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1.
Pak J Pharm Sci ; 37(2(Special)): 443-450, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38822548

ABSTRACT

Gastric cancer remains a global health concern, driving the exploration of natural products with anticancer potential. This study investigated the antiproliferative activity and chemical composition of a 70% ethanolic extract from Melissa officinalis L. against human gastric cancer cells. The extract was prepared and evaluated for total phenolic content, antioxidant capacity and flavonoid content. The MTT test checked how well it stopped the growth of human gastric adenocarcinoma (AGS) and normal dermal fibroblast (HDF) cells. Data analysis (SPSS Statistics) determined viable cell percentages and performed regression analysis (p<0.05). The extract exhibited significant antiproliferative activity against AGS cells compared to normal cells (p<0.05), with decreasing IC50 values (564.3, 258.0 and 122.5 µg/ml) over 24, 48 and 72 hours. It also displayed antioxidant activity (IC50=16.8±1.41µg/ml) and contained substantial phenolics (225.76±4.1 mg GAE/g) and flavonoids (22.36±2.6 mg RUT/g). This study suggests the 70% ethanolic extract of M. officinalis effectively suppresses AGS cell growth and possesses promising antioxidant properties, highlighting its potential as a natural source of anticancer and antioxidant agents, deserving further investigation.


Subject(s)
Adenocarcinoma , Antineoplastic Agents, Phytogenic , Antioxidants , Cell Proliferation , Melissa , Phenols , Plant Extracts , Stomach Neoplasms , Humans , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Melissa/chemistry , Phenols/pharmacology , Phenols/analysis , Cell Line, Tumor , Antioxidants/pharmacology , Antioxidants/isolation & purification , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Proliferation/drug effects , Flavonoids/pharmacology , Flavonoids/analysis , Cell Survival/drug effects
2.
Sci Rep ; 14(1): 13127, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849404

ABSTRACT

Improvement in the survival rate of gastric cancer, a prevalent global malignancy and the leading cause of cancer-related mortality calls for more avenues in molecular therapy. This work aims to comprehend drug resistance and explore multiple-drug combinations for enhanced therapeutic treatment. An endogenous network modeling clinic data with core gastric cancer molecules, functional modules, and pathways is constructed, which is then transformed into dynamics equations for in-silicon studies. Principal component analysis, hierarchical clustering, and K-means clustering are utilized to map the attractor domains of the stochastic model to the normal and pathological phenotypes identified from the clinical data. The analyses demonstrate gastric cancer as a cluster of stable states emerging within the stochastic dynamics and elucidate the cause of resistance to anti-VEGF monotherapy in cancer treatment as the limitation of the single pathway in preventing cancer progression. The feasibility of multiple objectives of therapy targeting specified molecules and/or pathways is explored. This study verifies the rationality of the platform of endogenous network modeling, which contributes to the development of cross-functional multi-target combinations in clinical trials.


Subject(s)
Stomach Neoplasms , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/metabolism , Humans , Drug Resistance, Neoplasm , Models, Biological , Molecular Targeted Therapy/methods , Cluster Analysis , Principal Component Analysis , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Signal Transduction/drug effects
4.
Article in English | MEDLINE | ID: mdl-38839368

ABSTRACT

Esophagogastric junction cancer (EGJC) is a rare malignant disease that occurs in the gastroesophageal transition zone. In recent years, its incidence has been rapidly increasing not only in Western countries but also in East Asia, and it has been attracting the attention of both clinicians and researchers. EGJC has a worse prognosis than gastric cancer (GC) and is characterized by complex lymphatic drainage pathways in the mediastinal and abdominal regions. EGJC was previously treated in the same way as GC or esophageal cancer, but, in recent years, it has been treated as an independent malignant disease, and treatment focusing only on EGJC has been developed. A recent multicenter prospective study revealed the frequency of lymph node metastasis by station and established the optimal extent of lymph node dissection. In perioperative treatment, the combination of multi-drug chemotherapy, radiation therapy, molecular targeted therapy, and immunotherapy is expected to improve the prognosis. In this review, we summarize previous clinical trials and their important evidence on surgical and perioperative treatments for EGJC.


Subject(s)
Esophageal Neoplasms , Esophagectomy , Esophagogastric Junction , Humans , Esophagogastric Junction/surgery , Esophagogastric Junction/pathology , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophageal Neoplasms/mortality , Esophageal Neoplasms/therapy , Treatment Outcome , Esophagectomy/adverse effects , Esophagectomy/mortality , Gastrectomy/mortality , Gastrectomy/adverse effects , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Stomach Neoplasms/therapy , Lymph Node Excision , Chemotherapy, Adjuvant , Lymphatic Metastasis , Risk Factors , Neoadjuvant Therapy/adverse effects , Neoadjuvant Therapy/mortality
5.
Crit Rev Eukaryot Gene Expr ; 34(5): 69-79, 2024.
Article in English | MEDLINE | ID: mdl-38842205

