Progress of Research on Combination of Intratumoral Immune Injection and Radiotherapy for Tumor / 肿瘤防治研究

With the rapid development of tumor immunotherapy in recent years, therapeutic cancer vaccines are attracting increased attention. Compared with personalized neoantigen vaccines, in situ vaccines could form an antigen reservoir in the tumor itself. Subsequently, antitumor immunity is initiated and the response to immune-checkpoint inhibitors of some patients improve without necessitating these patients to undergo the complicated procedures of detecting personalized antigen and customizing and synthesizing antigen peptide. At this stage, the potential of realizing the clinical translation of in situ vaccination is tremendous. In this review, we primarily introduce the mechanisms of radiotherapy and intratumoral immune injection as in situ vaccination and discuss the current status of preclinical study and clinical application of their combination to attract more attention from researchers and clinicians toward in situ vaccination.

A new therapeutic approach for bone metastasis in colorectal cancer: intratumoral melittin

Abstract Background: Melittin has shown antiproliferative effects on tumor cells. Therefore, it comprises a valuable compound for studies on cancer treatment. To the best of our knowledge, no studies have reported melittin effects on bone metastasis. Herein, we propose an approach based on intrametastatic melittin injection to treat bone metastases in colorectal cancer. Methods: Following the characterization of melittin and antiproliferative tests in vitro, a single dose was injected through intrametastatic route into the mouse bone metastasis model. Following treatment, metastasis growth was evaluated. Results: A single dose of melittin was able to inhibit metastasis growth. Histological analysis showed necrosis and inflammatory processes in melittin-treated metastasis. Except by mild weight loss, no other systemic effects were observed. Conclusion: Our data suggest that melittin might be a promising agent for the future development of treatment strategies aiming to reduce the bone metastasis skeletal-related impact in colorectal cancer patients with bone metastasis.

A new therapeutic approach for bone metastasis in colorectal cancer: intratumoral melittin

Background: Melittin has shown antiproliferative effects on tumor cells. Therefore, it comprises a valuable compound for studies on cancer treatment. To the best of our knowledge, no studies have reported melittin effects on bone metastasis. Herein, we propose an approach based on intrametastatic melittin injection to treat bone metastases in colorectal cancer. Methods: Following the characterization of melittin and antiproliferative tests in vitro, a single dose was injected through intrametastatic route into the mouse bone metastasis model. Following treatment, metastasis growth was evaluated. Results: A single dose of melittin was able to inhibit metastasis growth. Histological analysis showed necrosis and inflammatory processes in melittin-treated metastasis. Except by mild weight loss, no other systemic effects were observed. Conclusion: Our data suggest that melittin might be a promising agent for the future development of treatment strategies aiming to reduce the bone metastasis skeletal-related impact in colorectal cancer patients with bone metastasis.(AU)

Chinese medicine ligustrazine combined with percutaneous transhepatic tumor intramuscular injection of lipiodol pirarubicin combined with transhepatic arterial chemotherapy in advanced liver cancer and safety observation / 中国生化药物杂志

Objective Observing the clinical effect of Ligustrazine Phosphate Tablets combined with percutaneous intratumoral injection of lipiodol THP on advanced hepa-tocellular carcinoma.Methods83 patients with advanced hepatocellular carcinoma from January 2012 to September 2014 were analyzed.Double-blind, randomized method All patients were divided into the control group 41 cases and observation group 42 cases.The control group were treatedwith percutaneous transhepatic intratumoral injection of lipiodol THP, the observation groupwere given Ligustrazine Phosphate Tablets combined with percutaneous intratumoral injection of lipiodol THP to treat.After treatment, the two groups of patients with treatment efficacy, adverse reactions and Karnofsky and prothrombin time were analyzed.ResultsAftertreatment, the efficacy of the two groups of patients were compared, the results showed that patients in the observation group total effective rate of the control group (χ2=4.034),the difference was statistically significant (P<0.05);two groups adverse reactions in patients after treatment were compared, liver pain, blood toxicity, fever, gastrointestinal reactions similar proportion of patients, the difference was not statistically significant;Theproportion of patients in the observation group AFP<8.1ng/mL was significantly higher (χ2=4.338), the difference was statistically significant (P<0.05);patients were observed after treatment Karnofsky score was significantly higher, the difference was statistically significant (t=7.141, P<0.05);after two groups of patients were compared prothrombin time, the difference was not statistically significant.ConclusionHepatic arterial chemoembolization and percutaneous intratumoral injection of THP lipiodol emulsion on the basis of the combination of Ligustrazine Phosphate Tablets can effectively improve the efficacy of treatment, and has good security, which is a safe and effective methods of treatment should be to promote and use in clinical.

