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 ◽  
...  

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.

Author(s):  
Jarosław Jakubik ◽  
Joanna Kołodziejczyk-Czepas ◽  
Magdalena Kędzierska ◽  
Michał Kaczmarek ◽  
Paweł Nowak ◽  
...  

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.


2021 ◽  
Vol 66 (3) ◽  
pp. 139-146
Author(s):  
Nikolay Evgenievich Kushlinskii ◽  
E. S. Gershtein ◽  
V. L. Chang ◽  
E. A. Korotkova ◽  
A. A. Alferov ◽  
...  

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.


2018 ◽  
Vol 40 (4) ◽  
pp. 323-327 ◽  
Author(s):  
F Tas ◽  
S Karabulut ◽  
K Erturk ◽  
D Duranyildiz

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


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4538-4538
Author(s):  
Shu-zhong Cui ◽  
Han Liang ◽  
Yong Li ◽  
Yanbing Zhou ◽  
Kaixiong Tao ◽  
...  

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 .


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Min Wang ◽  
Shujuan Wang ◽  
Qiang Su ◽  
Tian Ma

Objective. To explore the clinical efficacy of combining early chemotherapy with Zhipu Liujunzi decoction under the concept of strengthening and consolidating body resistance for gastric cancer patients and nursing strategy. Methods. The clinical data of 100 patients undergoing radical gastrectomy in our hospital from July 2019 to July 2020 were selected for the retrospective analysis, and the patients were divided into the control group and experimental group according to different treatment methods, with 50 cases in each group. Early chemotherapy after surgery was given to patients in the control group, and on the basis of the aforesaid treatment and under the concept of strengthening and consolidating body resistance, patients in the experimental group took Zhipu Liujunzi decoction and received the nursing strategy, so as to compare their effective rate, adverse reaction rate (ARR), immune function indicators, KPS scores, and nursing satisfaction scores. Results. After treatment, the experimental group obtained significantly higher objective remission rate (ORR) and disease control rate (DCR) ( P < 0.05 ), lower carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels ( P < 0.001 ), higher immune parameters levels ( P < 0.001 ), higher KPS scores and lower TCM symptom scores ( P < 0.001 ), lower PSQI scores, SAS scores, and SDS scores ( P < 0.001 ) and higher nursing satisfaction scores ( P < 0.001 ), and lower total accidence rate of toxic side effects ( P < 0.05 ) than the control group. Conclusion. Under the concept of strengthening and consolidating body resistance, combining early chemotherapy with Zhipu Liujunzi decoction is a reliable method for improving the immune function and quality of life for gastric cancer patients with higher safety. Such a strategy greatly reduces the tumor marker levels in patients. Further research will be conducive to establishing a better solution for gastric cancer patients.


2017 ◽  
Vol 42 (5) ◽  
Author(s):  
Soykan Arikan ◽  
Alper Gümüş ◽  
Özlem Küçükhüseyin ◽  
Cihan Coşkun ◽  
Saime Turan ◽  
...  

AbstractObjective:Gastric cancer is one of the most common malignancies worldwide. The risk factors for gastric cancer include environmental and genetic factors. Inflammation and the immune system are known to contribute to the development of the gastric cancer. We examined the influence of critical polymorphisms of CTLA-4 and CD28 genes and circulating protein levels on the etiology of gastric cancer.Methods:Genotyping of SNPs was performed in 55 gastric cancer patients and 105 healthy individuals using the PCR-RFLP method, and circulating levels of sCTLA-4 and sCD28 were measured.Results:There were no significant differences in the genotype and allele distributions of the evaluated SNPs [CTLA-4-318 C>T (rs5742909), CTLA-4+49 A>G (rs231775), CD28 C>T (rs3116496)] between gastric cancer patients and controls (p=0.36, p=0.78, and p=0.80, respectively). The circulating levels of sCTLA-4 and sCD28 were significantly different between the gastric cancer group and the control group (p<0.001 and p<0.001, respectively).Conclusion:The present results suggest that the CTLA-4 and CD28 gene polymorphisms that were evaluated do not play an important role in Turkish patients with gastric cancer. However, sCTLA4 and sCD28 levels were higher in cancer patients and may be useful as an auxiliary parameter in the diagnosis and monitoring of gastric cancer.


2013 ◽  
Vol 7 (1) ◽  
pp. 72-79
Author(s):  
Ahmed Rushdi Abdullah ◽  
Shaimaa Yousif Abdulfattah ◽  
Farah Thamer Abdullah ◽  
Ali Talib Abid ◽  
Hussam Bassim Salah

Gastrointestinal cancers (GITs) are worldwide problem particularly in highly developed countries. In Iraq, gastric cancer(GC) is the 9th most common cancer while colorectal cancers (CRC) is considered as the 7th most common cancer among all cancer patients in both males and females. The Objective of this study was to estimate the serum level of transforming growth factor beta 2 (TGF-β) in Iraqi patients who are complying from gastric and colorectal cancers. Fifty four serum samples were collected starting from the 1st of March till the mid of May of 2011 to investigate the TGF-β serum level by using ELISA technique. Thirty eight samples were gastric (H.pylori +ve) and colorectal cancer patients (GC=17, CRC=21) while the other 16 samples considered as a healthy control group. The results showed that TGF-β serum levels of both GIT tumors were increased significantly (p<0.05) compared to the healthy control group. In conclusion, the presented study showed elevated serum level of TGF-β in Gastric cancer patients which could point out to use this elevation as a biomarker for tumor prognosis; while in colorectal cancer it may evade the immune system cancer killing mechanisms. We recommend further studies concerning the correlation between serum level of TGF-β in Gastric cancer patients with staging and grading, and more immunological techniques can be implied to know the exact immunological evading mechanism of colorectal cancer cells.


2020 ◽  
Author(s):  
Yulong Tian ◽  
Shougen Cao ◽  
Leping Li ◽  
Qingsi He ◽  
Lijian Xia ◽  
...  

Abstract Background: As well known, the incidence of gastric cancer in East Asian countries is much higher than the international average. Therefore, improving the prognosis of patients and establishing effective clinical pathways are important topics for the prevention and treatment of gastric cancer. At present, the enhanced recovery after surgery (ERAS) pathway is widely used in the field of gastric surgery. Many RCT studies have proven that the ERAS regimen can not improve the short-term clinical outcomes of gastric cancer patients. However, a prospective study on the effect of the ERAS pathway on the prognosis of gastric cancer patients has not been reported. This trial aims to confirm whether ERAS pathway can improve disease-free survival (DFS) and overall survival (OS) in patients undergoing laparoscopic-assisted radical resection for distal gastric cancer.Methods/design: This study is a prospective, multicenter, randomized controlled trial (RCT). This experiment will include randomly divided groups, the experimental group and the control group, according to a proportion of 1:1. The perioperative period of the experimental group will be managed according to the ERAS pathway, and the control group will be managed according to the traditional management mode. An estimated 400 patients will be enrolled. The main endpoint is to compare the 3-year OS and PFS between the two groups.Discussion: This RCT should demonstrate whether ERAS pathway is superior to traditional treatment on inflammatory indexes, short-term clinical outcome and survival for laparoscopic assisted radical resection of distal gastric cancer.Our data can provide evidence that the ERAS pathway improves survival in patients with gastric cancer.Trial registration: Chinese Clinical Trial Registry, CHiCTR1900022438. Registered on 11 April 2019


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