The establishing of the first cancer models created a new perspective on the identification and evaluation of new anti-cancer therapies in preclinical studies. Patient-derived xenograft models are created by tumor tissue engraftment. These models accurately represent the biology and heterogeneity of different cancers and recapitulate tumor microenvironment. These features have made it a reliable model along with the development of humanized models. Therefore, they are used in many studies, such as the development of anti-cancer drugs, co-clinical trials, personalized medicine, immunotherapy, and PDX biobanks. This review summarizes patient-derived xenograft models development procedures, drug development applications in various cancers, challenges and limitations.
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is an inflammatory condition that results in gastrointestinal tract damage. Various factors, including environmental and genetic agents, disrupt the function of the intestinal immune system that can lead to IBD. Mesenchymal stem cells (MSCs) display an immunoregulatory function and demonstrate regenerative potential by paracrine action. In this study, we evaluated the immunomodulatory effects of MSCs’ derived exosomes in the acute form of dextran sulfate sodium (DSS)‐induced colitis. Exosomes were isolated from adipose‐derived MSCs. Acute colitis was induced by DSS. The exosome was used by intraperitoneal injection into mice with acute colitis. Stool consistency, body weight changes, bleeding severity, colon length, and weight were examined. At the experimental endpoint (Day 7), the changes in the colon tissue were evaluated. The level of cytokines of interferon‐γ (IFN‐γ), tumor necrosis factor‐α (TNF‐α), interleukin‐17 (IL‐17), IL‐4, IL‐12, transforming growth factor‐β (TGF‐β) and, IL‐10, and Treg cells percentage were assayed. Results showed that exosome administration diminished colon shortening, bodyweight loss, bleeding, and colon injury. The levels of IFN‐γ, TNF‐α, IL‐12, and IL‐17 were decreased, and the level of TGF‐β, IL‐4, and IL‐10 were increased in lymph node and spleen of mice treated with exosome. Percentages of CD4+ CD25+ Foxp3+ Treg cells were grown in the lymph node and spleen of mice treated with exosomes. Overall, current data suggest that MSC‐derived exosome could regulate the Treg population and improves inflammation in DSS‐induced acute colitis.
Inflammatory bowel disease (IBD) as a chronic recurrent disorder is characterized by mucosal immune response dysregulation, which is more prevalent in the youth. Adipose-derived mesenchymal stem cells (ADMSCs) are the multipotent cells that can be effective in immune response regulation via cell-cell interaction and their secretions. In this study, the effects of ADMSCs and mesenchymal stem cell-conditioned medium (MSC-CM) were evaluated on dextran sulfate sodium (DSS)-induced colitis in mice. Chronic colitis was induced in female C57BL/6 mice using 2% DSS in drinking water for three cycles; there were 4 days of DSS-water administration that was followed by 7 days of DSS-free water, in a cycle. ADMSCs, 10 cells per mouse, were injected intraperitoneally (IP), whereas the MSC-CM injection was also performed six times from the last day of DSS in Cycle 1. Clinical symptoms were recorded daily. The colon pathological changes, cytokine levels, and regulatory T (Treg) cell percentages were then analyzed. After receiving ADMSCs and MSC-CM in colitis mice, the clinical symptoms and disease activity index were improved and the survival rate was increased. The histopathological examination also showed tissue healing in comparison with the nontreated group. In addition, the increased level of transforming growth factor beta, increased percentage of Treg cells, increased level of interleukin (IL)-10, and decreased level of IL-17 were observed after the treatment. This study showed the regulatory effects of ADMSCs and MSC-CM on inflammatory responses. Therefore, the use of ADMSCs and MSC-CM can be introduced as a new and effective therapeutic approach for patients with colitis.
Although Helicobacter pylori (H. pylori) infection has been known to be associated with several upper gastrointestinal disorders such as peptic ulcer and gastric cancer, the relationship between H. pylori infection and dyspeptic symptoms remains controversial. Furthermore, it is still not clear which factors are associated with H. pylori infection in the Iranian population. We investigated the prevalence of H. pylori infection in dyspeptic patients and factors associated with H. pylori infection in the Iranian population. In this cross-sectional study, 303 patients with dyspeptic symptoms underwent endoscopy. Clinical data and a questionnaire about gastrointestinal symptoms were collected from each patient. H. pylori status was evaluated by histological examination. Among the 303 patients, 263 (86.8%) were found to be positive for H. pylori. The prevalence of H. pylori infection decreased significantly with age. There was no difference in the prevalence of H. pylori infection between the patients with and those without a family history of gastroduodenal diseases. Among 250 patients with abdominal pain, 219 (87.6%) were infected with H. pylori. Among 211 patients with epigastric abdominal pain, 185 (87.7%) were infected with H. pylori. It was observed that belching was significantly associated with H. pylori infection (P = 0.03). Dyspepsia triggered by the consumption of tea was higher in H. pylori-positive patients than in H. pylori-negative patients (P=0.03). The prevalence of H. pylori infection in dyspeptic patients was quite high in Iran. Belching and dyspepsia triggered by tea consumption was related with H. pylori infection.
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