scholarly journals Abscopal Effect of Frozen Autograft Reconstruction Combined with an Immune Checkpoint Inhibitor Analyzed Using a Metastatic Bone Tumor Model

2021 ◽  
Vol 22 (4) ◽  
pp. 1973
Author(s):  
Noritaka Yonezawa ◽  
Hideki Murakami ◽  
Satoru Demura ◽  
Satoshi Kato ◽  
Shinji Miwa ◽  
...  
Keyword(s):  
Liquid Nitrogen ◽  
Tumor Model ◽  
Bone Grafts ◽  
Treated Group ◽  
Suppressive Effect ◽  
Interferon Γ ◽  
T Cell Response ◽  
Abscopal Effect ◽  
Tumor Bearing ◽  
Significant Difference

We evaluated the abscopal effect of re-implantation of liquid nitrogen-treated tumor-bearing bone grafts and the synergistic effect of anti-PD-1 (programmed death-1) therapy using a bone metastasis model, created by injecting MMT-060562 cells into the bilateral tibiae of 6–8-week-old female C3H mice. After 2 weeks, the lateral tumors were treated by excision, cryotreatment using liquid nitrogen, excision with anti-PD-1 treatment, and cryotreatment with anti-PD-1 treatment. Anti-mouse PD-1 4H2 was injected on days 1, 6, 12, and 18 post-treatment. The mice were euthanized after 3 weeks; the abscopal effect was evaluated by focusing on growth inhibition of the abscopal tumor. The re-implantation of frozen autografts significantly inhibited the growth of the remaining abscopal tumors. However, a more potent abscopal effect was observed in the anti-PD-1 antibody group. The number of CD8+ T cells infiltrating the abscopal tumor and tumor-specific interferon-γ (IFN-γ)-producing spleen cells increased in the liquid nitrogen-treated group compared with those in the excision group, with no significant difference. The number was significantly higher in the anti-PD-1 antibody-treated group than in the non-treated group. Overall, re-implantation of tumor-bearing frozen autograft has an abscopal effect on abscopal tumor growth, although re-implantation of liquid nitrogen-treated bone grafts did not induce a strong T-cell response or tumor-suppressive effect.

The JPJDF has Synergistic Effect with Fluoropyrimidine in the Maintenance Therapy for Metastatic Colorectal Cancer

2020 ◽  
Vol 15 (3) ◽  
pp. 257-269
Author(s):  
Xiaoling Fu ◽  
Yanbo Zhang ◽  
Lisheng Chang ◽  
Dengcheng Hui ◽  
Ru Jia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Synergistic Effect ◽  
Maintenance Therapy ◽  
Metastatic Colorectal Cancer ◽  
Maintenance Treatment ◽  
Advanced Colorectal Cancer ◽  
Treated Group ◽  
Induction Treatment ◽  
Chemotherapeutic Regimen ◽  
Significant Difference

Background: Maintenance chemotherapeutic regimen with low toxicity is needed for metastatic colorectal cancer. A recent patent has been issued on the spleen-strengthening and detoxification prescription (JPJDF), a traditional Chinese herbal medicinal formula with anti-angiogenesis effect. The clinical effect of JPJDF on the maintenance treatment of advanced colorectal cancer has not been evaluated. Objective: This study aims to evaluate the effectiveness and safety of JPJDF in combination with fluoropyrimidine compared to fluoropyrimidine alone as maintenance therapy for metastatic colorectal cancer. Methods: We applied a prospective, randomized, double-blinded, single center clinical study design. A total of 137 patients with advanced colorectal cancer were recruited. Patients received either Fluoropyrimidine (Flu-treated group, n = 68), or Fluoropyrimidine plus JPJDF (Flu-F-treated group, n = 69) as maintenance treatment after 6-cycle of FOLFOX4 or FOLFORI induction treatment. The primary endpoints were Progression-Free Survival (PFS) and Overall Survival (OS). The secondary endpoints were safety, Performance Status (PS) score and other symptoms. Results: The endpoint of disease progression was observed in 91.7% of patients. The PFS was 5.0 months and 3.0 months in the Flu-F-treated and Flu-treated groups, respectively. The OS was 15.0 months and 9.0 months in the Flu-F-treated and Flu-treated groups, respectively. Some common symptoms, such as hypodynamia, anepithymia, dizziness and tinnitus and shortness of breath, were improved in the Flu-F-treated group. There was no significant difference in the common adverse reactions between the two groups. Conclusion: JPJDF and fluoropyrimidine have synergistic effect in the maintenance treatment of mCRC.

