Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This stud...Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This study investigates whether the limited e±cacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the e±cacy.A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives(HpD-PDT).The anti-tumor effect of HpD-PDT was observed,as well as CD4þT,CD8þT and calreticulin(CRT)by immunohistochemistry and immunofluorescence.Immune checkpoints on T cells were analyzed byflow cytometry after HpD-PDT.When combining PDT with immune checkpoint inhibitors,the antitumor effect and immune effect were assessed.For HpD-PDT at 100 mW/cm2 and 40,60 and 80 J/cm2,primary tumors were suppressed and CD4þT,CD8þT and CRT were elevated;however,distant tumors couldn't be inhibited and survival could not be prolonged.Immune checkpoints on T cells,especially PD1 and LAG-3 after HpD-PDT,were upregulated,which may explain the reason for the limited HpD-PDT effect.After PDT combined with anti-PD1 antibody,but not with anti-LAG-3 antibody,both the primary and distant tumors were signi-cantly inhibited and the survival time was prolonged,additionally,CD4þT,CD8þT,IFN-þCD4þT and TNF-þCD4þT cells were signi-cantly increased compared with HpD-PDT.HpD-PDT could not combat metastatic breast cancer.PD1 and LAG-3 were upregulated after HpD-PDT.Anti-PD1 antibody,but not anti-LAG-3 antibody,could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.展开更多
Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart fa...Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart failure,but exercise has been well-established as one of the few safe and effective interventions,leading to improved outcomes in patients.However,a lack of patient adherence remains a significant barrier in the implementation of exercise-based therapy for the treatment of heart failure.The insulin-like growth factor 1(IGF1)phosphoinositide 3-kinase(PI3K)pathway has been recognized as perhaps the most critical pathway for mediating exercisedinduced heart growth and protection.Here,we discuss how modulating activity of the IGF1PI3K pathway may be a valuable approach for the development of therapies that mimic the protective effects of exercise on the heart.We outline some of the promising approaches being investigated that utilize PI3K-based therapy for the treatment of heart failure.We discuss the implications for cardiac pathology and cardiotoxicity that arise in a setting of reduced PI3K activity.Finally,we discuss the use of animal models of cardiac health and disease,and genetic mice with increased or decreased cardiac PI3K activity for the discovery of novel drug targets and biomarkers of cardiovascular disease.展开更多
Hepatocellular carcinoma is one of the most common cancers worldwide,and a leading cause of cancer-related death.Owing to unsatisfactory clinical outcomes under the current standard of care,there is a need to search f...Hepatocellular carcinoma is one of the most common cancers worldwide,and a leading cause of cancer-related death.Owing to unsatisfactory clinical outcomes under the current standard of care,there is a need to search for and identify novel and potent therapeutic targets to improve patient outcomes.Sorafenib is the first and only approved targeted therapy for the treatment of hepatocellular carcinoma.Besides functioning as a multiple tyrosine kinase,sorafenib also acts via a kinase-independent mechanism to target signal transducer and activator of transcription 3(STAT3) signaling in hepatocellular carcinoma cells.STAT3 is a key regulator of inflammation,cell survival,and tumorigenesis of liver cells,and the high percentage of hepatocellular carcinoma cells with constitutively active STAT3 justifies targeting it for the development of novel therapeutics.Sorafenib inactivates STAT3 and STAT3-related signaling by inducing a conformational change in and releasing the autoinhibition of Src homology region 2 domaincontaining phosphatase-1.This phosphatase negatively regulates STAT3 activity,which leads to the subsequent apoptosis of cancer cells.The novel anti-cancer property of sorafenib will be discussed in this review,not only adding information regarding its mechanism of action but also providing an innovative approach for the development of cancer therapeutics in the future.展开更多
Objective To evaluate the outcomes of T3 a prostate cancer with unfavorable prognostic factors treated with permanent interstitial brachytherapy combined with external radiotherapy and hormone therapy.Methods From Jan...Objective To evaluate the outcomes of T3 a prostate cancer with unfavorable prognostic factors treated with permanent interstitial brachytherapy combined with external radiotherapy and hormone therapy.Methods From January 2003 to December 2008,38 patients classified as T3 a prostate cancer with unfavorable prognostic factors were treated with trimodality therapy(brachytherapy + external radiotherapy + hormone therapy).The prescription dose of brachytherapy and external radiotherapy were 110 Gy and 45 Gy,respectively.The duration of hormone therapy was 2-3 years.The endpoints of this study included biochemical failure-free survival(BFFS),distant metastasis-free survival(DMFS),cancer-specific survival(CSS),and overall survival(OS).Survival curves were calculated using the Kaplan-Meier method.The Log-rank test was used to identify the prognostic predictors for univariate analysis.Results The median follow-up was 71 months.The serum pre-treatment prostate-specific antigen(PSA) level ranged from 10.0 to 99.8 ng/ml(mean 56.3 ng/ml),the Gleason score ranged from 5 to 9(median 8),and the percentage of positive biopsy cores ranged from 10% to 100%(mean 65%).The 5-year BFFS,DMFS,CSS,and OS rates were 44%,69%,82%,and 76%,respectively.All biochemical failures occurred within 40 months.The percentage of positive biopsy cores was significantly correlated with BFFS,DMFS,and OS(all P=0.000),and the Gleason score with DMFS(P=0.000) and OS(P=0.001).Conclusions T3 a prostate cancer with unfavorable prognostic factors presents not so optimistic outcome.Hormone therapy should be applied to prolong the biochemical progression-free or metastasis-free survival.The percentage of positive biopsy cores and the Gleason score are significant prognostic factors.展开更多
Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral g...Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral gene therapy to block caspase-3 gene expression using small interfering RNA(siRNA)delivered by polybutylcyanoacrylate nanoparticles(CaspNPs).In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells,and when injected intraocularly in vivo,CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9%in rats with optic nerve crush.Longitudinal,repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1%versus 63.4%in lesioned controls.Because non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons,siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological disorders.The animal study procedures were approved by the German National Act on the use of experimental animals(Ethic Committee Referat Verbraucherschutz,Veterinärangelegenheiten;Landesverwaltungsamt Sachsen-Anhalt,Halle,Germany,#IMP/G/01-1150/12 and#IMP/G/01-1469/17).展开更多
