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1.
J Cancer Res Ther ; 16(3): 440-444, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719248

RESUMO

Introduction: Crystallization test is based on the principle that, when a salt crystallizes out of an aqueous solution, the crystal growth is influenced by the presence of other substances in the solution, such as blood or plant extracts. If a mixture of copper chloride solution with a small amount of whole blood is allowed to crystallize under controlled experimental conditions, an aggregate of crystals forms. Crystallization method can be used as a diagnostic aid to provide information about the systemic conditions and general health of the patient. Aim: This study aims to study the patterns of crystallization and to further determine the efficacy of crystallization test as a screening modality in premalignant lesions and oral squamous cell carcinoma (OSCC). Materials and Methods: Fifty patients of OSCC, 50 patients of premalignant lesions, and 50 healthy individuals were selected. One drop of blood was collected from the study groups to perform crystallization using cupric chloride. Statistical Analysis Used: Statistical analysis was performed using Chi-square test, Student's t-test (two-tailed), and analysis of variance. Results: The different patterns of crystals formed were studied and statistically analyzed. Conclusion: Based on the study, it was concluded that Crystallization test can be used as an effective screening modality for detection of premalignant lesions and OSCC.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/diagnóstico , Cobre/química , Cristalização/métodos , Leucoplasia/sangue , Neoplasias Bucais/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/química , Estudos de Casos e Controles , Feminino , Humanos , Leucoplasia/patologia , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Neoplasias Bucais/sangue , Neoplasias Bucais/química , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/sangue , Adulto Jovem
2.
J Cancer Res Ther ; 16(3): 546-550, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719265

RESUMO

Background: The objective of this study was to evaluate the serum and salivary L-fucose in oral potentially malignant disorders (OPMDs) and oral cancer (OC) in order to investigate the possibility of using this as biomarker for early diagnosis. Materials and Methods: The study included 85 participants, who were grouped as control (30), OPMDs patients (25), and OC patients (30). Serum and unstimulated whole saliva were collected from participants of all groups and fucose estimation was done using spectrophotometry. The results were tabulated and analyzed statistically. Results: The mean serum L-fucose levels in normal, OPMDs, and OC group were 3.49, 19.18, and 35.75 mg/dl, respectively, while the levels of salivary L-fucose were 3.18, 7.02, and 11.66 mg/dl, respectively. A highly significant rise (P < 0.001) in serum and salivary L-fucose was observed in the study participants compared to control. Conclusions: The present study showed a significant and gradual increase in serum and salivary L-fucose from control to OPMDs to OC. From this study, we suggest that L-fucose can be used as a reliable biomarker and saliva can be used as a diagnostic fluid for screening and early detection of OC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/sangue , Fucose/metabolismo , Neoplasias Bucais/metabolismo , Lesões Pré-Cancerosas/sangue , Saliva/metabolismo , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Fucose/sangue , Fucose/química , Humanos , Masculino , Neoplasias Bucais/sangue , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Saliva/química
3.
J Cancer Res Ther ; 16(1): 127-131, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362622

RESUMO

Introduction: More than 70% of lung cancer comprises nonsmall-cell lung carcinoma and is associated with poor survival outcome owing to late diagnosis. Identification of lung cancer in early stages when no clinical signs or symptoms are evident, can drastically improve the prognosis. To this end, we aimed to evaluate the changes occurring at tissue level by assessing the expression of six microRNAs (miRNAs) in lung adenocarcinoma (AC) and squamous cell carcinoma (SCC). Materials and Methods: Peripheral blood of histopathologically proven cases of lung AC and SCC was collected and processed for the isolation of miRNAs using commercially available kit. Primers against mir-2114, mir-2115, mir-2116, mir-2117, mir-449c, and mir-548q with loading control Caenorhabditis elegans were used. Screening was carried out in thirty cases of both AC and SCC, whereas twenty healthy controls were included. Results: Real-time polymerase chain reaction data revealed that the expression of mir-2114 and mir-449c in AC and mir-2115 in SCC was significantly upregulated. The expression of these miRNAs was also confirmed in lung AC cell line. The differential pattern of expression of these miRNAs can be used for precise diagnosis of lung carcinoma. Conclusions: We have used a noninvasive technique to identify the subtype of lung cancer based on molecular genetic signatures. The results suggest that through molecular profiling of miRNA, we can screen high-risk cases for cancer interception.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , MicroRNA Circulante/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma/sangue , Adenocarcinoma/genética , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , MicroRNA Circulante/sangue , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Estadiamento de Neoplasias , Prognóstico
4.
J Cancer Res Clin Oncol ; 146(8): 1971-1978, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32447484

RESUMO

PURPOSE: Interleukin-10 (IL-10) is an immunoregulatory cytokine and its cervical and serum concentrations have been associated with a poor prognosis of cervical cancer. The rs1800872 polymorphism (c.-592C>A) in the promotor region of the IL-10 gene affects the production and expression of IL-10 and thus is able to determine the immune response profile in the cervix. Therefore, the aim of this work is to state the association between IL-10 c.-592C>A polymorphism and cervical cancer. METHODS: Genomic DNA was extracted from patient's peripheral blood and tumor biopsy. Socio-demographic, sexual behavior and reproductive characteristics data were collected using a questionnaire. RESULTS: Co-dominant model in logistic binary regression adjusted for confounders, showed that patients presenting with C/A genotype had 2.15 times more chances for developing cervical cancer (OR 2.15; CI95% 1.02-4.56). The dominant model, C/A + A/A, was also independently associated with 2.71 times more chances for cervical cancer development when compared to control patients (OR 2.71; CI95% 1.05-4.47). CONCLUSION: Our study analyses show the association between cervical cancer and IL-10 c.-592C>A polymorphism, demonstrating that the allele A presence was independently associated with higher risks of cervical cancer development.


