scholarly journals Evaluation of Glycosylated PTGS2 in Colorectal Cancer for NSAIDS-Based Adjuvant Therapy

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 683
Author(s):  
Roberta Venè ◽  
Delfina Costa ◽  
Raffaella Augugliaro ◽  
Sebastiano Carlone ◽  
Stefano Scabini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Interleukin 1 ◽  
Cost Benefit ◽  
Protective Role ◽  
Macrophage Population ◽  
M1 Macrophage ◽  
Luminal Area ◽  
Prostaglandin Endoperoxide Synthase ◽  
Positive Effect

Observational/retrospective studies indicate that prostaglandin-endoperoxide synthase-2 (PTGS2) inhibitors could positively affect colorectal cancer (CRC) patients’ survival after diagnosis. To obtain an acceptable cost/benefit balance, the inclusion of PTGS2 inhibitors in the adjuvant setting needs a selective criterion. We quantified the 72 kDa, CRC-associated, glycosylated form of PTGS2 in 100 frozen CRC specimens and evaluated PTGS2 localization by IHC in the same tumors, scoring tumor epithelial-derived and stroma-derived fractions. We also investigated the involvement of interleukin-1 beta (IL1β) in PTGS2 induction, both in vitro and in CRC lysates. Finally, we used overall survival (OS) as a criterion for patient selection. Glycosylated PTGS2 can be quantified with high sensibility in tissue lysates, but the expression in both tumor and stromal cells limits its use for predictive purposes. Immunohistochemistry (IHC) analysis indicates that stromal PTGS2 expression could exert a protective role on patient OS. Stromal PTGS2 was prevalently expressed by cancer-associated fibroblasts exerting a barrier function near the gut lumen, and it apparently favored the antitumor M1 macrophage population. IL1β was directly linked to gPTGS2 expression both in vitro and in tumors, but its activity was apparently prevalent on the stromal cell population. We suggest that stromal PTGS2 could exert a positive effect on patients OS when expressed in the luminal area of the tumor.

scholarly journals Nutrients Bioaccessibility and Anti-inflammatory Features of Fermented Bee Pollen: A Comprehensive Investigation

2021 ◽  
Vol 12 ◽  
Author(s):  
Pasquale Filannino ◽  
Raffaella Di Cagno ◽  
Olimpia Vincentini ◽  
Daniela Pinto ◽  
Andrea Polo ◽  
...  
Keyword(s):  
Colon Adenocarcinoma ◽  
Human Keratinocytes ◽  
Protective Role ◽  
Protective Effects ◽  
Adenocarcinoma Cell Line ◽  
Inflammatory Stimuli ◽  
Keratinocyte Cell ◽  
Functional Features ◽  
Positive Effect

We compared raw bee-collected pollen (Raw-BCP), spontaneously fermented BCP (Unstarted-BCP), and BCP fermented with selected microbial starters (Started-BCP) to deepen whether fermentation may favorably affect the nutrients bioaccessibility and functional features of BCP. Under in vitro gastrointestinal batches, the highest serum-availability of phenolic compounds was found in Started-BCP, highlighting the positive effect exerted by selected microbial starters. The same effect was not found in spontaneously fermented BCP. In colon adenocarcinoma cell line-2 (Caco-2) cells stressed by a pro-inflammatory stimulus, the treatment with Started-BCP halted the increase of pro-inflammatory mediator’s level. Started-BCP counteracted efficiently the deleterious effects of inflammatory stimuli on the integrity of the Caco-2 cells monolayer and its barrier function. Started-BCP successfully counteracted the H2O2-induced intracellular accumulation of reactive oxygen species (ROS) in Caco-2 cells. A protective role against lipopolysaccharide (LPS)-induced inflammation was exerted by Started-BCP in human keratinocytes. The same protective effects on Caco-2 and keratinocyte cell lines were negligible after treatments with Raw-BCP or Unstarted-BCP.

