Nanomaterials for refining tumor microenvironment and enhancing therapy in head and neck squamous cell carcinoma: a review

Head and neck squamous cell carcinoma (HNSCC) is a prevalent and lethal solid tumor with a high mortality rate. Conventional cancertreatments, including surgery, radiotherapy, and chemotherapy, primarily target cancer cell eradication. However, uncontrolled proliferation and metabolic activities of these cells result in abnormalities in nutrient levels, hypoxia, and immunosuppression within the tumor microenvironment (TME). These factors constrain the efficacy of traditional treatments by promoting drug resistance, recurrence, and metastasis. Nanomaterials (NMs), such as nanozymes, can exhibit enzymatic activity similar to that of natural enzymes and offer a promising avenuefor the direct modification of the TME through catalytic oxidation-reduction processes. Moreover, they can serve as sensitizers or drug deliverycarriers, enhancing the efficacy of traditional treatment methods. Recently, NMs have garnered significant attention from oncologists. Thisreview begins with an overview of the composition and unique characteristics of the TME. Subsequently, we comprehensively exploredthe application of NMs in the treatment of HNSCC. Finally, we discuss the potential prospects and challenges associated with usingNMs in biomedical research.

A biomimetic spore nanoplatform for boosting chemodynamic therapy and bacteria-mediated antitumor immunity for synergistic cancer treatment

Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer.However,the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations.Furthermore,monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors.In this study,based on our discovery that spore shell(SS)of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity,we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy,chemodynamic therapy and antitumor immunity for synergistic cancer treatment.In detail,SS is separated from probiotic spores and then attached to the surface of liposome(Lipo)that was loaded with hemoglobin(Hb),glucose oxidase(GOx)and JQ1to construct SS@Lipo/Hb/GOx/JQ1.In tumor tissue,highly toxic hydroxyl radicals(·OH)are generated via sequential catalytic reactions:GOx catalyzing glucose into H_(2)O_(2)and Fe^(2+)in Hb decomposing H_(2)O_(2)into·OH.The combination of·OH and SS adjuvant can improve tumor immunogenicity and activate immune system.Meanwhile,JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response.In this manner,SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis.To summarize,the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.

Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy

Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.

CA IX-targeted Ag_(2)S quantum dots bioprobe for NIR-II imaging-guided hypoxia tumor chemo-photothermal therapy

Hypoxia is the common characteristic of almost all solid tumors,which prevents therapeutic drugs from reaching the tumors.Therefore,the development of new targeted agents for the accurate diagnosis of hypoxia tumors is widely concerned.As carbonic anhydrase IX(CA IX)is abundantly distributed on the hypoxia tumor cells,it is considered as a potential tumor biomarker.4-(2-Aminoethyl)benzenesulfonamide(ABS)as a CA IX inhibitor has inherent inhibitory activity and good targeting effect.In this study,Ag_(2)S quantum dots(QDs)were used as the carrier to prepare a novel diagnostic and therapeutic bioprobe(Ag_(2)S@polyethylene glycol(PEG)-ABS)through ligand exchange and amide condensation reaction.Ag_(2)S@PEG-ABS can selectively target tumors by surface-modified ABS and achieve accurate tumor imaging by the near infrared-II(NIR-II)fluorescence characteristics of Ag_(2)S QDs.PEG modification of Ag_(2)S QDs greatly improves its water solubility and stability,and therefore achieves high photothermal stability and high photothermal conversion efficiency(PCE)of 45.17%.Under laser irradiation,Ag_(2)S@PEG-ABS has powerful photothermal and inherent antitumor combinations on colon cancer cells(CT-26)in vitro.It also has been proved that Ag_(2)S@PEG-ABS can realize the effective treatment of hypoxia tumors in vivo and show good biocompatibility.Therefore,it is a new efficient integrated platform for the diagnosis and treatment of hypoxia tumors.

