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As a method for local treatment, radiotherapy plays a key role in the management of tumors. In the past few decades, great progress has been made in radiotherapy technology, with improvements in conformity, homogeneity, and radiotherapy efficiency, and the results are encouraging. Nevertheless, the maximum tolerated dose of normal tissue has limited the further increase in radiotherapy dose in the tumor area. If radiation-induced toxicities can be reduced, a higher radiotherapy dose can be delivered to tumor tissue, so as to achieve a better treatment response. In recent years, the unique FLASH effect of ultra-high-dose-rate radiotherapy (FLASH-RT) is capable of maintaining a consistent tumor response whilst reducing radiation-induced toxicities in normal tissue, and therefore, FLASH-RT has become a research hotspot in the field of radiotherapy across the world. At present, some scholars tend to explain the FLASH effect using the theory of acute oxygen depletion, but the protective effect of FLASH-RT on normal tissue remains to be clarified. In addition, preliminary clinical studies have been conducted for FLASH-RT, and the results are promising. Based on existing evidence, this article elaborates on the research advances in FLASH-RT in the treatment of malignant tumor, so as to provide a reference for the translation and application of this new technique.
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In the process of tumor growth, with the proliferation and expansion of cancer cells, the reconstruction of extracellular matrix (ECM) of cancer tissues, the restriction of surrounding tissues and the flow of cancer tissue interstitial fluid, the special stress environment is formed in the tumor tissues. Significant differences are found in the mechanical environment and mechanical characteristics of different regions of tumor tissues, that is, mechanical heterogeneity. The reseach shows that the mechanical properties of tumor tissue invasion frontier areas are more significant and complex. In particular, the epithelial-mesenchymal transition (EMT) of tumor cells also prefers to concentrate on this area. The mechanical stress generated by the invasion front can induce EMT of tumor cells through TWIST1, TGF-β, WNT and other force signal transduction pathways, and promote tumor cell invasion. From the perspective of tumor biomechanics, this review focuses on the relationship between mechanical heterogeneity of tumor cells and EMT, so as to provide the theoretical basis for mechanoenvironment-targeted therapy of tumors.
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OBJECTIVE: This study aimed to assess miRNA-195 expression in the tumor tissues from a cohort of Brazilian female breast cancer patients undergoing neoadjuvant chemotherapy (NAC) and evaluate its correlation with various clinicopathological markers. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate the miRNA-195 expression in tumor tissues from a cohort of female breast cancer patients undergoing NAC. This expression was then correlated with the occurrence of several distinct breast cancer molecular subtypes and other clinicopathological variables. RESULTS: A total of 55 patients were included in this study, 28 (50.9%) of whom were treated using NAC. Tumor miRNA-195 expression was suppressed in breast cancer patients, regardless of their exposure to systemic treatments, histological grade, size, nodal status, and tumor-node-metastasis (TNM) staging. This was more pronounced in luminal and triple-negative patients, and patient's response to NAC was correlated with an increase in miRNA-195 expression. CONCLUSION: miRNA-195 is downregulated in the tumor tissues of Brazilian breast cancer patients regardless of NAC exposure; this reinforces its role as a tumor suppressor and a potential biomarker for chemotherapy response.
