5-nitro-thiophene-thiosemicarbazone derivative induces cell death, cell cycle arrest, and phospho-kinase shutdown in pancreatic ductal adenocarcinoma cells.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options. This study explores the potential of novel 5-nitro-thiophene-thiosemicarbazone derivatives as therapeutic agents for PDAC. METHODS: We evaluated the cytotoxicity of seven derivatives in peripheral blood mononuclear cells (PBMCs) and PDAC cell lines. Promising candidates (PR12 and PR17) were further analyzed for their effects on colony formation, cell cycle progression, and reactive oxygen species (ROS) production. PR17, the most promising derivative, was subjected to additional investigation, including analysis of autophagy-related genes and protein kinase inhibition. RESULTS: Three derivatives (PR16, PR19, and PR20) displayed cytotoxicity towards PBMCs. PR12 reduced colony formation and G0/G1 cell cycle arrest in PDAC cells. Notably, PR17 exhibited potent activity in MIA PaCa-2 cells, inducing S-phase cell cycle arrest, downregulating autophagy genes, and inhibiting key protein kinases. CONCLUSION: PR17, a 5-nitro-thiophene-thiosemicarbazone derivative, demonstrates promising antineoplastic activity against PDAC cells by potentially modulating cell cycle progression, autophagy, and protein kinase signaling. Further studies are warranted to elucidate the detailed mechanism of action and explore its efficacy in vivo.

Atypical phosphatase DUSP11 inhibition promotes nc886 expression and potentiates gemcitabine-mediated cell death through NF-kB modulation.

Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers among all solid tumors. First-line treatment relies on gemcitabine (Gem) and despite treatment improvements, refractoriness remains a universal challenge. Attempts to decipher how feedback-loops control signaling pathways towards drug resistance have gained attention in recent years, particularly focused on the role of phosphatases. In this study, a CRISPR/Cas9-based phenotypic screen was performed to identify members from the dual-specificity phosphatases (DUSP) family potentially acting on Gem response in PDAC cells. The approach revealed the atypical RNA phosphatase DUSP11 as a potential target, whose inhibition creates vulnerability of PDAC cells to Gem. DUSP11 genetic inhibition impaired cell survival and promoted apoptosis, synergistically enhancing Gem cytotoxicity. In silico transcriptome analysis of RNA-seq data from PDAC human samples identified NF-ĸB signaling pathway highly correlated with DUSP11 upregulation. Consistently, Gem-induced NF-ĸB phosphorylation was blocked upon DUSP11 inhibition in vitro. Mechanistically, we found that DUSP11 directly impacts nc886 expression and modulates PKR-NF-ĸB signaling cascade after Gem exposure in PDAC cells resulting in resistance to Gem-induced cell death. In conclusion, this study provides new insights on DUSP11 role in RNA biology and Gem response in PDAC cells.

Laparoscopic Versus Open Pancreatoduodenectomy for Periampullary Tumors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: Laparoscopic pancreatoduodenectomy (LPD) has emerged as an alternative to open technique in treating periampullary tumors. However, the safety and efficacy of LPD compared to open pancreatoduodenectomy (OPD) remain unclear. Thus, we conducted an updated meta-analysis to evaluate the efficacy and safety of LPD versus OPD in patients with periampullary tumors, with a particular focus on the pancreatic ductal adenocarcinoma patient subgroup. METHODS: According to PRISMA guidelines, we searched PubMed, Embase, and Cochrane Library in December 2023 for randomized controlled trials (RCTs) that directly compare LPD versus OPD in patients with periampullary tumors. Endpoints and sensitive analysis were conducted for short-term endpoints. All statistical analysis was performed using R software version 4.3.1 with a random-effects model. RESULTS: Five RCTs yielding 1018 patients with periampullary tumors were included, of whom 511 (50.2%) were randomized to the LPD group. Total follow-up time was 90 days. LPD was associated with a longer operation time (MD 66.75; 95% CI 26.59 to 106.92; p = 0.001; I2 = 87%; Fig. 1A), lower intraoperative blood loss (MD - 124.05; 95% CI - 178.56 to - 69.53; p < 0.001; I2 = 86%; Fig. 1B), and shorter length of stay (MD - 1.37; 95% IC - 2.31 to - 0.43; p = 0.004; I2 = 14%; Fig. 1C) as compared with OPD. In terms of 90-day mortality rates and number of lymph nodes yield, no significant differences were found between both groups. CONCLUSION: Our meta-analysis of RCTs suggests that LPD is an effective and safe alternative for patients with periampullary tumors, with lower intraoperative blood loss and shorter length of stay.