scholarly journals Simultaneous implant placement with autogenous onlay bone grafts: a systematic review and meta-analysis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Guoqiang Ma ◽  
Chaoan Wu ◽  
Miaoting Shao
Keyword(s):  
Meta Analysis ◽  
Survival Rates ◽  
Bone Grafts ◽  
Implant Survival ◽  
Analysis Model ◽  
Implant Placement ◽  
Significant Difference ◽  
Delayed Implant Placement ◽  
Onlay Grafts

AbstractSeveral authors have suggested that implants can be placed simultaneously with onlay bone grafts without affecting outcomes. Therefore, the purpose of this study was to answer the following clinical questions: (1) What are the outcomes of implants placed simultaneously with autogenous onlay bone grafts? And (2) is there a difference in outcomes between simultaneous vs delayed placement of implants with autogenous onlay bone grafts? Databases of PubMed, Embase, and Google Scholar were searched up to 15 November 2020. Data on implant survival was extracted from all the included studies (single arm and comparative) to calculate point estimates with 95% confidence intervals (CI) and pooled using the DerSimonian–Laird meta-analysis model. We also compared implant survival rates between the simultaneous and delayed placement of implants with data from comparative studies. Nineteen studies were included. Five of them compared simultaneous and delayed placement of implants. Dividing the studies based on follow-up duration, the pooled survival of implant placed simultaneously with onlay grafts after <2.5 years of follow-up was 93.1% (95% CI 82.6 to 97.4%) and after 2.5–5 years was 86% (95% CI 78.6 to 91.1%). Implant survival was found to be 85.8% (95% CI 79.6 to 90.3%) with iliac crest grafts and 95.7% (95% CI 83.9 to 93.0%) with intra-oral grafts. Our results indicated no statistically significant difference in implant survival between simultaneous and delayed placement (OR 0.43, 95% 0.07, 2.49, I2=59.04%). Data on implant success and bone loss were limited. Data indicates that implants placed simultaneously with autogenous onlay grafts have a survival rate of 93.1% and 86% after a follow-up of <2.5 years and 2.5–5years respectively. A limited number of studies indicate no significant difference in implant survival between the simultaneous and delayed placement of implants with onlay bone grafts. There is a need for randomized controlled trials comparing simultaneous and delayed implant placement to provide robust evidence.

Ethyl formate and phosphine fumigations on the two-spotted spider mite, Tetranychus urticae and their biochemical responses

2019 ◽  
Vol 62 (1) ◽  
Author(s):  
Kyeongnam Kim ◽  
Yong Ho Lee ◽  
Gayoung Kim ◽  
Byung-Ho Lee ◽  
Jeong-Oh Yang ◽  
...  
Keyword(s):  
Tetranychus Urticae ◽  
Respiratory Chain ◽  
Spider Mite ◽  
Ethyl Formate ◽  
Treated Group ◽  
Effective Control ◽  
Molecular Approaches ◽  
Significant Difference ◽  
Target Sites ◽  
Two Spotted Spider Mite

