Cancer cells with immunogenic properties having altered protein glycosylation, modified blood group substances have been widely studied. Due to the genetic instability occurring during carcinogenesis the glycosyltrans...Cancer cells with immunogenic properties having altered protein glycosylation, modified blood group substances have been widely studied. Due to the genetic instability occurring during carcinogenesis the glycosyltransferases may suffer from posttranslation sequence modification. The author describes 2 autopsy cases, where in the background of the unusual metastatic tumor presentation, incompatible blood group antigenic determinants have been demonstrated using blood group specific lectins and monoclonal antibodies (mAb). In the first case, reported here, a 10-year-old girl developed an acute myeloid leukemia and died in a septic endotoxin shock after successful cytostatic treatment of a juvenile signet ring cell cancer of her colon. At autopsy there were no signs of tumor except bilateral apple-sized mucinous ovarian (Krukenberg) metastases. While she had erythrocyte phenotype of blood group A, the signet ring adenocarcinoma cells expressed blood group B incompatible antigenic determinants with lectin/mAb. In the second case, the autopsy of a 78-year-old female resulted in no macroscopic tumor sign except a moderately enlarged, ham hard spleen. Light microscopy revealed adenocarcinomatous infiltration in the splenic sinusoids. The patient had blood group O, while the metastatic cells in the spleen reacted with Breast Carcinoma Antigen (BioGenex) and incompatible anti-B Banderiaeasimplicifolia agglutinin I and anti-B mAb. It proved to be a case of an occult, completely regressed breast cancer. Based on these observations the expression of tumor specific incompatible blood group antigens might occur from time to time, mostly in adenocarcinomas. Accordingly, blood group-based specific immuno-oncotherapy could be considered in some cancer cases.展开更多
Objective Isocitrate dehydrogenase gene(IDH)mutations are associated with tumor angiogenesis and therefore play an important role in glioma management.This study compared the performance of tumor blood vessels counted...Objective Isocitrate dehydrogenase gene(IDH)mutations are associated with tumor angiogenesis and therefore play an important role in glioma management.This study compared the performance of tumor blood vessels counted from contrast-enhanced 3D brain volume(3D-BRAVO)sequence and dynamic contrast-enhanced(DCE)MRI in differentiating IDH1 status in gliomas.Methods Forty-four glioma patients[16 with IDH1 mutant-type(IDH1-MT),28 with IDH1 wild-type(IDH1-WT)]were retrospectively analyzed.A blood vessel entering a tumor was defined as an intratumoral vessel;a blood vessel adjacent to the edge of a tumor was defined as a peritumoral vessel.Combined vessels were defined as the sum of the intratumoral and peritumoral vessels.DCE-derived metrics of tumor were normalized to the contralateral normal-appearing white matter.Results Intratumoral,peritumoral,and combined tumor blood vessels were all significantly different between IDH1-MT and IDH1-WT gliomas,and the range of area under curves(AUCs)was 0.816–0.855.For DCE-derived parameters,cerebral blood volume,cerebral blood flow,mean transit time,and volume transfer constant were significantly different between IDH1-MT and IDH1-WT gliomas,and the range of AUCs was 0.703–0.756.Combined vessels possessed the best performance for identifying IDH1 mutations in gliomas(AUC:0.855,sensitivity:0.857,specificity:0.812,P<0.001).Conclusion The number of tumor blood vessels has comparable diagnostic performance with DCE-derived parameters for differentiating IDH1 mutations and can serve as a potential imaging biomarker to reflect IDH1 mutations in gliomas.展开更多
BACKGROUND In traditional Chinese medicine(TCM),frankincense and myrrh are the main components of the antitumor drug Xihuang Pill.These compounds show anticancer activity in other biological systems.However,whether fr...BACKGROUND In traditional Chinese medicine(TCM),frankincense and myrrh are the main components of the antitumor drug Xihuang Pill.These compounds show anticancer activity in other biological systems.However,whether frankincense and/or myrrh can inhibit the occurrence of hepatocellular carcinoma(HCC)is unknown,and the potential molecular mechanism(s)has not yet been determined.AIM To predict and determine latent anti-HCC therapeutic targets and molecular mechanisms of frankincense and myrrh in vivo.METHODS In the present study,which was based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(http://tcmspw.com/tcmsp.php),Universal Protein database(http://www.uniprot.org),GeneCards:The Human Gene Database(http://www.genecards.org/)and Comparative Toxicogenomics Database(http://www.ctdbase.org/),the efficacy of and mechanism by which frankincense and myrrh act as anti-HCC compounds were predicted.The core prediction targets were screened by molecular docking.In vivo,SMMC-7721 human liver cancer cells were transplanted as xenografts into nude mice to establish a subcutaneous tumor model,and two doses of frankincense plus myrrh or one dose of an EGFR inhibitor was administered to these mice