RESUMO
BACKGROUND: Peripheral blood leukocyte (PBL) DNA methylation may serve as a surrogate marker to evaluate the susceptibility to and prognosis of gastric cancer (GC). In this study, blood-derived DNA methylation levels of two tumour-related genes, namely, ZNF331 and WIF1, and their impacts on the risk and prognosis of GC were evaluated. METHODS: In total, 398 GC cases and 397 controls were recruited for the study. Then, all cases were followed up for 5 years. ZNF331 and WIF1 promoter methylation status in PBLs was measured using a methylation-sensitive high-resolution melting method. Logistic and Cox regression models were used to analyse the correlation between gene methylation and the risk and prognosis of GC. Confounders were balanced through propensity score (PS) matching. RESULTS: High ZNF331 methylation significantly decreased GC risk after PS adjustment (OR = 0.580, 95% CI: 0.375-0.898, P = 0.015), which also presented in males (OR = 0.577, 95% CI: 0.343-0.970, P = 0.038). However, WIF1 methylation was not associated with GC risk. Additionally, significant combined effects between ZNF331 methylation and the intake of green vegetables and garlic were observed (OR = 0.073, 95% CI: 0.027-0.196, P < 0.001 and OR = 0.138, 95% CI: 0.080-0.238, P < 0.001, respectively). Furthermore, ZNF331 and WIF1 methylation had no impact on the prognosis of GC. CONCLUSION: ZNF331 methylation in PBLs may affect GC risk in combination with the consumption of green vegetables and garlic and may act as a potential biomarker of GC.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Biomarcadores Tumorais/genética , Metilação de DNA , Proteínas de Ligação a DNA/genética , Proteínas de Neoplasias/genética , Neoplasias Gástricas/epidemiologia , Proteínas Adaptadoras de Transdução de Sinal/sangue , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Proteínas de Ligação a DNA/sangue , Proteínas de Ligação a DNA/metabolismo , Inquéritos sobre Dietas/estatística & dados numéricos , Epigênese Genética , Feminino , Alho , Mucosa Gástrica/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/metabolismo , Prognóstico , Regiões Promotoras Genéticas/genética , Pontuação de Propensão , Fatores de Proteção , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/prevenção & controle , VerdurasRESUMO
BACKGROUND: The Japanese Gastric Cancer Treatment Guidelines recommend S-1 and S-1 plus docetaxel as postoperative chemotherapy for pathological stage II and III gastric cancer (GC). There is currently no strategy for using chemotherapy to treat high-risk recurrent pathological stage II/III. Previous studies reported that the several nutritional, immunological, and inflammatory markers examined the association with clinical outcomes after surgery for GC. METHODS: Ninety patients with GC (stage II, n = 48; stage III, n = 42) for whom gastrectomy was performed at our institution between November 2009 and September 2018 were examined. Nutritional, immunological, and inflammatory markers were calculated from blood samples within 1 week before surgery. RESULTS: The prognostic nutritional index (PNI) status correlated with the pathological stage and disease recurrence after surgery (p = 0.015 and p < 0.0001, respectively). Thirty-three patients had disease recurrence after gastrectomy (stage II, n = 11; stage III, n = 22). The PNI was significantly lower in the recurrent group than in the non-recurrent group (p = 0.0003). The PNI correlated with overall survival and recurrence-free survival after gastrectomy (p = 0.0021 and p = 0.0001, respectively). A multivariate analysis identified the PNI as an independent prognostic factor (p = 0.006). CONCLUSION: The PNI may be useful for predicting the outcomes of patients with pathological stage II/III GC and may contribute to the selection of an appropriate adjuvant chemotherapy regimen.
Assuntos
Docetaxel/uso terapêutico , Gastrectomia/métodos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Tegafur/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Estadiamento de Neoplasias , Avaliação Nutricional , Guias de Prática Clínica como Assunto , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Análise de Sobrevida , Resultado do TratamentoRESUMO
INTRODUCTION: Patients with gastric adenocarcinoma (GA) often develop malnutrition, which deteriorates after cancer surgery and negatively affects surgical outcomes. Despite being an abundant and versatile amino acid involved in the immune system and metabolic functions, glutamine levels are significantly depleted among patients who are critically ill or hypercatabolic. Therefore, this study aimed to investigate whether parenteral glutamine supplementation may improve nutritional status and surgical outcomes. METHODS: This retrospective, single-center cohort study included patients with GA who underwent gastrectomy between January 2007 and June 2019. Patients were classified into either the non-glutamine or glutamine group. Propensity score matching was used to minimize the bias in patient demographics. Furthermore, the average parenteral glutamine dose from the day of surgery to postoperative day four was calculated in g/kg/day. Surgical outcomes (length of hospitalization, major complication, and mortality) and changes in lymphocyte count and serum albumin levels 7 days post-surgery were assessed in both matched groups using adjusted models. RESULTS: A total of 1950 patients were reviewed, among whom 522 (26.8%) received parenteral glutamine supplementation (glutamine dose ranging from 0.05 to 0.49 g/kg/day). Among the included patients, 57.2% were males, and the median age was 64.9 years. After matching, there were 478 cases in each group. No differences in surgical outcomes and changes in lymphocyte count were observed between both matched groups. The glutamine group exhibited a smaller decrease in serum albumin levels compared to the non-glutamine group (-0.6 vs. -1.1 g/dL; P < 0.001). The adjusted matched model showed that glutamine dose contributed significantly toward increasing serum albumin levels (coefficient = 0.08 per 0.1 g/day/kg increment in glutamine; 95% confidence interval: 0.04 to 0.10; P < 0.001). CONCLUSIONS: Perioperative parenteral glutamine supplementation had a positive dose-dependent impact on the recovery of serum albumin levels among patients with GA undergoing gastrectomy, implying that glutamine supplementation improved postoperative nutritional suppression and ameliorated stress-associated inflammation. Although glutamine supplementation was not associated with surgical outcomes, further studies should be conducted to evaluate the clinical significance of serum albumin restoration.
