scholarly journals Scintigraphic Imaging of Neovascularization With 99mTc-3PRGD2 for Evaluating Early Response to Endostar Involved Therapies on Pancreatic Cancer Xenografts In Vivo

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaona Jin ◽  
Chengyan Dong ◽  
Kun Zheng ◽  
Ximin Shi ◽  
Yu Liu ◽  
...  

BackgroundMolecular imaging targeting angiogenesis can specifically monitor the early therapeutic effect of antiangiogenesis therapy. We explore the predictive values of an integrin αvβ3-targeted tracer, 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2), for monitoring the efficacy of Endostar antiangiogenic therapy and chemotherapy in animal models.MethodsThe pancreatic cancer xenograft mice were randomly divided into four groups, with seven animals in each group and treated in different groups with 10 mg/kg/day of Endostar, 10 mg/kg/day of gemcitabine, 10 mg/kg/day of Endostar +10 mg/kg/day of gemcitabine at the same time, and the control group with 0.9% saline (0.1 ml/day). 99mTc-3PRGD2 scintigraphic imaging was carried out to monitor therapeutic effects. Microvessel density (MVD) was measured using immunohistochemical staining of the tumor tissues. The region of interest (ROI) of tumor (T) and contralateral corresponding site (NT) was delineated, and the ratio of radioactivity (T/NT) was calculated. Two-way repeated-measure analysis of variance (ANOVA) was used to assess differences between treatment groups.ResultsTumor growth was significantly lower in treatment groups than that in the control group (p < 0.05), and the differences were noted on day 28 posttreatment. The differences of 99mTc-3PRGD2 uptakes were observed between the control group and Endostar group (p = 0.033) and the combined treatment group (p < 0.01) on day 7 posttreatment and on day 14 posttreatment between the control group and gemcitabine group (p < 0.01). The accumulation of 99mTc-3PRGD2 was significantly correlated with MVD (r = 0.998, p = 0.002).ConclusionWith 99mTc-3PRGD2 scintigraphic imaging, the tumor response to antiangiogenic therapy, chemotherapy, and the combined treatment can be observed at an early stage of the treatments, much earlier than the tumor volume change. It provides new opportunities for developing individualized therapies and dose optimization.

2021 ◽  
Author(s):  
Xiaona Jin ◽  
Chengyan Dong ◽  
Kun Zheng ◽  
Ximin Shi ◽  
Yu Liu ◽  
...  

Abstract BackgroundMolecular imaging targeting angiogenesis is warranted for specific monitoring of molecular changes as early therapeutic effects via antiangiogenesis. We explore the predictive value of 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) as an integrin αvβ3 targeting imaging agent for monitoring the efficacy of endostar antiangiogenic therapy and chemotherapy in an animal model, to find a specific pathway that could monitor early therapeutic effects.ResultsTumor growth was significantly lower in treatment groups than in the control group (P<0.05), and also in Endostar + Gemcitabine group than in Endostar group(P=0.034) or Gemcitabine group (P=0.021), and the differences was observed at 28 days after treatment. The difference of uptake of 99mTc-3PRGD2 was observed between the control group and Endostar group(P=0.033) or the combination therapy group(P<0.01) at 7 days after treatment, and at 14 days after treatment between the control group and Gemcitabine group(P<0.01). 99mTc-3PRGD2 accumulation was significantly correlated with microvessel density (r=0.998, P=0.002).ConclusionWith 99mTc-3PRGD2 SPECT, the tumor response to antiangiogenic therapy, chemotherapy, and combination therapy can be assessed at a very early stage of treatment, much earlier than the tumor volume change, which provides new opportunities to develop individualized therapeutic approaches and optimized dosages for effective treatments.


2015 ◽  
Vol 115 (1) ◽  
pp. 1-5 ◽  
Author(s):  
L. Alonso ◽  
J. Fontecha ◽  
P. Cuesta

AbstractA total of twenty-four Yorkshire gilt pigs of 6–7 weeks of age were used in a 2×2 factorial experiment to determine the individual and combined effects of the inclusion of two dietary factors (cholesterol rich, 3 %β-cyclodextrin (BCD) andLactobacillus acidophiluscultures) on total cholesterol and LDL-cholesterol levels in blood serum. Pigs were assigned randomly to treatment groups (n6). Total serum cholesterol concentrations decreased after 3 weeks in all the experimental treatment groups, including diets with BCD,L.acidophilusor both. Similar trends were observed for serum LDL-cholesterol concentrations among the experimental treatments. No statistically significant differences from the control group were observed in either total serum cholesterol or LDL-cholesterol concentrations (P<0·05) for each of the individual treatment groups: BCD orL.acidophilus. However, significant differences in total serum cholesterol concentrations were observed when comparing the combined treatment group (BCD andL.acidophilus) with the control group, which consisted of a basal diet and sterile milk. The combined treatment group exhibited 17·9 % lower total serum cholesterol concentration after 3 weeks. Similar significant differences were observed when comparing the combined effect experimental group with the control group after 3 weeks. The combined treatment group exhibited 27·9 % lower serum LDL-cholesterol concentrations.


Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4222
Author(s):  
Yuko Kobashi ◽  
Masateru Uchiyama ◽  
Junichi Matsui

Pancreatic invasive ductal adenocarcinoma (PDAC) has a poor prognosis, and the detection of PDAC during the early stage is thought to improve prognosis. In this study, we retrospectively investigated pancreatic morphological abnormalities that lead to the early diagnosis of PDAC with computed tomography (CT) imaging. In total, 41 out of 308 patients diagnosed with pancreatic cancer between 2011 and 2017 in our institution were enrolled. As a control group for the group with pancreatic cancer, 4277 patients without pancreato-biliary diseases were enrolled. We retrospectively reviewed and analyzed the clinical data including patient characteristics, the clinical course and preoperative CT imaging with pancreatic morphological features. Out of 41 patients, 24 patients (58.5%) showed local K-shaped constriction of the pancreatic parenchyma “K-sign” on preoperative CT images. Eight patients (19.5%) showed localized fatty change. Out of 4277 control patients, seven patients (0.16%) showed K-sign. “K-sign” may be used for the early diagnosis of PDAC by CT imaging.


2020 ◽  
Vol 27 (1) ◽  
pp. 107327482092255 ◽  
Author(s):  
Shanshan Liu ◽  
Fei Wu ◽  
Yanling Zhang ◽  
Rongsheng Qin ◽  
Nengping Zhu ◽  
...  

Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) are highly expressed in nasopharyngeal carcinoma; therefore, blocking the binding of VEGF and VEGFR may be a potential way to treat nasopharyngeal carcinoma. Apatinib inhibits tumor angiogenesis. Previous studies have suggested that treatment with apatinib has an antitumor effect on nasopharyngeal carcinoma. This study will investigate the effect of apatinib combined with radiotherapy. In this study, nude mice injected with CNE-2 nasopharyngeal carcinoma cells were randomly divided into 6 groups. Therapeutic effects were assessed by evaluating tumor inhibition rate, phosphorylation of VEGFR-2, CD31, partial oxygen pressure, and tumor metabolism. We found that the tumor inhibition of mice in the treated groups was better compared to that of the control group. In mice treated with apatinib alone, angiogenesis was prevented, and the tumor tissue partial oxygen pressure was reduced, thereby achieving an antitumor effect. Moreover, the tumor inhibitory effect of combined treatment was stronger than treatment with either apatinib or radiotherapy alone. Compared with monotherapy treatment, combined treatment better resisted angiogenesis. Apatinib combined with radiotherapy to treat nasopharyngeal carcinoma has synergistic effects, which may be related to enhanced antiangiogenesis.


Author(s):  
Kamara JR Rhynd ◽  
Daniel P Walsh ◽  
Linnell CM Arthur-Banfield

Trichuris spp. are common helminths in NHP, and benzimidazoles and avermectins have both been used to treat theseintestinal parasites. The current study compared the efficacy of fenbendazole and ivermectin against natural infection ofTrichuris spp. in African green monkeys (Chlorocebus sabaeus). Anthelmintic-naive animals (n = 65) were randomly assignedto 4 groups: an untreated control group, and 3 groups treated with either fenbendazole, ivermectin, or both compounds. Fecalsamples were collected before treatment and on days 7, 14, 28, and 60 after treatment, and fecal egg counts (FEC) were determined by using fecal flotation. The mean percentages of FEC reduction at day 60 were 100%, 86%, and 100% for treatmentwith fenbendazole, ivermectin, and both compounds, respectively. Analyzing the time series of FEC by using a Bayesian generalized linear model showed no significant difference in the proportional reduction in FEC among the 3 treatment groups, although all FEC from treated groups were significantly lower than the FEC of the control group. In contrast, the probability of shedding was highest in the ivermectin group and the lowest in the animals treated with both compounds. The probability of shedding differed significantly between the fenbendazole and ivermectin groups and between the ivermectin and combined-treatment groups. In conclusion, both fenbendazole and ivermectin are effective anthelmintics in treating Trichuris spp. infection in African green monkeys. All treatment groups showed significant reductions in FEC when compared with baseline counts and control animals; however, fenbendazole may be more effective than ivermectin when used solely or in combination with other anthelmintic treatments.


