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1.
Tumour Biol ; 42(7): 1010428320938494, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32628088

RESUMO

Radiotherapy and cisplatin lead to cell killing in head and neck squamous cell carcinoma patients, but adverse events and response to treatment are not the same in patients with similar clinicopathological aspects. The aim of this prospective study was to evaluate the roles of TP53 c.215G > C, FAS c.-671A > G, FAS c.-1378G > A, FASL c.-844 C > T, CASP3 c.-1191A > G, and CASP3 c.-182-247G > T single nucleotide variants in toxicity, response rate, and survival of cisplatin chemoradiation-treated head and neck squamous cell carcinoma patients. Genomic DNA was analyzed by polymerase chain reaction for genotyping. Differences between groups of patients were analyzed by chi-square test or Fisher's exact test, multiple logistic regression analysis, and Cox hazards model. One hundred nine patients with head and neck squamous cell carcinoma were enrolled in study. All patients were smokers and/or alcoholics. Patients with FAS c.-671GG genotype, FAS c.-671AG or GG genotype, and FASL c.-844CC genotype had 5.52 (95% confidence interval (CI): 1.42-21.43), 4.03 (95% CI: 1.51-10.79), and 5.77 (95% CI: 1.23-27.04) more chances of presenting chemoradiation-related anemia of grades 2-4, lymphopenia of grade 3 or 4, and ototoxicity of all grades, respectively, than those with the remaining genotypes. FAS c.-671GG genotype was also seen as an independent predictor of shorter event-free survival (hazard ratio (HR): 2.05; P = 0.007) and overall survival (HR: 1.83; P = 0.02) in our head and neck squamous cell carcinoma patients. These findings present, for the first time, preliminary evidence that inherited abnormalities in apoptosis pathway, related to FAS c.-671A > G and FASL c.-844 C > T single nucleotide variants, can alter toxicity and survival of tobacco- and alcohol-related head and neck squamous cell carcinoma patients homogeneously treated with cisplatin chemoradiation.

2.
Mol Biol Rep ; 46(6): 6557-6563, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31587185

RESUMO

The objective of this research was to assess the association of genetic polymorphisms related to intrinsic apoptosis pathway CASP8 rs3834129 and CASP3 rs4647601 with the risk, clinical and pathological aspects, and survival of oropharynx squamous cell carcinoma (OPSCC) patients that received cisplatin and radiotherapy. The genotypes were identified in 198 patients with OPSCC and 200 controls using polymerase chain reaction methods. Chi square or Fisher's exact test and logistic regression were applied for the detection of differences between groups. Patients' genotypes were statistically evaluated considering the event-free survival and overall analysis using Kaplan-Meier estimate and Cox regression. CASP3 rs4647601 GG genotype (44.4% vs. 30.0%, p = 0.03) and G allele (63.9% vs. 55.5%, p = 0.04) were more common in patients with OPSCC than in controls. Carriers of GG genotype and G allele were under 1.78-fold and 1.40-fold increased risk of OPSCC than others, respectively. The frequency of CASP8 rs3834129 DD genotype was higher in patients with OPSCC with poorly differentiated or undifferentiated tumors when compared to others (34.5% vs. 16.1%, p = 0.02). No influence of CASP8 and CASP3 polymorphisms on OPSCC patients' survival was seen in this study. Our results indicate that inherited genetic variants in the intrinsic apoptosis pathway related to CASP3 rs4647601 and CASP8 rs3834129 polymorphisms may be an important determinant of OPSCC risk and tumor cell differentiation.


Assuntos
Carcinoma de Células Escamosas/genética , Caspase 3/genética , Caspase 8/genética , Neoplasias Orofaríngeas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Carcinoma de Células Escamosas/mortalidade , Estudos de Casos e Controles , Diferenciação Celular , Progressão da Doença , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/mortalidade , Prognóstico , Análise de Sobrevida
3.
Tumour Biol ; 41(9): 1010428319872092, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31486713

