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The pancreaticobiliary duodenal junction (PBDJ) is the connecting area of the pancreatic duct, bile duct and duodenum. In a broad sense, it refers to a region formed by the head of the pancreas, the pancreatic segment of the common bile duct and the intraduodenal segment, the descending and the horizontal part of the duodenum, and the soft tissue around the pancreatic head. In a narrow sense, it refers to the anatomical Vater ampulla. Due to its complex and variable anatomical features, and the diversity of pathological changes, it is challenging to make an early diagnosis of malignancy at the PBDJ and define the histological type. The unique anatomical structure of this area may be the basis for the occurrence of malignant tumors. Therefore, understanding and subclassifying the anatomical configuration of the PBDJ is of great significance for the prevention and treatment of malignant tumors at their source. The present review comprehensively discusses commonly used imaging techniques and other new technologies for diagnosing malignancy at the PBDJ, offering evidence for physicians and patients to select appropriate examination methods. [ABSTRACT FROM AUTHOR]

The present study investigated if c-MYC and high mobility group AT-hook 2 (HMGA2) expression was associated with prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). A total of 102 patients undergoing surgery for PDAC were retrospectively reviewed. Immunohistochemistry was used to detect c-MYC and HMGA2 protein expression in PDAC and peritumoral tissue samples. Expression of c-MYC and HMGA2 was associated with clinicopathological characteristics and prognoses of patients with PDAC using multivariate analysis. HMGA2 and c-MYC protein expression was significantly higher in PDAC tissues compared with peritumoral tissue (P<0.001). HMGA2 and c-MYC expression was also significantly higher in patients with PDAC who had lymph node metastasis, invasion of regional tissues and tumor node metastasis (TNM) stage III or IV disease compared with those who had no lymph node metastasis, no invasion of regional tissues and TNM stage I or II disease (P<0.001). Multivariate logistic regression analysis was used to identify TNM stage (P=0.007) and invasion (P=0.003) as significant independent predictors of c-MYC expression (model AUC=0.8201), and lymph node metastasis (P=0.002) and invasion (P=0.003) as significant independent predictors of HMGA2 expression (model AUC=0.7638). Cox multivariate analysis showed that expression of c-MYC (P=0.019) and HMGA2 (P<0.001), TNM stage (P=0.014) and lymph node metastasis (P=0.032) were associated with reduced overall survival time. HMGA2 and c-MYC may be important biological markers and potential therapeutic targets involved in the tumorigenesis, metastasis, invasion and prognosis of PDAC. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are ubiquitously expressed, small, non-coding RNAs that regulate the expression of approximately 30% of the human genes at the post-transcriptional level. miRNAs have emerged as crucial modulators in the initiation and progression of various diseases, including numerous cancer types. The high incidence rate of cancer and the large number of cancer-associated cases of mortality are mostly due to a lack of effective treatments and biomarkers for early diagnosis. Therefore there is an urgent requirement to further understand the underlying mechanisms of tumorigenesis. MicroRNA-126 (miR-126) is significantly downregulated in a number of tumor types and is commonly identified as a tumor suppressor in digestive system cancers (DSCs). miR-126 downregulates various oncogenes, including disintegrin and metalloproteinase domain-containing protein 9, v-crk sarcoma virus CT10 oncogene homolog and phosphoinositide-3-kinase regulatory subunit 2. These genes are involved in a number of tumor-associated signaling pathways, including angiogenesis, epithelial-mensenchymal transition and metastasis pathways. The aim of the current review was to summarize the role of miR-126 in DSCs, in terms of its dysregulation, target genes and associated signaling pathways. In addition, the current review has discussed the potential clinical application of miR-126 as a biomarker and therapeutic target for DSCs. [ABSTRACT FROM AUTHOR]

The expression of nuclear factor of activated T cells c1 (NFATc1) is closely associated with the progression of numerous types of cancer. When NFATc1 expression becomes dysregulated in some types of cancer, this alteration can promote malignant transformation and thereby progression of cancer. NFATc1 expression has been demonstrated to be upregulated in lung cancer cells. This suggests that knockdown of NFATc1 in lung cancer cells may be a therapeutic marker for the treatment of cancer. In the present study, the effects of NFATc1 on the proliferation, apoptosis, invasion and migration of NCI-H1299 and A549 lung cancer cell lines were explored. Lentivirus infection was used to establish a cell model of NFATc1 knockdown in A549 and NCI-H1299 lung cancer cells. Reverse transcription-quantitative PCR was subsequently performed to detect NFATc1 expression in these human lung cancer cells. MTT, wound healing, colony formation and Transwell invasion assays, and flow cytometry were then performed to measure the proliferation, invasion, apoptosis and cell cycle of the cells. Finally, western blot analysis was performed to investigate the mechanism underlying the involvement of NFATc1 in these processes. NFATc1 knockdown was found to significantly inhibit the proliferation, clone formation, migration and invasion of the cells. Furthermore, the cell cycle was arrested at the G1 phase and the expression levels of the target proteins located downstream in the signaling pathway, namely CDK4, c-Myc, ERK, p38 and N-cadherin, were decreased. Following NFATc1 knockdown, the percentages of apoptotic cells were increased, and the expression levels of Bax, cleaved caspase-3 and E-cadherin were also increased. Taken together, the results of the present study suggested that NFATc1 serves an oncogenic role in lung cancer. In terms of the underlying mechanism, NFATc1 promoted the proliferation of lung cancer cells by inhibiting the MAPK and epithelial-to-mesenchymal transition signaling pathways, suggesting that NFATc1 may be a novel target for therapeutic intervention for the treatment of lung cancer. [ABSTRACT FROM AUTHOR]