Chronological pattern of venous thromboembolism (VTE) occurrence impacts in survival of pancreatic ductal adenocarcinoma (PDAC).

BACKGROUND: Limited data exist on the prognostic significance of the chronology of VTE in patients with PDAC. METHODS: Medical data and survival characteristics of patients treated for PDAC from 2019 to 2021 were retrospectively reviewed. Early VTE was defined as occurring within the three months of PDAC diagnosis. RESULTS: 197 patients were included, 54 (27.4%) developed a VTE. Early appearance of VTE was associated with worse prognosis: median overall survival (mOS) VTE < 3 months 8.5 months (HR 1.65, 95% CI 1.11-2.46; p = 0.014), mOS VTE > 3 months 12.8 months (HR 0.78, 95% CI 0.39-1.54; p = 0.5) and mOS patients without VTE 11.4 months (95% CI 10.1-15.4). There was no significant association between the patient's VTE risk according to the Khorana risk score (KRS) (chi2 test p-value = 0.9). CONCLUSION: Early VTE is a prognostic factor in PDAC, which may identify a more aggressive subtype.

BEYOND TRADITIONAL TOOLS: EXPLORING CONVOLUTIONAL NEURAL NETWORKS AS INNOVATIVE PROGNOSTIC MODELS IN PANCREATIC DUCTAL ADENOCARCINOMA.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and lethal form of cancer with limited prognostic accuracy using traditional factors. This has led to the exploration of innovative prognostic models, including convolutional neural networks (CNNs), in PDAC. CNNs, a type of artificial intelligence algorithm, have shown promise in various medical applications, including image analysis and pattern recognition. Their ability to extract complex features from medical images makes them suitable for improving prognostication in PDAC. However, implementing CNNs in clinical practice poses challenges, such as data availability and interpretability. Future research should focus on multi-center studies, integrating multiple data modalities, and combining CNN outputs with biomarker panels. Collaborative efforts and patient autonomy should be considered to ensure the ethical implementation of CNN-based prognostic models. Further validation and optimisation of CNN-based models are necessary to enhance their reliability and clinical utility in PDAC prognostication. BACKGROUND: •Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with limited prognostic accuracy through traditional methods. BACKGROUND: •Convolutional neural networks (CNNs) are being explored for prognostic models in PDAC. BACKGROUND: •They can extract complex features from images, aiding PDAC prognostication. BACKGROUND: •Further validation and optimization of CNN-based models are needed for better reliability and clinical utility in PDAC.

Assessing EUS-guided radiofrequency ablation in unresectable pancreatic ductal adenocarcinoma: a single-center historic cohort study.

BACKGROUND AND AIMS: EUS-guided radiofrequency ablation (EUS-RFA) has emerged as an alternative for the local treatment of unresectable pancreatic ductal adenocarcinoma (PDAC). We assessed the feasibility and safety of EUS-RFA in patients with unresectable PDAC. METHODS: This study followed an historic cohort compounded by locally advanced (LA-) and metastatic (m)PDAC-naïve patients who underwent EUS-RFA between October 2019 and March 2022. EUS-RFA was performed with a 19-gauge needle electrode with a 10-mm active tip for energy delivery. Study primary endpoints were feasibility, safety, and clinical follow-up, whereas secondary endpoints were performance status (PS), local control, and overall survival (OS). RESULTS: Twenty-six patients were selected: 15 with locally advanced pancreatic duct adenocarcinoma (LA-PDAC) and 11 with metastatic pancreatic duct adenocarcinoma (mPDAC). Technical success was achieved in all patients with no major adverse events. Six months after EUS-RFA, OS was seen in 11 of 26 patients (42.3%), with significant PS improvement (P = .03). Local control was achieved, with tumor reduction from 39.5 mm to 26 mm (P = .04). A post-treatment hypodense necrotic area was observed at the 6-month follow-up in 11 of 11 patients who were still alive. Metastatic disease was a significant factor for worsening OS (hazard ratio, 5.021; 95% confidence interval, 1.589-15.87; P = .004). CONCLUSIONS: EUS-RFA for the treatment of pancreatic adenocarcinoma is a minimally invasive and safe technique that may have an important role as targeted therapy for local treatment of unresectable cases and as an alternative for poor surgical candidates. Also, RFA may play a role in downstaging cancer with a potential increase in OS in nonmetastatic cases. Large prospective cohorts are required to evaluate this technique in clinical practice.