Assuntos
Adenocarcinoma/terapia , Glutamina/administração & dosagem , Desnutrição/terapia , Nutrição Parenteral/métodos , Albumina Sérica/metabolismo , Neoplasias Gástricas/terapia , Adenocarcinoma/sangue , Adenocarcinoma/complicações , Idoso , Suplementos Nutricionais , Feminino , Gastrectomia , Humanos , Masculino , Desnutrição/sangue , Desnutrição/etiologia , Pessoa de Meia-Idade , Estado Nutricional , Assistência Perioperatória/métodos , Período Pós-Operatório , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/complicações , Resultado do TratamentoRESUMO
This study aimed to explore novel microRNAs in plasma for predicting chemoresistance in adjuvant chemotherapy for patients with gastric cancer (GC). We used the Toray 3D-Gene microRNA array-based approach to compare preoperative plasma microRNA levels between GC patients with and without recurrences after curative gastrectomy. All patients underwent adjuvant chemotherapy with S-1, an oral fluoropyrimidine. Of 2566 candidates, six candidate microRNAs (miR-1229-3p, 1249-5p, 762, 711, 1268a and 1260b), which were highly expressed in the preoperative plasma of patients with subsequent recurrences, were selected. In a large-scale validation analysis by quantitative RT-PCR, we focused on high plasma levels of miR-1229-3p, which was an independent poor prognostic factor for recurrence free survival (P = 0.009, HR = 3.71). Overexpression of miR-1229-3p in GC cells induced significant chemoresistance to 5-fluorouracil (5-FU), up-regulation of thymidylate synthase (TS) and dihydroprimidine dehydrogenase (DPD) and down-regulation of SLC22A7 both in vitro and in vivo. Intraperitoneal injection of miR-1229-3p in mice induced significant chemoresistance to 5-FU, accompanied by high levels of miR-1229-3p in plasma and tumor tissue. These findings suggest that plasma miR-1229-3p might be a clinically useful biomarker for predicting chemoresistance to S-1 and selecting other or combined intensive chemotherapy regimens in GC patients.
Assuntos
Biomarcadores Tumorais/sangue , Resistencia a Medicamentos Antineoplásicos , MicroRNAs/sangue , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/sangue , Tegafur/uso terapêutico , Animais , Linhagem Celular Tumoral , Movimento Celular , Sobrevivência Celular , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Fluoruracila , Gastrectomia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Recidiva Local de Neoplasia , Transportadores de Ânions Orgânicos Sódio-Independentes/genética , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
PURPOSE: The goal of our analysis was to study pretherapeutic circulating 25-OHD plasma levels in patients with previously untreated advanced gastric cancer treated in the randomised controlled phase III Erbitux (cetuximab) in combination with Xeloda (capecitabine) and cisplatin in advanced esophago-gastric cancer (EXPAND) trial (NCT00678535) and to explore whether low 25-OHD plasma levels are associated with worse prognosis and may compromise the clinical efficacy of cetuximab. METHODS: Six hundred thirty patients with available pretherapeutic 25-OHD plasma levels and treated with chemotherapy based on capecitabine and cisplatin, or chemotherapy and cetuximab, were included. The Cox proportional hazard regression model was used to analyse the association between low 25-OHD and survival in both treatment arms. RESULTS: Majority of study patients were found to have severe vitamin D deficiency. No prognostic impact of 25-OHD plasma levels could be found in our patient cohort, and there was no indication of an interference of 25-OHD plasma levels and the efficacy of treatment with the anti-epidermal growth factor receptor monoclonal antibody cetuximab. CONCLUSIONS: Although majority of patients with advanced gastric cancer show hypovitaminosis D deficiency, there is no proof for a negative impact on survival or reduced treatment response. A prospective study is needed to investigate the potential benefit of vitamin D supplementation in this patient cohort during first-line chemotherapy.