Antitumor effects of a novel photosensitizer-mediated photodynamic therapy and its influence on the cell transcriptome

Photodynamic therapy(PDT)is a promising cancer treatment.This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]−10,15,20-triphenyl-porphyrin(DTP)mediated PDT(DTP-PDT).Cell viability,reactive oxygen species(ROS),and apoptosis were measured with a Cell Counting Kit-8 assay,DCFH-DA fluorescent probe,and Hoechst staining,respectively.Cell apoptosis-and autophagy-related proteins were examined using western blotting.RNA sequencing was used to screen differentially expressed mRNAs(DERs),and bioinformatic analysis was performed to identify the major biological events after DTP-PDT.Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells.The ROS scavenger N-acetyl-L-cysteine(NAC)and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity.DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2,which could also be inhibited by NAC or SB203580.The level of LC3B-Ⅱ,a marker of autophagy,was increased by DTP-PDT.A total of 3496 DERs were obtained after DTP-PDT.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes,the nuclear lumen,protein binding,cell cycle,protein targeting to the endoplasmic reticulum,and ribosomal DNA replication.Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints.Protein-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting genes.Therefore,DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy,partly through ROS and the P38 MAPK signaling pathway.Genes associated with the cell cycle,ribosomes,DNA replication,and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.

Codelivery of anti-CD47 antibody and chlorin e6 using a dual pH-sensitive nanodrug for photodynamic immunotherapy of osteosarcoma

Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.

Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer

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.

Verteporfin fluorescence in antineoplastic-treated pancreatic cancer cells found concentrated in mitochondria

BACKGROUND Traditional treatments for pancreatic cancer(PC)are inadequate.Photodynamic therapy(PDT)is non-invasive,and proven safe to kill cancer cells,including PC.However,the mitochondrial concentration of the photosensitizer,such as verteporfin,is key.AIM To investigate the distribution of fluorescence of verteporfin in PC cells treated with antitumor drugs,post-PDT.METHODS Workable survival rates of PC cells(AsPC-1,BxPC-3)were determined with chemotherapy[doxorubicin(DOX)and gemcitabine(GEM)]and non-chemotherapy[sirolimus(SRL)and cetuximab(CTX)]drugs in vitro,with or without verteporfin,as measured via MTT,flow cytometry,and laser confocal microscopy.Reduced cell proliferation was associated with GEM that was more enduring compared with DOX.Confocal laser microscopy allowed observation of GEM-and verteporfin-treated PC cells co-stained with 4’,6-diamidino-2-phenylindole and MitoTracker Green to differentiate living and dead cells and subcellular localization of verteporfin,respectively.RESULTS Cell survival significantly dropped upon exposure to either chemotherapy drug,but not to SRL or CTX.Both cell lines responded similarly to GEM.The intensity of fluorescence was associated with the concentration of verteporfin.Additional experiments using GEM showed that survival rates of the PC cells treated with 10μmol/L verteporfin(but not less)were significantly lower relative to nil verte-porfin.Living and dead stained cells treated with GEM were distinguishable.After GEM treatment,verteporfin was observed primarily in the mitochondria.CONCLUSION Verteporfin was observed in living cells.In GEM-treated human PC cells,verteporfin was particularly prevalent in the mitochondria.This study supports further study of PDT for the treatment of PC after neoadjuvant chemotherapy.

Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

Potential of photodynamic therapy in the management of infectious oral diseases

Photodynamic therapy(PDT)can take place in the presence of three elements:Light with an appropriate wavelength;a photosensitizer;and the presence of oxygen.This type of treatment is very effective overall against bacterial,viral and mycotic cells.In the last 10 years many papers have been published on PDT with different types of photosensitizers(e.g.,methylene blue,toluidine blue,indocyanine green,curcumin-based photosensitizers),different wavelengths(e.g.,460 nm,630 nm,660 nm,810 nm)and various parameters(e.g.,power of the light,time of illumination,number of sessions).In the scientific literature all types of PDT seem very effective,even if it is difficult to find a standard protocol for each oral pathology.PDT could be an interesting way to treat some dangerous oral infections refractory to common pharmacological therapies,such as candidiasis from multidrug-resistant Candida spp.

