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BACKGROUND: In the process of laparoscopic splenic vessels and spleen preservation distal pancreatectomy (LsvSPDP), because the splenic blood vessels have many small branches, how to safely separate the splenic blood vessels from the pancreas has always been the focus and difficulty of this operation. Many cases were switched to laparotomy, or the Warshaw method due to the inability to control bleeding during the separation of the splenic blood vessels. Therefore, we tried to use the selective splenic vascular control method when separating the splenic blood vessels to observe its effect on the conditions of the surgical patients during and after the operation. METHODS: We retrospectively collected 35 cases of LsvSPDP conducted in our center from September 2015 to December 2020, including 5 males and 30 females. Considering the influence of the surgical learning curve, the cases were divided into three groups. Finally, through statistics of its intraoperative and postoperative conditions, the effectiveness of selective splenic vascular control method can be judged. RESULTS: Patients in Group 2 and 3 showed significantly less blood loss (172.5 and 134.44 mL, respectively) compared to patients in Group 1 (541.43 mL; P=0.01). However, the amount of blood loss was not significantly different between Group 2 and 3. CONCLUSIONS: The amount of bleeding was significantly reduced by splenic blood vessel control technology. And it can improve the success rate of spleen preservation, preserve the success rate of splenic blood vessels, and reduce intraoperative bleeding.
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Pancreatic cancer is known for its notorious fast progression and poor prognosis. Long noncoding RNA (lncRNA) AL161431.1 has been reported to be involved in the pathogenesis of different cancers. In this study, we explored the role of lncRNA AL161431.1 in the development and progression of pancreatic cancer by bioinformatic analysis, in vitro and in vivo experiments in pancreatic cancer BxPC-3 and SW1990 cells, as well as clinical samples. We found that lncRNA AL161431.1 was highly expressed in pancreatic cancer cells and tissues. Knock down of lncRNA AL161431.1 led to increased cancer cell death and cell cycle arrest. Xenograft growth of SW1990 cells with stable knockdown of lncRNA AL161431.1 in mice was significantly slower than that of SW1990 cells with scrambled control shRNA. Finally, we showed the involvement of lncRNA AL161431.1 in pancreatic cancer was related to its promotion of epithelial mesenchymal transition process.
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OBJECTIVE: Our purpose is to explain the onset, diagnosis, and treatment of pancreatic tumor-associated pancreatitis (PTP), and inform clinicians about the management of PTP. It is hoped that clinicians can gain some experience and inspiration from this review, so that patients can obtain better treatment results. BACKGROUND: Acute pancreatitis (AP) is an inflammatory disease, and pancreatic tumors are one of the causes of pancreatitis. When pancreatic tumors and pancreatitis exist at the same time, and there is a "connection" between them, this type of pancreatitis is referred to as PTP. The manifestations of PTP can be as follows: (I) AP is the first symptom of pancreatic tumors; (II) pancreatitis is found in patients after pancreatic tumor diagnosis or during pancreatic tumor surgery. Because pancreatic tumors are not one of the most common causes of pancreatitis, PTP has not attracted the attention of researchers and clinicians, and there is no consistent and clear understanding of the diagnosis and treatment of PTP. METHODS: From the online database PubMed (https://pubmed.ncbi.nlm.nih.gov/) and Web of Science (https://webofknowledge.com/), we use specific retrieval strategies to retrieve relevant articles, and we review and discuss them. CONCLUSIONS: What we need to realize is that PTP is different from ordinary AP. It has its own characteristics in terms of diagnosis and treatment, which requires the attention of clinicians. More importantly, future research should design the best diagnosis and treatment algorithms for PTP.
