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Oncology Research 2024Despite the availability of chemotherapy drugs such as 5-fluorouracil (5-FU), the treatment of some cancers such as gastric cancer remains challenging due to drug...
BACKGROUND
Despite the availability of chemotherapy drugs such as 5-fluorouracil (5-FU), the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects. This study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines (AGS and EPG85-257).
MATERIALS AND METHODS
In this study, AGS and EPG85-257 cells were treated with different concentrations of celastrol, 5-FU, and their combination. Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The synergistic effect of 5-FU and celastrol was studied using Compusyn software. The DNA content at different phases of the cell cycle and apoptosis rate was measured using flow cytometry.
RESULTS
Co-treatment with low concentrations (10% inhibitory concentration (IC10)) of celastrol and 5-FU significantly reduced IC50 ( < 0.05) so that 48 h after treatment, IC50 was calculated at 3.77 and 6.9 μM for celastrol, 20.7 and 11.6 μM for 5-FU, and 5.03 and 4.57 μM for their combination for AGS and EPG85-257 cells, respectively. The mean percentage of apoptosis for AGS cells treated with celastrol, 5-FU, and their combination was obtained 23.9, 41.2, and 61.9, and for EPG85-257 cells 5.65, 46.9, and 55.7, respectively. In addition, the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis phase.
CONCLUSIONS
Although celastrol could decrease the concentration of 5-fluorouracil that sufficed to suppress gastric cancer cells, additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol.
Topics: Humans; Pentacyclic Triterpenes; Fluorouracil; Stomach Neoplasms; Apoptosis; Cell Proliferation; Cell Line, Tumor; Triterpenes; Drug Synergism; Antineoplastic Combined Chemotherapy Protocols; Cell Cycle
PubMed: 38948023
DOI: 10.32604/or.2024.047187 -
Endoscopic Ultrasound 2024To compare the efficacy of EUS-guided celiac plexus neurolysis (CPN) and celiac plexus irradiation with iodine-125 (I) seeds with absolute ethanol for relieving pain in...
Clinical efficacy of EUS-guided celiac plexus neurolysis EUS-guided celiac ganglion irradiation with iodine-125 seeds for pain relief in advanced pancreatic cancer: A long-term retrospective study.
BACKGROUND AND OBJECTIVE
To compare the efficacy of EUS-guided celiac plexus neurolysis (CPN) and celiac plexus irradiation with iodine-125 (I) seeds with absolute ethanol for relieving pain in patients with advanced pancreatic cancer.
METHODS
We retrospectively analyzed data of 81 patients with advanced pancreatic cancer who underwent EUS-CPN or EUS-I implantation between January 2017 and December 2020. Postoperative pain was assessed using visual analog scale (VAS) scores; self-assessments of quality of life and the median survival time were compared between the 2 groups.
RESULTS
EUS-CPN and I implantation were performed in 43 and 38 patients, respectively. Postoperative VAS scores were significantly lower than the preoperative levels in both groups. One week after the operation, 26 patients (60.5%) in the EUS-CPN group achieved partial pain relief, whereas no patients in the EUS-I seed group experienced pain relief. However, after 4 weeks postoperatively, VAS scores had decreased, and the rate of partial pain relief was higher for EUS-I seeds than for EUS-CPN. Self-assessments of quality of life were similar in both groups during the first 1 month after the procedure.
CONCLUSIONS
Both EUS-CPN and EUS-I seeds can safely and effectively relieve pain in patients with advanced pancreatic cancer. Although EUS-I seeds take additional time to show effects, the extent and duration of pain relief are better compared with CPN, and interestingly, the median survival time was different.
PubMed: 38947749
DOI: 10.1097/eus.0000000000000048 -
Cureus May 2024Gastric cancer is the fifth leading cause of cancer-related deaths in the world. The occurrence of bone metastases (BM) in gastric cancer without prior gastrointestinal...
