II (ADOII). Methods. This was a retrospective, monocentric study, conducted from January 2013 to December 2017. The study included patients treated by percutaneous closure of congenital VSDs with the ADOII device. Results. Twelve patients (6 boys; 6 girls) were included. The mean±SD of patients’ age and weight were 65±41 months and 23±10 kg, respectively. VSDs were peri-membranous (n=9) and muscular (n=3), and defects were restrictive (n=11) and non-restrictive (n=1). The mean (minimum-maximum) size of VSDs was 4.72 (3-6) mm. Eleven ADOII prostheses were successfully implanted. One failure procedure was noted with migration of the device into the pulmonary artery. A second child with perimembranous defect developed transient atrioventricular block. No deaths occurred. Conclusion. The present early experience shows that percutaneous closure with ADOII device of perimembranous and trabecular VSDs is safe and effective.     

Physiological instability is linked to mortality in primary central nervous system lymphoma: A case–control fMRI study

Primary central nervous system lymphoma (PCNSL) is an aggressive brain disease where lymphocytes invade along perivascular spaces of arteries and veins. The invasion markedly changes (peri)vascular structures but its effect on physiological brain pulsations has not been previously studied. Using physiological magnetic resonance encephalography (MREG_BOLD) scanning, this study aims to quantify the extent to which (peri)vascular PCNSL involvement alters the stability of physiological brain pulsations mediated by cerebral vasculature. Clinical implications and relevance were explored. In this study, 21 PCNSL patients (median 67y; 38% females) and 30 healthy age‐matched controls (median 63y; 73% females) were scanned for MREG_BOLD signal during 2018–2021. Motion effects were removed. Voxel‐by‐voxel Coefficient of Variation (CV) maps of MREG_BOLD signal was calculated to examine the stability of physiological brain pulsations. Group‐level differences in CV were examined using nonparametric covariate‐adjusted tests. Subject‐level CV alterations were examined against control population Z‐score maps wherein clusters of increased CV values were detected. Spatial distributions of clusters and findings from routine clinical neuroimaging were compared [contrast‐enhanced, diffusion‐weighted, fluid‐attenuated inversion recovery (FLAIR) data]. Whole‐brain mean CV was linked to short‐term mortality with 100% sensitivity and 100% specificity, as all deceased patients revealed higher values (n = 5, median 0.055) than surviving patients (n = 16, median 0.028) (p < .0001). After adjusting for medication, head motion, and age, patients revealed higher CV values (group median 0.035) than healthy controls (group median 0.024) around arterial territories (p ≤ .001). Abnormal clusters (median 1.10 × 10⁵mm³) extended spatially beyond FLAIR lesions (median 0.62 × 10⁵mm³) with differences in volumes (p = .0055).     

Anaphylactic reaction to polyethylene‐glycol conjugated‐asparaginase: Premedication and desensitization may not be sufficient

In hypersensitive reactions to native L‐asparaginase, either premedication and desensitization or substitution with polyethylene glycol conjugated asparaginase (PEG‐ASP) is preferred. Anaphylaxis with PEG‐ASP is rare. An 8‐year‐old girl and a 2.5‐year‐old boy, both diagnosed as having acute lymphoblastic leukemia, presented with native L‐asparaginase hypersensitivity and substitution with PEG‐ASP was preferred. They received a premedication (methylprednisolone, hydroxyzine and ranitidine) followed by desensitization with PEG‐ASP infusion. Both patients developed anaphylaxis with peg‐asparaginase. These are the first reported cases of anaphylactic reaction to PEG‐ASP, despite the application of both premedication and desensitization. Anaphylaxis with PEG‐ASP is very rare and premedication and desensitization protocols may not prevent these hypersensitive reactions.     

Genotoxic effects of a particular mixture of acetamiprid and α‐cypermethrin on chromosome aberration,sister chromatid exchange,and micronucleus formation in human peripheral blood lymphocytes

The genotoxic effects of a particular mixture of acetamiprid (Acm, neonicotinoid insecticide) and α‐cypermethrin (α‐cyp, pyrethroid insecticide) on human peripheral lymphocytes were examined in vitro by chromosomal aberrations (CAs), sister chromatid exchange (SCE), and micronucleus (MN) tests. The human peripheral lymphocytes were treated with 12.5 + 2.5, 15 + 5, 17.5 + 7.5, and 20 + 10 μg/mL of Acm+α‐cyp, respectively, for 24 and 48 h. The mixture of Acm+α‐cyp induced the CAs and SCEs at all concentrations and treatment times when compared with both the control and solvent control and these increases were concentration‐dependent in both treatment times. MN formation was significantly induced at 12.5 + 2.5, 15 + 5, 17.5 + 7.5, μg/mL of Acm+α‐cyp when compared with both controls although these increases were not concentration‐dependent. Binuclear cells could not be detected sufficiently in the highest concentration of the mixture (20 + 10 μg/mL) for both the 24‐ and 48‐h treatment times. Mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) significantly decreased because of the cytotoxic and cytostatic effects of the mixture, at all concentrations for two treatment periods. Significant decreases in MI and PI were concentration dependent at both treatment times. The decrease in NDI was also concentration‐dependent at 48‐h treatment period. In general, Acm+α‐cyp inhibited nuclear division more than positive control, mitomycin C (MMC) and showed a higher cytostatic effect than MMC. Furthermore, in this article, the results of combined effects of Acm+α‐cyp were compared with the results of single effects of Acm or α‐cyp (Kocaman and Topaktas, 2007 , 2009 , respectively). In conclusion, the particular mixture of Acm+α‐cyp synergistically induced the genotoxicity/cytotoxicity in human peripheral blood lymphocytes. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2010.