scholarly journals Interplay between Cellular and Molecular Inflammatory Mediators in Lung Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Mario Orozco-Morales ◽  
Giovanny Soca-Chafre ◽  
Pedro Barrios-Bernal ◽  
Norma Hernández-Pedro ◽  
Oscar Arrieta
Keyword(s):  
Lung Cancer ◽  
Immune Suppression ◽  
Critical Role ◽  
Inflammatory Cells ◽  
T Cell Response ◽  
Invasion And Metastasis ◽  
Remodeling Of Extracellular Matrix ◽  
Tumor Associated Neutrophils

Inflammation is a component of the tumor microenvironment and represents the 7th hallmark of cancer. Chronic inflammation plays a critical role in tumorigenesis. Tumor infiltrating inflammatory cells mediate processes associated with progression, immune suppression, promotion of neoangiogenesis and lymphangiogenesis, remodeling of extracellular matrix, invasion and metastasis, and, lastly, the inhibition of vaccine-induced antitumor T cell response. Accumulating evidence indicates a critical role of myeloid cells in the pathophysiology of human cancers. In contrast to the well-characterized tumor-associated macrophages (TAMs), the significance of granulocytes in cancer has only recently begun to emerge with the characterization of tumor-associated neutrophils (TANs). Recent studies show the importance of CD47 in the interaction with macrophages inhibiting phagocytosis and promoting the migration of neutrophils, increasing inflammation which can lead to recurrence and progression in lung cancer. Currently, therapies are targeted towards blocking CD47 and enhancing macrophage-mediated phagocytosis. However, antibody-based therapies may have adverse effects that limit its use.

scholarly journals The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eui Jung Moon ◽  
Stephano S. Mello ◽  
Caiyun G. Li ◽  
Jen-Tsan Chi ◽  
Kaushik Thakkar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Invasion ◽  
Critical Role ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Invasion And Metastasis ◽  
Stat3 Signaling ◽  
Inducible Genes ◽  
Transcriptional Target

AbstractHypoxia plays a critical role in tumor progression including invasion and metastasis. To determine critical genes regulated by hypoxia that promote invasion and metastasis, we screen fifty hypoxia inducible genes for their effects on invasion. In this study, we identify v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) as a potent regulator of tumor invasion without affecting cell viability. MAFF expression is elevated in metastatic breast cancer patients and is specifically correlated with hypoxic tumors. Combined ChIP- and RNA-sequencing identifies IL11 as a direct transcriptional target of the heterodimer between MAFF and BACH1, which leads to activation of STAT3 signaling. Inhibition of IL11 results in similar levels of metastatic suppression as inhibition of MAFF. This study demonstrates the oncogenic role of MAFF as an activator of the IL11/STAT3 pathways in breast cancer.

scholarly journals The Effect of Octapeptide Repeats on Prion Folding and Misfolding

2021 ◽  
Vol 22 (4) ◽  
pp. 1800
Author(s):  
Kun-Hua Yu ◽  
Mei-Yu Huang ◽  
Yi-Ru Lee ◽  
Yu-Kie Lin ◽  
Hau-Ren Chen ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Age Of Onset ◽  
Prion Diseases ◽  
Critical Role ◽  
Threshold Effect ◽  
Central Feature ◽  
Terminal Domain ◽  
Amyloid Aggregates

Misfolding of prion protein (PrP) into amyloid aggregates is the central feature of prion diseases. PrP has an amyloidogenic C-terminal domain with three α-helices and a flexible tail in the N-terminal domain in which multiple octapeptide repeats are present in most mammals. The role of the octapeptides in prion diseases has previously been underestimated because the octapeptides are not located in the amyloidogenic domain. Correlation between the number of octapeptide repeats and age of onset suggests the critical role of octapeptide repeats in prion diseases. In this study, we have investigated four PrP variants without any octapeptides and with 1, 5 and 8 octapeptide repeats. From the comparison of the protein structure and the thermal stability of these proteins, as well as the characterization of amyloids converted from these PrP variants, we found that octapeptide repeats affect both folding and misfolding of PrP creating amyloid fibrils with distinct structures. Deletion of octapeptides forms fewer twisted fibrils and weakens the cytotoxicity. Insertion of octapeptides enhances the formation of typical silk-like fibrils but it does not increase the cytotoxicity. There might be some threshold effect and increasing the number of peptides beyond a certain limit has no further effect on the cell viability, though the reasons are unclear at this stage. Overall, the results of this study elucidate the molecular mechanism of octapeptides at the onset of prion diseases.

scholarly journals Expression, Purification, and Characterization of (R)-Sulfolactate Dehydrogenase (ComC) from the Rumen MethanogenMethanobrevibacter milleraeSM9

Archaea ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-6
Author(s):  
Yanli Zhang ◽  
Linley R. Schofield ◽  
Carrie Sang ◽  
Debjit Dey ◽  
Ron S. Ronimus
Keyword(s):  
Biosynthetic Pathway ◽  
Critical Role ◽  
Reduction Reaction ◽  
Coenzyme M ◽  
Purification And Characterization ◽  
The Third ◽  
Optimal Activity ◽  
Methyl Coenzyme M Reductase

