Intratumoral bacteria have been proven to be widely exist in tumors,different tumors of different systems have different types of characteristic bacteria.Intratumoral bacteria will become a new and important biomarker...Intratumoral bacteria have been proven to be widely exist in tumors,different tumors of different systems have different types of characteristic bacteria.Intratumoral bacteria will become a new and important biomarker in the full cycle of tumor development.This article emphasizes the key role of intratumoral bacteria in the occurrence and progress of tumors,including promoting tumor development,accelerating tumor metastasis and promoting tumor cell resistance.In addition,this article also summarizes the application of intratumoral bacteria in tumor diagnosis and prognosis.Especially,this article outlines the treatment strategies of intratumoral bacteria,including non-nanodelivery therapy strategies and nanodelivery therapy strategies,such as antibiotic,macromolecular,inflammatory factor inhibitors,near-infrared-photothermal therapy,inorganic antibacterial agents,reactive species and microbes therapy,in these strategies,nano delivery system provides a promising treatment that solves the problem of drug resistance,reducing toxicity and improving patient compliance.This article is hoped to guide future research on intratumoral bacteria on tumors.展开更多
Background:Intratumoral flora and its metabolites play an important role in the occurrence,development and treatment of cancer,and are correlated with the genotype expression of breast cancer;However,the internal rela...Background:Intratumoral flora and its metabolites play an important role in the occurrence,development and treatment of cancer,and are correlated with the genotype expression of breast cancer;However,the internal relationship between intratumoral flora and triple negative breast cancer(TNBC)has not been elucidated.Methods:Fourteen patients with TNBC who met the criteria were included.The tumor tissues and adjacent tissues were respectively taken as the patient group and the control group.The 5R 16S sequencing technique was used to detect the abundance and distribution of the intratumoral flora between the two groups,and the differences between the groups were analyzed to find the bacteria with significant differences between groups(P<0.05).Results:The abundance of intratumoral microbiota in TNBC patients was significantly lower than that in adjacent tissues(P<0.05).The differential bacteria in TNBC tumors(P<0.05)included Acinetobacter,Renibacterium,Flavobacterium,Dechloromonas and others.The differential bacteria genera(P<0.05)in the adjacent tissues included Comamonas,Bacillus,Caulobacter,Afipia,Aerococcus,Roseomonas and so on.Conclusion:There is a significant difference in the flora structure between the tumor and normal tissues in TNBC patients.Proteobacteria plays an important role in the occurrence,development and treatment of TNBC.Among them,Acinetobacter may be the key reason for the metastasis of TNBC.展开更多
Objective To evaluate the therapeutic effects of percutaneous ethanol intratumoral injection (PEIT) for treatment of small primary liver cancer (SPLC).Methods 240 patients with surgically or pathologically proved SPLC...Objective To evaluate the therapeutic effects of percutaneous ethanol intratumoral injection (PEIT) for treatment of small primary liver cancer (SPLC).Methods 240 patients with surgically or pathologically proved SPLC ( < 3 cm in diameter) were treated by PEIT ( under the guidance of B-ultrasound) . Of the" 240 patients, 163 had recurrent liver cancer, 55 had inoperable liver cancer because of cardiac, pulmonary, hepatic and renal dysfunctions or due to the close proximity of tumor to the major vessels, and 22 refused to receive surgical resection. In 40 patients who received surgical resection after PEIT treatment, the resected tumors were pathologically evaluated for necrotic status and the patients were followed up postoperatively.Results Postoperative 1-, 2- and 3-year survival rate of the 240 patients was 94.9% , 84.2% and 66.3% respectively. Conclusion PEIT can be used as a non-invasive treatment for SPLC, and preoperative PEIT appears to be helpful in reducing recurrence of postoperative liver cancer.展开更多
AIM: To study the antineoplastic efficacy of 10% aspirin intralesional injection on VX2 hepatic tumors in a rabbit model. METHODS: Thirty-two male rabbits (age: 6-9 wk; body weight: 1700-2500 g) were inoculated with V...AIM: To study the antineoplastic efficacy of 10% aspirin intralesional injection on VX2 hepatic tumors in a rabbit model. METHODS: Thirty-two male rabbits (age: 6-9 wk; body weight: 1700-2500 g) were inoculated with VX2 hepatic tumor cells (104 cells/rabbit) via supraumbilical median laparotomy. On day 4 post-implantation, when the tumors were about 1 cm in diameter, the rabbits were randomly divided into the following groups (n = 8 each group) to assess early (24 h) and late (7 d) antineoplastic effects of intratumoral injection of 10% bicarbonate aspirin solution (experimental groups) in comparison to intratumoral injection of physiological saline solution (control groups): group 1, 24 h control; group 2, 24 h experimental; group 3, 7 d control; group 4, 7 d experimental. The serum biochemistry profile (measurements of glycemia, alkaline phosphatase, gamma-glutamyl transferase, aspartateaminotransferase, and alanine aminotransferase) and body weight measurements were obtained for all animals at the following time points: D0, before tumor implant; D4, day of treatment; D5, day of sacrifice for groups 1 and 2; D11, day of sacrifice for groups 3 and 4. Gross assessments of the abdominal and thoracic cavities were carried out upon sacrifice. The resected liver tissues, including hepatic tumors, were qualitatively (general morphology, signs of necrosis) and quantitatively (tumor area) assessed by histopathological analysis. RESULTS: Gross examination showed no alterations, besides the left hepatic lobe tumors, had occurred in the thoracic and abdominal cavities of any animal at any time point evaluated. However, the features of the tumor foci were distinctive between the groups. Compared to the control groups, which showed normal unabated tumor progression, the aspirin-treated groups showed imprecise but limited tumor boundaries and a general red-white coloration (indicating hemorrhaging) at 24 h post-treatment, and development of yellow-white areas of a cicatricial aspect at 7 d after treatment. At all time points evaluated, all except one biochemical parameters tested within the reference range (P > 0.05); a significant increase was detected in the alkaline phosphatase level of the control group 3 on D11 (P < 0.05). At 24 h post-treatment, the aspirintreated groups showed extensive coagulation necrosis accompanied by a remarkable absence of viable tumor foci; at 7 d after treatment, the tumors had completely disappeared in these animals and fibrous necrotic nod- ules had developed. In contrast, throughout the study course, the tumors of the control groups remained unchanged, showing tumor nodules without necrosis at the time point corresponding to 24 h post-treatment and increased amounts of tumor nodules at the time point corresponding to 7 d post-treatment. Quantitative analysis of the remaining tumor area revealed that the aspirin-treated groups had significantly smaller tumor foci at 24 h post-treatment (8.5% ± 0.7%) andat 7 d after treatment (11.0% ± 4.2%), compared to those in the control groups (24 h: 98.5% ± 1.5% and 7 d: 94.0% ± 2.7%; both,P < 0.005). CONCLUSION: Intralesional injection of a 10% aspirin solution causes destruction of VX2 hepatic tumors in rabbits without evidence of relapse at 7 d after treat- ment administration.展开更多
