scholarly journals The Preventive Effect of the Phenotype of Tumour-Associated Macrophages, Regulated by CD39, on Colon Cancer in Mice

2021 ◽  
Vol 22 (14) ◽  
pp. 7478
Author(s):  
Hyun-Jun Park ◽  
Eun-Hye Seo ◽  
Liyun Piao ◽  
Sang-Tae Park ◽  
Min-Ki Lee ◽  
...  

Background: This study was designed to investigate the effect of cluster differentiation (CD)39 and CD73 inhibitors on the expresion of tumour-associated macrophages (TAMs), M1- versus M2-tumour phenotypes in mice with colon cancer. Methods: An in vivo study of co-culture with colon cancer cells and immune cells from the bone marrow (BM) of mice was performed. After the confirmation of the effect of polyoxotungstate (POM-1) as an inhibitor of CD39 on TAMs, the mice were randomly divided into a control group without POM-1 and a study group with POM-1, respectively, after subcutaneous injection of CT26 cells. On day 14 after the injection, the mice were sacrificed, and TAMs were evaluated using fluorescence-activated cell sorting. Results: In the in vivo study, the co-culture with POM-1 significantly increased the apoptosis of CT26 cells. The cell population from the co-culture with POM-1 showed significant increases in the expression of CD11b+ for myeloid cells, lymphocyte antigen 6 complex, locus C (Ly6C+) for monocytes, M1-tumour phenotypes from TAMs, and F4/80+ for macrophages. In the in vivo study, tumour growth in the study group with POM-1 was significantly limited, compared with the control group without POM-1. The expressions of Ly6C+ and major histocompatibility complex class II+ for M1-tumour phenotypes from TAMs on F4/80+ from the tumour tissue in the study group had significantly higher values compared with the control group. Conclusion: The inhibition of CD39 with POM-1 prevented the growth of colon cancer in mice, and it was associated with the increased expression of M1-tumour phenotypes from TAMs in the cancer tissue.

2008 ◽  
Vol 74 (7) ◽  
pp. 1997-2003 ◽  
Author(s):  
Mathieu Millette ◽  
Gilbert Cornut ◽  
Claude Dupont ◽  
François Shareck ◽  
Denis Archambault ◽  
...  

ABSTRACT This study demonstrated the capacity of bacteriocin-producing lactic acid bacteria (LAB) to reduce intestinal colonization by vancomycin-resistant enterococci (VRE) in a mouse model. Lactococcus lactis MM19 and Pediococcus acidilactici MM33 are bacteriocin producers isolated from human feces. The bacteriocin secreted by P. acidilactici is identical to pediocin PA-1/AcH, while PCR analysis demonstrated that L. lactis harbors the nisin Z gene. LAB were acid and bile tolerant when assayed under simulated gastrointestinal conditions. A well diffusion assay using supernatants from LAB demonstrated strong activity against a clinical isolate of VRE. A first in vivo study was done using C57BL/6 mice that received daily intragastric doses of L. lactis MM19, P. acidilactici MM33, P. acidilactici MM33A (a pediocin mutant that had lost its ability to produce pediocin), or phosphate-buffered saline (PBS) for 18 days. This study showed that L. lactis and P. acidilactici MM33A increased the concentrations of total LAB and anaerobes while P. acidilactici MM33 decreased the Enterobacteriaceae populations. A second in vivo study was done using VRE-colonized mice that received the same inocula as those in the previous study for 16 days. In L. lactis-fed mice, fecal VRE levels 1.73 and 2.50 log10 CFU/g lower than those in the PBS group were observed at 1 and 3 days postinfection. In the P. acidilactici MM33-fed mice, no reduction was observed at 1 day postinfection but a reduction of 1.85 log10 CFU/g was measured at 3 days postinfection. Levels of VRE in both groups of mice treated with bacteriocin-producing LAB were undetectable at 6 days postinfection. No significant difference in mice fed the pediocin-negative strain compared to the control group was observed. This is the first demonstration that human L. lactis and P. acidilactici nisin- and pediocin-producing strains can reduce VRE intestinal colonization.