ABSTRACT

Gastric cancer is a most malignancy in digestive tract worldwide. This study aimed to investigate the roles of protein arginine methyltransferase 6 (PRMT6) in gastric cancer. Immunohistochemistry was performed to detect PRMT6 expression in gastric tumors. Real-time transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to detected mRNA levels. Protein expression was determined using western blot. Gastric cancer cells were co-cultured with CD8+ T cells. Colony formation assay was performed to detect cell proliferation. Flow cytometry was performed to determine CD8+ T cell function and tumor cell apoptosis. PRMT6 was overexpressed in gastric tumors. High level of PRMT6 predicted poor outcomes of gastric cancer patients and inhibition of CD8+ T cell infiltration. PRMT6 promoted proliferation of CD8+ T cells and enhanced its tumor killing ability. Moreover, PRMT6 upregulated annexin A1 (ANXA1) and promoted ANXA1 protein stability. ANXA1 overexpression suppressed the proliferation of CD8+ T cells and promoted tumor cell survival. PRMT6 functions as an oncogene in gastric cancer. PRMT6-mediated protein stability inhibits the infiltration of CD8+ T cells, resulting in immune evasion of gastric cancer. The PRMT6-ANXA1 may be a promising strategy for gastric cancer.


Subject(s)
Annexin A1 , CD8-Positive T-Lymphocytes , Cell Proliferation , Gene Expression Regulation, Neoplastic , Protein-Arginine N-Methyltransferases , Stomach Neoplasms , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Stomach Neoplasms/immunology , Stomach Neoplasms/metabolism , Humans , Protein-Arginine N-Methyltransferases/metabolism , Protein-Arginine N-Methyltransferases/genetics , Annexin A1/genetics , Annexin A1/metabolism , Cell Line, Tumor , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Up-Regulation , Apoptosis , Tumor Escape/genetics , Male , Immune Evasion , Female , Nuclear Proteins
6.
Zhonghua Bing Li Xue Za Zhi ; 53(6): 605-609, 2024 Jun 08.
Article in Chinese | MEDLINE | ID: mdl-38825907

ABSTRACT

Objective: To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. Methods: The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up. Results: Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features. Conclusions: Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.


Subject(s)
Hepatoblastoma , Kidney Neoplasms , Liver Neoplasms , Neoplasms, Multiple Primary , Rhabdoid Tumor , Stomach Neoplasms , Humans , Male , Child , Female , Child, Preschool , Neoplasms, Multiple Primary/genetics , Neoplasms, Multiple Primary/pathology , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/genetics , Infant , Stomach Neoplasms/pathology , Stomach Neoplasms/genetics , Rhabdoid Tumor/genetics , Rhabdoid Tumor/pathology , Hepatoblastoma/genetics , Hepatoblastoma/pathology , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma/diagnosis , Choroid Plexus Neoplasms/genetics , Choroid Plexus Neoplasms/pathology , Choroid Plexus Neoplasms/diagnosis , Adrenocortical Carcinoma/genetics , Adrenocortical Carcinoma/pathology , Adrenal Cortex Neoplasms/pathology , Adrenal Cortex Neoplasms/genetics , Teratoma/pathology , Teratoma/genetics , Teratoma/surgery , Brain Neoplasms/genetics , Brain Neoplasms/pathology , SMARCB1 Protein/genetics , MutL Protein Homolog 1/genetics , Neoplasms, Second Primary/pathology , Neoplasms, Second Primary/genetics , High-Throughput Nucleotide Sequencing , Neoplastic Syndromes, Hereditary/genetics , Neoplastic Syndromes, Hereditary/pathology
7.
Zhonghua Yi Xue Za Zhi ; 104(21): 2003-2006, 2024 Jun 04.
Article in Chinese | MEDLINE | ID: mdl-38825945

ABSTRACT

To investigate the clinical characteristics of metastatic tumors in small intestine. The clinical manifestations, imaging and endoscopic findings, treatment methods and follow-up of patients with small bowel metastatic tumors admitted to the First Affiliated Hospital of Zhengzhou University from January 1, 2018 to December 31, 2022 were retrospectively analyzed. A total of 10 patients were included, including 7 males and 3 females, aged 33-77 (56.4±12.6) years. The main clinical manifestations were intestinal obstruction (8 cases), such as abdominal pain, abdominal distension, nausea, vomiting, and reduced defecation. Some patients had intussusception (abdominal pain, vomiting, black stool and other symptoms, 1 case) or gastrointestinal bleeding (1 case) with early symptoms imperceptible. The primary tumors include gastric cancer (3 cases), malignant melanoma (2 cases), ovarian cancer (2 cases), colon cancer (1 case), rectal cancer (1 case), and lung cancer (1 case). Most of the primary tumors were poorly differentiated (6 cases) or moderately to poorly differentiated (2 cases). The median time from primary tumor surgery to detection of small bowel metastasis [M (Q1, Q3)] was 22 (18, 28) months.The metastatic lesions were single (6 cases) or multiple (4 cases), in both jejunum and ileum. Positron emission tomography-computed tomography (PET-CT, 3 cases) and endoscopy (2 cases) were helpful for detection of small intestinal metastases. The main treatment methods were surgical resection (9 cases), supplemented by radiotherapy, targeted drugs, immunotherapy, etc. Postoperative recurrence and metastasis occurred in some patients (5 cases). Most patients died within 4 to 29 months after diagnosis. Metastatic tumors in small intestine are rare in clinical practice with atypical early symptoms. The patients often present with complications such as intestinal obstruction, which is prone to delayed diagnosis and poor prognosis.