The in situ gelling hybrid hydrogel system has been reported to effectively concentratechemotherapeutic drugs at the tumor site and sustain their release for a long period.DTX-micelles(docetaxel-loaded mixed micelles)...The in situ gelling hybrid hydrogel system has been reported to effectively concentratechemotherapeutic drugs at the tumor site and sustain their release for a long period.DTX-micelles(docetaxel-loaded mixed micelles)are able to increase the solubility of DTX inwater,and then a high drug loading rate of hydrogels can be achieved by encapsulatingthe docetaxel-loaded mixed micelles into the hydrogels.The thermosensitive nature ofDTX-MM-hydrogels(thermosensitive hydrogels incorporated with docetaxel-loaded mixedmicelles)can accelerate the formation of a depot of this drug-loaded system at the siteof administration.Therefore,the hydrogels provide a much slower release compared withDTX-micelles and DTX-injection.An in vivo retention study has demonstrated that the DTX-MM-hydrogels can prolong the drug retention time and in viv o trials have shown that theDTX-MM-hydrogels have a higher antitumor efficacy and systemic safety.In conclusion,theDTX-MM-hydrogels prepared in this study have considerable potential as a drug deliverysystem,with higher tumor inhibition effects and are less toxic to normal tissues.展开更多
Purpose: Magnetic hyperthermia treatment (MHT) is a strategy for cancer therapy using the tem-perature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). Re-cently, a new imaging method c...Purpose: Magnetic hyperthermia treatment (MHT) is a strategy for cancer therapy using the tem-perature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). Re-cently, a new imaging method called magnetic particle imaging (MPI) has been introduced. MPI allows imaging of the spatial distribution of MNPs. The purpose of this study was to investigate the feasibility of visualizing and quantifying the intratumoral distribution and temporal change of MNPs and predicting the therapeutic effect of MHT using MPI. Materials and Methods: Colon-26 cells (1 × 106 cells) were implanted into the backs of eight-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, mice were divided into untreated (n = 10) and treated groups (n = 27). The tumors in the treated group were directly injected with MNPs (Resovist?) with iron concentrations of 500 mM (A, n = 9), 400 mM (B, n = 8), and 250 mM (C, n = 10), respectively, and MHT was performed using an AMF with a frequency of 600 kHz and a peak amplitude of 3.5 kA/m. The mice in the treated group were scanned using our MPI scanner immediately before, immediately after, 7 days, and 14 days after MHT. We drew a region of interest (ROI) on the tumor in the MPI image and calculated the average, maximum, and total MPI values and the number of pixels by taking the threshold value for extracting the contour as 40% of the maximum MPI value (pixel value) within the ROI. These parameters in the untreated group were taken as zero. We also measured the relative tumor volume growth (RTVG) defined by (V-V0)/V0, where V0 and V are the tumor volumes immediately before and after MHT, respectively. Results: The average, maximum, and total MPI values decreased up to 7 days after MHT and remained almost constant thereafter in all groups, whereas the number of pixels tended to increase with time. The RTVG values in Groups A and B were significantly lower than those in the control group 3 days or more and 5 days or more after MHT, respectively. The above four parameters were significantly inversely correlated with the RTVG values 5, 7, and 14 days after MHT. Conclusion: MPI can visualize and quantify the intratumoral distribution and temporal change of MNPs before and after MHT. Our results suggest that MPI will be useful for predicting the therapeutic effect of MHT and for the treatment planning of MHT.展开更多
The present study made in 92 mice showed that hydrogen peroxide com-pound injected directly into the tumor could to some extent sensitize the hypoxiccells of S180 solid tumor to radiate,for example,both the tumor regr...The present study made in 92 mice showed that hydrogen peroxide com-pound injected directly into the tumor could to some extent sensitize the hypoxiccells of S180 solid tumor to radiate,for example,both the tumor regression rateand the mouse survival rate 40d after radiation in the hydrogen peroxide com-pound group were significantly greater than those in the radiation alone group.The increasing rate of tumor diameter in 10d was 77.10%,47.09%,and 47.47%-10.4% in groups of control,radiation alone,radiosensitizer alone,radiationand hydrogen peroxide compound,respectively.Some of the problems aboutthe intratumoral injection of radiosensitizer were discussed.展开更多
As a key component of tumor microenvironment,the microbiota has gradually played a key role in cancer research.Particularly in colorectal cancer,the specific population of microbiota within the tumor shows a strong as...As a key component of tumor microenvironment,the microbiota has gradually played a key role in cancer research.Particularly in colorectal cancer,the specific population of microbiota within the tumor shows a strong association with the tumor type.Although the existence and potential role of microbiota in tumors have been recognized,the specific associations between the microbiota and tumor tissue and the mechanism of action still need to be further explored.This paper reviews the discovery,origin,and emerging role of the intratumor microbiota in the immune microenvironment and systematically outlines the oncogenic and metastasis-promoting strategies of the intratumor microbiota.Moreover,it comprehensively and holistically evaluates therapeutic strategies and prognostic performance on the basis of the intratumor microbiota,with the goal of providing strong support for future research and clinical practice.展开更多
The intratumor microbiome,one of the hallmarks of cancer,plays a crucial role in cancer progression through its interaction with the host.However,the underlying mechanisms remain poorly understood.In this study,six pu...The intratumor microbiome,one of the hallmarks of cancer,plays a crucial role in cancer progression through its interaction with the host.However,the underlying mechanisms remain poorly understood.In this study,six publicly available single-cell transcriptomic lung cancer datasets(comprising 178 samples)from multiple centers(Shanghai,New York,Seoul)were integrated to investigate the heterogeneity of host-microbiome interactions at the single-cell level using single-cell analysis of host-microbiome interactions(SAHMI).The results indicate that primary tumor tissues have a high proportion of fungi-associated cells,whereas metastatic brain tissues predominantly contain bacteria-associated cells.There are also distinct microbial distributions across cell types.Notably,the presence of specific bacteria significantly influences the transcriptome of resident host cells,including T cells and macrophages,by modulating pathways related to ribosomal RNA(rRNA)processing,cellular responses to stress and stimuli,and RNA and protein metabolism.Finally,specific cell-associated bacteria are significantly correlated with clinical features,such as lung cancer stages and smoking frequency.These single-cell insights into microbiome-host interactions improve current understanding about lung cancer development and progression and offer potential micro-ecological and diagnostic insights.展开更多