2018 ◽  
Vol 12 (1) ◽  
pp. 314-321
Author(s):  
Cristina Sánchez-Barahona ◽  
Gema Bolívar ◽  
Dimitrios G. Mikropoulos ◽  
Anastasios G. Konstas ◽  
Miguel A. Teus

Objective: To evaluate in an in vivo rabbit model, the effect of topical timolol maleate therapy on the central corneal thickness response to acute intraocular pressure increases. Method: In this prospective and interventional controlled study, the central corneal thickness and intraocular pressure were measured in vivo in 12 rabbit eyes treated with topical timolol maleate for 1 month and in 12 controls at baseline, and after the intraocular pressure (measured by direct cannulation of the anterior chamber) was increased to 15 and 30 mmHg using a forced saline infusion into the anterior chamber. Results: There were no significant differences in the basal central corneal thickness values (control group, 373.2±12.9 µm; study group, 377.5±19.2 µm, p=0.5) or the central corneal thickness values when the intraocular pressure was increased to 15 mmHg (control group, 335.2±14.3 µm; study group, 330.0±32.1 µm, p=0.6) and to 30 mmHg (study group, 318.8±25.3 µm; control group, 329.8±21.0 µm, p=0.3). Conclusion: Rabbit corneas treated with topical timolol maleate for 1 month did not show a strain response to acute intraocular pressure increases that differed from control eyes. This is in contrast to a previous finding in which rabbit eyes treated with prostaglandin analogues had a greater decrease in central corneal thickness in response to a sudden intraocular pressure increase compared with untreated corneas.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Alain J Poncelet ◽  
Johnatan Vercruysse ◽  
Alain Saliez ◽  
Pierre Gianello

Purpose Several reports have highlighted the low immunogenic profile of MSCs. Therefore, we decided to test in vivo the humoral response to allogeneic MSCs transplantation and the effect of transient immunosuppression in a porcine model. Methods/Material MHC-controlled mini-swine SLA cd and SLA dd were used as donor and recipients, respectively. Two sites of transplantation were selected: subcutaneous and intracardiac. In our control group (n = 5), animals received no immunosuppression. In the study group (n = 11), nearly 1 x 10 6 allogeneic MSC/kg were injected. FK-506 was given from day 0 –12 and adjusted to therapeutic blood levels. Sera were serially collected up to one year after transplantation. The presence of specific anti-donor IgM and IgG was tested by flow cytometry and by a complement-mediated cytotoxicity assay. Results In the control group, all animals developed humoral responses in both IgM/G classes that persisted up to ten weeks. When transplanted subcutaneously, a single injection failed to elicit a complement-mediated cytotoxic response but subsequent re-challenge did. In the study group, only 2/11 FK-treated animals developed a transient humoral response, both in IgM and IgG, whereas all others failed to develop donor-specific antibodies. However, none of the sera tested from those 11 animals could elicit a complement-mediated cytotoxic response. Conclusion Allogeneic MSCs injected subcutaneously or intra-cardially can elicit prolonged humoral responses despite their putative low immunogenic profile. As already shown for experimental allogeneic organ transplantation, a transient immunosuppressive regimen can overcome the initial B cell response. Our result suggests that in vitro and in vivo characteristics of MSCs might differ and emphasizes the importance of pursuing research on allogeneic stem cell transplantation.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15535-e15535
Author(s):  
Mehmet Artac ◽  
Ayca Ceylan ◽  
Melek Karakurt Eryılmaz ◽  
Murat Araz ◽  
Mustafa Karaagac ◽  
...  