RESUMO

Angiogenesis, induced by the vascular endothelial growth factor A through its ligation to the vascular endothelial growth receptor 2, has been described as a crucial point in high-grade glioma development. The aim of this study was to evaluate the influence of VEGFA-2578C/A, -2489C/T, -1154G/A, -634G/C, and -460C/T, and KDR-604T/C, -271G/A, +1192G/A, and +1719A/T single-nucleotide polymorphisms on risk and clinicopathological aspects of high-grade glioma. This case-control study enrolled 205 high-grade glioma patients and 205 controls. Individuals with VEGFA-2578 CC or CA, VEGFA-1154 GG, VEGFA-634 GC or CC, and VEGFA-460 CT or TT genotypes were under 2.56, 1.53, 1.54, and 1.84 increased risks of high-grade glioma, compared to others, respectively. And 1.61, 2.66, 2.52, 2.53, and 2.02 increased risks of high-grade glioma were seen in individuals with VEGFA-2578 CC plus VEGFA-1154 GG, VEGFA-2578 CC or CA plus VEGFA-634 GC or CC, VEGFA-2578 CC or CA plus VEGFA-460 CT or TT, VEGFA-1154 GG or GA plus VEGFA-634 GC or CC, and VEGFA 634 GC or CC plus VEGFA-460 CT or TT combined genotypes, respectively, when compared to others. The "CAGT" haplotype of KDR single-nucleotide polymorphisms was more common in patients with grade IV than in those with grade III tumors, and individuals carrying this haplotype were at 1.76 increased risk of developing grade IV tumors than others. We present, for the first time, preliminary evidence that VEGFA-2578C/A and VEGFA-1154G/A single-nucleotide polymorphisms increases high-grade glioma risk, and "CAGT" haplotype of the KDR gene alters high-grade glioma aggressiveness and risk of grade IV tumors in Brazil.


Assuntos
Glioma/genética , Haplótipos , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Fatores de Risco , Adulto Jovem
5.
PLoS One ; 14(3): e0213929, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30870506

RESUMO

BACKGROUND: Chemotherapy-induced nausea and vomiting are concerning adverse events resulting from cancer treatment, and current guidelines recommend the use of neurokinin-1-selective antagonists, such as fosaprepitant, in highly emetogenic schemes. However, the implementation of this strategy may be limited by the cost of treatment. GSTP1 c.313A>G genotype was recently described as a predictor of vomiting related to high-dose cisplatin. We hypothesized that the inclusion of routine GSTP1 c.313A>G screening may be promising in financial terms, in contrast to the wide-spread use of fosaprepitant. METHODS: A cost-minimization analysis was planned to compare GSTP1 c.313A>G genotyping versus overall fosaprepitant implementation for patients with head and neck cancer under chemoradiation therapy with high-dose cisplatin. A decision analytic tree was designed, and conditional probabilities were calculated under Markov chain Monte Carlo simulations using the Metropolis-Hastings algorithm. The observed data included patients under treatment without fosaprepitant, while priors were derived from published studies. RESULTS: To introduce screening with real-time polymerase chain reaction, an initial investment of U$ 39,379.97 would be required, with an amortization cost of U$ 7,272.97 per year. The mean cost of standard therapy with fosaprepitant is U$ 243.24 per patient, and although the initial cost of routine genotyping is higher, there is a tendency of progressive minimization at a threshold of 155 patients (Credible interval-CI: 119 to 216), provided more than one sample is incorporated for simultaneous analysis. A resulting reduction of 35.83% (CI: 30.31 to 41.74%) in fosaprepitant expenditures is then expected with the implementation of GSTP1 c.313A>G genotyping. CONCLUSION: GSTP1 c.313A>G genotyping may reduce the use of preventive support for chemotherapy induced nausea and lower the overall cost of treatment. Despite the results of this simulation, randomized, interventional studies are required to control for known and unknown confounders as well as unexpected expenses.