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OBJECTIVE: Although considerable progress has been made in our understanding of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, there are still some problems to be solved. BACKGROUND: IPMN is one of the most important precancerous lesions of pancreatic cancer, but the relationship between IPMN and pancreatic cancer, and the specific mechanism of the development from IPMN to invasive carcinoma, remain to be explored in depth. With the development of imaging, the detection rate of IPMN has been greatly improved. However, the degree of malignancy of IPMN is difficult to assess, and its classification criteria and surgical treatment strategies are still controversial. Therefore, there is an urgent need for the best treatment plan for IPMN and research that can better predict IPMN recurrence and tumor malignancy. METHODS: From the online database Web of Science (https://webofknowledge.com/) and PubMed (https://pubmed.ncbi.nlm.nih.gov/), we use specific retrieval strategies to retrieve relevant articles based on the topics we discussed, and we review and discuss them. CONCLUSIONS: This paper discusses the related research and progress of IPMN in recent years to improve the understanding of the incidence, diagnosis, treatment, and prognosis of this disease. The follow-up and monitoring of IPMN is particularly important, but the specific strategy also remains controversial.
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We report an extremely rare case of primary gastric melanoma with pancreatic metastasis. As far as we know, the concept of primary gastrointestinal melanoma is currently controversial, because there are very few reports of primary gastrointestinal melanoma. At the same time, isolated pancreatic metastases are also very rare. The patient was admitted to the hospital with a main complaint of decreased appetite, and then underwent gastroscopy and found a mass in the stomach. The mass was initially diagnosed as poorly differentiated adenocarcinoma following a gastroscopic biopsy. The patient underwent radical total gastrectomy, pancreatic body and tail resection, splenectomy, and Roux-en-Y esophagojejunostomy. After further immunohistochemical examination of the surgically removed tissue, malignant melanoma was diagnosed. The tumor cells were arranged in sheets or nests with infiltrating growth, the cell sizes were inconsistent, nucleoli were obvious, and melanin particles were seen in the cytoplasm of some cells. The tumor cells were positive for MITF and S-100. Detailed systemic and imaging examinations did not find any other primary lesions. The patient denied any melanoma and skin lesion history. We believe this is a manifestation of primary gastric melanoma. We report this rare case of gastric melanoma with the aim of increasing clinicians' awareness of non-cutaneous melanoma and its treatment methods.
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Melanoma , Neoplasias Pancreáticas , Neoplasias Gástricas , Gastrectomía , Humanos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Gástricas/diagnóstico por imagenRESUMEN
Inflammatory myofibroblastic tumor (IMT) is a rare disease of unknown etiology. It usually occurs in abdominal soft tissues and lung, and is extremely rare in the pancreas. IMT can occur in any part of a person at any age, however, it mostly affects children and young people. Its clinical manifestations are atypical, imaging examinations are not specific, and the differential diagnosis of pancreatic malignancies is difficult, making it easily misdiagnosed. Surgical resection is the preferred method of treatment for IMT. In this case report, we report a rare case of IMT in the neck of the pancreas and reviewed the relevant literature. In our case, the patient was a 57-year-old woman with an IMT in the neck of the pancreas. Abdominal pain was the only clinical symptom, and imaging features were not specific. She underwent surgery to remove the pancreatic mass, and the final diagnosis of IMT was based on histopathology and immunohistochemistry. After 6 months of regular follow-up, the patient had no complications or further incidents. The purpose is to emphasize the difficulty of the preoperative diagnosis of pancreatic IMT and the difficulty of distinguishing it from pancreatic malignancies. It is hoped that clinicians can gain a deeper understanding of pancreatic IMT through this case report.