Abstract Two spotted spider mite, Tetranychus urticae, is a polyphagous pest to a variety of plants and they are hard to be controlled due to occurrence of resistance to acaricides. In this study, biochemical evaluation after ethyl formate (EF) and phosphine (PH3) fumigation towards T. urticae might help officials to control them in quarantine purposes. PH3 fumigation controlled eggs (LC50; 0.158 mg/L), nymphs (LC50; 0.030 mg/L), and adults (LC50; 0.059 mg/L) of T. urticae, and EF effectively affected nymphs (LC50; 2.826 mg/L) rather than eggs (LC50; 6.797 mg/L) and adults (LC50; 5.836 mg/L). In a longer exposure time of 20 h, PH3 fumigation was 94.2-fold more effective tool for control of T. urticae than EF fumigant. EF and PH3 inhibited cytochrome c oxidase (COX) activity differently in both nymphs and adults of T. urticae. It confirmed COX is one of target sites of these fumigants in T. urticae and COX is involved in the respiratory chain as complex IV. Molecular approaches showed that EF fumigation completely down-regulated the expression of cox11 gene at the concentration of LC10 value, while PH3 up-regulated several genes greater than twofold in T. urticae nymphs treated with the concentration of LC50 value. These increased genes by PH3 fumigation are ndufv1, atpB, para, and ace, responsible for the expression of NADH dehydrogenase [ubiquinone] flavoprotein 1, ATP synthase, and acetylcholinesterase in insects, respectively. Lipidomic analyses exhibited a significant difference between two fumigants-exposed groups and the control, especially an ion with 815.46 m/z was analyzed less than twofold in the fumigants-treated group. It was identified as PI(15:1/18:3) and it may be used as a biomarker to EF and PH3 toxicity. These findings may contribute to set an effective control strategy on T. urticae by methyl bromide alternatives such as EF and PH3 because they have shared target sites on the respiratory chain in the pest.

scholarly journals Murine hepatoma treatment with mature dendritic cells stimulated by Trichinella spiralis excretory/secretory products

Parasite ◽  
2020 ◽  
Vol 27 ◽  
pp. 47
Author(s):  
Jing Ding ◽  
Xiaolei Liu ◽  
Bin Tang ◽  
Xue Bai ◽  
Yang Wang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Growth ◽  
Antitumor Effect ◽  
Trichinella Spiralis ◽  
Critical Role ◽  
Tumor Model ◽  
Control Group ◽  
Tumor Inhibition ◽  
Significant Difference ◽  
Secretory Products

Excretory/Secretory Products (ESPs) of the nematode Trichinella spiralis contain antitumor-active substances that inhibit tumor growth. Mature dendritic cells (DCs) play a critical role in the antitumor immunity of the organism. As pathogen-derived products, it ought to be discussed whether T. spiralis ESPs will reduce the antitumor effect of mature DCs from the host before it is applied to patients’ tumors. Therefore, the aim of this work was to evaluate the immunological effect of DCs stimulated by T. spiralis ESPs in H22 tumor-bearing mice. H22 tumor model mice in this study were randomly divided into four groups according to the treatment: PBS control group, ESP group, DCs group, and DCs stimulated with T. spiralis ESP (ESP+DCs group). The antitumor effect was evaluated by tumor inhibition rate and cytokine detection using ELISA. The results showed significant inhibition in tumor growth in the ESP+DCs, DCs and ESP groups when compared with the PBS control group (p < 0.01, p < 0.01, and p < 0.05, respectively). However, no significant difference was observed on tumor inhibition rates between the ESP+DCs and DCs groups. The decrease in IL-4, IL-6, and IL-10, and the increase in IFN-γ between the DCs and ESP+DCs groups were also not significant. Therefore, DCs stimulated by ESP did not reduce the antitumor effect of mature DCs, which demonstrated that the T. spiralis ESP would not affect the antitumor effect of mature DCs by modulating the immune response of the host, and that ESPs are safe in antitumor immunology when applied in a tumor model mice.

