scholarly journals The Intricate Metabolism of Pancreatic Cancers

2021 ◽  
pp. 77-88
Author(s):  
Felipe Camelo ◽  
Anne Le
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Poor Prognosis ◽  
Cancer Metabolism ◽  
Genetic Alterations ◽  
Cancer Growth ◽  
Cancer Death ◽  
Pancreatic Cancers ◽  
Close Relationship

AbstractCurrently, approximately 95% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC), which are the most aggressive form and the fourth leading cause of cancer death with extremely poor prognosis [1]. Poor prognosis is primarily attributed to the late diagnosis of the disease when patients are no longer candidates for surgical resection [2]. Cancer cells are dependent on the oncogenes that allow them to proliferate limitlessly. Thus, targeting the expression of known oncogenes in pancreatic cancer has been shown to lead to more effective treatment [3]. This chapter discusses the complexity of metabolic features in pancreatic cancers. In order to comprehend the heterogeneous nature of cancer metabolism fully, we need to take into account the close relationship between cancer metabolism and genetics. Gene expression varies tremendously, not only among different types of cancers but also within the same type of cancer among different patients. Cancer metabolism heterogeneity is often prompted and perpetuated not only by mutations in oncogenes and tumor-suppressor genes but also by the innate diversity of the tumor microenvironment. Much effort has been focused on elucidating the genetic alterations that correlate with disease progression and treatment response [4, 5]. However, the precise mechanisms by which tumor metabolism contributes to cancer growth, survival, mobility, and aggressiveness represent a functional readout of tumor progression (Fig. 1).

The Engaged Role of Tumor Microenvironment in Cancer Metabolism: Focusing on Cancer-Associated Fibroblast and Exosome Mediators

2020 ◽  
Vol 21 (2) ◽  
pp. 254-266 ◽  
Author(s):  
Khandan Ilkhani ◽  
Milad Bastami ◽  
Soheila Delgir ◽  
Asma Safi ◽  
Shahrzad Talebian ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Metabolism ◽  
Krebs Cycle ◽  
Metabolic Reprogramming ◽  
Cancer Management ◽  
Cancer Associated Fibroblast ◽  
Potential Biomarker ◽  
Close Relationship ◽  
Microenvironmental Factors

: Metabolic reprogramming is a significant property of various cancer cells, which most commonly arises from the Tumor Microenvironment (TME). The events of metabolic pathways include the Warburg effect, shifting in Krebs cycle metabolites, and the rate of oxidative phosphorylation, potentially providing energy and structural requirements for the development and invasiveness of cancer cells. TME and tumor metabolism shifting have a close relationship through bidirectional signaling pathways between stromal and tumor cells. Cancer- Associated Fibroblasts (CAFs), as the most dominant cells of TME, play a crucial role in the aberrant metabolism of cancer. Furthermore, the stated relationship can affect survival, progression, and metastasis in cancer development. Recently, exosomes are considered one of the most prominent factors in cellular communications considering effective content and bidirectional mediatory effect between tumor and stromal cells. In this regard, CAF-Derived Exosomes (CDE) exhibit an efficient obligation to induce metabolic reprogramming for promoting growth and metastasis of cancer cells. The understanding of cancer metabolism, including factors related to TME, could lead to the discovery of a potential biomarker for diagnostic and therapeutic approaches in cancer management. This review focuses on the association between metabolic reprogramming and engaged microenvironmental, factors such as CAFs, and the associated derived exosomes.