More than 10 million people are suffering from hepatitis C virus(HCV) in Pakistan,The available treatment option is a combination of interferon and ribavirin.Treatment response is linked with several factors and also ...More than 10 million people are suffering from hepatitis C virus(HCV) in Pakistan,The available treatment option is a combination of interferon and ribavirin.Treatment response is linked with several factors and also induces a number of side effects.We searched in Pubmed.Pak Medi Net and Coogle Scholar for the articles presenting the effect of interferon plus ribavirin therapy on HCV patients from Pakistan,their side effects and future prospects.The major prevalent HCV genotype in Pakistan is 3.Conventional interferon alpha plus ribavirin showed sustained virological response of 54%-64%while pegylaled interferon alpha plus ribavirin showed sustained virological response of 58%-75%.IL-28 B CC genotype is linked with better sustained virological response.Studies on patients with HCV genotype 3 infections showed no correlation between treatment response and interferon sensitivity determining region mutations.Interferon therapy is linked with a number of side effects like thyroid dysfuncton.hactnatological disorders,weight loss,gastrointestinal tract side effects and neuropsychiatric side effects.Unusual side effects of clubbing of fingers and seizures were also observed in a couple of patients.Interferon alpha plus ribavirin therapy showed better response rate in HCV genotype 3 patients from Pakistan with number of side effects.A couple of interferon free therapies are light of hope for the patients living with HCV.展开更多
Recombinant adenoviruses encoding murine IL 2 gene or IL 3 gene were directly injected into established subcutaneous tumor model of G422 glioblastoma cells. After treatment, the tumor size and survival of the gliobl...Recombinant adenoviruses encoding murine IL 2 gene or IL 3 gene were directly injected into established subcutaneous tumor model of G422 glioblastoma cells. After treatment, the tumor size and survival of the glioblastoma bearing mice were observed. The splenic NK and CTL cytotoxicities were detected by standard 4 hour 51 Cr release assay. We also examined the histopathological changes of tumor by hematoxylin and eosin staining. The results showed that intratumoral injection of adenoviruses encoding murine IL 2 gene or IL 3 gene significantly inhibited the growth of G422 glioblastoma and prolonged the survival period of glioblastoma bearing mice. The CTL cytotoxicity of the gene therapy groups was significantly higher than that of the control groups, but NK activity remained unchanged, indicating that specific immunity contributes to the in vivo antitumor effect of the direct gene therapy. There were much more tumor necrosis and inflammatory cell infiltration in the tumor of the gene therapy groups. Combined IL 2/IL 3 gene therapy could induce higher level of CTL and enhance the therapeutic potential further. The results suggest that intratumoral injection of recombinant adenoviruses encoding certain kind of cytokines may be a useful approach in the treatment of a malignancy of the central nervous system.展开更多
AIM:To establish whether activation of adenosine type-3 receptors(A3Rs)and inhibition of interleukin- 1β-induced inflammation is beneficial in combination with antibiotic therapy to increase survival of mice challeng...AIM:To establish whether activation of adenosine type-3 receptors(A3Rs)and inhibition of interleukin- 1β-induced inflammation is beneficial in combination with antibiotic therapy to increase survival of mice challenged with anthrax spores. METHODS:DBA/2 mice were challenged with Bacillus anthracis spores of the toxigenic Sterne strain 43F2. Survival of animals was monitored for 15 d.Ciprofloxacin treatment(50 mg/kg,once daily,intraperitoneally) was initiated at day+1 simultaneously with the ad- ministration of inhibitors,and continued for 10 d.Two doses(2.5 mg/kg and 12.5 mg/kg)of acetyl-tyrosylvalyl-alanyl-aspartyl-chloromethylketone(YVAD)and three doses(0.05,0.15 and 0.3 mg/kg)of 1-[2-Chloro- 6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1- deoxy-N-methyl-β-D-ribofuranuronamide(Cl-IB-MECA) were tested.Animals received YVAD on days 1-4,and Cl-IB-MECA on days 1-10 once daily,subcutaneously. Human lung epithelial cells in culture were challenged with spores or edema toxin and the effects of IB-MECAon phosphorylation of AKT and generation of cAMP were tested. RESULTS:We showed that the outcome of antibiotic treatment in a murine anthrax model could be substantially improved by co-administration of the caspase-1/4 inhibitor YVAD and the A3R agonist Cl-IB-MECA.Combination treatment with these substances and ciprofloxacin resulted in up to 90%synergistic protection.All untreated mice died,and antibiotic alone protected only 30% of animals.We conclude that both substances target the aberrant host signaling that underpins anthrax mortality. CONCLUSION:Our findings suggest new possibilities for combination therapy of anthrax with antibiotics,A3R agonists and caspase-1 inhibitors.展开更多
A comprehensive study of yarn architecture of two-step rectangle 3D braided composites is presented. Firstly, the braided surface, the shapes of yarns and the intertwining between braider yams and axial yams are analy...A comprehensive study of yarn architecture of two-step rectangle 3D braided composites is presented. Firstly, the braided surface, the shapes of yarns and the intertwining between braider yams and axial yams are analyzed from experimentation. With the microstructure being defined, three levels of unit cell structure are identified, i.e. large unit cell, second unit cell and minimal unit cell. Secondly, based on the minimal unit cell in the interior and on the boundary of the entire cross-section, the deformations of axial yams squashed by braider yams contribute to the increase of the fiber packing factors of axial yams. Finally, the predicted fiber volume fraction of the composites decreases with the increase of linear density of the braider yam and the pitch length. Favorable correlations between the predicted and the experimental results arc found for six groups of the composites.展开更多
Modern therapy of acute myeloid leukemia(AML)began in 1973 with the first report of the successful combination of daunorubicin and cytarabine,which led to complete remission in approximately 45%of patients.Accurate AM...Modern therapy of acute myeloid leukemia(AML)began in 1973 with the first report of the successful combination of daunorubicin and cytarabine,which led to complete remission in approximately 45%of patients.Accurate AML diagnosis was dependent on morphology,aided initially only by cytochemistry.Unlike acute lymphoblastic leukemia(ALL),immunophenotyping offered little in the diagnosis of AML,at least during the 1970s and 1980s.The advent of reliable cytogenetics changed the entire prognostic outlook of AML.With karyotypic analysis,different groups of AML could be classified and stratified for various therapies.Unique mutational profiling was a major advance in further categorizing AML patients,aided by the immunophenotypic identification of antigenic markers on the cells.All these advances were occurring as the understanding of the importance of the tumor burden—known as minimal residual disease(MRD)—became crucial for the management of AML patients.The efficacy of MRD has rapidly progressed in the past decade,from a specificity of 103 with immunophenotyping to 104 with polymerase chain reaction(PCR),which is only appropriate for some patients with AML,and finally to 105 or even 106 cells with the extraordinary sensitivity of next-generation sequencing(NGS).All of these advances have promoted the concept of personalized medicine,which has led to the advent of targeted agents that can accurately be used for specific diagnostic subtypes.Responses can be predicted and measured accurately.Such targeted agents have now become a cornerstone in the management of AML,increasing effi-cacy and dramatically reducing toxicity.The focus of this review is on one of the most well-studied targeted agents in AML:the FMS-like tyrosine kinase 3(FLT3)inhibitors,which have impacted the prognostication and therapeutics of AML.This review selectively discusses the FLT3 inhibitors in detail,as a model for the other burgeoning targeted agents that have already been approved,as well as those that are currently in development.展开更多