Assuntos
Interleucina-10/genética , Neoplasias do Colo do Útero/genética , Adenocarcinoma/sangue , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adulto , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Estudos de Casos e Controles , DNA/sangue , DNA/genética , Feminino , Genótipo , Humanos , Interleucina-10/biossíntese , Interleucina-10/imunologia , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/imunologia
5.
Anticancer Res ; 40(4): 2365-2371, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234939

RESUMO

BACKGROUND: Several immune-inflammatory markers are associated with cancer progression. The purpose of the present study was to clarify the influence of the preoperative C-reactive protein-to-albumin ratio (CRP/ALB ratio) on survival of patients with esophageal cancer and recurrence after curative resection. PATIENTS AND METHODS: The preoperative CRP/ALB ratio was evaluated in 122 patients who underwent radical resection for esophageal cancer from 2005 to 2018. The correlations between the CRP/ALB ratio and cancer-specific overall (OS), recurrence-free (RFS) survival and the clinicopathological status were analyzed. RESULTS: The optimal cut-off value of the CRP/ALB ratio determined using receiver operating characteristic curve analysis was 0.04. Patients were divided into two groups based on this cut-off value: the low CRP/ALB group (n=59) and the high CRP/ALB group (n=50). The OS rate at 5 years after surgery was significantly lower in the group with high CRP/ALB at 40.5% whilst it was 63.5% in the low CRP/ALB group (p=0.005). The corresponding RFS rates at 5 years after surgery were 32.5% and 48.3%, respectively, which was a statistically significant difference (p=0.007). A multivariate analysis showed that a high CRP/ALB ratio was a significant independent risk factor for poorer cancer-specific OS and RFS. CONCLUSION: The preoperative CRP/ALB ratio was a strong prognostic marker for patients with esophageal cancer. The surgical strategy, including procedure and perioperative care should be carefully planned for patients with a high CRP/ALB ratio.


Assuntos
Proteína C-Reativa/análise , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Albumina Sérica/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos
6.
Sci Rep ; 10(1): 6083, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32269293

RESUMO

PURPOSE: This study compares the detection sensitivity of two separate liquid biopsy sources, cell-free (cf) DNA/RNA and extracellular vesicle (EV)-associated DNA/RNA (EV-DNA/RNA), to identify circulating Human Papilloma Virus (HPV) DNA/RNA in plasma obtained from patients with oropharyngeal squamous cell carcinoma (OPCSCC). We also report on the longitudinal changes observed in HPV-DNA levels in response to treatment. EXPERIMENTAL DESIGN: A prospective study was conducted that included 22 patients with locally advanced disease and six patients with metastatic OPCSCC. Twenty-three patients had HPV-related OPCSCC defined by p16 immunohistochemistry. Levels of circulating HPV-DNA and HPV-RNA from plasma-derived cf-DNA/RNA and EV-DNA/RNA were quantified using digital droplet PCR. RESULTS: Circulating HPV-DNA was detected with higher sensitivity in cf-DNA compared to EV-DNA at 91% vs. 42% (p = <0.001). Similarly, circulating tumoral HPV-RNA was detected at a higher sensitivity in cf-RNA compared to EV-RNA, at 83% vs. 50% (p = 0.0019). In the locally advanced cohort, 100% (n = 16) of HPV-OPCSCC patients demonstrated a reduction in circulating HPV-DNA levels in cf-DNA following curative treatment, with 81% of patients demonstrating complete clearance to undetectable levels. However, in metastatic HPV-OPCSCC patients (n = 4), HPV-DNA levels did not correlate with treatment response. CONCLUSION: Our study demonstrates that although HPV-DNA/RNA can be detected in EV associated DNA/RNA, cf-DNA/RNA is the more sensitive liquid biopsy medium. As circulating HPV-DNA levels were found to only correlate with treatment response in the locally advanced but not metastatic setting in our small cohort of patients, the use of HPV-DNA as a dynamic biomarker to monitor treatment response requires further evaluation.