Role of Tumor Microenvironment on Gene Expression in Pancreatic Cancer Tumor Models

2011 ◽  
Vol 171 (1) ◽  
pp. 136-142 ◽  
Author(s):  
Soeren Torge Mees ◽  
Wolf Arif Mardin ◽  
Christina Schleicher ◽  
Mario Colombo-Benkmann ◽  
Norbert Senninger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Tumor Models ◽  
Cancer Tumor

scholarly journals Advance in Pancreatic Cancer Diagnosis and Therapy

2020 ◽  
Author(s):  
Xiaojie Cai ◽  
Jie Gao ◽  
Yanfang Liu ◽  
Ming Wang ◽  
Qiulian Ma ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Survival Rate ◽  
Tumor Microenvironment ◽  
Cancer Diagnosis ◽  
Treatment Resistance ◽  
Serum Markers ◽  
Molecular Probes ◽  
Cancer Death ◽  
Cancer Diagnosis And Therapy

Pancreatic carcinoma is the fourth leading cause of cancer death in the word wild. Although the advance in treatment this disease, the 5-years survival rate is still rather low. In the recent year, many new therapy and treatment avenues have been developed for pancreatic cancer. In this chapter, we mainly focus on the following aspect: 1) the treatment modality in pancreatic cancer, including chemotherapy, radiotherapy, and immunotherapy; 2) the mechanism of pancreatic cancer treatment resistance, especially in cancer stem cells and tumor microenvironment; 3) the diagnosis tools in pancreatic cancer, including serum markers, imaging methods and endoscopic ultrasonography. Novel molecular probes based on the nanotechnology in the diagnosis of pancreatic cancer are also discussed.

scholarly journals Author Correction: PRMT1 promotes pancreatic cancer growth and predicts poor prognosis

2019 ◽  
Vol 43 (1) ◽  
pp. 63-64
Author(s):  
Chao Song ◽  
Tianwei Chen ◽  
Lan He ◽  
Ning Ma ◽  
Jian-ang Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Poor Prognosis ◽  
Cancer Growth

PRMT1 promotes pancreatic cancer growth and predicts poor prognosis

2019 ◽  
Vol 43 (1) ◽  
pp. 51-62 ◽  
Author(s):  
Chao Song ◽  
Tianwei Chen ◽  
Lan He ◽  
Ning Ma ◽  
Jian-ang Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Poor Prognosis ◽  
Cancer Growth

scholarly journals From Genetic Alterations to Tumor Microenvironment: The Ariadne’s String in Pancreatic Cancer

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 309 ◽  
Author(s):  
Chiara Bazzichetto ◽  
Fabiana Conciatori ◽  
Claudio Luchini ◽  
Francesca Simionato ◽  
Raffaela Santoro ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Current Knowledge ◽  
Myeloid Cells ◽  
Genetic Alterations ◽  
Molecular Characteristics ◽  
Precision Oncology ◽  
Cancer Type ◽  
Tumor Type ◽  
Driver Genes

The threatening notoriety of pancreatic cancer mainly arises from its negligible early diagnosis, highly aggressive progression, failure of conventional therapeutic options and consequent very poor prognosis. The most important driver genes of pancreatic cancer are the oncogene KRAS and the tumor suppressors TP53, CDKN2A, and SMAD4. Although the presence of few drivers, several signaling pathways are involved in the oncogenesis of this cancer type, some of them with promising targets for precision oncology. Pancreatic cancer is recognized as one of immunosuppressive phenotype cancer: it is characterized by a fibrotic-desmoplastic stroma, in which there is an intensive cross-talk between several cellular (e.g., fibroblasts, myeloid cells, lymphocytes, endothelial, and myeloid cells) and acellular (collagen, fibronectin, and soluble factors) components. In this review; we aim to describe the current knowledge of the genetic/biological landscape of pancreatic cancer and the composition of its tumor microenvironment; in order to better direct in the intrinsic labyrinth of this complex tumor type. Indeed; disentangling the genetic and molecular characteristics of cancer cells and the environment in which they evolve may represent the crucial step towards more effective therapeutic strategies