MOG extracellular domain (p1–125) triggers elevated frequency of CXCR3+ CD4+ Th1 cells in the CNS of mice and induces greater incidence of severe EAE

2014 ◽  
Vol 20 (10) ◽  
pp. 1312-1321 ◽  
Author(s):  
Jyothi T Mony ◽  
Reza Khorooshi ◽  
Trevor Owens
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Cd8 T Cell ◽  
Interferon Γ ◽  
T Cell Response ◽  
Receptor Expression ◽  
Myelin Proteins ◽  
Mhc Ii

Background: Myelin-specific T cells are implicated in multiple sclerosis (MS) and drive experimental autoimmune encephalomyelitis (EAE). EAE is commonly induced with short peptides, whereas in MS, whole myelin proteins are available for immune response. We asked whether immunization with the immunoglobulin-like domain of myelin oligodendrocyte glycoprotein (MOGIgd, residues 1–125) might induce distinct CD4+ T-cell response and/or a stronger CD8+ T-cell response, compared to the 21 amino acid immunodominant MHC II-associating peptide (p35–55). Objectives: Compare both EAE and T-cell responses in C57BL/6 mice immunized with MOGIgd and MOG p35–55. Methods: Cytokine production, and chemokine receptor expression by CD4+ and CD8+ T cells in the mouse central nervous system (CNS), were analyzed by flow cytometry. Results: MOGIgd triggered progression to more severe EAE than MOG p35–55, despite similar time of onset and overall incidence. EAE in MOGIgd-immunized mice was characterized by an increased percentage of CXCR3+ interferon-γ-producing CD4+ T cells in CNS. The CD8+ T-cell response to both immunogens was similar. Conclusions: Increased incidence of severe disease following MOGIgd immunization, accompanied by an increased percentage of CD4+ T cells in the CNS expressing CXCR3 and producing interferon-γ, identifies a pathogenic role for interferon-γ that is not seen when disease is induced with a single Major Histocompatibility Complex (MHC) II-associating epitope.

scholarly journals Role of Macrophage Migration Inhibitory Factor in the Regulatory T Cell Response of Tumor-Bearing Mice

2012 ◽  
Vol 189 (8) ◽  
pp. 3905-3913 ◽  
Author(s):  
Susanna Choi ◽  
Hang-Rae Kim ◽  
Lin Leng ◽  
Insoo Kang ◽  
William L. Jorgensen ◽  
...  
Keyword(s):  
T Cell ◽  
Migration Inhibitory Factor ◽  
Regulatory T Cell ◽  
Cell Response ◽  
Macrophage Migration Inhibitory Factor ◽  
T Cell Response ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Tumor Bearing

scholarly journals Interferon-γ Production by Peripheral Lymphocytes Predicts Survival of Tumor-Bearing Mice Receiving Dual PD-1/CTLA-4 Blockade

2016 ◽  
Vol 4 (8) ◽  
pp. 650-657 ◽  
Author(s):  
Michael J. McNamara ◽  
Ian Hilgart-Martiszus ◽  
Diego M. Barragan Echenique ◽  
Stefanie N. Linch ◽  
Melissa J. Kasiewicz ◽  
...  
Keyword(s):  
Interferon Γ ◽  
Tumor Bearing ◽  
Peripheral Lymphocytes

scholarly journals Inhibition of Leukocyte Entry into the Brain by the Selectin Blocker Fucoidin Decreases Interleukin-1 (IL-1) Levels but Increases IL-8 Levels in Cerebrospinal Fluid during Experimental Pneumococcal Meningitis in Rabbits

2000 ◽  
Vol 68 (6) ◽  
pp. 3153-3157 ◽  
Author(s):  
Christian Østergaard ◽  
Runa Vavia Yieng-Kow ◽  
Thomas Benfield ◽  
Niels Frimodt-Møller ◽  
Frank Espersen ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Pneumococcal Meningitis ◽  
Interleukin 1 ◽  
Treated Group ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Significant Difference ◽  
The Brain ◽  
Experimental Pneumococcal Meningitis