Clinical analysis of treatment of airway stenosis caused by advanced central lung cancer with bronchoscopic endobronchial ultrasound guided intratumoral injection of Cisplatin (10 cases) / 中国内镜杂志

Objective To explore the clinical application value of bronchoscopic endobronchial ultrasound (EBUS) guided intratumoral injection of Cisplatin in treatment of airway stenosis caused by advanced central lung cancer. Methods The clinical data of 10 cases of airway stenosis caused by advanced central lung cancer between Nov 2015 and Jan 2017 were analyzed retrospectively. Results 10 cases airway stenosis caused by advanced central lung cancer received EBUS guided intratumoral injection of Cisplatin treatment. Assessed by bronchoscopic, there were 8 cases of patients showed favorable effects after the treatment; Assessed by CT scan, 6 cases showed effects;And 8 cases relieved dyspnea. Conclusion EBUS guided intratumoral injection of Cisplatin in treatment of airway stenosis caused by advanced central lung cancer have some effect.

Formula Screening and in vitro Drug Release of Tegafur Thermo-sensitive Gel for Intratumor Injection / 中国药师

Objective:To screen the best formula of tegafur temperature-sensitive gel for intratumor injection and investigate the in vitro drug release behavior. Methods:The drug dose was determined by cytotoxicity experiment. The thermo-sensitive gel was prepared with PLGA-PEG-PLGA and HPMC as the matrix. With the in vitro release as the index, the effects of PLGA-PEG-PLGA and HPMC at different concentrations on gel were investigated. The gelation temperature, viscosity and pH were detected. Results:The best formula was as follows:25% PLGA-PEG-PLGA, 1% HPMC, and tegafur dose of 1 mg·ml-1 . The average gelation temperature was 36. 7℃, the average viscosity was 7550 mPa·s, and the average pH was 7. 2. Conclusion:Tegafur thermo-sensitive gel for intratumor in-jection shows temperature sensitivity and obvious sustained-release property, which provides experimental basis for the further clinical research.

Effect and apoptosis of percutaneous intratumoral injection with 188Re labeled stannic sulfur colloid on VX2 liver tumor in rabbits / 中华肝胆外科杂志

Objective To evaluate the efficacy and safety of rabbit VX2 liver tumor model by percutaneous intratumoral injection with 188Re labeled stannic sulfur colloid.Methods The VX2 liver tumor model was established in 45 rabbits,which were randomly assigned to 3 groups (n =15) according to material used in intratumoral injections,as follows:0.1 ml normal saline (Group A,control group),absolute ethanol 1ml (Group B),37MBq (1mCi) 188Re labeled stannic sulfur colloid 0.1 ml (Group C).Five rabbits from each group were killed at intervals of 1,4 and 7d after injection and the volume of tumors were measured.Meanwhile,the histopathological changes and extent of cell apoptosis were evaluated.ALT and urea levels before the operation and at intervals of 1,4,7d post injection were also detected.Results In the first day after the injection,there was no significant statistical heterogeneity of the tumor volumes between each group.At 4th day post injection,tumor volumes of group A [(1 873.1 ± 77.3) mm3] showed significant statistical heterogeneity with group B [(905.7 ± 113.3) mm3] and C [(860.2 ± 59.6) mm3] (P ＜0.01),while there were no obvious statistical significance between group B and group C (P =0.421).At 7th day post injection,there were marked statistical significance of tumor volumes between A,B and C groups[respectively,(4093.1 ± 126.5)mm3,[(2569.5 ±64.6)mm3 and (2 169.6 ± 141.9)mm3](P＜0.01).At any time after injection,the apoptosis index (AI) of peritumoral tissue in group B and C was higher than control group with statistical significance (P ＜ 0.001).At 4th day post injection,AI of group C remained higher than group B (P ＜ 0.05).At 7th day,AI of group C progressively decreased,and there were no statistical difference between group B and group C (P ＞ 0.05).Conclusion Percutaneous intratumoral injection of 188Re labeled stannic sulfur colloid is a safety and effective approach to the treatment of VX2 liver tumor in rabbits.

Image-Guided Percutaneous Lipiodol-Pingyangmycin Suspension Injection Therapy for Sacral Chordoma

A 74-year-old man presented with a progressively worsening pain in sacrum and was diagnosed to have a sacral chordoma by biopsy in May, 2004. Percutaneous intratumoral injection with lipiodol-pingyangmycin suspension (LPS) was carried out under image guidance and repeated when the pain in sacrum recurred and the tumor increased. During a 6-year follow-up period, three sessions of this treatment were executed. CT imaging and Karnofsky Performance Score were used to evaluate the size of tumor and quality of life, respectively. The patient was free of pain after each procedure and had a high quality of life with a Karnofsky Performance Score above 80 points. The tumor lesion in sacral area was effectively controlled. No complications were observed. Percutaneous intratumoral injection with LPS under image guidance may be an effective and safe alternative for the patients with sacral chordoma.