Metastatic dissemination is the major cause of death from breast-cancer(BC).Fusobacterium nucleatum(F.n)is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metast...Metastatic dissemination is the major cause of death from breast-cancer(BC).Fusobacterium nucleatum(F.n)is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis.Here,with an experimental model,we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes.Therefore,the F.n may be a potential target to prevent metastasis.Given the fact that cancer-associated fibroblasts(CAFs)are abundant in BC and located near blood vessels,we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37,with the characteristics of biosafety and freely intercellular trafficking,for depleting intratumoral F.n,leading to a 72.1%reduction in lung metastatic nodules number without affecting the balance of the systemic flora.Notably,mild photothermal treatment was found that could normalize CAF,contributing to synergistically inhibiting BC metastasis.In addition,the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor.Together,our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.展开更多
Intratumoral microorganisms have been detected in multiple cancer types,which can significantly affect the tumor progression and antitumor treatment efficacy.Considering the important role of intratumoral microorganis...Intratumoral microorganisms have been detected in multiple cancer types,which can significantly affect the tumor progression and antitumor treatment efficacy.Considering the important role of intratumoral microorganisms in cancer development,novel therapeutic and diagnostic approaches based on living bacteria have received increasing attention in oncology.In addition to wild types,bacteria can also be programmed through synthetic biology techniques to enhance the spatial and temporal controllability.Therefore,once perfected,intratumoral microorganisms can be combined with immunotherapy or other powerful antitumor agents and possibly unlock the next generation of precision cancer diagnosis and therapy.Moreover,the current challenges and perspectives have also been discussed.展开更多
The intestinal and intratumoral microbiota are closely associated with tumor progression and response to antitumor treatments.The antibacterial or tumor microenvironment(TME)-modulating approaches have been shown to m...The intestinal and intratumoral microbiota are closely associated with tumor progression and response to antitumor treatments.The antibacterial or tumor microenvironment(TME)-modulating approaches have been shown to markedly improve antitumor efficacy,strategies focused on normalizing the microbial environment are rarely reported.Here,we reported the development of an orally administered inulin-based hydrogel with colon-targeting and retention effects,containing hollow MnO^(2) nanocarrier loaded with the chemotherapeutic drug Oxa(Oxa@HMI).On the one hand,beneficial bacteria in the colon specifically metabolized Oxa@HMI,resulting in the degradation of inulin and the generation of short-chain fatty acids(SCFAs).These SCFAs play a crucial role in modulating microbiota and stimulating immune responses.On the other hand,the hydrogel matrix underwent colon microbiota-specific degradation,enabling the targeted release of Oxa and production of reactive oxygen species in the acidic TME.In this study,we have established,for the first time,a microbiota-targeted drug delivery system Oxa@HMI that exhibited high efficiency in colorectal cancer targeting and colon retention.Oxa@HMI promoted chemotherapy efficiency and activated antitumor immune responses by intervening in the microbial environment within the tumor tissue,providing a crucial clinical approach for the treatment of colorectal cancer that susceptible to microbial invasion.展开更多
To the Editor:As early as in the mid-19th century,microbiologists first recognized multiple microorganisms within human tumors.Nevertheless,the perceptions of intratumor microbiome have made little progression during ...To the Editor:As early as in the mid-19th century,microbiologists first recognized multiple microorganisms within human tumors.Nevertheless,the perceptions of intratumor microbiome have made little progression during the first 50 years of the 20th century owing to contamination interference,experimental irreproducibility,and technical limitations.Strikingly,in the past decade,the advances in detection techniques and analytical tools have been opening unprecedented opportunities to widely investigate the manifold characteristics of low-biomass intratumor microbiome and host–microbe interplays.In the early second decade of the 21st century,researchers focusing on the intratumor microbiome gradually emerged.Initially,this adventurous perspective failed to draw much attention because tumors were still considered sterile in the mainstream belief at that time.展开更多
Gemcitabine(Gem)is the gold-standard chemotherapeutic drug for pancreatic cancer therapy in clinic.However,intratumoral bacteria can metabolize Gem into an inactive form,leading to Gem resistance.To address this chall...Gemcitabine(Gem)is the gold-standard chemotherapeutic drug for pancreatic cancer therapy in clinic.However,intratumoral bacteria can metabolize Gem into an inactive form,leading to Gem resistance.To address this challenge,Zn^(2+)-containing nanoparticles(ZGP NPs)are used to eliminate intracellular bacteria to enhance the therapeutic efficacy of Gem in pancreatic therapy.ZGP NPs are prepared via a facile one-pot method using Zn2+,epigallocatechin gallate(EGCG),and polyethylene glycol(PEG),which prevents metal ion chelation by proteins and ensures antibacterial activity.Leveraging the pH-responsive disassembly of metal-phenolic networks,ZGP NPs can be degraded in acidic lysosomes after cellular uptake,releasing Zn^(2+)to eliminate intracellular bacteria and thereby protecting Gem from bacteria-mediated inactivation.Moreover,the elimination of intratumoral bacteria enhances immunotherapy.The delivery of Zn^(2+)via ZGP NPs presents a promising strategy to eliminate intratumoral bacteria to overcome Gem resistance in pancreatic cancer therapy.展开更多
Dear Editor,In patients with early-stage non-small cell lung cancer(NSCLC),the risk of post-surgical recurrence(REC)is 20%–50%,[1]and the risk of developing a second primary lung cancer(2P)is 3–4 times higher than i...Dear Editor,In patients with early-stage non-small cell lung cancer(NSCLC),the risk of post-surgical recurrence(REC)is 20%–50%,[1]and the risk of developing a second primary lung cancer(2P)is 3–4 times higher than in the general population[2].Distinguishing between REC and 2P can be challenging,complicating treatment of these so called“equivocal”(EQU)cases.展开更多
Brain tumors are the most prevalent solid tumors in pediatrics,with atypical teratoid and rhabdoid tumor(ATRT)and embryonal tumor with multilayered rosettes(ETMR)presenting particularly poor prognoses.