DNA Damage-driven Inflammatory Cytokines:Reprogramming of Tumor Immune Microenvironment and Application of Oncotherapy

DNA damage occurs across tumorigenesis and tumor development.Tumor intrinsic DNA damage can not only increase the risk of mutations responsible for tumor generation but also initiate a cellular stress response to orchestrate the tumor immune microenvironment(TIME)and dominate tumor progression.Accumulating evidence documents that multiple signaling pathways,including cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)and ataxia telangiectasia-mutated protein/ataxia telangiectasia and Rad3-related protein(ATM/ATR),are activated downstream of DNA damage and they are associated with the secretion of diverse cytokines.These cytokines possess multifaced functions in the anti-tumor immune response.Thus,it is necessary to deeply interpret the complex TIME reshaped by damaged DNA and tumor-derived cytokines,critical for the development of effective tumor therapies.This manuscript comprehensively reviews the relationship between the DNA damage response and related cytokines in tumors and depicts the dual immunoregulatory roles of these cytokines.We also summarize clinical trials targeting signaling pathways and cytokines associated with DNA damage and provide future perspectives on emerging technologies.

New method of local adjuvant therapy with bicarbonate Ringer’s solution for tumoral calcinosis: A case report

BACKGROUND Tumoral calcinosis is a condition characterized by deposits of calcium phosphate crystals in extra-articular soft tissues,occurring in hemodialysis patients.Calcium phosphate crystals are mainly composed of hydroxyapatite,which is highly infilt-rative to tissues,thus making complete resection difficult.An adjuvant method to remove or resolve the residual crystals during the operation is necessary.CASE SUMMARY A bicarbonate Ringer’s solution with bicarbonate ions(28 mEq/L)was used as the adjuvant.After resecting calcium phosphate deposits of tumoral calcinosis as much as possible,while filling with the solution,residual calcium phosphate deposits at the pseudocyst wall can be gently scraped by fingers or gauze in the operative field.A 49-year-old female undergoing hemodialysis for 15 years had swelling with calcium deposition for 2 years in the shoulders,bilateral hip joints,and the right foot.A shoulder lesion was resected,but the calcification remained and early re-deposition was observed.Considering the difficulty of a complete rection,we devised a bicarbonate dissolution method and excised the foot lesion.After resection of the calcified material,the residual calcified material was washed away with bicarbonate Ringer’s solution.CONCLUSION The bicarbonate dissolution method is a new,simple,and effective treatment for tumoral calcinosis in hemodialysis patients.

Systemic therapy in gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.

Effect of Individualized Exercise Therapy on Cancer-related Fatigue and Negative Emotion in Patients with Gastrointestinal Tumor during Perioperative Period

[Objectives]To investigate the effect of exercise therapy in gastric cancer patients during perioperative period.[Methods]100 patients with gastric cancer who underwent elective operation in the Department of Gastrointestinal Surgery of Taihe Hospital Affiliated to Hubei University of Medicine were divided into observation group and control group by convenience sampling.The control group received routine nursing measures,and the experimental group received exercise therapy intervention measures on the basis of the control group.The patients were evaluated by the General Information Questionnaire,Self-Rating Anxiety Scale,Self-Rating Depression Scale and Cancer-related Fatigue Scale at the time of admission,the second week and the sixth week after operation.[Results]The time effect,intervention effect and interaction effect of anxiety score,depression score and cancer-related fatigue score were significant(all P<0.05)and the index of enhanced recovery after surgery was significant(P<0.05)in the two groups at the second and sixth week after operation.[Conclusions]Exercise therapy is beneficial to promoting the enhanced recovery after surgery in advance,reduce cancer-related fatigue,negative emotion and accelerate rehabilitation in patients with gastrointestinal tumors.