continuously for 14 d.The tumors were collected and evaluated:the tumor volume and growth rate were gauged to evaluate tumor growth;hematoxylineosin staining was performed to estimate histopathological changes;immunofluorescence(IF)was performed to detect the expression of CD31,α-SMA and collagen IV;transmission electron microscopy(TEM)was conducted to observe the morphological structure of vascular cells;enzyme-linked immunosorbent assay(ELISA)was performed to measure the levels of secreted HIF-1αand TNF-α;reverse transcription-polymerase chain reaction(RT-qPCR)was performed to measure the mRNA expression of HIF-1α,TNF-α,VEGF and MMP-9;and Western blot(WB)was performed to determine the levels of proteins expressed in the EGFR-mediated PI3K/Akt and MAPK signaling pathways.RESULTS The results of the network pharmacology analysis showed that there were 35 active components in the frankincense and myrrh extracts targeting 151 key targets.The molecular docking analysis showed that both boswellic acid and stigmasterol showed strong affinity for the targets,with the greatest affinity for EGFR.Frankincense and myrrh treatment may play a role in the treatment of HCC by regulating hypoxia responses and vascular system-related pathological processes,such as cytokine-receptor binding,and pathways,such as those involving serine/threonine protein kinase complexes and MAPK,HIF-1 and ErbB signaling cascades.The animal experiment results were verified.First,we found that,through frankincense and/or myrrh treatment,the volume of subcutaneously transplanted HCC tumors was significantly reduced,and the pathological morphology was attenuated.Then,IF and TEM showed that frankincense and/or myrrh treatment reduced CD31 and collagen IV expression,increased the coverage of perivascular cells,tightened the connection between cells,and improved the shape of blood vessels.In addition,ELISA,RT-qPCR and WB analyses showed that frankincense and/or myrrh treatment inhibited the levels of hypoxia-inducible factors,inflammatory factors and angiogenesis-related factors,namely,HIF-1α,TNF-α,VEGF and MMP-9.Furthermore,mechanistic experiments illustrated that the effect of frankincense plus myrrh treatment was similar to that of an EGFR inhibitor with regard to controlling EGFR activation,thereby inhibiting the phosphorylation activity of its downstream targets:the PI3K/Akt and MAPK(ERK,p38 and JNK)pathways.CONCLUSION In summary,frankincense and myrrh treatment targets tumor blood vessels to exert anti-HCC effects via EGFR-activated PI3K/Akt and MAPK signaling pathways,highlighting the potential of this dual TCM compound as an anti-HCC candidate.展开更多
A coupled intravascular-transvascular-interstitial fluid flow model is developed to study the distributions of blood flow and interstitial fluid pressure in solid tumor microcirculation based on a tumor-induced microv...A coupled intravascular-transvascular-interstitial fluid flow model is developed to study the distributions of blood flow and interstitial fluid pressure in solid tumor microcirculation based on a tumor-induced microvascular network. This is generated from a 2D nine-point discrete mathematical model of tumor angiogenesis and contains two parent vessels. Blood flow through the microvascular network and interstitial fluid flow in tumor tissues are performed by the extended Poiseuille's law and Darcy's law, respectively, transvascular flow is described by Starling's law; effects of the vascular permeability and the interstitial hydraulic conductivity are also considered. The simulation results predict the heterogeneous blood supply, interstitial hypertension and low convection on the inside of the tumor, which are consistent with physiological observed facts. These results may provide beneficial information for anti-angiogenesis treatment of tumor and further clinical research.展开更多
<strong>Objective:</strong> To investigate the value of the number of circulating tumor cells (CTC) in peripheral blood in the prognosis and coagulation-related indicators of patients with renal cancer. &l...<strong>Objective:</strong> To investigate the value of the number of circulating tumor cells (CTC) in peripheral blood in the prognosis and coagulation-related indicators of patients with renal cancer. <strong>Methods:</strong> 65 patients with renal cell carcinoma (RCC) confirmed pathologically were divided into CTC positive group and CTC negative group according to the CTC count (5 pcs/3.5 ml). Compare the age, gender, tumor location, TNM (clinical stage), pathological grade, tissue type, lymph node metastasis, distant metastasis, prognosis and prothrombin time (PT), fibrinogen (FIB), partial coagulation of the two groups of patients The correlation between the results of zymogen time (APTT) and D-dimer (DD) and the number of CTC. <strong>Results:</strong> There were significant differences in TNM, lymph node metastasis, and distant metastasis between the two groups (P < 0.05). The number of CTC in patients was correlated with FIB and D-D levels (P < 0.05). <strong>Conclusion:</strong> The number of CTC in patients with renal cell carcinoma is correlated with some clinical phenotypes (TNM, lymph node metastasis, distant metastasis) and some coagulation indexes (FIB, D-D), and can jointly predict the prognosis of renal cancer.展开更多