Mini-patient-derived xenograft (mini-PDX) is a novel, rapid and accurate method used to assess in vivo drug susceptibility. In the present study, a mini-PDX combined with next-generation sequencing (NGS) was used to guide the individualized treatment of a patient with metastatic a-fetoprotein-producing and human epidermal growth factor receptor 2 (HER-2) amplified gastric cancer (GC). Tumor cells were isolated from the tumor tissue obtained from gastroscopic biopsy, transferred into capsules and implanted into severe combined immunodeficiency mice to determine their sensitivity to various drug regimens. NGS was also performed to assess the mutation spectrum of the cells. The results were analyzed to select the most appropriate treatment regimen for the patient. The mini-PDX model confirmed that the patient's tumor was sensitive to a combination regimen of irinotecan and tegafur-gimeracil-oteracil (S-1). Fluorescence in situ hybridization assay of the tumor tissue confirmed HER-2 amplification. The NGS results indicated ERBB2 amplification, and tumor protein P53 [c.659A>G (p.Y220C)], ataxia-telengiectasia mutated [c.125A>G (p.H42R)] and MutS homolog 6 [c.3254C(8>7) (p.F1088Sfs*2)] mutation, in which UGT1A1*28, TA6/7 (rs8175347) was a mutant heterozygote. After six courses of treatment with a regimen comprising 300 mg irinotecan on day 1 + 40 mg S-1 twice daily on days 2–15 + 350 mg trastuzumab once-every 3 weeks, the patient continued with S-1 treatment for 4 courses and trastuzumab for 1 year. The patient retained progression-free survival status at the 32-month follow-up. Thus, the mini-PDX model combined with the NGS rapidly assessed drug sensitivity in a patient with GC and revealed key genetic mutations. However, the proposed technique requires further research to confirm its potential in the individualized treatment of patients with refractory malignancies. [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma (PAAD) is one of the most fatal types of cancer in humans. However, the molecular mechanisms underlying the migration and invasion abilities of PAAD cells remain unclear. The aim of the present study was to explore the regulatory roles of microRNA (miR)-32-5p in PAAD cells. miR-32-5p mimic and inhibitor were used to transfect the human PAAD AsPC-1 cell line to determine the role of miR-32-5p in cell proliferation and metastasis. The starBase database predicted the binding of miR-32-5p to the target gene TBC/LysM-associated domain containing 1 (TLDC1). Further analyses were performed to assess miR-32-5p and TLDC1 expression levels in healthy and PAAD tissues, as well as the association between miR-32-5p or TLDC1 expression and the prognosis of patients with PAAD. The interaction between miR-32-5p and TLDC1 was verified using the dual-luciferase reporter assay. miR-32-5p and TLDC1 expression levels were detected by reverse transcription-quantitative PCR and western blotting, respectively. The Cell Counting Kit-8 assay was utilised to assess cell proliferation, whereas the wound-healing and Transwell assays were conducted to assess cell migration and invasion, respectively. miR-32-5p expression levels were markedly lower in PAAD tissue compared with those in healthy tissue, and were significantly lower in PAAD cell lines compared with those in the human pancreatic duct cell line HPDE6, which corresponded with poor prognosis. miR-32-5p significantly inhibited the proliferation of PAAD cells and markedly reduced migration and invasion compared with the negative controls. miR-32-5p was shown to target TLDC1, with miR-32-5p expression in PAAD being negatively correlated with TLDC1 expression. High TLDC1 expression levels were associated with a poorer prognosis compared with low TLDC1 expression levels. Co-transfection of miR-32-5p mimic and pcDNA/TLDC1 demonstrated that TLDC1 significantly reversed miR-32-5p-mediated inhibition of the proliferation, migration and invasion of PAAD cells. Overall, the present study demonstrated that miR-32-5p may serve as a tumor-suppressor gene by inhibiting the proliferation and migration and invasion of PAAD cells via the downregulation of TLDC1. Therefore, miR-32-5p may serve as a potential diagnostic or prognostic marker for PAAD. [ABSTRACT FROM AUTHOR]

