scholarly journals Combination therapy using intratumoral bacillus Calmette-Guerin (BCG) and vincristine in dogs with transmissible venereal tumours : therapeutic efficacy and histological changes : article

2009 ◽  
Vol 80 (2) ◽  
Author(s):  
S. Mukaratirwa ◽  
S. Chitanga ◽  
T. Chimatira ◽  
C. Makuleke ◽  
S.T. Sayi ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Mitotic Index ◽  
Tumour Cell ◽  
Cell Apoptosis ◽  
Therapeutic Efficacy ◽  
Control Group ◽  
Tumour Regression ◽  
Bacillus Calmette Guerin ◽  
Histological Changes ◽  
Apoptosis And Necrosis

Therapeutic efficacy and histological changes after bacillus Calmette-Guerin (BCG), vincristine and BCG/vincristine combination therapy of canine transmissible venereal tumours (CTVT) were studied. Twenty dogs with naturally occurring CTVT in the progression stage were divided into 4 groups and treated with intratumoral BCG, vincristine, BCG/vincristine combination therapy or intratumoral buffered saline (control group). Tumour sizes were determined weekly and tumour response to therapy was assessed. Tumour biopsies were taken weekly to evaluate histological changes. Complete tumour regression was observed in all the dogs treated with BCG, vincristine and BCG/vincristine combination therapy. BCG/vincristine combination therapy had a statistically significantly shorter regression time than BCG or vincristine therapy. No tumour regression was observed in the control group. Intratumoral BCG treatment resulted in the appearance of macrophages and increased numbers of tumour infiltrating lymphocytes (TILs) followed by tumour cell apoptosis and necrosis. Treatment with vincristine resulted in increased tumour cell apoptosis, reduction in the mitotic index and a decrease in the number of TILs. Tumours from dogs on BCG/vincristine combination were characterised by reduction in the mitotic index, and appearance of numerous TILs and macrophages followed by marked tumour cell apoptosis and necrosis. This study indicates that combined BCG and vincristine therapy is more effective than vincristine in treating CTVT, suggesting that the clinical course of this disease may be altered by immunochemotherapy.

scholarly journals Immunoregulatory Role of MicroRNA-21 in Macrophages in Response to Bacillus Calmette-Guerin Infection Involves Modulation of the TLR4/MyD88 Signaling Pathway

2017 ◽  
Vol 42 (1) ◽  
pp. 91-102 ◽  
Author(s):  
Xin Xue ◽  
Yi Qiu ◽  
Hong-Li Yang
Keyword(s):  
Cell Viability ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Bacillus Calmette Guerin ◽  
Myd88 Signaling ◽  
Apoptosis And Necrosis

Background/Aims: The purpose of this study is to explore the immunoregulatory role of microRNA-21 (miR-21) targeting of the TLR4/MyD88 signaling pathway in macrophages in response to Bacillus Calmette-Guerin (BCG) infection. Methods: After infection with BCG, mouse RAW246.7 cells were assigned into control, BCG, miR-21 mimic + BCG, mimic-negative control (NC) + BCG, miR-21 inhibitor + BCG, inhibitor-NC + BCG, BCG + TAK242 (an inhibitor of the TLR4 signaling pathway), and miR-21 inhibitor + TAK242 + BCG groups. Western blotting and qRT-PCR were used to detect the expression of miR-21, TLR4 and MyD88. The levels of TNF-a, IL-6 and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). Cell viability was measured using an MTT assay. Cell apoptosis and necrosis rates were detected using flow cytometry. Results: Compared with the control group, miR-21 expression and levels of TNF-a, IL-6 and IL-10, as well as cell apoptosis and necrosis rates, were elevated, while expression of TLR4 and MyD88, as well as cell viability, were reduced in BCG infection groups. Compared with the BCG group, miR-21 expression was increased in the miR-21 mimic + BCG group but decreased in the miR-21 inhibitor + BCG and miR-21 inhibitor + TAK242 + BCG groups. The expression of TLR4 and MyD88, as well as the cell viability, were decreased, while levels of TNF-a, IL-6 and IL-10, as well as cell apoptosis and necrosis rates, were increased in the miR-21 mimic + BCG and TAK242 + BCG groups. The opposite trends were found in the miR-21 inhibitor + BCG group. Compared with the TAK242 + BCG group, the miR-21 inhibitor + TAK242 + BCG group had higher expression of TLR4 and MyD88 as well as higher cell viability and lower levels of TNF-a, IL-6, IL-10, cell apoptosis and necrosis rates. However, the miR-21 inhibitor + TAK242 + BCG group exhibited the opposite trends when compared with the miR-21 inhibitor + BCG group. Conclusion: Our results suggest that miR-21 can negatively modulate the TLR4/MyD88 signaling pathway, resulting in decreased cell viability, increased cell apoptosis and increased levels of inflammatory factors following BCG infection in macrophages.

