An unusual T-cell childhood acute lymphoblastic leukemia harboring a yet unreported near-tetraploid karyotype

<p>Abstract</p> <p>Background</p> <p>Near-tetraploid (model #81-103) and near-triploid (model #67-81) karyotypes are found in around 1% of childhood acute lymphoblastic leukemia. Due to its rarity, these two cytogenetic subgroups are generally included in the hyperdiploid group (model # > 51). Therefore separate informations about these two subgroups are limited to a few reports. Some studies found that near-tetraploidy is relatively more frequent in higher median ages and it is associated to Frech-American-British Classification subtype L2. Although the mechanisms by which leukemic blast cells divide is still unclear, studies have suggested that hyperdiploidy, near-triploidy and near-tetraploidy do not seem to share the same mechanism.</p> <p>Findings</p> <p>Herewith, we present a new childhood T-acute lymphoblastic leukemia case of near-tetraploid karyotype with loss of two p53-gene copies, characterized in detail by cytogenetic and molecular studies.</p> <p>Conclusion</p> <p>We suggest that p53 is a good target gene to be screened, once p53 is one of the main effectors of cell cycle checkpoints.</p

Style modification in breast and Colorectal Cancer Patients: results of a pilot study Long-Survivors

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Out-patient high-dose-rate endobronchial brachytherapy for palliation of lung cancer: an observational study

Background and Aim. Out-patient high-dose-rate endobronchial brachytherapy (HDREB) is a possible option in the palliation of symptoms in patients with advanced lung cancer, but literature data is limited and the technique is still under development in Italy. Our aim was to evaluate safety and effectiveness of out-patient HDREB for palliation of malignant endobronchial tumours in the context of a multidisciplinary approach. Methods. Out-patient HDREB sessions were scheduled at weekly intervals (500-1000 cGy per session) with prior Diodi-laser resection in some cases. Response was assessed bronchoscopically, clinically and functionally at the end of treatment and one month after the last HDREB session. Inclusion criteria was: histological evidence of malignant tumour not susceptible to surgical treatment for extension or co-morbidity. Results. 150 outpatient HDREB sessions were carried out on consecutive 35 patients (mean age 69 yrs, M/F 29/6) with symptoms due to central airway obstruction. A shortterm endoscopic response was observed in 15/28 patients. After delivering 2000 cGy dyspnoea decreased significantly. After one month cough decreased and haemoptysis disappeared. Palliation was obtained in all patients except one during. Lung function tests did not significantly improve after HDREB. No fatal complication occurred. A temporary radiation bronchitis was observed in six patients. Conclusions. This non-comparative, prospective observational study showed a palliative response of HDREB in most of patients with advanced endoluminal lung cancer. The safety of the procedure was good and the rate of non-fatal serious complications was very low

Impact of gastro-oesophageal reflux on microRNA expression, location and function

We have shown that miRNA expression is altered in the oesophageal squamous mucosa from individuals with gastro-oesophageal reflux and ulcerative oesophagitis. These changes in miR-143, miR-145 and miR-205 expression appear to be most pronounced in the basal layer of the oesophageal epithelium. In the context of gastro-oesophageal reflux these expression changes might influence proliferation and apoptosis and thereby regulate epithelial restoration. It is reasonable to hypothesise that they could represent early molecular events preceding the development of Barrett’s oesophagus, although proving this will require further studies as described above. Future detailed analyses of the role of these miRNAs in progression from gastro-oesophageal reflux to Barrett’s oesophagus, and then to oesophageal adenocarcinoma will be valuable, and may help in efforts to control and treat these diseases.This study was funded by a Competing Project Grant from the National Health and Medical Research Council of Australia. Cameron Smith was supported by a PROBE-NET PhD scholarship funded by a Strategic research Partnerships Grant from the Cancer Council of New South Wales

The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients

Purposes: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results: PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions: This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT02326857).Fil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Abdelhay, Eliana Saul Furquim Werneck. Instituto Nacional de Cancer; BrasilFil: Artagaveytia, Nora. Universidad de la Republica; UruguayFil: Daneri Navarro, Adrián. Universidad de Guadalajara; MéxicoFil: Müller, Bettina. Instituto Nacional del Cáncer; ChileFil: Velazquez, Carlos. Universidad de Sonora; MéxicoFil: Alcoba, Elsa B.. Hospital Maria Curie; ArgentinaFil: Alonso, Isabel. Centro Hospitalario Pereira Rossell; UruguayFil: Alves Da Quinta, Daniela Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Argentina de la Empresa; ArgentinaFil: Binato, Renata. Instituto Nacional de Cancer; BrasilFil: Bravo, Alicia Inés. Hospital Regional de Agudos Eva Perón; ArgentinaFil: Camejo, Natalia. Universidad de la Republica; UruguayFil: Carraro, Dirce Maria. Centro Internacional de Pesquisa; BrasilFil: Castro, Mónica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Castro Cervantes, Juan M.. Umae Hospital de Especialidades Centro Medico Nacional Siglo XXI; MéxicoFil: Cataldi, Sandra. Instituto Nacional del Cáncer; UruguayFil: Cayota, Alfonso. Instituto Pasteur de Montevideo; UruguayFil: Cerda, Mauricio. Universidad de Chile; ChileFil: Colombo, Alicia. Universidad de Chile; ChileFil: Crocamo, Susanne. National Cancer Institute; Estados UnidosFil: Del Toro Arreola, Alicia. Universidad de Guadalajara; MéxicoFil: Delgadillo Cisterna, Raúl. Umae Hospital de Especialidades Centro Medico Nacional Siglo Xxi; MéxicoFil: Delgado, Lucía. Universidad de la Republica; UruguayFil: Fernandez, Elmer Andres. Area de Cs. Agrarias, Ingeniería, Cs. Biológicas y de la Salud de la Universidad Catollica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Fejerman, Laura. University of California at Davis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Trinchero, Alejandra. Hospital Regional de Agudos Eva Perón; ArgentinaFil: Valenzuela, Olivia. Universidad de Sonora; MéxicoFil: Vedham, Vidya. National Cancer Institute; Estados UnidosFil: Zagame, Livia. Instituto Jalisciense de Cancerología; MéxicoFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Parallel Grasp With Path-Relinking For Job Shop Scheduling

In the job shop scheduling problem (JSP), a finite set of jobs is processed on a finite set of machines. Each job is required to complete a set of operations in a fixed order. Each operation is processed on a specific machine for a fixed duration. A machine can process no more than one job at a time and once a job initiates processing on a given machine it must complete processing without interruption. A schedule is an assignment of operations to time slots on the machines. The objective of the JSP is to find a schedule that minimizes the maximum completion time, or makespan, of the jobs. In this paper, we describe a parallel greedy randomized adaptive search procedure (GRASP) with path-relinking for the JSP. A GRASP is a metaheuristic for combinatorial optimization. It usually consists of a construction procedure based on a greedy randomized algorithm and of a local search. Path-relinking is an intensification strategy that explores trajectories that connect high quality solutions. Independent and cooperative parallelization strategies are described and implemented. Computational experience on a large set of standard test problems indicates that the parallel GRASP with path-relinking finds goodquality approximate solutions of the job shop scheduling problem