scholarly journals Current Understanding of the Role of PPARγin Gastrointestinal Cancers

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Bing Zou ◽  
Liang Qiao ◽  
Benjamin C. Y. Wong
Keyword(s):  
Antitumor Effect ◽  
Cell Cycle Control ◽  
Control Cell ◽  
Multiple Roles ◽  
Gastrointestinal Cancers ◽  
Recent Developments ◽  
Positive Results ◽  
Prevention And Therapy

Numerous studies have indicated that PPARγplays multiple roles such as in inflammation, cell cycle control, cell proliferation, apoptosis, and carcinogenesis, thus PPARγcontributes to the homeostasis. Many in vitro studies have showed that ligand-induced activation of PPARγpossess antitumor effect in many cancers including CRC. However, the role of PPARγin gastrointestinal cancers, especially in colorectal cancer, is rather controversial. Nevertheless, some recent studies with the positive results on the possible application of PPARγligands, such as Bezafibrate or Rosiglitazone in gastrointestinal cancers, have suggested a potential usefulness of PPARγagonists in cancer prevention and therapy. In this review, the authors discuss the recent developments in the role of PPARγin gastrointestinal cancers.

scholarly journals The State of the Art and Prospects for Osteoimmunomodulatory Biomaterials

Materials ◽  
2021 ◽  
Vol 14 (6) ◽  
pp. 1357
Author(s):  
Andreea-Mariana Negrescu ◽  
Anisoara Cimpean
Keyword(s):  
Foreign Bodies ◽  
Structural Characteristics ◽  
Critical Role ◽  
Fibrous Tissue ◽  
Bioactive Molecules ◽  
New Bone Formation ◽  
Recent Developments

The critical role of the immune system in host defense against foreign bodies and pathogens has been long recognized. With the introduction of a new field of research called osteoimmunology, the crosstalk between the immune and bone-forming cells has been studied more thoroughly, leading to the conclusion that the two systems are intimately connected through various cytokines, signaling molecules, transcription factors and receptors. The host immune reaction triggered by biomaterial implantation determines the in vivo fate of the implant, either in new bone formation or in fibrous tissue encapsulation. The traditional biomaterial design consisted in fabricating inert biomaterials capable of stimulating osteogenesis; however, inconsistencies between the in vitro and in vivo results were reported. This led to a shift in the development of biomaterials towards implants with osteoimmunomodulatory properties. By endowing the orthopedic biomaterials with favorable osteoimmunomodulatory properties, a desired immune response can be triggered in order to obtain a proper bone regeneration process. In this context, various approaches, such as the modification of chemical/structural characteristics or the incorporation of bioactive molecules, have been employed in order to modulate the crosstalk with the immune cells. The current review provides an overview of recent developments in such applied strategies.

scholarly journals Dual oxidase 1 limits the IFNγ-associated antitumor effect of macrophages

2020 ◽  
Vol 8 (1) ◽  
pp. e000622
Author(s):  
Lydia Meziani ◽  
Marine Gerbé de Thoré ◽  
Pauline Hamon ◽  
Sophie Bockel ◽  
Ruy Andrade Louzada ◽  
...  
Keyword(s):  
Antitumor Effect ◽  
Therapeutic Strategy ◽  
Critical Role ◽  
Tumor Development ◽  
Intratumoral Injection ◽  
Histocompatibility Complex ◽  
Dual Oxidase

BackgroundMacrophages play pivotal roles in tumor progression and the response to anticancer therapies, including radiotherapy (RT). Dual oxidase (DUOX) 1 is a transmembrane enzyme that plays a critical role in oxidant generation.MethodsSince we found DUOX1 expression in macrophages from human lung samples exposed to ionizing radiation, we aimed to assess the involvement of DUOX1 in macrophage activation and the role of these macrophages in tumor development.ResultsUsing Duox1−/− mice, we demonstrated that the lack of DUOX1 in proinflammatory macrophages improved the antitumor effect of these cells. Furthermore, intratumoral injection of Duox1−/− proinflammatory macrophages significantly enhanced the antitumor effect of RT. Mechanistically, DUOX1 deficiency increased the production of proinflammatory cytokines (IFNγ, CXCL9, CCL3 and TNFα) by activated macrophages in vitro and the expression of major histocompatibility complex class II in the membranes of macrophages. We also demonstrated that DUOX1 was involved in the phagocytotic function of macrophages in vitro and in vivo. The antitumor effect of Duox1−/− macrophages was associated with a significant increase in IFNγ production by both lymphoid and myeloid immune cells.ConclusionsOur data indicate that DUOX1 is a new target for macrophage reprogramming and suggest that DUOX1 inhibition in macrophages combined with RT is a new therapeutic strategy for the management of cancers.

