Surgical Trauma Leads to a Shorter Survival in a Murine Orthotopic Pancreatic Cancer Model

2014 ◽  
Vol 54 (1-2) ◽  
pp. 87-94 ◽  
Author(s):  
Pia Menges ◽  
Christian Klöcker ◽  
Stephan Diedrich ◽  
Matthias Sendler ◽  
Stefan Maier ◽  
...  

Background: Abdominal surgery is frequently followed by immune dysfunction usually lasting for several days. This is especially important in cases with tumour diseases as an intact immune function is essential in this situation. Therefore, we analysed the outcome of tumour-bearing mice in a mouse model of surgically induced immune dysfunction (SID). Methods: In male C57BL/6 mice, a pancreatic tumour was implanted orthotopically. Following tumour implantation, the model of SID was applied. The control groups were either laparotomised or underwent no surgical procedure. The survival rate was determined by observation for >60 days. The tumour growth progress was imaged by a 7-tesla small animal MRI. Results: On day 60 after tumour implantation, the survival rate in SID mice was reduced to 41%. In the laparotomised group, 81% of mice survived, while the control group had a survival rate of 75%. These differences were significant (SID vs. control: p < 0.02, and SID vs. laparotomy: p < 0.002). The tumour volume was not influenced by the degree of surgical trauma. Conclusion: In pancreatic cancer, the SID model is ideally suited to investigate the influence of SID on this tumour entity.

2019 ◽  
Author(s):  
Ranajay Mandal ◽  
Nishant Babaria ◽  
Jiayue Cao ◽  
Kun-Han Lu ◽  
Zhongming Liu

AbstractBioelectric stimulation during concurrent magnetic resonance imaging (MRI) is of interest to basic and translational studies. However, existing stimulation systems often interfere with MRI, are difficult to use or scale up, have limited efficacy, or cause safety concerns. To address these issues, we present a novel device capable of supplying current stimulation synchronized with MRI while being wirelessly powered by the MRI gradient fields. Results from testing it with phantoms and live animals in a 7 Tesla small-animal MRI system suggest that the device is able to harvest up to 72 (or 18) mW power during typical echo-planar imaging (or fast low angle shot imaging) and usable for stimulating peripheral muscle or nerve to modulate the brain or the gut, with minimal effects on MRI image quality. As a compact and standalone system, the plug-and-play device is suitable for animal research and merits further development for human applications.


2021 ◽  
Author(s):  
Jing Zhang ◽  
Yan Zhang Tian ◽  
Shao Jian Mo ◽  
Xi Feng Fu

Abstract Background: Pancreatic cancer is a common malignant tumor of digestive system. It has the characteristics of low early detection rate, large surgical trauma and high mortality. Multiple studies have shown that the PLOD family genes are closely associated with tumor progression and metastasis in many human cancers. However, The prognosis and biological function of PLOD family genes in PAAD have not been deeply discussed.Methods: GEPIA,GEO,HPA,CCLE,Kaplan-Meier Plotter,cBioPortal, LinkedOmics, DAVID6.8, STRING and TIMER were used to determine the prognostic values and biological function of PLOD family members in pancreatic cancer.Results: The mRNA and protein expression patterns of PLOD family members were noticeably upregulated in PAAD compared to normal tissue. In addition, PLOD family gene expression is also upregulated in pancreatic cancer cell lines.PLOD1 was significantly correlated with histological grade and pathological grade of pancreatic cancer. PLOD2 is related to histological grade.The high expression of PLOD1-2 was significantly correlated with the poor overall survival rate and relapse-free survival rate in patients with PAAD. In addition, PLODs has high sensitivity and specificity in distinguishing pancreatic cancer from normal tissues.Through the functional enrichment analysis of PLODs-related genes in pancreatic cancer, we found that PLODs was enriched in collagen fiber tissue structure, lysine degradation and collagen biosynthesis.Pathway analysis was confirmed PLODs regulates the proliferation, migration, and metastasis of pancreatic cancer through the RalGEF-Ral signaling pathway.The expression levels of PLOD1–2 were positively correlated with the activities of tumor-infiltrating immune cells, including CD8+T cells, neutrophils, macrophages and dendritic cells.The expression level of PLOD3 was inversely correlated with the infiltration level of CD8+T cells.The expression levels of PLOD1 were higher in pancreatic cancers with TP53 mutations as compared to pancreatic cancers without mutations.PLOD2 expression levels were increased in KRAS mutant pancreatic cancer.However, the expression level of PLOD3 is elevated in SMAD4 wild-type pancreatic cancer.Conclusion: The findings of this study could propose that individual PLOD genes or PLOD family genes as a whole could be potential prognostic biomarkers for PAAD.


