scholarly journals A preliminary evaluation of oxidative stress in patients with gastric cancer before chemotherapy

2021 ◽  
Author(s):  
Jarosław Jakubik ◽  
Joanna Kołodziejczyk-Czepas ◽  
Magdalena Kędzierska ◽  
Michał Kaczmarek ◽  
Paweł Nowak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gastric Cancer ◽  
Blood Plasma ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Control Group ◽  
Lipid Hydroperoxides ◽  
Thiol Groups ◽  
Gastric Cancer Patients ◽  
In Blood Plasma

IntroductionBackground: Due to an imbalanced redox status, cancer cells generate intrinsically higher levels of reactive oxygen species (ROS), compared to normal cells. Targeting ROS is an important therapeutic strategy for cancer as exemplified by cancer drugs, which induce ROS-dependent synergistic cytotoxicity in gastric cancer cells. The present study was designed to assess the level of selected oxidative stress biomarkers in blood plasma, derived from gastric cancer patients.Material and methodsThe study included the assessment of the oxidative/nitrative biomarkers in blood plasma isolated form 51gastric (adenocarcinoma) cancer patients, compared to a control group of 32 healthy volunteers. Oxidative stress was evaluated using a panel of biomarkers such as plasma protein thiol groups and 3-nitrotyrosine levels as well as indicators of plasma lipid peroxidation, i.e. lipid hydroperoxides (LOOH) and thiobarbituric acid-reactive substances (TBARS). Additionally, the total antioxidant capacity of blood plasma (non-enzymatic capacity of blood plasma, NEAC) was also estimated.ResultsOur results showed that patients with gastric cancer had changed levels of thiol groups (a decrease, p<0.001) and 3-nitrotyrosine (an increase, p<0.0001), LOOH (an increase, p<0.05), TBARS (an increase, p<0.05), NEAC (a decrease, p<0.0001), compared to the control group.ConclusionsThe presented study indicates on a considerable oxidative/nitrative stress in gastric cancer patients. Our pilot study shows that not a single marker, but a biomarkers panel may be a more reliable representation of oxidative stress in patients with gastric cancer.

SOLUBLE FORMS OF PD-1 AND PD-L1 IN BLOOD PLASMA OF GASTRIC CANCER PATIENTS AND THEIR ASSOCIATIONS WITH CLINICAL AND MORPHOLOGICAL CHARACTERISTICS OF THE DISEASE

2020 ◽  
Vol 65 (6) ◽  
pp. 347-352 ◽  
Author(s):  
E. S. Gershtein ◽  
N. A. Ognerubov ◽  
V. L. Chang ◽  
V. V. Delektorskaya ◽  
E. A. Korotkova ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Blood Plasma ◽  
Cancer Patients ◽  
Cell Cancer ◽  
Morphological Characteristics ◽  
Control Group ◽  
Tnm System ◽  
Healthy Donors ◽  
Gastric Cancer Patients ◽  
In Blood Plasma

Results of comparative ELISA investigation of pretreatment sPD-1 and sPD-L1 content in blood plasma of 100 gastric cancer patients at various disease stages aged 25 to 81 years are presented. Control group included 60 practically healthy donors aged 18 - 68 years. Plasma sPD-L1 concentrations did not differ between gastric cancer patients and control group, and sPD-1 levels were statistically significantly lower in patients than in healthy donors (p<0.0001). Positive correlation (R=0.38; p=0.003) was revealed between plasma sPD-1 and sPD-L1 levels in control group and negative (R= -0.26; p=0,009) - in gastric cancer patients. ROC curve revealed the best sPD-1 cut-off level (< 21 pg/ml) with 77% sensitivity and 63.3% specificity, which is not sufficient for its application as diagnostic marker. Statistically significant increase of plasma sPD-L1 from stage I to stage IIIC (R=0.50; p=0.000011) was found. Analysis of associations between the evaluated markers’ levels and indices of gastric cancer expansion according to TNM system revealed statistically significant positive associations of plasma sPD-L1 levels with T (tumor invasion depth) and N (number of affected lymph nodes) indices: R=0.33; p=0.00093, and R=0.27; p=0.0099 respectively. sPD-L1 level was significantly increased in patients with low differentiated adenocarcinoma and cricoid-cell cancer as compared to highly differentiated adenocarcinoma (p=0.02 and p=0.004 respectively); in patients with cricoid-cell cancer it was also higher than in those with moderately differentiated adenocarcinoma (p=0.043) and undifferentiated cancer (p=0.049). Plasma sPD-1 level did not depend on disease stage, TNM system indices and tumor histological structure. Thus, soluble ligand sPD-L1, but not its receptor sPD-1, plasma level is increased in patients with unfavorable clinical and morphological characteristics, may be regarded as potentially valuable prognostic factor for gastric cancer patients’ survival, and probably as a predictor of anti - PD-1/PD-L1 treatment efficiency.

