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
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
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
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
目的构建并表征胃癌三维多细胞球体模型,用于评价化疗药物的瘤内穿透。方法将12000个小鼠胃癌MFC细胞系接种于96 U 3D细胞培养板,以构建MFC多细胞肿瘤球体(MFC MCTS);将8000个MFC细胞和4000个小鼠成纤维NIH/3T3细胞系共同接种于96 U 3D...目的构建并表征胃癌三维多细胞球体模型,用于评价化疗药物的瘤内穿透。方法将12000个小鼠胃癌MFC细胞系接种于96 U 3D细胞培养板,以构建MFC多细胞肿瘤球体(MFC MCTS);将8000个MFC细胞和4000个小鼠成纤维NIH/3T3细胞系共同接种于96 U 3D细胞培养板,以构建MFC-NIH/3T3共培养多细胞肿瘤球体(CO MCTS);通过活细胞成像表征球体的直径、圆度、面积和透光率;通过激光共聚焦成像表征球体微环境和化疗药物(LipoDOX,5.0μg/ml)的瘤内穿透。结果培养5 d时,两种球体的透光率最低,圆度>0.90,直径约为530μm,面积约为0.23 mm^(2)。两种球体模型内均检测到3种微环境荧光探针分布。LipoDOX能相对均匀地穿透MFC MCTS,却在CO MCTS内表现出外多内少的不均匀穿透,药物荧光强度降低约58.3%(P<0.01)。结论本研究构建了两种具有良好圆度、高紧实度、适中直径和面积的胃癌三维多细胞球体模型,两种胃癌球体模型均表现出酸性、缺氧和氧化还原微环境,可精准、高效地评价化疗药物的瘤内穿透。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
Increasing evidence suggests that intratumoral microbiota plays a pivotal role in tumor progression,immunosurveillance,metastasis,and chemosensitivity.Particularly,in pancreatic ductal adenocarcinoma,tumor-resident Ga...Increasing evidence suggests that intratumoral microbiota plays a pivotal role in tumor progression,immunosurveillance,metastasis,and chemosensitivity.Particularly,in pancreatic ductal adenocarcinoma,tumor-resident Gammaproteobacteria could transform the chemotherapeutic drug gemcitabine(Gem)into its inactive form,thus rendering chemotherapy ineffective.Herein,a strategy for selectively eradicating intratumoral bacteria was described for overcoming Gem resistance in a pancreatic cancer animal model.An antimicrobial peptide was linked with photosensitizer through a poly(ethylene glycol)chain,which can self-assemble into micelles with a diameter of∼20 nm.The micelles could efficiently kill bacteria under light irradiation by inducing membrane depolarization,thereby inhibiting Gem metabolism.In a bacteria-resident pancreatic cancer animal model,the selective photodynamic eradication of intratumoral bacteria was demonstrated to efficiently reverse Gem resistance.This research highlights antibacterial photodynamic therapy as a promising adjuvant strategy for cancer therapy by modulating intratumoral microbiota.展开更多
BACKGROUND Recently,vessels encapsulating tumor clusters(VETC)was considered as a distinct pattern of tumor vascularization which can primarily facilitate the entry of the whole tumor cluster into the bloodstream in a...BACKGROUND Recently,vessels encapsulating tumor clusters(VETC)was considered as a distinct pattern of tumor vascularization which can primarily facilitate the entry of the whole tumor cluster into the bloodstream in an invasion independent manner,and was regarded as an independent risk factor for poor prognosis in hepatocellular carcinoma(HCC).AIM To develop and validate a preoperative nomogram using contrast-enhanced computed tomography(CECT)to predict the presence of VETC+in HCC.METHODS We retrospectively evaluated 190 patients with pathologically confirmed HCC who underwent CECT scanning and immunochemical staining for cluster of differentiation 34 at two medical centers.Radiomics analysis was conducted on intratumoral and peritumoral regions in the portal vein phase.Radiomics features,essential for identifying VETC+HCC,were extracted and utilized to develop a radiomics model using machine learning algorithms in the training set.The model’s performance was validated on two separate test sets.Receiver operating characteristic(ROC)analysis was employed to compare the identified performance of three models in predicting the VETC status of HCC on both training and test sets.The most predictive model was then used to constructed a radiomics nomogram that integrated the independent clinical-radiological features.ROC and decision curve analysis were used to assess the performance characteristics of the clinical-radiological features,the radiomics features and the radiomics nomogram.RESULTS The study included 190 individuals from two independent centers,with the majority being male(81%)and a median age of 57 years(interquartile range:51-66).The area under the curve(AUC)for the combined radiomics features selected from the intratumoral and peritumoral areas were 0.825,0.788,and 0.680 in the training set and the two test sets.A total of 13 features were selected to construct the Rad-score.The nomogram,combining clinicalradiological and combined radiomics features could accurately predict VETC+in all three sets,with AUC values of 0.859,0.848 and 0.757.Decision curve analysis revealed that the radiomics nomogram was more clinically useful than both the clinical-radiological feature and the combined radiomics models.CONCLUSION This study demonstrates the potential utility of a CECT-based radiomics nomogram,incorporating clinicalradiological features and combined radiomics features,in the identification of VETC+HCC.展开更多
目的探讨平阳霉素治疗眼部血管瘤的疗效和作用机理。方法采用平阳霉素8 mg+0.5%利多卡因3-6 m l溶解后注射,一次未愈,间隔1-4周重复给药,5次为一疗程,总量不超过80 mg。结果62例患者,经6月-3年随访,治愈率69.35%,显效率24.19%,有效率6.4...目的探讨平阳霉素治疗眼部血管瘤的疗效和作用机理。方法采用平阳霉素8 mg+0.5%利多卡因3-6 m l溶解后注射,一次未愈,间隔1-4周重复给药,5次为一疗程,总量不超过80 mg。结果62例患者,经6月-3年随访,治愈率69.35%,显效率24.19%,有效率6.45%,总有效率93.55%。结论本方法疗效显著,副作用小,外观满意,是一种安全、可靠、简便、易行的治疗方法。展开更多
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.