2022 ◽  
Vol 11 ◽  
Author(s):  
Wojciech Blogowski ◽  
Katarzyna Dolegowska ◽  
Anna Deskur ◽  
Barbara Dolegowska ◽  
Teresa Starzynska

Eicosanoids are bioactive lipids derived from arachidonic acid, which have emerged as key regulators of a wide variety of pathophysiological processes in recent times and are implicated as mediators of gastrointestinal cancer. In this study, we investigated the systemic levels of lipoxygenase (LOX)-derived lipoxin A4 and B4, together with resolvin D1 and D2 in patients with pancreatic adenocarcinoma (n = 68), as well as in healthy individuals (n = 32). Systemic concentrations of the aforementioned immunoresolvents were measured using an enzyme-linked immunosorbent assay (ELISA). In this study, we observed that compared with concentrations in healthy individuals, the peripheral concentrations of the aforementioned eicosanoids were significantly elevated (2- to 10-fold) in patients with pancreatic cancer (in all cases p&lt;0.00001). No significant association was observed between eicosanoid levels and the TNM clinical staging. Furthermore, we observed no significant differences in concentrations of the analyzed bioactive lipids between patients diagnosed with early-stage (TNM stage I-II) and more advanced disease (TNM stage III-IV). Receiver operating characteristic (ROC) curve analysis of each aforementioned immunoresolvent showed area under the curve values ranging between 0.79 and 1.00. Sensitivity, specificity, as well as positive and negative predictive values of the eicosanoids involved in the detection/differentiation of pancreatic adenocarcinoma ranged between 56.8% and 100%. In summary, our research is the first study that provides clinical evidence to support a systemic imbalance in LOX-derived lipoxins and resolvins as the mechanism underlying the pathogenesis of pancreatic adenocarcinoma. This phenomenon occurs regardless of the clinical TNM stage of the disease. Furthermore, our study is the first to preliminarily highlight the role of peripheral levels of immunoresolvents, particularly resolvin D1, as potential novel biomarkers of pancreatic cancer in humans.


Author(s):  
A. V. Averyanov ◽  
A. G. Konoplyannikov ◽  
F. G. Zabozlaev ◽  
O. V. Danilevskaya ◽  
M. A. Konoplyannikov ◽  
...  

Aim:to perform a comparative analysis of the effi cacy of the inhaled and intravenous delivery of equivalent doses of bone marrow mesenchymal stem cells (BMMSCs) in rabbits according to the standard model of bleomycin pulmonary fi brosis.Materials and methods.After bronchoscopic instillation of bleomycin, 5 rabbits received intravenous transplantation of 2 × 106 allogeneic BMMSCs, other 5 rabbits – 2 × 107 MSCs inhaled via compressor nebulizer; control healthy and bleomycin group included 5 animals each.Results.Both groups treated with BMMSCs had a signifi cantly lower Ashcroft fi brosis index than the bleomycin control group. Expression of collagen in lung tissue in all groups with bleomycin injury was superior to healthy controls, but in animals underwent intravenous BMMSC transplantation collagen score was 0.74 points, and in inhaled treated group – 0.51 points, while in bleomycin controls – 2.1 point. Levels of TNF-α and TGF-β1 in BAL fl uids tended to decrease in treatment groups, but did not differ signifi cantly from control. A similar picture was observed in the cytological analysis of BAL.Conclusion.In general, both methods of delivering of BMMSCs to the lungs demonstrated similar therapeutic effects in inhibiting the development of experimental fi brosis, indicating that both intravenous and inhalational way of introduction can be used for subsequent clinical studies. 


2006 ◽  
Vol 34 (06) ◽  
pp. 937-947 ◽  
Author(s):  
Shao Li ◽  
Ruiqin Wang ◽  
Yulong Zhang ◽  
Xuegong Zhang ◽  
A. Joseph Layon ◽  
...  

Severe acute respiratory syndrome (SARS) is an infectious disease and some of its symptoms were clinically indistinguishable of those from similar diseases. This study aimed to find the symptom combinations associated with adverse outcome and the therapeutic effects in a cohort of patients with probable SARS retrospectively. In 2003, 123 SARS cases in Beijing were subjected to a strictly western medicine (WM) treatment, or a combined treatment (WM plus Herba houttuyniae injection, addition of individualized herbal treatments when necessary), of which 115 were followed till death or discharge; 8 were transferred and lost to follow-up. In both treatment groups, clinical manifestations were evaluated daily; development of signs and symptoms, and their possible relationship with outcome, were assessed. The relationships between these sign/symptom complexes and outcome under two treatment protocols were evaluated and differences were noted. Dynamic symptom combinations, dividing into the early, the medium-term and the durational symptom clusters, were identified as likely being related to the adverse outcomes of SARS ( p < 0.05, p < 0.01). Compared with a strictly WM treatment, the combined treatment resulted in a longer hospital stay ( p = 0.028), a non-statistically significant mortality rate decrease (combined treatment: 9.6% versus WM: 11.1%), and a significant improvement of arthralgia and myalgia ( p < 0.05) in the early symptom cluster. Additionally, the combined protocol improved arterial oxyhemoglobin saturation significantly at day 22 ( p < 0.05). In conclusion, the progress and outcome of SARS may be associated with specific temporal patterns of development in combination of several non-specific signs and symptom complexes, which are also helpful for evaluating the therapeutic effects on SARS patients.