Effect of KRAS and P-STAT3 inhibition by SBT-100 on gemcitabine and pancreatic cancer growth in vivo.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15727-e15727
Author(s):  
Sunanda Singh ◽  
Genoveva Murillo ◽  
Avani Singh ◽  
Samara Singh ◽  
Meenakshi S Parihar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Targeted Therapy ◽  
Western Blot ◽  
Cancer Cells ◽  
Mtt Assay ◽  
Blot Analysis ◽  
Cancer Growth ◽  
Pancreatic Cancers ◽  
Pancreatic Cancer Cells

e15727 Background: Over 90% of pancreatic cancers have KRAS mutations and hyper-expression of P-STAT3 oncoproteins, which if specifically targeted may help treatment of pancreatic cancers. Singh Biotechnology’s proprietary technology engineered SBT-100, a single domain antibody that is bispecific for KRAS & STAT3, which can cross the cell membranes and bind to these intracellular oncoproteins. Combining this targeted therapy with an established chemotherapy, such as gemcitabine, may improve patient’s response to treatment. Methods: Human pancreatic cancer cells (PANC-1 and BX-PC3) were used. Biacore assay demonstrates SBT-100 binding to KRAS, KRAS (G12D), and STAT3. Immunoprecipitation (IP) and western blot analysis confirmed binding to STAT3 by SBT-100. Pancreatic cancer cells were treated at varying doses of SBT-100 ranging from 0µg/ml to 200µg/ml ± gemcitabine, and after 72 hours growth inhibition was determined by a MTT assay. PANC-1 tumors were grown in athymic nude mice, divided into four groups and staged to a range of 100-150mm3 before treatment. Groups were: vehicle only, SBT-100, gemcitabine, and SBT-100 & gemcitabine. Animals received treatments for 14 days, then monitored for 7 days. Results: Biacore study shows SBT-100 binds KRAS with an affinity of 10-9M, KRAS (G12D) with 10-8M, and STAT3 with 10-8M. IP and western blot analysis demonstrates that SBT-100 binds P-STAT3. MTT assay demonstrates SBT-100 inhibits the growth of PANC-1 and BX-PC3 (p < 0.001). In PANC1 cells a combination of SBT-100 & gemcitabine demonstrates synergism in inhibiting growth of PANC-1, even at 1/8th the gemcitabine IC50 concentration. PANC-1 xenograft study demonstrates that combination therapy of SBT-100 & gemcitabine is superior to either SBT-100 or gemcitabine alone. Compared to the vehicle group, SBT-100 & gemcitabine is far superior (p < 0.001) and gives statistically significant suppression of pancreatic cancer growth in vivo. Conclusions: Targeted therapy for KRAS and P-STAT3 expressing tumors with SBT-100 & gemcitabine is synergistic for the treatment of pancreatic cancer. This study suggests that synergism maybe achieved with lower doses of gemcitabine, thereby reducing toxicity in patients.

scholarly journals Early Detection and Investigation of Extracellular Vesicles Biomarkers in Breast Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Erika Bandini ◽  
Tania Rossi ◽  
Emanuela Scarpi ◽  
Giulia Gallerani ◽  
Ivan Vannini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Early Detection ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Cancer Death ◽  
Female Population ◽  
Flow Cytometric ◽  
Metastatic Development

Breast cancer (BC) is the most commonly diagnosed malignant tumor in women worldwide, and the leading cause of cancer death in the female population. The percentage of patients experiencing poor prognosis along with the risk of developing metastasis remains high, also affecting the resistance to current main therapies. Cancer progression and metastatic development are no longer due entirely to their intrinsic characteristics, but also regulated by signals derived from cells of the tumor microenvironment. Extracellular vesicles (EVs) packed with DNA, RNA, and proteins, are the most attractive targets for both diagnostic and therapeutic applications, and represent a decisive challenge as liquid biopsy-based markers. Here we performed a study based on a multiplexed phenotyping flow cytometric approach to characterize BC-derived EVs from BC patients and cell lines, through the detection of multiple antigens. Our data reveal the expression of EVs-related biomarkers derived from BC patient plasma and cell line supernatants, suggesting that EVs could be exploited for characterizing and monitoring disease progression.