Advances in biomimetic three-dimensional(3D) melanoma models have brought new prospects of drug screening and disease modeling, since their physiological relevancy for recapitulating in vivo tumor architectures is mor...Advances in biomimetic three-dimensional(3D) melanoma models have brought new prospects of drug screening and disease modeling, since their physiological relevancy for recapitulating in vivo tumor architectures is more accurate than traditional two-dimensional(2D) cell culture. Gelatin methacryloyl(GelMA) is widely used as a tissue-engineered scaffold hydrogel for 3D cell culture. In the present study, an in vitro 3D malignant melanoma model based on Gel MA was fabricated to evaluate the efficiency of hypericin(Hy)-loaded microemulsion(ME) in photodynamic therapy against melanoma. The ME was produced by the spontaneous emulsification method to enhance the bioavailability of Hy at tumor sites. Hy-loaded MEs were applied to a 3D malignant melanoma model made using 6% Gel MA and the co-culture of B16F10 and Balb/c 3T3 cells,followed by crosslinking using violet light(403 nm). The observation revealed excellent cell viability and the presence of F-actin cytoskeleton network. Hy-loaded MEs exhibited higher phototoxicity and cell accumulation(about threefold) than free Hy, and the cells cultured in the 3D system displayed lower susceptibility(about 2.5-fold) than those in 2D culture.These findings indicate that the developed MEs are potential delivery carriers for Hy;furthermore, Gel MA hydrogel-based modeling in polydimethylsiloxane(PDMS) molds is a user-friendly and cost-effective in vitro platform to investigate drug penetration and provide a basis for evaluating nanocarrier efficiency for skin cancer and other skin-related diseases.展开更多
Tin(IV)oxide(Sn_(3)O_(4))is layered tin and exhibits mixed valence states.It has emerged as a highly promising visible-light pho-tocatalyst,attracting considerable attention.This comprehensive review is aimed at provi...Tin(IV)oxide(Sn_(3)O_(4))is layered tin and exhibits mixed valence states.It has emerged as a highly promising visible-light pho-tocatalyst,attracting considerable attention.This comprehensive review is aimed at providing a detailed overview of the latest advance-ments in research,applications,advantages,and challenges associated with Sn_(3)O_(4)photocatalytic nanomaterials.The fundamental con-cepts and principles of Sn_(3)O_(4)are introduced.Sn_(3)O_(4)possesses a unique crystal structure and optoelectronic properties that allow it to ab-sorb visible light efficiently and generate photoexcited charge carriers that drive photocatalytic reactions.Subsequently,strategies for the control and improved performance of Sn_(3)O_(4)photocatalytic nanomaterials are discussed.Morphology control,ion doping,and hetero-structure construction are widely employed in the optimization of the photocatalytic performance of Sn_(3)O_(4)materials.The effective imple-mentation of these strategies improves the photocatalytic activity and stability of Sn_(3)O_(4)nanomaterials.Furthermore,the review explores the diverse applications of Sn_(3)O_(4)photocatalytic nanomaterials in various fields,such as photocatalytic degradation,photocatalytic hydro-gen production,photocatalytic reduction of carbon dioxide,solar cells,photocatalytic sterilization,and optoelectronic sensors.The discus-sion focuses on the potential of Sn_(3)O_(4)-based nanomaterials in these applications,highlighting their unique attributes and functionalities.Finally,the review provides an outlook on the future development directions in the field and offers guidance for the exploration and de-velopment of novel and efficient Sn_(3)O_(4)-based nanomaterials.Through the identification of emerging research areas and potential avenues for improvement,this review aims to stimulate further advancements in Sn_(3)O_(4)-based photocatalysis and facilitate the translation of this promising technology into practical applications.展开更多
Objective: The aim of the study was to explore the efficacy of three-dimensional conformal radiotherapy (3D- CRT) combined with TP concurrent chemotherapy in treatment of recurrent cervical cancers. Methods: From ...Objective: The aim of the study was to explore the efficacy of three-dimensional conformal radiotherapy (3D- CRT) combined with TP concurrent chemotherapy in treatment of recurrent cervical cancers. Methods: From May 2005 to May 2009, 36 patients with recurrent cervical cancer were treated by 3D-CRT of 60-66 Gy and TP (docetaxel 70 mg/m^2, d1; cisplatin 20 mg/m^2, dl-d3; 21 days per cycle, totally 2 cycles) concurrent chemotherapy. Results: All of the patients had finished the 3D-CRT, the total response rate, complete response rate and partial response rate were 80.0% (28/35), 45.7% (16/35), and 34.3% (12/35), respectively. The pain-alleviation rate was 91.4% (32/35). The hemorrhage control rate was 94.3% (33/35). The median overall survival was 21.2 months. The 1-, 2- and 3-year survival rates were 54.3%, 37.1% and 22.8%, respectively. The life qualities of the patients were improved, without any treatment related death. Conclusion: Radiotherapy is effective and well-tolerated for recurrent cervical cancers, and it can promote regional control of the disease and prolong survival time.展开更多
STAT3 plays a particularly important role in several cancer-related signal transduction pathways.Silencing STAT3 via RNA interference or small molecule inhibitors induces the apoptosis of tumor cells,thereby inhibitin...STAT3 plays a particularly important role in several cancer-related signal transduction pathways.Silencing STAT3 via RNA interference or small molecule inhibitors induces the apoptosis of tumor cells,thereby inhibiting the growth of the tumors.In this study,short-hairpin RNA sequences targeting the STAT3 genes were designed,synthesized,and then connected to pGPU6/GFP/Neo plasmids as the shRNA-expression vectors.The expression of STAT3-shRNA was analyzed by real-time PCR,western blotting,and cell apoptosis assay to study the growth and apoptosis of the cells.Then,the effect of STAT3 knockdown on the NCI-H1650 cells was studied in a tumor mouse model.The results revealed that,after an in vitro transfection,the proliferation of NCI-H1650 cells was inhibited,and the cells were induced to apoptosis.The mRNA and protein expression levels of STAT3 were downregulated in the STAT3-shRNA group.In vivo,the tumor mass and volume in the STAT3-shRNA group were significantly lower than in the other two groups.Both the in vivo and in vitro results demonstrated a long-period inhibiting effect on NSCLC,especially in vivo,when the tumor inhibition rate could reach 50%in the STAT3-shRNA group,which is an exciting outcome.Moreover,the study of the conjugation of STAT3-shRNA and chitosan-based vectors revealed that they could be combined steadily with good cytocompati-bility and transfection efficiency.These results together provide convincing evidence for the application of STAT3-shRNA used in the treatment of non-small lung cancer,which could be a promoting prospect for the development of gene therapy.展开更多