Gastric cancer is the fifth leading cause of cancer-related deaths in the world. The occurrence of bone metastases (BM) in gastric cancer without prior gastrointestinal (GI) symptoms is a rare phenomenon that has been sporadically documented in the existing literature. We report a case of a 27-year-old male presenting with chief complaints of severe backache for one month. After an upper gastrointestinal endoscopy and biopsy, the primary source of cancer was identified as a solitary gastric adenocarcinoma, supporting the diagnosis of bony metastases on the magnetic resonance imaging (MRI) of the spine. The patient was planned to start on palliative chemotherapy (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel {FLOT} regimen) with palliative radiotherapy of 20 Gy in five fractions to bony metastasis. The patient denied treatment and was discharged against medical advice.
PubMed: 38947693
DOI: 10.7759/cureus.61421 -
Heliyon Jun 2024Lynch syndrome (LS) is the most frequent cancer predisposition syndrome affecting the colon and rectum. A pathogenic variant (PV) disrupting one of the mismatch repair...
Lynch syndrome (LS) is the most frequent cancer predisposition syndrome affecting the colon and rectum. A pathogenic variant (PV) disrupting one of the mismatch repair (MMR) genes is responsible for the disease. The spectrum of tumors in LS is heterogeneous and includes cancer of the colon and rectum (CRC), endometrium, ovaries, stomach, small bowel, urinary tract, bladder, pancreas, and skin. Knowledge of the phenotypic variation of patients with LS, the type and frequency of PVs, and cascade testing studies in the Latin American population is limited. The present study aims to recognize the PVs in MMR genes, describe the phenotype in Mexican-Mestizo patients and their relatives, and identify the acceptance rate of cascade testing of relatives at risk. We included 40 carriers of a MMR gene PV and 142 relatives that developed a LS-related neoplasm. Patients' clinical data, number, and type of malignancies were obtained from their medical records. Amsterdam I-II, Bethesda criteria, and PREMM5® predictive model score were estimated. Available immunohistochemistry (IHC) reports were analyzed. Relatives at risk were determined from index cases pedigrees. The distribution of MMR gene mutations among 40 probands was: (67.5 %) (22.5 %) (7.5 %), and (2.5 %). Out of the 182 LS cases, 58 % exhibited the LS phenotype before age 50. The most common tumor was CRC, followed by endometrial cancer in women and gastric cancer in males. We found a 90.0 % concordance between the IHC and germline PV. The most frequent PV in our sample was c.676C > T, occurring in 1/6 index cases. All probands disclosed their molecular test result to their family. Out of the 451 asymptomatic relatives at risk, 28.2 % underwent germline testing. Our results highlight the importance of conducting germline genetic studies in LS since it allows the establishment of appropriate cancer screening, risk-reducing measures, and genetic cascade testing among relatives at risk. Interestingly, we observed a significantly higher prevalence of the c.676C > T variant in probably a singular characteristic of the Mexican-Mestizo population. New strategies to facilitate accurate communication between index cases and relatives should be implemented to improve the cascade testing acceptance rate.
PubMed: 38947473
DOI: 10.1016/j.heliyon.2024.e31855 -
Journal of Cancer 2024SIVA-1 has been reported to play a key role in cell apoptosis and gastric cancer (GC) chemoresistance . Nevertheless, the clinical significance of SIVA-1 in GC...
SIVA-1 has been reported to play a key role in cell apoptosis and gastric cancer (GC) chemoresistance . Nevertheless, the clinical significance of SIVA-1 in GC chemotherapy remains unclear. Immunohistochemistry and histoculture drug response assays were used to determine SIVA-1 expression and the inhibition rate (IR) of agents to GC and to further analyze the relationship between these two phenomena. Additionally, cisplatin (DDP)-resistant GC cells were used to elucidate the role and mechanism of SIVA-1 . The results demonstrated that SIVA-1 expression was positively correlated with the IR of DDP to GC but not with those of 5-fluorouracil (5-FU) or adriamycin (ADM). Furthermore, SIVA-1 overexpression with DDP treatment synergistically inhibited tumor growth by increasing PCBP1 and decreasing Bcl-2 and Bcl-xL expression. Our study demonstrated that SIVA-1 may serve as an indicator of the GC sensitivity to DDP, and the mechanism of SIVA-1 in GC resistance to DDP was preliminarily revealed.