Subject(s)
Intestinal Neoplasms , Intestine, Small , Humans , Female , Middle Aged , Male , Aged , Intestine, Small/pathology , Adult , Retrospective Studies , Intestinal Neoplasms/pathology , Intestinal Obstruction/etiology , Melanoma/pathology , Stomach Neoplasms/pathology
8.
Zhonghua Yi Xue Za Zhi ; 104(21): 1979-1986, 2024 Jun 04.
Article in Chinese | MEDLINE | ID: mdl-38825941

ABSTRACT

Objective: To analyze the efficacy of alternate titanium clip closure in preventing postoperative complications for patients with gastric mucosal lesions after endoscopic submucosal dissection (ESD). Methods: Clinical data of patients with gastric mucosal lesions who underwent ESD in the Department of Gastroenterology, Zhongda Hospital, Southeast University, were retrospectively collected from January 1, 2013 to August 31, 2023. According to the postoperative wound closure status, the patients were divided into completely closed group (complete closure of ESD wounds using alternate titanium clip closure), partially closed group (partial closure of ESD wounds), and unclosed group (without use of clips for treatment of ESD wounds). The incidence of postoperative complications as well as wound healing at 1 month and 3 months after surgery were compared among three groups, and the factors related to delayed bleeding after ESD for gastric mucosal lesions were analyzed through multiple logistic regression analysis. Results: A total of 846 patients were included, 430 cases in the completely closed group, including 300 males and 130 females, age [M (Q1, Q3)] was 65(56, 72) years old; one hundred and nine cases in unclosed group, including 78 males and 31 females, aged 66 (60, 71) years; and 307 cases in the partially closed group, including 214 males and 93 females, aged 66 (59, 71) years. The difference in the rate of delayed postoperative bleeding between the completely closed group [2.1% (9/430)] and the unclosed group [5.5% (6/109)] was not statistically significant (P=0.072), but both were lower than that of the partially closed group [9.4% (29/307), P<0.05)]. Further stratified analysis showed that, for the lesions located in the lower 1/3 of the stomach, the rate of postoperative bleeding was lower in the completely closed group than in the partially closed and unclosed groups [0.9% (2/222) vs 11.4% (4/35) vs 9.5% (7/74), respectively, P<0.001]. For lesions≥50 mm in length, the rate of postoperative bleeding was lower in the completely closed group than that in the partially closed and unclosed group[0 vs 11.8% (2/17) vs 20.5% (15/73), respectively, P=0.004]. The incidence of postoperative abdominal pain in the completely closed group [84.2% (363/430)] was lower than that in the unclosed group [97.2% (106/109)] and the partially closed group [95.4% (293/307), both P<0.001)]. The score of postoperative abdominal pain in the completely closed group [0 (0, 1)], was lower than that in the unclosed group [3 (2, 3)], and that in the partially closed group [2 (1, 3)] (both P<0.001). The wound healing rate of the completely closed group [80% (176/220)] was higher than that of the unclosed group [52.3% (33/63)] and the partially closed group [52.2% (83/159)] at 1 month postoperatively (both P<0.001); the healing rate of all three groups reached 100% at 3 months postoperatively. Multiple logistic regression analysis showed that the presence of ulcers or scars on the surface of the lesion (OR=2.930, 95%CI:1.503-5.712, P=0.002), and the diameter (OR=1.031, 95%CI:1.015-1.047,P<0.001) were related factors for postoperative bleeding. Conclusions: The alternate titanium clip closure surgery can reduce postoperative abdominal pain and shorten wound healing time in patients with gastric mucosal lesions after ESD surgery. The risk of postoperative bleeding can be reduced for lesions with a diameter≥50 mm and located in the lower 1/3 of the stomach.


