Telomere length shortening is associated with treatment-free remission in chronic myeloid leukemia patients

We studied telomere length in 32 CML patients who discontinued imatinib after achieving complete molecular remission and 32 age-sex-matched controls. The relative telomere length (RTL) was determined by q-PCR as the telomere to single copy gene (36B4) ratio normalized to a reference sample (K-562 DNA). Age-corrected RTL (acRTL) was also obtained. The 36-month probability of treatment-free remission (TFR) was 59.4 %. TFR patients showed shorter acRTL compared to relapsed (mean ± SD = 0.01 ± 0.14 vs 0.20 ± 0.21; p = 0.01). TFR was significantly higher in CML patients with acRTL ≤0.09 (78.9 vs 30.8 %, p = 0.002). CML stem cells harboring longer telomeres possibly maintain a proliferative potential after treatment discontinuation

Spectroscopie d'émission vuv-visible provenant de plasmas basse pression : applications aux traitements de surfaces polymériques

Plasmas et radiation ultraviolette lointaine -- Spectroscopie ultraviolette lointaine des plasmas micro-onde. L'effet des paramètres "externes" -- Spectroscopie ultraviolette lointaine -- Visible des plasmas onde de surface. L'effet de la fréquence d'excitation -- Étude de l'effet de l'ultraviolet lointain sur les polymères

Occurrence of immune thrombocytopenic purpura in a patient with essential thrombocythemia: How the immune system can overcome a neoplastic clone

Our case highlights the possible coexistence of essential thrombocythemia (ET) and idiopathic thrombocytopenic purpura (ITP), two pathological entities with opposite clinical and laboratory manifestations. It also underlines how an autoimmune attack has been temporarily able to overcome a neoplastic clone

Unbalanced 1q Whole-Arm Translocation Resulting in der(14)t(1;14)(q11–12;p11) in Myelodysplastic Syndrome

Unbalanced whole-arm translocations (WATs) of the long arm of chromosome 1, resulting in complete trisomy 1q, are chromosomal abnormalities detectable in both solid tumors and hematologic neoplasms. Among the WATs of 1q to acrocentric chromosomes, a few patients with der(1;15) described as a dicentric chromosome have been reported so far, whereas cases of der(1;14) are much rarer. We report on a case of der(1;14) detected as single anomaly in a patient with myelodysplastic syndrome. The aim of our work was to investigate the breakpoints of the (1;14) translocation leading to the der(1;14). Fluorescence in situ hybridization (FISH) experiments have been performed on chromosome preparations from bone marrow aspirate, using specific centromeric probes of both chromosomes, as well as a probe mapping to 1q11 band. FISH results showed that in our patient the derivative chromosome was monocentric with a unique centromere derived from chromosome 14. The breakpoints of the translocation were located in the short arm of chromosome 14 and in the long arm of chromosome 1, between the alphoid D1Z5 and the satellite II domains. The 1q breakpoint was within the pericentromeric region of chromosome 1, which is notoriously an unstable chromosomal region, involved in different chromosomal rearrangements

Syk kinase inhibitors synergize with artemisinins by enhancing oxidative stress in plasmodium falciparum-parasitized erythrocytes