Assuntos
Carcinoma de Células Escamosas/patologia , Ácidos Nucleicos Livres/análise , DNA Viral/análise , Vesículas Extracelulares/virologia , Testes de DNA para Papilomavírus Humano/métodos , Neoplasias Orofaríngeas/patologia , Idoso , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/virologia , Ácidos Nucleicos Livres/genética , DNA Viral/genética , Feminino , Testes de DNA para Papilomavírus Humano/normas , Humanos , Limite de Detecção , Biópsia Líquida/métodos , Biópsia Líquida/normas , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/sangue , Neoplasias Orofaríngeas/virologia
7.
Cancer Immunol Immunother ; 69(7): 1229-1236, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32152703

RESUMO

The efficacy of immune checkpoint inhibitors (ICIs) in elderly and poor performance status (PS) patients is controversial, because clinical evidence is limited. This study aimed to find a predictive biomarker for the efficacy of anti-programmed cell death 1 (PD-1) antibodies in these patient populations. We retrospectively reviewed medical records of advanced non-small-cell lung cancer (NSCLC) patients who were ≥ 75 years of age or classified as PS 2 and received anti-PD-1 antibody treatment between December 2015 and May 2018. We evaluated the association between the efficacy of the anti-PD-1 antibody in these patients and the clinical variables thought to affect ICI efficacy. A total of 235 patients with advanced NSCLC were treated with anti-PD-1 antibodies, among whom 31 patients were ≥ 75 years of age and 22 were PS 2. A Cox proportional hazard model showed that only high levels of serum vascular endothelial growth factor (VEGF) were significantly associated with a shorter progression-free survival in patients aged ≥ 75 years and those with PS 2. Among these cohorts, the overall response rate to anti-PD-1 treatment tended to be lower when serum VEGF was high compared to patients with low serum VEGF. Our results demonstrate that serum VEGF concentration may be a negative predictive biomarker in elderly and poor PS advanced NSCLC patients receiving anti-PD-1 antibody treatment. This finding may help identify patients who will not benefit from anti-PD-1 antibody therapy.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/sangue , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
8.
BMC Cancer ; 20(1): 138, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32085736

RESUMO

BACKGROUND: To study the kinetic profile and clinicopathological implications of squamous cell carcinoma antigen (SCC-Ag) in cervical cancer patients who underwent surgery by a self-developed SCC-Ag single molecule assay (Simoa) prototype immunoassay. METHODS: Participants were prospectively enrolled between 04/2016 and 06/2017. Consecutive serum samples were collected at five points: day 0 (the day before surgery), postoperative day 4, weeks 2-4, months 2-4 and months 5-7. In total, 92 patients and 352 samples were included. The kinetic change in SCC-Ag levels and their associations with clinicopathological characteristics were studied. RESULTS: Simoa SCC-Ag was validated by comparison with the Architect assay. SCC-Ag levels measured by the Simoa assay were highly correlated with the Architect assay's levels (Pearson's correlation coefficient = 0.979, Passing-Bablok regression slope 0.894 (0.847 to 0.949), intercept - 0.009 (- 0.047 to 0.027)). The median values for each time-point detected by the Simoa assay were 2.49, 0.66, 0.61, 0.72, and 0.71 ng/mL, respectively. The SCC-Ag levels decreased dramatically after surgery and then stabilized and fluctuated to some extent within 6 months. Patients with certain risk factors had significantly higher SCC-Ag values than their negative counterparts before surgery and at earlier time points after surgery, while no difference existed at the end of observation. Furthermore, although patients with positive lymph nodes had sustained higher SCC-Ag levels compared to those with negative lymph nodes, similar kinetic patterns of SCC-Ag levels were observed after surgery. Patients who received postoperative treatment had significantly higher SCC-Ag values than those with surgery only at diagnosis, while no difference existed after treatment. CONCLUSIONS: The Simoa SCC-Ag prototype was established for clinical settings. The SCC-Ag levels were higher in patients with risk factors, whereas the kinetic trend of SCC-Ag might be mainly affected by postoperative adjuvant therapy. These data indicate that the SCC-Ag level might be a good predictor for the status of cervical cancer, including disease aggressiveness and treatment response.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/patologia , Histerectomia/métodos , Serpinas/sangue , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Estudos Longitudinais , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Fatores de Risco , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/cirurgia
9.
Braz. j. otorhinolaryngol. (Impr.) ; 86(1): 105-110, Jan.-Feb. 2020. tab
Artigo em Inglês | LILACS | ID: biblio-1089368

RESUMO

Abstract Introduction Recently it has been reported that a high preoperative neutrophil-lymphocyte ratio and platelet-lymphocyte ratio may be related to increased recurrence risk, tumor aggressiveness, and worsened prognosis in various malignancies. Objective The objective of this research is to explore whether neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in parotid tumors may or may not be used as a cancer marker. Methods This retrospective research has been conducted on a total of 228 patients consisting of 83 healthy persons and 145 patients with a mass in the parotid gland, who applied to a tertiary referral center and underwent surgery. Patients have been divided into two groups by their histopathological findings as malignant or benign parotid tumor. A third group consisting of healthy people has been defined as the control group. Also the malignant parotid tumor group has been divided into two subgroups as early stage and advanced stage. The groups have been compared in terms of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and other laboratory data. Results The average neutrophil-lymphocyte ratio values of malignant parotid tumor, benign parotid tumor, healthy control groups were 2.51, 2.01, 1.79 respectively and the difference was statistically significant (p < 0.001). There was no significant difference between advanced stage and early stage parotid tumor groups in terms of average neutrophil-lymphocyte ratio value (p = 0.782). In dual comparisons, the platelet-lymphocyte ratio value of patients in the malignant group was found out to be statistically significantly higher than that of benign and control groups (p < 0.001 and p = 0.001 respectively). Conclusion To the best of our knowledge our research is the first in the medical literature comparing neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with parotid tumor. neutrophil-lymphocyte ratio and platelet-lymphocyte ratio can serve as cost-effective, repeatable, easily accessible, and helpful inflammatory markers in order to distinguish patients with malignant parotid tumor from healthy people.