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BACKGROUND: Long non-coding ribonucleic acid (lncRNA) ELFN1 antisense RNA 1 (ELFN1-AS1) is involved in the pathogenesis of many different cancers. But the current research on the relationship between lncRNA ELFN1-AS1 and pancreatic cancer is still blank. METHODS: We investigated the role of lncRNA ELFN1-AS1 in the pathogenesis of pancreatic cancer using bioinformatics, in vitro and in vivo experiments in pancreatic cancer cell lines, and surgically removed clinical samples. RESULTS: Through bio-information analysis and in vitro and in vivo experiments, we found that LncRNA ELFN1-AS1 was highly enriched in pancreatic cancer data sets and highly expressed in pancreatic cancer cell lines and tissues. The knocking down of lncRNA ELFN1-AS1 significantly increased cancer cell death and growth arrest. Xenografts in nude mice showed that the growth of SW1990 cells in the mice group with a stable knock down of lncRNA ELFN1-AS1 was significantly slower than that in the control group. CONCLUSIONS: The experimental results show that the expression of LncRNA ELFN1-AS1 is related to the growth and invasion ability of pancreatic cancer cells. By further studying the function of LncRNA ELFN1-AS1 in pancreatic cancer, LncRNA ELFN1-AS1 was found to be involved in the epithelial-mesenchymal transition process in pancreatic cancer.
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Growing evidence indicates that circular RNAs (circRNAs) are closely involved in tumorigenesis, but the association between circRNAs and pancreatic ductal adenocarcinoma (PDAC) is far from clear. Here, we focused on the functional investigation of circ-0005105, a newly identified circRNA, in PDAC progression. In the present study, we assessed circ-0005105 expression in PDAC tissues and cell lines with quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The biological functions of circ-0005105 in cellular proliferation and invasion were identified through gain- and loss-of-function experiments in vitro and in vivo. The interaction between circ-0005105 and the microRNA (miR)-20a-3p-COL11A1 (collagen type XI alpha 1) axis was examined using luciferase reporter and RNA immunoprecipitation assays. We found that circ-0005105 expression was upregulated in both PDAC tissues and cell lines. Higher circ-0005105 expression correlated positively with the malignant clinical phenotype and poor prognosis of patients with PDAC. Gain- and loss-of-function analysis showed that circ-0005105 facilitated both in vitro and in vivo cellular proliferation and invasion. Mechanistically, circ-000510 served as a competing endogenous RNA (ceRNA) of miR-20a-3p and indirectly modulated COL11A1 expression, leading to activation of epithelial-mesenchymal transition (EMT). Rescue experiments suggested that the oncogenic activity of circ-0005105 was dependent on the modulation of the miR-20a-3p-COL11A1 axis. More importantly, COL11A1 overexpression was significantly associated with poor prognosis in PDAC, and silencing COL11A1 reduced PDAC cell tumorigenicity and metastasis. Taken together, our findings confirm for the first time that circ-0005105 has critical functions by regulating the miR-20a-3p-COL11A1 axis. In the clinic, circ-0005105 can act as a potential prognostic marker and therapeutic target in PDAC.
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Carcinoma Ductal Pancreático/metabolismo , Colágeno Tipo XI/metabolismo , MicroARNs/metabolismo , Neoplasias Pancreáticas/metabolismo , ARN Circular/metabolismo , Animales , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/secundario , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Colágeno Tipo XI/genética , Bases de Datos Genéticas , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , ARN Circular/genética , Transducción de SeñalRESUMEN
Y chromosomal short tandem repeats (Y-STRs) have been widely harnessed for forensic applications, such as pedigree source searching from public security databases and male identification from male-female mixed samples. For various populations, databases composed of Y-STR haplotypes have been built to provide investigating leads for solving difficult or cold cases. Recently, the supplementary application of Y chromosomal haplogroup-determining single-nucleotide polymorphisms (SNPs) for forensic purposes was under heated debate. This study provides Y-STR haplotypes for 27 markers typed by the Yfiler™ Plus kit and Y-SNP haplogroups defined by 24 loci within the Y-SNP Pedigree Tagging System for Shandong Han (n = 305) and Yunnan Han (n = 565) populations. The genetic backgrounds of these two populations were explicitly characterized by the analysis of molecular variance (AMOVA) and multi-dimensional scaling (MDS) plots based on 27 Y-STRs. Then, population comparisons were conducted by observing Y-SNP allelic frequencies and Y-SNP haplogroups distribution, estimating forensic parameters, and depicting distribution spectrums of Y-STR alleles in sub-haplogroups. The Y-STR variants, including null alleles, intermedia alleles, and copy number variations (CNVs), were co-listed, and a strong correlation between Y-STR allele variants ("DYS518~.2" alleles) and the Y-SNP haplogroup QR-M45 was observed. A network was reconstructed to illustrate the evolutionary pathway and to figure out the ancestral mutation event. Also, a phylogenetic tree on the individual level was constructed to observe the relevance of the Y-STR haplotypes to the Y-SNP haplogroups. This study provides the evidence that basic genetic backgrounds, which were revealed by both Y-STR and Y-SNP loci, would be useful for uncovering detailed population differences and, more importantly, demonstrates the contributing role of Y-SNPs in population differentiation and male pedigree discrimination.