PubMed: 38947376
DOI: 10.7150/jca.92963 -
World Journal of Gastroenterology Jun 2024This editorial is an analysis the review article by Nabi recently published in this journal. Achalasia Cardia is a disease whose pathophysiology is still unclear. It is...
This editorial is an analysis the review article by Nabi recently published in this journal. Achalasia Cardia is a disease whose pathophysiology is still unclear. It is known that there is inflammation of unknown aetiology leading to loss of ganglion cells in the muscularis propria. The end result is lower oesophageal sphincter spasm, loss of receptive relaxation, decreased oesophageal peristalsis, all leading on to varying degrees of dysphagia. The treatment of this condition is palliative in nature, performed by myotomy of the lower oesophagus either surgically or endoscopically. Gastroesophageal reflux disease (GERD) has been associated with the myotomy performed, particularly with the Peroral Endoscopic Myotomy (POEM) procedure. Nabi have provided an excellent overview of the latest developments in predicting, preventing, evaluating, and managing GERD subsequent to POEM. Based on this theme, this review article explores the concept of using histology of the oesophageal muscle layer, to grade the disease and thereby help tailoring the length/type of myotomy performed during the POEM procedure. In the future, will a histology based algorithm available preoperatively, help modify the POEM procedure, thereby decreasing the incidence of GERD associated with POEM?
Topics: Humans; Esophageal Achalasia; Esophageal Sphincter, Lower; Esophagoscopy; Gastroesophageal Reflux; Myotomy; Natural Orifice Endoscopic Surgery; Pyloromyotomy; Treatment Outcome
PubMed: 38947293
DOI: 10.3748/wjg.v30.i22.2834 -
World Journal of Gastroenterology Jun 2024Gastric cancer (GC) is the most common malignant tumor and ranks third for cancer-related deaths among the worldwide. The disease poses a serious public health problem... (Comparative Study)
Comparative Study
BACKGROUND
Gastric cancer (GC) is the most common malignant tumor and ranks third for cancer-related deaths among the worldwide. The disease poses a serious public health problem in China, ranking fifth for incidence and third for mortality. Knowledge of the invasive depth of the tumor is vital to treatment decisions.
AIM
To evaluate the diagnostic performance of double contrast-enhanced ultrasonography (DCEUS) for preoperative T staging in patients with GC by comparing with multi-detector computed tomography (MDCT).
METHODS
This single prospective study enrolled patients with GC confirmed by preoperative gastroscopy from July 2021 to March 2023. Patients underwent DCEUS, including ultrasonography (US) and intravenous contrast-enhanced ultrasonography (CEUS), and MDCT examinations for the assessment of preoperative T staging. Features of GC were identified on DCEUS and criteria developed to evaluate T staging according to the 8 edition of AJCC cancer staging manual. The diagnostic performance of DCEUS was evaluated by comparing it with that of MDCT and surgical-pathological findings were considered as the gold standard.
RESULTS
A total of 229 patients with GC (80 T1, 33 T2, 59 T3 and 57 T4) were included. Overall accuracies were 86.9% for DCEUS and 61.1% for MDCT ( < 0.001). DCEUS was superior to MDCT for T1 (92.5% 70.0%, < 0.001), T2 (72.7% 51.5%, = 0.041), T3 (86.4% 45.8%, < 0.001) and T4 (87.7% 70.2%, = 0.022) staging of GC.
CONCLUSION
DCEUS improved the diagnostic accuracy of preoperative T staging in patients with GC compared with MDCT, and constitutes a promising imaging modality for preoperative evaluation of GC to aid individualized treatment decision-making.
Topics: Humans; Stomach Neoplasms; Middle Aged; Male; Female; Neoplasm Staging; Contrast Media; Prospective Studies; Aged; Ultrasonography; Multidetector Computed Tomography; Adult; China; Gastroscopy; Stomach; Aged, 80 and over
PubMed: 38946876
DOI: 10.3748/wjg.v30.i23.3005 -
World Journal of Gastroenterology Jun 2024In this editorial, we respond to a review article by Nabi , in which the authors discussed gastroesophageal reflux (GER) following peroral endoscopic myotomy (POEM)....
