RESUMO
The possible role of radical species in the formation of the long-lived triplet states observed for 2-thiocytosine upon UV irradiation was theoretically investigated. It is predicted that the radical fragments arising from the homolytic rupture of the NH group of the thiobase can be yielded upon ultraviolet-A radiation. Recombination of the radicals through the most favorable singlet channel yields the lowest-lying tautomer of the 2-thiocytosine (the amino-thiol form) through a barrierless pathway. The rebounding of the radical fragments along the triplet channels that emerge from the attack of the hydrogen to the nitrogen atoms next to the C-S bond leads to stable structures for the amino-thion-N1H and amino-thion-N3H tautomers. These results allow for the rationalization of the near-unity triplet yields observed when this pure light-atom organic molecule is exposed to UV irradiation, without invoking intersystem crossings between the electronic states of different spin-multiplicities. A similar study for cytosine showed that the energy required to induce the homolytic breaking of the N-H bond of the nucleobase is not attainable under UVA radiation. This result is consistent with the experimental fact that no triplet states are observed when this molecule is exposed to that light.
RESUMO
ABSTRACT Myelodysplastic syndrome with deletion of chromosome 5q (5q-syndrome) has a favorable prognosis and a low risk of transformation to acute myeloid leukemia, when treated with lenalidomide. Azacitidine leads to complete remission even as second-line therapy and in patients with clonal evolution. We report a 70 years old female without previous exposure to myelotoxic drugs, presenting with three weeks with fatigue and dyspnea. She had anemia with normal white blood cell and platelet count. Bone marrow biopsy showed 50% cellularity and the karyotype analysis revealed a (5) (q33q34) deletion in 22% of the metaphases. A diagnosis of 5q-syndrome with low risk calculated using the Revised International Prognostic Scoring System (IPSS-R), was made. Since lenalidomide was not affordable, thalidomide 100 mg/day was initiated, achieving transfusion independence for three years. Afterwards, she developed pancytopenia and a bone marrow biopsy showed erythroid and megakaryocyte dysplasia with a complex karyotype, which worsened prognosis (IPSS-R of five points). Therefore, azacitidine (by donation) was administered. She achieved complete remission with a normal karyotype and completed 12 cycles of treatment. Thereafter, she relapsed and received only supportive care for a year. She suffered an ischemic stroke and died two weeks later.
El síndrome mielodisplásico con deleción del cromosoma 5q (síndrome 5q) tiene un pronóstico favorable y riesgo bajo de transformación a leucemia aguda en pacientes que son tratados con lenalidomida (tratamiento estándar). El uso Azactidina tiene respuestas completas incluso como segunda línea de tratamiento en pacientes con evolución clonal. Presentamos una mujer de 71 años, sin exposición a mielotóxicos que debutó con un síndrome anémico. Se realizó biopsia de medula ósea que mostró celularidad del 50% y en el análisis citogenético se detectó una deleción del cromosoma 5 en 22% de las metafases analizadas, lo que llevó al diagnóstico de Síndrome 5q- de riesgo bajo de acuerdo con el puntaje IPSS-R (Revised International Prognostic Scoring System). Ya que no se pudo costear lenalidomida, se trató con talidomida (100 mg/día). Permaneció tres años sin requerir soporte transfusional. Posteriormente, presentó pancitopenia y en el nuevo aspirado de médula ósea se observó displasia de la serie roja y megacariocitos, con cariotipo complejo y peor pronóstico (IPSS-R 5 puntos). Se trató con 12 ciclos de azacitidina con lo que logró respuesta completa. Recayó 12 meses después y continuó manejo de soporte por un año. Finalmente falleció debido a un accidente vascular cerebral.
Assuntos
Idoso , Feminino , Humanos , Talidomida , Síndromes Mielodisplásicas , Deleção Cromossômica , Inibidores da Angiogênese , Anemia Macrocítica , Talidomida/uso terapêutico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Cromossomos Humanos Par 5/genética , Resultado do Tratamento , Inibidores da Angiogênese/uso terapêutico , Lenalidomida , Anemia Macrocítica/genética , Anemia Macrocítica/tratamento farmacológicoRESUMO
Myelodysplastic syndrome with deletion of chromosome 5q (5q-syndrome) has a favorable prognosis and a low risk of transformation to acute myeloid leukemia, when treated with lenalidomide. Azacitidine leads to complete remission even as second-line therapy and in patients with clonal evolution. We report a 70 years old female without previous exposure to myelotoxic drugs, presenting with three weeks with fatigue and dyspnea. She had anemia with normal white blood cell and platelet count. Bone marrow biopsy showed 50% cellularity and the karyotype analysis revealed a (5) (q33q34) deletion in 22% of the metaphases. A diagnosis of 5q-syndrome with low risk calculated using the Revised International Prognostic Scoring System (IPSS-R), was made. Since lenalidomide was not affordable, thalidomide 100 mg/day was initiated, achieving transfusion independence for three years. Afterwards, she developed pancytopenia and a bone marrow biopsy showed erythroid and megakaryocyte dysplasia with a complex karyotype, which worsened prognosis (IPSS-R of five points). Therefore, azacitidine (by donation) was administered. She achieved complete remission with a normal karyotype and completed 12 cycles of treatment. Thereafter, she relapsed and received only supportive care for a year. She suffered an ischemic stroke and died two weeks later.