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Cromosomas Humanos Y/genética , Genética Forense/métodos , Repeticiones de Microsatélite , Polimorfismo de Nucleótido Simple , Población/genética , China , Técnicas de Genotipaje/métodos , Humanos , Masculino , LinajeRESUMEN
BACKGROUND: Ileocecal intussusception caused by two different tumors is rare, according to a literature review. We describe a case of a male patient with a cauliflower-like mass in the middle of the transverse colon observed by colonoscopy before surgery. It was considered to be intussusception caused by colon cancer. However, a substantial lipomatous mass was seen in the distal end of the intussusception by computed tomography before surgery, which posed a challenge in the preoperative diagnosis. CASE SUMMARY: We report a 72-year-old male patient with intussusception. The patient underwent right hemicolectomy and cholecystectomy in our hospital on April 29, 2019. During operation, the ileum was inserted into the ascending colon by about 15 cm, and a tumor with a diameter of approximately 3.0 cm was observed in the distal part of the intestine. An atypical liposarcoma/highly differentiated liposarcoma in the adipose tissue was suspected in the postoperative pathology, and a lipoma was diagnosed after MDM2 gene testing. A 4.0 cm × 5.0 cm polypoid mass was seen immediately adjacent to the mass, and the postoperative pathology report suggested a high-level tubular adenoma. The patient was eventually cured and discharged with an uneventful follow-up. CONCLUSION: Intussusception caused by two different types of masses is extremely rare. At present, surgery is the best treatment once intussusception is diagnosed.
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The Y chromosomal short tandem repeats (Y-STRs) have been used widely to establish paternal relatedness and examine sub-structures in different geographical regions. However, the applications of Y-STRs showed their limitations when it comes to resolving the complicated relationships within close relatives or among unrelated individuals from different geographic areas. Here, we overcome these limitations by introducing a new strategy for Y-SNP multiplex typing using rapid ARMS (amplification-refractory mutation system) PCR. Newly developed Y-SNP Pedigree Tagging System is able to profile 24 Y-SNPs in a single reaction while the whole process takes 4-5 hours. The panel precisely defines the 11 haplogroups (E-M96, D-JST021355, N-M231, C-M130, O-P186, I-M170, IJ-M429, K-M9, QR-M45, G-M201, and IJK-M522) and 13 sub-haplogroups (D1a1a1-N1, D1a2a-P47, C2-M217, N1a1-M46, O1a-M119, O1b-M268, O1b2-M176, O2-M122, O2a1-KL1, O2a2-P201, O2a2b-P164, O2a2a1a2-M7 and O2a2b1a1-M117). This system could contribute to providing the haplogroup affiliation of unknown pedigree and resolving the sub-structures of East Asian populations. In this study, the multiplex system was validated for: ability to detect degraded DNA, sensitivity, species specificity, reproducibility/repeatability, stability, performance in different scenarios, mixture studies, PCR amplification conditions, and population surveys. The Y-SNP information showed a consistent pattern within 40 father-son or brother-brother pairs. The results of this multiplex system showed the different distribution patterns of male donors from two Chinese Han populations. In this study, we try to discriminate the suspect's pedigree on the level of Y-SNP haplogroups. These results show that Y-SNP Pedigree Tagging System is a robust and reliable amplification kit which can be used for male haplogroup determination.