Innovative strategies for photodynamic therapy against hypoxic tumor

Photodynamic therapy(PDT)is applied as a robust therapeutic option for tumor,which exhibits some advantages of unique selectivity and irreversible damage to tumor cells.Among which,photosensitizer(PS),appropriate laser irradiation and oxygen(O_(2))are three essential components for PDT,but the hypoxic tumor microenvironment(TME)restricts the O_(2) supply in tumor tissues.Even worse,tumor metastasis and drug resistance frequently happen under hypoxic condition,which further deteriorate the antitumor effect of PDT.To enhance the PDT efficiency,critical attention has been received by relieving tumor hypoxia,and innovative strategies on this topic continue to emerge.Traditionally,the O_(2) supplement strategy is considered as a direct and effective strategy to relieve TME,whereas it is confronted with great challenges for continuous O_(2) supply.Recently,O_(2)-independent PDT provides a brand new strategy to enhance the antitumor efficiency,which can avoid the influence of TME.In addition,PDT can synergize with other antitumor strategies,such as chemotherapy,immunotherapy,photothermal therapy(PTT)and starvation therapy,to remedy the inadequate PDT effect under hypoxia conditions.In this paper,we summarized the latest progresses in the development of innovative strategies to improve PDT efficacy against hypoxic tumor,which were classified into O_(2)-dependent PDT,O_(2)-independent PDT and synergistic therapy.Furthermore,the advantages and deficiencies of various strategies were also discussed to envisage the prospects and challenges in future study.

Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022)

Background In China's Mainland,patients with neovascular age-related macular degeneration(nAMD)have approximately an 40%prevalence of polypoidal choroidal vasculopathy(PCV).This disease leads to recurrent retinal pigment epithelium detachment(PED),extensive subretinal or vitreous hemorrhages,and severe vision loss.China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes,regarding opinions on inactive PCV,choices of anti-vascular endothelial growth factor(anti-VEGF)monotherapy,photodynamic therapy(PDT)monotherapy or combined therapy,patients with persistent subretinal fluid(SRF)or intraretinal fluid(IRF)after loading dose anti-VEGF,and patients with massive subretinal hemorrhage.An evidence synthesis team conducted systematic reviews,which informed the recommendations that address these questions.This guideline used the GRADE(Grading of Recommendations,Assessment,Development,and Evaluation)approach to assess the certainty of evidence and grade the strengths of recommendations.Results The panel proposed the following six conditional recommendations regarding treatment choices.(1)For patients with inactive PCV,we suggest observation over treatment.(2)For treatment-na?ve PCV patients,we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy.(3)For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment,we suggest later/rescue PDT over initiate PDT.(4)For PCV patients who plan to initiate anti-VEGF monotherapy,we suggest the treat and extend(TE)regimen rather than the pro re nata(PRN)regimen following three monthly loading doses.(5)For patients with persistent SRF or IRF on optical coherence tomography(OCT)after three monthly anti-VEGF treatments,we suggest proceeding with anti-VEGF treatment rather than observation.(6)For PCV patients with massive subretinal hemorrhage(equal to or more than four optic disc areas)involving the central macula,we suggest surgery(vitrectomy in combination with tissue-plasminogen activator(tPA)intraocular injection and gas tamponade)rather than anti-VEGF monotherapy.Conclusions Six evidence-based recommendations support optimal care for PCV patients'management.