2018 ◽  
Vol 9 (4) ◽  
pp. 4-14
Author(s):  
A. V. Averyanov ◽  
A. G. Konoplyannikov ◽  
F. G. Zabozlaev ◽  
A. G. Sotnikova ◽  
O. V. Danilevskaya ◽  
...  

Background: Transplantation of mesenchymal stem cells (MSCs) is one of the most promising directions in the treatment of idiopathic pulmonary fibrosis. In experimental small animal studies, intravenous and endobronchial (installation) techniques are used for the cell preparation delivery, while in humans inhalation of drugs is the simplest and most available method. Aim: The aim of the study was to determine the optimal type of a nebulizer for viability of MSCs during nebulization, followed by a comparison of the effects of inhalation and intravenous delivery methods in a standard model of bleomycin pulmonary fibrosis in rabbits. Methods: At the first stage, the survival of MSCs was assessed ex vivo after 10 minutes of compressor, ultrasound and mesh nebulization. Subsequently we used a nebulizer, which showed the best result in the cells, viability. At the next stage аfter bronchoscopic installation of bleomycin, 5 rabbits received intravenous transplantation of 2×106 allogeneic BMMSCs, other 5 rabbits — 2×107 MSCs inhaled via a compressor nebulizer; the control healthy and bleomycin groups included 5 animals each. Results: The highest degree of viability of MSC was maintained after passing via the compressor nebulizer (72%), a significantly lower survival rate was observed in ultrasonic nebulization (20%) and no live cells were detected after mesh nebulization. Both groups treated with MSC had a significantly lower fibrosis index on the Ashcroft morphometric scale than the control group of bleomycin fibrosis. Collagen expression in the lung tissue was significantly higher in all the groups with bleomycin injury, but in animals which underwent MSC inhalation, it was significantly different (0.51 point) from the bleomycin group without treatment (2.1 points). The level of neutrophils in the BAL fluid was significantly lower in animals which received the intravenous MSC therapy. The levels of TNF-α and TGF-β1 in the BAL fluids tended to decrease in the treatment groups, but did not differ significantly from control. Conclusions: The highest survival rate of MSCs is observed when using a compressor nebulizer, which apparently should be considered as the best way for delivering cells to the respiratory tract. Both inhalation and intravenous administration of MSCs cause similar effects of inhibiting the development of bleomycin-induced pulmonary fibrosis, which indicates the possibility of using both ways of cell delivery without loss of effectiveness.


Epigenomes ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 18
Author(s):  
Murat Toruner ◽  
Martin E. Fernandez-Zapico ◽  
Christopher L. Pin

Pancreatic cancer remains among the deadliest forms of cancer with a 5 year survival rate less than 10%. With increasing numbers being observed, there is an urgent need to elucidate the pathogenesis of pancreatic cancer. While both contribute to disease progression, neither genetic nor environmental factors completely explain susceptibility or pathogenesis. Defining the links between genetic and environmental events represents an opportunity to understand the pathogenesis of pancreatic cancer. Epigenetics, the study of mitotically heritable changes in genome function without a change in nucleotide sequence, is an emerging field of research in pancreatic cancer. The main epigenetic mechanisms include DNA methylation, histone modifications and RNA interference, all of which are altered by changes to the environment. Epigenetic mechanisms are being investigated to clarify the underlying pathogenesis of pancreatic cancer including an increasing number of studies examining the role as possible diagnostic and prognostic biomarkers. These mechanisms also provide targets for promising new therapeutic approaches for this devastating malignancy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Peng Li ◽  
Xi Liang ◽  
Shan Xu ◽  
Ye Xiong ◽  
Jianrong Huang

AbstractWe aim to determine the impact of an artificial liver support system (ALSS) treatment before liver transplantation (LT), and identify the prognostic factors and evaluate the predictive values of the current commonly used ACLF prognostic models for short-term prognosis after LT. Data from 166 patients who underwent LT with acute-on-chronic liver failure (ACLF) were retrospectively collected from January 2011 to December 2018 from the First Affiliated Hospital of Zhejiang University School of Medicine. Patients were divided into two groups depending on whether they received ALSS treatment pre-LT. In the observation group, liver function tests and prognostic scores were significantly lower after ALSS treatment, and the waiting time for a donor liver was significantly longer than that of the control group. Both intraoperative blood loss and period of postoperative ICU care were significantly lower; however, there were no significant differences between groups in terms of total postoperative hospital stays. Postoperative 4-week and 12-week survival rates in the observation group were significantly higher than those of the control group. Similar trends were also observed at 48 and 96 weeks, however, without significant difference. Multivariate Cox regression analysis of the risk factors related to prognosis showed that preoperative ALSS treatment, neutrophil–lymphocyte ratio, and intraoperative blood loss were independent predicting factors for 4-week survival rate after transplantation. ALSS treatment combined with LT in patients with HBV-related ACLF improved short-term survival. ALSS treatment pre-LT is an independent protective factor affecting the 4-week survival rate after LT.