Subject(s)
Endoscopic Mucosal Resection , Gastric Mucosa , Postoperative Complications , Humans , Endoscopic Mucosal Resection/adverse effects , Endoscopic Mucosal Resection/methods , Male , Aged , Female , Gastric Mucosa/surgery , Postoperative Complications/prevention & control , Middle Aged , Surgical Instruments , Stomach Neoplasms/surgery , Titanium , Wound Healing , Gastroscopy
9.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 92-96, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38836675

ABSTRACT

The currest study aimed to measure the effects of laparoscopic radical gastrectomy on inflammatory response along with immune function in gastric cancer (GC) patients. Seventy patients with GC in our hospital were retrospectively chosen to be the study objects and separated into control group (CG, 35 cases) and observation group (OG, 35 cases). Patients in the OG received radical laparotomy. Patients in the OG received laparoscopic radical gastrectomy. The surgical indicators, postoperative recovery indicators, inflammatory factors, immune function, incidence of adverse reactions along with quality of life of patients in both groups were compared. In contrast to the CG, the operation time of the OG presented as shorter (P<0.05), and the amount of intraoperative blood loss together with postoperative VAS score in the OG presented lower (P<0.05), but the number of lymph nodes dissection presented not statistically significant between 2 groups (P>0.05). The postoperative exhaust time, feeding time as well as hospital stay in the OG presented shorter relative to the CG (P<0.05). The serum levels of CRP, and IL-6 together with TNF-α presented elevated in both groups after surgery, and those in the OG presented lower when compared with the CG (P<0.05). The serum levels of IgA, and IgG together with IgM presented declined in both groups after surgery, and those in the OG presented higher when compared with the CG (P<0.05). The incidence of postoperative complications in the OG presented reduction relative to the CG (P<0.05). The GLQI scores of the OG presented significantly higher relative to the CG at discharge (P<0.05). Compared with radical gastrectomy, laparoscopic radical gastrectomy is more suitable for the treatment of GC, which can reduce the inflammatory response and promote the immune function of GC patients.


Subject(s)
Gastrectomy , Inflammation , Laparoscopy , Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/immunology , Gastrectomy/methods , Gastrectomy/adverse effects , Laparoscopy/adverse effects , Laparoscopy/methods , Male , Female , Middle Aged , Inflammation/immunology , Aged , Quality of Life , Retrospective Studies , C-Reactive Protein/metabolism , Postoperative Complications/immunology , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Tumor Necrosis Factor-alpha/blood , Interleukin-6/blood
10.
Langenbecks Arch Surg ; 409(1): 174, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38837064

ABSTRACT

BACKGROUND: Despite being oncologically acceptable for esophagogastric junction adenocarcinoma with an esophageal invasion length of 3-4 cm, the transhiatal approach has not yet become a standard method given the difficulty of reconstruction in a narrow space and the risk of severe anastomotic leakage. This study aimed to clarify the safety and feasibility of the open left diaphragm method during the transhiatal approach for esophagogastric junction adenocarcinoma. METHODS: This retrospective study compared the clinical outcomes of patients who underwent proximal or total gastrectomy with lower esophagectomy for Siewert type II/III adenocarcinomas with esophageal invasion via the laparoscopic transhiatal approach with or without the open left diaphragm method from April 2013 to December 2021. RESULTS: Overall, 42 and 13 patients did and did not undergo surgery with the open left diaphragm method, respectively. The median operative time was only slightly shorter in the open left diaphragm group than in the non-open left diaphragm group (369 vs. 482 min; P = 0.07). Grade ≥ II postoperative respiratory complications were significantly less common in the open left diaphragm group than in the non-open left diaphragm group (17% vs. 46%, P = 0.03). Neither group had grade ≥ IV anastomotic leakage, and two cases of anastomotic leakage requiring reoperation were drained using the left diaphragmatic release technique. CONCLUSIONS: Transhiatal lower esophagectomy with gastrectomy using the open left diaphragm method is safe, highlighting its advantages for Siewert type II/III esophagogastric junction adenocarcinoma with an esophageal invasion length of ≤ 4 cm.


Subject(s)
Adenocarcinoma , Diaphragm , Esophageal Neoplasms , Esophagectomy , Esophagogastric Junction , Gastrectomy , Laparoscopy , Stomach Neoplasms , Humans , Esophagogastric Junction/surgery , Adenocarcinoma/surgery , Adenocarcinoma/pathology , Female , Male , Retrospective Studies , Middle Aged , Laparoscopy/methods , Esophageal Neoplasms/surgery , Esophageal Neoplasms/pathology , Aged , Gastrectomy/methods , Esophagectomy/methods , Diaphragm/surgery , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Plastic Surgery Procedures/methods
11.
Am J Gastroenterol ; 119(6): 1056-1065, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38832708