scholarly journals Effect of Combination Therapy with Neuroprotective and Vasoprotective Agents on Cerebral Ischemia

2018 ◽  
Vol 45 (3) ◽  
pp. 325-331
Author(s):  
Jiping Yang ◽  
Bei Yang ◽  
Baoxin Xiu ◽  
Jinchong Qi ◽  
Huaijun Liu
Keyword(s):  
Growth Factor ◽  
Combination Therapy ◽  
Water Content ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Time Window ◽  
Infarct Volume ◽  
Neural Cell ◽  
Control Group ◽  
Solution Saline

AbstractBecause most tested drugs are active against only one of the damaging processes associated with stroke, other mechanisms may cause cellular death. Thus, a combination of protective agents targeting different pathophysiological mechanisms may obtain better effects than a single agent. The major objective of this study was to investigate the effect of combination therapy with vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) after controlled ischemic brain injury in rabbits.Methods:Animals were randomly assigned to one of the following groups: sham group, saline-treated control group or NGF+VEGF-treated group. Animals received an intracerebral microinjection of VEGF and NGF or saline at 5 or 8 hours after ischemia. The two specified time points of administration were greater than or equal to the existing therapeutic time window for monoterapy with VEGF or NGF alone (3 or 5 hours of ischemia). Infarct volume, water content, neurological deficits, neural cell apoptosis and the expression of caspase-3 and Bcl-2 were measured.Results:Compared with saline-treated controls, the combination therapy of VEGF and NGF significantly reduced infarct volume, water content, neural cell apoptosis and the expression of caspase-3, up-regulated the expression of Bcl-2 and improved functional recovery (bothp<0.01) when administered 5 or 8 hours after ischemia. The earlier the administration the better the neuroprotection.Conclusions:These results showed that the combination therapy with VEGF and NGF provided neuroprotective effects. In addition, the time window of combination treatment should be at least 8 hours after ischemia, which was wider than monotherapy.RÉSUMÉ:Les effets d’une polythérapie combinant agents neuro-protecteurs et agents vasoprotecteurs dans les cas d’ischémie cérébrale.Contexte:Étant donné que la plupart des médicaments préalablement testés tendent à n’agir contre seulement un des processus de dommage associés aux AVC, il est possible que d’autres processus entraînent une mort cellulaire. À cet effet, il se pourrait qu’une combinaison d’agents protecteurs ciblant divers mécanismes physiopathologiques permette d’obtenir de meilleurs résultats qu’un simple agent. Après avoir suscité de façon contrôlée des lésions cérébrales ischémiques chez des lapins, l’objectif principal de la présente étude a donc été de se pencher sur l’impact d’une polythérapie combinant la protéine dite « facteur de croissance de l’endothélium vasculaire » (ou « VEGF » en anglais) avec le « facteur de croissance des nerfs » (ou « NGF » en anglais).Méthodes:Les animaux ont été attribués au hasard à l’un des groupes suivants : ceux ayant reçu un traitement fictif ; ceux, du groupe témoin, ayant bénéficié d’un traitement à base de solution saline ; et finalement ceux ayant été traités au moyen des VEGF et NGF. À noter que les lapins ont reçu une micro-injection intracérébrale de VEGF et de NGF ou de solution saline 5 heures ou 8 heures à la suite de leur AVC. Ces deux délais d’administration des VEGF et NGF sont équivalents ou supérieurs aux délais actuels d’administration des VEGF ou NGF à titre de monothérapie (3 heures ou 5 heures à la suite d’un AVC). Tant le volume des infarctus, le contenu en eau, les déficits neurologiques ainsi causés, l’apoptose des neurones que l’expression des protéases caspase 3 et des protéines Bcl-2 ont été mesurés.Résultats:Si on la compare au traitement à base de solution saline administré au groupe témoin, la polythérapie à base de VEGF et de NGF, lorsqu’administrée 5 heures ou 8 heures à la suite de l’AVC, a su réduire de façon notable le volume des infarctus, le contenu en eau, l’apoptose des neurones et l’expression des protéases caspase 3. Elle a également permis de réguler à la hausse l’expression des protéines Bcl-2 en plus d’entraîner une amélioration de la récupération fonctionnelle (p< 0,01 pour ces deux aspects). Ainsi donc, plus tôt l’on opte pour cette polythérapie, meilleure sera la neuroprotection encourue.Conclusions:Ces résultats démontrent que la polythérapie à base de VEGF et de NGF procure des effets neuroprotecteurs. Quant au délai d’administration de ce traitement combinatoire, il devrait être d’au moins 8 heures à la suite d’un AVC, ce qui est plus élevé que la monothérapie.