Nanoparticle-mediated synergistic anticancer effect of ferroptosis and photodynamic therapy:Novel insights and perspectives

Current antitumor monotherapy has many limitations,highlighting the need for novel synergistic anticancer strategies.Ferroptosis is an iron-dependent form of nonapoptotic cell death that plays a pivotal regulatory role in tumorigenesis and treatment.Photodynamic therapy(PDT)causes irreversible chemical damage to target lesions and is widely used in antitumor therapy.However,PDT’s effectiveness is usually hindered by several obstacles,such as hypoxia,excess glutathione(GSH),and tumor resistance.Ferroptosis improves the anticancer efficacy of PDT by increasing oxygen and reactive oxygen species(ROS)or reducing GSH levels,and PDT also enhances ferroptosis induction due to the ROS effect in the tumor microenvironment(TME).Strategies based on nanoparticles(NPs)can subtly exploit the potential synergy of ferroptosis and PDT.This review explores recent advances and current challenges in the landscape of the underlyingmechanisms regulating ferroptosis and PDT,as well as nano delivery system-mediated synergistic anticancer activity.These include polymers,biomimetic materials,metal organic frameworks(MOFs),inorganics,and carrier-free NPs.Finally,we highlight future perspectives of this novel emerging paradigm in targeted cancer therapies.

Different approaches for treating myopic choroidal neovascularization:a network Meta-analysis

AIM:To evaluate the efficacy of intravitreal injection of anti-vascular endothelial growth factor(anti-VEGF),photodynamic therapy(PDT),and laser treatment(LT)for anatomical and functional improvement in myopic choroidal neovascularization(mCNV)patients.METHODS:Two researchers independently searched PubMed,Cochrane Library,Web of Science,and other databases to screen studies comparing best-corrected vision acuity(BCVA)and foveal center thickness(FCT)changes after mCNV treatment.Post-treatment chorioretinal atrophy(CRA)is a secondary outcome indicator.The retrieval time limit is from the database construction to January 30,2023.RESULTS:A total of 1072 eyes in 16 articles were included.In the RCTs,intravitreal bevacizumab(IVB)and intravitreal ranibizumab(IVR)were superior to PDT(MD=0.18,95%CI:0.02,0.40,MD=0.18,95%CI:0.01,0.42)in improving BCVA of mCNV patients(P<0.05).The relative effectiveness in improving BCVA,from high to low,appeared to be IVR,intravitreal aflibercept(IVA),IVB,LT,PDT,and sham first followed by IVA(Sham/IVA).While improving the FCT from high to low was IVA,IVR,IVB,PDT.In retrospective studies,the results of BCVA after long-term treatment showed that all the therapeutic effects from high to low was IVA,intravitreal conbercept(IVC),IVR,IVB,IVB/IVR,PDT with IVB/IVR,PDT.The effect of improving FCT was IVA,IVR,IVC,PDT,and IVB from high to low.And in the effects of improving CRA,the IVB appeared to be higher than IVR,while the PDT was the smallest,but none of the differences in the results were statistically significant.CONCLUSION:Anti-VEGF has the best effect on longterm vision improvement in mCNV patients,using IVB or IVR alone to treat mCNV may be better than IVB or IVR combined with PDT.There is no significant difference in the improvement of visual acuity,macular edema,and CRA in mCNV patients treated with any different anti-VEGF drugs.

Photodynamic therapy with TBZPy regulates the PI3K/AKT and endoplasmic reticulum stress-related PERK/eIF2α pathways in HeLa cells