Resumo Introdução Recentemente, tem sido relatado que as relações neutrófilo-linfócito e plaqueta-linfócito aumentadas no pré-operatório podem estar relacionadas ao aumento do risco de recorrência e agressividade do tumor e pior prognóstico em várias neoplasias malignas. Objetivo Investigar se as relações neutrófilo-linfócito e plaqueta-linfócito em tumores da parótida podem ou não serem utilizadas como marcadores de câncer. Método Esta pesquisa retrospectiva foi conduzida com 228 indivíduos, 83 saudáveis e 145 com tumor de parótida, os quais foram encaminhados a um centro de referência terciária e operados. Os pacientes foram divididos em dois grupos de acordo com os achados histopatológicos de malignidade e benignidade. O terceiro grupo foi composto por indivíduos saudáveis, foi definido como o grupo controle. Além disso, o grupo com tumores malignos da parótida foi dividido em dois subgrupos, um com pacientes em estágio inicial da doença e o outro com pacientes em estágio avançado. Os grupos foram comparados em termos das relações neutrófilo-linfócito e plaqueta-linfócito e outros dados laboratoriais. Resultados Os valores médios da relação neutrófilo-linfócito do tumor maligno de parótida, do tumor benigno de parótida e do grupo controle foram de 2,51, 2,01 e 1,79, respectivamente, com uma diferença estatisticamente significante (p < 0,001). Não houve diferença estatística entre os grupos em estágio avançado e em estágio inicial em termos de valor médio da relação neutrófilo-linfócito (p = 0,782). Em comparações duplas, o valor da relação plaqueta-linfócito dos pacientes do grupo do grupo com tumor maligno foi estatisticamente maior do que nos grupos com tumor benigno e controle (p < 0,001 e p = 0,001, respectivamente). Conclusão Que seja de nosso conhecimento, nosso estudo é o primeiro na literatura médica a comparar a relação neutrófilo-linfócito e a relação plaqueta-linfócito em pacientes com tumor de parótida. As relações neutrófilo-linfócito e plaqueta-linfócito podem servir como marcadores inflamatórios de baixo custo, reproduzíveis, de fácil acesso e úteis, a fim de distinguir os pacientes com tumor maligno de parótida de pessoas saudáveis.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Neoplasias Parotídeas/patologia , Linfócitos/citologia , Carcinoma de Células Escamosas/patologia , Adenoma Pleomorfo/patologia , Neutrófilos/citologia , Contagem de Plaquetas , Prognóstico , Cuidados Pré-Operatórios , Neoplasias Parotídeas/cirurgia , Neoplasias Parotídeas/sangue , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/sangue , Estudos Retrospectivos , Adenoma Pleomorfo/cirurgia , Adenoma Pleomorfo/sangue , Contagem de Linfócitos , Biomarcadores Ambientais , Estadiamento de Neoplasias
10.
Clin Immunol ; 212: 108345, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31953149

RESUMO

BACKGROUND: Biomarkers in non-colorectal gastrointestinal (GI) cancer patients receiving immune checkpoint blockades (ICBs) are still limited. METHODS: Data were prospectively collected from a discovery cohort (n = 53) and a validation cohort (n = 107) in patients with non-colorectal GI cancer receiving ICB, as well as a chemotherapy-only cohort (n = 171). System inflammatory markers and derived neutrophil-to-lymphocyte ratio (dNLR) were determined as biomarkers by univariate and multivariate analyses. RESULTS: A higher level of dNLR (cutoff = 3) was associated with shorter overall survival (OS) in discovery and validation cohorts. In pooled cohort, disease control rate (DCR) (28% vs. 48.1%) was associated with dNLR (p = .017). In univariate analysis, original tumor site, tumor histopathology, number of metastases, and dNLR were correlated with OS. In multivariate analysis, higher dNLR level was correlated with reduced OS (10.43 months vs. 4.20 months, p < .001). In chemotherapy-only cohort, dNLR was also correlated with DCR and OS. CONCLUSION: Higher dNLR level was correlated with worse outcomes, suggesting that dNLR may help risk-group stratification and assist disease management strategies as a prognostic biomarker for non-colorectal GI patients receiving ICB.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Contagem de Linfócitos , Neutrófilos , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Biomarcadores , Antígeno CTLA-4/antagonistas & inibidores , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Neoplasias do Sistema Digestório/sangue , Neoplasias do Sistema Digestório/tratamento farmacológico , Neoplasias do Sistema Digestório/patologia , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/patologia , Feminino , Neoplasias da Vesícula Biliar/sangue , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/patologia , Humanos , Contagem de Leucócitos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Adulto Jovem
11.
J Steroid Biochem Mol Biol ; 199: 105603, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31981799