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Cromosomas Humanos Y , Reacción en Cadena de la Polimerasa Multiplex/métodos , Linaje , Polimorfismo de Nucleótido Simple , China , Etnicidad/genética , Genética Forense/métodos , Humanos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Especificidad de la EspecieRESUMEN
Newborn hearing screening is not designed to detect delayed-onset prelingual hearing loss or aminoglycoside-antibiotic-induced ototoxicity. Cases with severe to profound hearing loss have been reported to have been missed by newborn hearing screens. The aim of this study was to evaluate the efficacy of concurrent hearing and genetic screening in the general population and demonstrate its benefits in practice. Enrolled newborns received concurrent hearing and genetic screens between September 1, 2015 and January 31, 2018. Of the 239,636 eligible infants (median age, 19 months), 548 (0.23%) had prelingual hearing loss. Genetic screening identified 14 hearing loss patients with positive genotypes and 27 patients with inconclusive genotypes who had passed the hearing screens. In addition, the genetic screen identified 0.23% (570/239,636) of the newborns and their family members as at-risk for ototoxicity, which is undetectable by hearing screens. In conclusion, genetic screening complements newborn hearing screening by improving the detection of infants at risk of hereditary hearing loss and ototoxicity, and by informing genotype-based clinical management for affected infants and their family members. Our findings suggest that the practice should be further validated in other populations and rigorous cost-effectiveness analyses are warranted.
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Pruebas Genéticas , Pérdida Auditiva , Tamizaje Neonatal , Femenino , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/genética , Pruebas Auditivas , Humanos , Lactante , Recién Nacido , Masculino , Estudios RetrospectivosRESUMEN
The incidence of inborn errors of metabolisms (IEMs) varies dramatically in different countries and regions. Expanded newborn screening for IEMs by tandem mass spectrometry (MS/MS) is an efficient approach for early diagnosis and presymptomatic treatment to prevent severe permanent sequelae and death. To determine the characteristics of IEMs and IEMs-associated mutations in newborns in Jining area, China, 48,297 healthy neonates were recruited for expanded newborn screening by MS/MS. The incidence of IEMs was 1/1178 in Jining, while methylmalonic acidemia, phenylketonuria, and primary carnitine deficiency ranked the top 3 of all detected IEMs. Thirty mutations in nine IEMs-associated genes were identified in 28 confirmed cases. As 19 cases with the mutations in phenylalanine hydroxylase (PAH), solute carrier family 22 member 5 (SLC22A5), and methylmalonic aciduria (cobalamin deficiency) cblC type with homocystinuria (MMACHC) genes, respectively, it suggested that mutations in the PAH, SLC22A5, and MMACHC genes are the predominant causes of IEMs, leading to the high incidence of phenylketonuria, primary carnitine deficiency, and methylmalonic acidemia, respectively. Our work indicated that the overall incidence of IEMs is high and the mutations in PAH, SLC22A5, and MMACHC genes are the leading causes of IEMs in Jining area. Therefore, it is critical to increase the coverage of expanded newborn screening by MS/MS and prenatal genetic consulting in Jining area.
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Extraskeletal Ewing's sarcoma/peripheral primitive neuroectodermal tumor (E-EWS/pPNET) is a rare aggressive malignant small round cell tumor. In this report, we present the case of a 15-year-old boy who suffered from acute abdominal pain accompanied by hematemesis and melena, and was eventually diagnosed with E-EWS/pPNET. To date, there have been only five reported cases of E-EWS/pPNET of the small bowel including the patient in this report. To the best of our knowledge, this is the first documentation of a pPNET of the small bowel mesentery at nonage. All these have made this report rare and significant.