In this editorial, we respond to a review article by Nabi , in which the authors discussed gastroesophageal reflux (GER) following peroral endoscopic myotomy (POEM). POEM is presently the primary therapeutic option for achalasia, which is both safe and effective. A few adverse effects were documented after POEM, including GER. The diagnostic criteria were not clear enough because approximately 60% of patients have a long acid exposure time, while only 10% experience reflux symptoms. Multiple predictors of high disease incidence have been identified, including old age, female sex, obesity, and a baseline lower esophageal sphincter pressure of less than 45 mmHg. Some technical steps during the procedure, such as a lengthy or full-thickness myotomy, may further enhance the risk. Proton pump inhibitors are currently the first line of treatment. Emerging voices are increasingly advocating for the routine combining of POEM with an endoscopic fundoplication method, such as peroral endoscopic fundoplication or transoral incisionless fundoplication. However, more research is necessary to determine the safety and effectiveness of these procedures in the long term for patients who have undergone them.
Topics: Humans; Esophageal Achalasia; Esophageal Sphincter, Lower; Esophagoscopy; Fundoplication; Gastroesophageal Reflux; Myotomy; Natural Orifice Endoscopic Surgery; Proton Pump Inhibitors; Risk Factors; Treatment Outcome
PubMed: 38946871
DOI: 10.3748/wjg.v30.i23.2947 -
World Journal of Gastrointestinal... Jun 2024The escalating prevalence of gastrointestinal cancers underscores the urgency for transformative approaches. Current treatment costs amount to billions of dollars...
The escalating prevalence of gastrointestinal cancers underscores the urgency for transformative approaches. Current treatment costs amount to billions of dollars annually, combined with the risks and comorbidities associated with invasive surgery. This highlights the importance of less invasive alternatives with organ preservation being a central aspect of the treatment paradigm. The current standard of care typically involves neoadjuvant systemic therapy followed by surgical resection. There is a growing interest in organ preservation approaches by way of minimizing extensive surgical resections. Endoscopic ablation has proven to be useful in precursor lesions, as well as in palliative cases of unresectable disease. More recently, there has been an increase in reports on the utility of adjunct endoscopic ablative techniques for downstaging disease as well as contributing to non-surgical complete clinical response. This expansive field within endoscopic oncology holds great potential for advancing patient care. By addressing challenges, fostering collaboration, and embracing technological advancements, the gastrointestinal cancer treatment paradigm can shift towards a more sustainable and patient-centric future emphasizing organ and function preservation. This editorial examines the evolving landscape of endoscopic ablation strategies, emphasizing their potential to improve patient outcomes. We briefly review current applications of endoscopic ablation in the esophagus, stomach, duodenum, pancreas, bile ducts, and colon.
PubMed: 38946859
DOI: 10.4253/wjge.v16.i6.282 -
World Journal of Gastrointestinal... Jun 2024Glucagon-like peptide receptor agonists (GLP-1RA) are used to treat type 2 diabetes mellitus and, more recently, have garnered attention for their effectiveness in...
Glucagon-like peptide receptor agonists (GLP-1RA) are used to treat type 2 diabetes mellitus and, more recently, have garnered attention for their effectiveness in promoting weight loss. They have been associated with several gastrointestinal adverse effects, including nausea and vomiting. These side effects are presumed to be due to increased residual gastric contents. Given the potential risk of aspiration and based on limited data, the American Society of Anesthesiologists updated the guidelines concerning the preoperative management of patients on GLP-1RA in 2023. They included the duration of mandated cessation of GLP-1RA before sedation and usage of "full stomach" precautions if these medications were not appropriately held before the procedure. This has led to additional challenges, such as extended waiting time, higher costs, and increased risk for patients. In this editorial, we review the current societal guidelines, clinical practice, and future directions regarding the usage of GLP-1RA in patients undergoing an endoscopic procedure.
PubMed: 38946857
DOI: 10.4253/wjge.v16.i6.292