Effects of angiotensin Ⅱ and other six vasoactive agents on tissue blood flow of Yoahida rat ascites hepatoma AH109A and normal liver were measured by the hydrogen clearance method. The mean blood flow in the tumor p...Effects of angiotensin Ⅱ and other six vasoactive agents on tissue blood flow of Yoahida rat ascites hepatoma AH109A and normal liver were measured by the hydrogen clearance method. The mean blood flow in the tumor peripheral part under normal tension was 11. 9±8. 2ml/ min/100g tissue and was not influenced by tumor size. Tumor blood flow was more significantly increased in infusion angiotensin Ⅱthan 0.5mg/ ml methoxamine, however, normal liver blood flow of tumor-bearing rats was unchanged in contrast to an Increase seen in the tumor. A pronounced reduction of tumor blood flow was found after administration of epinephrine, norepinephrin and ethylphenylephrine. In addition, metaraminol and phenyleprine as well as 1. 0 and 2. 5mg/ ml methoxamine were not found to significantly change blood flow of the tumor.展开更多
Female adult BUF rats (6-8 weeks) received Sham operation (Sham); 70% hepatectomy (PH); Sham or PH with blood transfusion (BT or PH+BT). BUF 7316A hepatoma cells were inoculated subcutaneously in the neck of rats on t...Female adult BUF rats (6-8 weeks) received Sham operation (Sham); 70% hepatectomy (PH); Sham or PH with blood transfusion (BT or PH+BT). BUF 7316A hepatoma cells were inoculated subcutaneously in the neck of rats on the operation day. Tumor size was measured from day 7 to 20 after inoculation. Sera and splenic adherent cell harvested on day 5 from Sham and PH rat were added into Mixed Lymphocyte Cultures (MLR). The result showed that tumor growth in PH or BT rats was significantly promoted as compared to that in Sham rats (P<0.01,P<0.05). The most marked enhancement of tumor growth was observed in PH+BT rats (P<0.001). Sera and splenic adherent cell from PH rat significantly inhibited MLR (P<0.05). Those results suggest that partial hepatectomy and blood transfusion are responsible for the enhancement of tumor growth. Some immunosuppressive factor might be produced in the process of liver regeneration, and blood transfusion might have an additive immunosuppressive effect.展开更多
Objective:To determine the clinical value of combined detection of circulating tumor cells(CTCs)and cell-free DNA(cfDNA)in peripheral blood of patients with triple-negative breast cancer.Method:41 patients with breast...Objective:To determine the clinical value of combined detection of circulating tumor cells(CTCs)and cell-free DNA(cfDNA)in peripheral blood of patients with triple-negative breast cancer.Method:41 patients with breast cancer admitted to the First Central Hospital of Baoding from January 2020 to December 2021 were selected and recruited into the experimental group,42 patients with benign breast cancer admitted during the same period were recruited into the conditional control group,and 41 healthy patients admitted during the same period were recruited into the blank control group.The positive rate of peripheral blood CTCs,the level of cfDNA,and the diagnostic efficacy of peripheral blood CTCs,cfDNA alone and the combination thereof for breast cancer were analyzed.Result:The positive rates of peripheral blood CTCs in the experimental group,the conditional control group,and the blank control group were 43.90%,11.90%,and 9.74%,respectively,and there was significant difference among the groups.The levels of cfDNA in peripheral blood of the experimental group,the conditional control group,and the blank control group were 0.26±0.08 bp,0.17±0.03 bp,and 0.15±0.04 bp,respectively,which were statistically significant.The detection levels of 100 bp hTERT/ng mT1 and 241 bp hTERT/ng-mT1 in the experimental group were significantly higher than those in the conditional control group and the blank control group.The accuracy of peripheral blood CTCs detection in the three groups was 66.21%,the accuracy of cfDA241 bp/100 hp hTERT detection was 80.41%,and the accuracy of combined detection of peripheral blood CTCs and cfDNA was 94.03%.Conclusion:The clinical application of peripheral blood CTCs combined with cfDNA level detection can increase detection accuracy,provide data support for clinicians,and improve the clinical diagnostic effect of triple-negative breast cancer.展开更多
Objectives: The aim of the investigation was to study the hormonal status (sex hormones: estradiol (E2), progesterone (P), testosterone (T);non-sex gonadotropic hormones-luteinizing hormone (LH) and follicle-stimulati...Objectives: The aim of the investigation was to study the hormonal status (sex hormones: estradiol (E2), progesterone (P), testosterone (T);non-sex gonadotropic hormones-luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) of women with benign and malignant tumors of uterine body in the reproductive, menopause and postmenopause periods. Also the distribution features of the blood ABO system phenotype groups and their link to the development of uterine body tumors have been studied. Methods: The determination of hormones was made by the enzyme analysis method (ELAIZA), provided by the proper