Assuntos
Anemia Macrocítica , Inibidores da Angiogênese , Deleção Cromossômica , Síndromes Mielodisplásicas , Talidomida , Idoso , Anemia Macrocítica/tratamento farmacológico , Anemia Macrocítica/genética , Inibidores da Angiogênese/uso terapêutico , Cromossomos Humanos Par 5/genética , Feminino , Humanos , Lenalidomida , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Talidomida/uso terapêutico , Resultado do TratamentoRESUMO
Energy profiles for the lowest lying triplet and singlet electronic pathways that link the reactants Zr + CH3CH3 with the products observed under matrix-isolation conditions were obtained from DFT and CASSCF-MRMP2 calculations. The insertion of the metal into the C-H bond of the organic molecule to yield the oxidative addition product is not favorable for any of the investigated channels. However, the inserted structure H-Zr-CH2CH3 can be obtained from two sequential reactions involving the radical species ZrH and CH2CH3. According to this scheme, a first reaction produces the radical fragments from the ground state of the reactants. Then, the radicals can recombine themselves in a second reaction to form the inserted species H-Zr-CH2CH3. As the triplet and singlet radical asymptotes ZrH + CH2CH3 that vary only in spin of the non-metallic fragment are degenerate, the rebounding of the radicals can occur through both multiplicity channels. It is shown that the low spin channel leads to the most stable structures of the dihydride ZrH2-(CH2)2 and the vinyl metal trihydride complexes ZrH3-CH=CH2 experimentally determined for this reaction under matrix-isolation conditions. The description attained for this interaction does not invoke interactions between the triplet and singlet electronic states emerging from the reactants, as proposed by other authors.
RESUMO
BACKGROUND: Prognostic factors in oral cavity and oropharyngeal squamous cell carcinoma (SCC) are debated. The purpose of this study was to investigate the association of prognostic factors with oncologic outcomes. METHODS: Patients with oral cavity and oropharyngeal SCC treated from 1997 to 2012 were included in this retrospective cohort study. Associations of prognostic factors with locoregional recurrence (LRR) or overall survival (OS) were analyzed using the logistic regression and the Cox models. RESULTS: Six hundred thirty-four patients were included in this study; tumor size, surgical margins, and N classification were associated with LRR (p < .0001); considering histopathology: perineural invasion, lymphocytic infiltration, infiltrative borders, and N classification were significant determinants of LRR. Tumor size, N classification, alcoholism, and surgical margins were associated with OS (p < .0001); considering pathologic prognostic factors, perivascular invasion, islands borders, and surgical margins were independently associated with OS (p < .0001). CONCLUSION: Surgical margins, perineural and perivascular invasion, lymphocytic infiltration, and infiltrative patterns of tumor invasion are significant prognostic factors in oral cavity and oropharyngeal SCC.
Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Boca/patologia , Neoplasias Orofaríngeas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Estudos de Coortes , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Recidiva Local de Neoplasia/patologia , Neoplasias Orofaríngeas/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Adulto JovemRESUMO
OBJETIVE: In patients with non-small cell lung cancer (NSCLC), knowledge of the epidermal growth factor receptor (EGFR) mutation status is fundamental for selecting the treatment involving EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Little information is available regarding the response and progression-free survival (PFS) in platinum-based chemotherapy (CT) versus EGFR-TKIs in the presence or absence of KRAS mutation, particularly in patients without EGFR mutation. METHODS: From 2007 to 2010, 353 patients with NSCLC were treated with first-line CT, EGFR-TKIs were used in the second or third line of treatment. Tests were performed for EGFR and KRAS mutation and the results of the mutations were obtained 3 to 4 months after the start of the treatment. We analyzed clinical characteristics, mutation profile, response and PFS to CT and EGFR-TKIs, and overall survival. The protocol is registered with ClinicalTrials.gov, number NCT01023828. RESULTS: Presence of the wild-type (WT) KRAS was independently associated with increased response rate to first-line CT when compared with KRAS mutation (41.4% vs. 14.7%; P=0.001). The EGFR mutation (57.8% vs. 11.7%; P<0.001) and WT-KRAS (39.6% vs. 3.3%; P=0.001) were associated with the EGFR-TKIs response. PFS of patients with WT-EGFR and KRAS mutation treated with EGFR-TKIs was shorter when compared with patients with WT-EGFR and WT-KRAS (P<0.001). CONCLUSIONS: KRAS mutation status is a good biomarker for response to EGFR-TKIs in patients with NSCLC. KRAS mutational status could impact the decision to give CT or EGFR-TKIs as a second line of treatment to patients with NSCLC, particularly in patients with WT-EGFR.