2021 ◽  
Vol 28 ◽  
pp. 107327482199743
Author(s):  
Ke Chen ◽  
Xiao Wang ◽  
Liu Yang ◽  
Zheling Chen

Background: Treatment options for advanced gastric esophageal cancer are quite limited. Chemotherapy is unavoidable at certain stages, and research on targeted therapies has mostly failed. The advent of immunotherapy has brought hope for the treatment of advanced gastric esophageal cancer. The aim of the study was to analyze the safety of anti-PD-1/PD-L1 immunotherapy and the long-term survival of patients who were diagnosed as gastric esophageal cancer and received anti-PD-1/PD-L1 immunotherapy. Method: Studies on anti-PD-1/PD-L1 immunotherapy of advanced gastric esophageal cancer published before February 1, 2020 were searched online. The survival (e.g. 6-month overall survival, 12-month overall survival (OS), progression-free survival (PFS), objective response rates (ORR)) and adverse effects of immunotherapy were compared to that of control therapy (physician’s choice of therapy). Results: After screening 185 studies, 4 comparative cohort studies which reported the long-term survival of patients receiving immunotherapy were included. Compared to control group, the 12-month survival (OR = 1.67, 95% CI: 1.31 to 2.12, P < 0.0001) and 18-month survival (OR = 1.98, 95% CI: 1.39 to 2.81, P = 0.0001) were significantly longer in immunotherapy group. The 3-month survival rate (OR = 1.05, 95% CI: 0.36 to 3.06, P = 0.92) and 18-month survival rate (OR = 1.44, 95% CI: 0.98 to 2.12, P = 0.07) were not significantly different between immunotherapy group and control group. The ORR were not significantly different between immunotherapy group and control group (OR = 1.54, 95% CI: 0.65 to 3.66, P = 0.01). Meta-analysis pointed out that in the PD-L1 CPS ≥10 sub group population, the immunotherapy could obviously benefit the patients in tumor response rates (OR = 3.80, 95% CI: 1.89 to 7.61, P = 0.0002). Conclusion: For the treatment of advanced gastric esophageal cancer, the therapeutic efficacy of anti-PD-1/PD-L1 immunotherapy was superior to that of chemotherapy or palliative care.


Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 41
Author(s):  
Changyong Mu ◽  
Qiwang Zhong ◽  
Yan Meng ◽  
Yong Zhou ◽  
Nan Jiang ◽  
...  

The grass carp reovirus (GCRV) causes severe hemorrhagic disease with high mortality and leads to serious economic losses in the grass carp (Ctenopharyngodon idella) industry in China. Oral vaccine has been proven to be an effective method to provide protection against fish viruses. In this study, a recombinant baculovirus BmNPV-VP35-VP4 was generated to express VP35 and VP4 proteins from GCRV type Ⅱ via Bac-to-Bac baculovirus expression system. The expression of recombinant VP35-VP4 protein (rVP35-VP4) in Bombyx mori embryo cells (BmE) and silkworm pupae was confirmed by Western blotting and immunofluorescence assay (IFA) after infection with BmNPV-VP35-VP4. To vaccinate the grass carp by oral route, the silkworm pupae expressing the rVP35-VP4 proteins were converted into a powder after freeze-drying, added to artificial feed at 5% and fed to grass carp (18 ± 1.5 g) for six weeks, and the immune response and protective efficacy in grass carp after oral vaccination trial was thoroughly investigated. This included blood cell counting and classification, serum antibody titer detection, immune-related gene expression and the relative percent survival rate in immunized grass carp. The results of blood cell counts show that the number of white blood cells in the peripheral blood of immunized grass carp increased significantly from 14 to 28 days post-immunization (dpi). The differential leukocyte count of neutrophils and monocytes were significantly higher than those in the control group at 14 dpi. Additionally, the number of lymphocytes increased significantly and reached a peak at 28 dpi. The serum antibody levels were significantly increased at Day 14 and continued until 42 days post-vaccination. The mRNA expression levels of immune-related genes (IFN-1, TLR22, IL-1β, MHC I, Mx and IgM) were significantly upregulated in liver, spleen, kidney and hindgut after immunization. Four weeks post-immunization, fish were challenged with virulent GCRV by intraperitoneal injection. The results of this challenge study show that orally immunized group exhibited a survival rate of 60% and relative percent survival (RPS) of 56%, whereas the control group had a survival rate of 13% and RPS of 4%. Taken together, our results demonstrate that the silkworm pupae powder containing baculovirus-expressed VP35-VP4 proteins could induce both non-specific and specific immune responses and protect grass carp against GCRV infection, suggesting it could be used as an oral vaccine.


AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masarra M. Sakr ◽  
Walid F. Elkhatib ◽  
Khaled M. Aboshanab ◽  
Eman M. Mantawy ◽  
Mahmoud A. Yassien ◽  
...  

AbstractFailure in the treatment of P. aeruginosa, due to its broad spectrum of resistance, has been associated with increased patient mortality. One alternative approach for infection control is quorum quenching which was found to decrease virulence of such pathogen. In this study, the efficiency of a recombinant Ahl-1 lactonase formulated as a hydrogel was investigated to control the infection of multidrug resistant (MDR) P. aeruginosa infected burn using a murine model. The recombinant N-acylhomoserine lactonase (Ahl-1) was formulated as a hydrogel. To test its ability to control the infection of MDR P. aeruginosa, a thermal injury model was used. Survival rate, and systemic spread of the infection were evaluated. Histopathological examination of the animal dorsal skin was also done for monitoring the healing and cellular changes at the site of infection. Survival rate in the treated group was 100% relative to 40% in the control group. A decrease of up to 3 logs of bacterial count in the blood samples of the treated animals relative to the control group and a decrease of up to 4 logs and 2.3 logs of bacteria in lung and liver samples, respectively were observed. Histopathological examination revealed more enhanced healing process in the treated group. Accordingly, by promoting healing of infected MDR P. aeruginosa burn and by reducing systemic spread of the infection as well as decreasing mortality rate, Ahl-1 hydrogel application is a promising strategy that can be used to combat and control P. aeruginosa burn infections.


2021 ◽  
Vol 8 (7) ◽  
pp. 130
Author(s):  
Simona Sagona ◽  
Baldassare Fronte ◽  
Francesca Coppola ◽  
Elena Tafi ◽  
Matteo Giusti ◽  
...  

β-glucans can activate the animal innate immune system by acting as immune-modulators and inducing various stimulatory effects. The aim of this study was to investigate the effect of 1,3-1,6 β-glucans administered orally for 96 h on Apis mellifera workers (newly emerged and nurse bees). β-glucans were included in honey and syrup. Survival rate and phenoloxidase activity were measured. In both newly emerged and nurse bees, β-glucans supplementation did not affect survival rate (p > 0.05). Conversely, phenoloxidase activity was higher in both newly emerged bees (p = 0.048) and nurse bees (p = 0.014) fed with a honey diet enriched with β-glucans compared to those fed with only honey. In both the newly emerged and nurse bees, no statistical differences in phenoloxidase activity were recorded between the group fed with a syrup-based diet enriched with β-glucans and the control group (p > 0.05). The absence of significant variation in survival suggests that the potential negative effect of β-glucans in healthy bees could be mitigated by their metabolism. Conversely, the inclusion of β-glucans in a honey-based diet determined an increase of phenoloxidase activity, suggesting that the effect of β-glucan inclusion in the diet of healthy bees on phenoloxidase activity could be linked to the type of base-diet. Further investigations on β-glucans metabolism in bees, on molecular mechanism of phenoloxidase activation by 1,3-1,6 β-glucans, and relative thresholds are desirable. Moreover, investigation on the combined action of honey and β-glucans on phenoloxidase activity are needed.


Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 280
Author(s):  
Linh Nguyen Thi Truc ◽  
Tuu Nguyen Thanh ◽  
To Tran Thi Hong ◽  
Day Pham Van ◽  
Minh Vo Thi Tuyet ◽  
...  

This study aimed to evaluate the growth, survival rate, and resistance to acute hepatopancreatic necrosis disease (AHPND) of white leg shrimp (Penaeus vannamei) by using Lactobacillus plantarum, Lactobacillus fermentum, and Pediococcus pentosaceus mixed with feed, and at the same time supplying CNP in a ratio of 15:1:0.1 to the water. As a result, the treatments that shrimp were fed with feed containing lactic acid bacteria (LAB), especially L. plantarum, have increased shrimp growth, total hemocyte cells, granulocyte cells, and hyaline cells significantly (p < 0.05) in comparison to the control group. The supply of CNP to the water has promoted the intensity of V. parahaemolyticus effects on shrimp health and significantly decreased total hemocyte cells, granulocyte cells, and hyaline cells by 30–50% in the period after three days of the challenge, except in L. plantarum treatment, which had only a 20% decrease compared to other treatments. In CNP supplying treatments, the AHPND infected rate and mortality of shrimp were higher than those in other treatments. In summary, the supply of CNP had significantly reduced the shrimp’s immune response and promoted the susceptibility of shrimp to AHPND in both cases of use with and without LAB-containing diets.


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