Biopsias endoscópicas en la era de la inmunoterapia y oncogenética: ¿podemos cumplir los requerimientos? / Endoscopic biopsies in the era of immunotherapy and oncogenetics: can we meet the requirements?

Pancreatic ductal adenocarcinoma has increased its incidence in recent years. In approximately half of the cases, the diagnosis is made when the disease is in the metastatic stage. In advanced stages, treatment with immunotherapy is included with promising results. Histopathological diagnosis is required for the administra - tion of chemotherapy. Endosonography biopsy has benefits due to its high sensitivity and specificity, absence of the need for hospitalization, and low adverse events. Fine biopsy needles are classified according to two characteristics: diameter (19, 22 and 25 G) and tissue acquisition mechanism (FNA and FNB). The emergence of immunotherapy guided by tumor oncogenetics requires an increase in sample size. There are no significant differences between the presence of the pathologist in taking the sample (rapid on-side evaluation, ROSE) over the macroscopic visualization of the biopsy by the endosonographer (macroscopic on-side evaluation, MOSE). The use of FNB for biopsy is recommended over FNA with ROSE when it is necessary to make a diagnosis or genetic study and it is not possible to perform it with the ROSE modality. The factors that determine an adequate sample collection are the location of the biopsy (pancreas 54.3% vs. lymph nodes/metastasis 76.5%) and the diameter/type of needle.

El adenocarcinoma ductal pancreático ha presentado un aumento de su incidencia en los últimos años En aproximadamente la mitad de los casos se realiza el diagnóstico cuando la enfermedad se encuentra en etapa metastásica. En etapas avanzadas se incluye el tratamiento con inmunoterapia con resultados promisorios. Para la administración de quimioterapia se requiere el diagnóstico histopatológico. La biopsia por endosonografía presenta beneficios debido a su alta sensibilidad y especificidad, ausencia de necesidad de hospitalización y bajos eventos adversos. Las agujas finas de biopsia se clasifican según dos características: diámetro (19, 22 y 25 G) y mecanismo de adquisición del tejido (FNA y FNB). La aparición de la inmunoterapia guiada por la oncogenética tumoral requiere un incremento del tamaño de las muestras. No existen diferencias significativas entre la presencia del anatomopatólogo en la toma de la muestra ( rapid on-side evaluation, ROSE) por sobre la visualización macroscópica de la biopsia por parte del endosonografista (macroscopic on-side evaluation, MOSE). Se recomienda el uso de FNB para toma de biopsia por sobre FNA con ROSE cuando es necesario hacer diagnóstico, estudio genético y no es posible realizarlo con modalidad ROSE. Los factores que determi - nan una toma de muestra adecuada son la localización de la biopsia (páncreas 54,3% vs. linfonodos/metástasis 76,5%) y el diámetro/tipo de aguja

Synergistic effect of antagonists to KRas4B/PDE6 molecular complex in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis among all human cancers as it is highly resistant to chemotherapy. K-Ras mutations usually trigger the development and progression of PDAC. We hypothesized that compounds stabilizing the KRas4B/PDE6δ complex could serve as PDAC treatments. Using in silico approaches, we identified the small molecules C14 and P8 that reduced K-Ras activation in primary PDAC cells. Importantly, C14 and P8 significantly prevented tumor growth in patient-derived xenotransplants. Combined treatment with C14 and P8 strongly increased cytotoxicity in PDAC cell lines and primary cultures and showed strong synergistic antineoplastic effects in preclinical murine PDAC models that were superior to conventional therapeutics without causing side effects. Mechanistically, C14 and P8 reduced tumor growth by inhibiting AKT and ERK signaling downstream of K-RAS leading to apoptosis, specifically in PDAC cells. Thus, combined treatment with C14 and P8 may be a superior pharmaceutical strategy to improve the outcome of PDAC.