scholarly journals Differential phosphorylation signals control endocytosis of GPR15

2017 ◽  
Vol 28 (17) ◽  
pp. 2267-2281 ◽  
Author(s):  
Yukari Okamoto ◽  
Sojin Shikano
Keyword(s):  
Surface Density ◽  
Functional Role ◽  
Control Cell ◽  
Phosphorylation Site ◽  
Hek293 Cells ◽  
C Terminus ◽  
Differential Phosphorylation ◽  
G Protein Coupled

GPR15 is an orphan G protein–coupled receptor (GPCR) that serves for an HIV coreceptor and was also recently found as a novel homing receptor for T-cells implicated in colitis. We show that GPR15 undergoes a constitutive endocytosis in the absence of ligand. The endocytosis was clathrin dependent and partially dependent on β-arrestin in HEK293 cells, and nearly half of the internalized GPR15 receptors were recycled to the plasma membrane. An Ala mutation of the distal C-terminal Arg-354 or Ser-357, which forms a consensus phosphorylation site for basophilic kinases, markedly reduced the endocytosis, whereas phosphomimetic mutation of Ser-357 to Asp did not. Ser-357 was phosphorylated in vitro by multiple kinases, including PKA and PKC, and pharmacological activation of these kinases enhanced both phosphorylation of Ser-357 and endocytosis of GPR15. These results suggested that Ser-357 phosphorylation critically controls the ligand-independent endocytosis of GPR15. The functional role of Ser-357 in endocytosis was distinct from that of a conserved Ser/Thr cluster in the more proximal C-terminus, which was responsible for the β-arrestin– and GPCR kinase–dependent endocytosis of GPR15. Thus phosphorylation signals may differentially control cell surface density of GPR15 through endocytosis.

scholarly journals Therapeutic Use of MicroRNAs in Lung Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Orazio Fortunato ◽  
Mattia Boeri ◽  
Carla Verri ◽  
Massimo Moro ◽  
Gabriella Sozzi
Keyword(s):  
Lung Cancer ◽  
Target Genes ◽  
Current Knowledge ◽  
Cell Cycle Control ◽  
Control Cell ◽  
Systemic Delivery ◽  
Small Noncoding Rnas ◽  
Gene And Protein Expression

Lung cancer is a leading cause of cancer deaths worldwide. Although the molecular pathways of lung cancer have been partly known, the high mortality rate is not markedly changed. MicroRNAs (miRNAs) are small noncoding RNAs that actively modulate cell physiological processes as apoptosis, cell-cycle control, cell proliferation, DNA repair, and metabolism. Several studies demonstrated that miRNAs are involved in the pathogenesis of lung diseases including lung cancer and they negatively regulate gene and protein expression by acting as oncogenes or tumor suppressors. In this review we summarize the current knowledge on the role of miRNAs and their target genes in lung tumorigenesis and evaluate their potential use as therapeutic agents in lung cancer. In particular, we describe methodological approaches such as inhibition of oncogenic miRNAs or replacement of tumor suppressor miRNAs, both inin vitroandin vivoassays. Furthermore we discuss new strategies to achievein vivotissue specific delivery, potential off-target effects, and safety of miRNAs systemic delivery.

Perspective of strategic plasma therapy for prognostic improvement of patients with ovarian cancer

2013 ◽  
Vol 1598 ◽  
Author(s):  
Hiroaki Kajiyama ◽  
Fumi Utsumi ◽  
Kae Nakamura ◽  
Hiromasa Tanaka ◽  
Masaru Hori ◽  
...  
Keyword(s):  
Atmospheric Pressure ◽  
Antitumor Effect ◽  
Intraperitoneal Administration ◽  
Atmospheric Pressure Plasma ◽  
Plasma Therapy ◽  
Intracellular Mechanism ◽  
Patients Experience

ABSTRACTEpithelial ovarian carcinoma (EOC) is the leading cause of cancer-related death in women in Western countries. Once patients experience recurrence, complete cure is almost impossible. We elucidated the effect of nonequilibrium atmospheric pressure plasma on the growth of EOC, particularly in plasma-activated medium (PAM). Furthermore, we examined the role of reactive oxygen species (ROS) or their scavengers in chronic antineoplastic-resistant EOC cells. As a result, we showed PAM induced the antitumor effect of EOC cells in vitro and in vivo, even in chemoresistant cells. To apply the plasma treatment for advanced or recurrent EOC, we suggest adopting indirect plasma therapy instead of direct plasma considering intraperitoneal administration in the future. However, there are several problems under investigation, including intracellular mechanism of antitumor effect by PAM and adverse event in vivo.