Multifaceted p21 in carcinogenesis,stemness of tumor and tumor therapy

Cancer cells possess metabolic properties that are different from those of benign cells.p21,encoded by CDKN1A gene,also named p21Cip1/WAF1,was first identified as a cyclin-dependent kinase regulator that suppresses cell cycle G1/S phase and retinoblastoma protein phosphorylation.CDKN1A(p21)acts as the downstream target gene of TP53(p53),and its expression is induced by wild-type p53 and it is not associated with mutant p53.p21 has been characterized as a vital regulator that involves multiple cell functions,including G1/S cell cycle progression,cell growth,DNA damage,and cell stemness.In 1994,p21 was found as a tumor suppressor in brain,lung and colon cancer by targeting p53 and was associated with tumorigenesis and metastasis.Notably,p21 plays a significant role in tumor development through p53-dependent and p53-independent pathways.In addition,expression of p21 is closely related to the resting state or terminal differentiation of cells.p21 is also associated with cancer stem cells and acts as a biomarker for such cells.In cancer therapy,given the importance of p21 in regulating the G1/S and G2 check points,it is not surprising that p21 is implicated in response to many cancer treatments and p21 promotes the effect of oncolytic virotherapy.

Immune modulations of the tumor microenvironment in response to phototherapy

The tumor microenvironment(TME)promotes pro-tumor and anti-infammatory metabolismsand suppresses the host immune system.It prevents immune cells from fighting against cancereffectively,resulting in limited efficacy of many current cancer treatment modalities.Differenttherapies aim to overcome the immunosuppressive TME by combining various approaches tosynergize their effects for enhanced antitumor activity and augmented stimulation of the im-mune system.Immunotherapy has become a major therapeutic strategy because it unleashes thepower of the immune system by activating,enhancing,and directing immune responses to pre-vent,control,and eliminate cancer.Phototherapy uses light iradiation to induce tumor celldeath through photothermal,photochemical,and photo-immunological interactions.Photo-therapy induces tumor immunogenic cell death,which is a precursor and enhancer for anti-tumorimmunity.However,phototherapy alone has limited effects on long-term and systemic anti-tumor immune responses.Phototherapy can be combined with immunotherapy to improve thetumoricidal effect by killing target tumor cells,enhancing immune cell infiltration in tumors,andrewiring pathways in the TME from antinfammatory to pro-inflammatory.Phototherapy-enhanced immunotherapy triggers effective cooperation bet ween innate and adaptive immunities,specifically targeting the tumor cells,whether they are localized or distant.Herein,the successes and limitations of phototherapy combined with other cancer treatmentmodalities will be discussed.Specifically,we will review the symergistic effects of phototherapy combined with different cancer therapies on tumor elimination and remodeling of the immuno-suppressive TME.Overll,phototherapy,in combination with other therapeutic modalities,canestablish anti-tumor pro-infammatory phenotypes in activated tumor-infiltrating T cells andB cells and activate systemic anti-tumor immune responses.

Recombination Mutant Human Tumor Necrosis Factor Combined with Chemotherapy in the Treatment of Advanced Cancer

Objective: Past studies showed that tumor necrosis factor (TNF) assisted anti-tumor treatment and intensified the sensitivity of chemotherapy. However its clinical application has been curbed because of its low purity, high dosage, and strong toxicity. The objective of present study is to evaluate the therapeutic effects and adverse reactions of recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy in patients with advanced malignant tumor. Methods: 105 patients with advanced malignant tumor were randomly divided into trial group, 69 patients, and control group, 36 patients. rmhTNF was injected intramuscularly to the trial group at a dose of 4×106 U/m2, from the 1st to 7th days, the 11th to 17th days combined with chemotherapy course. The chemotherapy plan was as follows: CAP for patients with the NSCLC; FAM for patients with gastric cancer; FC for patients with colorectal cancer. One treatment cycle lasted for 21 days and two cycles were scheduled. The control group was given only the same chemotherapy as the trial group. Results: In the trial group there was 1 CR case and 12 PR cases, and the response rate was 13/69 (18.84%); in the control group 1 PR case, the response rate 1/36 (2.78%). The response rate in the trial group was significantly higher than that in the control group (P=0.022). The response rate for NSCLC in the trial group was 8/17 (47.06%), and 1/6 (16.67%) in the control group. The response rates for gastric cancer and colorectal cancer in the trial groups also were higher than those in the control groups. After the treatment the KPS was 89.00±9.92 in the trial group, and 84.17±8.84 in the control group, with a significant difference between the two groups (P=0.028). The adverse reactions of rmhTNF injection included: pain in the injection area, chill, hardening and swelling and redness in the injection area, fever, ostealgia and myosalgia, and cold-like symptoms. All these adverse reactions were mild and bearable. Conclusion: The administration of rmhTNF in combination with general chemotherapy is an effective and secure means in treating advanced malignant tumor.