Pancreatic cancer orthotopic graft in a murine model.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with increasing incidence. Even if progress have been made, the five-year overall survival remains lower than 10%. There is a desperate need in therapeutic improvements. In the last two decades, new in-vitro models have been developed and improved, including tridimensional-culture spheroids and organoids. However, animal studies remain mandatory in the upscaling before clinical studies. Orthotopic and syngeneic grafting is a robust model to test a drug efficiency in a tumor and its microenvironment. METHODS: We described a method for orthotopic and syngeneic graft of KRAS mutated, p53 wildtype, 8305 cells in a C57BL/6J mouse model. RESULTS: With this microsurgical method, 30 mice were grafted, 24 by a junior and six by a senior, resulting in 95,8 and 100% of (partial and total) successful tumoral implantation, respectively. Twenty mice underwent ultrasound follow-up. It was an efficient method for the tumoral growth evaluation. At day 16 after grafting, 85% of the tumors were detectable by ultrasound, and at day 22 all tumors were detected. CONCLUSIONS: The presented method appears to be a robust and reliable method for pre-clinical studies. A junior master student can provide positive results using this technique, which can be improved with training.

Tumor Microenvironment Role in Pancreatic Cancer Stem Cells.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a majority of patients presenting with unresectable or metastatic disease, resulting in a poor 5-year survival rate. This, in turn, is due to a highly complex tumor microenvironment and the presence of cancer stem cells, both of which induce therapy resistance and tumor relapse. Therefore, understanding and targeting the tumor microenvironment and cancer stem cells may be key strategies for designing effective PDAC therapies. In the present review, we summarized recent advances in the role of tumor microenvironment in pancreatic neoplastic progression.

Pancreatic Cancer: Genetic Conditions and Epigenetic Alterations.

BACKGROUND: Pancreatic cancer is a lethal proliferative disease driven by multiple genetic and epigenetic alterations. Microarrays and omics-based sequencing techniques are potent tools that have facilitated a broader understanding of the complex biological processes that drive pancreatic ductal adenocarcinoma (PDAC). In turn, these tools have resulted in the identification of novel disease markers, prognostic factors, and therapeutic targets. Herein, we provide a review of the genetic and epigenetic drivers of PDAC relative to recent discoveries that impact patient management. METHODS: A review of PubMed, Medline, Clinical Key, and Index Medicus was conducted to identify literature from January 1995 to July 2022 that is related to PDAC genetics and epigenetics. Articles in Spanish and English were considered during selection. RESULTS: Molecular, genetic, and epigenetic diagnostic tools, novel biomarkers, and promising therapeutic targets have emerged in the treatment of pancreatic cancer. The implementation of microarray technology and application of large omics-based data repositories have facilitated recent discoveries in PDAC. Multiple molecular analyses based on RNA interference have been instrumental in the identification of novel therapeutic targets for patients with PDAC. Moreover, microarrays and next-generation omics-based discoveries have been instrumental in the characterization of subtypes of pancreatic cancer, thereby improving prognostication and refining patient selection for available targeted therapies. CONCLUSION: Advances in molecular biology, genetics, and epigenetics have ushered in a new era of discovery in the pathobiology of PDAC. Current efforts are underway to translate these findings into clinical tools and therapies to improve outcomes in patients with PDAC.

Prognostic Factors in Resected Pancreatic Ductal Adenocarcinoma: Is Neutrophil-Lymphocyte Ratio a Useful Marker?