Background:((1-triphenylaminebenzo[c][1,2,5]thiadiazole-4-yl)styryl)-1-methylpyridin methylpyridin-1-ium iodide salt(TBZPy)is a novel photosensitizer that displays excellent photodynamic properties.However,There are few reports on the mechanism of action of the TBZPy photodynamic.Previous studies revealed that photodynamic therapy(PDT)could induce endoplasmic reticulum stress by acting on the endoplasmic reticulum.Therefore,in this study,we investigated the effects of endoplasmic reticulum stress induced by TBZPy-PDT in treating High-risk human papillomavirus(HR-HPV)infection and their underlying mechanisms.Methods:The human cervical cancer cell line HeLa(containing whole genome of HR-HPV18)was treated with TBZPy-PDT.Cell migration,invasion,and colony-forming ability were evaluated using wound-healing,Transwell invasion,and colonyforming assays,respectively.Through western blot analysis,we determined the level of expression of the PI3K/AKT and PERK/eIF2αpathway proteins and the proteins associated with calcium trafficking and apoptosis.The calcium levels in the cytoplasm were detected via flow cytometry.Results:The result shows that TBZPy-PDT could inhibite the migration,invasion,and colony forming ability of infected HeLa cells by downregulating the PI3K/AKT pathway in vitro.And we found that TBZPy-PDT induced endoplasmic reticulum stress-specific apoptosis via the PERK/eIF2αpathway.Moreover,TBZPy-PDT increased the levels of calcium and calmodulin,while decreasing the levels of endoplasmic reticulum calcium-binding proteins.Conclusions:TBZPy-PDT is effective on treating human papillomavirus-infected cells.Targeting the PI3K/AKT and PERK/eIF2αpathways and the endoplasmic reticulum stress process may help improve the effects of TBZPy-PDT for treating high-risk human papillomavirus infection.

Reversing ferroptosis resistance by MOFs through regulation intracellular redox homeostasis

As a non-apoptotic cell death form,ferroptosis offers an alternative approach to overcome cancer chemotherapy resistance.However,accumulating evidence indicates cancer cells can develop ferroptosis resistance by evolving antioxidative defense mechanisms.To address this issue,we prepared a Buthionine-(S,R)-sulfoximine(BSO)loaded metal organic framework(MOF)of BSO-MOF-HA(BMH)with the combination effect of boosting oxidative damage and inhibiting antioxidative defense.MOF nanoparticle was constructed by the photosensitizer of[4,4,4,4-(porphine-5,10,15,20-tetrayl)tetrakis(benzoic acid)](TCPP)and the metal ion of Zr6,which was further decorated with hyaluronic acid(HA)in order to impart active targeting to CD44 receptors overexpressed cancer cells.BMH exhibited a negative charge and spherical shape with average particle size about 162.5nm.BMH was found to restore the susceptibility of 4T1 cells to ferroptosis under irradiation.This was attributed to the combination of photodynamic therapy(PDT)andγ-glutamylcysteine synthetase inhibitor of BSO,shifting the redox balance to oxidative stress.Enhanced ferroptosis also induced the release of damage associated molecular patterns(DAMPs)to maturate dendritic cells and activated T lymphocytes,leading to superior anti-tumor performance in vivo.Taken together,our findings demonstrated that boosting oxidative damage with photosensitizer serves as an effective strategy to reverse ferroptosis resistance.

Endoscopic biliary treatment of unresectable cholangiocarcinoma: A meta-analysis of survival outcomes and systematic review

BACKGROUND Endoscopic radiofrequency ablation(ERFA),percutaneous radiofrequency ablation(PRFA),and photodynamic therapy(PDT),when used in conjunction with conventional biliary stenting,have demonstrated a survival benefit in patients with unresectable cholangiocarcinoma.AIM To compare pooled survival outcomes,adverse event rates,and mean stent patency for those undergoing these procedures.METHODS A comprehensive literature review of published studies and abstracts from January 2011 to December 2020 was performed comparing survival outcomes in patients undergoing ERFA with stenting,biliary stenting alone,PRFA with stenting,and PDT with stenting for unresectable cholangiocarcinoma(CCA).RESULTS Data from four studies demonstrated a pooled mean survival favoring ERFA as compared to biliary stenting alone(12.0±0.9 mo vs 6.8±0.3 mo,P<0.001)as well as statistically improved median survival time(13 mo vs 8 mo,P<0.001).Both ERFA with stenting and PRFA with stenting groups demonstrated statistical superiority to biliary stenting alone(P<0.001 and P=0.004,respectively).However,when comparing ERFA to PRFA,pooled data demonstrated overall higher mean survival in the ERFA with stenting cohort as compared to PRFA with stent cohort(12.0+0.9 mo vs 8.1+2.1 mo,P<0.0001).Data from two studies demonstrated a pooled median survival favoring ERFA with stenting as compared to PDT with stenting(11.3 mo vs 8.5 mo,P=0.02).CONCLUSION While further prospective,randomized studies are needed to assess efficacy of ERFA,our metaanalysis demonstrated that this technique offers endoscopists a reasonable palliative method by which to treat patients with unresectable CCA that results in longer survival as compared to biliary stenting alone,percutaneous radiofrequency ablation with biliary stenting,and PDT with biliary stenting as well as an acceptable adverse event profile based on available published data.