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Humans , Female , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , MicroRNAs/genetics , Prognosis , Brazil , Antineoplastic Combined Chemotherapy Protocols , Biomarkers, Tumor/genetics , Neoadjuvant Therapy , Neoplasm StagingABSTRACT
BACKGROUND: Many methods have been developed to establish a rabbit VX2 tumor model, but the reliability of each method has not been explored. In order to develop a reliable method, we made some improvements based on the existing methods. OBJECTIVE: To investigate the reliability of rabbit VX2 tumor tissue block implantation and cell suspension via modified and traditional implantation to make the rabbit tibia VX2 tumor model. METHODS: Forty healthy adult New Zealand white rabbits were randomly divided into two groups. Group A was treated with tissue block implantation for tibia VX2 tumor modeling, and group B was treated with cell suspension for tibia VX2 tumor modeling. Modified and traditional implantation was performed on the left and right tibia of the experimental animals, respectively. One hour after successful modeling, ultrasound examination of the puncture site was performed to determine whether there is hematoma. All experimental animals were sacrificed at 3 weeks. X-ray examination of the bilateral tibia was performed to confirm the tumor growth range. Tumor tissue and soft tissue around the puncture site were taken for general and pathological observation to compare the size of the tumor and identify whether there is tumor cell metastasis. RESULTS AND CONCLUSION: One rabbit died in the tissue block group, and all the experimental animals in the cell suspension group survived. X-ray examination indicated the tumors in the tissue block group invaded the cortex, but the tumors in the cell suspension group did not invade the cortex. Gross observation revealed that the tumor volume of the tissue block group was greater than that of the cell suspension group. In the tissue block group, there were one and seven cases of hematoma around the puncture site at 1 hour after modified and traditional implantation, respectively. In the cell suspension group, there were two and nine cases of hematoma around the puncture site at 1 hour after modified and traditional implantation, respectively. Pathological examination showed that local tumor invasion was found in 1 and 8 cases in the tissue block group as well as in 2 and 11 cases in the cell suspension group at 3 months after modified and traditional implantation, respectively. Our findings indicate that the tissue block implantation method is easier and more convenient than the cell suspension method for making rabbit VX2 bone tumors, and the tumor invasion rate of the tissue block implantation method is lower than that of the cell suspension method. Improved tissue block implantation can effectively reduce the tumor invasion rate during modeling.
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Objective: To investigate the pharmacokinetics and the distribution in tumor tissues of docetaxel nanomicelles. Method: The docetaxel nanomicelles was prepared by filming-rehydration method.HPLC was employed to determine the content of docetaxel in biological samples and the corresponding methodological evaluation was carried out.The mouse Lewis lung carcinoma model was established,when dosage of administration in tail vein was 20 mg·kg-1,and then the effect of free drug(DTX),non-pH-sensitive drug-loaded micelles(PELA-DTX) and pH-sensitive drug-loaded micelles(PBAE-DTX) on the pharmacokinetics and tissue distribution of tumor-bearing mice were investigated. Result: The docetaxel nanomicelles(PELA-DTX and PBAE-DTX) were successfully prepared.The method for the determination of docetaxel in mice was established by HPLC,the linearity,precision of the method and the recovery rate of samples all met the requirements.In the pharmacokinetic study,the plasma concentration of PBAE-DTX was always at a high level within 24 h.Compared with PELA-DTX and DTX,the areas under the curve(AUC0-∞) of PBAE-DTX were increased by 3.63% and 8.96%,the mean residence times(MRT) were extended by 2.86% and 6.43%,the half-life and the drug blood circulation time were prolonged.In the tissue distribution study,it was found that three docetaxel preparations were distributed in the heart,liver,spleen,lung,kidney and tumor tissue within 1 h after administration,but the distribution of these drugs in the tissues was reduced along with the extension of time,the accumulation of PBAE-DTX in tumor tissue was significantly higher than that in DTX and PELA-DTX at 24 h. Conclusion: PBAE-DTX can prolong the circulation time of docetaxel in the blood,increase its bioavailability,and significantly increase its distribution in tumor tissue.
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The present study aimed to research pathogenesis and therapeutics of hepatocellular carcinoma (HCC) with the method of tissue metabolomics.A combined gas chromatography-mass spectrometry (GC-MS) method was developed suitable for analyzing the endogenous small molecule of liver cancer tissues and adjacent tissues.The unidimensional and multidimensional statistics were used to look for differential metabolites.And then,the KEGG and HMDB database were utilized to find related differential pathways and pathogenesis of HCC.The PCA and PLS-DA showed that there were significant differences on the endogenous small molecule of liver cancer tissues and adjacent tissues.Through the OPLS-Loading plot analysis,there were 25 differential metabolites and 36 relevant pathways.The differential pathways belong to carbohydrate metabolism,amino acid metabolism and mitochondrial transfer.There were 16 metabolites' area under the ROC curve which was bigger than 0.8,which were related with ATP-binding cassette (ABC) transporters,galactose metabolism,amino sugar and nucleotide sugar metabolism.It was concluded that the Warburg effect exists in HCC cells.The energy of HCC cell was from glycolytic function,because the glycolysis was enhanced and the citric acid cycle decreased.Mitochondrial dysfunction and the increased cobalt content may correlate with the Warburg effect,which may be one of the pathogenesis of liver cancer,and expected to become the breakthrough point of a new targeting therapeutic approach.