Prognostic significance of soluble forms of immune checkpoint PD-1/PDL1 receptor and ligand in blood plasma of gastric cancer patients

2021 ◽  
Vol 66 (3) ◽  
pp. 139-146
Author(s):  
Nikolay Evgenievich Kushlinskii ◽  
E. S. Gershtein ◽  
V. L. Chang ◽  
E. A. Korotkova ◽  
A. A. Alferov ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Blood Plasma ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Prognostic Significance ◽  
Specific Treatment ◽  
Long Term Treatment ◽  
Gastric Cancer Patients ◽  
In Blood Plasma

Analysis of long-term treatment results of 101 primary gastric cancer patients at various stages of the tumor process followed during 1 - 41 months (median - 6,4 months) from the onset of specific treatment are presented depending on the levels of soluble forms (s) of PD-1 receptor and its ligand PD-L1 in blood plasma. Overall survival assessed by Kaplan-Meyer analysis and with the help of Cox multiparametric regression model was applied as the criterion of prognostic value. It was found that at high (≥ 35 pg/ml) sPD-L1 levels in blood plasma, the overall survival of patients with gastric cancer was statistically significantly lower than at the marker’s levels below 35 pg / ml (p <0.045): 1-year survival comprised 78 and 96%, 2-year - 52 and 78%; 3-year - 40 and 61% at high and low sPD-L1 respectively. Median survival of patients with high plasma sPD-L1 comprised 29 months, of those with low sPD-L1 was not achieved during the whole follow-up period. This trend was observed not only in the total group of stage I-IV gastric cancer patients, but also in patients at the early stages of the disease, though sPD-L1 did not show an independent prognostic value in multiparametric model. At the same time, the overall survival of patients with gastric cancer did not depend on the baseline levels sPD-1 in blood plasma. Thus, soluble ligand sPD-L1 can be considered as a potentially valuable factor for prognosis of gastric cancer patients’ survival, and, probably, of anti-PD-1/PD-L1 treatment efficiency, but further studies and patients’ monitoring are required to prove this statement.

CLINICAL SIGNIFICANCE OF SERUM CAVEOLIN-1 LEVELS IN GASTRIC CANCER PATIENTS

2018 ◽  
Vol 40 (4) ◽  
pp. 323-327 ◽  
Author(s):  
F Tas ◽  
S Karabulut ◽  
K Erturk ◽  
D Duranyildiz
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Histological Grade ◽  
Clinical Importance ◽  
Disease Stage ◽  
Control Group ◽  
Tissue Samples ◽  
Caveolin 1 ◽  
Study Results ◽  
Gastric Cancer Patients

Aim: Caveolin-1 plays a significant role in the pathogenesis of various carcinomas and its expression affects the survival of cancer patients. However, the molecular function of caveolin-1 and its possible clinical importance has remained uncertain in gastric cancer. No clinical trial has examined serum caveolin-1 levels in gastric cancer patients so far, instead all available results were provided from studies conducted on tissue samples. In the current study, we analyzed the soluble serum caveolin-1 levels in gastric cancer patients, and specified its associations with the clinical factors and prognosis. Material and Methods: Sixty-three patients with pathologically confirmed gastric cancer were enrolled into the trial. Serum caveolin-1 concentrations were detected by ELISA method. Thirty healthy subjects were also included in the study. Results: The median age of patients was 62 years, ranging from 28 to 82 years. The serum caveolin-1 levels in gastric cancer patients were significantly higher than those in control group (p < 0.001). The common clinical parameters including patient age, sex, lesion localization, histopathology, histological grade, disease stage, and various serum tumor markers (e.g. LDH, CEA, and CA 19.9) were not found to be associated with serum caveolin-1 levels (p > 0.05). Similarly, no correlation existed between serum caveolin-1 concentration and chemotherapy responsiveness (p = 0.93). Furthermore, serum caveolin-1 level was not found to have a prognostic role (p = 0.16). Conclusion: Even though it is neither predictive nor prognostic, serum caveolin-1 level may be a valuable diagnostic indicator in patients with gastric cancer. Key

scholarly journals Down-regulation of HIF-1α inhibits the proliferation, migration, and invasion of gastric cancer by inhibiting PI3K/AKT pathway and VEGF expression

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Jingjing Zhang ◽  
Jun Xu ◽  
Yonghong Dong ◽  
Bo Huang
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Vegf Expression ◽  
Gastric Cancer Cells ◽  
Tumor Tissues ◽  
Sirna Silencing ◽  
Gastric Cancer Patients

In view of the high incidence of gastric cancer and the functions of hypoxia-inducible factor 1α (HIF-1α), our study aimed to investigate the functionality of HIF-1α in gastric cancer, and to explore the diagnostic and prognostic values of HIF-1α for this disease. Expression of HIF-1α in tumor tissues and adjacent healthy tissues as well as serum collected from both gastric cancer patients and normal healthy controls was detected by qRT-PCR. Survival analysis was performed using Kaplan–Meier method. HIF-1α siRNA silencing cell lines were established. Effects of HIF-1α siRNA silencing as well as PI3K activator sc3036 on proliferation, migration, and invasion of gastric cancer cells were detected by Cell counting kit (CCK-8) assay, and Transwell migration and invasion assay. Effects of HIF-1α siRNA silencing on AKT and VEGF were detected by Western blot. Expression of HIF-1α was significantly down-regulated in tumor tissues than in adjacent healthy tissues in most gastric cancer patients. Serum levels of HIF-1α were also higher in gastric cancer patients than in normal healthy people. Serum HIF-1α showed promising diagnostic and prognostic values for gastric cancer. HIF-1α siRNA silencing inhibited the proliferation, migration, and invasion of gastric cancer cells, while PI3K activator sc3036 treatment reduced those inhibitory effects. Down-regulation of HIF-1α can inhibit the proliferation, migration, and invasion of gastric cancer possibly by inhibiting PI3K/AKT pathway and VEGF expression.