Tumor-targeted delivery of nanomedicine is of great importance to improve therapeutic efficacy of cancer and minimize systemic side effects.Unfortunately,nowadays the targeting efficiency of nanomedicine toward tumor ...Tumor-targeted delivery of nanomedicine is of great importance to improve therapeutic efficacy of cancer and minimize systemic side effects.Unfortunately,nowadays the targeting efficiency of nanomedicine toward tumor is still quite limited and far from clinical requirements.In this work,we develop an innovative peptide-based nanoparticle to realize light-triggered nitric oxide(NO)release and structural transformation for enhanced intratumoral retention and simultaneously sensitizing photodynamic therapy(PDT).The designed nanoparticle is self-assembled from a chimeric peptide monomer,TPP-RRRKLVFFK-Ce6,which contains a photosensitive moiety(chlorin e6,Ce6),aβ-sheet-forming peptide domain(Lys-Leu-Val-Phe-Phe,KLVFF),an oligoarginine domain(RRR)as NO donor and a triphenylphosphonium(TPP)moiety for targeting mitochondria.When irradiated by light,the constructed nanoparticles undergo rapid structural transformation from nanosphere to nanorod,enabling to achieve a significantly higher intratumoral accumulation by 3.26 times compared to that without light irradiation.More importantly,the conversion of generated NO and reactive oxygen species(ROS)in a light-responsive way to peroxynitrite anions(ONOO)with higher cytotoxicity enables NO to sensitize PDT in cancer treatment.Both in vitro and in vivo studies demonstrate that NO sensitized PDT based on the well-designed transformable nanoparticles enables to eradicate tumors efficiently.The light-triggered transformable nanoplatform developed in this work provides a new strategy for enhanced intratumoral retention and improved therapeutic outcome.展开更多
Insufficient intratumoral penetration greatly hurdles the anticancer performance of nanomedicine. To realize highly efficient tumor penetration in a precisely and spatiotemporally controlled manner, far-red light-resp...Insufficient intratumoral penetration greatly hurdles the anticancer performance of nanomedicine. To realize highly efficient tumor penetration in a precisely and spatiotemporally controlled manner, far-red light-responsive nanoclusters (NCs) capable of size shrinkage and charge conversion were developed and co-administered with iRGD to synergistically improve the intratumoral penetration and the anticancer efficacy. The NCs were constructed using the singlet oxygen-sensitive (SOS) polyethylene glycolpolyurethane-polyethylene glycol (PEG-(1O2)PU-PEG) triblock copolymer to encapsulate the doxorubicin (DOX)-loaded, chlorin e6 (Ce6)-conjugated polyamindoamine (PAMAM) dendrimer (DCD) via the double-emulsion method. Co-administration of iRGD notably increased the permeability of NCs within tumor vasculature and tumor tissues. In addition, upon far-red light irradiation (660 nm) of tumors at low optical density (10 mW/cm2), the generated 1O2 could disintegrate the NCs and release the DCD with positive surface charge and ultra-small size (~ 5 nm), which synergized with iRGD to enable deep intratumoral penetration. Consequently, the local 1O2 at lethal concentrations along with the released DOX efficiently and cooperatively eradicated tumor cells. This study provides a convenient approach to spatiotemporally promote the intratumoral penetration of nanomedicine and mediate programmed anticancer therapy.展开更多
The intratumoral microbiome(TM)refers to the microorganisms in the tumor tissues,including bacteria,fungi,viruses,and so on,and is distinct from the gut microbiome and circulating microbiota.TM is strongly associated ...The intratumoral microbiome(TM)refers to the microorganisms in the tumor tissues,including bacteria,fungi,viruses,and so on,and is distinct from the gut microbiome and circulating microbiota.TM is strongly associated with tumorigenesis,progression,metastasis,and response to therapy.This paper highlights the current status of TM.Tract sources,adjacent normal tissue,circulatory system,and concomitant tumor co-metastasis are the main origin of TM.The advanced techniques in TM analysis are comprehensively summarized.Besides,TMis involved in tumor progression through several mechanisms,including DNA damage,activation of oncogenic signaling pathways(phosphoinositide 3-kinase[PI3K],signal transducer and activator of transcription[STAT],WNT/β-catenin,and extracellular regulated protein kinases[ERK]),influence of cytokines and induce inflammatory responses,and interaction with the tumor microenvironment(anti-tumor immunity,pro-tumor immunity,and microbial-derived metabolites).Moreover,promising directions of TM in tumor therapy include immunotherapy,chemotherapy,radiotherapy,the application of probiotics/prebiotics/synbiotics,fecal microbiome transplantation,engineered microbiota,phage therapy,and oncolytic virus therapy.The inherent challenges of clinical application are also summarized.This review provides a comprehensive landscape for analyzing TM,especially the TM-related mechanisms and TM-based treatment in cancer.展开更多
基金supported by CAMS Innovation Fund for Medical Sciences(CIFMS),China(No.2021-I2M-1-026)。
文摘Intratumoral bacteria have been proven to be widely exist in tumors,different tumors of different systems have different types of characteristic bacteria.Intratumoral bacteria will become a new and important biomarker in the full cycle of tumor development.This article emphasizes the key role of intratumoral bacteria in the occurrence and progress of tumors,including promoting tumor development,accelerating tumor metastasis and promoting tumor cell resistance.In addition,this article also summarizes the application of intratumoral bacteria in tumor diagnosis and prognosis.Especially,this article outlines the treatment strategies of intratumoral bacteria,including non-nanodelivery therapy strategies and nanodelivery therapy strategies,such as antibiotic,macromolecular,inflammatory factor inhibitors,near-infrared-photothermal therapy,inorganic antibacterial agents,reactive species and microbes therapy,in these strategies,nano delivery system provides a promising treatment that solves the problem of drug resistance,reducing toxicity and improving patient compliance.This article is hoped to guide future research on intratumoral bacteria on tumors.