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.

scholarly journals Activation of Heterophils and Monocytes in Chicken with a Formulation Containing a Seaweed Extract from Ulva armoricana

2021 ◽  
Vol 6 (1) ◽  
pp. 1-8
Author(s):  
Bussy F
Keyword(s):  
Interleukin 1 ◽  
Interferon Γ ◽  
Protective Role ◽  
Interferon Α ◽  
Dependent Manner ◽  
Additional Layer ◽  
Transcription Profiles ◽  
Ulva Armoricana

Responsiveness to invasive pathogens, clearance via the inflammatory response, and activation of appropriate acquired responses are all coordinated by innate host defenses. We have previously demonstrated that a purified ulvan extract of Ulva armoricana is able to activate avian heterophils and monocytes in vitro and in vivo , leading to in vivo release of cytokines including interleukin 1 β (IL1β), interferon α (IFNα) and interferon γ (IFNγ), in a transient and dose-dependent manner. In this study, we used the same protocol to evaluate a formulated version of this extract, called Searup ® . Our experiments showed that a single oral administration of this product at the dose recommended for use in the farm, results in heterophils and monocytes activation. In heterophils, activation was evidenced by β-D-glucuronidase release and increased mRNA expression of IL1β, IFNα and IFNγ. In monocytes, the expression of IFNγ and inducible nitrite oxide synthase (iNOS) were also up-regulated. Finally, plasmatic NO increased significantly on day 1, decreased on day 2 and was no longer significant at day 3. A similar pattern was observed for β-D-glucuronidase and for the modifications of the transcription profiles in monocytes as well as in heterophils. The only notable exception is gene transcription of 2'-5' Oligoadenylate Synthase, which is maximal at day 2 in monocytes. Due to its protective role in virus infection, this may constitute an additional layer of protection for this class of pathogens. Together our results show that the formulated solution, Searup ® , similarly to the purified extract allow to activate monocytes and heterophils but with some variations in the cytokines profiles and may provide protection against a larger variety of pathogens.

scholarly journals Safflower Polysaccharide Inhibits AOM/DSS-Induced Mice Colorectal Cancer Through the Regulation of Macrophage Polarization

2021 ◽  
Vol 12 ◽  
Author(s):  
Qun Wang ◽  
Yun Huang ◽  
Min Jia ◽  
Dong Lu ◽  
Hong-Wei Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Therapeutic Option ◽  
Macrophage Polarization ◽  
Raw 264.7 ◽  
Macrophage Phenotype ◽  
Antitumor Effects ◽  
M1 Macrophage ◽  
Safflower Polysaccharide

Safflower polysaccharide (SPS) is one of the active fractions extracted from safflower petals (Carthamus tinctorius L.) which has been reported to possess antitumor and immune control roles. However, its antitumor mechanisms by regulating the immune pathway remain barely understood. In this study, a mouse model was established by azoxymethane (AOM)/dextran sodium sulfate (DSS) to evaluate the antitumor effect of SPS on colorectal cancer (CRC). The results showed that 50 mg/kg SPS-1, an active fraction isolated from SPS, could significantly inhibit CRC induced by AOM/DSS and changed the polarization of macrophages to the M1 phenotype. Meanwhile, SPS-1 treatment significantly alleviated the characteristic AOM/DSS-induced pathological symptoms, in terms of decreasing the nucleoplasmic ratio, nuclear polarity extinction, and gland hyperplasia. However, the results in vitro showed that SPS-1 did not directly inhibit the growth of CRC cells but could upregulate the NF-κB signal and trigger M1 macrophage transformation. Thus, the condition medium (CM) of Mφ pretreated with SPS-1 was used against CRC cells. As expected, SPS-1–activated Raw 264.7 markedly exhibited antitumor effects by inhibiting cell proliferation and suppressing cell colony formation. In addition, SPS-1–activated Raw 264.7 could also induce CRC cell apoptosis by upregulating the levels of tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Further results suggested that SPS-1–induced transition of the macrophage phenotype could be suppressed by an NF-κB inhibitor, PDTC. Moreover, SPS-1–activated Raw 264.7 inhibiting CRC cell proliferation and inducing apoptosis were also rescued by PDTC. Taken together, all results suggested that SPS-1 could be a therapeutic option for the prevention and treatment of CRC.