2021 ◽  
Vol 8 ◽  
Author(s):  
Amany M. Ramez ◽  
Ehab Kotb Elmahallawy ◽  
Gehad E. Elshopakey ◽  
Amira A. Saleh ◽  
Samar M. Moustafa ◽  
...  

Schistosomiasis, a major parasitic illness, has high morbidity and negative financial effects in subtropical and tropical countries, including Egypt. The present study investigated the therapeutic effects of Spirulina platensis (SP) and matcha green tea (MGT) in Schistosoma mansoni-infected mice combined with tracing their possible antioxidant and anti-inflammatory impacts and their protective potency. A total of 60 Swiss albino mice were randomly allocated into six groups (n = 10): control group (CNT, received normal saline); SP–MGT group [received oral SP (3 g/kg bodyweight/day) plus MGT (3 g/kg bodyweight/day)]; S. mansoni group (infected with S. mansoni cercariae, 100 ± 10/mouse, using the tail immersion method); SP-infected group (infected with S. mansoni and received oral SP); MGT-infected group (received oral MGT after S. mansoni infection); and SP–MGT-infected group (received combined treatment of SP and MGT after S. mansoni infection). Treatment with SP and MGT started 4 weeks after S. mansoni infection and ended 10 weeks after. SP and MGT treatment (SP-infected and MGT-infected groups) and the combined treatment (SP–MGT-infected group) minimized the hepatic damage induced by S. mansoni; circulating alanine aminotransferase and aspartate transaminase decreased, and total protein, albumin, and globulin serum levels increased. The serum level of malondialdehyde significantly declined, and catalase, glutathione peroxidase, superoxide dismutase, and total antioxidant capacity increased in SP-infected, MGT-infected, and SP–MGT-infected groups compared with the infected group. Co-administration of SP and MGT reduced serum cytokine levels (tumor necrosis factor-alpha, interferon-gamma, and interleukin-13) and increased interleukin-10 levels after S. mansoni infection compared with the infected group. Moreover, treatment with SP and/or MGT decreased the number of granulomas in hepatic and splenic tissues compared with the infected group. Collectively, our results suggest that combined SP and MGT treatment is effective for S. mansoni infection. Liver and spleen tissue alterations were improved, the antioxidant systems were stimulated, and the inflammatory response was suppressed. Further research is recommended to investigate the mechanisms of the combined SP and MGT treatment effects to facilitate the development of novel therapies against this disease.


Author(s):  
Zeinab Mahdian ◽  
Fereshteh Amiri ◽  
Zohreh Mohammadi ◽  
Parviz Farzadinia ◽  
Fahimeh Safizadeh ◽  
...  

Background and Aims: Burn injury remain as a major medical problem throughout the world. This injury is accompanied with inflammatory and wound healing responses. Since royal jelly (RJ) has anti-inflammatory and wound healing activity therefore, the aim of this study was to evaluate the repairing effects of RJ on skin burn- damage. Materials and Methods: In an experimental study, 40 male Wistar rats (8 weeks old) were engaged. The animals were divided into five equal groups. Group 1 was considered healthy control. Group 2 (positive control) was treated topically with Silver Sulfadiazine Cream, group 3 received Eucerin as negative control, and group 4, 5 treated with RJ (10 and 30%). Sampling was performed after observing the second-degree burns on the first, seventh and fourteenth days. Then after 28 days, rats were sacrificed and their skin tissues were used for morphological and morphometric assessments. Results: The results of this study showed that the amount and arrangement of collagen type 1 protein was higher in the RJ treatment groups versus control group. Reconstruction and thickening of the epithelium in RJ treated groups confirmed therapeutic effects of RJ. In addition, RJ increased angiogenesis compared to the control group. The woundchr('39')s surface area was reduced in the RJ treatment groups compared to the control group. In addition, fibroblast cell proliferation was increased in the groups receiving RJ versus control. Conclusions: It could be concluded that, RJ induce wound healing effects and might be considered as potential treatment option to improve the burn wound healing.


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