Advances in photodynamic therapy for port-wine stain and our experience

Port-wine stain(PWS)is a congenital capillary malformation that occurs in 0.3%–0.5%of newborns.The pulsed dye laser is the current gold standard treatment for PWS;however,its efficacy is poor.Photosensitizer photodynamic therapy(PDT)is considered a promising treatment for PWS.Here we provide a comprehensive overview of PDT.

新型长波长光敏剂对HL-60细胞光毒作用的参数研究

细菌叶绿素锌作为一类潜在的长波长光敏剂,具有重要生物医学研究价值。本文采用MTT法研究Zn-BCA-PDT灭杀HL-60细胞的浓度、暗孵育时间、照光时间和光波长等参数,总结对HL-60白血病肿瘤细胞进行Zn-BCA-PDT的较佳处理方案:细胞密度1×105个/mL,Zn-BCA浓度10μg/mL,暗室孵育3h,照光时间50min,光源波长为800nm。

新金属菌绿素对HL-60肿瘤细胞光毒作用的参数研究

细菌叶绿素锌作为一类潜在的长波长光敏剂,具有重要生物医学研究价值.采用MTT法研究Zn-BCA-PDT灭杀HL-60细胞的浓度、暗孵育时间、照光时间和光波长等参数,总结对HL-60白血病肿瘤细胞进行Zn-BCA-PDT的较佳处理方案:细胞密度1×105个/mL,Zn-BCA浓度10μg/mL,暗室孵育3 h,照光时间50 min,光源波长为800 nm.

Treatment of Helicobacter pylori infection: Current and future insights

Helicobacter pylori(H.pylori) is an important major cause of peptic ulcer disease and gastric malignancies such as mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma worldwide.H.pylori treatment still remains a challenge,since many determinants for successful therapy are involved such as individual primary or secondary antibiotics resistance,mucosal drug concentration,patient compliance,side-effect profile and cost.While no new drug has been developed,current therapy still relies on different mixture of known antibiotics and anti-secretory agents.A standard triple therapy consisting of two antibiotics and a proton-pump inhibitor proposed as the first-line regimen.Bismuthcontaining quadruple treatment,sequential treatment or a non-bismuth quadruple treatment(concomitant) are also an alternative therapy.Levofloxacin containing triple treatment are recommended as rescue treatment for infection of H.pylori after defeat of first-line therapy.The rapid acquisition of antibiotic resistance reduces the effectiveness of any regimens involving these remedies.Therefore,adding probiotic to the medications,developing anti-H.pylori photodynamic or phytomedicine therapy,and achieving a successful H.pylori vaccine may have the promising to present synergistic or additive consequence against H.pylori,because each of them exert different effects.

Role of endoscopic therapy in early esophageal cancer

Esophageal carcinoma is a highly lethal cancer associated with high morbidity and mortality. Esophageal squamous cell carcinoma and esophageal adenocarcinoma are the two distinct histological types. There has been significant progress in endoscopic diagnosis and treatment of early stages of cancer using resection and ablation techniques, as shown in several trials in the recent past. Earlier detection of esophageal cancer and advances in treatment modalities have lead to improvement in the 5-year survival from 5% to about 20% in the past decade. Endoscopic eradication therapy is the preferred modality of treatment in cancer limited to mucosal layer of the esophagus as there is very low risk of lymph node metastasis, leading to high cure rates, low risk of recurrence and with few adverse effects. The most common adverse events seen are strictures, bleeding and rarely perforation which can be endoscopically managed. In patients with recurrent advanced disease or invasive tumor, esophagectomy with lymph node dissection remains the mainstay of treatment. There is debate on post-endoscopic surveillance with some studies suggesting closer follow up with upper endoscopy every 6 mo for the first 1-2 years and then annually for the 3 years while others recommending the appropriate action only if symptoms or other abnormalities develop. Overall, the field of endoscopic therapy is still evolving and focus should be placed on careful patient selection using a multidisciplinary approach.