Combination treatment with intrahepatic arterial infusion and intratumoral injection chemotherapy in patients with far-advanced hepatocellular carcinoma and arterioportal or arteriovenous shunts: preliminary results / 대한간학회지

BACKGROUND/AIMS: Combination treatment consisting of hepatic arterial infusion chemotherapy with epirubicin and cisplatin (HAIC-EC) and systemic infusion of low-dose 5-fluorouracil (5-FU) are sometimes effective against advanced hepatocellular carcinoma (HCC). However, there is no effective treatment for advanced HCCs with arterioportal shunts (APS) or arteriovenous shunts (AVS). METHODS: We investigated a response and adverse events of a new combination protocol of repeated HAIC-EC and percutaneous intratumoral injection chemotherapy with a mixture of recombinant interferon-gamma (IFN-gamma) and 5-FU (PIC-IF) in patients with far-advanced HCCs with large APSs or AVSs. RESULTS: There was a complete response (CR) for the large vascular shunts in all three patients and for all tumor burdens in two patients. Significant side effects were flu-like symptoms (grade 2) and bone marrow suppression (grade 2 or 3) after each cycle, but these were well-tolerated. CONCLUSIONS: These results suggest that the combination of HAIC-EC and PIC-IF is a new and promising approach for advanced HCC accompanied by a large APS or AVS.

Hydroxyapatite nanoparticles intratumoral injection for treatment of liver VX2 tumor in rabbits / 中华肝胆外科杂志

Objective To study the inhibitory effects of hydroxyapatite nanoparticles on liver VX2 tumor in rabbits after intratumoral injection. Methods 40 rabbits with implantation of liver VX2 tumors were randomly divided into 4 groups and intratumorally injected with different preparations.Group A: (control group), 1 ml nomal saline containing 0.2% CMC-Na; Group B: ( 5-Fu group),20 mg/ml 5-Fu 1 ml; Group C: (Nano HAP), 20 mg/ml Nano HAP 1 ml; Group D: (5-Fu+Nano HAP), 20 mg/ml 5-Fu 1 ml and 20 mg/ml Nano HAP 1 ml. Ultrasonography was performed to measure liver tumor volume 7, 14, 21 d after treatment. Survival durations of the animals were recorded. Tumor tissues and liver tissues close to tumor were obtained and examined histologically.Results The average tumor volumes 7, 14 and 21 d after treatment were (4.93 ±0.76)cm3,(15. 67±2.75)cm3 and (52. 36±10. 57)cm3 in group A, (4. 16±0. 33)cm3 , (10. 26± 1.60)cm3 and (18. 89±4.65)cm3 in group B, (1.43±0.13)cm3 , (3.69±0.77)cm3 and (9.51±2.09)cm3 in group C, (2. 80±0.46)cm3 , (3. 77±0. 91)cm3 and (8. 46±0.95)cm3 in group D respectively. The average tumor volumes of groups B, C and D were significantly smaller than that of group A in the same time phases after treatment. The life span of group C was longer than that of other three groups, and there was no statistically significant difference between group B and group D, although the two groups were significantly longer than group A. Blood flow was not detected by color Doppler or power Doppler in group C and group D. Pathological examination showed that there was obvious intratumoral necrosis in group C and D. Tumor in group B exhibited thoroughgoing necrosis. Conclusion Hydroxyapatite nanoparticles intratumoral injection is safe and feasible for treatment of liver tumor. Hydroxyapatite nanoparticles can exert a significant inhibitory effect on liver VX2 tumor growth in rabbits without liver toxicity.

Intratumoral injection for infant maxillofacial hemangioma / 重庆医科大学学报

Objective:To observe and summarize the therapeutic effects of intratumoral injection with Triamcinolone Acetonide Acetate and Pingyangmycin on infant maxillofacial hemangioma.Methods:Local injection with Triamcinolone Acetonide Acetate(TAA)and Pingyangmycin(PYM)was executed to treat infant maxillofacial hemangioma.If the lesion did not disappear,the treatment would be performed again every four to six weeks at intervals,and the total dose of TAA and PYM could not be more than 100mg and 40mg respectively.The injection treatment was repeated 4 times for one course and the therapeutic effects of maxillofacial hemangioma were detected.Results: 84 cases with maxillofacial hemangioma,treated by local injection with TAA and PYM,had been followed up for one to three years.The cure rate was 90.4%,the notable rate was 7.1%,and the ineffective rate was 2.4%.Conclusions:The intratumoral injection with Triamcinolone Acetonide Acetate and Pingyangmycin is the reliable therapy method with less side effects.It is valuable for treatment of infant maxillofacial hemangioma.