scholarly journals Micro- and Mycobiota Dysbiosis in Pancreatic Ductal Adenocarcinoma Development

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3431
Author(s):  
Ruben Bellotti ◽  
Cornelia Speth ◽  
Timon E. Adolph ◽  
Cornelia Lass-Flörl ◽  
Maria Effenberger ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Intestinal Flora ◽  
Treatment Strategies ◽  
Fusobacterium Nucleatum ◽  
Pancreatic Tissue ◽  
Individual Variability ◽  
Ductal Adenocarcinoma

Background: Dysbiosis of the intestinal flora has emerged as an oncogenic contributor in different malignancies. Recent findings suggest a crucial tumor-promoting role of micro- and mycobiome alterations also in the development of pancreatic ductal adenocarcinoma (PDAC). Methods: To summarize the current knowledge about this topic, a systematic literature search of articles published until October 2020 was performed in MEDLINE (PubMed). Results: An increasing number of publications describe associations between bacterial and fungal species and PDAC development. Despite the high inter-individual variability of the commensal flora, some studies identify specific microbial signatures in PDAC patients, including oral commensals like Porphyromonas gingivalis and Fusobacterium nucleatum or Gram-negative bacteria like Proteobacteria. The role of Helicobacter spp. remains unclear. Recent isolation of Malassezia globosa from PDAC tissue suggest also the mycobiota as a crucial player of tumorigenesis. Based on described molecular mechanisms and interactions between the pancreatic tissue and the immune system this review proposes a model of how the micro- and the mycobial dysbiosis could contribute to tumorigenesis in PDAC. Conclusions: The presence of micro- and mycobial dysbiosis in pancreatic tumor tissue opens a fascinating perspective on PDAC oncogenesis. Further studies will pave the way for novel tumor markers and treatment strategies.

scholarly journals The Emerging Role of Cyclin-Dependent Kinases (CDKs) in Pancreatic Ductal Adenocarcinoma

2018 ◽  
Vol 19 (10) ◽  
pp. 3219 ◽  
Author(s):  
Balbina García-Reyes ◽  
Anna-Laura Kretz ◽  
Jan-Philipp Ruff ◽  
Silvia von Karstedt ◽  
Andreas Hillenbrand ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Ductal Adenocarcinoma ◽  
Transcriptional Elongation ◽  
Cyclin Dependent Kinases ◽  
Dismal Prognosis ◽  
The Family ◽  
Cycle Regulation

The family of cyclin-dependent kinases (CDKs) has critical functions in cell cycle regulation and controlling of transcriptional elongation. Moreover, dysregulated CDKs have been linked to cancer initiation and progression. Pharmacological CDK inhibition has recently emerged as a novel and promising approach in cancer therapy. This idea is of particular interest to combat pancreatic ductal adenocarcinoma (PDAC), a cancer entity with a dismal prognosis which is owed mainly to PDAC’s resistance to conventional therapies. Here, we review the current knowledge of CDK biology, its role in cancer and the therapeutic potential to target CDKs as a novel treatment strategy for PDAC.

scholarly journals The Emerging Role of Microbiota and Microbiome in Pancreatic Ductal Adenocarcinoma

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 565
Author(s):  
Sona Ciernikova ◽  
Maria Novisedlakova ◽  
Danka Cholujova ◽  
Viola Stevurkova ◽  
Michal Mego
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Malignant Tumors ◽  
Current Knowledge ◽  
Early Stage ◽  
Poor Response ◽  
Response To Therapy ◽  
Oral Microbiome ◽  
Ductal Adenocarcinoma ◽  
The Impact