ABSTRACT

INTRODUCTION: Ultra-processed food (UPF) intake has been associated with a higher risk of obesity, hypertension, type 2 diabetes, and cardiovascular diseases. The initial data on the relationship between UPF consumption and cancer risk were derived from retrospective observational studies with conflicting results. This systematic review and meta-analysis of prospective cohort studies aimed to investigate the association between UPF consumption and gastrointestinal cancer risk. METHODS: PubMed, Embase, and Cochrane databases were searched for prospective cohort studies that compared the highest vs the lowest level of UPF consumption according to NOVA food classification and reported the risk of gastrointestinal cancers by subsite. The association with cancer was quantified as hazard ratios (HR) using a random-effects model. RESULTS: Five prospective cohort studies were included in this review comprising 1,128,243 participants (241,201 participants in the highest and 223,366 in the lowest levels of UPF consumption). The mean follow-up ranged from 5.4 to 28 years. The highest UPF consumption was significantly associated with an increased risk of colorectal cancer (HR 1.11; 95% confidence interval [CI] 1.03-1.21; P = 0.01; I2 = 31%), colon cancer (HR 1.12; 95% CI 1.02-1.23; P = 0.02; I2 = 0%), and non-cardia gastric cancer (HR 1.43; 95% CI 1.02-2.00; P = 0.04; I2 = 0%) compared with the lowest UPF intake. However, no association was found between high UPF consumption and hepatocellular, esophageal, pancreatic, gastric cardia, and rectal cancer. DISCUSSION: The highest level of UPF consumption was significantly associated with colorectal and non-cardia gastric cancer.


Subject(s)
Fast Foods , Gastrointestinal Neoplasms , Humans , Gastrointestinal Neoplasms/epidemiology , Gastrointestinal Neoplasms/etiology , Fast Foods/adverse effects , Risk Factors , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/etiology , Stomach Neoplasms/epidemiology , Stomach Neoplasms/etiology , Food, Processed
12.
J Robot Surg ; 18(1): 238, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833096

ABSTRACT

The objective of this meta-analysis was to assess the comparative efficacy of robot-assisted and laparoscopic surgery in treating gastric cancer among patients characterized by a high visceral fat area (VFA). In April 2024, we conducted a comprehensive literature review using major international databases, such as PubMed, Embase, and Google Scholar. We restricted our selection to articles written in English, excluding reviews, protocols without published data, conference abstracts, and irrelevant content. Our analysis focused on continuous data using 95% confidence intervals (CIs) and standard mean differences (SMDs), while dichotomous data were assessed with odds ratios (ORs) and 95% CIs. We set the threshold for statistical significance at P < 0.05. Data extraction included baseline characteristics, primary outcomes (such as operative time, major complications, lymph node yield, and anastomotic leakage), and secondary outcomes. The meta-analysis included three cohort studies totaling 970 patients. The robotic-assisted group demonstrated a significantly longer operative time compared to the laparoscopic group, with a weighted mean difference (WMD) of - 55.76 min (95% CI - 74.03 to - 37.50; P < 0.00001). This group also showed a reduction in major complications, with an odds ratio (OR) of 2.48 (95% CI 1.09-5.66; P = 0.03) and fewer occurrences of abdominal infections (OR 3.17, 95% CI 1.41-7.14; P = 0.005), abdominal abscesses (OR 3.83, 95% CI 1.53-9.57; P = 0.004), anastomotic leaks (OR 4.09, 95% CI 1.73-9.65; P = 0.001), and pancreatic leaks (OR 8.93, 95% CI 2.33-34.13; P = 0.001). However, no significant differences were observed between the groups regarding length of hospital stay, overall complications, estimated blood loss, or lymph node yield. Based on our findings, robot-assisted gastric cancer surgery in obese patients with visceral fat appears to be correlated with fewer major complications compared to laparoscopic surgery, while maintaining similar outcomes in other surgical aspects. However, it is important to note that robot-assisted procedures do tend to have longer operative times.


Subject(s)
Laparoscopy , Obesity, Abdominal , Operative Time , Robotic Surgical Procedures , Stomach Neoplasms , Humans , Laparoscopy/methods , Robotic Surgical Procedures/methods , Robotic Surgical Procedures/adverse effects , Stomach Neoplasms/surgery , Treatment Outcome , Obesity, Abdominal/complications , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Gastrectomy/methods , Anastomotic Leak/etiology , Anastomotic Leak/epidemiology
15.
Sci Rep ; 14(1): 12658, 2024 06 03.
Article in English | MEDLINE | ID: mdl-38830895