Assuntos
Cisplatino/efeitos adversos , Glutationa S-Transferase pi/genética , Náusea/induzido quimicamente , Náusea/prevenção & controle , Vômito/induzido quimicamente , Vômito/prevenção & controle , Algoritmos , Antieméticos/economia , Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Teorema de Bayes , Quimiorradioterapia/efeitos adversos , Simulação por Computador , Custos e Análise de Custo , Árvores de Decisões , Custos de Medicamentos , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Cadeias de Markov , Método de Monte Carlo , Morfolinas/economia , Morfolinas/uso terapêutico , Náusea/genética , Antagonistas do Receptor de Neuroquinina-1/economia , Antagonistas do Receptor de Neuroquinina-1/uso terapêutico , Testes Farmacogenômicos/economia , Reação em Cadeia da Polimerase em Tempo Real/economia , Vômito/genética
6.
Head Neck ; 41(8): 2665-2670, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30903678

RESUMO

BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes that act in intrinsic apoptosis pathway may modulate cancer susceptibility. This study investigated the roles of CASP9 c.-1339A>G (rs4645978) and CASP3 c.-1191A>G (rs12108497) SNPs on risk and behavior of head and neck (HN) squamous cell carcinoma (SCC). METHODS: DNA of 350 patients with HNSCC and 350 controls was analyzed by polymerase chain reaction method for genotyping. RESULTS: CASP3 c.-1191AG or GG genotype was more common in patients with HNSCC and oral cavity or oropharynx SCC than in controls; carriers of this genotype were under 2.15 and 2.81-fold increased risks of the respective tumors. CASP9 c.-1339AG or GG plus CASP3 c.-1191AG or GG genotypes were associated with oral cavity or oropharynx SCC early onset. CONCLUSION: These findings present, for the first time, preliminary evidence that inherited abnormalities related to CASP9 c.-1339A>G and CASP3 c.-1191A>G SNPs are determinants of HNSCC risk and clinical aspects.

7.
Rev Assoc Med Bras (1992) ; 65(2): 136-140, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30892435

RESUMO

We describe the case of a female patient, 52 years old, with dizziness and left motor incoordination for 2 weeks. Brain MRI magnetic resonance imaging) revealed a hyperintense lesion on T2-weighted images, without restricted diffusion, in the left middle cerebellar peduncle. Spectroscopy demonstrated peak of lipids and perfusion did not show any elevation in relative cerebral blood volume (rCBV). The patient underwent an open biopsy and resection, and the diagnosis of diffuse large B-cell lymphoma (DLBCL) was established. The patient received intravenous dexamethasone with symptoms remission, followed by four cycles of methotrexate plus cytarabine. After 3 months, the patient returned with decreased consciences level and a new MRI revealed a right superior frontal gyrus lesion with features suggesting a lymphomatous lesion. The patient died five days after her relapse.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Evolução Fatal , Feminino , Humanos , Imunocompetência , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia
8.
Exp Dermatol ; 28(5): 631-635, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30883948

RESUMO

We aimed to evaluate whether variants in repair (XPD Asp312Asn, XPD Lys751Gln) and detoxification (GSTM1, GSTT1) genes alter risk, clinicopathological aspects and survival of cutaneous melanoma (CM). Genotyping was performed in 229 CM patients and 258 controls. Individuals with XPD 312Asp/Asn or Asn/Asn plus GSTT1 null genotype were under 2.00 (95% CI: 1.06-3.79), and XPD 312Asn/Gln haplotype was under 1.44-fold (95% CI: 0.99-2.08) increased risks to CM than others. Individuals with GSTM1 plus GSTT1 null genotype had 9.61-fold (95% CI: 2.28-40.38) increased risk of metastatic CM. At 60 months of follow-up, patients with XPD 751Gln/Gln plus GSTT1 null and GSTM1 null plus GSTT1 null genotype presented 7.36 and 3.05 more chances of evolving to death in multivariate Cox analysis, respectively. In conclusion, our data indicate, for the first time, that specific variant combinations of XPD, GSTM1 and GSTT1 may increase susceptibility to CM and influence patients' clinicopathological features and survival.

9.
Rev. Assoc. Med. Bras. (1992) ; 65(2): 136-140, Feb. 2019. graf
Artigo em Inglês | LILACS-Express | ID: biblio-990325

RESUMO

SUMMARY We describe the case of a female patient, 52 years old, with dizziness and left motor incoordination for 2 weeks. Brain MRI magnetic resonance imaging) revealed a hyperintense lesion on T2-weighted images, without restricted diffusion, in the left middle cerebellar peduncle. Spectroscopy demonstrated peak of lipids and perfusion did not show any elevation in relative cerebral blood volume (rCBV). The patient underwent an open biopsy and resection, and the diagnosis of diffuse large B-cell lymphoma (DLBCL) was established. The patient received intravenous dexamethasone with symptoms remission, followed by four cycles of methotrexate plus cytarabine. After 3 months, the patient returned with decreased consciences level and a new MRI revealed a right superior frontal gyrus lesion with features suggesting a lymphomatous lesion. The patient died five days after her relapse.