ABSTRACT The polysaccharide fucoidin is a selectin blocker that inhibits leukocyte recruitment into the cerebrospinal fluid (CSF) during experimental pneumococcal meningitis. In the present study, the effect of fucoidin treatment on the release of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), and IL-8 into the CSF was investigated. Rabbits (n = 7) were treated intravenously with 10 mg of fucoidin/kg of body weight every second hour starting 4 h after intracisternal inoculation of ∼106 CFU of Streptococcus pneumoniae type 3 (untreated control group, n = 7). CSF samples were obtained every second hour during a 16-h study period. Treatment with fucoidin caused a consistent and significant decrease in CSF IL-1 levels (in picograms per milliliter) between 12 and 16 h (0 versus 170, 0 versus 526, and 60 versus 1,467, respectively;P < 0.02). A less consistent decrease in CSF TNF-α levels was observed in the fucoidin-treated group, but with no significant difference between the two groups (P > 0.05). In contrast, there was no attenuation in CSF IL-8 levels. Indeed, there was a significant increase in CSF IL-8 levels (in picograms per milliliter) in the fucoidin-treated group at 10 and 12 h (921 versus 574 and 1,397 versus 569, respectively;P < 0.09). In conclusion, our results suggest that blood-derived leukocytes mainly are responsible for the release of IL-1 and to some degree TNF-α into the CSF during pneumococcal meningitis, whereas IL-8 may be produced by local cells within the brain.

A two different chemoprophylaxis approaches after phacoemulsification surgery in one thousand patients in Iraq

2020 ◽  
Vol 1 (3) ◽  
pp. 154-159
Author(s):  
Suzan Amana Rattan ◽  
◽  
Mahir Kadhim Mutashar ◽  
Keyword(s):  
Treated Group ◽  
The Other ◽  
Eye Drops ◽  
Topical Medication ◽  
Group Methods ◽  
Significant Difference ◽  
Infection And Inflammation ◽  
Group 2 ◽  
Age Range

AIM: To evaluate the effectivity of the combination of intracameral moxifloxacin 0.1% with subconjunctival triamcinolone acetonide 4 mg as prophylaxis of infection and inflammation after phacoemulsification in comparison with topical medication treated group. METHODS: A total one thousand patients with age range from 38 to 70 years old who scheduled for phacoemulsification were divided into 2 groups of no statistically significant differences in age, preoperative intraocular pressure (IOP) and central macular thickness (CMT), P=0.6, 0.9 and 0.8 respectively. The surgeries were done by 2 surgeons each one planned to use one method of prophylaxis at Eye Speciality Private hospital, Baghdad, Iraq. For the 1st group of patients (500) a topical moxifloxacin hydrochloride 0.5% and dexamethasone 0.1% eye drops were prescribed four times a day for 1mo postoperatively. For the 2nd group intracameral (IC) diluted moxifloxacin at 0.1% with subconjunctival (SC) triamcinolone 4mg in 0.4 cc were administered at the conclusion of the surgery. Follow up visits were on the first postoperative day, 1wk, 1mo, and 3mo postoperatively. Anterior chamber (AC) reaction was examined during the 4 visits while IOP was measured during the last 3 and CMT was measured only in the last one. RESULTS: The current clinical trial study compared 2 samples with 2 different prophylaxis methods. No endophthalmitis case reported in both group. By a 2-Sample t-test, the IC-treated group (group 2) had statistically significant lower AC cells at the 1st day postoperative visit than the other group while there were no statistically significant differences at 1wk, 1 mo and 3mo visits between the 2 groups. There was no statistically significant difference at 3mo visits in IOP and CMT between the two groups. A breakthrough inflammation rate with the topical medication was (9.6%) while in the other group (IC treated ) was 4.0%. A significant IOP elevation ≥10 mm Hg at 1mo in 2.4% within the topical medication group which was higher than the rate in the other group (0.8%). CONCLUSION: In addition to the safety and effectivity of the combination of intracameral moxifloxacin and subconjunctival triamcinolone in preventing infection and inflammation after cataract surgery. The majority (480) of our included patients didn’t require any topical postoperative medication that is cost saving for the patient, helped patients who were unable to administer topical medication, and decreased chance of complication related to patient poor adherence to postoperative medication.

