New somatic TERT promoter variants enhance the Telomerase activity in Glioblastoma

The catalytic activity of human Telomerase Reverse Transcriptase (TERT) compensates for the loss of telomere length, eroded during each cell cycle, to ensure a correct division of stem and germinal cells. In human tumors, ectopic TERT reactivation, most frequently due to hotspot mutations in the promoter region (TERTp), i.e. c.1-124 C > T, c.1-146 C > T, confers a proliferative advantage to neoplastic cells. In gliomas, TERTp mutations (TERTpmut) mainly occur in oligodendroglioma and glioblastoma. We screened, for TERTp hotspot mutations, 301 adult patients with gliomas and identified heterozygous mutations in 239 cases: 94% of oligodendroglioma, 85% of glioblastoma, and 37.5% of diffuse/anaplastic astrocytoma. Besides the recurrent c.1-124 C > T and c.1-146 C > T, two cases of glioblastoma harbored novel somatic TERTp variants, which consisted of a tandem duplications of 22 nucleotides, i.e. a TERTp c.1-100_1-79dup and TERTp c.1-110_1-89, both located downstream c.1-124 C > T and c.1-146 C > T. In silico analysis predicted the formation of 119 and 108 new transcription factor's recognition sites for TERTp c.1-100_1-79dup and TERTp c.1-110_1-89, respectively. TERTp duplications (TERTpdup) mainly affected the binding capacity of two transcription factors' families, i.e. the members of the E-twenty-six and the Specificity Protein/Krüppel-Like Factor groups. In fact, these new TERTpdup significantly enhanced the E-twenty-six transcription factors' binding capacity, which is also typically increased by the two c.1-124 C > T/c.1-146 C > T hotspot TERTpmut. On the other hand, they were distinguished by enhanced affinity for the Krüppel proteins. The luciferase assay confirmed that TERTpdup behaved as gain-of-function mutations causing a 2,3-2,5 fold increase of TERT transcription. The present study provides new insights into TERTp mutational spectrum occurring in central nervous system tumors, with the identification of new recurrent somatic gain-of-function mutations, occurring in 0.8% of glioblastoma IDH-wildtype

Quantum information processes in protein microtubules of brain neurons

We study biologically ‘orchestrated’ coherent quantum processes in collections of protein microtubules of brain neurons, which correlate with, and regulate, neuronal synaptic and membrane activity. In this situation the continuous Schrodinger evolution of each such process terminates in accordance with the specific Diosi-Penrose (DP) scheme of ‘objective reduction’ (‘OR’) of the quantum state. This orchestrated OR activity (‘Orch OR’) is taken to result in moments of conscious awareness and/or choice. We analyze Orch OR in light of advances and developments in quantum physics, computational neuroscience and quantum biology. Much attention is also devoted to the ‘beat frequencies’ of faster microtubule vibrations as a possible source of the observed electroencephalographic (‘EEG’) correlates of consciousness

Linkage of AIDS and Cancer Registries in Italy.

Linkage of AIDS and Cancer Registrie

Birth place and classic Kaposi\u2019s Sarcoma in Italy

Birth place and classic Kaposi\u2019s Sarcom

Results from an historical survey of cancer patients treated with L. Di Bella therapy.

Abstract BACKGROUND: The Italian media have given wide coverage to a number of successes in treating cancer patients with an alternative therapy developed by Dr. Luigi Di Bella, a physician in Modena, Italy. In 1998, the Ministry of Health, under considerable pressure from the public, decided to promote studies to evaluate its efficacy. METHODS: Follow-up was conducted for cancer patients previously treated during the years 1971-1997 by Dr. Di Bella and registered in his archive. Identified cases were searched in cancer registries for diagnostic confirmation, date of diagnosis, and follow-up. Survival was compared with that in individually matched cancer cases derived from a pool of Italian cancer registries (the ITACARE data base). Kaplan-Meier survival curves were produced for all adult cancer patients as well as for children with leukemia and, in the matched analysis, for patients with cancer at the major anatomic sites and for all cancer patients combined. The homogeneity of survival curves between the two groups was tested by means of the log rank test. RESULTS: After several exclusions, 314 patients were entered into the study. Follow-up was completed for 79%. Only four patients received Di Bella Multitherapy (MDB) as their only anticancer therapy. Of these, only 1 is still alive 2 years after diagnosis. Five-year survival rates for children with leukemia and adult cancer patients were both 29.4%. Five-year survival was significantly lower in comparison with ITACARE cases for patients with childhood leukemia, breast carcinoma, and adult leukemia, and for all cancer patients combined. Twenty-seven MDB patients survived 10 years or longer after diagnosis. In only three cases was this long survival unexpected. CONCLUSIONS: The results for this series did not give any evidence that MDB improved the survival of the cancer patients

Promote equal access to COVID19 vaccination: strategies of the Local Authority Toscana SudEst, Italy

The creation of dedicated interventions guaranteed to achieve high vaccination coverage in all nationalitie