RESUMO

Calcitriol, the active metabolite of vitamin D, has been widely studied for its preventive and therapeutic activity against several cancers including oral squamous cell carcinoma (OSCC). However, the impact of dietary vitamin D supplementation on initiation and progression of OSCC is unclear. To address this gap in knowledge, we conducted preclinical trials using the 4-nitroquinoline-1-oxide 4NQO carcinogen model of oral carcinogenesis. Female C57BL/6 mice were maintained on one of three vitamin D diets [25 IU, 100 IU, 10,000 IU] and exposed to 4NQO in drinking water for 16 weeks followed by regular water for 10 weeks. Body weight measurements obtained through the study duration did not reveal any differences between the three diets. Animals on 100 IU diet showed lower incidence of high-grade dysplasia/OSCC and higher CD3 + T cells compared to animals on 25 IU and 10,000 IU diets. Serum 25OHD3 levels were highest in animals on 10,000 IU diet at week 0 prior to carcinogen exposure but showed ∼50 % reduction at week 26. Histologic evaluation revealed highest incidence of OSCC in animals maintained on 10,000 IU diet. Animals on 100 IU and 10,000 IU diets showed higher vitamin D receptor VDR and CYP24A1 immunostaining in high-grade dysplastic lesions and OSCC compared to normal tongue. Validation studies performed in a 4NQO-derived OSCC model showed that short-term treatment of animals on a 25 IU diet with calcitriol significantly inhibited tumor growth compared to controls but did not affect tumor growth in animals on reference diet 1000 IU. Collectively, our results highlight the complex dynamics between vitamin D status and oral carcinogenesis. Our observations also suggest that therapeutic benefits of short-term calcitriol treatment may be more pronounced in vitamin D deficient hosts.


Assuntos
Carcinoma de Células Escamosas/dietoterapia , Neoplasias Bucais/dietoterapia , Receptores de Calcitriol/genética , Vitamina D3 24-Hidroxilase/genética , Vitamina D/genética , 4-Nitroquinolina-1-Óxido/toxicidade , Animais , Peso Corporal , Calcitriol/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/patologia , Suplementos Nutricionais/efeitos adversos , Modelos Animais de Doenças , Progressão da Doença , Humanos , Camundongos , Neoplasias Bucais/sangue , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/patologia , Vitamina D/sangue , Deficiência de Vitamina D/dietoterapia , Deficiência de Vitamina D/genética , Deficiência de Vitamina D/patologia
12.
Anal Chim Acta ; 1100: 118-130, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31987131

RESUMO

Oral cavity cancer is a common cancer type that presents an increasingly serious global problem. Oral squamous cell carcinoma (OSCC) accounts for >90% oral cancer cases. No biomarker tests are currently available for management of this cancer type in clinical practice. Previously, we validated matrix metalloproteinase-1 (MMP1) as one of the most promising salivary biomarkers for OSCC detection. Development of a convenient, rapid and high-throughput assay should further facilitate application of salivary MMP1 measurement for early detection of OSCC. The present study aimed to develop a workflow comprising dry saliva spot (DSS) sampling and immunoenrichment-coupled MALDI-TOF MS (immuno-MALDI) analysis to quantify salivary MMP1. We generated recombinant MMP1 protein and anti-peptide antibodies against MMP1, which were used to optimize the procedures of the entire workflow, including DSS sampling, on-paper protein digestion and elution, KingFisher magnetic particle processor-assisted immuno-enrichment and MALDI-TOF MS analysis. The established workflow was applied to measure salivary MMP1 levels in DSS samples from 5 healthy donors and 9 OSCC cases. The newly developed workflow showed good precision (intra-day and inter-day variations <10%) and accuracy (80-100%) in quantification of MMP1 in DSS samples, with the limit of quantification at 3.07 ng/ml. Using this assay, we successfully detected elevated salivary MMP1 levels (ranging from 5.95 to 242.52 ng/ml) in 7 of 9 OSCC cases while MMP1 was not detectable in samples from the 5 healthy donors. In comparison, the traditional immunoassay was not effective in measuring MMP1 in DSS samples, highlighting the significant advantage of our immuno-MALDI assay. The DSS sampling format confers high flexibility and convenience of collection, storage and delivery of saliva specimens and the KingFisher-assisted immuno-MALDI analysis renders the assay as suitable for high-throughput screening. By combining the two features, the workflow developed in this study should facilitate improvement of molecular diagnostic tests for OSCC using salivary MMP1 as a biomarker.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Teste em Amostras de Sangue Seco , Metaloproteinase 1 da Matriz/sangue , Neoplasias Bucais/sangue , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/enzimologia , Humanos , Imunoquímica , Metaloproteinase 1 da Matriz/metabolismo , Neoplasias Bucais/enzimologia , Proteínas Recombinantes/sangue , Proteínas Recombinantes/metabolismo , Saliva , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
13.
Surg Oncol ; 32: 99-107, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31983439