P–061 Protective effect of melatonin against bleomycin, etoposide, and cisplatin (BEP) chemotherapy-induced testicular toxicity in Wistar rats: A biochemical, immunohistochemical and apoptotic genes based evidence

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Moradi ◽  
A Faramarzi ◽  
N Goodarzi ◽  
A H Hashemian ◽  
H Cheraghi ◽  
...  
Keyword(s):  
Testosterone Level ◽  
Wistar Rats ◽  
Caspase 3 ◽  
Treated Group ◽  
Serum Testosterone Level ◽  
Dependent Manner ◽  
Qrt Pcr ◽  
Tnf Α ◽  
Significant Difference ◽  
Bep Chemotherapy

Abstract Study question Does exogenous melatonin (MLT) attenuate BEP-induced damage in testicular cells and spermatogenesis in a dose-dependent manner? Summary answer Melatonin protected the testes against BEP-induced testis damage through ameliorating nitro-oxidative stress, apoptosis, and inflammation. However, there was no significant difference between melatonin-treated groups. What is known already Recently, the prevalence of testicular cancer (TC), accounting for the most common cancer among young people of reproductive age (15–40 years), has risen internationally. BEP chemotherapy has increased the 5-year survival rate of TC patients at all stages of testicular germ cell tumors to 90–95%. However, BEP creates a high incidence of male infertility and even long-term genotoxic effects, which emerges as a critical health issue. Melatonin is a well-known potent antioxidant with widespread clinical applications that recently has been giving increasing attention to its role in male sub/infertility. Study design, size, duration 60 Adult male Wistar rats were randomly assigned to six groups (n = 10/group). Group 1, 3, and 4 were injected with vehicle, 10 and 20 mg/kg of melatonin, respectively. Other groups received one cycle of bleomycin, etoposide, and cisplatin for a total of 3 weeks with or without melatonin. Melatonin administration started daily one week before BEP initiation continued on days 2, 9, and 16; and one week after the completion of the BEP cycle. Participants/materials, setting, methods Bodyweight, testes weight, Sperm parameters (count, motility, viability, and morphology), testosterone hormone level, testicular histopathology, stereological parameters, testicular level of malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC), the expression of Bcl–2, Bax, Caspase–3, p53, and TNF-α (Real-time PCR and immunohistochemistry) were evaluated at the end of the study (day 35). Main results and the role of chance Our findings showed that melatonin restores the BEP-induced reduction in the body and testes weight (P&lt;.05). the evaluation of quantitative analysis of the testes stereological procedures, QRT-PCR examination and immunohistochemical (IHC) staining revealed that melatonin reverses the BEP-induced impaired spermatogenesis (P&lt;.05). Furthermore, melatonin rectifies BEP-induced disturbance on sperm count, motility, viability, and morphology. The testosterone level in the BEP-treated group was decreased significantly by comparison with the control group (P&lt;.01). By contrast, co-administration of 10 and 20 mg/kg of melatonin could enhance the serum testosterone level significantly (P&lt;.05). Moreover, melatonin enhanced the antioxidant status of the testis by elevating TAC and ameliorating MDA and NO levels. More notably, QRT-PCR examination indicated that melatonin therapy suppressed BEP-induced apoptosis by modulating apoptosis-associated genes such as Bcl–2, Bax, Caspase–3, p53 in the testis (P&lt;.01). Besides, Co-administration of 10 and 20 mg/kg of melatonin with BEP regimen decreased significantly the population of p53 (54.21 ±6.18% and 51.83±8.45, respectively) and TNF-α positive cells (42.91±9.92% and 33.57±2.97, respectively) by comparison to the BEP group. Also, melatonin with low and high doses could enhance the expression of Bcl–2 protein in spermatogenic cells line (59.19±10.18%, 63.08±5.23, respectively) compared to the BEP-treated group. Limitations, reasons for caution Owing to limited laboratory facilities we were not able to perform further studies to verify the mechanism of melatonin in the specific targets by using transfection technique and transgenic. Wider implications of the findings: These findings can draw attention to the clinical application of melatonin and also suggest that melatonin may be an attractive agent for attenuating chemotherapy-associated male sub/infertility. This indolamine also may shorten the fertility recovery period in patients undergoing chemotherapy with the BEP regimen. Trial registration number N/A

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