RESUMO Descrevemos o caso de uma paciente do sexo feminino, de 52 anos, apresentando história de tontura e perda da coordenação motora do lado esquerdo há duas semanas. A RM (ressonância magnética) de crânio revelou uma lesão hiperintensa nas imagens ponderadas em T2, sem restrição à difusão, localizada no pedúnculo cerebelar médio esquerdo. A espectroscopia demonstrou pico de lipídeos, sem elevação do volume sanguíneo cerebral relativo (rCBV) à perfusão. A paciente foi submetida à biópsia a céu aberto, estabelecendo o diagnóstico de linfoma difuso de grandes células B (DLBCL). Houve remissão dos sintomas após o início do tratamento com dexametasona endovenosa, seguida de quatro ciclos de metotrexato associado à citarabina. Após três meses, a paciente retornou apresentando rebaixamento do nível de consciência, e a RM de crânio revelou uma nova lesão de origem linfomatosa no giro frontal superior direito. A paciente faleceu após cinco dias.

10.
BMJ Open ; 8(10): e019505, 2018 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-30341109

RESUMO

INTRODUCTION: Oral mucositis is an iatrogenic condition of erythematous inflammatory changes which tends to occur on buccal and labial surfaces, the ventral surface of the tongue, the floor of the mouth and the soft palate of patients receiving chemotherapy. This protocol of ongoing randomised parallel group clinical trial aims to access the therapeutic effect of an herbal gel containing 2.5% Arrabidaea chica Verlot standardised extract on oral mucositis in patients with head and neck cancer compared with low-level laser therapy. METHODS AND ANALYSIS: Patients with head and neck cancer held at Clinics Hospital of University of Campinas, Sao Paulo, who develop early signs/symptoms of oral mucositis are eligible. Baseline characteristics of participants include oral mucositis grade and quality of life assessments. Enrolment started in November 2017 with allocation of patients to one of the study groups by means of randomisation. Patients will be treated either with Arrabidaea chica or laser until wound healing. Monitoring includes daily assessment of mucositis grade and diameter measurement by photographs and millimetre periodontal probe. Treatments will be concluded once mucositis is healed. A blinded assessor will evaluate mucositis cure after referred by the study team. At this point, the gel tube will be weighed to indirectly assess patient's compliance. At close-out, data will be analysed by a blinded researcher following the procedures described in the statistical analyses. ETHICS AND DISSEMINATION: This clinical trial was approved by the ethics committee of research in humans at the Faculty of Medical Sciences of University of Campinas (report no. 1,613,563/2016). Results from this trial will be communicated in peer-reviewed publications and scientific presentations. TRIAL REGISTRATION NUMBER: RBR-5×4397.


Assuntos
Protocolos Antineoplásicos/normas , Bignoniaceae , Terapia com Luz de Baixa Intensidade/métodos , Extratos Vegetais/uso terapêutico , Estomatite/tratamento farmacológico , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Am J Case Rep ; 19: 1168-1174, 2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30275439

RESUMO

BACKGROUND The clivus is a depression in the anterior occipital bone of the skull base, posterior to the dorsum sellae, at the junction with the sphenoid bone. Chordoma is a rare tumor arising from embryonic remnants of the notochord and can be locally aggressive with a tendency to recur. The optimal management of this rare tumor remains controversial. A report of a case of recurrent chordoma of the clivus is presented to illustrate the value of volumetric three-dimensional (3-D) reconstruction with computed tomography (CT) and magnetic resonance imaging (MRI) to determine optimal surgical management. CASE REPORT A 53-year-old man presented with pain in the right orbital cavity, right proptosis, swelling of the right cheek, and bilateral loss of vision. He also had adrenal insufficiency. CT and contrast-enhanced (gadolinium) T1-weighted MRI with multiplanar acquisition were performed with volumetric 3-D reconstruction of the tumor, to increase the chances of treatment success. Surgical resection was performed to remove the tumor and reduce the risk of recurrence. Histology of the tumor was consistent with chordoma, supported by positive immunohistochemical staining for S-100 and epithelial membrane antigen (EMA). CONCLUSIONS This report highlighted the value of 3-D volume imaging in the diagnosis and treatment planning in a rare case of recurrent chordoma of the clivus. Analysis of tumor volume may be an indicator of the efficacy of surgery, complementing the Response Evaluation Criteria In Solid Tumors (RECIST) system and as a valuable tool to predict treatment outcome.