The depressing (negative) effect of oestradiol benzoate on the in vitro secretion of LH and FSH by the pituitary gland of the LRH-pretreated long-term ovariectomized rat changes into the augmentative (positive) effect after discontinuation of the LRH-pretreatment

1985 ◽  
Vol 110 (3) ◽  
pp. 329-337 ◽  
Author(s):  
G. A. Schuiling ◽  
H. Moes ◽  
T. R. Koiter
Keyword(s):  
Depressing Effect ◽  
Ovx Rats ◽  
Gonadotrophin Secretion ◽  
Oestradiol Benzoate ◽  
Negative Effect ◽  
Positive Effect ◽  
Perifusion System

Abstract. The effect of pretreatment in vivo with oestradiol benzoate on in vitro secretion of LH and FSH was studied in long-term ovariectomized (OVX) rats both at the end of a 5-day continuous in vivo pretreatment with LRH and 4-days after cessation of such LRH pretreatment. Rats were on day 0 sc implanted with osmotic minipumps which released LRH at the rate of 250 ng/h. Control rats were implanted with a piece of silicone elastomer with the dimensions of a minipump. On days 2 and 4 the rats were injected with either 3 μg EB or with oil. On day 5 part of the rats were decapitated and the in vitro autonomous (i.e. non-LRH-stimulated) and 'supra-maximally' LRHstimulated release of LH and FSH was studied using a perifusion system. From other rats the minipumps were removed on day 5 and perifusion was performed on day 9. On the 5th day of the in vivo LRH pretreatment the pituitary LH/FSH stores were partially depleted; the pituitaries of the EB-treated rats more so than those of the oil-injected rats. EB alone had no significant effect on the content of the pituitary LH- and FSH stores. On day 9, i.e. 4 days after removal of the minipumps, the pituitary LH and FSH contents had increased in both the oil- and the EB injected rats, but had not yet recovered to control values. In rats not subjected to the 5-days pretreatment with LRH EB had a positive effect on the supra-maximally LRH-stimulated secretion of LH and FSH as well as on the non-stimulated secretion of LH. EB had no effect on the non-stimulated secretion of FSH. After 5 days of in vivo pretreatment with LRH only, the in vitro non-stimulated and supra-maximally LRH-stimulated secretion of both LH and FSH were strongly impaired, the effect correlating well with the LRH-induced depletion of the pituitary LH/FSH stores. In such LRH-pretreated rats EB had on day 5 a negative effect on the (already depressed) LRH-stimulated secretion of LH (not on that of FSH). EB had no effect on the non-stimulated LH/FSH secretion. It could be demonstrated that the negative effect of the combined LRH/EB pretreatment was mainly due to the depressing effect of this treatment on the pituitary LH and FSH stores: the effect of oestradiol on the pituitary LRH-responsiveness (release as related to pituitary gonadotrophin content) remained positive. In LRH-pretreated rats, however, this positive effect of EB was smaller than in rats not pretreated with LRH. Four days after removal of the minipumps there was again a positive effect of EB on the LRH-stimulated secretion of LH and FSH as well as on the non-stimulated secretion of LH. The positive effect of EB on the pituitary LRH-responsiveness was as strong as in rats which had not been exposed to exogenous LRH. The non-stimulated secretion of FSH was again not affected by EB. The results demonstrate that the effect of EB on the oestrogen-sensitive components of gonadotrophin secretion consists of two components: an effect on the pituitary LRH-responsiveness proper, and an effect on the pituitary LH/FSH stores. The magnitude of the effect of EB on the LRH-responsiveness is LRH dependent: it is very weak (almost zero) in LRH-pretreated rats, but strong in rats not exposed to LRH as well as in rats of which the LRH-pretreatment was stopped 4 days previously. Similarly, the effect of EB on the pituitary LH and FSH stores is LRH-dependent: in the absence of LRH, EB has no influence on the contents of these stores, but EB can potentiate the depleting effect of LRH on the LH/FSH-stores. Also this effect disappear after cessation of the LRH-pretreatment.