ELAIZA kits. For the study of blood ABO system antigens, internationally recognized immunoserology methods were used. Results: Investigations revealed the increased level of E2 and T on the background of the reduced P in the blood of the women with uterine tumors in the reproductive, menopause and post-menopause period. As for gonadotropic hormones, the decreased levels of LH and FSH have also been detected. From the ABO system phenotype groups A(II) group had the highest frequency between the women with malignant uterine tumor in the reproductive age. O (I) phenotype group was the most frequent in case of menopause and post-menopause women with uterine malignant tumors. Conclusions: Hormonal imbalance creates good conditions for the proliferation of uterine tissues and hence causes the development of benign and malignant uterine tumors. The imbalance of the sex steroid and gonadotropic hormones in the blood of post-menopause women indicates on the genotoxic mechanism of cancer development on the background of age-related changes. A(II) group had the highest frequency between the reproductive age women with uterine malignant tumor, while O (I) group was the most frequent in case of menopause and post-menopause patients.展开更多
Epithelial glioma is the most common brain cancer,accounting for 35.26%-60.69%of intracranial tumors with an average of 44.69%,and it remains the greatest challenge in the field of neurosurgery.The median survival tim...Epithelial glioma is the most common brain cancer,accounting for 35.26%-60.69%of intracranial tumors with an average of 44.69%,and it remains the greatest challenge in the field of neurosurgery.The median survival time of patients with advanced glioma is only 12 to 18 months due to the characteristics of high aggression,and the therapeutic effect was poor though surgery,chemotherapy,and targeted drug therapy being treated.Because of the presence of heterogeneity and the differentiation disorder,only a small number of glioma cells are the source of tumor growth and metastasis,which are highly resistant to traditional treatments.They are deemed as the“seed”tumor cells as they could get rid of the effect of the treatment and reconstruct the organization of tumor.They are also termed as brain tumor stem cell(BTSC)or glioma stem cells(GSCs)since neural stem cells share similar features with them.Recent data reveal that they are directly related with invasion,angiogenesis,tolerance,chemotherapy,recurrence of glioma.Based on the research result by the team,the paper elaborates the characteristics of GSCs and the relationship with the tumor angiogenesis.展开更多
The changes of blood perfusion and oxygen transport in tumors during tumor vascular normalization are studied with 3-dimensional mathematical modeling and numerical simulation. The models of tumor angiogenesis and vas...The changes of blood perfusion and oxygen transport in tumors during tumor vascular normalization are studied with 3-dimensional mathematical modeling and numerical simulation. The models of tumor angiogenesis and vascular-disrupting are used to simulate "un-normalized" and "normalized" vasculatures. A new model combining tumor hemodynamics and oxygen transport is developed. In this model, the intravasculartransvascular-interstitial flow with red blood cell(RBC) delivery is tightly coupled, and the oxygen resource is produced by heterogeneous distribution of hematocrit from the flow simulation. The results show that both tumor blood perfusion and hematocrit in the vessels increase, and the hypoxia microenvironment in the tumor center is greatly improved during vascular normalization. The total oxygen content inside the tumor tissue increases by about 67%, 51%, and 95% for the three approaches of vascular normalization,respectively. The elevation of oxygen concentration in tumors can improve its metabolic environment, and consequently reduce malignancy of tumor cells. It can also enhance radiation and chemotherapeutics to tumors.展开更多
BACKGROUND Hematological tumors are common malignant tumors,with high morbidity and mortality rates.Most patients with hematological malignancies develop sleep disorders that seriously affect their life and health bec...BACKGROUND Hematological tumors are common malignant tumors,with high morbidity and mortality rates.Most patients with hematological malignancies develop sleep disorders that seriously affect their life and health because of acute onset of disease,rapid progression,high recurrence rates,complex treatment methods,and treatment costs.AIM To explore the mediating effect of resilience on fear of disease progression and sleep quality in patients with hematological malignancies.METHODS A cross-sectional analysis of 100 patients with hematological malignancies,treated in the First Affiliated Hospital of Jinzhou Medical University between August 2022 and August 2023,was conducted.Patients were assessed using a general data survey,a simplified scale for the fear of progression(FoP)of disease,a resilience scale,and the Pittsburgh Sleep Quality Index.Statistical analysis was conducted to determine the relationship between various patient characteristics and FoP,resilience,and sleep quality.Spearman’s correlation analysis was used to