The association of an exosomal form of PD-L1 with immunosuppressive activity and gastric cancer prognosis.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 47-47
Author(s):  
Yibo Fan ◽  
Xiaofang Che ◽  
Zhi Li ◽  
Xiujuan Qu ◽  
Yunpeng Liu
Keyword(s):  
Gastric Cancer ◽  
Cell Membrane ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Gastric Cancer Cell ◽  
Tumor Cell Membrane ◽  
Gastric Cancer Cell Lines ◽  
Gastric Cancer Patients

47 Background: The greatest challenge in cancer immunotherapy is to identify efficient predictive biomarkers to select patients for treatment. Though tumor cell membrane PD-L1 has been most anticipated, tumor cell membrane PD-L1 does not correlate with higher response rates and predict for clinical benefit. Subsequently studies showed that the prognostic value of tumor cell membrane PD-L1 in cancer patients remains controversial. In addition to membrane-associated PD-L1, tumor cell also secreted extracellular soluble PD-L1 in the microenvironment. However, even if extracellular soluble PD-L1 was detected, it did not solve the problem mentioned above. In the present study, we discovered another form of PD-L1 in extracellular microenvironment in cancer cells, that is exosomal PD-L1. However, the predictive role and the effect of tumor-derived exosomal PD-L1 is unclear. Methods: We evaluated the prognostic value of exosomal PD-L1 in the plasma of gastric cancer patients by ELISA and the effect of exosomal PD-L1-derived from gastric cancer cell lines by Western blot and Flow cytometry analysis. Results: Exosomal PD-L1 was detected in plasma samples from 69 gastric cancer patients, and exosomal PD-L1 content was significantly associated with T stage (P = 0.012). Overall Survival was significantly lower in the high exosomal PD-L1 group (p = 0.021). Additionally, gastric cancer cells also secreted exosomal PD-L1, with the amounts positively associated with PD-L1 amounts in the corresponding gastric cancer cell lines. Besides, exosomal PD-L1 was more stable and showed stronger immunosuppressive effects in the microenvironment compared with soluble PD-L1. Conclusions: Exosomal PD-L1 might predict the survival in gastric cancer, and induces higher T-cell apoptosis levels compared with soluble PD-L1.

PILGRIM: Phase III clinical trial in evaluating the role of hyperthermic intraperitoneal chemotherapy for locally advanced gastric cancer patients after radical gastrectomy with D2 lymphadenectomy(HIPEC-01).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4538-4538
Author(s):  
Shu-zhong Cui ◽  
Han Liang ◽  
Yong Li ◽  
Yanbing Zhou ◽  
Kaixiong Tao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Locally Advanced ◽  
Control Group ◽  
Radical Gastrectomy ◽  
Node Dissection ◽  
D2 Lymph Node Dissection ◽  
Locally Advanced Gastric Cancer ◽  
Gastric Cancer Patients

4538 Background: Gastric cancer remains the 3rd leading cancer related death worldwide due to early disease recurrence. We hypothesize that hyperthermic intraperitoneal chemotherapy (HIPEC) may effectively prevent local regional recurrence for locally advanced gastric cancer patients who received curative intent surgery. Methods: Pathology proven gastric cancer patients with clinical T3/T4NxM0 disease are eligible for the study and will be randomized to either control group, who will receive standard radical gastrectomy and D2 lymph node dissection or HIPEC group, who will receive the same surgery and HIPEC with paclitaxel x 2 within the first week after surgery. All patients will receive either XELOX or SOX adjuvant chemotherapy. The primary end point is overall survival. Results: 648 patients from 16 high volume gastric medical centers were enrolled between May, 2015 and March, 2019. 331 and 317 patients were randomized to control and HIPEC groups respectively. The median follow-up time is 12.1 months. The common grade 3/4 toxicities ( > 5%) in control and HIPEC groups are anemia 6% vs. 4.1%, intraabdominal infection 5.4% vs. 3.8%, pneumonia 9.7% vs. 9.8%, fever 10.6% vs. 11.4% and hypoalbunemia 15.1% vs. 16.7% respectively. All three perioperative death (within 30 days after surgery) occurred in control group. One patient died from duodenum stump leak which led to multiple organ failure. One patient died from anastomotic led to intraabdominal infection and shock. The 3rd death was suicide caused by severe depression. At the time of this report, the number of event has not reached for final efficacy analysis. Conclusions: It is safe to administer HIPEC to patients received radical gastrectomy with D2 lymph node dissection within one week of surgery. The primary analysis will be expected in one year. Clinical trial information: NCT02356276 .

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