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant tumors due to the absence of biomarkers for early-stage detection and poor response to therapy. Since mounting evidence supports the role of microbiota composition in tumorigenesis and cancer treatment, the link between microbiome and PDAC has been described. In this review, we summarize the current knowledge regarding the impact of the gut and oral microbiome on the risk of PDAC development. Microenvironment-driven therapy and immune system interactions are also discussed. More importantly, we provide an overview of the clinical trials evaluating the microbiota role in the risk, prognosis, and treatment of patients suffering from PDAC and solid tumors. According to the research findings, immune tolerance might result from the microbiota-derived remodeling of pancreatic tumor microenvironment. Thus, microbiome profiling and targeting represent the potential trend to enhance antitumor immunity and improve the efficacy of PDAC treatment.

scholarly journals Molecular Mechanisms Underlying the Role of MicroRNAs in the Chemoresistance of Pancreatic Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Ingrid Garajová ◽  
Tessa Y. Le Large ◽  
Adam E. Frampton ◽  
Christian Rolfo ◽  
Johannes Voortman ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Severe Disease ◽  
Predictive Biomarkers ◽  
Incidence Rates ◽  
Ductal Adenocarcinoma ◽  
Specific Expression ◽  
Response To Chemotherapy ◽  
Tumor Types

Pancreatic ductal adenocarcinoma (PDAC) is an extremely severe disease where the mortality and incidence rates are almost identical. This is mainly due to late diagnosis and limited response to current treatments. The tumor macroenvironment/microenvironment have been frequently reported as the major contributors to chemoresistance in PDAC, preventing the drugs from reaching their intended site of action (i.e., the malignant duct cells). However, the recent discovery of microRNAs (miRNAs) has provided new directions for research on mechanisms underlying response to chemotherapy. Due to their tissue-/disease-specific expression and high stability in tissues and biofluids, miRNAs represent new promising diagnostic and prognostic/predictive biomarkers and therapeutic targets. Furthermore, several studies have documented that selected miRNAs, such as miR-21 and miR-34a, may influence response to chemotherapy in several tumor types, including PDAC. In this review, we summarize the current knowledge on the role of miRNAs in PDAC and recent advances in understanding their role in chemoresistance through multiple molecular mechanisms.

scholarly journals YAP1 oncogene is a context-specific driver for pancreatic ductal adenocarcinoma

2018 ◽  
Author(s):  
Bo Tu ◽  
Jun Yao ◽  
Sammy Ferri-Borgogno ◽  
Jun Zhao ◽  
Shujuan Chen ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Poor Prognosis ◽  
Clinical Characteristics ◽  
Molecular Mechanisms ◽  
Molecular Subtypes ◽  
Ductal Adenocarcinoma ◽  
Wnt5a Expression ◽  
Context Specific ◽  
Aggressive Clinical Behavior

AbstractTranscriptomic profiling classifies pancreatic ductal adenocarcinoma (PDAC) into several molecular subtypes with distinctive histological and clinical characteristics. However, little is known about the molecular mechanisms that define each subtype and their correlation with clinical outcome. Mutant KRAS is the most prominent driver in PDAC, present in over 90% of tumors, but the dependence of tumors on oncogenic KRAS signaling varies between subtypes. In particular, squamous subtype are relatively independent of oncogenic KRAS signaling and typically display much more aggressive clinical behavior versus progenitor subtype. Here, we identified that YAP1 activation is enriched in the squamous subtype and associated with poor prognosis. Activation of YAP1 in progenitor subtype cancer cells profoundly enhanced malignant phenotypes and transformed progenitor subtype cells into squamous subtype. Conversely, depletion of YAP1 specifically suppressed tumorigenicity of squamous subtype PDAC cells. Mechanistically, we uncovered a significant positive correlation between WNT5A expression and the YAP1 activity in human PDAC, and demonstrated that WNT5A overexpression led to YAP1 activation and recapitulated YAP1-dependent but Kras-independent phenotype of tumor progression and maintenance. Thus, our study identifies YAP1 oncogene as a major driver of squamous subtype PDAC and uncovers the role of WNT5A in driving PDAC malignancy through activation of the YAP pathway.

scholarly journals SMAD4 and the TGFβ Pathway in Patients with Pancreatic Ductal Adenocarcinoma