(R)-Sulfolactate dehydrogenase (EC 1.1.1.337), termed ComC, is a member of an NADH/NADPH-dependent oxidoreductase family of enzymes that catalyze the interconversion of 2-hydroxyacids into their corresponding 2-oxoacids. The ComC reaction is reversible and in the biosynthetic direction causes the conversion of (R)-sulfolactate to sulfopyruvate in the production of coenzyme M (2-mercaptoethanesulfonic acid). Coenzyme M is an essential cofactor required for the production of methane by the methyl-coenzyme M reductase complex. ComC catalyzes the third step in the first established biosynthetic pathway of coenzyme M and is also involved in methanopterin biosynthesis. In this study, ComC fromMethanobrevibacter milleraeSM9 was cloned and expressed inEscherichia coliand biochemically characterized. Sulfopyruvate was the preferred substrate using the reduction reaction, with 31% activity seen for oxaloacetate and 0.2% seen forα-ketoglutarate. Optimal activity was observed at pH 6.5. The apparentKMfor coenzyme (NADH) was 55.1 μM, and for sulfopyruvate, it was 196 μM (for sulfopyruvate theVmaxwas 93.9 μmol min−1 mg−1andkcatwas 62.8 s−1). The critical role of ComC in two separate cofactor pathways makes this enzyme a potential means of developing methanogen-specific inhibitors for controlling ruminant methane emissions which are increasingly being recognized as contributing to climate change.

scholarly journals The Role of WAVE2 Signaling in Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1217
Author(s):  
Priyanka Shailendra Rana ◽  
Akram Alkrekshi ◽  
Wei Wang ◽  
Vesna Markovic ◽  
Khalid Sossey-Alaoui
Keyword(s):  
Actin Cytoskeleton ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Critical Role ◽  
Therapeutic Strategies ◽  
Small Gtpases ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
Regulatory Complex

The Wiskott–Aldrich syndrome protein (WASP) and WASP family verprolin-homologous protein (WAVE)—WAVE1, WAVE2 and WAVE3 regulate rapid reorganization of cortical actin filaments and have been shown to form a key link between small GTPases and the actin cytoskeleton. Upon receiving upstream signals from Rho-family GTPases, the WASP and WAVE family proteins play a significant role in polymerization of actin cytoskeleton through activation of actin-related protein 2/3 complex (Arp2/3). The Arp2/3 complex, once activated, forms actin-based membrane protrusions essential for cell migration and cancer cell invasion. Thus, by activation of Arp2/3 complex, the WAVE and WASP family proteins, as part of the WAVE regulatory complex (WRC), have been shown to play a critical role in cancer cell invasion and metastasis, drawing significant research interest over recent years. Several studies have highlighted the potential for targeting the genes encoding either part of or a complete protein from the WASP/WAVE family as therapeutic strategies for preventing the invasion and metastasis of cancer cells. WAVE2 is well documented to be associated with the pathogenesis of several human cancers, including lung, liver, pancreatic, prostate, colorectal and breast cancer, as well as other hematologic malignancies. This review focuses mainly on the role of WAVE2 in the development, invasion and metastasis of different types of cancer. This review also summarizes the molecular mechanisms that regulate the activity of WAVE2, as well as those oncogenic pathways that are regulated by WAVE2 to promote the cancer phenotype. Finally, we discuss potential therapeutic strategies that target WAVE2 or the WAVE regulatory complex, aimed at preventing or inhibiting cancer invasion and metastasis.

Abstract A02: The origin and role of APC-like hybrid tumor-associated neutrophils in early-stage human lung cancer

2016 ◽  
Author(s):  
Evgeniy Eruslanov ◽  
Pratik Bhojnagarwala ◽  
Jon Quatromoni ◽  
Shaun O'Brien ◽  
Edmund Moon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Human Lung ◽  
Early Stage ◽  
Human Lung Cancer ◽  
Hybrid Tumor ◽  
Tumor Associated Neutrophils

scholarly journals Radiotherapy Planning and Molecular Imaging in Lung Cancer

2020 ◽  
Vol 13 (3) ◽  
pp. 204-217
Author(s):  
Angelina Filice ◽  
Massimiliano Casali ◽  
Patrizia Ciammella ◽  
Marco Galaverni ◽  
Federica Fioroni ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Case Reports ◽  
Locally Advanced ◽  
Inflammatory Cells ◽  
High Rate ◽  
Radiotherapy Planning ◽  
High Dose ◽  
18F Fdg