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Deficiência de Vitamina D/epidemiologia , Vitamina D/sangue , Adenocarcinoma/sangue , Adenocarcinoma/mortalidade , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Capecitabina/uso terapêutico , Cetuximab/uso terapêutico , Cisplatino/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to study the effect of ω-3 supplementation on the nutritional status and the immune and inflammatory profiles of patients with gastric cancer during antineoplastic pretreatment. METHODS: This was a randomized, open, controlled longitudinal study with intervention in outpatient patients with gastric cancer. Sixty-eight patients were randomized into two groups and received either a formula enriched with ω-3 (intervention group [IG]) or standard formula without ω-3 (control group) for 30 d consecutively. Nutritional status (based on patient-generated subjective global assessment, bioimpedance, and anthropometric measurements) and immune and inflammatory parameters were collected before and after supplementation. Results were expressed as frequency, median, and interquartile intervals and were compared by non-parametric test. P < 0.05 was considered statistically significant. RESULTS: Thirty-four patients were included in each group. Of the patients, 64.7% were men, 44.1% were older than 60 years, and 45.6% had stage III disease. There was an increase in C-reactive protein in the control group before and after supplementation, in addition to the worsening in some anthropometric parameters, such as arm muscle area and arm muscle circumference. There was maintenance of the immune profile in both groups. An increase in weight gain was observed in the IG but not in the control group (1.2 [0.9-9] versus 0.7 kg [0.4-1.3]; Pâ¯=â¯0.03), as was a reduction of interleukin-6 (5.7 [4.1-6.4] versus 6.3 pg/mL [5.6-8.6]; Pâ¯=â¯0.03) and a maintenance of nutritional status, after supplementation. CONCLUSIONS: Supplementation with ω-3 leads to weight gain, reduction in the inflammatory profile, and maintenance of the nutritional and immune profiles of these patients, but further studies are needed to examine changes in body composition.
Assuntos
Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Estado Nutricional , Neoplasias Gástricas/sangue , Neoplasias Gástricas/terapia , Adulto , Idoso , Antropometria , Proteína C-Reativa/efeitos dos fármacos , Feminino , Alimentos Formulados , Humanos , Interleucina-6/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Aumento de Peso/efeitos dos fármacosRESUMO
A positive family history is a strong and consistently reported risk factor for gastric cancer (GC). So far, it has been demonstrated that serum pepsinogens (PGs), and gastrin 17 (G17) are useful for screening individuals at elevated risk to develop atrophic gastritis but they are suboptimal biomarkers to screen individuals for GC. The main purpose of this study was to investigate serum metabolomic profiles to find additional biomarkers that could be integrated with serum PGs and G17 to improve the diagnosis of GC and the selection of first-degree relatives (FDR) at higher risk of GC development. Serum metabolomic profiles included 188 serum metabolites, covering amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, sphingomyelins and hexoses. Serum metabolomic profiles were performed with tandem mass spectrometry using the Biocrates AbsoluteIDQ p180 kit. The initial cohort (training set) consisted of n = 49 GC patients and n = 37 FDR. Differential metabolomic signatures among the two groups were investigated by univariate and multivariate partial least square differential analysis. The most significant metabolites were further selected and validated in an independent group of n = 22 GC patients and n = 17 FDR (validation set). Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic power and the optimal cut-off for each of the discriminant markers. Multivariate analysis was applied to associate the selected serum metabolites, PGs, G17 and risk factors such as age, gender and Helicobacter pylori (H. pylori) infection with the GC and FDR has been performed and an integrative risk prediction algorithm was developed. In the training set, 40 metabolites mainly belonging to phospholipids and acylcarnitines classes were differentially expressed between GC and FDR. Out of these 40 metabolites, 9 were further confirmed in the validation set. Compared with FDR, GC patients were characterized by lower levels of hydroxylated sphingomyelins (SM(OH)22:1, SM(OH)22:2, SM(OH)24:1) and phosphatidylcholines (PC ae 40:1, PC ae 42:2, PC ae 42:3) and by higher levels of acylcarnitines derivatives (C2, C16, C18:1). The specificity and sensitivity of the integrative risk prediction analysis of metabolites for GC was 73.47% and 83.78% respectively with an area under the curve of the ROC curve of 0.811 that improves to 0.90 when metabolites were integrated with the serum PGs. The predictive risk algorithm composed of the C16, SM(OH)22:1 and PG-II serum levels according to the age of individuals, could be used to stratify FDR at high risk of GC development, and then this can be addressed with diagnostic gastroscopy.