Assuntos
Cordoma/diagnóstico por imagem , Fossa Craniana Posterior/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias da Base do Crânio/diagnóstico por imagem , Cordoma/cirurgia , Fossa Craniana Posterior/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Imageamento Tridimensional , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Base do Crânio/cirurgia , Tomografia Computadorizada por Raios X
12.
Appl Clin Genet ; 11: 89-92, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30127633

RESUMO

Xeroderma pigmentosum is a rare autosomal recessive genetic disease characterized by extreme sensitivity due to solar radiation and deficiency in excision repair DNA. Those factors promote a set of skin abnormalities such as keratosis, hyperpigmentation, tumors in areas exposed to sunlight, and ocular and, eventually, neurological disorders. In the present review, we summarize the main clinical features related to a case of xeroderma pigmentosum in a man who was not diagnosed until he was 45 years old.

13.
Oncotarget ; 9(51): 29538-29547, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-30038702

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is treated with cisplatin (CDDP) and radiotherapy (RT), and distinct results are observed among patients with similar clinicopathological aspects. This prospective study aimed to investigate whether MLH1 c.-93G>A (rs1800734), MSH2 c.211+9C>G (rs2303426), MSH3 c.3133G>A (rs26279), EXO1 c.1765G>A (rs1047840), and EXO1 c.2270C>T (rs9350) single nucleotide polymorphisms (SNPs) of the mismatch repair (MMR) pathway change side effects and response rate of 90 HNSCC patients treated with CDDP and RT. DNA from peripheral blood was analyzed by PCR-based methods to obtain genotypes. It was observed 4.27-fold and 4.69-fold increased risks of presenting pronounced nephrotoxicity with treatment in patients with MSH3 GG and EXO1 rs9350 CC genotypes compared with patients with GA or AA and CT or TT genotypes, respectively. MSH3 GG or GA and GT haplotype of EXO1 rs1047840 and rs9350 SNPs conferred to patients 10.29 and 4.00 more chances of presenting pronounced ototoxicity after treatment than MSH3 AA genotype and other EXO1 haplotypes, respectively. Patients with EXO1 rs1047840 GA or AA genotype and AC haplotype of EXO1 rs1047840 and rs9350 SNPs had both 9.55-fold increased risks of achieving partial response or stable disease instead of complete remission after treatment than patients with EXO1 GG genotype and other EXO1 haplotypes, respectively. For the first time, our data show preliminary indication that inherited alterations of DNA MMR pathway, related to MSH3 rs26279, EXO1 rs1047840 and EXO1 rs9350 SNPs, modify toxicity and response to chemoradiation in HNSCC, and may contribute to future personalized treatment of patients.

15.
BMC Cancer ; 17(1): 831, 2017 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-29212535

RESUMO

BACKGROUND: Leukocytoclastic vasculitis is typically mediated by deposition of immune complexes and is related to many causes, including medication. To the best of our knowledge, leukocytoclastic vasculitis related to cisplatin has not yet been described in the scientific literature. CASE PRESENTATION: We report a rare case of leukocytoclastic vasculitis after the first cycle of high-dose cisplatin chemotherapy in a patient with larynx carcinoma. A 48-year-old Caucasian man with larynx carcinoma received a high-dose of cisplatin monochemotherapy (100 mg/m2 every 21 days), along with 70 Gy of radiotherapy divided into 35 sessions, as a therapeutic schedule. Twelve days after the first chemotherapy administration and after 8 sessions of radiotherapy (total of 16 Gy), the patient presented with acute onset of palpable purpura in the lower limbs. The patient was hospitalized for 10 days, and during this period, he underwent several examinations to rule out infectious, autoimmune, and neoplastic disorders. A skin biopsy showed leukocytoclastic vasculitis with a positive pattern for IgM and C3, as detected through direct immunofluorescence. Twenty-five days after cisplatin administration, the chemotherapy regimen was changed to carboplatin AUC 5, and the episodes of purpura ceased, reinforcing the hypothesis of an adverse reaction to cisplatin. CONCLUSIONS: Cisplatin can induce leukocytoclastic vasculitis and clinicians should be aware of this potential effect for better case management and diagnosis.


Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Neoplasias Laríngeas/tratamento farmacológico , Vasculite Leucocitoclástica Cutânea/induzido quimicamente , Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Humanos , Neoplasias Laríngeas/complicações , Neoplasias Laríngeas/radioterapia , Perna (Membro)/irrigação sanguínea , Perna (Membro)/patologia , Masculino , Pessoa de Meia-Idade , Pele/irrigação sanguínea , Pele/patologia , Vasculite Leucocitoclástica Cutânea/complicações , Vasculite Leucocitoclástica Cutânea/patologia
16.
Basic Clin Pharmacol Toxicol ; 121(6): 520-525, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28686330

RESUMO

Cisplatin (CDDP) chemotherapy associated with radiation (RT) has been used in advanced head and neck squamous cell carcinoma (HNSCC) patients, and vomiting is a common side effect during treatment. This prospective study aimed to identify the roles of GSTM1 and GSTT1 (presents or nulls), GSTP1 c.313A>G, XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C, ERCC1 c.354C>T, MLH1 c.-93G>A, MSH2 c.211 + 9C>G, MSH3 c.3133G>A, EXO1 c.1765G>A, TP53 c.215G>C, CASP3 c.-1191A>G and c.-1168G>T, CASP9 c.-1339A>G, CASP8 c.-937_-932delAGTAAG, FAS c.-1378G>A and c.-671A>G, and FASL c.-157-687C>T single nucleotide polymorphisms, involved in CDDP metabolism, in vomiting severity in 88 HNSCC patients treated with CDDP and RT. Ondansetron and dexamethasone were administered as anti-emetic therapy. Patients with GSTP1 c.313AG or GG genotype alone and combined with XPD c.934GA or AA, XPF c.2505TC or CC, and CASP9 c.-1339AG or GG genotypes had 4.28, 5.00, 5.45 and 5.38 more chances of presenting moderate/severe vomiting than patients with others genotypes. Our data suggest, for the first time, that inherited abnormality in apoptosis pathway alone or combined with inherited abnormalities in DNA repair pathway, is capable of modulating emesis in HNSCC patients under CDDP chemoradiation and may be used for selecting patients who should receive pre-emptive anti-emetic therapy.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/efeitos adversos , Cisplatino/efeitos adversos , Predisposição Genética para Doença/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Vômito/induzido quimicamente , Vômito/genética , Adulto , Idoso , Antieméticos/uso terapêutico , Antineoplásicos/farmacocinética , Carcinoma de Células Escamosas/complicações , Cisplatino/farmacocinética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço , Vômito/tratamento farmacológico
17.
Daru ; 25(1): 12, 2017 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-28438219

RESUMO

BACKGROUND: Cisplatin is a high-potency anticancer agent; however, it causes significant adverse drug reactions (ADRs). Potential pharmacokinetic markers must be studied to predict or prevent cisplatin-induced ADRs and achieve better prognosis. This study was designed to investigate the relationship between ADRs and kinetics of cisplatin excretion in the urine of patients undergoing high-dose cisplatin chemotherapy and radiotherapy for head and neck cancer. METHODS: Outpatients with head and neck cancer received a first cycle of high-dose cisplatin chemotherapy (80-100 mg/m2) concurrent to radiotherapy. ADRs (haematological, renal, and gastrointestinal reactions) were classified based on severity by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 4, grade 0-4). The kinetics of cisplatin excretion in urine was evaluated by high-performance liquid chromatography over three time periods: 0-12, 12-24, and 24-48 h after the administration of cisplatin. Spearman Correlation test and regression analysis were performed to assess the relationship between ADRs and cisplatin excretion in the urine. RESULTS: In total, 59 patients with a mean age of 55.6 ± 9.4 years were analysed; most patients were male (86.4%), white (79.7%), and with pharyngeal tumours in advanced stages (66.1%). The most frequently observed ADRs were anaemia (81.4%), lymphopenia (78%), and nausea (64.4%); mostly grades 1 and 2 of toxicity. The mean cisplatin excretion was 70.3 ± 64.4, 7.3 ± 6.3, and 5 ± 4 µg/mg creatinine at 0-12, 12-24, and 24-48 h, respectively. Statistical analysis showed that the amount of cisplatin excreted did not influence the severity of ADRs. CONCLUSIONS: The most frequent ADRs were anaemia, lymphopenia, and nausea. Grades 1 and 2 were the severities for most ADRs. The period over which the highest cisplatin excretion observed was 0-12 h after chemotherapy, and cisplatin excretion could not predict toxicity.


Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , Anemia/induzido quimicamente , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Antineoplásicos/urina , Quimiorradioterapia/métodos , Cisplatino/farmacocinética , Cisplatino/uso terapêutico , Cisplatino/urina , Feminino , Humanos , Linfopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neoplasias Faríngeas/terapia , Estudos Prospectivos
19.
Oral Surg Oral Med Oral Pathol Oral Radiol ; 123(5): e170-e175, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28407991

RESUMO

OBJECTIVE: Ghost cell odontogenic carcinoma is a very rare malignant neoplasm. Tumor volume may be a more precise alternative for determining size, which is usually measured by maximum linear dimension. The purpose of this case report is to highlight the importance of obtaining 3-dimensional (3-D) images of the tumor for volumetric analysis to improve the chances of surgical success. This report presents a case of ghost cell odontogenic carcinoma infiltrating the maxillary sinus through the palate. The lesion was surgically treated and subsequently selected for volumetric reconstruction and analysis of the tumor by using InVesalius software. In this case report, we describe the use of a pictorial technique in which the tumor volume was calculated to help predict the surgical results. RESULTS: The tumor could be visualized in 3-D, with color improving the image of the segmented volume and thus increasing the perception of boundaries and depth. CONCLUSIONS: Recognition of the lesion shape by volumetric analysis can provide the surgical team with clearer information, thereby helping in surgical planning and consequently increasing the chances of surgical success.


Assuntos
Neoplasias Maxilares/diagnóstico por imagem , Tumores Odontogênicos/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Imageamento Tridimensional , Neoplasias Maxilares/patologia , Neoplasias Maxilares/cirurgia , Pessoa de Meia-Idade , Tumores Odontogênicos/patologia , Tumores Odontogênicos/cirurgia , Software
20.
Clin Breast Cancer ; 17(4): e199-e208, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28330681

RESUMO

INTRODUCTION: Polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) modify the risk and severity of sporadic breast cancer (BC). In this context, the MTHFR C677T and A1298C polymorphisms have been associated with risk and severity of sporadic BC. PATIENTS AND METHODS: In total, 253 women with BC and 257 controls were enrolled in this study. Polymorphisms were analyzed using restriction fragment length polymorphism - polymerase chain reaction. Epidemiology, tumor characteristics, and reproductive factors were considered in the analysis. Statistical tests included the χ2 test, the Fisher exact test, and the Mann-Whitney and Kruskal-Wallis tests, or parametric equivalents. RESULTS: MTHFR polymorphisms were not a risk factor for BC. The 677CC genotype was associated with distant metastasis (odds ratio [OR] = 5.311; 95% confidence interval [CI] = 1.124-25.09) and lower estrogen receptor expression, whereas the 1298AA genotype was associated with stage 0 (OR = 0.244; 95% CI = 0.077-0.771) and increased estrogen receptor expression. In haplotype analysis, 677CC/1298AA was associated with hypertension (OR = 1.979; 95% CI = 1.036-3.782), and 677CT/1298AC was associated with invasive carcinoma of no special type (OR = 0.472; 95% CI = 0.243-0.918) and stage 0 (OR = 3.476; 95% CI = 1.341-10.47). CONCLUSION: The MTHFR C677T and A1298C polymorphisms do not alter the risk of BC, but are associated with the clinical severity of BC.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/secundário , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença
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