Objective:In our investigation,we studied the patients with medulloblastoma who received 3-dimensional conformal radiation therapy(3DCRT) and recorded their effects,side effects and failure reasons.Methods:From August...Objective:In our investigation,we studied the patients with medulloblastoma who received 3-dimensional conformal radiation therapy(3DCRT) and recorded their effects,side effects and failure reasons.Methods:From August 2001 to August 2007,34 children with medulloblastoma were treated in our hospital.The age at diagnosis was 3-16 years old,and the mean age at diagnosis was 9.5 years old.Among all the patients,16 cases were included in the high risk group and 18 cases were included in the low risk group.All the patients were performed total resection or subtotal resection and no patients received radiotherapy or chemotherapy before operation.All patients received 3DCRT within 3 weeks after resection.The dose of 30 Gy were given to the whole brain and whole spine,followed by 20-25 Gy boosted to the posterior brain fossa.The median fraction dose was 180 cGy.Every patient received the chemotherapy scheme of the Lomustine,Cisplatinum and Vincristine.Nobody received intrathecal chemotherapy.The tests of the complete blood count,blood biochemistry,hepatic and renal functions were required before every cycle of chemotherapy.Results:5-year overall survival(OS) and 5-year disease free survival(DFS) were 71% and 62% respectively.The median follow-up time was 36.5 months.The 5-year OS of the high risk group was 71% compared to 62% of the low risk group.There were significant difference between the two groups(P = 0.01).There were 13 failure cases in all the patients.Of these 13 patients,10 were dead and the other 3 were alive with tumor.The complete remission(CR) rate was 70.5% and the partial remission(PR) rate was 14%.Among the failure patients,there were 3 patients(8.8%) with the recurrences located in the brain of cribriform region.The 5-year OS of the patients with preoperative metastases was 12.5%(1/8),and which of the patients with residual tumor volume > 1.5 cm3 was 0%(0/5).Through the statistic analysis,it was found that both whether or not the metastases were found before surgery and residual tumor volume have the significant impacts on the prognosis of the children with medulloblastoma(P < 0.05).The major adverse reactions were hematological toxicity(7/34,20.6%) and gastrointestinal reaction(4/34,11.8%).Conclusion:Through the using of 3DCRT for the children with medulloblastoma,the severe side effects rate was not high.The prognosis of the patients in low risk group was satisfied which was opposite to that of the patients in high risk group.And the patients with residual tumor volume > 1.5 cm3 and preoperative metastases also had poor prognosis.It is needed to pay attention to the possible low dose of the brain of cribriform region.展开更多
Purpose: To study the safety and efficacy of 1/3-dose verteporfin photodynamic therapy (PDT) for subacute central serous chorioretinopathy (CSC). Methods: In this case series, 59 eyes (59 patients) diagnosed with suba...Purpose: To study the safety and efficacy of 1/3-dose verteporfin photodynamic therapy (PDT) for subacute central serous chorioretinopathy (CSC). Methods: In this case series, 59 eyes (59 patients) diagnosed with subacute CSC in Shenyang the 4th hospital from January 2014 to December 2015 were treated with 1/3-dose verteporfin PDT and followed up for at least 1 year. The symptoms and the diagnosed history were more than 3 months but shorter than 6 months. The central foveal thickness (CFT), neuroretinal thickness (NRT), height of subfoveal retinal fluid (SRF), and subfoveal choroidal thickness (SCT) were observed at baseline and after treated at 1, 2, 3, 6 and 12 months with EDI-OCT, Best-corrected visual acuity ( BCVA) was also studied at the same time. Results: After 1, 2, 3 and 6 months of 1/3-dose verteporfin PDT treatment, the BCVA improved significantly (P 0.05). The height of SRF changed significantly. There was no retinal pigment epithelium atrophy and choroidal neovascularization (CNV) in all cases after more than 12 months follow-up. Conclusion: Treatment of 1/3 dose verteporfin PDT could safely and effectively reduce expansion of choroidal vessel and choroidal choriocapillary, promoting absorbance of subretinal fluid for subacute CSC. 1/3-dose verteporfin PDT may be an alternative method to treat the subacute CSC.展开更多
BACKGROUND Renal cell carcinoma(RCC)with Xp11.2 translocation/TFE3 gene fusion is a rare and distinct subtype of RCC that is classified under tumors with translocation of the microphthalmia-associated transcriptional ...BACKGROUND Renal cell carcinoma(RCC)with Xp11.2 translocation/TFE3 gene fusion is a rare and distinct subtype of RCC that is classified under tumors with translocation of the microphthalmia-associated transcriptional factor.CASE SUMMARY We report an adult case of Xp11.2 translocation advanced RCC with metastasis(T3a N1M1),after targeted treatment,alcohol ablation,and transarterial chemoembolization,who eventually underwent successful surgical excision.No recurrence or transfer was seen within one year,and the survival period was more than 3 years.A review of the relevant literature was conducted to improve our understanding of the pathogenesis,epidemiology,clinical manifestations,diagnosis,differential diagnosis,treatment,and other aspects of the disease.CONCLUSION Transarterial chemoembolization and ablation did not achieve the desired tumor reduction in this patient,but had a significant effect on reducing intraoperative bleeding and inhibiting tumor activity.展开更多
Introduction: Radiation therapy after breast surgery is an integral part of the treatment of early breast cancer. The goal of radiation therapy is to achieve the best possible coverage of the planning target volume (P...Introduction: Radiation therapy after breast surgery is an integral part of the treatment of early breast cancer. The goal of radiation therapy is to achieve the best possible coverage of the planning target volume (PTV), while reducing the dose to organs at risk (OARs) which are normal tissues whose sensitivity to irradiation could cause damage that can lead to modification of the treatment plan. In the last decade, radiation oncologist started to use the Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) for irradiating the breast, in order to achieve better dose distribution and target dose to the PTV and OAR. The aim of this study is to compare 2 external radiotherapy techniques (VMAT vs 3D) for patients with node-positive left breast cancer. Patients and Methods: We randomly selected 10 cases of postoperative radiotherapy for breast cancer in our hospital. The patients are all female, the average age was 45.4 years old, and the primary lesions are left breast. The ANOVA test was used to compare the mean difference between subgroups, and the p value Results: Dose volume histogram (DVH) was used to analyze each evaluation dose of clinical target volume (CTV) and organs at risk (OARs). Compared to 3DCRT plans, VMAT provided more uniform coverage to the breast and regional lymph nodes. The max point dose for tVMAT was lower on average (106.4% for VMAT versus 109% for 3DCRT). OAR sparing was improved with tVMAT, with a lower average V17Gy for the left lung (27.91% for VMAT versus 30.04% for 3DCRT, p and lower for V28Gy (13.75% for VMAT versus 22.34% for 3DCRT, p = 0.01). We also found a lower V35Gy for the heart on VMAT plan (p = 0.02). On the contrary, dose of contralateral breast was lower in 3DCRT than VMAT (0.59 Gy vs 3.65 Gy, p = 0.00). Conclusion: The both types of plans can meet the clinical dosimetry demands of postoperative radiotherapy for left breast cancer. The VMAT plan has a better conformity, but 3CDRT can provide a lower dose to the contralateral organs (breast and lung) to avoid the risk of secondary cancers.展开更多
基金supported by the National Key Research and Development Program of China[2018YFB0407200]National Natural Science Foundation of China[61975239]Medical and Health Technology Innovation Project of the Chinese Academy of Medical Sciences[2019-I2M-5061].