e15535 Background: VEGF receptors have an important role for inhibiting adaptive immun response in colon cancer. Therefore, we analyzed VEGF receptors in circulating T cell subsets according to stage in colon cancer patients. Methods: The prospective study group consisted of 50 patients with histologically confirmed colon cancer and 30 person without any cancer history as a control group. Peripheral blood specimens were collected from the patients after the diagnosis before inducing chemotherapy and radiotherapy. Patients with active infections or autoimmune disorders, who were treated with steroids and antibiotics in the last four weeks before the study enrollment were excluded from the study group. VEGFR2 expressions in circulating T cell subsets (Th1, Th2, Th17, CTL) were analyzed by flow cyctometry. Results: Age and gender were not different between the all study groups. Mean circulating CD4+ folicullar cells were less in colon cancer patients (9.54%±3.99) than the control group (12.03%±4.34), (p < 0.01). Mean circulating CD8+ follicular cells were higher in metastatic colon cancer (n = 26) 2.48% ± 1.68, than the non-metastatic colon cancer patients (n = 24) 1.63% ± 1.37, (p = 0.02). Mean VEGFR2 expressions in Th1 cells were higher in colon cancer patients 248.8 (Mean Flourescein intensity-MFI) than the control group 224.6, (P = 0.006). Mean VEGFR2 expressions in CTL were higher in colon cancer patients (381.8) than the control group (284.7), (p < 0.001). PD-1 expressions were not different between the colon cancer patients and the control group in all circulating T cell subsets. Mean VEGFR2 expressions in Th17 cells were higher non-metastatic colon cancer patients than the metastatic colon cancer patients (326.5 and 268.4 MFI, respectively, p = 0.02). Conclusions: VEGFR2 expressions are increased in circulating Th1 and CTL subsets in colon cancer patients. Whereas PD-1 expressions were not different in circulating T cell subsets than the control. VEGFRs may play an important role for the inhibition of circulating T cell subsets in colon cancer.


2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Guifeng Wang ◽  
Ning Ma ◽  
Feng He ◽  
Shosuke Kawanishi ◽  
Hatasu Kobayashi ◽  
...  

Taurine (2-aminoethane-sulfonic acid) is a type of amino acids and has numerous physiological and therapeutic functions, including anti-inflammation. However, there are few studies on the anticancer action of taurine. Our previous studies have demonstrated that taurine exhibits an apoptosis-inducing effect on human nasopharyngeal carcinoma cells in vitro. In this study, we have investigated whether taurine has an anticancer effect, using azoxymethane (AOM)/sulfate sodium (DSS)- induced mouse model for colon carcinogenesis. All mice, except those in control group, received a single intraperitoneal injection of AOM and DSS in the drinking water for 7 days twice, with 1-week interval. After the first DSS treatment, mice were given distilled water (model group) or taurine in the drinking water (taurine group) ad libitum. No tumor was observed in the control group. Taurine significantly suppressed AOM+DSS-induced tumor formation. Histopathological examination revealed AOM/DSS treatment induced colon cancer in all mice (8/8, 100%), and taurine significantly inhibited the progression of colon cancer (4/9, 44.4%). Taurine significantly attenuated cell proliferation in cancer tissues detected by Ki-67 staining. Taurine significantly increased the levels of an apoptosis marker cleaved caspase-9 and tumor suppressor protein PTEN. This is the first study that demonstrated that taurine significantly reduced carcinogenicity in vivo using AOM/DSS-induced colon cancer mouse model.


Perfusion ◽  
2001 ◽  
Vol 16 (6) ◽  
pp. 519-524 ◽  
Author(s):  
A Pierangeli ◽  
V Masieri ◽  
F Bruzzi ◽  
E De Toni ◽  
G Grillone ◽  
...  