Molecular regulation of vasculogenic mimicry in tumors and potential tumor-target therapy

"Vasculogenic mimicry(VM)",is a term that describes the unique ability of highly aggressive tumor cells to express a multipotent,stem cell-like phenotype,and form a pattern of vasculogenic-like networks in threedimensional culture.As an angiogenesis-independent pathway,VM and/or periodic acid-schiff-positive patterns are associated with poor prognosis in tumor patients.Moreover,VM is resistant to angiogenesis inhibitors.Here,we will review the advances in research on biochemical and molecular signaling pathways of VM in tumors and on potential anti-VM therapy strategy.

Recent Advancements in Nanomedicine for‘Cold’Tumor Immunotherapy

Although current anticancer immunotherapies using immune checkpoint inhibitors(ICIs)have been reported with a high clinical success rate,numerous patients still bear‘cold’tumors with insufficient T cell infiltration and low immunogenicity,responding poorly to ICI therapy.Considering the advancements in precision medicine,in-depth mechanism studies on the tumor immune microenvironment(TIME)among cold tumors are required to improve the treatment for these patients.Nanomedicine has emerged as a promising drug delivery system in anticancer immunotherapy,activates immune function,modulates the TIME,and has been applied in combination with other anticancer therapeutic strategies.This review initially summarizes the mechanisms underlying immunosuppressive TIME in cold tumors and addresses the recent advancements in nanotechnology for cold TIME reversal-based therapies,as well as a brief talk about the feasibility of clinical translation.

Precision radiotherapy for brain tumors A 10-year bibliometric analysis

OBJECTIVE： Precision radiotherapy plays an important role in the management of brain tumors. This study aimed to identify global research trends in precision radiotherapy for brain tumors using a bibliometric analysis of the Web of Science. DATA RETRIEVAL： We performed a bibliometric analysis of data retrievals for precision radiotherapy for brain tumors containing the key words cerebral tumor, brain tumor, intensity-modulated radiotherapy, stereotactic body radiation therapy, stereotactic ablative radiotherapy, imaging-guided radiotherapy, dose-guided radiotherapy, stereotactic brachytherapy, and stereotactic radiotherapy using the Web of Science. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed articles on precision radiotherapy for brain tumors which were published and indexed in the Web of Science; （b） type of articles： original research articles and reviews; （c） year of publication： 2002-2011. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） Corrected papers or book chapters. MAIN OUTCOME MEASURES： （1） Annual publication output; （2） distribution according to country; （3） distribution according to institution; （4） top cited publications; （5） distribution according to journals; and （6） comparison of study results on precision radiotherapy for brain tumors. RESULTS： The stereotactic radiotherapy, intensity-modulated radiotherapy, and imaging-guided radiotherapy are three major methods of precision radiotherapy for brain tumors. There were 260 research articles addressing precision radiotherapy for brain tumors found within the Web of Science. The USA published the most papers on precision radiotherapy for brain tumors, followed by Germany and France. European Synchrotron Radiation Facility, German Cancer Research Center and Heidelberg University were the most prolific research institutes for publications on precision radiotherapy for brain tumors. Among the top 13 research institutes publishing in this field, seven are in the USA, three are in Germany, two are in France, and there is one institute in India. Research interests including urology and nephrology, clinical neurology, as well as rehabilitation are involved in precision radiotherapy for brain tumors studies. CONCLUSION： Precision radiotherapy for brain tumors remains a highly active area of research and development.