文摘Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This study investigates whether the limited e±cacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the e±cacy.A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives(HpD-PDT).The anti-tumor effect of HpD-PDT was observed,as well as CD4þT,CD8þT and calreticulin(CRT)by immunohistochemistry and immunofluorescence.Immune checkpoints on T cells were analyzed byflow cytometry after HpD-PDT.When combining PDT with immune checkpoint inhibitors,the antitumor effect and immune effect were assessed.For HpD-PDT at 100 mW/cm2 and 40,60 and 80 J/cm2,primary tumors were suppressed and CD4þT,CD8þT and CRT were elevated;however,distant tumors couldn't be inhibited and survival could not be prolonged.Immune checkpoints on T cells,especially PD1 and LAG-3 after HpD-PDT,were upregulated,which may explain the reason for the limited HpD-PDT effect.After PDT combined with anti-PD1 antibody,but not with anti-LAG-3 antibody,both the primary and distant tumors were signi-cantly inhibited and the survival time was prolonged,additionally,CD4þT,CD8þT,IFN-þCD4þT and TNF-þCD4þT cells were signi-cantly increased compared with HpD-PDT.HpD-PDT could not combat metastatic breast cancer.PD1 and LAG-3 were upregulated after HpD-PDT.Anti-PD1 antibody,but not anti-LAG-3 antibody,could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.
基金All authors are supported by the Victorian Government’s Operational Infrastructure Support ProgramSBS is supported by a joint Baker Heart and Diabetes Institute-La Trobe University doctoral scholarshipRM is supported by a National Health and Medical Research Council Senior Research Fellowship(Grant No.1078985).
文摘Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart failure,but exercise has been well-established as one of the few safe and effective interventions,leading to improved outcomes in patients.However,a lack of patient adherence remains a significant barrier in the implementation of exercise-based therapy for the treatment of heart failure.The insulin-like growth factor 1(IGF1)phosphoinositide 3-kinase(PI3K)pathway has been recognized as perhaps the most critical pathway for mediating exercisedinduced heart growth and protection.Here,we discuss how modulating activity of the IGF1PI3K pathway may be a valuable approach for the development of therapies that mimic the protective effects of exercise on the heart.We outline some of the promising approaches being investigated that utilize PI3K-based therapy for the treatment of heart failure.We discuss the implications for cardiac pathology and cardiotoxicity that arise in a setting of reduced PI3K activity.Finally,we discuss the use of animal models of cardiac health and disease,and genetic mice with increased or decreased cardiac PI3K activity for the discovery of novel drug targets and biomarkers of cardiovascular disease.
文摘Hepatocellular carcinoma is one of the most common cancers worldwide,and a leading cause of cancer-related death.Owing to unsatisfactory clinical outcomes under the current standard of care,there is a need to search for and identify novel and potent therapeutic targets to improve patient outcomes.Sorafenib is the first and only approved targeted therapy for the treatment of hepatocellular carcinoma.Besides functioning as a multiple tyrosine kinase,sorafenib also acts via a kinase-independent mechanism to target signal transducer and activator of transcription 3(STAT3) signaling in hepatocellular carcinoma cells.STAT3 is a key regulator of inflammation,cell survival,and tumorigenesis of liver cells,and the high percentage of hepatocellular carcinoma cells with constitutively active STAT3 justifies targeting it for the development of novel therapeutics.Sorafenib inactivates STAT3 and STAT3-related signaling by inducing a conformational change in and releasing the autoinhibition of Src homology region 2 domaincontaining phosphatase-1.This phosphatase negatively regulates STAT3 activity,which leads to the subsequent apoptosis of cancer cells.The novel anti-cancer property of sorafenib will be discussed in this review,not only adding information regarding its mechanism of action but also providing an innovative approach for the development of cancer therapeutics in the future.
文摘Objective To evaluate the outcomes of T3 a prostate cancer with unfavorable prognostic factors treated with permanent interstitial brachytherapy combined with external radiotherapy and hormone therapy.Methods From January 2003 to December 2008,38 patients classified as T3 a prostate cancer with unfavorable prognostic factors were treated with trimodality therapy(brachytherapy + external radiotherapy + hormone therapy).The prescription dose of brachytherapy and external radiotherapy were 110 Gy and 45 Gy,respectively.The duration of hormone therapy was 2-3 years.The endpoints of this study included biochemical failure-free survival(BFFS),distant metastasis-free survival(DMFS),cancer-specific survival(CSS),and overall survival(OS).Survival curves were calculated using the Kaplan-Meier method.The Log-rank test was used to identify the prognostic predictors for univariate analysis.Results The median follow-up was 71 months.The serum pre-treatment prostate-specific antigen(PSA) level ranged from 10.0 to 99.8 ng/ml(mean 56.3 ng/ml),the Gleason score ranged from 5 to 9(median 8),and the percentage of positive biopsy cores ranged from 10% to 100%(mean 65%).The 5-year BFFS,DMFS,CSS,and OS rates were 44%,69%,82%,and 76%,respectively.All biochemical failures occurred within 40 months.The percentage of positive biopsy cores was significantly correlated with BFFS,DMFS,and OS(all P=0.000),and the Gleason score with DMFS(P=0.000) and OS(P=0.001).Conclusions T3 a prostate cancer with unfavorable prognostic factors presents not so optimistic outcome.Hormone therapy should be applied to prolong the biochemical progression-free or metastasis-free survival.The percentage of positive biopsy cores and the Gleason score are significant prognostic factors.
基金MT was funded by the Leistungsorientierte Mittelvergabe(LOM)scholarship offered by the medical faculty of Magdeburg and the Deutscher Akademischer Austauschdienst(DAAD).
文摘Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral gene therapy to block caspase-3 gene expression using small interfering RNA(siRNA)delivered by polybutylcyanoacrylate nanoparticles(CaspNPs).In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells,and when injected intraocularly in vivo,CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9%in rats with optic nerve crush.Longitudinal,repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1%versus 63.4%in lesioned controls.Because non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons,siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological disorders.The animal study procedures were approved by the German National Act on the use of experimental animals(Ethic Committee Referat Verbraucherschutz,Veterinärangelegenheiten;Landesverwaltungsamt Sachsen-Anhalt,Halle,Germany,#IMP/G/01-1150/12 and#IMP/G/01-1469/17).