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OBJECTIVE:To observe the effects of single administration of carboplatin by different ways on drug accumulation concentration and treatment of tumor tissue before surgery. METHODS:60 patients with resectable advanced gastric cancer were randomly divided into intraperitoneal administration group(30 cases)and intravenous administration group(30 cases). All patients received 50 mg/m2 Carboplatin injection,intravenous administration,it stopped 4 weeks after continuous 5 d,repeated 3 times, when the last chemotherapy,intraperitoneal administration group was given 30 mg/m2 Carboplatin injection,adding into 750 ml 0.9% Sodium chloride injection,and placed in 37 ℃ water bath for preheating,taking paracentesis for disposable rapid injection. Intravenous administration group was 30 mg/m2 Carboplatin injection,adding into 750 ml 0.9%Sodium chloride injection,by intra-venous infusion within 30 min. Both groups were administered once for at least 1 week,then surgery was taken after 5 d. The car-boplatin accumulation concentration in 2 groups was determined after 160-180 min and 250-260 min,respectively,and the efficacy in the 5th day and incidence of adverse reactions during treatment were recorded. RESULTS:The total effective rate after 5 d,peri-toneal fluid,portal vein and peripheral blood after 160-180 min,and carboplatin accumulation concentration in cancer tissues,adja-cent normal tissues,peritoneum,omentum and negative lymph node after 250-260 min in intraperitoneal administration group were significantly higher than intravenous administration group,the incidence of adverse reactions was significantly lower than intrave-nous administration group,the differences were statistically significant(P<0.05). CONCLUSIONS:Compared with intravenous in-fusion,intraperitoneal injection of carboplatin before surgery can improve the local accumulation concentration and chemotherapeu-tic effect and reduce incidence of adverse reactions.
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Background and purpose:Cancer of unknown primary (CUP) represents approximately 5%~10%of malignant neoplasms. For CUP patients, identiifcation of tumor origin allows for more speciifc therapeutic regimens and improves outcomes.Methods:By retrieving the gene expression data from ArrayExpress and Gene Expression Omnibus data repositories, we established a comprehensive gene expression database of 5 800 tumor samples encom-passing 22 main tumor types. The support vector machine-recursive feature elimination algorithm was used for feature selection and classiifcation modelling. We further optimized the RNA isolation and real-time quantitative polymerase chain reaction (RTQ-PCR) methods for candidate gene expression proifling and applied the RTQ-PCR assays to a set of formalin-fixed, paraffin-embedded tumor samples.Results:Based on the pan-cancer transcriptome database, we identiifed a list of 96-tumor speciifc genes, including common tumor markers, such as cadherin 1 (CDH1), kallikrein-re-lated peptidase 3 (KLK3), and epidermal growth factor receptor (EGFR). Furthermore, we successfully translated the microarray-based gene expression signature to the RTQ-PCR assays, which allowed an overall success rate of 88.4% (95%CI: 83.2%-92.4%) in classifying 22 different tumor types of 206 formalin-fixed, paraffin-embedded samples. Conclusion:The 96-gene RTQ-PCR assay represents a useful tool for accurately identifying tumor origins. The assay uses RTQ-PCR and routine formalin-ifxed, paraffn-embedded samples, making it suitable for rapid clinical adoption.
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Objective To explore renal clear cell carcinoma ( CCRCC) expression and significance of CD146 mR-NA in tumor tissue of patients with. Methods ELISA method for quantitative detection was used for CD146 protein and real-time PCR technique for the detection of CCRCC in 102 ( CCRCC) expression in tumor tissue of patients with CD146 mRNA, and 51 cases of renal patients with non tumor tissues as control. Results Found metastasis in patients with CCRCC, the CD146 protein concentration was statistically significant compared with the control group (F=52.1, P<0.01),the average expression of CD146 mRNA value (0.043 8±0.002 4) was significantly high-er than that of in situ CCRCC patients (0.038 2±0.001 1, P= 0.018) and control group (0.034 4±0.001 0, P=0.001 ) . Conclusion Pathological grading and lymph node up regulation of CD146 mRNA expression in renal cell carcinoma and metastasis, is expected to become a new index, evaluation of malignant degree of CCRCC me-tastasis and prognosis, and provide a reliable basis for the intervention of clinical treatment.