Biomedical overview of melanin.1.Updating melanin biology and chemistry,physico-chemical properties,melanoma tumors,and photothermal therapy

Melanins(eumelanin,pheomelanin,and allomelanin)represent a very,if not themost,important group of biological pigments.Their biological roles are multiple,from photoprotection to antioxidant activity,heavy metal disposal or the myriad uses of color in organisms across all Phyla.In the first part of this review,eumelanin biology and some chemical aspects will be presented,as well as key physico-chemical features that make this biological pigment so interesting.The principal characteristics of the melanocyte,the melanin-synthesizing cell in mammals,will also be introduced.Transformed melanocytes are the cause of one of the most devastating known cancers:the malignant melanoma.Epidemiology and molecular signaling aspects will be presented next,as well as the principal advances in promising oncotherapies designed and applied for the treatment of melanoma.In particular,on account of the photo-physical properties of melanin,special details will be provided regarding the use of photothermal therapy for melanoma treatment.

Discovering metabolic vulnerability using spatially resolved metabolomics for antitumor small molecule-drug conjugates development as a precise cancer therapy strategy

Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.

MR IMAGING ASSESSMENT OF IRREGULAR SHRINKAGE OF TUMOR MORPHOLOGY AND VOLUME IN CERVICAL CANCER DURING RADIATION THERAPY

To study the clinical significance of the morphological and volume changes in cervical cancer during an ongoing course of radiation therapy (RT) using MR imaging. Methods: Serial MR imaging examinations were performed in 60 advanced cervical cancer patients. MR imaging was obtained at the start of RT, at 20-25 Gy (2-2.5 weeks of RT), at 45-50 Gy (4-5 weeks of RT), and 1-2 month post-RT. Tumor morphology was classified qualitatively as well-defined (round/oval with a well-demarcated smooth margin) vs. lobulated vs. irregular and tumor volume was assessed in each serial MR examination independently by ROI volumetry and diameter volumetry. ROI volumetry was traced on the computer workstation with a trackball in each sagittal T2-weighted image and calculated by the summation of all tumor areas in each slice and multiplication by the slice profile. Diameter volumetry was to measure the largest three orthogonal tumor diameters in each orthogonal measurement plane and calculate as an ellipsoid formula (V=d1 x d2 x d3 x p/6). Serial tumor volume was compared between the two measurement methods. Results: The proportion of lobulated and irregular tumors increased early during RT and declined lately post-RT (68% pre-RT, 80% at 2-2.5 weeks of RT, 72% at 4-5 weeks of RT, 33% post-RT). Accordingly, ROI volumetry and diameter volumetry correlated well pre-RT (r1=0.89) and post-RT (r4=0.80), but poorly during RT (r2 = 0.17 at 2-2.5 weeks of RT, r3 = 0.69 at 4-5 weeks of RT). Conclusions: Cervical cancers regress in a non-uniform fashion during RT and undergo increasingly irregular shrinkage. Measurement with ROI volumetry techniques, which can optimally measure irregular volumes, provides better assessment of radiation response during treatment than diameter volumetry.

Evaluation of epithelial-mesenchymal transitioned circulating tumor cells in patients with resectable gastric cancer: Relevance to therapy response

AIM: To evaluate the epithelial-to-mesenchymal transition(EMT) of circulating tumor cells(CTCs) in gastric cancer patients.METHODS: We detected tumor cells for expression of four epithelial(E^+) transcripts(keratins 8, 18, and 19 and epithelial cell adhesion molecule) and two mesenchymal(M^+) transcripts(Vimentin and Twist) by a quantifiable, dual-colorimetric RNA-in situ hybridization assay. Between July 2014 and October 2014, 44 patients with gastric cancer were recruited for CTC evaluation. Blood samples were obtained from selected patients during the treatment course [before surgery, after surgery and at the 6^(th) cycle of XELOX based chemotherapy(about 6 mo postoperatively)].RESULTS: We found the EMT phenomenon in which there were a few biphenotypic E^+/M^+ cells in primary human gastric cancer specimens. Of the 44 patients, the presence of CTCs was reported in 35(79.5%) patients at baseline. Five types of cells including from exclusively E^+ CTCs to intermediate CTCs and exclusively M^+ CTCs were identified(4 patients with M^+ CTCs and 10 patients with M^+ or M^+ > E^+ CTCs). Further, a chemotherapy patient having progressive disease showed a proportional increase of mesenchymal CTCs in the post-treatment blood specimens. We used NCI-N87 cells to analyze the linearity and sensitivity of Can Patrol^(TM) system and the correlation coefficient(R^2) was 0.999.CONCLUSION: The findings suggest that the EMT phenomenon was both in a few cells of primary tumors and abundantly in CTCs from the blood of gastric cancer patients, which might be used to monitor therapy response.