scholarly journals Forskolin enhances the antitumor effect of oncolytic measles virus by promoting Rab27a dependent vesicular transport system in the lung cancer A549 cells in vitro

2020 ◽  
Author(s):  
Mao Xia ◽  
Yongquan Xia ◽  
Xuejing Xu ◽  
Gang Meng ◽  
Hong Yan ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Transport System ◽  
Measles Virus ◽  
Antitumor Effect ◽  
Vesicular Transport ◽  
A549 Cells ◽  
Over Expression ◽  
Combined Strategy

Abstract Background: Measles vaccine strain viruses (MV-Edm) are an ideal platform for developing safe and effective oncolytic vectors. However, despite the promising pre-clinical data, understanding of determinants of efficacy and, thus, the interplay of the oncolytic virus with particular agents remains limited.Methods: We investigated the potency of forskolin enhancing the antitumor effect of oncolytic measles virus by promoting Rab27a dependent vesicular transport system. Cells were infected with MV-Edm and the vesicles were observed by TEM. The oncolytic effects of MV-Edm/Forskolin were investigated in vitro. Results: Here we demonstrate that the MV-Edm infection and spread in tumor, which are indispensable processes for the viral oncolysis, depend on the vesicular transport system of tumor cells. On the contrary, the tumor cells display a responsive mechanism to restrain the MV-Edm spread by down-regulating the expression of Rab27a, which is a key member of the vesicle transport system. Over-expression of Rab27a promotes the oncolytic efficacy of MV-Edm towards A549 tumor cells. Finally, we find a Rab27a agonist Forskolin, is capable of promoting the oncolytic effect of MV-Edm in vitro. Conclusions: Our study reveals the important role of vesicle transporter Rab27a in the whole program of MV-Edm mediated oncolysis. We also provide a combined strategy of Forskolin and MV-Edm, which may exert a synergistic anti-tumor effect, for clinical treatment for patients with tumor.

scholarly journals The Multiple Roles of the Cdc14 Phosphatase in Cell Cycle Control

2020 ◽  
Vol 21 (3) ◽  
pp. 709
Author(s):  
Javier Manzano-López ◽  
Fernando Monje-Casas
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Cell Cycle Control ◽  
Multiple Roles ◽  
Special Focus ◽  
Cyclin Dependent Kinase ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cycle Progression

The Cdc14 phosphatase is a key regulator of mitosis in the budding yeast Saccharomyces cerevisiae. Cdc14 was initially described as playing an essential role in the control of cell cycle progression by promoting mitotic exit on the basis of its capacity to counteract the activity of the cyclin-dependent kinase Cdc28/Cdk1. A compiling body of evidence, however, has later demonstrated that this phosphatase plays other multiple roles in the regulation of mitosis at different cell cycle stages. Here, we summarize our current knowledge about the pivotal role of Cdc14 in cell cycle control, with a special focus in the most recently uncovered functions of the phosphatase.

Anti-angiogenesis Potential of Phytochemicals for the Therapeutic Management of Tumors

2020 ◽  
Vol 26 (2) ◽  
pp. 265-278 ◽  
Author(s):  
Samman Munir ◽  
Asad A. Shah ◽  
Muhammad Shahid ◽  
Muhammad S. Ahmed ◽  
Aqsa Shahid ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Angiogenesis Inhibitors ◽  
Metastatic Potential ◽  
Biologically Active ◽  
Angiogenic Potential ◽  
Recent Developments ◽  
Pharmaceutical Industries ◽  
Pathological Stages

The role of angiogeneses during the growth and progression of tumors is well documented. Likewise, a balance is generally maintained between the cellular proliferation and the apoptosis, therefore, the tumors can persist for years in a dormant phase. During the past few years, many hypotheses have been proposed relating to the importance of tumor angiogenesis for the development and spread of tumors and preventive or therapeutic capacity of angiogenesis inhibitors as a potential target for controlling the growth of cancerous tissue. The antiangiogenic based therapeutic approaches are considered as the most promising method for the control of tumors, as this therapeutic approach is less likely to attain the drug resistance. Further, the tumor vasculature is an important prognostic marker that can independently predict the pathological stages as well as the metastatic potential of tumors. Various biologically active phytochemicals have been extracted from the dietary sources and the plants that have engaged the scientist and pharmaceutical industries around the globe. The antioxidant, antiinflammatory, anti-proliferative and anti-angiogenic potential of these bioactive phytochemicals is evident from the in vitro studies using cell lines and investigations involving the animal models..The present review is focused on the promising role of anti-angiogenesis-based therapies for the management of tumors and the recent developments relating to the interplay of phytochemicals and angiogenesis for the suppression of tumor cells.