基金Administration of Traditional Chinese Medicine of Zhejiang Province and Young Talents Fund Project of Zhejiang Province Traditional Chinese Medicine Scienese and Technology Project(2022ZQ015).
文摘Background:Intratumoral flora and its metabolites play an important role in the occurrence,development and treatment of cancer,and are correlated with the genotype expression of breast cancer;However,the internal relationship between intratumoral flora and triple negative breast cancer(TNBC)has not been elucidated.Methods:Fourteen patients with TNBC who met the criteria were included.The tumor tissues and adjacent tissues were respectively taken as the patient group and the control group.The 5R 16S sequencing technique was used to detect the abundance and distribution of the intratumoral flora between the two groups,and the differences between the groups were analyzed to find the bacteria with significant differences between groups(P<0.05).Results:The abundance of intratumoral microbiota in TNBC patients was significantly lower than that in adjacent tissues(P<0.05).The differential bacteria in TNBC tumors(P<0.05)included Acinetobacter,Renibacterium,Flavobacterium,Dechloromonas and others.The differential bacteria genera(P<0.05)in the adjacent tissues included Comamonas,Bacillus,Caulobacter,Afipia,Aerococcus,Roseomonas and so on.Conclusion:There is a significant difference in the flora structure between the tumor and normal tissues in TNBC patients.Proteobacteria plays an important role in the occurrence,development and treatment of TNBC.Among them,Acinetobacter may be the key reason for the metastasis of TNBC.
文摘Objective To evaluate the therapeutic effects of percutaneous ethanol intratumoral injection (PEIT) for treatment of small primary liver cancer (SPLC).Methods 240 patients with surgically or pathologically proved SPLC ( < 3 cm in diameter) were treated by PEIT ( under the guidance of B-ultrasound) . Of the" 240 patients, 163 had recurrent liver cancer, 55 had inoperable liver cancer because of cardiac, pulmonary, hepatic and renal dysfunctions or due to the close proximity of tumor to the major vessels, and 22 refused to receive surgical resection. In 40 patients who received surgical resection after PEIT treatment, the resected tumors were pathologically evaluated for necrotic status and the patients were followed up postoperatively.Results Postoperative 1-, 2- and 3-year survival rate of the 240 patients was 94.9% , 84.2% and 66.3% respectively. Conclusion PEIT can be used as a non-invasive treatment for SPLC, and preoperative PEIT appears to be helpful in reducing recurrence of postoperative liver cancer.
文摘AIM: To study the antineoplastic efficacy of 10% aspirin intralesional injection on VX2 hepatic tumors in a rabbit model. METHODS: Thirty-two male rabbits (age: 6-9 wk; body weight: 1700-2500 g) were inoculated with VX2 hepatic tumor cells (104 cells/rabbit) via supraumbilical median laparotomy. On day 4 post-implantation, when the tumors were about 1 cm in diameter, the rabbits were randomly divided into the following groups (n = 8 each group) to assess early (24 h) and late (7 d) antineoplastic effects of intratumoral injection of 10% bicarbonate aspirin solution (experimental groups) in comparison to intratumoral injection of physiological saline solution (control groups): group 1, 24 h control; group 2, 24 h experimental; group 3, 7 d control; group 4, 7 d experimental. The serum biochemistry profile (measurements of glycemia, alkaline phosphatase, gamma-glutamyl transferase, aspartateaminotransferase, and alanine aminotransferase) and body weight measurements were obtained for all animals at the following time points: D0, before tumor implant; D4, day of treatment; D5, day of sacrifice for groups 1 and 2; D11, day of sacrifice for groups 3 and 4. Gross assessments of the abdominal and thoracic cavities were carried out upon sacrifice. The resected liver tissues, including hepatic tumors, were qualitatively (general morphology, signs of necrosis) and quantitatively (tumor area) assessed by histopathological analysis. RESULTS: Gross examination showed no alterations, besides the left hepatic lobe tumors, had occurred in the thoracic and abdominal cavities of any animal at any time point evaluated. However, the features of the tumor foci were distinctive between the groups. Compared to the control groups, which showed normal unabated tumor progression, the aspirin-treated groups showed imprecise but limited tumor boundaries and a general red-white coloration (indicating hemorrhaging) at 24 h post-treatment, and development of yellow-white areas of a cicatricial aspect at 7 d after treatment. At all time points evaluated, all except one biochemical parameters tested within the reference range (P > 0.05); a significant increase was detected in the alkaline phosphatase level of the control group 3 on D11 (P < 0.05). At 24 h post-treatment, the aspirintreated groups showed extensive coagulation necrosis accompanied by a remarkable absence of viable tumor foci; at 7 d after treatment, the tumors had completely disappeared in these animals and fibrous necrotic nod- ules had developed. In contrast, throughout the study course, the tumors of the control groups remained unchanged, showing tumor nodules without necrosis at the time point corresponding to 24 h post-treatment and increased amounts of tumor nodules at the time point corresponding to 7 d post-treatment. Quantitative analysis of the remaining tumor area revealed that the aspirin-treated groups had significantly smaller tumor foci at 24 h post-treatment (8.5% ± 0.7%) andat 7 d after treatment (11.0% ± 4.2%), compared to those in the control groups (24 h: 98.5% ± 1.5% and 7 d: 94.0% ± 2.7%; both,P < 0.005). CONCLUSION: Intralesional injection of a 10% aspirin solution causes destruction of VX2 hepatic tumors in rabbits without evidence of relapse at 7 d after treat- ment administration.