Favorable Effects of Astaxanthin on Brain Damage due to Ischemia- Reperfusion Injury

2020 ◽  
Vol 23 (3) ◽  
pp. 214-224 ◽  
Author(s):  
Esra Cakir ◽  
Ufuk Cakir ◽  
Cuneyt Tayman ◽  
Tugba Taskin Turkmenoglu ◽  
Ataman Gonel ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Brain Damage ◽  
Neurological Deficit ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Degradation Products ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Cortex Cell

Background: Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect. Objective: The aim of this study was to investigate the role of ASX on brain IRI. Methods: A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. Oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated. Results: In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p<0.05). There was a significant decrease in hippocampal and cortex cell apoptosis and a significant increase in the number of neuronal cells in the IRI + ASX group compared to the IRI group alone (p<0.05). The neurological deficit score which was significantly lower in the IRI group compared to the control group was found to be significantly improved in the IRI + ASX group (p<0.05). Conclusion: Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury.

Use of Propentofylline in Feline Bronchial Disease: Prospective, Randomized, Positive-Controlled Study

2010 ◽  
Vol 46 (5) ◽  
pp. 318-326 ◽  
Author(s):  
Ulrike Stursberg ◽  
Isabella Zenker ◽  
Silke Hecht ◽  
Katrin Hartmann ◽  
Bianka S. Schulz
Keyword(s):  
Combination Therapy ◽  
Low Dose ◽  
Respiratory Pattern ◽  
Controlled Study ◽  
Control Group ◽  
Bronchial Disease ◽  
Observation Period

Propentofylline is a methylxanthine derivative with bronchodilating actions similar to those of theophylline. Nineteen cats with bronchial disease were enrolled in this study. All cats received a low dose of prednisolone; 10 of the cats additionally received propentofylline. Propentofylline-treated cats significantly improved in their auscultation scores, respiratory pattern scores, and radiological bronchial markings score over the observation period, and they coughed less and slept less at the end of the study. No significant changes were noted in the control group. This study provides evidence that a combination therapy with prednisolone and propentofylline in cats with bronchial disease might be superior over monotherapy with prednisolone.

scholarly journals IMMU-19. TARGETING GLIOBLASTOMA IMMUNOSUPPRESSION AND TREATMENT RESISTANCE WITH IBRUTINIB IN COMBINATION WITH STEREOTACTIC RADIATION AND IMMUNE CHECKPOINT BLOCKADE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii108-ii108
Author(s):  
Jayeeta Ghose ◽  
Baisakhi Raychaudhuri ◽  
Kevin Liu ◽  
William Jiang ◽  
Pooja Gulati ◽  
...  
Keyword(s):  
T Cells ◽  
Combination Therapy ◽  
Median Survival ◽  
Immune Checkpoint ◽  
Survival Benefit ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Control Group ◽  
Triple Combination ◽  
Triple Combination Therapy

Abstract BACKGROUND Glioblastoma (GBM) is associated with systemic and intratumoral immunosuppression. Part of this immunosuppression is mediated by myeloid derived suppressor cells (MDSCs). Preclinical evidence shows that ibrutinib, a tyrosine kinase inhibitor FDA approved for use in chronic lymphocytic leukemia and known to be CNS penetrant, can decrease MDSC generation and function. Also, focal radiation therapy (RT) synergizes with anti-PD-1 therapy in mouse GBM models. Thus, we aimed to test the combination of these approaches on immune activation and survival in a preclinical immune-intact GBM mouse model. METHODS C57BL/6 mice intracranially implanted with the murine glioma cell line GL261-Luc2 were divided into 8 groups consisting of treatments with ibrutinib, RT (10 Gy SRS), or anti-PD-1 individually or in each combination (along with a no treatment control group). Immune cell subset changes (flow-cytometry) and animal survival (Kaplan-Meier) were assessed (n=10 mice per group). RESULTS Median survival of the following groups including control (28 days), ibrutinib (27 days), RT (30 days) or anti-PD-1 (32 days) showed no significant differences. However, a significant improvement in median survival was seen in mice given combinations of ibrutinib+RT (35 days), ibrutinib+anti-PD-1 (38 days), and triple therapy with ibrutinib+RT+anti-PD-1 (48 days, p &lt; 0.05) compared to controls or single treatment groups. The reproducible survival benefit of triple combination therapy was abrogated in the setting of CD4+ and CD8+ T cell depletion. Contralateral intracranial tumor re-challenge in long-term surviving mice suggested generation of tumor-specific immune memory responses. The immune profile of the tumor microenvironment (TME) showed increased cytotoxic CD8+ T cells and decreased MDSCs and regulatory T cells in the triple combination therapy mice compared to controls. CONCLUSION The combination of ibrutinib, focal RT, and anti-PD-1 immune checkpoint blockade led to a significant survival benefit compared to controls in a preclinical model of GBM.