RESUMO

Growing evidences have demonstrated a pivotal role of chronic inflammation in oral squamous cell carcinoma (OSCC) through the modulation of inflammatory cells and cytokine production. IL-37 is newly discovered anti-inflammatory member of IL-1 family and can bind to IL-18 receptor to inhibit IL-18 (pro-inflammatory member of IL-1 family) function. Investigation on the balance of IL-18/IL-37 would provide new insights into the function of IL-1 family in OSCC. Thus, serum IL-18 and IL-37 levels of OSCC patients (n = 108), leukoplakia patients (n = 40), and healthy donors (n = 36) were collected to analyze the balance of IL-18 and IL-37, and also determine their diagnostic value and prognostic significance in OSCC. The results showed that OSCC patients had high IL-18 and low IL-37 levels in serum and peripheral blood mononuclear cell (PBMC). The ratio of IL-18/IL-37 in serum efficiently distinguished non-cancer individuals from OSCC patients (cut off value: 2.15). Moreover, patients with high IL-18 and low IL-37 were susceptible to develop advanced tumor stage and lymph node metastasis (Odd ratios of IL-18/IL-37 is 4.903 and 12.613, respectively). Meanwhile, higher IL-18/IL-37 ratio could predict shorter overall survival and disease-free survival of OSCC patients, although it was not an independent prognostic factor. We further analyze the correlations of serum IL-18/IL-37 with immunocytes in peripheral blood and found that high IL-18 level was associated with more CD19+ B cells, while serum IL-37 seem to be associated with reduced percentage of CD3+CD8+ T cells, indicating its balance could change the adaptive immune response. Unexpectedly, we first revealed the different function of IL-18/IL-37 in serum and tumor tissues. High mRNA expression of IL-18 in tumor tissues correlated with low lymph node metastasis rate and low tumor stage, which was contradictory to the pro-tumor role of IL-18 in serum. In conclusion, enhanced ratio of IL-18/IL-37 level in serum could be an efficient biomarker for OSCC. Its balance might regulate CD19+ B cells and CD3+ CD8+ T cells for OSCC progression.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/secundário , Interleucina-18/sangue , Interleucina-1/sangue , Leucócitos Mononucleares/patologia , Neoplasias Bucais/patologia , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/cirurgia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Seguimentos , Humanos , Interleucina-1/genética , Interleucina-18/genética , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/sangue , Neoplasias Bucais/cirurgia , Prognóstico , Taxa de Sobrevida
14.
Braz J Otorhinolaryngol ; 86(1): 105-110, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31122885

RESUMO

INTRODUCTION: Recently it has been reported that a high preoperative neutrophil-lymphocyte ratio and platelet-lymphocyte ratio may be related to increased recurrence risk, tumor aggressiveness, and worsened prognosis in various malignancies. OBJECTIVE: The objective of this research is to explore whether neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in parotid tumors may or may not be used as a cancer marker. METHODS: This retrospective research has been conducted on a total of 228 patients consisting of 83 healthy persons and 145 patients with a mass in the parotid gland, who applied to a tertiary referral center and underwent surgery. Patients have been divided into two groups by their histopathological findings as malignant or benign parotid tumor. A third group consisting of healthy people has been defined as the control group. Also the malignant parotid tumor group has been divided into two subgroups as early stage and advanced stage. The groups have been compared in terms of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and other laboratory data. RESULTS: The average neutrophil-lymphocyte ratio values of malignant parotid tumor, benign parotid tumor, healthy control groups were 2.51, 2.01, 1.79 respectively and the difference was statistically significant (p<0.001). There was no significant difference between advanced stage and early stage parotid tumor groups in terms of average neutrophil-lymphocyte ratio value (p=0.782). In dual comparisons, the platelet-lymphocyte ratio value of patients in the malignant group was found out to be statistically significantly higher than that of benign and control groups (p<0.001 and p=0.001 respectively). CONCLUSION: To the best of our knowledge our research is the first in the medical literature comparing neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with parotid tumor. neutrophil-lymphocyte ratio and platelet-lymphocyte ratio can serve as cost-effective, repeatable, easily accessible, and helpful inflammatory markers in order to distinguish patients with malignant parotid tumor from healthy people.


Assuntos
Adenoma Pleomorfo/patologia , Carcinoma de Células Escamosas/patologia , Linfócitos/citologia , Neutrófilos/citologia , Neoplasias Parotídeas/patologia , Adenoma Pleomorfo/sangue , Adenoma Pleomorfo/cirurgia , Adulto , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/cirurgia , Biomarcadores Ambientais , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Parotídeas/sangue , Neoplasias Parotídeas/cirurgia , Contagem de Plaquetas , Cuidados Pré-Operatórios , Prognóstico , Estudos Retrospectivos
15.
Int J Cancer ; 146(9): 2394-2405, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276202

RESUMO

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Inflamação/complicações , Neoplasias Pulmonares/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Adenocarcinoma de Pulmão/sangue , Adenocarcinoma de Pulmão/etiologia , Adulto , Idoso , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/etiologia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/etiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Inflamação/sangue , Inflamação/imunologia , Cinurenina/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Neopterina/sangue , Prognóstico , Estudos Prospectivos , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/etiologia , Triptofano/sangue
16.
Eur J Surg Oncol ; 46(1): 131-138, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31481274