ABSTRACT

The combination of trifluridine/tipiracil hydrochloride (FTD/TPI) plus ramucirumab has demonstrated clinical activity in patients with advanced gastric cancer (AGC). We evaluated the efficacy and safety of this combination compared with those of FTD/TPI monotherapy in patients with AGC. We retrospectively reviewed data of patients with AGC who received FTD/TPI plus ramucirumab or FTD/TPI monotherapy as third- or later-line treatment. This study included 36 patients treated with FTD/TPI plus ramucirumab and 70 patients receiving FTD/TPI monotherapy. The objective response rate (ORR) and disease control rate (DCR) were 25.8% and 58.1%, respectively, in the FTD/TPI plus ramucirumab group and 5.0% and 38.3%, respectively, in the FTD/TPI group (ORR, P = 0.007; DCR, P = 0.081). The median progression-free survival (PFS) was significantly longer in the FTD/TPI plus ramucirumab group (median PFS, 2.9 vs. 1.8 months; hazard ratio [HR]: 0.52; P = 0.001). A numerical survival benefit was also observed (median overall survival, 7.9 months vs. 5.0 months; HR: 0.68, P = 0.089). In the multivariate analysis, PFS was significantly longer in the FTD/TPI plus ramucirumab group than in the FTD/TPI monotherapy group (HR: 0.61, P = 0.030). The incidence of febrile neutropenia was higher in the FTD/TPI plus ramucirumab group than in the FTD/TPI group (13.8% vs. 2.9%); however, no new safety signals were identified. Compared with FTD/TPI monotherapy, FTD/TPI plus ramucirumab offers clinical benefits with acceptable toxicity in heavily pretreated patients with AGC. Further investigation via randomized trials is warranted to confirm these findings.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Drug Combinations , Pyrrolidines , Ramucirumab , Stomach Neoplasms , Thymine , Trifluridine , Humans , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Male , Female , Middle Aged , Aged , Trifluridine/therapeutic use , Trifluridine/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Pyrrolidines/therapeutic use , Pyrrolidines/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Retrospective Studies , Adult , Aged, 80 and over , Treatment Outcome , Uracil/analogs & derivatives , Uracil/therapeutic use , Uracil/administration & dosage , Progression-Free Survival
16.
Sci Rep ; 14(1): 12758, 2024 06 04.
Article in English | MEDLINE | ID: mdl-38830909

ABSTRACT

Circulating tumor cells (CTCs) as a liquid biopsy have great potential in clinical applications and basic cancer research, but their clinical use in gastric cancer remains unclear. This study investigated whether CTCs could be used as a potential prognosis predictor in patients with gastric cancer. A total of 120 patients with pathologically confirmed gastric cancer were enrolled from January 1, 2015, to December 1, 2019. All patients were initially diagnosed without previous treatment, and then the number of CTCs was detected using the NEimFISH method before radical surgical resection. Regular follow-up was performed in all patients, and the correlations between the number of CTCs and clinical endpoints, such as disease-free survival (DFS) and overall survival (OS), were evaluated. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. Based on the number of CTCs, we defined CTCs ≥ 2 per 7.5 mL of whole blood as the positive group and CTCs < 2 as the negative group. Among the 120 patients who underwent CTC detection before surgery, the rate of CTC-positive patients was 64.17% (77/120) of which stage I and II patients accounted for 22.50% and stage III patients accounted for 41.67% (P = 0.014). By detecting CTCs before surgery and at the time of recurrence, the number of CTCs tends to increase concomitantly with disease progression (median: 2 VS 5 per 7.5 mL). Multivariate analysis showed that age (HR, 0.259; 95% CI, 0.101-0.662; P = 0.005), D-dimer (HR, 3.146; 95% CI, 1.169-8.461; P = 0.023), and lymph node metastasis (HR, 0.207; 95% CI, 0.0071-0.603; P = 0.004) were factors correlated with CTCs. In addition, the median follow-up of all the patients was 38.0 months (range of 28-80 months); the DFS in CTC-positive patients was significantly shorter than that of the CTC-negative patients, and a significant difference was found based on the Cox proportional hazard regression model analysis (44.52 ± 2.83 m vs. 74.99 ± 2.78 m, HR = 4.550, P = 0.018). The OS was shorter in the CTC-positive group than in the CTC-negative group before the operation, but the result was not significant based on the Cox proportional hazard regression model analysis (47.58 ± 2.46 m vs. 70.68 ± 3.53 m, HR = 2.261, P = 0.083). The number of CTCs tends to increase concomitantly with disease progression. In addition, the detection of CTCs was an independent predictor of shorter DFS in gastric cancer. However, the relationship between CTCs and OS needs to be determined in future studies.


Subject(s)
Neoplasm Recurrence, Local , Neoplastic Cells, Circulating , Stomach Neoplasms , Humans , Neoplastic Cells, Circulating/pathology , Stomach Neoplasms/pathology , Stomach Neoplasms/blood , Stomach Neoplasms/surgery , Stomach Neoplasms/mortality , Male , Female , Middle Aged , Aged , Neoplasm Recurrence, Local/pathology , Prognosis , Adult , Biomarkers, Tumor/blood , Disease-Free Survival , Neoplasm Staging , Proportional Hazards Models
17.
Cancer Rep (Hoboken) ; 7(6): e2101, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38831124