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.
基金National Natural Science Foundation of China,Grant/Award Numbers:52273300,82102062,81930047China Postdoctoral Science Foundation,Grant/Award Number:2020TQ0008。
文摘Increasing evidence suggests that intratumoral microbiota plays a pivotal role in tumor progression,immunosurveillance,metastasis,and chemosensitivity.Particularly,in pancreatic ductal adenocarcinoma,tumor-resident Gammaproteobacteria could transform the chemotherapeutic drug gemcitabine(Gem)into its inactive form,thus rendering chemotherapy ineffective.Herein,a strategy for selectively eradicating intratumoral bacteria was described for overcoming Gem resistance in a pancreatic cancer animal model.An antimicrobial peptide was linked with photosensitizer through a poly(ethylene glycol)chain,which can self-assemble into micelles with a diameter of∼20 nm.The micelles could efficiently kill bacteria under light irradiation by inducing membrane depolarization,thereby inhibiting Gem metabolism.In a bacteria-resident pancreatic cancer animal model,the selective photodynamic eradication of intratumoral bacteria was demonstrated to efficiently reverse Gem resistance.This research highlights antibacterial photodynamic therapy as a promising adjuvant strategy for cancer therapy by modulating intratumoral microbiota.
基金The study was reviewed and approved by the Second Hospital of Shandong University Institutional Review Board,IRB No.KYLL-2023LW044.
文摘BACKGROUND Recently,vessels encapsulating tumor clusters(VETC)was considered as a distinct pattern of tumor vascularization which can primarily facilitate the entry of the whole tumor cluster into the bloodstream in an invasion independent manner,and was regarded as an independent risk factor for poor prognosis in hepatocellular carcinoma(HCC).AIM To develop and validate a preoperative nomogram using contrast-enhanced computed tomography(CECT)to predict the presence of VETC+in HCC.METHODS We retrospectively evaluated 190 patients with pathologically confirmed HCC who underwent CECT scanning and immunochemical staining for cluster of differentiation 34 at two medical centers.Radiomics analysis was conducted on intratumoral and peritumoral regions in the portal vein phase.Radiomics features,essential for identifying VETC+HCC,were extracted and utilized to develop a radiomics model using machine learning algorithms in the training set.The model’s performance was validated on two separate test sets.Receiver operating characteristic(ROC)analysis was employed to compare the identified performance of three models in predicting the VETC status of HCC on both training and test sets.The most predictive model was then used to constructed a radiomics nomogram that integrated the independent clinical-radiological features.ROC and decision curve analysis were used to assess the performance characteristics of the clinical-radiological features,the radiomics features and the radiomics nomogram.RESULTS The study included 190 individuals from two independent centers,with the majority being male(81%)and a median age of 57 years(interquartile range:51-66).The area under the curve(AUC)for the combined radiomics features selected from the intratumoral and peritumoral areas were 0.825,0.788,and 0.680 in the training set and the two test sets.A total of 13 features were selected to construct the Rad-score.The nomogram,combining clinicalradiological and combined radiomics features could accurately predict VETC+in all three sets,with AUC values of 0.859,0.848 and 0.757.Decision curve analysis revealed that the radiomics nomogram was more clinically useful than both the clinical-radiological feature and the combined radiomics models.CONCLUSION This study demonstrates the potential utility of a CECT-based radiomics nomogram,incorporating clinicalradiological features and combined radiomics features,in the identification of VETC+HCC.
文摘目的探讨平阳霉素治疗眼部血管瘤的疗效和作用机理。方法采用平阳霉素8 mg+0.5%利多卡因3-6 m l溶解后注射,一次未愈,间隔1-4周重复给药,5次为一疗程,总量不超过80 mg。结果62例患者,经6月-3年随访,治愈率69.35%,显效率24.19%,有效率6.45%,总有效率93.55%。结论本方法疗效显著,副作用小,外观满意,是一种安全、可靠、简便、易行的治疗方法。