examine the correlations between mental resilience,FoP,and sleep quality.RESULTS The total FoP score mean value in patients with hematological malignancies was 38.09±5.16;the total resilience score mean value was 40.73±7.04;and the Pittsburgh Sleep Quality Index score mean value was 10.72±1.90.FoP,resilience,and sleep quality of the patients were associated with family per capita monthly income and patient education level(P<0.05).Spearman correlation analysis revealed that FoP was negatively correlated with resilience and sleep quality scores(r=-0.560,-0.537,P<0.01),respectively,and resilience was significantly associated with sleep quality scores(r=0.688,P<0.01).Mediation analysis showed that the mediating effect of resilience between FoP and sleep quality in patients with hematological malignancies was-0.100 and accounted for 50.51%of the total effect.This indicated that FoP directly and indirectly affected sleep quality through the mesomeric effect of resilience.CONCLUSION Resilience is an intermediary variable between FoP and sleep quality in patients with hematological malignancies.Medical staff should evaluate and follow-up FoP and resilience to implement measures to improve sleep quality.展开更多
文摘Cancer cells with immunogenic properties having altered protein glycosylation, modified blood group substances have been widely studied. Due to the genetic instability occurring during carcinogenesis the glycosyltransferases may suffer from posttranslation sequence modification. The author describes 2 autopsy cases, where in the background of the unusual metastatic tumor presentation, incompatible blood group antigenic determinants have been demonstrated using blood group specific lectins and monoclonal antibodies (mAb). In the first case, reported here, a 10-year-old girl developed an acute myeloid leukemia and died in a septic endotoxin shock after successful cytostatic treatment of a juvenile signet ring cell cancer of her colon. At autopsy there were no signs of tumor except bilateral apple-sized mucinous ovarian (Krukenberg) metastases. While she had erythrocyte phenotype of blood group A, the signet ring adenocarcinoma cells expressed blood group B incompatible antigenic determinants with lectin/mAb. In the second case, the autopsy of a 78-year-old female resulted in no macroscopic tumor sign except a moderately enlarged, ham hard spleen. Light microscopy revealed adenocarcinomatous infiltration in the splenic sinusoids. The patient had blood group O, while the metastatic cells in the spleen reacted with Breast Carcinoma Antigen (BioGenex) and incompatible anti-B Banderiaeasimplicifolia agglutinin I and anti-B mAb. It proved to be a case of an occult, completely regressed breast cancer. Based on these observations the expression of tumor specific incompatible blood group antigens might occur from time to time, mostly in adenocarcinomas. Accordingly, blood group-based specific immuno-oncotherapy could be considered in some cancer cases.
基金the National Natural Science Foundation of China(No.81730049 and No.81801666)the Fundamental Research Funds for the Central Universities,HUST(No.2019JYCXJJ044).
文摘Objective Isocitrate dehydrogenase gene(IDH)mutations are associated with tumor angiogenesis and therefore play an important role in glioma management.This study compared the performance of tumor blood vessels counted from contrast-enhanced 3D brain volume(3D-BRAVO)sequence and dynamic contrast-enhanced(DCE)MRI in differentiating IDH1 status in gliomas.Methods Forty-four glioma patients[16 with IDH1 mutant-type(IDH1-MT),28 with IDH1 wild-type(IDH1-WT)]were retrospectively analyzed.A blood vessel entering a tumor was defined as an intratumoral vessel;a blood vessel adjacent to the edge of a tumor was defined as a peritumoral vessel.Combined vessels were defined as the sum of the intratumoral and peritumoral vessels.DCE-derived metrics of tumor were normalized to the contralateral normal-appearing white matter.Results Intratumoral,peritumoral,and combined tumor blood vessels were all significantly different between IDH1-MT and IDH1-WT gliomas,and the range of area under curves(AUCs)was 0.816–0.855.For DCE-derived parameters,cerebral blood volume,cerebral blood flow,mean transit time,and volume transfer constant were significantly different between IDH1-MT and IDH1-WT gliomas,and the range of AUCs was 0.703–0.756.Combined vessels possessed the best performance for identifying IDH1 mutations in gliomas(AUC:0.855,sensitivity:0.857,specificity:0.812,P<0.001).Conclusion The number of tumor blood vessels has comparable diagnostic performance with DCE-derived parameters for differentiating IDH1 mutations and can serve as a potential imaging biomarker to reflect IDH1 mutations in gliomas.
基金the National Natural Science Foundation of China,No.U20A20408(Major Program)and No.82074450(General Program)Natural Science Foundation of Hunan Province,No.2020JJ4066+2 种基金Hunan Province Research and innovation projects for Postgraduates,No.CX20190541Hunan Province"domestic firstclass cultivation discipline"Integrated Traditional Chinese and Western medicine open fund project,No.2018ZXYJH03Hunan University Undergraduate Research Learning and Innovative Experiment Project,No.201609030114.