Modern cancer immunotherapy techniques are aimed at enhancing the responses of the patients' immune systems to fight against the cancer. The main promising strategies include active vaccination of tumor antigens, passive vaccination with antibodies specific to cancer antigens, adoptive transfer of cancer-specific T cells and manipulation of the patient's immune response by inhibiting immune checkpoints. The application of immunogenic cell death (ICD) inducers has been proven to enhance the immunity of patients undergoing various types of immunotherapy. The dying, stressed or injured cells release or present molecules on the cell surface, which function as either adjuvants or danger signals for detection by the innate immune system. These molecules are now termed 'damage-associated molecular patterns'. The term 'ICD' indicates a type of cell death that triggers an immune response against dead-cell antigens, particularly those derived from cancer cells, and it was initially proposed with regards to the effects of anticancer chemotherapy with conventional cytotoxic drugs. The aim of the present study was to review and discuss the role and mechanisms of ICD as a promising combined immunotherapy for gastrointestinal tumors. [ABSTRACT FROM AUTHOR]

Pancreatic stellate cells (PSCs) play a key role in desmoplastic stroma, which is a characteristic of pancreatic ductal adenocarcinoma (PDAC), and they also enhance the malignancy of pancreatic cancer cells. Our previous study reported chloroquine's mitigating effects on PSC activation; however, the drug is known to induce adverse effects in clinical practice. The present study aimed to reduce chloroquine doses and develop a useful pre-treatment that targets PSCs using nanoparticles. Poly lactic-co-glycolic acid (PLGA) nanoparticles were used as carriers and loaded with indocyanine green (Nano-ICG) or chloroquine (Nano-CQ). Tumor accumulation of Nano-ICG was evaluated using an in vivo imaging system. The effects of chloroquine, Nano-CQ and/or chemotherapy drug gemcitabine were investigated in an orthotopic xenograft mouse model. Nano-ICG selectively accumulated in pancreatic tumors and persisted therein for over 7 days after administration. Additionally, Nano-ICG accumulated in the peritoneal metastasized regions, but not in the liver, kidney and normal pancreatic tissues. Nano-CQ reduced the density of activated PSCs at lower chloroquine doses and significantly restrained tumor progression in combination with gemcitabine. In conclusion, the PLGA nanosystem successfully delivered the drug to pancreatic tumors. Nano-CQ efficiently reduced PSC activation and may be a promising novel pre-treatment strategy for PDAC. [ABSTRACT FROM AUTHOR]

The present study aimed to illustrate the role of LINC00565 in aggravating colorectal cancer (CRC) by targeting enhancer of zeste homolog 2 (EZH2). The relative levels of LINC00565 and EZH2 in CRC tissues, based on their Tumor-Node-Metastasis stage and tumor size, were detected by reverse transcription-quantitative polymerase chain reaction. The diagnostic value of LINC00565 in CRC was assessed by depicting receiver operating characteristic curves. Pearson's correlation test was applied to analyze the expression correlation between LINC00565 and EZH2 in CRC tissues. The transfection efficacy of three LINC00565 small interfering RNAs was examined in CRC HCT116 and SW480 cell lines. After knockdown of LINC00565, the proliferative and migratory abilities of CRC cells were detected by Cell Counting Kit-8 and Transwell assays, respectively. The subcellular distribution of LINC00565 was analyzed, and the interaction between LINC00565 and EZH2 was determined by RNA immunoprecipitation. Finally, co-regulation of LINC00565 and EZH2 on CRC cell functions was explored by performing rescue experiments. Results showed that LINC00565 was upregulated in CRC tissues, especially in patients with stage III+IV and in those with large tumor sizes, suggesting its diagnostic value in CRC. EZH2 was also upregulated in CRC tissues, showing a positive correlation with LINC00565. LINC00565 was mainly expressed in the cytoplasm and was found to bind with EZH2. Validation was performed by overexpressing EZH2, which abolished the role of silenced LINC00565 in regulating proliferative and migratory abilities in CRC. Therefore, the upregulation of LINC00565 in CRC tissues was found to stimulate the aggravation of CRC by upregulating EZH2. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with a specific tumor immune microenvironment (TIME). Therefore, investigating prognostic immune-related genes (IRGs) that are closely associated with TIME to predict PDAC clinical outcomes is necessary. In the present study, 459 samples of PDAC from the Genotype-Tissue Expression database, The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) were included and a survival-associated module was identified using weighted gene co-expression network analysis. Based on the Cox regression analysis and least absolute shrinkage and selection operator analysis, four IRGs (2′-5′-oligoadenylate synthetase 1, MET proto-oncogene, receptor tyrosine kinase, interleukin 1 receptor type 2 and interleukin 20 receptor subunit β) were included in the prognostic model to calculate the risk score (RS), and patients with PDAC were divided into high- and low-RS groups. Kaplan-Meier survival and receiver operating characteristic curve analyses demonstrated that the low-RS group had significantly improved survival conditions compared with the high-RS group in TCGA training set. The prognostic function of the model was also validated using ICGC and GEO cohorts. To investigate the mechanism of different overall survival between the high- and low-RS groups, the present study included Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data and Cell Type Identification by Estimating Relative Subset of Known RNA Transcripts algorithms to investigate the state of the tumor microenvironment and immune infiltration inpatients in the cohort from TCGA. In summary, four genes associated with the TIME of PDAC were identified, which may provide a reference for clinical treatment. [ABSTRACT FROM AUTHOR]