Recent Advances in Tumor Microenvironment Hydrogen Peroxide-Responsive Materials for Cancer Photodynamic Therapy

Photodynamic therapy(PDT),as one of the noninvasive clinical cancer phototherapies,suffers from the key drawback associated with hypoxia at the tumor microenvironment(TME),which plays an important role in protecting tumor cells from damage caused by common treatments.High concentration of hydrogen peroxide(H2O2),one of the hallmarks of TME,has been recognized as a double-edged sword,posing both challenges,and opportunities for cancer therapy.The promising perspectives,strategies,and approaches for enhanced tumor therapies,including PDT,have been developed based on the fast advances in H2O2-enabled theranostic nanomedicine.In this review,we outline the latest advances in H2O2-responsive materials,including organic and inorganic materials for enhanced PDT.Finally,the challenges and opportunities for further research on H2O2-responsive anticancer agents are envisioned.

Endostatin enhances antitumor effect of tumor antigen-pulsed dendritic cell therapy in mouse xenograft model of lung carcinoma

Objective： To investigate the antitumor effect of endostatin combined with tumor antigen-pulsed dendritic cell （DC）-T cell therapy on lung cancer. Methods： Transplanted Lewis lung cancer （LLC） models of C57BL/6 mice were established by subcutaneous injection of LLC cells in left extremity axillary. Tumor antigen-pulsed DC-T cells from spleen cells and bone of mice were cultured in vitro. Tumor-bearing mice were randomly divided into three groups, including DC- T＋endostatin group, DC-T group, and phosphate-buffered saline （PBS） control group. Microvessel density （MVD） of tumor tissue in tumor-bearing mice was determined by immunohistochemistry （IHC）. The expressions of vascular endothelial growth factor （VEGF） and hypoxia-inducible factor-1α （HIF-1α） were determined by Western blotting and IHC staining. The proportions of CD8＋ T cells, mature dendritic cells （mDC）, tumor-associated macrophages [TAM （M1/M2）], and myeloid-derived suppressor cells （MDSC） in suspended cells of tumor tissue were determined by flow cytometry. The expressions of inter｜eukin （IL）-6, IL-10, IL-17, transforming growth factor-β（TGF-β） and interferon-γ （IFN-γ） in suspended cells of tumor tissue were detected by enzyme-linked immune sorbent assay （ELISA）. Results： DC-T cells combined with endostatin remarkably suppressed tumor growth. MVD of mice in DC- T＋endostatin group was significantly lower than that of the control group and DC-T monotherapy group. The expressions of VEGF, IL-6 and IL-17 in tumors were markedly decreased, but IFN-γ, and HIF-1α increased after treating with DC-T cells combined with endostatin, compared to control group and DC-T group. In the DC- T＋endostatin group, the proportions of MDSC and TAM （M2 type） were significantly decreased, mDC and TAM （Nil type） were up-regulated, and CD8＋ T cells were recruited to infiltrate tumors, in contrast to PBS control and DC-T monotherapy. DC-T cells combined with endostatin potently reduced the expressions of IL-6, IL-10, TGF-β and IL-17 in tumor tissue, and enhanced the expression of IFN-γ. Conclusions： The study indicated the synergic antitumor effects between endostatin and tumor antigen-pulsed DC-T cells, which may be a prospective therapy strategy to achieve potent antitumor effects on lung cancer.