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miR-204 was found to be downregulated in gastric cancer (GC) tissues, and the effect of miR-204 function on gastric cancer remains as a mystery. Therefore, this study was aimed at investigating the potential role of miR-204 involved in GC progression. Tissues collected from 60 gastric cancer patients were selected as the case group, while the matched normal paracancer tissues as controls. miR-204 expression levels in tissues and GC cells were detected using real-time fluorescent quantitative PCR. Luciferase assay was adopted to validate the interaction between potential gene targets and miR-204. Transwell assay was performed to evaluate the metastasis of GC cells. By building the epithelial-mesenchymal transition (EMT) model in vitro through the addition of transforming growth factor beta 1 (TGF-ß1), expressions of miR-204 and snai1 in the EMT model together with their respective effects on EMT were evaluated. miR-204 was significantly downregulated in GC tissues and invasive GC cells (P < 0.05). The over-expression of miR-204 or downregulation of snai1 could significantly inhibit the metastasis and invasion of GC cells both in vitro and in vivo. The upregulated miR-204 expression or inhibited snai1 expression could suppress the EMT process in EMT in vitro models. Our study provided evidence that miR-204 may suppress the metastasis and invasion of GC cells through the regulation of the EMT process by targeting snai1.
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Transición Epitelial-Mesenquimal/genética , MicroARNs/genética , Factores de Transcripción de la Familia Snail/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Western Blotting , Línea Celular Tumoral , Movimiento Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Invasividad Neoplásica/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Transcripción de la Familia Snail/metabolismo , Neoplasias Gástricas/metabolismo , TransfecciónRESUMEN
OBJECTIVE: To detect the expression profiles of microRNA-218 (miR-218) in human pancreatic cancer tissue (PCT) and cells and their effects on the biological features of human pancreatic cancer cell line PANC-1 and observe the effect of miR-218 on the expression of the target gene high mobility group box 1 (HMGB1), with an attempt to provide new treatment methods and strategies for pancreatic cancer. METHODS: The expressions of miR-218 in PCT and normal pancreas tissue as well as in various pancreatic cancer cell lines including AsPC-1, BxPC-3, and PANC-1 were determined with quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The change of miR-218 expression in PANC-1 cells was detected using qRT-PCT after the transfection of miR-218 mimic for 48 h. Cell Counting Kit-8 (CCK-8) was applied for detecting the effect of miR-218 on the activity of PANC-1 cells. The effects of miR-218 on the proliferation and apoptosis of PANC-1 cells were analyzed using the flow cytometry. The effect of miR-218 on the migration of PANC-1 cells was detected using the Trans-well migration assay. The HMGB1 was found to be a target gene of miR-218 by luciferase reporter assay, and the effect of miR-218 on the expression of HMGB1 protein in cells were determined using Western blotting. RESULTS: As shown by qRT-PCR, the expressions of miR-218 in PCT and in pancreatic cancer cell line significantly decreased when compared with the normal pancreatic tissue (NPT) (P<0.01). Compared with the control group, the miR-218 expression significantly increased in the PANC-1 group after the transfection of miR-218 mimic for 48 h (P<0.01). Growth curve showed that the cell viability significantly dropped after the overexpression of miR-218 in the PANC-1 cells for two days (P<0.05). Flow cytometry showed that the S-phase fraction significantly dropped after the overexpression of miR-218 (P<0.01) and the percentage of apoptotic cells significantly increased (P<0.01). As shown by the Trans-well migration assay, the enhanced miR-218 expression was associated with a significantly lower number of cells that passed through a Transwell chamber (P<0.01). Luciferase reporter assay showed that, compared with the control group, the relative luciferase activity significantly decreased in the miR-218 mimic group (P<0.01). As shown by the Western blotting, compared with the control group, the HMGB1 protein expression significantly decreased in the PANC-1 group after the transfection of miR-218 mimic for 48 h (P<0.01). CONCLUSIONS: The miR-218 expression decreases in human PCT and cell lines. miR-218 can negatively regulate the HMGB1 protein expression and inhibit the proliferation and invasion of pancreatic cancer cells. A treatment strategy by enhancing the miR-218 expression may benefit the patients with pancreatic cancer.