Assuntos
Família , Metaboloma , Metabolômica , Neoplasias Gástricas/sangue , Neoplasias Gástricas/epidemiologia , Fatores Etários , Biomarcadores Tumorais , Carnitina/análogos & derivados , Carnitina/sangue , Biologia Computacional/métodos , Detecção Precoce de Câncer , Feminino , Infecções por Helicobacter/complicações , Humanos , Masculino , Metabolômica/métodos , Curva ROC , Medição de Risco , Esfingomielinas/sangue , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etiologiaRESUMO
Helicobacter pylori (H. pylori) infection can interfere with the absorption of most elements, and the variations of some element levels are related to the incidence of gastric cancer. However, there have been conflicting results concerning the influence of H. pylori infection on serum element levels. The present study aimed to compare the serum element concentrations of H. pylori-infected local residents with uninfected residents from Lujiang County with high gastric cancer risk in Eastern China. We used data and serum samples from the H. pylori screening-survey program which was a cross-sectional study. We took 155 samples randomly from the screening survey, identified 74 H. pylori-positive residents and 81 H. pylori-negative residents by a serological test. The serum concentrations of 15 elements (calcium, magnesium, iron, zinc, selenium, copper, molybdenum, chromium, cobalt, nickel, lead, cadmium, mercury, arsenic, and aluminum) were determined using inductively coupled plasma mass spectrometry. Serum cobalt was found at higher levels in the H. pylori-infected residents than the H. pylori-uninfected residents (0.246 vs 0.205 µg/L, P = 0.022), but no statistically significant differences in the serum levels of other elements were found. This is the first study to report the serum concentrations of 15 elements and their relationships with the infection status of H. pylori among local residents from Lujiang County with high gastric cancer risk. Although the International Agency for Research on Cancer has classified cobalt and other soluble cobalt salts as possibly carcinogenic to human beings, our results may provide a clue to the relationships between cobalt, H. pylori, and gastric cancer.
Assuntos
Infecções por Helicobacter/sangue , Helicobacter pylori/química , Neoplasias Gástricas/sangue , Adulto , Idoso , Alumínio/sangue , Arsênio/sangue , Cádmio/sangue , Cálcio/sangue , China , Cromo/sangue , Cobalto/sangue , Cobre/sangue , Estudos Transversais , Feminino , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Humanos , Ferro/sangue , Chumbo/sangue , Magnésio/sangue , Masculino , Espectrometria de Massas , Mercúrio/sangue , Pessoa de Meia-Idade , Molibdênio/sangue , Níquel/sangue , Fatores de Risco , Selênio/sangue , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/microbiologia , Zinco/sangueRESUMO
BACKGROUND: The potential prognostic value of survivin is variably reported depending on the gastric cancer. OBJECTIVE: Evaluation of the prognostic and predictive significance of serum survivin and its relation with survival and treatment response rates in patients with locally advanced gastric cancer (LAGC). METHODS: Serum samples were prospectively collected from 50 patients with newly diagnosed LAGC. Serum samples of 32 healthy subjects were also collected as control groups for survivin levels. Serum survivin levels were evaluated at baseline and after three cycles of neoadjuvant chemotherapy in LAGC patients. RESULTS: Median survivin level was 147 IU/L (range = 4.4-4936) at baseline and was 27 IU/L (range = 4.2-4737) after neoadjuvant chemotherapy. The difference between survivin levels of the control group (26 IU/L, range = 3.8-1430) and pre-treatment patient group was statistically significant (p< 0.001). Clinical response to mDCF regimen was classified as progressive (progressive disease) and non-progressive groups (partial response + stable disease). Baseline survivin levels were similar between patients in progressive and non-progressive groups (p= 0.55). Survivin levels were significantly reduced after chemotherapy in non-progressive group (p< 0.001). In contrast, serum survivin levels increased in a stepwise fashion from baseline to post-chemotherapy in patients with progressive disease (p= 0.06). Patients were divided into low and high survivin groups according to baseline median survivin levels. Median DFS was 12.4 and 14.6 months for low and high groups, respectively (p= 0.18). Moreover, median OS was 14.4 and 24.9 months for low and high group, respectively (p= 0.14). CONCLUSION: It can be suggested that serum survivin can be used as a predictor of response to chemotherapy- but not survival- in LAGC patients receiving neoadjuvant mDCF chemotherapy. However, large multicenter prospective studies are required to confirm these results.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Proteínas Inibidoras de Apoptose/sangue , Neoplasias Gástricas/sangue , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Biomarcadores Tumorais/biossíntese , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Humanos , Proteínas Inibidoras de Apoptose/biossíntese , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Gástricas/cirurgia , Survivina , Taxoides/administração & dosagemRESUMO
Bone disease in long-term survivors after gastric cancer resection has received little research attention. This study aimed to investigate bone health after curative resection of gastric cancer and the consequences of high-dose vitamin D supplementation in patients with low levels of 25-(OH)-vitamin D. Disease-free patients at least 24 months after gastric cancer resection represented the study cohort. Serum markers of bone metabolism were assessed at baseline and at 3 and 12 months. Bone mineral density and presence of fractures were assessed by X-ray at baseline. Patients with 25-(OH)-vitamin D ≤30 ng/mL at baseline received 16,000 IU of vitamin D3 every 10 days during the 1-year follow-up. Forty patients were included in the study. Mean time from surgery was 48.9 (24-109) months. Vitamin D insufficiency and secondary hyperparathyroidism were observed in 38 and 20 patients, respectively. Densitometry showed osteoporosis in 14 women and seven men and prevalent fractures in 12 women and six men at baseline. After 3 months of vitamin D supplementation, 35 patients reached values of 25-(OH)-vitamin D over 30 ng/mL. After 12 months, 38 patients were in the normal range of 25-(OH)-vitamin D. At the same time, iPTH levels and markers of bone turnover (C-terminal cross-linked telopeptide of type-I collagen, serum concentrations of bone-specific alkaline phosphatase and osteocalcin) significantly decreased after vitamin D intervention. Oral administration of high doses of vitamin D is easily implemented and restored 25-(OH)-vitamin D and iPTH values, which are frequently disturbed after gastric cancer resection.