Influence of Photodynamic Therapy on Apoptosis and Invasion of Human Cholangiocarcinoma QBC939 Cell Line

Objective To investigate the effect of photodynamic therapy(PDT) mediated by hematoporphyrin derivative(HPD) on apoptosis and invasion of cholangiocarcinoma QBC939 cell lines. Methods In vitro cultured cholangiocarcinoma QBC939 cell line was exposed to 2, 4, 6, 8, 10, 12, and 14 μg/ml HPD with 5, 10, and 15 J/cm2 light intensity, respectively. The optical density at 450 nm of the QBC939 cells was measured by CCK8 assay and its growth inhibition ratio was calculated. Flow cytometry and transwell migration assay were applied to detect cell apoptosis and invasion respectively. RT-PCR and immunocytochemistry analyses were used to detect expressions of vascular endothelial growth factor-C(VEGF-C), cyclooxygenase-2(COX-2), and proliferating cell nuclear antigen(PCNA). Enzyme-linked immunosorbent assay(ELISA) was carried out to examine the secretion of VEGF-C and COX-2 in QBC939 cells. Results Exposure to HPD-PDT can significantly suppress the growth of QBC939 cells(all P<0.05). HPD-PDT can promote apoptosis of QBC939 cells at the early stage. When the concentration of HPD was 2 μg/ml and light irradiation was 5 J/cm2, HPD-PDT had no obvious inhibitory effect on QBC939 cell growth, but can obviously inhibit cell invasion, and significant difference was observed between the HPD-PDT and control groups(P<0.01). The HPD-PDT can reduce the m RNA and protein expressions of VEGF-C, COX-2, and PCNA, and decrease the secretion of VEGF-C and COX-2 in QBC939 cells. Conclusion PDT could promote apoptosis and inhibit growth and invasion of cholangiocarcinoma cells QBC939 in vitro.

Single NIR Laser-Activated Multifunctional Nanoparticles for Cascaded Photothermal and Oxygen-Independent Photodynamic Therapy

Inconvenient dual-laser irradiation and tumor hypoxic environment as well as limited judgment of treating region have impeded the development of combined photothermal and photodynamic therapies(PTT and PDT).Herein,Bi2Se3@AIPH nanoparticles(NPs)are facilely developed to overcome these problems.Through a one-step method,free radical generator(AIPH)and phase transition material(lauric acid,LA,44-46°C)are encapsulated in hollow bismuth selenide nanoparticles(Bi2Se3 NPs).Under a single 808-nm laser irradiation at the tumor area,hyperthermia produced by Bi2Se3 not only directly leads to cell death,but also promotes AIPH release by melting LA and triggers free radical generation,which could further eradicate tumor cells in hypoxic environments.Moreover,Bi2Se3 with high X-ray attenuation coefficient endows the NPs with high computed tomography(CT)imaging capability,which is important for treating area determination.The results exhibit that Bi2Se3@AIPH NPs possesses 31.2%photothermal conversion efficiency for enhanced PTT,ideal free radical generation for oxygen-independent PDT,and 37.77 HU mL mg?1 X-ray attenuation coefficient for CT imaging with high quality.Most importantly,the tumor growth inhibition rate by synergistic PTT,PDT,and following immunotherapy is 99.6%,and even one tumor disappears completely,which demonstrates excellent cascaded synergistic effect of Bi2Se3@AIPH NPs for the tumor therapy.