BACKGROUND: The aim of this study is to analyze the role of neutrophil-lymphocyte ratio (NLR) and its variation pre- and postoperatively (delta NLR) in the overall survival after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) at a single center and to identify factors associated with overall survival. METHODS: A retrospective study of consecutive patients undergoing pancreatectomy due to PDAC or undifferentiated carcinoma from January 2010 to January 2020 was performed. Association between the evaluated factors and overall survival was analyzed using a log-rank test and Cox proportional hazard regression model. RESULTS: Overall, 242 patients underwent pancreatectomy for PDAC or undifferentiated carcinoma. OS was 22.8 months (95% confidence interval (CI): 19.5-29), and survival rates at 1, 3, and 5 years were 72%, 32.5%, and 20.8%, respectively. NLR and delta NLR were not significantly associated with survival (hazard ratio (HR) = 1.14, 95%CI: 0.77-1.68, p = 0.5). Lymph node ratio was significantly associated (HR = 1.66, 95%CI: 1.21-2.26, p = 0.001) in the bivariate analysis. In multivariable analysis, the only factors that were significantly associated with survival were perineural invasion (HR = 1.94, 95%CI: 1.21-3.14, p = 0.006), surgical margin (HR = 1.83, 95%CI: 1.10-3.02, p = 0.019), tumor size (HR = 1.01, 95%CI: 1.003-1.027, p = 0.16), postoperative CA 19-9 level (HR = 1.001, p < 0.001), and completion of adjuvant treatment (HR = 0.53, 95%CI: 0.35-0.8, p = 0.002). CONCLUSION: Neutrophil-lymphocyte ratio and delta NLR were not associated with the overall survival in this cohort. Risk factors such as perineural invasion, surgical margins, CA19-9 level, and tumor size showed worse survival in this study, whereas completing adjuvant treatment was a protective factor.

[Survival of patients with pancreatic ductal adenocarcinoma]. / Sobrevida del adenocarcinoma ductal de páncreas.

OBJECTIVE: The objective of this study is to analyze the epidemiological presentation and survival of patients with pancreatic ductal adenocarcinoma according to their clinical stage and the type of intervention performed, in a cohort of patients treated at a clinic in Lima, Peru. MATERIALS AND METHODS: A retrospective cohort study evaluated patients diagnosed with pancreatic ductal adenocarcinoma from January 2015 to February 2021, considering various epidemiological factors, radiological findings, oncological staging, receipt of neoadjuvant or adjuvant chemotherapy, undergoing surgery, and post-intervention survival. RESULTS: Out of the 249 patients analyzed, 75 of them required resective surgery. Among the main findings, it was observed that those with a CA 19-9 level below 200 U/mL had a higher median survival compared to those with a CA 19-9 level above 200 U/mL (HR: 1.96; 95% CI: 0.18-0.53; p≤0.001). Furthermore, when comparing patients according to their stage, those with resectable tumors had a median survival of 37.72 months, while those with locally advanced tumors had a median survival of 13.47 months, and those with metastatic tumors had a median survival of 7.69 months (HR: 0.87; 95% CI: 0.31-0.25; p≤0.001). Additionally, receiving neoadjuvant treatment was associated with a better prognosis of survival for patients (HR: 0.32; 95% CI: 0.19-0.53; p≤0.001). Furthermore, 5 pancreatectomies with metastatic resection were performed in oligometastatic patients treated with salvage chemotherapy, and the median survival for these patients was 22.51 months. CONCLUSION: Resective surgery at an early clinical stage, CA 19-9 levels below 200 U/mL, and receiving neoadjuvant chemotherapy are statistically correlated with a higher overall survival.

Combination immunotherapy for pancreatic cancer: challenges and future considerations.

INTRODUCTION: Immune checkpoint inhibitors (ICI) have not yielded significant efficacy in pancreatic ductal adenocarcinoma (PDA), despite the role of the innate and adaptive immune systems on progression and survival. However, recently identified pathways have identified new targets and generated promising clinical investigations into promoting an effective immune-mediated antitumor response in PDA. AREAS COVERED: We review biological mechanisms associated with immunotherapy resistance and outline strategies for therapeutic combinations with established and novel therapies in PDA. EXPERT OPINION: Pancreatic cancers rarely benefit from treatment with ICI due to an immunosuppressive tumor microenvironment (TME). New understandings of factors associated with the suppressive TME include low- and poor-quality neoantigens, constrained effector T cells infiltration, and the presence of a dense, suppressive myeloid cell population. These findings have been translated into new clinical investigations evaluating novel therapies in combination with ICI and/or standard systemic chemotherapy and radiotherapy. The epithelial, immune, and stromal compartments are intricately related in PDA, and the framework for successful targeting of this disease requires a comprehensive and personalized approach.

