Aim: To establish a cellular model correctly mimicking the gastric epithelium to overcome the limitation in the study of Helicobacter pylori (H. pylori) infection.
Methods: Aiming to overcome this limitation, clones of the heterogenic cancer-derived NCI-N87 cell line were isolated, by stably-transducing it with the human telomerase reverse-transcriptase (hTERT) catalytic subunit gene. The clones were first characterized regarding their cell growth pattern and phenotype. For that we measured the clones' adherence properties, expression of cell-cell junctions' markers (ZO-1 and E-cadherin) and ability to generate a sustained transepithelial electrical resistance. The gastric properties of the clones, concerning expression of mucins, zymogens and glycan contents, were then evaluated by haematoxylin and eosin staining, Periodic acid Schiff (PAS) and PAS/Alcian Blue-staining, immunocytochemistry and Western blot. In addition, we assessed the usefulness of the hTERT-expressing gastric cell line for H. pylori research, by performing co-culture assays and measuring the IL-8 secretion, by ELISA, upon infection with two H. pylori strains differing in virulence.
Results: Compared with the parental cell line, the most promising NCI-hTERT-derived clones (CL5 and CL6) were composed of cells with homogenous phenotype, presented higher relative telomerase activities, better adhesion properties, ability to be maintained in culture for longer periods after confluency, and were more efficient in PAS-reactive mucins secretion. Both clones were shown to produce high amounts of MUC1, MUC2 and MUC13. NCI-hTERT-CL5 mucins were shown to be decorated with blood group H type 2 (BG-H), Lewis-x (Le(x)), Le(y) and Le(a) and, in a less extent, with BG-A antigens, but the former two antigens were not detected in the NCI-hTERT-CL6. None of the clones exhibited detectable levels of MUC6 nor sialylated Le(x) and Le(a) glycans. Entailing good gastric properties, both NCI-hTERT-clones were found to produce pepsinogen-5 and human gastric lipase. The progenitor-like phenotype of NCI-hTERT-CL6 cells was highlighted by large nuclei and by the apical vesicular-like distribution of mucin 5AC and Pg5, supporting the accumulation of mucus-secreting and zymogens-chief mature cells functions.
Conclusion: These traits, in addition to resistance to microaerobic conditions and good responsiveness to H. pylori co-culture, in a strain virulence-dependent manner, make the NCI-hTERT-CL6 a promising model for future in vitro studies.
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http://dx.doi.org/10.3748/wjg.v21.i21.6526 | DOI Listing |
Eur J Endocrinol
January 2025
Department of Internal Medicine IV, LMU University Hospital, LMU Munich, 80336 Munich, Germany.
Objective: The effects of sex hormones remain largely unexplored in pheochromocytomas and paragangliomas (PPGLs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
Methods: We evaluated the effects of estradiol, progesterone, Dehydroepiandrosterone sulfate (DHEAS), and testosterone on human patient-derived PPGL/GEP-NET primary culture cell viability (n = 38/n = 12), performed next-generation sequencing and immunohistochemical hormone receptor analysis in patient-derived PPGL tumor tissues (n = 36).
Results: In PPGLs, estradiol and progesterone (1 µm) demonstrated overall significant antitumor effects with the strongest efficacy in PPGLs with NF1 (cluster 2) pathogenic variants.
Langenbecks Arch Surg
January 2025
Department of Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Hospital, Leipzig, Germany.
Purpose: Obesity and type 2 diabetes (T2DM) are major risk factors for hepatic steatosis. Diet or bariatric surgery can reduce liver volume, fat content, and inflammation. However, little is known about their effects on liver function, as evaluated here using the LiMAx test.
View Article and Find Full Text PDFJ Vis Exp
December 2024
Department of General Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science;
Single-incision plus one-port laparoscopic proximal gastrectomy with double-channel anastomosis (SILT-DT) is a minimally invasive surgical approach for treating proximal gastric cancer. This technique includes comprehensive laparoscopic resection of the proximal stomach, lymph node dissection, and double-tract anastomosis. By integrating single-port laparoscopic surgery with an auxiliary operating hole, SILT-DT reduces procedural difficulty while facilitating the placement of an abdominal drainage tube.
View Article and Find Full Text PDFAm J Cancer Res
December 2024
Hangzhou DAC Biotechnology Co., Ltd. No. 369 Qiaoxin Road, Qiantang District, Hangzhou 310018, Zhejiang, China.
Gastric cancer is a common malignant tumor with high incidence and mortality. The overexpression of Human epidermal growth factor receptor 2 (HER2) is associated with increased metastatic potential and poor clinical outcome in gastric cancer. Despite the proven clinical response rates of approved HER2-targeted therapies, including Trastuzumab combined with chemotherapy, their limited long-term clinical benefits and inevitable disease progression still pose significant challenges to the clinical treatment of gastric cancer.
View Article and Find Full Text PDFDrug Des Devel Ther
January 2025
School of Medicine, Kyungpook National University and Department of Clinical Pharmacology and Therapeutics, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea.
Background: YYD601 is a new dual delayed-release formulation of esomeprazole, developed to enhance plasma exposure and prolong the duration of acid suppression.
Purpose: This study aimed to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of YYD601 20 mg following single and multiple oral administrations in healthy, fasting adult Koreans, and to compare these outcomes to those of the conventional esomeprazole 20 mg capsule.
Methods: A randomized, open-label, two-period crossover study was conducted in 28 participants, who were divided into two treatment groups: one group received YYD601 20 mg, and the other received conventional esomeprazole 20 mg, once daily for five consecutive days.
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