Ixocarpalactone A from dietary tomatillo inhibits pancreatic cancer growth by targeting PHGDH

2019 ◽  
Vol 10 (6) ◽  
pp. 3386-3395 ◽  
Author(s):  
Mengzhu Zheng ◽  
Jing Guo ◽  
Jiamin Xu ◽  
Kaiyin Yang ◽  
Ruotian Tang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Growth ◽  
The Novel ◽  
Pancreatic Cancers ◽  
Phosphoglycerate Dehydrogenase

3-Phosphoglycerate dehydrogenase (PHGDH) has been reported to associate with tumorigenesis in many cancers. IoxA, a natural withanolide obtained from dietary tomatillo (Physalis ixocarpa), was identified as the novel natural PHGDH inhibitor with high targeting and low toxicities for treatment of pancreatic cancers.

The Expression Signatures of Mammary Tumor Associated Macrophages.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3850-3850
Author(s):  
Laureen S. Ojalvo ◽  
Jeffrey W. Pollard
Keyword(s):  
Gene Expression ◽  
Flow Cytometry ◽  
Cell Migration ◽  
Tumor Microenvironment ◽  
Poor Prognosis ◽  
Transcript Abundance ◽  
Carcinoma Cells ◽  
Tumor Cell Migration ◽  
Two Populations

Abstract It is well established that an increased density of tumor-associated macrophages (TAMs) correlates with poor prognosis in many types of solid tumors. This evidence is particularly strong for breast cancers. A causal relationship between TAMs and poor prognosis was suggested by experiments whereby a genetic depletion of macrophages in a mouse model of breast cancer caused by the mammary restricted expression of the Polyoma Middle T oncoprotein (PyMT) slowed tumor progression and inhibited metastasis. Subsequent studies in these primary mammary tumors showed that TAMs directly or indirectly promote tumor angiogenesis as well as tumor cell migration, invasion and intravasion. TAMs are also thought to affect the inflammatory context of the tumor microenvironment by suppressing adaptive immune responses that would normally reject the growing tumor. The varied tasks ascribed to TAMs suggested that the tumor microenvironment educates different population of macrophages to perform specific tasks. In this study, we isolated TAMs from the PyMT primary tumors in order to evaluate their gene expression signatures compared to a resident splenic population in order to define specific tumor associated functions. To perform these studies mice that express enhanced green fluorescent protein (eGFP) from the colony stimulating factor 1 receptor (CSF-1R) mononuclear phagocytic restricted promoter were crossed to the PyMT animals to generate offspring with eGFP+ TAMs. Animals were injected with dye-conjugated dextran two hours prior to sacrifice in order to identify phagocytic cells, a characteristic of macrophages. We have established that these eGFP+/dextran+ cells are F4/80+ and define the TAM population. EGFP+/dextran+ TAMs were isolated using flow cytometry from late-stage tumors and splenic macrophages were sorted from non-tumor bearing animals using an identical protocol. These two populations were analyzed on gene expression oligoarrays to better elucidate specific mediators of TAM pathogenicity. We have identified approximately 100 genes whose transcript abundance are up or down regulated in the TAM population including genes mediating angiogenesis, adhesion and inflammation. Furthermore, genes previously described to define the tumor associated suppressor macrophage (MIF-1, MIP1α and TGFβ, high; IL-18, low) were similarly regulated amongst the three biological repeats. To further define individual TAM populations, we used an in vivo invasion assay to isolate a subset of TAMs that promote carcinoma cell motility in vivo. This assay involves the collection of invasive tumor cells and co-migrating invasive TAMs into EGF-containing microneedles placed directly into the primary tumor of an MMTV-PyMT animal. Previously, this assay was used to describe a paracrine loop in which carcinoma cells secrete CSF-1 that binds CSF-1R on TAMs leading to TAM secretion of epidermal growth factor (EGF) that binds the EGF receptor on carcinoma cells and stimulate their motility. Disrupting this paracrine loop is known to block the invasion of both cell types. Invasive TAMs isolated via this assay and separated from invasive carcinoma cells using CD11b magnetic beads were compared by gene expression arrays to TAMs sorted by flow cytometry (F4/80+/dextran+). The transcript abundance of about 200 genes were differentially regulated between these two populations. Together, these two studies illustrate key genes expressed in TAMs that may regulate tumor progression and furthermore, define a specific sub-population of TAMs that directly promotes tumor cell migration and invasion.

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