Although artemisinin-based combination therapies (ACTs) treat Plasmodium falciparum malaria effectively throughout most of the world, the recent expansion of ACT-resistant strains in some countries of the Greater Mekong Subregion (GMS) further increased the interest in improving the effectiveness of treatment and counteracting resistance. Recognizing that (1) partially denatured hemoglobin containing reactive iron (hemichromes) is generated in parasitized red blood cells (pRBC) by oxidative stress, (2) redox-active hemichromes have the potential to enhance oxidative stress triggered by the parasite and the activation of artemisinin to its pharmaceutically active form, and (3) Syk kinase inhibitors block the release of membrane microparticles containing hemichromes, we hypothesized that increasing hemichrome content in parasitized erythrocytes through the inhibition of Syk kinase might trigger a virtuous cycle involving the activation of artemisinin, the enhancement of oxidative stress elicited by activated artemisinin, and a further increase in hemichrome production. We demonstrate here that artemisinin indeed augments oxidative stress within parasitized RBCs and that Syk kinase inhibitors further increase iron-dependent oxidative stress, synergizing with artemisinin in killing the parasite. We then demonstrate that Syk kinase inhibitors achieve this oxidative enhancement by preventing parasite-induced release of erythrocyte-derived microparticles containing redox-active hemichromes. We also observe that Syk kinase inhibitors do not promote oxidative toxicity to healthy RBCs as they do not produce appreciable amounts of hemichromes. Since some Syk kinase inhibitors can be taken daily with minimal side effects, we propose that Syk kinase inhibitors could evidently contribute to the potentiation of ACTs

Antisenescence Effect of REAC Biomodulation to Counteract the Evolution of Myelodysplastic Syndrome

About 30 percent of patients diagnosed with myelodysplastic syndromes (MDS) progress to acute myeloid leukemia (AML). The senescence of bone marrow‐derived mesenchymal stem cells (BMSCs) seems to be one of the determining factors in inducing this drift. Research is continuously looking for new methodologies and technologies that can use bioelectric signals to act on senescence and cell differentiation towards the phenotype of interest. The Radio Electric Asymmetric Conveyer (REAC) technology, aimed at reorganizing the endogenous bioelectric activity, has already shown to be able to determine direct cell reprogramming effects and counteract the senescence mechanisms in stem cells. Aim of the present study was to prove if the anti-senescence results previously obtained in different kind of stem cells with the REAC Tissue optimization – regenerative (TO-RGN) treatment, could also be observed in BMSCs, evaluating cell viability, telomerase activity, p19ARF, P21, P53, and hTERT gene expression. The results show that the REAC TORGN treatment may be a useful tool to counteract the BMSCs senescence which can be the basis of AML drift. Nevertheless, further clinical studies on humans are needed to confirm this hypothesis

The Margins' Challenge: Risk Factors of Residual Disease After Breast Conserving Surgery in Early-stage Breast Cancer

open19noBACKGROUND/AIM: Clinicopathological features of patients undergoing margin enlargement after lumpectomy for early breast cancer with positive/close excision margins were analyzed in order to define whether a re-operative procedure could have been avoided. Furthermore, a standardized protocol of specimen orientation was adopted in order to optimize both the widening procedure as well as the oncologic outcome. PATIENTS AND METHODS: A retrospective analysis was performed including pre-, peri-, and post-operative parameters, and a predictive score by means of a multivariate model was developed using all clinically and statistically significant variables associated with residual disease (RD). RESULTS: RD was significantly related to positive tumor margins, hormone receptor negative, HER2-positive, and tumors with high Ki67 proliferation index (p<0.001); the corresponding contribution to the prognostic score was as follows: close margins, 3 points; hormone receptor positive disease, 2 points; low Ki67, 2 points; HER2 negativity, 1 point. In 102 patients with a score >3, only 2 patients (2.0%) had RD, while in 81 patients with a score ≤3, 55 patients (67.9%) had RD (p<0.001). CONCLUSION: This predictive model might aid in clinical-decision making of patients with positive margins who actually require a widening procedure after intraoperative and/or definitive histology.openFregatti P.; Gipponi M.; Atzori G.; Rosa R.; Diaz R.; Cornacchia C.; Sparavigna M.; Garlaschi A.; Belgioia L.; Fozza A.; Pitto F.; Boni L.; Blondeaux E.; Depaoli F.; Murelli F.; Franchelli S.; Zoppoli G.; Lambertini M.; Friedman D.Fregatti, P.; Gipponi, M.; Atzori, G.; Rosa, R.; Diaz, R.; Cornacchia, C.; Sparavigna, M.; Garlaschi, A.; Belgioia, L.; Fozza, A.; Pitto, F.; Boni, L.; Blondeaux, E.; Depaoli, F.; Murelli, F.; Franchelli, S.; Zoppoli, G.; Lambertini, M.; Friedman, D