During cardiopulmonary bypass (CPB) the collection of the patient’s blood from the operating area is of fundamental importance. This blood is collected in the cardiotomy reservoir using field suckers and can be managed in different ways. It can be filtered in the cardiotomy reservoir and redirected to the venous reservoir, then oxygenated and returned to the patient, or it can be managed separately: collected in the cardiotomy reservoir, treated at the end of the operation and only after this, returned to the patient. The aim of this study is to determine in vivo the effect of a separate management of the suction blood from the operative field, using the Avant D903 oxygenator (Dideco, Mirandola, Italy). Twenty-one patients undergoing coronary artery bypass graft surgery with CPB were selected and put into two groups at random. In the control group ( n 10) the suction blood in the cardiotomy reservoir was filtered and immediately redirected into the venous reservoir, oxygenated and returned to the patient. In the study group ( n 11) the suctioned blood was collected in the D903 Avant’s (Dideco) cardiotomy reservoir and returned to the patient only after having been washed at the end of the operation, using a Compact Advanced (Dideco), as required. Clinical data demonstrated that while in the study group it was possible to keep the free plasma haemoglobin (FPH) concentrations the same as at the beginning, in the control group there was a significant increase in FPH from 5.0 3.5 mg/dl (baseline) to 37 16.7 mg/dl (120 min after CPB).


Author(s):  
Yang zhi Jiang ◽  
Qing Guo Tao ◽  
fei yan Zhu

BACKGROUND AIM To explore the correlation between the expression of miRNA-135a and Bach1 in colorectal cancer tissue and the patient's clinical information.  Methods   60 patients with colorectal carcinoma were treated as a control group. Real-time quantitative PCR assays and immunohistochemistry method were performed to detect the expression of miRNA-135a and Bach1 in 60 colorectal carcinomas and adjacent normal tissues, and the clinical and pathological classifications had also been investigated. The SPSS 19.00 software was used. All data represented mean±SD of three independent experiments. P&lt;0.05 was considered statistically significant. Results  miRNA-135a expression levels increased significantly in the colon cancer tissues compared with the non-tumor control tissues(P&lt;0.01). miRNA-135a expression levels were higher in stage III/IV than in stage I/II colon cancer patients. The expression level of Bach1 in colorectal cancer was significantly lower(P&lt;0.01). Bach1 and miRNA-135a were negatively correlated.  Conclusions:  The levels of miRNA-135a and Bach1 were opposite, the over-expression of miRNA-135a might downregulated the expression of Bach1, which might be involved in the pathogenesis of colorectal cancer.


2021 ◽  
Vol 20 (3) ◽  
pp. 76-81
Author(s):  
S. V. Volkov ◽  
S. V. Lobanov ◽  
P. P. Tereshkov

 Objective: to determine the level of growth factors in the blood serum of patients with left-sided colon cancer and to assess the feasibility of using these findings in the tumor detection.Material and Methods. The study group included 63 patients aged 20 to 75 years who underwent surgery for left-sided colon adenocarcinoma (descending, sigmoid, rectosigmoid) with stage i (t1–2n0m0), ii (t3–4an0m0), and iii (t1–2n1m0). Only 5 patients developed metastases in one regional lymph node. The remaining patients had no regional metastases. In all patients, before hospitalization, the tumor was confirmed by colonoscopy followed by histological examination. The group of comparison consisted of 25 patients with chronic hemorrhoids without exacerbation, who underwent colonoscopy. In patients of the study group, blood tests were drawn on the day of surgery before its starting. In patients of the comparison group, blood was taken after excluding colon cancer (after colonoscopy). Blood tests were carried out using a test system (Biolegend): multiplex set for determining growth factors (angiopoietin-2, (ang-2), egf, epo, FGF-basic, G-csf, GM-csf, HGF, M-csf, pdgf-aa, pdgf-BB, scf, tgf-α, vegf).Results. In cancer patients, the levels of egf, HGF, M-csf, pdgf-aa, and pdgf-BB were several times higher than in the control group (p <0.05). The level of pdgf-aa was 10 times higher in cancer patients than in controls. In addition to quantitative changes, statistically significant differences were observed between the vegf level and sex of the patients; angio protein-2, G-csf, epo, M-csf, pdgf-aa, pdgf-BB, vegf levels and the age of the patients; tgf-α, HGF levels and the histological grade of the tumor.Conclusion. It was found that changes in the level of biologically active substances that occur in colon cancer can serve as additional diagnostic markers for cancer detection.