Introduction: In patients suitable for radical chemoradiotherapy for lung cancer, 18F-FDGPET/ CT is a proposed management to improve the accuracy of high dose radiotherapy. However, there is a high rate of locoregional failure in patients with locally advanced non-small cell lung cancer (NSCLC), probably due to the fact that standard dosing may not be effective in all patients. The aim of the present review was to address some criticisms associated with the radiotherapy image-guided in NSCLC. Materials and Methods: A systematic literature search was conducted. Only published articles that met the following criteria were included: articles, only original papers, radiopharmaceutical ([18F]FDG and any tracer other than [18F]FDG), target, only specific for lung cancer radiotherapy planning, and experimental design (eventually “in vitro” studies were excluded). Peer-reviewed indexed journals, regardless of publication status (published, ahead of print, in press, etc.) were included. Reviews, case reports, abstracts, editorials, poster presentations, and publications in languages other than English were excluded. The decision to include or exclude an article was made by consensus and any disagreement was resolved through discussion. Results: Hundred eligible full-text articles were assessed. Diverse information is now available in the literature about the role of FDG and new alternative radiopharmaceuticals for the planning of radiotherapy in NSCLC. In particular, the role of alternative technologies for the segmentation of FDG uptake is essential, although indeterminate for RT planning. The pros and cons of the available techniques have been extensively reported. : Conclusion: PET/CT has a central place in the planning of radiotherapy for lung cancer and, in particular, for NSCLC assuming a substantial role in the delineation of tumor volume. The development of new radiopharmaceuticals can help overcome the problems related to the disadvantage of FDG to accumulate also in activated inflammatory cells, thus improving tumor characterization and providing new prognostic biomarkers.

scholarly journals Critical Role of Gα12 and Gα13 for Human Small Cell Lung Cancer Cell Proliferation In vitro and Tumor Growth In vivo

2010 ◽  
Vol 16 (5) ◽  
pp. 1402-1415 ◽  
Author(s):  
Marius Grzelinski ◽  
Olaf Pinkenburg ◽  
Thomas Büch ◽  
Maike Gold ◽  
Stefanie Stohr ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Critical Role ◽  
Small Cell ◽  
Cancer Cell Proliferation ◽  
Lung Cancer Cell ◽  
Small Cell Lung ◽  
Proliferation In Vitro

scholarly journals The Chlamydia-Secreted Protease CPAF Promotes Chlamydial Survival in the Mouse Lower Genital Tract

2016 ◽  
Vol 84 (9) ◽  
pp. 2697-2702 ◽  
Author(s):  
Zhangsheng Yang ◽  
Lingli Tang ◽  
Lili Shao ◽  
Yuyang Zhang ◽  
Tianyuan Zhang ◽  
...  
Keyword(s):  
Genital Tract ◽  
Chlamydial Infection ◽  
Critical Role ◽  
Content Type ◽  
Lower Genital Tract ◽  
Successful Infection ◽  
Multiple Strains

Despite the extensivein vitrocharacterization of CPAF (chlamydialprotease/proteasome-likeactivityfactor), its role in chlamydial infection and pathogenesis remains unclear. We now report that aChlamydia trachomatisstrain deficient in expression of CPAF (L2-17) is no longer able to establish a successful infection in the mouse lower genital tract following an intravaginal inoculation. The L2-17 organisms were cleared from the mouse lower genital tract within a few days, while a CPAF-sufficientC. trachomatisstrain (L2-5) survived in the lower genital tract for more than 3 weeks. However, both the L2-17 and L2-5 organisms maintained robust infection courses that lasted up to 4 weeks when they were directly delivered into the mouse upper genital tract. The CPAF-dependent chlamydial survival in the lower genital tract was confirmed in multiple strains of mice. Thus, we have demonstrated a critical role of CPAF in promotingC. trachomatissurvival in the mouse lower genital tracts. It will be interesting to further investigate the mechanisms of the CPAF-dependent chlamydial pathogenicity.

scholarly journals Molecular insights into regulation of JAK2 in myeloproliferative neoplasms

Blood ◽  
2015 ◽  
Vol 125 (22) ◽  
pp. 3388-3392 ◽  
Author(s):  
Olli Silvennoinen ◽  
Stevan R. Hubbard
Keyword(s):  
Molecular Characterization ◽  
Human Disease ◽  
Molecular Mechanisms ◽  
Myeloproliferative Neoplasms ◽  
Critical Role ◽  
Hematologic Malignancies ◽  
Janus Kinase ◽  
Constitutive Activation

Abstract The critical role of Janus kinase-2 (JAK2) in regulation of myelopoiesis was established 2 decades ago, but identification of mutations in the pseudokinase domain of JAK2 in myeloproliferative neoplasms (MPNs) and in other hematologic malignancies highlighted the role of JAK2 in human disease. These findings have revolutionized the diagnostics of MPNs and led to development of novel JAK2 therapeutics. However, the molecular mechanisms by which mutations in the pseudokinase domain lead to hyperactivation of JAK2 and clinical disease have been unclear. Here, we describe recent advances in the molecular characterization of the JAK2 pseudokinase domain and how pathogenic mutations lead to constitutive activation of JAK2.

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