scholarly journals MiR-206 regulates the progression of osteoporosis via targeting HDAC4

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Zhiyuan Lu ◽  
Dawei Wang ◽  
Xuming Wang ◽  
Jilong Zou ◽  
Jiabing Sun ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Diagnostic Value ◽  
Expression Level ◽  
Luciferase Reporter ◽  
Control Group ◽  
Luciferase Reporter Gene ◽  
Mineral Density ◽  
Gene Assay

Abstract Background More and more studies have confirmed that miRNAs play an important role in maintaining bone remodeling and bone metabolism. This study investigated the expression level of miR-206 in the serum of osteoporosis (OP) patients and explored the effect and mechanism of miR-206 on the occurrence and development of osteoporosis. Methods 120 postmenopausal women were recruited, including 63 cases with OP and 57 women without OP. The levels of miR-206 were determined by qRT-PCR technology. Spearman correlation coefficient was used to evaluate the correlation of miR-206 with bone mineral density (BMD). An ROC curve was used to evaluate the diagnostic value of miR-206 in osteoporosis. The effects of miR-206 on cell proliferation and cell apoptosis of hFOBs were measured by CCK-8 assay and flow cytometry, respectively. Luciferase reporter gene assay was used to confirm the interaction of miR-206 and the 3′UTR of HDAC4. Results Serum miR-206 had low expression level in osteoporosis patient group compared with control group. The expression level of serum miR-206 had diagnostic value for osteoporosis, and the serum miR-206 levels were positively correlated with BMD. The down-regulated miR-206 could inhibit cell proliferation and promote cell apoptosis. Luciferase analysis indicated that HDAC4 was the target gene of miR-206. Conclusions MiR-206 could be used as a new potential diagnostic biomarker for osteoporosis, and in in vitro cell experiments, miR-206 may regulate osteoblast cell proliferation and apoptosis by targeting HDAC4.

Effects of LncRNA HOX Transcript Antisense RNA Targeting miRNA-761 on Cervical Cancer Cell Proliferation and Apoptosis

2021 ◽  
Vol 11 (10) ◽  
pp. 2081-2086
Author(s):  
Bin Qiu ◽  
Hui Zhong ◽  
Shenqiu Ming ◽  
Chunxia Zhu
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Control Group ◽  
Normal Tissues ◽  
Cell Clones ◽  
Cervical Cancer Cells ◽  
Set Up ◽  
Cancer Tissues ◽  
Lncrna Hotair

Abnormal LncRNA HOTAIR level is correlated with various cancers and miR-761 can inhibit cancers. LncRNA HOTAIR targets miR-761 by StarBase 2.0 analysis. Our study investigated whether LncRNA HOTAIR can affect cervical cancer cells by regulating miR-761. The control group (NC group), LncRNA HOTAIR group and LncRNA HOTAIR + miR-761 Mimics group were set up to measure LncRNA HOTAIR and miR-761 level by qRT-PCR. Dual fluorescein reporter assay assessed whether miR-761 binds LncRNA HOTAIR. Western blot was used to measure Cyclin D1, Bcl-2 and Tubulin expression and clone formation assay was to assess cell proliferation and Annexin VFITC/PI staining was to detect cell apoptosis. Compared with normal tissues, LncRNA HOTAIR level was significantly higher in cervical cancer tissues, while miR-761 was lower (P < 0.01). LncRNA HOTAIR targets miR-761. Compared with NC group, CyclinD1 and Bcl-2 in LncRNA HOTAIR group were significantly increased (P < 0.01), which were significantly lower in LncRNA HOTAIR + miR-761 Mimics group (P < 0.05). Compared to NC group, miR-761 in LncRNA HOTAIR group was significantly reduced (P < 0.01) and elevated by miR-761 Mimics. In addition, compared to NC group, the number of cell clones in LncRNA HOTAIR group was increased, cell proliferation was increased, and number of apoptotic cells was decreased, which were all reversed in the LncRNA HOTAIR + miR-761 Mimics group. LncRNA HOTAIR targets miR-761, promotes cell proliferation and reduces cell apoptosis. miR-761 mimics can partially prevent the effects of LncRNA HOTAIR.