文摘BACKGROUND In traditional Chinese medicine(TCM),frankincense and myrrh are the main components of the antitumor drug Xihuang Pill.These compounds show anticancer activity in other biological systems.However,whether frankincense and/or myrrh can inhibit the occurrence of hepatocellular carcinoma(HCC)is unknown,and the potential molecular mechanism(s)has not yet been determined.AIM To predict and determine latent anti-HCC therapeutic targets and molecular mechanisms of frankincense and myrrh in vivo.METHODS In the present study,which was based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(http://tcmspw.com/tcmsp.php),Universal Protein database(http://www.uniprot.org),GeneCards:The Human Gene Database(http://www.genecards.org/)and Comparative Toxicogenomics Database(http://www.ctdbase.org/),the efficacy of and mechanism by which frankincense and myrrh act as anti-HCC compounds were predicted.The core prediction targets were screened by molecular docking.In vivo,SMMC-7721 human liver cancer cells were transplanted as xenografts into nude mice to establish a subcutaneous tumor model,and two doses of frankincense plus myrrh or one dose of an EGFR inhibitor was administered to these mice continuously for 14 d.The tumors were collected and evaluated:the tumor volume and growth rate were gauged to evaluate tumor growth;hematoxylineosin staining was performed to estimate histopathological changes;immunofluorescence(IF)was performed to detect the expression of CD31,α-SMA and collagen IV;transmission electron microscopy(TEM)was conducted to observe the morphological structure of vascular cells;enzyme-linked immunosorbent assay(ELISA)was performed to measure the levels of secreted HIF-1αand TNF-α;reverse transcription-polymerase chain reaction(RT-qPCR)was performed to measure the mRNA expression of HIF-1α,TNF-α,VEGF and MMP-9;and Western blot(WB)was performed to determine the levels of proteins expressed in the EGFR-mediated PI3K/Akt and MAPK signaling pathways.RESULTS The results of the network pharmacology analysis showed that there were 35 active components in the frankincense and myrrh extracts targeting 151 key targets.The molecular docking analysis showed that both boswellic acid and stigmasterol showed strong affinity for the targets,with the greatest affinity for EGFR.Frankincense and myrrh treatment may play a role in the treatment of HCC by regulating hypoxia responses and vascular system-related pathological processes,such as cytokine-receptor binding,and pathways,such as those involving serine/threonine protein kinase complexes and MAPK,HIF-1 and ErbB signaling cascades.The animal experiment results were verified.First,we found that,through frankincense and/or myrrh treatment,the volume of subcutaneously transplanted HCC tumors was significantly reduced,and the pathological morphology was attenuated.Then,IF and TEM showed that frankincense and/or myrrh treatment reduced CD31 and collagen IV expression,increased the coverage of perivascular cells,tightened the connection between cells,and improved the shape of blood vessels.In addition,ELISA,RT-qPCR and WB analyses showed that frankincense and/or myrrh treatment inhibited the levels of hypoxia-inducible factors,inflammatory factors and angiogenesis-related factors,namely,HIF-1α,TNF-α,VEGF and MMP-9.Furthermore,mechanistic experiments illustrated that the effect of frankincense plus myrrh treatment was similar to that of an EGFR inhibitor with regard to controlling EGFR activation,thereby inhibiting the phosphorylation activity of its downstream targets:the PI3K/Akt and MAPK(ERK,p38 and JNK)pathways.CONCLUSION In summary,frankincense and myrrh treatment targets tumor blood vessels to exert anti-HCC effects via EGFR-activated PI3K/Akt and MAPK signaling pathways,highlighting the potential of this dual TCM compound as an anti-HCC candidate.
基金The project supported by the National Natural Science Foundation of China(10372026)
文摘A coupled intravascular-transvascular-interstitial fluid flow model is developed to study the distributions of blood flow and interstitial fluid pressure in solid tumor microcirculation based on a tumor-induced microvascular network. This is generated from a 2D nine-point discrete mathematical model of tumor angiogenesis and contains two parent vessels. Blood flow through the microvascular network and interstitial fluid flow in tumor tissues are performed by the extended Poiseuille's law and Darcy's law, respectively, transvascular flow is described by Starling's law; effects of the vascular permeability and the interstitial hydraulic conductivity are also considered. The simulation results predict the heterogeneous blood supply, interstitial hypertension and low convection on the inside of the tumor, which are consistent with physiological observed facts. These results may provide beneficial information for anti-angiogenesis treatment of tumor and further clinical research.
文摘<strong>Objective:</strong> To investigate the value of the number of circulating tumor cells (CTC) in peripheral blood in the prognosis and coagulation-related indicators of patients with renal cancer. <strong>Methods:</strong> 65 patients with renal cell carcinoma (RCC) confirmed pathologically were divided into CTC positive group and CTC negative group according to the CTC count (5 pcs/3.5 ml). Compare the age, gender, tumor location, TNM (clinical stage), pathological grade, tissue type, lymph node metastasis, distant metastasis, prognosis and prothrombin time (PT), fibrinogen (FIB), partial coagulation of the two groups of patients The correlation between the results of zymogen time (APTT) and D-dimer (DD) and the number of CTC. <strong>Results:</strong> There were significant differences in TNM, lymph node metastasis, and distant metastasis between the two groups (P < 0.05). The number of CTC in patients was correlated with FIB and D-D levels (P < 0.05). <strong>Conclusion:</strong> The number of CTC in patients with renal cell carcinoma is correlated with some clinical phenotypes (TNM, lymph node metastasis, distant metastasis) and some coagulation indexes (FIB, D-D), and can jointly predict the prognosis of renal cancer.