Assuntos
Osso e Ossos/patologia , Sobreviventes de Câncer , Suplementos Nutricionais , Neoplasias Gástricas/patologia , Vitamina D/administração & dosagem , Vitamina D/uso terapêutico , Idoso , Biomarcadores/sangue , Densidade Óssea , Remodelação Óssea , Osso e Ossos/metabolismo , Cálcio/metabolismo , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Fraturas Ósseas/sangue , Fraturas Ósseas/complicações , Fraturas Ósseas/tratamento farmacológico , Fraturas Ósseas/fisiopatologia , Humanos , Masculino , Hormônio Paratireóideo/sangue , Estudos Prospectivos , Neoplasias Gástricas/sangue , Vitamina D/sangueRESUMO
BACKGROUND & AIMS: Chronic inflammation is related with cancer and leads to worsening prognosis in cancer patients. n-3 polyunsaturated fatty acids (PUFAs) supplementation has been proposed as adjuvant treatment in cancer due anti-inflammatory properties. In the present meta-analysis, we pooled randomized clinical trials (RCTs) assessing the effects of n-3 PUFAs (from fish oil isolated or added in an immunonutrition formula) on inflammatory markers in gastric cancer. METHODS: A comprehensive literature search was performed in Medline, Scopus, Cochrane library, Science Direct and Web of Science, besides GOOGLE Scholar and a hand searching of reference lists, through July 2016. We pooled the effect size from individual studies using a random-effect model and carried out heterogeneity and sensitivity analyses. RESULTS: Nine trials (698 patients) fulfilled the entry criteria and were included in the synthesis of the systematic review. Eight were carried out in surgical patients and one in patients that received chemotherapy. Four used only fish oil as intervention and five used an immunonutrition formula. Global meta-analysis demonstrated higher albumin (7 studies, SMD 0.28; 95% CI 0.07, 0.48) and prealbumin (4 studies, SMD 0.56; 95% CI 0.12, 1.00) concentrations, and lower IL-6 (2 studies, SMD -0.71; 95% CI -1.15, -0.27) and TNF-α (2 studies, SMD -0.92; 95% CI -1.58, -0.26) concentrations in patients of the intervention group as compared to control group. However, total protein, transferrin and CRP concentrations were not improved by n-3 PUFAs supplementation. CONCLUSION: This study provides evidence that n-3 PUFAs supplementation from fish oil or added an immunonutrition formula has favorable effects on inflammatory markers in gastric cancer patients undergoing surgical procedures.
Assuntos
Proteínas de Fase Aguda/análise , Citocinas/sangue , Ácidos Graxos Ômega-3/administração & dosagem , Neoplasias Gástricas/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Suplementos Nutricionais , Feminino , Óleos de Peixe/administração & dosagem , Humanos , Inflamação/sangue , Interleucina-6/sangue , MEDLINE , Masculino , Pré-Albumina/análise , Ensaios Clínicos Controlados Aleatórios como Assunto , Albumina Sérica/análise , Neoplasias Gástricas/cirurgia , Transferrina/análise , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND/AIMS: Carnitine plays an important role in the metabolism of fatty acids. It has also been reported that the administration of anticancer drugs may lead to reductions in serum carnitine levels due to decreased activity of organic cation transporter novel 2, which plays a role in the reabsorption of carnitine in the tubules of the kidney. We therefore studied the change in carnitine levels when chemotherapy was administered repeatedly to patients with gastric cancer. METHODS: Ten patients with upper gastrointestinal cancer were enrolled in this study between December 2014 and August 2015. All patients were administered chemotherapy consisting of TS-1 and cisplatin every 3 weeks: 3 received it as adjuvant therapy post resection, the remaining 7 received it as treatment for unresectable tumors. Before the start of each chemotherapy cycle, serum was collected. RESULTS: The mean total carnitine level was 54.5 ± 13.7 µmol/L prior to commencing chemotherapy; it was 46.7 ± 13.5 and 41.4 ± 14.8 µmol/L at the second and third cycles respectively. The total carnitine level was decreased in a statistically significant manner (p = 0.0039). The serum level of total protein and cholinesterase was also decreased significantly (p = 0.0218 and p = 0.0418). CONCLUSION: Carnitine levels decreased during repeated chemotherapy in patients with gastric cancer, and they are associated with the nutritional status.