2021 ◽  
Vol 12 (4) ◽  
pp. 800-806
Author(s):  
Amrit Malik ◽  
Chinky Goyal ◽  
Abhiram S P ◽  
Gramopadhye N G

Introduction- As Acharya Charaka has explained the local application of Kshirivruksha Twak to cure all types of keeta visha, hence Nyagrodh (Ficus benghalensis L.) Twak Lepa with water as base is selected as Trial drug on Apis Cerana Indica bee sting poisoning. Material and Methods- An in-vivo study on albino mice to know the efficacy of trial drug has been planned after animal ethical clearance. 18 albino mice were prorated into three groups with 6 animals in each group viz. Control group, Trial drug (Nyagrodh Twak Lepa Churna) group and Standard drug (Beclomethasone Dipropionate 0.025% w/w) group. 6 stings were given to each mice and 3 stings were removed after sting operation. All mice were observed for allergic reactions viz. erythema, scaling, fissures, oedema and mortality for a period of 7 days. Histo-pathological changes were also noted after completion of study. Statistical analysis was done using Paired t test. Results- Results revealed that Trial drug had worked more efficiently on Erythema and Oedema while Standard drug worked more efficiently on Scaling and Fissure. Histo-pathology showed that wound healed with Nyagrodh twak lepa and Standard drug have shown almost similar changes while wound in control group showed extensive areas of necrosis. Conclusion- Present study suggests that both Nyagrodh and Beclomethasone can be used in Honey bee sting poisoning but as Nyagrodh being a religious tree can be easily identified by a common man, it can be employed as preliminary treatment for the same before reaching hospital. 


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Marlena Matulka ◽  
Aneta Konopka ◽  
Barbara Mroczko ◽  
Anna Pryczynicz ◽  
Andrzej Kemona ◽  
...  

The aim of this study was to assess the expression of MMP-9 and TIMP-1 in cancerous tissue as well as in the serum and plasma concentrations of these proteins in patients with laryngeal cancer and compare the results to the inflammatory reaction in healthy subjects. Twenty-seven patients who were diagnosed with laryngeal carcinoma and selected for total laryngectomy were included in the study group. MMP-9 and TIMP-1 expression in tissues was assessed using immunohistochemical assays. Immunoenzymatic ELISA methods were used to measure MMP-9 and TIMP-1 concentrations in serum and plasma. MMP-9 and TIMP-1 were identified in tumor cells and in the tumor stroma compartment, as well as in macroscopically healthy mucous membrane. MMP-9 expression was more significant in tumor stroma than in the perimatrix of the mucous membrane (p=0.047). TIMP-1 expression was significantly higher in the matrix and perimatrix of the mucous membrane than in cancer tissue (p=0.0093) and the tumor stroma compartment (p<0.0001). Expression of TIMP-1 was observed more frequently in tumors without infiltrated lymph nodes (p=0.009). Serum concentrations of MMP-9 and TIMP-1 as well as plasma TIMP-1 concentration were significantly higher in the study group than in the control group (p=0.0004, p=0.002, and p=0.0001, respectively). A significantly higher TIMP-1 level in plasma was found in patients with poorly differentiated tumors compared to G1 and G2 (p=0.046). MMP-9/TIMP-1 rate in serum was significantly higher in the study group than in the control group. The balance between the level of MMP-9 and TIMP-1 is disrupted in laryngeal cancer. The significant correlation between TIMP-1 expression and the presence of lymph node metastases, as well as that between TIMP-1 plasma concentration and stage of cancer histological differentiation, might indicate the importance of this molecule as a prognostic factor during carcinogenesis.


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