文摘Effects of angiotensin Ⅱ and other six vasoactive agents on tissue blood flow of Yoahida rat ascites hepatoma AH109A and normal liver were measured by the hydrogen clearance method. The mean blood flow in the tumor peripheral part under normal tension was 11. 9±8. 2ml/ min/100g tissue and was not influenced by tumor size. Tumor blood flow was more significantly increased in infusion angiotensin Ⅱthan 0.5mg/ ml methoxamine, however, normal liver blood flow of tumor-bearing rats was unchanged in contrast to an Increase seen in the tumor. A pronounced reduction of tumor blood flow was found after administration of epinephrine, norepinephrin and ethylphenylephrine. In addition, metaraminol and phenyleprine as well as 1. 0 and 2. 5mg/ ml methoxamine were not found to significantly change blood flow of the tumor.
文摘Female adult BUF rats (6-8 weeks) received Sham operation (Sham); 70% hepatectomy (PH); Sham or PH with blood transfusion (BT or PH+BT). BUF 7316A hepatoma cells were inoculated subcutaneously in the neck of rats on the operation day. Tumor size was measured from day 7 to 20 after inoculation. Sera and splenic adherent cell harvested on day 5 from Sham and PH rat were added into Mixed Lymphocyte Cultures (MLR). The result showed that tumor growth in PH or BT rats was significantly promoted as compared to that in Sham rats (P<0.01,P<0.05). The most marked enhancement of tumor growth was observed in PH+BT rats (P<0.001). Sera and splenic adherent cell from PH rat significantly inhibited MLR (P<0.05). Those results suggest that partial hepatectomy and blood transfusion are responsible for the enhancement of tumor growth. Some immunosuppressive factor might be produced in the process of liver regeneration, and blood transfusion might have an additive immunosuppressive effect.
基金This present study was financially supported by Baoding City Science and Technology Plan project(2041ZF084)Key Laboratory of Molecular Pathology and Early Diagnosis of Tumor in Hebei Province.
文摘Objective:To determine the clinical value of combined detection of circulating tumor cells(CTCs)and cell-free DNA(cfDNA)in peripheral blood of patients with triple-negative breast cancer.Method:41 patients with breast cancer admitted to the First Central Hospital of Baoding from January 2020 to December 2021 were selected and recruited into the experimental group,42 patients with benign breast cancer admitted during the same period were recruited into the conditional control group,and 41 healthy patients admitted during the same period were recruited into the blank control group.The positive rate of peripheral blood CTCs,the level of cfDNA,and the diagnostic efficacy of peripheral blood CTCs,cfDNA alone and the combination thereof for breast cancer were analyzed.Result:The positive rates of peripheral blood CTCs in the experimental group,the conditional control group,and the blank control group were 43.90%,11.90%,and 9.74%,respectively,and there was significant difference among the groups.The levels of cfDNA in peripheral blood of the experimental group,the conditional control group,and the blank control group were 0.26±0.08 bp,0.17±0.03 bp,and 0.15±0.04 bp,respectively,which were statistically significant.The detection levels of 100 bp hTERT/ng mT1 and 241 bp hTERT/ng-mT1 in the experimental group were significantly higher than those in the conditional control group and the blank control group.The accuracy of peripheral blood CTCs detection in the three groups was 66.21%,the accuracy of cfDA241 bp/100 hp hTERT detection was 80.41%,and the accuracy of combined detection of peripheral blood CTCs and cfDNA was 94.03%.Conclusion:The clinical application of peripheral blood CTCs combined with cfDNA level detection can increase detection accuracy,provide data support for clinicians,and improve the clinical diagnostic effect of triple-negative breast cancer.
文摘Objectives: The aim of the investigation was to study the hormonal status (sex hormones: estradiol (E2), progesterone (P), testosterone (T);non-sex gonadotropic hormones-luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) of women with benign and malignant tumors of uterine body in the reproductive, menopause and postmenopause periods. Also the distribution features of the blood ABO system phenotype groups and their link to the development of uterine body tumors have been studied. Methods: The determination of hormones was made by the enzyme analysis method (ELAIZA), provided by the proper ELAIZA kits. For the study of blood ABO system antigens, internationally recognized immunoserology methods were used. Results: Investigations revealed the increased level of E2 and T on the background of the reduced P in the blood of the women with uterine tumors in the reproductive, menopause and post-menopause period. As for gonadotropic hormones, the decreased levels of LH and FSH have also been detected. From the ABO system phenotype groups A(II) group had the highest frequency between the women with malignant uterine tumor in the reproductive age. O (I) phenotype group was the most frequent in case of menopause and post-menopause women with uterine malignant tumors. Conclusions: Hormonal imbalance creates good conditions for the proliferation of uterine tissues and hence causes the development of benign and malignant uterine tumors. The imbalance of the sex steroid and gonadotropic hormones in the blood of post-menopause women indicates on the genotoxic mechanism of cancer development on the background of age-related changes. A(II) group had the highest frequency between the reproductive age women with uterine malignant tumor, while O (I) group was the most frequent in case of menopause and post-menopause patients.
