The evolution of hematopoietic cells under cancer therapy

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Asociación Española Contra el Cáncer (AECC) (GC16173697BIGA); Severo Ochoa Centre of Excellence Award from the Spanish Ministry of Economy and Competitiveness (MINECO; Government of Spain); CERCA (Generalitat de Catalunya); Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia; Barcelona Institute of Science and Technology (BIST); Hartwig Medical Foundation; Center for Personalized Cancer Treatment (CPCT).Chemotherapies may increase mutagenesis of healthy cells and change the selective pressures in tissues, thus influencing their evolution. However, their contributions to the mutation burden and clonal expansions of healthy somatic tissues are not clear. Here, exploiting the mutational footprint of some chemotherapies, we explore their influence on the evolution of hematopoietic cells. Cells of Acute Myeloid Leukemia (AML) secondary to treatment with platinum-based drugs show the mutational footprint of these drugs, indicating that non-malignant blood cells receive chemotherapy mutations. No trace of the 5-fluorouracil (5FU) mutational signature is found in AMLs secondary to exposure to 5FU, suggesting that cells establishing the leukemia could be quiescent during treatment. Using the platinum-based mutational signature as a barcode, we determine that the clonal expansion originating the secondary AMLs begins after the start of the cytotoxic treatment. Its absence in clonal hematopoiesis cases is consistent with the start of the clonal expansion predating the exposure to platinum-based drugs

Role of early extraction of odontogenic focus in deep neck infections

Odontogenic deep neck infections remain a common condition that presents a challenging issue due to the complex involvement of the neck and adjacent structures and its potential life-threatening risk. Periapical infection of the second or third molar with spread to the submandibular and parapharyngeal spaces is the most commonly observed scenario. However, the time of dental extraction of the infection focus remains controversial. The aim of this study is to provide an overview of the epidemiology, clinical and radiological features, and management in patients diagnosed with ODNI and to identify the role of early dental extraction on patient outcomes and recovery. This retrospective study included patients over 18 years old with a diagnosis of ODNI who were admitted to the University Hospital ?Dr Jose Eleuterio Gonzalez? from January 2017 to January 2022. ODNI diagnosis was based on clinical and radiological evidence of the disease supplemented by dental and maxillofacial evaluation for an odontogenic aetiology. A total of 68 patients were included in the study. The patients? mean age was 40.96 ± 14.9. Diabetes mellitus was the most common comorbidity. The submandibular space was the most common deep neck space involved (n=59, 86.8%). Mediastinitis, marginal nerve injury and orocervical fistula were observed in 7.5% of patients, with no fatality in this series. A delay of >3 days for dental extraction of the involved tooth was associated with an increased rate of mediastinitis (n=3, 100%, p= 0.022), number of surgical interventions (1.45 ± 0.61, p= 0.006), ICU stay (n=8, 40%, p= 0.019), and ICU length of stay (0.85 ± 0.8, p= 0.001). Expedited management with surgical drainage and intravenous antibiotic treatment, along with early extraction of the involved tooth, is mandatory

The neural histogenetic origin of the oral granular cell tumor : an immunohistochemical evidence

Aims: Granular cell tumor (GCT) is a rare neoplasm that can appear in any site of the body, but most are located intraorally. Its histogenetic origin remains unclear. This report analyzes the immunoprofile of 15 cases of granular cell tumors, occurring in 13 women and 2 men and the lesions were located on the tongue or upper lip. Patient age ranged from 7 to 52. Methods: The patients demographic data and the cytological and architectural features of the lesions were analyzed in oral GCTs (n = 15). The lesions were also submitted to a panel of immunohistochemical stains with antibodies against S-100, p75, NSE, CD-68, Ki-67, Synaptofisin, HHF-35, SMA, EMA, Chromogranin, Progesterone, Androgen and Estrogen. Results: Among the fifteen cases analyzed, the most common location was the tongue (84.6%). Histologically, the tumors exhibited cellular proliferation composed mainly by polygonal cells presenting an abundant granular eosinophilic cytoplasm. The nuclei were central, and the cell membranes were moderately clear. No mitotic figures were observed. The immunohistochemical analysis showed positivity in all cases for S-100, p75, NSE and CD-68, and no immunoreactivity for Ki-67, Synaptofisin, HHF-35, SMA, EMA, Chromogranin, Progesterone, Androgen and Estrogen. Conclusion: The immunoprofile of granular cell tumors showed nerve sheath differentiation ? lending support to their neural origin ? and helping to establish a differential diagnosis between this lesion and other oral granular cell tumors, whether benign or malignant

Novel mutations in the PITX2 gene in Pakistani and Mexican families with Axenfeld-Rieger syndrome

Purpose Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant disorder that affects the anterior segment of the eye. The aim of this study was to examine the PITX2 gene to identify possible novel mutations in Pakistani and Mexican families affected by the ARS phenotype. Methods Three unrelated probands with a diagnosis of ARS were recruited for this study. Genomic DNA was isolated from the peripheral blood of the probands and their family members. Polymerase chain reaction and Sanger sequencing were used for the analysis of coding exons and the flanking intronic regions of the PITX2 gene. Bioinformatics tools and database (VarSome, Provean, and MutationTaster, SIFT, PolyPhen-2, and HOPE) were evaluated to explore missense variants. Results We identified novel heterozygous variations in the PITX2 gene that segregated with the ARS phenotype within the families. The variant NM_153426.2(PITX2):c.226G > T or p.(Ala76Ser) and the mutation NM_153426.2(PITX2):c.455G > A or p.(Cys152Tyr) were identified in two Pakistani pedigrees, and the mutation NM_153426.2(PITX2):c.242_265del or p.(Lys81_Gln88del), segregated in a Mexican family. Conclusion Our study extends the spectrum of PITX2 mutations in individuals with ARS, enabling an improved diagnosis of this rare but serious syndrome

Advances in the study of coke formation over zeolite catalysts in the methanol-to-hydrocarbon process

Methanol-to-hydrocarbon (MTH) process over acidic zeolite catalysts has been widely utilised to yield many types of hydrocarbons, some of which are eventually converted into the highly dehydrogenated (graphitized) carbonaceous species (cokes). The coking process can be divided into two parallel pathways based on the accepted hydrocarbon pool theory. From extensive investigations, it is reasonable to conclude that inner zeollite cavity/channel reactions at acidic sites generate cokes. However, coke formation and accumulation over the zeolite external surfaces play a major role in reaction deactivation as they contribute a great portion to the total coke amount. Herein we have reviewed previous literatures and included some recent works from KOPRC in understanding the nature and mechanism of coke formation, particularly during an H-ZSM-5 catalysed MTH reaction. We specially conclude that rapid aromatics formation at the zeolite crystalite edges is the main reason for later stage coke accumulation on the zeolite external surfaces. Accordingly, the catalyst deactivation is in a great certain to arise at those edge areas due to having the earliest contact with the incoming methanol reactant. The final coke structure is therefore built up with layers of poly-aromatics, as the potential sp2 carbons leading to pre-graphite structure. We have proposed a coke formation model particularly for the acidic catalyst, which we believe will be of assistance in understanding—and hence minimising—the coke formation mechanisms