MICRObiota on BILIOpancreatic malignant diseases [MICROBILIO]: A systematic review.

INTRODUCTION: The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose to analyze new findings on the association between microbiota and Pancreatic Ductal Adenocarcinoma (PDAC) or Cholangiocarcinoma (CCA). METHODS: This systematic review was carried out according to the items of Preferred Reports for Systematic Reviews and Protocol Meta-Analysis (PRISMA-P). This study was registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020192748 before the review was carried out. Articles were selected from the PUBMED, EMBASE, and Cochrane databases. RESULTS: Most studies (86.67%) used 16s rRNA as a sequencing method. The main comorbidities found were diabetes mellitus, systemic arterial hypertension, and dyslipidemia. Many studies were limited by the small number of participants, but the biases were mostly low. There was very little concordance about the composition of the microbiome of different sites, for both case and control groups when compared to other studies' results. Bile sample analysis was the one with a greater agreement between studies, as three out of four studies found Escherichia in cases of CCA. CONCLUSION: There was great disagreement in the characterization of both the microbiota of cases and control groups. Studies are still scarce, making it difficult to adequately assess the data in this regard. It was not possible to specify any marker or to associate any genus of microbiota bacteria with PDAC or CCA.

Sesquiterpene Lactones as Promising Candidates for Cancer Therapy: Focus on Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease which confers to patients a poor prognosis at short term. PDAC is the fourth leading cause of death among cancers in the Western world. The rate of new cases of pancreatic cancer (incidence) is 10 per 100,000 but present a 5-year survival of less than 10%, highlighting the poor prognosis of this pathology. Furthermore, 90% of advanced PDAC tumor present KRAS mutations impacting in several oncogenic signaling pathways, many of them associated with cell proliferation and tumor progression. Different combinations of chemotherapeutic agents have been tested over the years without an improvement of significance in its treatment. PDAC remains as one the more challenging biomedical topics thus far. The lack of a proper early diagnosis, the notable mortality statistics and the poor outcome with the available therapies urge the entire scientific community to find novel approaches against PDAC with real improvements in patients' survival and life quality. Natural compounds have played an important role in the process of discovery and development of new drugs. Among them, terpenoids, such as sesquiterpene lactones, stand out due to their biological activities and pharmacological potential as antitumor agents. In this review, we will describe the sesquiterpene lactones with in vitro and in vivo activity against pancreatic tumor cells. We will also discuss the mechanism of action of the compounds as well as the signaling pathways associated with their activity.

Human umbilical cord mesenchymal stem cell-derived exosomes carrying hsa-miRNA-128-3p suppress pancreatic ductal cell carcinoma by inhibiting Galectin-3.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignant tumors of the digestive system. Many patients are diagnosed at an advanced stage and lose eligibility for surgery. Moreover, there are few effective methods for treating pancreatic ductal cell carcinoma. Increasing attention has been given to microRNAs (miRNAs) and their regulatory roles in tumor progression. In this study, we investigated the effects of exosomes extracted from human umbilical cord mesenchymal stem cells (HUCMSCs) carrying hsa-miRNA-128-3p on pancreatic cancer cells. METHODS: Based on existing experimental and database information, we selected Galectin-3, which is associated with pancreatic cancer, and the corresponding upstream hsa-miRNA-128-3p. We extracted HUCMSCs from a fresh umbilical cord, hsa-miRNA-128-3p was transfected into HUCMSCs, and exosomes containing hsa-miRNA-128-3p were extracted and collected. The effect of exosomes rich in hsa-miRNA-128-3p on pancreatic cancer cells was analyzed. RESULTS: The expression of Galectin-3 in normal pancreatic duct epithelial cells was significantly lower than that in PDAC cell lines. We successfully extracted HUCMSCs from the umbilical cord and transfected hsa-miRNA-128-3p into HUCMSCs. Then we demonstrated that HUCMSC-derived exosomes with hsa-miRNA-128-3p could suppress the proliferation, invasion, and migration of PANC-1 cells in vitro by targeting Galectin-3. CONCLUSION: Hsa-miRNA-128-3p could be considered as a potential therapy for pancreatic cancer. We provided a new idea for targeted therapy of PDAC.