文摘More than 10 million people are suffering from hepatitis C virus(HCV) in Pakistan,The available treatment option is a combination of interferon and ribavirin.Treatment response is linked with several factors and also induces a number of side effects.We searched in Pubmed.Pak Medi Net and Coogle Scholar for the articles presenting the effect of interferon plus ribavirin therapy on HCV patients from Pakistan,their side effects and future prospects.The major prevalent HCV genotype in Pakistan is 3.Conventional interferon alpha plus ribavirin showed sustained virological response of 54%-64%while pegylaled interferon alpha plus ribavirin showed sustained virological response of 58%-75%.IL-28 B CC genotype is linked with better sustained virological response.Studies on patients with HCV genotype 3 infections showed no correlation between treatment response and interferon sensitivity determining region mutations.Interferon therapy is linked with a number of side effects like thyroid dysfuncton.hactnatological disorders,weight loss,gastrointestinal tract side effects and neuropsychiatric side effects.Unusual side effects of clubbing of fingers and seizures were also observed in a couple of patients.Interferon alpha plus ribavirin therapy showed better response rate in HCV genotype 3 patients from Pakistan with number of side effects.A couple of interferon free therapies are light of hope for the patients living with HCV.
文摘Recombinant adenoviruses encoding murine IL 2 gene or IL 3 gene were directly injected into established subcutaneous tumor model of G422 glioblastoma cells. After treatment, the tumor size and survival of the glioblastoma bearing mice were observed. The splenic NK and CTL cytotoxicities were detected by standard 4 hour 51 Cr release assay. We also examined the histopathological changes of tumor by hematoxylin and eosin staining. The results showed that intratumoral injection of adenoviruses encoding murine IL 2 gene or IL 3 gene significantly inhibited the growth of G422 glioblastoma and prolonged the survival period of glioblastoma bearing mice. The CTL cytotoxicity of the gene therapy groups was significantly higher than that of the control groups, but NK activity remained unchanged, indicating that specific immunity contributes to the in vivo antitumor effect of the direct gene therapy. There were much more tumor necrosis and inflammatory cell infiltration in the tumor of the gene therapy groups. Combined IL 2/IL 3 gene therapy could induce higher level of CTL and enhance the therapeutic potential further. The results suggest that intratumoral injection of recombinant adenoviruses encoding certain kind of cytokines may be a useful approach in the treatment of a malignancy of the central nervous system.
基金Supported by The US Department of Defense grant DAMD17-03-C-0122
文摘AIM:To establish whether activation of adenosine type-3 receptors(A3Rs)and inhibition of interleukin- 1β-induced inflammation is beneficial in combination with antibiotic therapy to increase survival of mice challenged with anthrax spores. METHODS:DBA/2 mice were challenged with Bacillus anthracis spores of the toxigenic Sterne strain 43F2. Survival of animals was monitored for 15 d.Ciprofloxacin treatment(50 mg/kg,once daily,intraperitoneally) was initiated at day+1 simultaneously with the ad- ministration of inhibitors,and continued for 10 d.Two doses(2.5 mg/kg and 12.5 mg/kg)of acetyl-tyrosylvalyl-alanyl-aspartyl-chloromethylketone(YVAD)and three doses(0.05,0.15 and 0.3 mg/kg)of 1-[2-Chloro- 6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1- deoxy-N-methyl-β-D-ribofuranuronamide(Cl-IB-MECA) were tested.Animals received YVAD on days 1-4,and Cl-IB-MECA on days 1-10 once daily,subcutaneously. Human lung epithelial cells in culture were challenged with spores or edema toxin and the effects of IB-MECAon phosphorylation of AKT and generation of cAMP were tested. RESULTS:We showed that the outcome of antibiotic treatment in a murine anthrax model could be substantially improved by co-administration of the caspase-1/4 inhibitor YVAD and the A3R agonist Cl-IB-MECA.Combination treatment with these substances and ciprofloxacin resulted in up to 90%synergistic protection.All untreated mice died,and antibiotic alone protected only 30% of animals.We conclude that both substances target the aberrant host signaling that underpins anthrax mortality. CONCLUSION:Our findings suggest new possibilities for combination therapy of anthrax with antibiotics,A3R agonists and caspase-1 inhibitors.
基金This research was funded by Scientific Research Fund of National Ministry of Education (00135)
文摘A comprehensive study of yarn architecture of two-step rectangle 3D braided composites is presented. Firstly, the braided surface, the shapes of yarns and the intertwining between braider yams and axial yams are analyzed from experimentation. With the microstructure being defined, three levels of unit cell structure are identified, i.e. large unit cell, second unit cell and minimal unit cell. Secondly, based on the minimal unit cell in the interior and on the boundary of the entire cross-section, the deformations of axial yams squashed by braider yams contribute to the increase of the fiber packing factors of axial yams. Finally, the predicted fiber volume fraction of the composites decreases with the increase of linear density of the braider yam and the pitch length. Favorable correlations between the predicted and the experimental results arc found for six groups of the composites.
文摘Modern therapy of acute myeloid leukemia(AML)began in 1973 with the first report of the successful combination of daunorubicin and cytarabine,which led to complete remission in approximately 45%of patients.Accurate AML diagnosis was dependent on morphology,aided initially only by cytochemistry.Unlike acute lymphoblastic leukemia(ALL),immunophenotyping offered little in the diagnosis of AML,at least during the 1970s and 1980s.The advent of reliable cytogenetics changed the entire prognostic outlook of AML.With karyotypic analysis,different groups of AML could be classified and stratified for various therapies.Unique mutational profiling was a major advance in further categorizing AML patients,aided by the immunophenotypic identification of antigenic markers on the cells.All these advances were occurring as the understanding of the importance of the tumor burden—known as minimal residual disease(MRD)—became crucial for the management of AML patients.The efficacy of MRD has rapidly progressed in the past decade,from a specificity of 103 with immunophenotyping to 104 with polymerase chain reaction(PCR),which is only appropriate for some patients with AML,and finally to 105 or even 106 cells with the extraordinary sensitivity of next-generation sequencing(NGS).All of these advances have promoted the concept of personalized medicine,which has led to the advent of targeted agents that can accurately be used for specific diagnostic subtypes.Responses can be predicted and measured accurately.Such targeted agents have now become a cornerstone in the management of AML,increasing effi-cacy and dramatically reducing toxicity.The focus of this review is on one of the most well-studied targeted agents in AML:the FMS-like tyrosine kinase 3(FLT3)inhibitors,which have impacted the prognostication and therapeutics of AML.This review selectively discusses the FLT3 inhibitors in detail,as a model for the other burgeoning targeted agents that have already been approved,as well as those that are currently in development.