基金financial support to the National Natural Science Foundation of China(81202480,81302723)the Natural Science Foundation of Liaoning Province(2015020749)+1 种基金the Innovative training program for college students(201710163000080)support of the Pharmacology Laboratory Centre and the Animal Centre of Shenyang Pharmaceutical University
文摘The in situ gelling hybrid hydrogel system has been reported to effectively concentratechemotherapeutic drugs at the tumor site and sustain their release for a long period.DTX-micelles(docetaxel-loaded mixed micelles)are able to increase the solubility of DTX inwater,and then a high drug loading rate of hydrogels can be achieved by encapsulatingthe docetaxel-loaded mixed micelles into the hydrogels.The thermosensitive nature ofDTX-MM-hydrogels(thermosensitive hydrogels incorporated with docetaxel-loaded mixedmicelles)can accelerate the formation of a depot of this drug-loaded system at the siteof administration.Therefore,the hydrogels provide a much slower release compared withDTX-micelles and DTX-injection.An in vivo retention study has demonstrated that the DTX-MM-hydrogels can prolong the drug retention time and in viv o trials have shown that theDTX-MM-hydrogels have a higher antitumor efficacy and systemic safety.In conclusion,theDTX-MM-hydrogels prepared in this study have considerable potential as a drug deliverysystem,with higher tumor inhibition effects and are less toxic to normal tissues.
文摘Purpose: Magnetic hyperthermia treatment (MHT) is a strategy for cancer therapy using the tem-perature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). Re-cently, a new imaging method called magnetic particle imaging (MPI) has been introduced. MPI allows imaging of the spatial distribution of MNPs. The purpose of this study was to investigate the feasibility of visualizing and quantifying the intratumoral distribution and temporal change of MNPs and predicting the therapeutic effect of MHT using MPI. Materials and Methods: Colon-26 cells (1 × 106 cells) were implanted into the backs of eight-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, mice were divided into untreated (n = 10) and treated groups (n = 27). The tumors in the treated group were directly injected with MNPs (Resovist?) with iron concentrations of 500 mM (A, n = 9), 400 mM (B, n = 8), and 250 mM (C, n = 10), respectively, and MHT was performed using an AMF with a frequency of 600 kHz and a peak amplitude of 3.5 kA/m. The mice in the treated group were scanned using our MPI scanner immediately before, immediately after, 7 days, and 14 days after MHT. We drew a region of interest (ROI) on the tumor in the MPI image and calculated the average, maximum, and total MPI values and the number of pixels by taking the threshold value for extracting the contour as 40% of the maximum MPI value (pixel value) within the ROI. These parameters in the untreated group were taken as zero. We also measured the relative tumor volume growth (RTVG) defined by (V-V0)/V0, where V0 and V are the tumor volumes immediately before and after MHT, respectively. Results: The average, maximum, and total MPI values decreased up to 7 days after MHT and remained almost constant thereafter in all groups, whereas the number of pixels tended to increase with time. The RTVG values in Groups A and B were significantly lower than those in the control group 3 days or more and 5 days or more after MHT, respectively. The above four parameters were significantly inversely correlated with the RTVG values 5, 7, and 14 days after MHT. Conclusion: MPI can visualize and quantify the intratumoral distribution and temporal change of MNPs before and after MHT. Our results suggest that MPI will be useful for predicting the therapeutic effect of MHT and for the treatment planning of MHT.
文摘The present study made in 92 mice showed that hydrogen peroxide com-pound injected directly into the tumor could to some extent sensitize the hypoxiccells of S180 solid tumor to radiate,for example,both the tumor regression rateand the mouse survival rate 40d after radiation in the hydrogen peroxide com-pound group were significantly greater than those in the radiation alone group.The increasing rate of tumor diameter in 10d was 77.10%,47.09%,and 47.47%-10.4% in groups of control,radiation alone,radiosensitizer alone,radiationand hydrogen peroxide compound,respectively.Some of the problems aboutthe intratumoral injection of radiosensitizer were discussed.
基金funded by the National Natural Science Foundation of China(No.82060453,82103645 and 82260596)the Natural Science Foundation of Jiangxi Province(No.20242BAB25506)the China Postdoctoral Science Foundation(No.2023M741523)。
文摘As a key component of tumor microenvironment,the microbiota has gradually played a key role in cancer research.Particularly in colorectal cancer,the specific population of microbiota within the tumor shows a strong association with the tumor type.Although the existence and potential role of microbiota in tumors have been recognized,the specific associations between the microbiota and tumor tissue and the mechanism of action still need to be further explored.This paper reviews the discovery,origin,and emerging role of the intratumor microbiota in the immune microenvironment and systematically outlines the oncogenic and metastasis-promoting strategies of the intratumor microbiota.Moreover,it comprehensively and holistically evaluates therapeutic strategies and prognostic performance on the basis of the intratumor microbiota,with the goal of providing strong support for future research and clinical practice.
基金funding from the MOST Key R&D Program of China(Grant numbers 2022YFC2304703 and 2020YFA0907200)the Natural Science Foundation of China(Grant numbers 32270202 and 62372286)+2 种基金Program of Shanghai Academic/Technology Research Leader(Grant number 23XD1422300)Science and Technology Innovation Plan of Shanghai(Grant number 23JC1403200)Innovative research team of high-level local universities in Shanghai are greatly appreciated by all the authors.
文摘The intratumor microbiome,one of the hallmarks of cancer,plays a crucial role in cancer progression through its interaction with the host.However,the underlying mechanisms remain poorly understood.In this study,six publicly available single-cell transcriptomic lung cancer datasets(comprising 178 samples)from multiple centers(Shanghai,New York,Seoul)were integrated to investigate the heterogeneity of host-microbiome interactions at the single-cell level using single-cell analysis of host-microbiome interactions(SAHMI).The results indicate that primary tumor tissues have a high proportion of fungi-associated cells,whereas metastatic brain tissues predominantly contain bacteria-associated cells.There are also distinct microbial distributions across cell types.Notably,the presence of specific bacteria significantly influences the transcriptome of resident host cells,including T cells and macrophages,by modulating pathways related to ribosomal RNA(rRNA)processing,cellular responses to stress and stimuli,and RNA and protein metabolism.Finally,specific cell-associated bacteria are significantly correlated with clinical features,such as lung cancer stages and smoking frequency.These single-cell insights into microbiome-host interactions improve current understanding about lung cancer development and progression and offer potential micro-ecological and diagnostic insights.