Efficacy of adjuvant chemotherapy schedules for breast cancer according to body mass index: results from the phase III GIM2 trial

Background: The phase III GIM2 trial showed improved disease-free survival (DFS) and overall survival (OS) with adjuvant dose-dense (DD) as compared with standard-interval (SI) chemotherapy in women with node-positive early-stage breast cancer (BC). This exploratory analysis aimed to investigate the benefit of different schedules according to body mass index (BMI) in this trial. Patients and methods: This analysis explored the efficacy, in terms of DFS and OS, of different chemotherapy schedules according to BMI. Univariate and multivariable Cox proportional hazard models, adjusted for relevant prognostic factors, were used. Results: Out of 2091 patients enrolled, 1925 with known baseline BMI were randomized in the DD versus SI comparison and therefore included in this analysis: 31.6% were overweight and 19.3% obese. Overweight and obesity were significantly associated with postmenopausal status, pT >2, and pN >2 tumors. After a median follow-up of 15.0 years (interquartile range 8.4-16.3 years), multivariable Cox survival models demonstrated no association of different BMI categories on DFS [adjusted hazard ratio (adjHR) 0.96, 95% confidence interval (CI) 0.80-1.15 and adjHR 1.11, 95% CI 0.91-1.35 for overweight and obese patients, respectively, compared to patients with normal BMI] or OS (adjHR 0.90, 95% CI 0.71-1.14 and adjHR 1.18, 95% CI 0.92-1.52 for overweight and obese patients, respectively). No significant interaction was found between BMI and treatment schedule in terms of DFS (Pfor interaction = 0.56) or OS (Pfor interaction = 0.19). The survival benefit of DD chemotherapy was observed irrespective of different BMI categories, with a more pronounced benefit for overweight and obese patients. Conclusion: In node-positive BC patients, DD schedule should be considered the preferred schedule irrespective of BMI

Low low-density lipoprotein (LDL), cholesterol and triglycerides plasma levels are associated with reduced risk of arterial occlusive events in chronic myeloid leukemia patients treated with ponatinib in the real-life. A Campus CML study

36noopenopenCaocci G.; Mulas O.; Capodanno I.; Abruzzese E.; Iurlo A.; Luciano L.; Albano F.; Annunziata M.; Tiribelli M.; Bonifacio M.; Galimberti S.; Castagnetti F.; Sgherza N.; Stagno F.; Gozzini A.; Orlandi E.M.; Luzi D.; Binotto G.; Pregno P.; Fozza C.; Efficace F.; Simula M.P.; Trawinska M.M.; Cattaneo D.; De Gregorio F.; Attolico I.; Stella R.; Scaffidi L.; Barate C.; Gugliotta G.; Scalzulli E.; Elena C.; Pirillo F.; Foa R.; Breccia M.; Nasa G.L.Caocci, G.; Mulas, O.; Capodanno, I.; Abruzzese, E.; Iurlo, A.; Luciano, L.; Albano, F.; Annunziata, M.; Tiribelli, M.; Bonifacio, M.; Galimberti, S.; Castagnetti, F.; Sgherza, N.; Stagno, F.; Gozzini, A.; Orlandi, E. M.; Luzi, D.; Binotto, G.; Pregno, P.; Fozza, C.; Efficace, F.; Simula, M. P.; Trawinska, M. M.; Cattaneo, D.; De Gregorio, F.; Attolico, I.; Stella, R.; Scaffidi, L.; Barate, C.; Gugliotta, G.; Scalzulli, E.; Elena, C.; Pirillo, F.; Foa, R.; Breccia, M.; Nasa, G. L