基金supported in part by the FAPESPINCTBio (Process 2014/50867-3)FAPESP-CEPOF (2013/072761)+1 种基金support by the Brigham Research InstituteLCV thanks FAPESP for financial support (Process 2013/01284-2)。
文摘Advances in biomimetic three-dimensional(3D) melanoma models have brought new prospects of drug screening and disease modeling, since their physiological relevancy for recapitulating in vivo tumor architectures is more accurate than traditional two-dimensional(2D) cell culture. Gelatin methacryloyl(GelMA) is widely used as a tissue-engineered scaffold hydrogel for 3D cell culture. In the present study, an in vitro 3D malignant melanoma model based on Gel MA was fabricated to evaluate the efficiency of hypericin(Hy)-loaded microemulsion(ME) in photodynamic therapy against melanoma. The ME was produced by the spontaneous emulsification method to enhance the bioavailability of Hy at tumor sites. Hy-loaded MEs were applied to a 3D malignant melanoma model made using 6% Gel MA and the co-culture of B16F10 and Balb/c 3T3 cells,followed by crosslinking using violet light(403 nm). The observation revealed excellent cell viability and the presence of F-actin cytoskeleton network. Hy-loaded MEs exhibited higher phototoxicity and cell accumulation(about threefold) than free Hy, and the cells cultured in the 3D system displayed lower susceptibility(about 2.5-fold) than those in 2D culture.These findings indicate that the developed MEs are potential delivery carriers for Hy;furthermore, Gel MA hydrogel-based modeling in polydimethylsiloxane(PDMS) molds is a user-friendly and cost-effective in vitro platform to investigate drug penetration and provide a basis for evaluating nanocarrier efficiency for skin cancer and other skin-related diseases.
基金the National Natural Science Foundation of China(No.52272212)the Natural Science Foundation of Shandong Province(Nos.ZR2022JQ20 and ZR2023MB126)+2 种基金the Taishan Scholar Project of Shandong Province(No.tsqn202211168)the Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science,MOE(No.M2022-7)the STIEI scientific research funding project(No.GCC2023036).
文摘Tin(IV)oxide(Sn_(3)O_(4))is layered tin and exhibits mixed valence states.It has emerged as a highly promising visible-light pho-tocatalyst,attracting considerable attention.This comprehensive review is aimed at providing a detailed overview of the latest advance-ments in research,applications,advantages,and challenges associated with Sn_(3)O_(4)photocatalytic nanomaterials.The fundamental con-cepts and principles of Sn_(3)O_(4)are introduced.Sn_(3)O_(4)possesses a unique crystal structure and optoelectronic properties that allow it to ab-sorb visible light efficiently and generate photoexcited charge carriers that drive photocatalytic reactions.Subsequently,strategies for the control and improved performance of Sn_(3)O_(4)photocatalytic nanomaterials are discussed.Morphology control,ion doping,and hetero-structure construction are widely employed in the optimization of the photocatalytic performance of Sn_(3)O_(4)materials.The effective imple-mentation of these strategies improves the photocatalytic activity and stability of Sn_(3)O_(4)nanomaterials.Furthermore,the review explores the diverse applications of Sn_(3)O_(4)photocatalytic nanomaterials in various fields,such as photocatalytic degradation,photocatalytic hydro-gen production,photocatalytic reduction of carbon dioxide,solar cells,photocatalytic sterilization,and optoelectronic sensors.The discus-sion focuses on the potential of Sn_(3)O_(4)-based nanomaterials in these applications,highlighting their unique attributes and functionalities.Finally,the review provides an outlook on the future development directions in the field and offers guidance for the exploration and de-velopment of novel and efficient Sn_(3)O_(4)-based nanomaterials.Through the identification of emerging research areas and potential avenues for improvement,this review aims to stimulate further advancements in Sn_(3)O_(4)-based photocatalysis and facilitate the translation of this promising technology into practical applications.
文摘Objective: The aim of the study was to explore the efficacy of three-dimensional conformal radiotherapy (3D- CRT) combined with TP concurrent chemotherapy in treatment of recurrent cervical cancers. Methods: From May 2005 to May 2009, 36 patients with recurrent cervical cancer were treated by 3D-CRT of 60-66 Gy and TP (docetaxel 70 mg/m^2, d1; cisplatin 20 mg/m^2, dl-d3; 21 days per cycle, totally 2 cycles) concurrent chemotherapy. Results: All of the patients had finished the 3D-CRT, the total response rate, complete response rate and partial response rate were 80.0% (28/35), 45.7% (16/35), and 34.3% (12/35), respectively. The pain-alleviation rate was 91.4% (32/35). The hemorrhage control rate was 94.3% (33/35). The median overall survival was 21.2 months. The 1-, 2- and 3-year survival rates were 54.3%, 37.1% and 22.8%, respectively. The life qualities of the patients were improved, without any treatment related death. Conclusion: Radiotherapy is effective and well-tolerated for recurrent cervical cancers, and it can promote regional control of the disease and prolong survival time.
基金The authors wish to thank the National Natural Science Foundation of China(No.51773188)the Natural Science Foundation of Shandong Province(No.ZR2017MC072)+3 种基金the National Key Research and Development Program(No.2018YFC1105602)the Key Research and Development Program of Shandong Province(No.2016YYSP018)the Second Maker Program of Marine Biomedical Research Institute of Qingdao(No.MGTD20170002M)the Scientific and Technological Innovation Project Financially Supported by Qingdao National Laboratory for Marine Science and Technology(No.2015ASKJ02).
文摘STAT3 plays a particularly important role in several cancer-related signal transduction pathways.Silencing STAT3 via RNA interference or small molecule inhibitors induces the apoptosis of tumor cells,thereby inhibiting the growth of the tumors.In this study,short-hairpin RNA sequences targeting the STAT3 genes were designed,synthesized,and then connected to pGPU6/GFP/Neo plasmids as the shRNA-expression vectors.The expression of STAT3-shRNA was analyzed by real-time PCR,western blotting,and cell apoptosis assay to study the growth and apoptosis of the cells.Then,the effect of STAT3 knockdown on the NCI-H1650 cells was studied in a tumor mouse model.The results revealed that,after an in vitro transfection,the proliferation of NCI-H1650 cells was inhibited,and the cells were induced to apoptosis.The mRNA and protein expression levels of STAT3 were downregulated in the STAT3-shRNA group.In vivo,the tumor mass and volume in the STAT3-shRNA group were significantly lower than in the other two groups.Both the in vivo and in vitro results demonstrated a long-period inhibiting effect on NSCLC,especially in vivo,when the tumor inhibition rate could reach 50%in the STAT3-shRNA group,which is an exciting outcome.Moreover,the study of the conjugation of STAT3-shRNA and chitosan-based vectors revealed that they could be combined steadily with good cytocompati-bility and transfection efficiency.These results together provide convincing evidence for the application of STAT3-shRNA used in the treatment of non-small lung cancer,which could be a promoting prospect for the development of gene therapy.