基金supported by the National Natural Science Foundation of China(82172762,21904119,and 82073395)Science and technology innovation talents support project of Henan Province(23HASTIT041)Henan Science Fund for Outstanding Young Scholars(232300421051,China).
文摘Metastatic dissemination is the major cause of death from breast-cancer(BC).Fusobacterium nucleatum(F.n)is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis.Here,with an experimental model,we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes.Therefore,the F.n may be a potential target to prevent metastasis.Given the fact that cancer-associated fibroblasts(CAFs)are abundant in BC and located near blood vessels,we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37,with the characteristics of biosafety and freely intercellular trafficking,for depleting intratumoral F.n,leading to a 72.1%reduction in lung metastatic nodules number without affecting the balance of the systemic flora.Notably,mild photothermal treatment was found that could normalize CAF,contributing to synergistically inhibiting BC metastasis.In addition,the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor.Together,our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.
基金supported by grants from the National Key R&D Program of China(2021YFA0909900)the CAS Project for Young Scientists in Basic Research(YSBR-010)+2 种基金the Beijing Natural Science Foundation(Z200020)the Beijing Nova Program(Z201100006820031)the National Natural Science Foundation of China(32222045 and 32171384).
文摘Intratumoral microorganisms have been detected in multiple cancer types,which can significantly affect the tumor progression and antitumor treatment efficacy.Considering the important role of intratumoral microorganisms in cancer development,novel therapeutic and diagnostic approaches based on living bacteria have received increasing attention in oncology.In addition to wild types,bacteria can also be programmed through synthetic biology techniques to enhance the spatial and temporal controllability.Therefore,once perfected,intratumoral microorganisms can be combined with immunotherapy or other powerful antitumor agents and possibly unlock the next generation of precision cancer diagnosis and therapy.Moreover,the current challenges and perspectives have also been discussed.
基金supported by the Natural Science Foundation of Guangdong Province(2023A1515030291)Science and Technology Program of Guangzhou(202201011130280065)Dongguan Science and Technology of Social Development Program(20211800905282).
文摘The intestinal and intratumoral microbiota are closely associated with tumor progression and response to antitumor treatments.The antibacterial or tumor microenvironment(TME)-modulating approaches have been shown to markedly improve antitumor efficacy,strategies focused on normalizing the microbial environment are rarely reported.Here,we reported the development of an orally administered inulin-based hydrogel with colon-targeting and retention effects,containing hollow MnO^(2) nanocarrier loaded with the chemotherapeutic drug Oxa(Oxa@HMI).On the one hand,beneficial bacteria in the colon specifically metabolized Oxa@HMI,resulting in the degradation of inulin and the generation of short-chain fatty acids(SCFAs).These SCFAs play a crucial role in modulating microbiota and stimulating immune responses.On the other hand,the hydrogel matrix underwent colon microbiota-specific degradation,enabling the targeted release of Oxa and production of reactive oxygen species in the acidic TME.In this study,we have established,for the first time,a microbiota-targeted drug delivery system Oxa@HMI that exhibited high efficiency in colorectal cancer targeting and colon retention.Oxa@HMI promoted chemotherapy efficiency and activated antitumor immune responses by intervening in the microbial environment within the tumor tissue,providing a crucial clinical approach for the treatment of colorectal cancer that susceptible to microbial invasion.
基金This work was supported by the National Natural Science Foundation of China(No.82150006)Chinese Society of Clinical Oncology Research Foundation(Nos.Y-HR2017-117,Y-HH202102-0060)+2 种基金Beijing Medical and Health Foundation(No.YWJKJJHKYJJ-F3046D)Qujiang District Quzhou City Life Oasis Public Service Center(No.BJHA-CRP-040)Wu Jieping Medical Foundation(No.320.6750.2023-05-10)to Yawen Gao.
文摘To the Editor:As early as in the mid-19th century,microbiologists first recognized multiple microorganisms within human tumors.Nevertheless,the perceptions of intratumor microbiome have made little progression during the first 50 years of the 20th century owing to contamination interference,experimental irreproducibility,and technical limitations.Strikingly,in the past decade,the advances in detection techniques and analytical tools have been opening unprecedented opportunities to widely investigate the manifold characteristics of low-biomass intratumor microbiome and host–microbe interplays.In the early second decade of the 21st century,researchers focusing on the intratumor microbiome gradually emerged.Initially,this adventurous perspective failed to draw much attention because tumors were still considered sterile in the mainstream belief at that time.
基金the National Natural Science Foundation of China(Nos.52473152,and 52273154)the Key Project of Natural Science Foundation of Zhejiang Province(No.LZ23B040002)is gratefully acknowledged.
文摘Gemcitabine(Gem)is the gold-standard chemotherapeutic drug for pancreatic cancer therapy in clinic.However,intratumoral bacteria can metabolize Gem into an inactive form,leading to Gem resistance.To address this challenge,Zn^(2+)-containing nanoparticles(ZGP NPs)are used to eliminate intracellular bacteria to enhance the therapeutic efficacy of Gem in pancreatic therapy.ZGP NPs are prepared via a facile one-pot method using Zn2+,epigallocatechin gallate(EGCG),and polyethylene glycol(PEG),which prevents metal ion chelation by proteins and ensures antibacterial activity.Leveraging the pH-responsive disassembly of metal-phenolic networks,ZGP NPs can be degraded in acidic lysosomes after cellular uptake,releasing Zn^(2+)to eliminate intracellular bacteria and thereby protecting Gem from bacteria-mediated inactivation.Moreover,the elimination of intratumoral bacteria enhances immunotherapy.The delivery of Zn^(2+)via ZGP NPs presents a promising strategy to eliminate intratumoral bacteria to overcome Gem resistance in pancreatic cancer therapy.
基金supported by the National Cancer Institute(Grants No.R01-80127,Yang and R01-84354,P.Y.)the National Institutes of Health(Grant No.LM-R01-13438,L.L.,J.W.,and P.Y.).