RESUMO

OBJECTIVE: We seek to explore the clinical significance of serum squamous cell carcinoma antigen (SCC-Ag) and the optimal cut-off value for predicting tumor recurrence and survival in operable cervical squamous cell carcinoma patients. METHODS: A total of 3471 patients with cervical squamous cell carcinoma who underwent radical surgery were enrolled in this study. The cut-off value of serum SCC-Ag for tumor recurrence was calculated using the receiver operating characteristic (ROC) curve. The progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method and multivariate analysis was further performed. RESULTS: The optimal cut-off value of serum SCC-Ag level for predicting tumor recurrence was calculated and set at 2.75 ng/mL. Compared to the value of 1.5 ng/mL used in clinical practice, our results showed that serum SCC-Ag level >2.75 ng/mL was closely related to extrapelvic metastases in relapsed patients (P = 0.035). Multivariate analysis showed that neither serum SCC-Ag level >1.5 ng/mL nor serum SCC-Ag level >2.75 ng/mL was independent risk factors for PFS and OS in all patients. However, among 964 patients with at least one high-risk factor (parametrial invasion, vaginal margin invasion and lymph node metastasis), serum SCC-Ag level > 2.75 ng/mL, instead of serum SCC-Ag level > 1.5 ng/mL, could be used as an independent factor affecting PFS (P = 0.018). CONCLUSION: Preoperative serum SCC-Ag level > 2.75 ng/mL is closely related to extrapelvic recurrence, and is an independent factor for tumor recurrence and survival in cervical squamous cell carcinoma patients with high-risk factors.


Assuntos
Antígenos de Neoplasias/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/cirurgia , Recidiva Local de Neoplasia/sangue , Serpinas/sangue , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
17.
Gastroenterology ; 158(3): 494-505.e6, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31711920

RESUMO

BACKGROUND & AIMS: Biomarkers are needed to risk stratify after chemoradiotherapy for localized esophageal cancer. These could improve identification of patients at risk for cancer progression and selection of additional therapy. METHODS: We performed deep sequencing (CAncer Personalized Profiling by deep Sequencing, [CAPP-Seq]) analyses of plasma cell-free DNA collected from 45 patients before and after chemoradiotherapy for esophageal cancer, as well as DNA from leukocytes and fixed esophageal tumor biopsy samples collected during esophagogastroduodenoscopy. Patients were treated from May 2010 through October 2015; 23 patients subsequently underwent esophagectomy, and 22 did not undergo surgery. We also sequenced DNA from blood samples from 40 healthy control individuals. We analyzed 802 regions of 607 genes for single-nucleotide variants previously associated with esophageal adenocarcinoma or squamous cell carcinoma. Patients underwent imaging analyses 6-8 weeks after chemoradiotherapy and were followed for 5 years. Our primary aim was to determine whether detection of circulating tumor DNA (ctDNA) after chemoradiotherapy is associated with risk of tumor progression (growth of local, regional, or distant tumors, detected by imaging or biopsy). RESULTS: The median proportion of tumor-derived DNA in total cell-free DNA before treatment was 0.07%, indicating that ultrasensitive assays are needed for quantification and analysis of ctDNA from localized esophageal tumors. Detection of ctDNA after chemoradiotherapy was associated with tumor progression (hazard ratio, 18.7; P < .0001), formation of distant metastases (hazard ratio, 32.1; P < .0001), and shorter disease-specific survival times (hazard ratio, 23.1; P < .0001). A higher proportion of patients with tumor progression had new mutations detected in plasma samples collected after chemoradiotherapy than patients without progression (P = .03). Detection of ctDNA after chemoradiotherapy preceded radiographic evidence of tumor progression by an average of 2.8 months. Among patients who received chemoradiotherapy without surgery, combined ctDNA and metabolic imaging analysis predicted progression in 100% of patients with tumor progression, compared with 71% for only ctDNA detection and 57% for only metabolic imaging analysis (P < .001 for comparison of either technique to combined analysis). CONCLUSIONS: In an analysis of cell-free DNA in blood samples from patients who underwent chemoradiotherapy for esophageal cancer, detection of ctDNA was associated with tumor progression, metastasis, and disease-specific survival. Analysis of ctDNA might be used to identify patients at highest risk for tumor progression.