Reprogrammed M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 extends lifespan of mice with experimental carcinoma

2017 ◽  
pp. 4-9
Author(s):  
С.В. Калиш ◽  
С.В. Лямина ◽  
А.А. Раецкая ◽  
И.Ю. Малышев
Keyword(s):  
Tumor Growth ◽  
Culture Medium ◽  
Ehrlich Carcinoma ◽  
Macrophage Phenotype ◽  
M1 Macrophages ◽  
M1 Macrophage ◽  
Ec Cells ◽  
Experimental Carcinoma

Цель исследования. Репрограммирование М1 фенотипа макрофагов с ингибированными факторами транскрипции М2 фенотипа STAT3, STAТ6 и SMAD и оценка их влияния на развитие карциномы Эрлиха (КЭ) in vitro и in vivo. Методика. Рост опухоли иницировали in vitro путем добавления клеток КЭ в среду культивирования RPMI-1640 и in vivo путем внутрибрюшинной инъекции клеток КЭ мышам. Результаты. Установлено, что M1макрофаги и in vitro, и in vivo оказывают выраженный противоопухолевый эффект, который превосходит антиопухолевые эффекты М1, M1, M1 макрофагов и цисплатина. Заключение. М1 макрофаги с ингибированными STAT3, STAT6 и/или SMAD3 эффективно ограничивают рост опухоли. Полученные данные обосновывают разработку новой технологии противоопухолевой клеточной терапии. Objective. Reprogramming of M1 macrophage phenotype with inhibited M2 phenotype transcription factors, such as STAT3, STAT6 and SMAD and assess their impact on the development of Ehrlich carcinoma (EC) in vitro and in vivo . Methods. Tumor growth in vitro was initiated by addition of EC cells in RPMI-1640 culture medium and in vivo by intraperitoneal of EC cell injection into mice. Results. It was found that M1 macrophages have a pronounced anti-tumor effect in vitro , and in vivo , which was greater than anti-tumor effects of M1, M1, M1 macrophages and cisplatin. Conclusion. M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 effectively restrict tumor growth. The findings justify the development of new anti-tumor cell therapy technology.

Bioactive Peptides Sensitize Cells to Anticancer Effects of Oxaliplatin in Human Colorectal Cancer Xenografts in Nude Mice

2019 ◽  
Vol 26 (7) ◽  
pp. 512-522
Author(s):  
Xian Li ◽  
Long Xia ◽  
Xiaohui Ouyang ◽  
Qimuge Suyila ◽  
Liya Su ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Nude Mice ◽  
Low Dose ◽  
Bioactive Peptides ◽  
Human Colorectal Cancer ◽  
Short Term ◽  
Hct 116