文摘Dear Editor,In patients with early-stage non-small cell lung cancer(NSCLC),the risk of post-surgical recurrence(REC)is 20%–50%,[1]and the risk of developing a second primary lung cancer(2P)is 3–4 times higher than in the general population[2].Distinguishing between REC and 2P can be challenging,complicating treatment of these so called“equivocal”(EQU)cases.
基金supported by funds from the“Medizinerkolleg Münster”(21-0007)as well as Paula Aust(22-0028)KorneliusKerl received funding fromFight Kids Cancer(“EpiRT”),“Deutsche Forschungsgemeinschaft”(KE 2004/4-1)Deutsche Kinderkrebshilfe(70114460).
文摘Brain tumors are the most prevalent solid tumors in pediatrics,with atypical teratoid and rhabdoid tumor(ATRT)and embryonal tumor with multilayered rosettes(ETMR)presenting particularly poor prognoses.
基金financially supported by National Natural Science Foundation of China(51872188)Shenzhen Basic Research Program(SGDX20201103093600004)+3 种基金Special Funds for the Development of Strategic Emerging Industries in Shenzhen(20180309154519685)SZU Top Ranking Project(860-00000210)Basic and Applied Basic Research Foundation of Guangdong Province(2019A1515110294)the Postdoctoral Science Foundation of China(2020M672798).
文摘Tumor-targeted delivery of nanomedicine is of great importance to improve therapeutic efficacy of cancer and minimize systemic side effects.Unfortunately,nowadays the targeting efficiency of nanomedicine toward tumor is still quite limited and far from clinical requirements.In this work,we develop an innovative peptide-based nanoparticle to realize light-triggered nitric oxide(NO)release and structural transformation for enhanced intratumoral retention and simultaneously sensitizing photodynamic therapy(PDT).The designed nanoparticle is self-assembled from a chimeric peptide monomer,TPP-RRRKLVFFK-Ce6,which contains a photosensitive moiety(chlorin e6,Ce6),aβ-sheet-forming peptide domain(Lys-Leu-Val-Phe-Phe,KLVFF),an oligoarginine domain(RRR)as NO donor and a triphenylphosphonium(TPP)moiety for targeting mitochondria.When irradiated by light,the constructed nanoparticles undergo rapid structural transformation from nanosphere to nanorod,enabling to achieve a significantly higher intratumoral accumulation by 3.26 times compared to that without light irradiation.More importantly,the conversion of generated NO and reactive oxygen species(ROS)in a light-responsive way to peroxynitrite anions(ONOO)with higher cytotoxicity enables NO to sensitize PDT in cancer treatment.Both in vitro and in vivo studies demonstrate that NO sensitized PDT based on the well-designed transformable nanoparticles enables to eradicate tumors efficiently.The light-triggered transformable nanoplatform developed in this work provides a new strategy for enhanced intratumoral retention and improved therapeutic outcome.
基金The research was financially supported by the National Natural Science Foundation of China(Nos.51873142,51722305,and 81903068)the Ministry of Science and Technology of China(No.2016YFA0201200)111 project,and the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Insufficient intratumoral penetration greatly hurdles the anticancer performance of nanomedicine. To realize highly efficient tumor penetration in a precisely and spatiotemporally controlled manner, far-red light-responsive nanoclusters (NCs) capable of size shrinkage and charge conversion were developed and co-administered with iRGD to synergistically improve the intratumoral penetration and the anticancer efficacy. The NCs were constructed using the singlet oxygen-sensitive (SOS) polyethylene glycolpolyurethane-polyethylene glycol (PEG-(1O2)PU-PEG) triblock copolymer to encapsulate the doxorubicin (DOX)-loaded, chlorin e6 (Ce6)-conjugated polyamindoamine (PAMAM) dendrimer (DCD) via the double-emulsion method. Co-administration of iRGD notably increased the permeability of NCs within tumor vasculature and tumor tissues. In addition, upon far-red light irradiation (660 nm) of tumors at low optical density (10 mW/cm2), the generated 1O2 could disintegrate the NCs and release the DCD with positive surface charge and ultra-small size (~ 5 nm), which synergized with iRGD to enable deep intratumoral penetration. Consequently, the local 1O2 at lethal concentrations along with the released DOX efficiently and cooperatively eradicated tumor cells. This study provides a convenient approach to spatiotemporally promote the intratumoral penetration of nanomedicine and mediate programmed anticancer therapy.
基金National Natural Science Foundation of China,Grant/Award Numbers:82372943,82303610Hunan Provincial Natural Science Foundation of China,Grant/Award Number:2022JJ20095+4 种基金Hunan Youth Science and Technology Talent Project,Grant/Award Number:2023RC3074China Postdoctoral Science Foundation,Grant/Award Number:2023MD734131Chongqing Postdoctoral Science Foundation,Grant/Award Number:CSTB2023NSCQBHX0002Kuanren Talents Program of the second affiliated hospital of Chongqing Medical UniversityChongqing Postdoctoral Research Special Funding Project,Grant/Award Number:2023CQBSHTB3095。
文摘The intratumoral microbiome(TM)refers to the microorganisms in the tumor tissues,including bacteria,fungi,viruses,and so on,and is distinct from the gut microbiome and circulating microbiota.TM is strongly associated with tumorigenesis,progression,metastasis,and response to therapy.This paper highlights the current status of TM.Tract sources,adjacent normal tissue,circulatory system,and concomitant tumor co-metastasis are the main origin of TM.The advanced techniques in TM analysis are comprehensively summarized.Besides,TMis involved in tumor progression through several mechanisms,including DNA damage,activation of oncogenic signaling pathways(phosphoinositide 3-kinase[PI3K],signal transducer and activator of transcription[STAT],WNT/β-catenin,and extracellular regulated protein kinases[ERK]),influence of cytokines and induce inflammatory responses,and interaction with the tumor microenvironment(anti-tumor immunity,pro-tumor immunity,and microbial-derived metabolites).Moreover,promising directions of TM in tumor therapy include immunotherapy,chemotherapy,radiotherapy,the application of probiotics/prebiotics/synbiotics,fecal microbiome transplantation,engineered microbiota,phage therapy,and oncolytic virus therapy.The inherent challenges of clinical application are also summarized.This review provides a comprehensive landscape for analyzing TM,especially the TM-related mechanisms and TM-based treatment in cancer.