ABSTRACT

BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) is a rare and aggressive subtype of gastric cancer (GC), accounting for less than 1% of all cases. It is characterized by frequent liver metastasis recurrence and a poorer prognosis than conventional GC. However, established treatment guidelines for HAS are currently not available.In this report, we present the results of a clinicopathological study of 19 patients diagnosed with HAS, including seven patients with liver metastasis, conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO) between 2016 and 2018. AIMS: The aim of the study was to retrospectively observe the outcomes of HAS with gastrectomy and hepatectomy for liver metastasis and determine relevant prognostic factor. We also examined the criteria and outcomes of hepatectomy for liver metastasis and aimed to suggest the optimal treatment for HAS, including chemotherapy. METHODS AND RESULTS: A total of 2147 patients underwent gastrectomy for GC at HiSCO-affiliated institutions during the study period; 19 patients, all male with a mean age of 70.9 years, were diagnosed with HAS by hematoxylin-eosin and immunohistochemical staining. Patients underwent gastrectomy at varying pathological stages: six at Stage I, three at Stage II, seven at Stage III, and three at Stage IV. Ten patients received postoperative chemotherapy and the 5-year survival rate was 67.7% after gastrectomy. Among the seven patients with pre or postoperative liver metastasis, five patients underwent hepatectomy. Although one patient had recurrence, the 3-year survival rate was 100% after hepatectomy. CONCLUSION: Contrary to previous reports suggesting a 3-year survival rate of approximmately 30% for HAS, our findings indicate that the prognosis for HAS may not be as poor as reported previously. This study contributes valuable insights into the management and potential treatment strategies for HAS.


Subject(s)
Adenocarcinoma , Gastrectomy , Hepatectomy , Liver Neoplasms , Stomach Neoplasms , Humans , Male , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Stomach Neoplasms/therapy , Stomach Neoplasms/surgery , Retrospective Studies , Aged , Middle Aged , Adenocarcinoma/pathology , Adenocarcinoma/mortality , Adenocarcinoma/therapy , Adenocarcinoma/surgery , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Liver Neoplasms/mortality , Liver Neoplasms/therapy , Prognosis , Survival Rate , Aged, 80 and over , Neoplasm Staging , Neoplasm Recurrence, Local/pathology , Female
18.
Cancer Immunol Immunother ; 73(8): 151, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832951

ABSTRACT

BACKGROUND: Immunotherapy for gastric cancer remains a challenge due to its limited efficacy. Metabolic reprogramming toward glycolysis has emerged as a promising avenue for enhancing the sensitivity of tumors to immunotherapy. Pyruvate dehydrogenase kinases (PDKs) play pivotal roles in regulating glycolysis. The importance of PDKs in the context of gastric cancer immunotherapy and their potential as therapeutic targets have not been fully explored. METHODS: PDK and PD-L1 expression was analyzed using data from the GSE66229 and The Cancer Genome Atlas (TCGA) cohorts. Additionally, the Immune Checkpoint Blockade Therapy Atlas (ICBatlas) database was utilized to assess PDK expression in an immune checkpoint blockade (ICB) therapy group. Subsequently, the upregulation of PD-L1 and the enhancement of anticancer effects achieved by targeting PDK were validated through in vivo and in vitro assays. The impact of PDK on histone acetylation was investigated using ChIP‒qPCR to detect changes in histone acetylation levels. RESULTS: Our analysis revealed a notable negative correlation between PD-L1 and PDK expression. Downregulation of PDK led to a significant increase in PD-L1 expression. PDK inhibition increased histone acetylation levels by promoting acetyl-CoA generation. The augmentation of acetyl-CoA production and concurrent inhibition of histone deacetylation were found to upregulate PD-L1 expression in gastric cancer cells. Additionally, we observed a significant increase in the anticancer effect of PD-L1 antibodies following treatment with a PDK inhibitor. CONCLUSIONS: Downregulation of PDK in gastric cancer cells leads to an increase in PD-L1 expression levels, thus potentially improving the efficacy of PD-L1 immune checkpoint blockade therapy.


Subject(s)
B7-H1 Antigen , Glycolysis , Immunotherapy , Pyruvate Dehydrogenase Acetyl-Transferring Kinase , Stomach Neoplasms , Up-Regulation , B7-H1 Antigen/metabolism , Humans , Animals , Pyruvate Dehydrogenase Acetyl-Transferring Kinase/metabolism , Pyruvate Dehydrogenase Acetyl-Transferring Kinase/genetics , Stomach Neoplasms/metabolism , Stomach Neoplasms/immunology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Immunotherapy/methods , Mice , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Xenograft Model Antitumor Assays , Mice, Nude
19.
Cancer Immunol Immunother ; 73(8): 144, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832979