Assuntos
Antineoplásicos/administração & dosagem , Carnitina/sangue , Cisplatino/administração & dosagem , Estado Nutricional , Neoplasias Gástricas/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Gástricas/sangueRESUMO
Previous studies have found associations between one-carbon metabolism nutrients and risk of several cancers, but little is known regarding upper gastrointestinal tract (UGI) cancer. We analyzed prediagnostic serum concentrations of several one-carbon metabolism nutrients (vitamin B12, folate, vitamin B6, riboflavin and homocysteine) in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of male smokers, which was undertaken in Finland between 1985 and 1988. We conducted a nested case-control study including 127 noncardia gastric adenocarcinoma (NCGA), 41 esophagogastric junctional adenocarcinoma and 60 esophageal squamous cell carcinoma incident cases identified within ATBC. Controls were matched to cases on age, date of serum collection and follow-up time. One-carbon nutrient concentrations were measured in fasting serum samples collected at baseline (up to 17 years prior to cancer diagnosis). Odds ratios and 95% confidence intervals (CI) were calculated using conditional logistic regression. Lower prediagnostic vitamin B12 concentrations at baseline were associated with a 5.8-fold increased risk of NCGA (95% CI = 2.7-12.6 for lowest compared to highest quartile, p-trend <0.001). This association remained in participants who developed cancer more than 10 years after blood collection, and after restricting the analysis to participants with clinically normal serum vitamin B12 (>300 pmol/L). In contrast, pepsinogen I, a known serologic marker of gastric atrophy, was not associated with NCGA in this population. As vitamin B12 absorption requires intact gastric mucosa to produce acid and intrinsic factor, our findings suggest vitamin B12 as a possible serologic marker for the atrophic gastritis that precedes NCGA, one more strongly associated with subsequent NCGA than pepsinogen.
Assuntos
Carcinoma de Células Escamosas/sangue , Neoplasias Esofágicas/sangue , Neoplasias Gástricas/sangue , Deficiência de Vitamina B 12/sangue , Vitamina B 12/sangue , Idoso , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Suplementos Nutricionais , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Finlândia/epidemiologia , Ácido Fólico/sangue , Homocisteína/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Riboflavina/sangue , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Deficiência de Vitamina B 12/patologia , alfa-Tocoferol/administração & dosagem , beta Caroteno/administração & dosagemRESUMO
Diallyl trisulfide (DATS), a natural agent derived from garlic, has been tested for its antigastric cancer activities in various preliminary studies. However, more systematic pharmacodymatic (PD) and mechanistic evaluations are clearly needed. The aim of this study was to investigate the antitumor effects of DATS in the treatment of human gastric cancer cell SGC-7901 both in vitro and in vivo using widely recommended study procedures. DATS suppressed cancer cells proliferation and induced cell cycle arrest accompanied by an increase in the expressions of cyclin A2 and cyclin B1 in SGC-7901 cancer cells. DATS also caused an increase in apoptotic cell death, which involved in accumulations of bax, p53, and cytochrome C and reduction of Bcl-2 expressions. Besides, activation of JNK, ERK and p38 phosphorylation in DATS-treated cells suggested that mitogen-activated protein kinase (MAPKs) pathways were involved in DATS-induced apoptosis. Meanwhile, DATS significantly inhibited tumor growth and promoted tumor apoptosis in a xenograft model of gastric cancer cell SGC-7901. DATS inhibited tumor migration and invasion by modulating MMP9 and E-cadherin protein expressions. In addition, DATS treatment evidently increased the cytokine secretions of IL-12, TNF-α and IFN-γ (p<0.05). Biochemical serum analysis and histopathological examination indicated no obvious side effects in major mouse organs. Therefore, our findings provide a framework for further exploration of DATS as a novel chemotherapeutic for human gastric cancer.
Assuntos
Compostos Alílicos , Antineoplásicos , Neoplasias Gástricas/tratamento farmacológico , Sulfetos , Compostos Alílicos/farmacologia , Compostos Alílicos/uso terapêutico , Compostos Alílicos/toxicidade , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Citocinas/sangue , Citocinas/genética , Feminino , Alho , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Sulfetos/farmacologia , Sulfetos/uso terapêutico , Sulfetos/toxicidade , Carga Tumoral/efeitos dos fármacosRESUMO