<P>Background: Despite new agent development and short-term benefits in patients with Colorectal Cancer (CRC), metastatic CRC cure rates have not improved due to high rates of oxaliplatin resistance and toxicity. There is an urgent need for effective tools to prevent and treat CRC and reduce morbidity and mortality of CRC patients. Exploring the effects of bioactive peptides on the antitumor to CRC was of vital importance to the clinical application. </P><P> Objective: This study aimed to investigate the therapeutic impact of Anticancer Bioactive Peptides (ACBP) on anticancer effect of oxaliplatin (LOHP) in human colorectal cancer xenografts models in nude mice. </P><P> Methods: HCT-116 cells were cultured in vitro via CCK-8 assays and the absorbance was measured at 450 nm. Apoptosis and cell cycle were assessed by Flow Cytometry (FCM) in vitro. HCT-116 human colorectal cancer cells inoculated subcutaneously in nude mice of treatment with PBS (GG), ACBP, LOHP, ACBP+LOHP (A+L) in vivo. The quality of life was assessed by dietary amount of nude mice, the weight of nude mice, inhibition rates, tumor weight and tumor volume. Immunohistochemistry and RT-qPCR method was conducted to determine the levels of apoptosisregulating proteins/genes in transplanted tumors. </P><P> Results: ACBP induced substantial reductions in viable cell numbers and apoptosis of HCT116 cells in combined with LOHP in vitro. Compared with the control GG group, ACBP combined low dose oxaliplatin (U) group demonstrated significantly different tumor volume, the rate of apoptosis, the expression levels of Cyt-C, caspase-3,8,9 proteins and corresponding RNAs (P<0.05). The expression of pro-apoptotic proteins in the cytoplasm around the nucleus was significantly enhanced by ACBP. Short term intermittent use of ACBP alone indicted a certain inhibitory effect on tumor growth, and improve the quality of life of tumor bearing nude mice. </P><P> Conclusion: ACBP significantly increased the anti-cancer responses of low dose oxaliplatin (L-LOHP), thus, significantly improving the quality of life of tumor-bearing nude mice.</P>

Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4626-4638 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Seyed M. Hassanian ◽  
Farzad Rahmani ◽  
Seyed H. Aghaee-Bakhtiari ◽  
Amir Avan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Vegf Signaling ◽  
Anticancer Effects ◽  
Inhibition Of Angiogenesis ◽  
Underlying Mechanisms ◽  
Apoptotic Activity

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

Apigenin Alleviates Renal Fibroblast Activation through AMPK and ERK Signaling Pathways In Vitro

2020 ◽  
Vol 21 (11) ◽  
pp. 1107-1118
Author(s):  
Ningning Li ◽  
Zhan Wang ◽  
Tao Sun ◽  
Yanfei Lei ◽  
Xianghua Liu ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Protective Role ◽  
Fibroblast Proliferation ◽  
Fibroblast Activation ◽  
And Function ◽  
Activated Fibroblasts ◽  
Tgf Β1

Objective: Renal fibrosis is a common pathway leading to the progression of chronic kidney disease. Activated fibroblasts contribute remarkably to the development of renal fibrosis. Although apigenin has been demonstrated to play a protective role from fibrotic diseases, its pharmacological effect on renal fibroblast activation remains largely unknown. Materials and Methods: Here, we examined the functional role of apigenin in the activation of renal fibroblasts response to transforming growth factor (TGF)-β1 and its potential mechanisms. Cultured renal fibroblasts (NRK-49F) were exposed to apigenin (1, 5, 10 and 20 μM), followed by the stimulation of TGF-β1 (2 ng/mL) for 24 h. The markers of fibroblast activation were determined. In order to confirm the anti-fibrosis effect of apigenin, the expression of fibrosis-associated genes in renal fibroblasts was assessed. As a consequence, apigenin alleviated fibroblast proliferation and fibroblastmyofibroblast differentiation induced by TGF-β1. Result: Notably, apigenin significantly inhibited the fibrosis-associated genes expression in renal fibroblasts. Moreover, apigenin treatment significantly increased the phosphorylation of AMP-activated protein kinase (AMPK). Apigenin treatment also obviously reduced TGF-β1 induced phosphorylation of ERK1/2 but not Smad2/3, p38 and JNK MAPK in renal fibroblasts. Conclusion: In a summary, these results indicate that apigenin inhibits renal fibroblast proliferation, differentiation and function by AMPK activation and reduced ERK1/2 phosphorylation, suggesting it could be an attractive therapeutic potential for the treatment of renal fibrosis.

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