ABSTRACT

BACKGROUND: The beneficial effects of first-line programmed death-1 (PD-1) inhibitors plus chemotherapy in patients with low programmed death-ligand 1 (PD-L1)-expressing advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma are controversial. METHODS: We conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with PD-1 inhibitors plus chemotherapy between October 2017 and May 2022. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). SPSS software V27.0 was used for data analysis. RESULTS: Of 345 enrolled patients, 290 had measurable lesions. The overall ORR was 59.3%. PD-L1 status was available in 171 patients, and 67.8% of them were considered as low PD-L1 expression level (combined positive score (CPS) < 5). Patients with PD-L1 CPS < 5 showed a lower response rate (51.1% vs 70.8%, P = 0.024) and a worse PFS (P = 0.009) compared to those with PD-L1 CPS ≥ 5. In the PD-L1 low-expression cohort, patients with non-diffuse type, GEJ cancer, synchronous metastasis, distant lymph node metastasis, liver metastasis, non-peritoneal metastasis, and HER2 positive were significantly associated with higher response rates to PD-1 inhibitors plus chemotherapy (P < 0.05). The presence of peritoneal metastasis (P = 0.028) and diffuse type (P = 0.046) were identified as independent predictors of poor PFS in multivariate analysis of the PD-L1 CPS < 5 subgroup. When evaluated for correlation with overall survival (OS) in the PD-L1 low-expression subgroup, peritoneal metastasis was found to be the only independent prognostic factor of an increased risk of death (hazard ratio: 2.31, 95% CI 1.09-4.90; P = 0.029). CONCLUSIONS: PD-L1 CPS ≥ 5 is significantly associated with improved response and extended PFS in G/GEJ cancer patients treated with a combination of PD-1 inhibitors and chemotherapy. Specific subgroups within the low PD-L1-expressing population, such as those with non-diffuse-type tumors and without peritoneal metastases, may also benefit from immunotherapy combined with chemotherapy.


Subject(s)
Adenocarcinoma , Antineoplastic Combined Chemotherapy Protocols , B7-H1 Antigen , Biomarkers, Tumor , Esophageal Neoplasms , Esophagogastric Junction , Immune Checkpoint Inhibitors , Stomach Neoplasms , Humans , Male , Stomach Neoplasms/drug therapy , Stomach Neoplasms/metabolism , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Female , Middle Aged , Esophagogastric Junction/pathology , Esophagogastric Junction/metabolism , Adenocarcinoma/drug therapy , Adenocarcinoma/metabolism , Adenocarcinoma/mortality , Adenocarcinoma/pathology , B7-H1 Antigen/metabolism , B7-H1 Antigen/antagonists & inhibitors , Aged , Retrospective Studies , Biomarkers, Tumor/metabolism , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Immune Checkpoint Inhibitors/therapeutic use , Aged, 80 and over , Prognosis
20.
Cancer Immunol Immunother ; 73(8): 154, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833154

ABSTRACT

BACKGROUND: Alpha-fetoprotein elevated gastric cancer (AFPGC) got growing interests for its aggressive nature and unfavorable prognosis. Here, a phase 1 dose escalation study was conducted to evaluate safety and efficacy of zimberelimab (GLS-010, anti-PD-1) plus lenvatinib and chemotherapy (XELOX) as the first-line treatment for AFPGC. METHODS: Histologically confirmed HER2-negative, advanced GC patients with elevated serum AFP level (≥ 20 ng/ml) were screened. Using a 3 + 3 dose escalation design, patients were administered varying doses of lenvatinib (12, 16, 20 mg) with GLS-010 and XELOX. The primary endpoints were safety and determination of recommended phase II dose (RP2D). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and disease control rate. RESULTS: Nine patients were enrolled with no dose-limiting toxicities observed. Most frequent treatment-related AEs were fatigue (55.6%), hand-foot syndrome (55.6%) and rash (55.6%), and no grade ≥ 4 AEs were reported. All patients exhibited disease control with ORR reaching 33.3%. The median PFS and OS reached 7.67 months (95% CI 4.07-11.27) and 13.17 months (95% CI 2.78-23.56), respectively. Serum AFP level was found correlated with therapeutic responses. Further 16s rRNA sequencing analysis demonstrated altered gut microbiota with elevated abundance of Lachnospiraceae bacterium-GAM79 and Roseburia hominis A2-183. CONCLUSIONS: GLS-010 plus lenvatinib and XELOX demonstrated a manageable safety profile with promising efficacy for AFPGC. With RP2D of lenvatinib determined as 16 mg, further expansion cohort is now ongoing. Translational investigation suggested that serum AFP can be indictive for therapeutic responses and certain microbiota species indicating favorable responses to immunotherapy was elevated after the combinational treatment.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Phenylurea Compounds , Quinolines , Stomach Neoplasms , alpha-Fetoproteins , Humans , Quinolines/therapeutic use , Quinolines/administration & dosage , Male , Female , Middle Aged , Phenylurea Compounds/therapeutic use , Phenylurea Compounds/administration & dosage , Phenylurea Compounds/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Stomach Neoplasms/drug therapy , Stomach Neoplasms/mortality , Aged , alpha-Fetoproteins/metabolism , alpha-Fetoproteins/analysis , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Adult , Prognosis
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