Objective: To study the predictive and prognostic significance of high-sensitivity modified Glasgow Prognostic Score (HS-mGPS) on the effect of neoadjuvant chemotherapy for advanced gastric cancer. Methods: 117 patients with advanced gastric cancer received neoadjuvant chemotherapy with SOX (oxaliplatin+ S1) or mFOLFOX 6(oxaliplatin+ CF+ 5-FU) regimen. HS-mGPS was calculated according to blood C-reactive protein (CRP) concentration and serum albumin (ALB) level. The correlation between HS-mGPS and clinicopathological characteristics was determined and the predictors of survival were analyzed. Results: 117 patients with stage â ¡B (43 cases), stage â ¢ (60), and stage â £ (14) received preoperative neoadjuvant chemotherapy. The overall response rate of neoadjuvant chemotherapy was 61.5%(72/117), and the tumor control rate was 88.0% (103/117), with a pathological response rate of 91.5% (107/117). The R0 resection rate was 81.2% (95/117). The median disease-free survival (DFS) was 21.0 (95% CI 6.4-35.6) months. The median overall survival (OS) was 39.0 (95% CI 21.4-56.6) months. Higher HS-mGPS was associated with higher T stage, local lymph-node metastasis, distant metastasis, lower chemotherapy overall response rate and lower pathological response rate (all P<0.05). The univariate analysis and multivariate analysis showed that higher HS-mGPS, presence of local lymph-node metastasis and non R0 resection were associated with poorer DFS and OS (P<0.05). Conclusion: HS-mGPS can be used to predict the benefits of neoadjuvant chemotherapy and as an independent prognostic factor for survival in patients with advanced gastric cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Proteína C-Reativa/análise , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Compostos Organoplatínicos/administração & dosagem , Prognóstico , Estudos Retrospectivos , Albumina Sérica/análise , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: The nonessential amino acid cysteine is known to be involved in many antioxidant and anticarcinogenic pathways. Cysteinylglycine is a pro-oxidant metabolite of glutathione and a precursor of cysteine. OBJECTIVE: To examine the relation between serum cysteine and cysteinylglycine and risk of gastric adenocarcinomas, esophageal squamous cell carcinomas, and head and neck squamous cell carcinomas, we conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study of male Finnish smokers aged 50-69 y at baseline. DESIGN: In total, 170 gastric adenocarcinomas, 68 esophageal squamous cell carcinomas, and 270 head and neck squamous cell carcinomas (identified from the Finnish Cancer Registry) were matched one-to-one with cancer-free control subjects on age and the date of serum collection. We calculated ORs and 95% CIs with the use of a multivariate-adjusted conditional logistic regression. RESULTS: Cysteine had a U-shaped association with gastric adenocarcinomas; a model that included a linear and a squared term had a significant global P-test (P = 0.036). Serum cysteinylglycine was inversely associated with adenocarcinomas of the gastric cardia (OR for above the median compared with below the median: 0.07; 95% CI: 0.01, 0.70; n = 38 cases) but not for other sites. Both cysteine and cysteinylglycine were not associated with esophageal squamous cell carcinoma or head and neck squamous cell carcinoma. CONCLUSIONS: We observed associations between serum cysteine and cysteinylglycine with upper gastrointestinal cancer risk. Future studies are needed to replicate these findings. This trial was registered at clininicaltrials.gov as NCT00342992.
Assuntos
Adenocarcinoma/etiologia , Cisteína/sangue , Deficiências Nutricionais/fisiopatologia , Dipeptídeos/sangue , Hiper-Homocisteinemia/fisiopatologia , Fumar/efeitos adversos , Neoplasias Gástricas/etiologia , Adenocarcinoma/sangue , Adenocarcinoma/epidemiologia , Adenocarcinoma/prevenção & controle , Antioxidantes/uso terapêutico , Biomarcadores/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/prevenção & controle , Estudos de Casos e Controles , Estudos de Coortes , Cisteína/deficiência , Deficiências Nutricionais/etiologia , Suplementos Nutricionais , Finlândia/epidemiologia , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/prevenção & controle , Humanos , Hiper-Homocisteinemia/etiologia , Incidência , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Fatores de Risco , Neoplasias Gástricas/sangue , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/prevenção & controleRESUMO
AIM: To evaluate the epithelial-to-mesenchymal transition (EMT) of circulating tumor cells (CTCs) in gastric cancer patients. METHODS: We detected tumor cells for expression of four epithelial (E(+)) transcripts (keratins 8, 18, and 19 and epithelial cell adhesion molecule) and two mesenchymal (M(+)) transcripts (Vimentin and Twist) by a quantifiable, dual-colorimetric RNA-in situ hybridization assay. Between July 2014 and October 2014, 44 patients with gastric cancer were recruited for CTC evaluation. Blood samples were obtained from selected patients during the treatment course [before surgery, after surgery and at the 6(th) cycle of XELOX based chemotherapy (about 6 mo postoperatively)]. RESULTS: We found the EMT phenomenon in which there were a few biphenotypic E(+)/M(+) cells in primary human gastric cancer specimens. Of the 44 patients, the presence of CTCs was reported in 35 (79.5%) patients at baseline. Five types of cells including from exclusively E(+) CTCs to intermediate CTCs and exclusively M(+) CTCs were identified (4 patients with M(+) CTCs and 10 patients with M(+) or M(+) > E(+) CTCs). Further, a chemotherapy patient having progressive disease showed a proportional increase of mesenchymal CTCs in the post-treatment blood specimens. We used NCI-N87 cells to analyze the linearity and sensitivity of CanPatrol(TM) system and the correlation coefficient (R(2)) was 0.999. CONCLUSION: The findings suggest that the EMT phenomenon was both in a few cells of primary tumors and abundantly in CTCs from the blood of gastric cancer patients, which might be used to monitor therapy response.
Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Transição Epitelial-Mesenquimal , Gastrectomia , Células Neoplásicas Circulantes/patologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adenocarcinoma/sangue , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Capecitabina , Estudos de Casos e Controles , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Monitoramento de Medicamentos/métodos , Feminino , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , Humanos , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/metabolismo , Oxaloacetatos , Fenótipo , Neoplasias Gástricas/sangue , Neoplasias Gástricas/genética , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The aim of the present study was to evaluate the clinical significance of protein-bound polysaccharide K (PSK) in patients with primary gastric cancer who were being treated with an oral fluoropyrimidine (S-1). METHODS: Clinical reports of 190 gastric cancer patients treated with S-1 chemotherapy, with or without PSK, at Kochi Medical School between 2007 and 2012 were investigated retrospectively to analyze survival. The neutrophil:lymphocyte ratio (NLR) was also evaluated as indicator of the immunoenhancing effect of PSK. RESULTS: Overall survival was significantly longer in patients treated with S-1 + PSK than in those given S-1 alone (hazard ratio for death, 0.608; 95% confidence interval 0.375-0.985; P = 0.041). Furthermore, there was a tendency for changes in the NLR during chemotherapy to be lower in the S-1 + PSK group than in the S-1 group, but the difference did not reach statistical significance (P = 0.054). When patients were divided into groups based on preoperative NLR (i.e. <2.5 and ≥2.5), the mean (±SEM) NLR 1 month after the beginning of chemotherapy in the NLR ≥2.5 subgroup was significantly lower in patients treated with S-1 + PSK rather than S-1 alone (1.7 ± 0.7 vs. 3.3 ± 4.1, respectively; P = 0.043). CONCLUSIONS: Immunochemotherapy using PSK improves the survival of patients with advanced gastric cancer. The NLR may be a useful biomarker for evaluating prognosis in these patients.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos , Neutrófilos , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/sangue , Adenocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Combinação de Medicamentos , Feminino , Proteínas Fúngicas/administração & dosagem , Proteínas Fúngicas/imunologia , Humanos , Imunoterapia , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Polissacarídeos/administração & dosagem , Polissacarídeos/imunologia , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Tegafur/administração & dosagemRESUMO
BACKGROUND: Traditional Uighur medicine shares an origin with Greco-Arab medicine. It describes the health of a human body as the dynamic homeostasis of four normal Hilits (humours), known as Kan, Phlegm, Safra, and Savda. An abnormal change in one Hilit may cause imbalance among the Hilits, leading to the development of a syndrome. Abnormal Savda is a major syndrome of complex diseases that are associated with common biological changes during disease development. Here, we studied the protein expression profile common to tumour patients with Abnormal Savda to elucidate the biological basis of this syndrome and identify potential biomarkers associated with Abnormal Savda. METHODS: Patients with malignant tumours were classified by the diagnosis of Uighur medicine into two groups: Abnormal Savda type tumour (ASt) and non-Abnormal Savda type tumour (nASt), which includes other syndromes. The profile of proteins that were differentially expressed in ASt compared with nASt and normal controls (NC) was analysed by iTRAQ proteomics and evaluated by bioinformatics using MetaCore™ software and an online database. The expression of candidate proteins was verified in all plasma samples by enzyme-linked immunosorbent assay (ELISA). RESULTS: We identified 31 plasma proteins that were differentially expressed in ASt compared with nASt, of which only 10 showed quantitatively different expression between ASt and NC. Bioinformatics analysis indicated that most of these proteins are known biomarkers for neoplasms of the stomach, breast, and lung. ELISA detection showed significant upregulation of plasma SAA1 and SPP24 and downregulation of PIGR and FASN in ASt compared with nASt and NC (p < 0.05). CONCLUSIONS: Abnormal Savda may be causally associated with changes in the whole regulation network of protein expression during carcinogenesis. The expression of potential biomarkers might be used to distinguish Abnormal Savda from other syndromes.
Assuntos
Proteínas Sanguíneas/metabolismo , Medicina Tradicional , Neoplasias/sangue , Biomarcadores/sangue , Pesquisa Biomédica , Neoplasias da Mama/sangue , Estudos de Casos e Controles , Biologia Computacional , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Estudos Prospectivos , Proteômica , Neoplasias Gástricas/sangue , SíndromeRESUMO
AIM: To investigate the molecular mechanisms of miRNA in advanced gastric cancers (AGCs) before and after cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A miRNA microarray containing human mature and precursor miRNA sequences was used to compare expression profiles in serum samples of 5 patients with AGC before and after CRS + HIPEC. The upregulation of miR-218 was confirmed by real-time reverse transcription polymerase chain reaction and its expression was analyzed in SGC7901 gastric cancer cells. RESULTS: miRNA microarray chip analysis found that the level of miR-218 expression was upregulated more than 8 fold after CRS + HIPEC. Furthermore, miR-218 increased gastric cancer cell chemosensitivity to cisplatin in vitro and inhibited gastric cell tumor growth in nude mice in vivo (0.5 vs 0.78, P < 0.05). CONCLUSION: Our results indicated that targeting miR-218 may provide a strategy for blocking the development of gastric cancer and reverse the multi-drug resistance of gastric cell lines.