[Pancreatic cancer screening in a clinical practice setting: it is the moment of Prevention]. / Cribado de cáncer de páncreas en la práctica clínica: es el momento de la prevención.

Pancreatic cancer surveillance can improve outcomes in high-risk individuals. However, little is known about its applicability and findings in routine clinical practice. Our aim was to evaluate findings on screening tests in high-risk individuals in a clinical practice setting and to analyze factors associated with the presence of relevant pancreatic lesions. We developed a prospective observational study of pancreatic cancer high risk patients that meet criteria of surveillance from the International Cancer of the Pancreas Screening Consortium. The demographic variables, other risk factors and imaging findings are collected. Patients with significant findings are compared to those without noteworthy findings. Of 70 high-risk individuals, 25 fitted the criteria for pancreatic cancer surveillance. The most frequent condition was hereditary breast and ovarian cancer syndrome (60%). We identified eleven abnormal imaging findings (44%) and three of them (12%) were relevant: two intraductal papillary mucinous neoplasms and one localized pancreatic neoplasm. BRCA2 mutation was more frequent in patients with significant lesions (66.7% vs 30%, p=0.376) but smoking and diabetes were not associated with relevant findings (0 vs 18 %, p=0.578 and 0 vs 4.5%, p=0.880 respectively). Screening test could detect early-stage or resectable lesions in a significant in a significant percentage of the selected high-risk population. The most relevant findings were in patients belonging to hereditary breast and ovarian cancer syndrome.

The Role of lncRNAs in the Stem Phenotype of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma is one of the deadliest tumors. This neoplasia is characterized by an important cellular and phenotypic heterogeneity. In particular, it has been shown that at least two subtypes can be found: basal-like, which presents stem-like properties, and classical. Cancer stem cells have been isolated and characterized from these tumors, showing their dependance on general and tissue-specific stem transcription factors and signaling pathways. Nevertheless, little is known about their tissue microenvironment and cell non-autonomous regulators, such as long-non-coding RNAs. (lncRNAs). In this review, we summarize the current knowledge about the positive and negative effects of lncRNAs in the stemness phenotype of pancreatic ductal adenocarcinoma cancer (PDAC).

Prognostic factors in advanced pancreatic ductal adenocarcinoma patients-receiving second-line treatment: a single institution experience.

BACKGROUND: Second-line (2L) treatments for advanced pancreatic ductal adenocarcinoma (PDAC) achieve a modest benefit at the expense of potential toxicity. In the absence of predictive factors of response, the identification of prognostic factors could help in the therapeutic decisions-making. The purpose of this study was to assess the prognostic factors associated with shorter survival in patients with advanced PDAC who received 2L treatment. METHODS: We conducted a single institution retrospective study, which included all patients with advanced PDAC who received 2L treatment between September 2006 and February 2020 at La Paz University Hospital, Madrid (Spain). Significant variables in the logistic regression model were used to create a prognostic score. RESULTS: We included 108 patients. The median overall survival (OS) was 5.10 months (95%CI 4.02-6.17). In the multivariate analysis, time to progression (TTP) shorter than 4 months after first-line treatment (OR 4.53 [95%CI 1.28-16.00] p = 0.01), neutrophil-to-lymphocyte ratio (NLR) greater than 3 at the beginning of 2L (OR 9.07 [95%CI 1.82-45.16] p = 0.01) and CA-19.9 level higher than the upper limit of normal at the beginning of 2L (OR 7.83 [95%CI 1.30-49.97] p = 0.02) were independently associated with OS shorter than 3 months. The prognostic score classified patients into three prognostic groups (good, intermediate and poor) with significant differences in OS (p < 0.001). CONCLUSIONS: TTP shorter than 4 months after first-line treatment, NLR greater than 3 and CA-19.9 level higher than the upper limit of normal at the beginning of 2L were associated with shorter overall survival. We developed a prognostic score that classifies patients with advanced PDAC into three prognostic groups after progression to the first-line. This score could help in the decision-making for 2L treatment.