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OBJECTIVE: The purpose of this study was to examine the effect of gemcitabine (GEM) on microRNA-218 (miR-218) expression in human pancreatic cancer cells. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to examine the differences in miR-218 expression between the GEM-sensitive BxPC-3 pancreatic cancer cells and GEM-resistant PANC-1 cells. The effect of GEM on the expression of miR-218 in PANC-1 cells was also investigated. PANC-1 cells were transfected either with HMGB1 siRNA to knock down the expression of HMGB1 or with the recombinant HMGB1 expression vector (pcDNA3.1-HMGB1) to overexpress HMGB1. The effect of ectopic expression of HMGB1 on the apoptosis of miR-218-transfected and GEM-treated PANC-1 cells was examined by flow cytometric analysis. RESULTS: The miR-218 expression level was lower in GEM-resistant PANC-1 cells compared to GEM-sensitive BxPC-3 cells (P<0.05). The percentage of apoptotic PANC-1 cells was significantly increased in the miR-218 mimic + GEM group compared to the mimic ctrl + GEM group and the normal control group (P<0.01). The HMGB1 expression level was markedly decreased in PANC-1 cells transfected with HMGB1 siRNA but was significantly increased in PANC-1 cells transfected with the recombinant HMGB1 expression vector, pcDNA3.1-HMGB1 (P<0.01). The proportion of apoptotic PANC-1 cells was significantly lower in the miR-218 mimic + GEM + pcDNA3.1-HMGB1 group compared to the miR-218 mimic + GEM + HMGB1 siRNA group (P<0.01). CONCLUSIONS: The expression level of miR-218 was downregulated in the GEM-resistant cell line. miR-218 promoted the sensitivity of PANC-1 cells to GEM, which was achieved mainly through regulating the expression of HMGB1 in PANC-1 cells.
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CCL18 is a chemokine that is primarily expressed in monocytes, macrophages and immature dendritic cells and plays a crucial role in immune and inflammation responses. Recently, CCL18 was found to play pivotal roles in the development of several kinds of cancers, but its expression status and role during the tumorigenesis of pancreatic cancer remain unknown. In this study, we performed immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) to evaluate the expression of CCL18 in human pancreatic ductal adenocarcinoma (PDAC) tissues and preoperative serum, respectively. The results showed that both cancer epithelial cells and mesenchymal macrophages in PDAC tissues positively expressed CCL18. Serum CCL18 levels were significantly higher in patients with PDAC in comparison to healthy controls. The expression of CCL18 in both cancer epithelial cells and mesenchymal cells was correlated with lymph node metastasis, histopathological grading and overall survival in 62 PDAC patients. In vitro assays showed that the gene and protein expression of CCL18 from U937 and THP-1 cell- derived macrophages were significantly higher than that from unstimulated U937 cells and THP-1 cells. In contrast, pancreatic cancer cell lines showed little to no CCL18 expression even after IL4 stimulation. Intriguingly, pancreatic cancer cell lines expressed the potential CCL18 receptors PITPNM3, CCR6 and GPR3. Furthermore, treatment with recombinant human CCL18 promoted the migration and invasion of pancreatic cancer cells, but had no effect on cell proliferation. Consistent with these results, CCL18 induced the expression of the epithelial-mesenchymal transition (EMT) related gene SNAIL1. Our findings suggest that the serum level of CCL18 is a potential biomarker for the diagnosis and prognosis of PDAC, and that the combined functions of CCL18 in mesenchymal and cancer cells might accelerate the progression of PDAC by promoting the epithelial-mesenchymal transition, invasion and migration of pancreatic cancer cells.