Assuntos
Adenocarcinoma/terapia , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/diagnóstico , Quimiorradioterapia , DNA Tumoral Circulante/sangue , Neoplasias Esofágicas/terapia , Adenocarcinoma/sangue , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Idoso , Biomarcadores Tumorais/isolamento & purificação , Biópsia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , DNA Tumoral Circulante/isolamento & purificação , Progressão da Doença , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/mortalidade , Esôfago/diagnóstico por imagem , Esôfago/patologia , Estudos de Viabilidade , Feminino , Voluntários Saudáveis , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Intervalo Livre de Progressão , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco/métodos , Tomografia Computadorizada por Raios X
18.
Br J Cancer ; 122(3): 340-347, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31761899

RESUMO

BACKGROUND: Accessible biomarkers are needed for immunotherapy in advanced non-small-cell lung cancer (NSCLC). We previously described a multivariate risk prediction model, the iSEND, which categorises advanced NSCLC patients treated with nivolumab into Good, Intermediate or Poor groups. This model was developed by using only clinical and analytical variables (sex, ECOG-performance status, neutrophil-to-lymphocyte ratio [NLR] and post-treatment delta NLR). METHODS: An international database of 439 patients who received post-platinum PD-1/L1 monotherapies was collected for validation. Performance of the iSEND to different PD-L1 groups was compared by using time-dependent positive predictive value (PPV) for their mortality events. RESULTS: Median follow-up was 18.2 months (95% CI: 15.9-19.6). The overall survival of the iSEND Good (HR = 0.31, 95% CI: 0.22-0.43, p < 0.0001) was superior to the iSEND Poor. Time-dependent PPV for mortality of iSEND Poor was superior to PD-L1 = 0% group at 12 (75 vs. 53%, p = 0.01) and 18 months (85 vs. 46%, p = 0.03). However, female gender did not independently associate with better outcome in the validation cohort. CONCLUSION: The iSEND model is associated with the outcome of post-platinum PD-1/L1 monotherapy in advanced NSCLC patients. The iSEND Poor demonstrated a superior performance to PD-L1 = 0% in negative prognostication. Prospective investigation and modelling with other significant parameters in a larger cohort are warranted.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/fisiopatologia , Feminino , Humanos , Contagem de Leucócitos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/fisiopatologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Nivolumabe/uso terapêutico , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais
19.
J Oncol Pharm Pract ; 26(5): 1266-1269, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31840564

RESUMO

INTRODUCTION: Elevated serum beta human chorionic gonadotrophin (ß-hCG) in a female normally indicates pregnancy or possibly, gestational trophoblastic disease or ovarian germ cell tumours. Expression of ß-hCG has been demonstrated in cervical and endometrial carcinoma and other non-germ cell tumours of the ovary, vulva, breast, prostate, lung, colon, oral/facial tissue and stomach. CASE REPORT: We report a 43-year-old premenopausal woman with p16 positive squamous cell anal cancer. Pre-treatment urinary screening was positive for ß-hCG (218 IU/L), which was confirmed on serum and expressed in the tumour. Pelvic ultrasound ruled out pregnancy. Cervical cytology detected human papilloma virus p16 infection and a potential squamous intraepithelial lesion. Management and outcome: She received definitive chemoradiation (Mitomycin/5-fluorouracil) for six weeks. ß-hCG, taken four weeks post completion, had returned to normal levels (<2 IU/L). DISCUSSION: Cases of elevated serum ß-hCG are documented in different cancers including breast, gastric, lung, ovarian and renal cell. In our case, the elevated ß-hCG is probably ectopic excretion by the squamous cell carcinoma tumour in the anus. While this has never been reported previously in the anus, it is likely due to the documented risk of development of precancerous as well as cancerous anal and cervical lesions through human papilloma virus infection. Raised levels of ß-hCG have been reported in cervical cancers. Other possible causes of ß-hCG elevation were excluded. Following treatment, her ß-hCG level returned to normal strengthening the hypothesis that ß-hCG elevation was due to the anal carcinoma. In conclusion, unexplained ectopic secretion of ß-hCG may be the first sign of a primary malignancy.


Assuntos
Neoplasias do Ânus/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Gonadotropina Coriônica Humana Subunidade beta/sangue , Adulto , Neoplasias do Ânus/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Feminino , Humanos
20.
Acta Otolaryngol ; 140(2): 181-187, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31825711

RESUMO

Background: Nivolumab has been approved for recurrent or metastatic head and neck cancer (R/M HNC) on March 2017 in Japan. Recently, many researchers have been actively studying the prognostic and predictive markers. However, they have not been clarified. In this study, we evaluate the prognostic and predictive markers of the anticancer effect of nivolumab.Objective: This study assessed baseline neutrophil-to-lymphocyte ratio (NLR) as a prognostic and predictive marker for nivolumab efficacy in patients with recurrent/metastatic head and neck cancer (R/M HNC).Material and methods: This retrospective cohort study used medical records of patients with R/M HNC treated with nivolumab from May 2017 to January 2018 at a university hospital in Japan.Results: Twenty-nine patients (median age, 64 years) were included. In univariate analyses, baseline NLR ≥5 was significantly associated with overall survival (HR 4.88; p = .045) and progressive disease (HR 5.0; p = .046). More patients with baseline NLR ≥5 changed from nivolumab to best supportive care, compared to patients with baseline NLR <5 (64.3% vs 26.7%, respectively).Conclusions and significance: Baseline NLR was associated with clinical benefit from nivolumab in patients with R/M HNC. We propose that baseline NLR be used as a predictive or prognostic marker for nivolumab efficacy in these patients.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Nivolumabe/uso terapêutico , Idoso , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/mortalidade , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Japão/epidemiologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/mortalidade , Estudos Retrospectivos
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