文摘Objective:In our investigation,we studied the patients with medulloblastoma who received 3-dimensional conformal radiation therapy(3DCRT) and recorded their effects,side effects and failure reasons.Methods:From August 2001 to August 2007,34 children with medulloblastoma were treated in our hospital.The age at diagnosis was 3-16 years old,and the mean age at diagnosis was 9.5 years old.Among all the patients,16 cases were included in the high risk group and 18 cases were included in the low risk group.All the patients were performed total resection or subtotal resection and no patients received radiotherapy or chemotherapy before operation.All patients received 3DCRT within 3 weeks after resection.The dose of 30 Gy were given to the whole brain and whole spine,followed by 20-25 Gy boosted to the posterior brain fossa.The median fraction dose was 180 cGy.Every patient received the chemotherapy scheme of the Lomustine,Cisplatinum and Vincristine.Nobody received intrathecal chemotherapy.The tests of the complete blood count,blood biochemistry,hepatic and renal functions were required before every cycle of chemotherapy.Results:5-year overall survival(OS) and 5-year disease free survival(DFS) were 71% and 62% respectively.The median follow-up time was 36.5 months.The 5-year OS of the high risk group was 71% compared to 62% of the low risk group.There were significant difference between the two groups(P = 0.01).There were 13 failure cases in all the patients.Of these 13 patients,10 were dead and the other 3 were alive with tumor.The complete remission(CR) rate was 70.5% and the partial remission(PR) rate was 14%.Among the failure patients,there were 3 patients(8.8%) with the recurrences located in the brain of cribriform region.The 5-year OS of the patients with preoperative metastases was 12.5%(1/8),and which of the patients with residual tumor volume > 1.5 cm3 was 0%(0/5).Through the statistic analysis,it was found that both whether or not the metastases were found before surgery and residual tumor volume have the significant impacts on the prognosis of the children with medulloblastoma(P < 0.05).The major adverse reactions were hematological toxicity(7/34,20.6%) and gastrointestinal reaction(4/34,11.8%).Conclusion:Through the using of 3DCRT for the children with medulloblastoma,the severe side effects rate was not high.The prognosis of the patients in low risk group was satisfied which was opposite to that of the patients in high risk group.And the patients with residual tumor volume > 1.5 cm3 and preoperative metastases also had poor prognosis.It is needed to pay attention to the possible low dose of the brain of cribriform region.
文摘Purpose: To study the safety and efficacy of 1/3-dose verteporfin photodynamic therapy (PDT) for subacute central serous chorioretinopathy (CSC). Methods: In this case series, 59 eyes (59 patients) diagnosed with subacute CSC in Shenyang the 4th hospital from January 2014 to December 2015 were treated with 1/3-dose verteporfin PDT and followed up for at least 1 year. The symptoms and the diagnosed history were more than 3 months but shorter than 6 months. The central foveal thickness (CFT), neuroretinal thickness (NRT), height of subfoveal retinal fluid (SRF), and subfoveal choroidal thickness (SCT) were observed at baseline and after treated at 1, 2, 3, 6 and 12 months with EDI-OCT, Best-corrected visual acuity ( BCVA) was also studied at the same time. Results: After 1, 2, 3 and 6 months of 1/3-dose verteporfin PDT treatment, the BCVA improved significantly (P 0.05). The height of SRF changed significantly. There was no retinal pigment epithelium atrophy and choroidal neovascularization (CNV) in all cases after more than 12 months follow-up. Conclusion: Treatment of 1/3 dose verteporfin PDT could safely and effectively reduce expansion of choroidal vessel and choroidal choriocapillary, promoting absorbance of subretinal fluid for subacute CSC. 1/3-dose verteporfin PDT may be an alternative method to treat the subacute CSC.
基金Supported by the Research and Development Program of The General Hospital of Western Theater Command,No.2021-XZYG-C04 and 2021-XZYG-C05。
文摘BACKGROUND Renal cell carcinoma(RCC)with Xp11.2 translocation/TFE3 gene fusion is a rare and distinct subtype of RCC that is classified under tumors with translocation of the microphthalmia-associated transcriptional factor.CASE SUMMARY We report an adult case of Xp11.2 translocation advanced RCC with metastasis(T3a N1M1),after targeted treatment,alcohol ablation,and transarterial chemoembolization,who eventually underwent successful surgical excision.No recurrence or transfer was seen within one year,and the survival period was more than 3 years.A review of the relevant literature was conducted to improve our understanding of the pathogenesis,epidemiology,clinical manifestations,diagnosis,differential diagnosis,treatment,and other aspects of the disease.CONCLUSION Transarterial chemoembolization and ablation did not achieve the desired tumor reduction in this patient,but had a significant effect on reducing intraoperative bleeding and inhibiting tumor activity.
文摘Introduction: Radiation therapy after breast surgery is an integral part of the treatment of early breast cancer. The goal of radiation therapy is to achieve the best possible coverage of the planning target volume (PTV), while reducing the dose to organs at risk (OARs) which are normal tissues whose sensitivity to irradiation could cause damage that can lead to modification of the treatment plan. In the last decade, radiation oncologist started to use the Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) for irradiating the breast, in order to achieve better dose distribution and target dose to the PTV and OAR. The aim of this study is to compare 2 external radiotherapy techniques (VMAT vs 3D) for patients with node-positive left breast cancer. Patients and Methods: We randomly selected 10 cases of postoperative radiotherapy for breast cancer in our hospital. The patients are all female, the average age was 45.4 years old, and the primary lesions are left breast. The ANOVA test was used to compare the mean difference between subgroups, and the p value Results: Dose volume histogram (DVH) was used to analyze each evaluation dose of clinical target volume (CTV) and organs at risk (OARs). Compared to 3DCRT plans, VMAT provided more uniform coverage to the breast and regional lymph nodes. The max point dose for tVMAT was lower on average (106.4% for VMAT versus 109% for 3DCRT). OAR sparing was improved with tVMAT, with a lower average V17Gy for the left lung (27.91% for VMAT versus 30.04% for 3DCRT, p and lower for V28Gy (13.75% for VMAT versus 22.34% for 3DCRT, p = 0.01). We also found a lower V35Gy for the heart on VMAT plan (p = 0.02). On the contrary, dose of contralateral breast was lower in 3DCRT than VMAT (0.59 Gy vs 3.65 Gy, p = 0.00). Conclusion: The both types of plans can meet the clinical dosimetry demands of postoperative radiotherapy for left breast cancer. The VMAT plan has a better conformity, but 3CDRT can provide a lower dose to the contralateral organs (breast and lung) to avoid the risk of secondary cancers.