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Carcinoma Ductal Pancreático/patología , Quimiocinas CC/fisiología , Transición Epitelial-Mesenquimal/genética , Neoplasias Pancreáticas/patología , Adulto , Anciano , Carcinoma Ductal Pancreático/genética , Línea Celular Tumoral , Movimiento Celular/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Pancreáticas/genética , Células U937RESUMEN
Pancreatic adenocarcinoma (PA) is a leading cause of adult cancer mortality, and surgery is still the best available treatment strategy. However, PA can recur at any time and has limited prognosis. It is therefore necessary to explore novel serum biomarkers of PA to allow the early diagnosis of PA. Soluble a-proliferation-inducing ligand (sAPRIL), a promising inducer of the epithelial-mesenchymal transition (EMT), is often found overexpressed in a variety of autoimmune diseases. To determine whether serum sAPRIL can constitute a PA biomarker, the protein level of sAPRIL was examined by immunohistochemistry and western blot, and the mRNA level was quantified by RT-qPCR. The PA cell line PanC-1 was transfected with vectors bearing the sAPRIL gene and sAPRIL short hairpin RNA (shRNA) oligos. Increased expression of serum sAPRIL was observed in patients with PA recurrence or metastasis after five-year surgery compared to subjects without PA recurrence or metastasis. The growth rate of PanC-1 cells transfected with the sAPRIL expression vector was increased by 23% (P<0.01, vs. control group), and was reduced by 17% (P<0.01, vs. control group) in the sAPRIL shRNA-silenced cell line. Thus, sAPRIL is highly expressed in PA, and serum levels of sAPRIL can serve as a useful indicator for the recurrence or metastasis of PA after surgery. Additional validation studies on the use of serum sAPRIL as a diagnostic marker in PA are however needed.
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Adenocarcinoma/patología , Neoplasias Pancreáticas/patología , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/sangre , Adenocarcinoma/metabolismo , Adenocarcinoma/cirugía , Anciano , Biomarcadores/sangre , Línea Celular Tumoral , Proliferación Celular , Femenino , Vectores Genéticos/metabolismo , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/cirugía , Interferencia de ARN , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Transfección , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/antagonistas & inhibidores , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/genéticaRESUMEN
In this study, the impact of pancreatic cancer cell interaction with macrophages on the differentiation and function of macrophages and the behaviors of pancreatic cancer cells in vitro is evaluated. The expression of immunocompetent cell-associated markers in 22 pancreatic cancer specimens was characterized by immunohistochemistry. The impact of pancreatic cancer cells (PANC-1 and BxPC-3) on the differentiation and migration of human U937 monocytes and the effect of U937-derived macrophages on the proliferation and invasion of PANC-1 and BxPC-3 were determined by transwell assays. The potential effect on U937-derived macrophages or on the behaviors of pancreatic cancer cells following coculture in a transwell system was analyzed by quantitative real-time polymerase chain reaction. The high levels of macrophage-related CD68 and CD163 expression were detected in the pancreatic cancer specimens. Pancreatic cancer cells promoted the differentiation of U937 cells and migration of U937-derived macrophages, but decreased the mRNA transcripts of macrophage polarization-related genes of interleukin (IL)-10, IL-12p40, inducible nitric oxide synthase (iNOS), and CD163, particularly for iNOS. Furthermore, U937-derived M2 macrophages inhibited the proliferation of pancreatic cancer cells, but promoted their invasion. Coculture of pancreatic cancer cells with U937-derived macrophages upregulated the mRNA expression of genes associated with the epithelial-mesenchymal transition process, angiogenesis, and stemness of pancreatic cancer, but downregulated the expression of E-cadherin in pancreatic cancer cells. The interaction between pancreatic cancer cells and tumor-associated macrophages may play a pivotal role in the progression of pancreatic cancer.