GATA-1 Overexpression Does Not Restore Deficient Erythropoiesis in Myelodysplastic Syndromes.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3430-3430
Author(s):  
Alexandra Rideau ◽  
Stephane Durual ◽  
Maciej Wiznerowics ◽  
Sylvie Ruault ◽  
Vincent Piguet ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Culture System ◽  
Cell Cycle Control ◽  
Erythroid Differentiation ◽  
Erythroid Progenitors ◽  
Differentiation Markers ◽  
Cd34 Cells ◽  
Erythroleukemic Cell

Abstract Introduction: Transcription factor GATA-1 is essential for erythroid and megakaryocytic maturation. A role of GATA-1 in cell cycle control is suggested by the fact that GATA-1 mutations are associated with hematopoietic precursor proliferation and leukemogenesis and that defective GATA-1 expression is observed in in vitro cultures of erythroid myelodysplastic precursors. In order to study more in detail a potential role of GATA-1 dysregulation in myelodysplastic syndromes (MDS), we constructed lentiviral vectors with the aim to overexpress GATA-1 protein or to inhibit its production in erythroid progenitors. Methods and Results: Using RNA interference technology we tested how GATA-1 inhibition interfered with erythroid differentiation. We selected one GATA-1 specific siRNA, which abolished expression of GATA-1 protein in K562 and HEL erythroleukemic cell lines, as verified by Western blot. Interestingly, we observed in parallel to the disappearance of GATA-1 protein, decreased proliferation rates (170x for K562 and 30x for HEL after 17 days of culture) and increased apoptosis. Normal CD34+ cells cultured in our culture system and transduced with the siRNA vector were practically blocked in their erythroid differentiation: 14 % glyco+/CD36- mature erythroid cells versus 81 % in untransduced and 80 % in cultures transduced with control lentivector (obtained after 14 days of culture). Differentiation into myeloid cells was not affected. To overexpress GATA-1 we cloned the wild-type as well as a mutated, caspase-resistant, form of GATA-1 in a pWPIR-ires-GFP bicistronic lentivector. Functionality of both lentivectors was validated in HeLa cells. For the study of GATA-1 in primary human hematopoietic cells we used an in vitro culture system in which CD34+ progenitors differentiate into mature red blood cells in the presence of erythropoietin, IL-3, and SCF. Transduction of CD34+ cells with lentivectors led to increase of GATA-1 mRNA (400-fold) measured by Realtime RT-PCR and to detection of protein. No difference was observed in cell numbers, expression of erythroid differentiation markers and survival between cells transduced with control vector and with pWPIR-GATA-1-ires-GFP. CD34+ cells from 3 patients with low-risk MDS in this culture system proliferated less (15x ± 13 amplification after 14 days of culture versus 72x ± 35 for normal precursors) differentiated less, and became apoptotic earlier than normal cells. However, overexpression of GATA-1 did not restore proliferation rate, nor did it lead to increased erythroid differentiation, or increase in survival. Conclusion: GATA-1 overexpression was not able to overcome defective erythroid differentiation of myelodysplastic progenitors, nor did it increase differentiation of normal erythroid progenitors. On the other hand, GATA-1 inhibition in normal erythroid precursors led to blockage of erythroid differentiation. We therefore assume that either factors upstream of GATA-1 or additional, GATA-1 independent factors, are responsible for the myelodysplastic phenotype.

scholarly journals Bornlisy Attenuates Colitis-Associated Colorectal Cancer via Inhibiting GPR43-Mediated Glycolysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Xia Lu ◽  
Shuping Qiao ◽  
Chen Peng ◽  
Wenyue Yan ◽  
Zhen Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Antitumor Effect ◽  
Intervention Strategy ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Erk Pathway ◽  
Proliferation And Metastasis

There is evidence that probiotics have a broad antitumor effect in colorectal cancer (CRC). However, the mechanism remains obscure. Here, we investigated the effect of Bornlisy (BO)-cocktails of three probiotics on colitis-associated colon cancer (CAC) and the underlying mechanism. The treatment of CAC mice with BO resulted in decreased tumor loads as compared with their counterparts. BO also inhibited the proliferation and metastasis of CRC cells in vitro. Furthermore, BO inhibited cell proliferation through downregulating glycolysis. Activating glycolysis reversed the protective role of BO in the CAC mice. Mechanically, BO administration promoted the activation of GPR43, followed by its downstream PLC-PKC-ERK pathway, which led to decreased glucose metabolism. These results suggest that BO may provide an intervention strategy for CRC therapy, while GPR43 is a potential targeting receptor during the BO treatment.

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