文摘Epithelial glioma is the most common brain cancer,accounting for 35.26%-60.69%of intracranial tumors with an average of 44.69%,and it remains the greatest challenge in the field of neurosurgery.The median survival time of patients with advanced glioma is only 12 to 18 months due to the characteristics of high aggression,and the therapeutic effect was poor though surgery,chemotherapy,and targeted drug therapy being treated.Because of the presence of heterogeneity and the differentiation disorder,only a small number of glioma cells are the source of tumor growth and metastasis,which are highly resistant to traditional treatments.They are deemed as the“seed”tumor cells as they could get rid of the effect of the treatment and reconstruct the organization of tumor.They are also termed as brain tumor stem cell(BTSC)or glioma stem cells(GSCs)since neural stem cells share similar features with them.Recent data reveal that they are directly related with invasion,angiogenesis,tolerance,chemotherapy,recurrence of glioma.Based on the research result by the team,the paper elaborates the characteristics of GSCs and the relationship with the tumor angiogenesis.
基金Project supported by the National Natural Science Foundation of China(Nos.11102113 and81301816)the New Teachers Start Program of Shanghai Jiao Tong University+1 种基金the Chenxing Young Scholars Program B of Shanghai Jiao Tong University(No.13X100010070)the Natural Science Research Foundation of Shanghai Jiao Tong University School of Medicine(No.13XJ10037)
文摘The changes of blood perfusion and oxygen transport in tumors during tumor vascular normalization are studied with 3-dimensional mathematical modeling and numerical simulation. The models of tumor angiogenesis and vascular-disrupting are used to simulate "un-normalized" and "normalized" vasculatures. A new model combining tumor hemodynamics and oxygen transport is developed. In this model, the intravasculartransvascular-interstitial flow with red blood cell(RBC) delivery is tightly coupled, and the oxygen resource is produced by heterogeneous distribution of hematocrit from the flow simulation. The results show that both tumor blood perfusion and hematocrit in the vessels increase, and the hypoxia microenvironment in the tumor center is greatly improved during vascular normalization. The total oxygen content inside the tumor tissue increases by about 67%, 51%, and 95% for the three approaches of vascular normalization,respectively. The elevation of oxygen concentration in tumors can improve its metabolic environment, and consequently reduce malignancy of tumor cells. It can also enhance radiation and chemotherapeutics to tumors.
文摘BACKGROUND Hematological tumors are common malignant tumors,with high morbidity and mortality rates.Most patients with hematological malignancies develop sleep disorders that seriously affect their life and health because of acute onset of disease,rapid progression,high recurrence rates,complex treatment methods,and treatment costs.AIM To explore the mediating effect of resilience on fear of disease progression and sleep quality in patients with hematological malignancies.METHODS A cross-sectional analysis of 100 patients with hematological malignancies,treated in the First Affiliated Hospital of Jinzhou Medical University between August 2022 and August 2023,was conducted.Patients were assessed using a general data survey,a simplified scale for the fear of progression(FoP)of disease,a resilience scale,and the Pittsburgh Sleep Quality Index.Statistical analysis was conducted to determine the relationship between various patient characteristics and FoP,resilience,and sleep quality.Spearman’s correlation analysis was used to examine the correlations between mental resilience,FoP,and sleep quality.RESULTS The total FoP score mean value in patients with hematological malignancies was 38.09±5.16;the total resilience score mean value was 40.73±7.04;and the Pittsburgh Sleep Quality Index score mean value was 10.72±1.90.FoP,resilience,and sleep quality of the patients were associated with family per capita monthly income and patient education level(P<0.05).Spearman correlation analysis revealed that FoP was negatively correlated with resilience and sleep quality scores(r=-0.560,-0.537,P<0.01),respectively,and resilience was significantly associated with sleep quality scores(r=0.688,P<0.01).Mediation analysis showed that the mediating effect of resilience between FoP and sleep quality in patients with hematological malignancies was-0.100 and accounted for 50.51%of the total effect.This indicated that FoP directly and indirectly affected sleep quality through the mesomeric effect of resilience.CONCLUSION Resilience is an intermediary variable between FoP and sleep quality in patients with hematological malignancies.Medical staff should evaluate and follow-up FoP and resilience to implement measures to improve sleep quality.