2020 ◽  
Vol 21 (10) ◽  
pp. 3534
Author(s):  
Julie Dardare ◽  
Andréa Witz ◽  
Jean-Louis Merlin ◽  
Pauline Gilson ◽  
Alexandre Harlé
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Current Knowledge ◽  
Ductal Adenocarcinoma ◽  
Tgfβ Signaling ◽  
Potent Inducer ◽  
Mesenchymal Transition ◽  
Tgfβ Pathway

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death worldwide. PDAC is an aggressive disease with an 11-month median overall survival and a five-year survival of less than 5%. Incidence of PDAC is constantly increasing and is predicted to become the second leading cause of cancer in Western countries within a decade. Despite research and therapeutic development, current knowledge about PDAC molecular mechanisms still needs improvements and it seems crucial to identify novel therapeutic targets. Genomic analyses of PDAC revealed that transforming growth factor β (TGFβ) signaling pathways are modified and the SMAD4 gene is altered in 47% and 60% of cases, respectively, highlighting their major roles in PDAC development. TGFβ can play a dual role in malignancy depending on the context, sometimes as an inhibitor and sometimes as an inducer of tumor progression. TGFβ signaling was identified as a potent inducer of epithelial-to-mesenchymal transition (EMT), a process that confers migratory and invasive properties to epithelial cells during cancer. Therefore, aberrant TGFβ signaling and EMT are linked to promoting PDAC aggressiveness. TGFβ and SMAD pathways were extensively studied but the mechanisms leading to cancer promotion and development still remain unclear. This review aims to describe the complex role of SMAD4 in the TGFβ pathway in patients with PDAC.

scholarly journals The Role of lncRNAs in the Stem Phenotype of Pancreatic Ductal Adenocarcinoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6374
Author(s):  
Jorge Melendez-Zajgla ◽  
Vilma Maldonado
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Cancer Stem Cells ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Current Knowledge ◽  
Ductal Adenocarcinoma ◽  
Negative Effects ◽  
Tissue Microenvironment ◽  
Non Coding Rnas

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).

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

scholarly journals A Proteomic Study on the Personalized Protein Corona of Liposomes. Relevance for Early Diagnosis of Pancreatic DUCTAL Adenocarcinoma and Biomarker Detection

2021 ◽  
Vol 2 (2) ◽  
pp. 82-93
Author(s):  
Luca Digiacomo ◽  
Francesca Giulimondi ◽  
Daniela Pozzi ◽  
Alessandro Coppola ◽  
Vincenzo La Vaccara ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Diagnosis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Protein Corona ◽  
Detection Sensitivity ◽  
Ductal Adenocarcinoma ◽  
Protein Biomarkers ◽  
Ca 19.9 ◽  
Proteomic Study

Due to late diagnosis, high incidence of metastasis, and poor survival rate, pancreatic cancer is one of the most leading cause of cancer-related death. Although manifold recent efforts have been done to achieve an early diagnosis of pancreatic cancer, CA-19.9 is currently the unique biomarker that is adopted for the detection, despite its limits in terms of sensitivity and specificity. To identify potential protein biomarkers for pancreatic ductal adenocarcinoma (PDAC), we used three model liposomes as nanoplatforms that accumulate proteins from human plasma and studied the composition of this biomolecular layer, which is known as protein corona. Indeed, plasma proteins adsorb on nanoparticle surface according to their abundance and affinity to the employed nanomaterial, thus even small differences between healthy and PDAC protein expression levels can be, in principle, detected. By mass spectrometry experiments, we quantified such differences and identified possible biomarkers for PDAC. Some of them are already known to exhibit different expressions in PDAC proteomes, whereas the role of other relevant proteins is still not clear. Therefore, we predict that the employment of nanomaterials and their protein corona may represent a useful tool to amplify the detection sensitivity of cancer biomarkers, which may be used for the early diagnosis of PDAC, with clinical implication for the subsequent therapy in the context of personalized medicine.

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