Xijiao Dihuang Decoction Alleviates Lung Injury Induced by Sepsis Through Regulating Glycerinpho Spholipid Metabolism Based Lipidomics

2021 ◽  
Author(s):  
Chen Huai yu ◽  
Lin Ming rui ◽  
Wen Dan ◽  
Su Jun feng ◽  
Yao Jie ◽  
...  
Keyword(s):  
Lung Injury ◽  
Sepsis Group ◽  
Control Group ◽  
Multivariate Statistical ◽  
Histological Changes ◽  
Lipidomic Analysis ◽  
Lipid Disorders ◽  
Group A ◽  
Underlying Mechanisms ◽  
Fatty Acyls

Abstract Background and Objective: To observe the effect of Xijiao Dihuang Decoction (XJDHT) on lung injury of sepsis mice with lipidomic analysis, and explore the underlying mechanisms.Materials and Methods: C57BL/6 mice were induced sepsis by lipopolysaccharide (LPS) administration. Animals are pretreated with XJDHT 2 days before LPS regimen, then continue treatment for addition 3 days. Lung tissue are collected for lipidomic analysis by LC/MS/MS. The survival rate is monitor after treatment. Results: After treatment with XJDHT, the histological changes of lung of the sepsis mice were relieved. The lipidomic profiles of the lung in sepsis group were evidently disordered when compared to the control group. A total of 40 significantly differential lipids expression between the sepsis-control groups were identified by multivariate statistical analysis. Septic lung injury may result from such lipid disorders, which are related to fatty acyls metabolism, glycerophospholipid metabolism, phosphosphingolipids metabolism and glycerides metabolism. After XJDHT treatment, the lipidomic profiles of the disorders tend towards alleviated when compared to the sepsis group. Twelve lipid molecules were identified and some glycerophospholipids levels returned close to the normal level. Conclusion: Glycerophospholipid metabolism may play an important role in the treatment of septic lung injury using XJDHT.

The treatment effi cacy of disturbed swallowing function in patients with ischemic stroke and neurogenic dysphagia

2021 ◽  
Vol 26 (3) ◽  
pp. 51-57
Author(s):  
V. I. Ershov ◽  
A. A. Borzdyko ◽  
V. V. Silkin
Keyword(s):  
Ischemic Stroke ◽  
Combination Therapy ◽  
Comparison Group ◽  
Dynamic Assessment ◽  
Control Group ◽  
Training Method ◽  
Severity Scale ◽  
Neurogenic Dysphagia ◽  
Swallowing Function ◽  
Penetration Aspiration Scale

The aim. To evaluate the effi cacy of swallowing recovery of patients with ischemic stroke carried out with the use of training rehabilitation method using special nutrient mixtures as part of combination therapy. Material and methods. The study included 65 patients (35 men and 30 women, aged 45 to 80 years) with dysphagia in the acute period of ischemic stroke. Thirty patients (control group) were treated with special binding compounds as part of a combination therapy. Thirty fi ve patients (comparison group) did not use the mixture. The dynamics of the recovery function of swallowing using the Penetration–Aspiration Scale (PAS) and the Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS), as well as the transition from tube to independent feeding were studied. Results. The training method of rehabilitation using special nutritional mixtures is eff ective assessed with PAS and FEDSS in patients with ischemic stroke and neurogenic dysphagia (p < 0.05). The most pronounced eff ect was achieved in the group of patients with pseudobulbar syndrome. In patients with bulbar syndrome no statistically signifi cant diff erences were observed in the dynamic assessment of the severity of dysphagia on the PAS and FEDSS scales. The application of the training method leads to a signifi cantly better transition from tube to independent feeding. Conclusion. The training method of rehabilitation using special nutritional mixtures is eff ective in patients with ischemic stroke and neurogenic dysphagia and leads to a signifi cantly better transition from tube to independent feeding.

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