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Objective To detect aberrant methylation in the promoter of FHIT and RASSF1A genes in peripheral plasma and tumor tissues from patients with hepatocellular carcinoma (HCC) and to determine its clinical significance.Methods The methylation status of FHIT and RASSF1A genes in peripheral plasma and tumor tissues from 36 patients with HCC were detected by methylation-specific polymerase chain reaction(MSP).The correlation between methylation status in plasma and clinicopathological features was analyzed.Results The frequency of promoter methylation of FHIT in tissues was 75％ (27/36) and in plasma 52.8％ (19/36),and the correlation coefficient was r=0.482 (P=0.003).The frequency of promoter methylation of RASSF1A in tumor tissues was 83.3％ (30/36) and in plasma 61.1％ (22/36),and the correlation coefficient was r=0.561 (P=0.0004).Aberrant methylation of FHIT,RASSF1A gene in the plasma and tissues had no correlation with the patients' clinicopathological features such as gender,age,HBV/HCV infection,hepatic cirrhosis,tumor size,alpha-fetoprotein (AFP) level,pathological grade,staging,vascular tumour thrombus and recurrence.The sensitivity of AFP ≥400 μg/L was 44.4％,and AFP ≥20 μg/L 69.4％.The sensitivity of FHIT and RASSF1A gene promoter hypermethylation in 36 HCC patients was 72.2％.In 20 patients whose AFP ＜400 μg/L,the frequency of hypermethylation of the two genes together was 80％.When AFP ＜20 μg/L,the frequency of hypermethylation of the two genes together was 54.5 ％.Conclusions There was a significant concordance between plasma and tumor tissue methylation profiles.The methylation status in plasma and tumor tissues had no correlation with the patients' clinicopathological features.Combining promoter methylation of FHIT and RASSF1A genes was superior to AFP in the diagnosis of HCC.
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PURPOSE: DNA methylation is a major epigenetic mechanism for modification of genetic expression without a change in the DNA sequence. MBD2 (methyl-CpG-binding domain 2 protein) belongs to a family of enzymes concerning of DNA demethylation and suppresses the hypermethylation of the CpG island and DNA transcription. In this study, we investigated the change of MBD2 expression in the blood and tissue of colorectal cancer patients and compared the two expression levels. METHODS: The 68 patients included in this study were patients with colorectal cancer who had undergone surgery at our hospital, and 50 other patients with no malignant disease were recruited from normal populations. Total RNA samples were isolated from whole blood samples and cancer tissues of specimens using a TRI REAGENT BD kit. MBD 2 expression was measured by real-time quantitative reverse transcription-polymerase chain reaction assays. RESULTS: The mean age was older in the case group than in the control group. The mean expression level of MBD2 in blood was not different between the two groups. In the case group, the tissue MBD2 expression was lower than the blood MBD2 expression under all conditions, and that difference was statistically significant (P<0.01). The expression of MBD2 in cancer tissue showed a negative correlation with that in the blood of cancer patients, correlation coefficient of R=0.073, but that result was not statistically significant (P=0.611). CONCLUSIONS: The blood MBD2 expression was statistically the same in the cancer and the control groups. In the cancer group, blood MBD2 expression was significantly higher than tissue MBD2 expression. The reverse correlation between blood MBD2 expression and tissue MBD2 expression in cancer patients suggests that MBD2 may affect the mechanism of carcinogenesis.
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Humans , Base Sequence , Colorectal Neoplasms , CpG Islands , DNA , DNA Methylation , Epigenomics , RNAABSTRACT
[Objective]To discuss the significance of tissue repairing and functional reconstruction in treatment of extremity malignant tumors by allogeneic bone graft and replanting devitalized bone after malignant bone tumor resection. [Method]A retrospective study of 56 patients with malignant bone tumor was conducted, including 35 male patients and 21 female patients. The age was between 9 and 60, with an average of 18.Tumor in 9 cases was in the proximal hunerus, 30 in the distal femur, and 17 in the proximal cnemis.Thirty-two cases were osteogenic sarcoma,17 cases were chondroma sarcomatosum,3 cases were maligant giant cell tumor of bone and 4 cases were metastatic.Soft tissue was repaired and extremity function was reconstructed by adopting allogeneic bone graft and replanting devitalized bone. Extremity functions, bone healing conditions, and complication were estimated according to Mankin metheds.[Result]Among these 56 patients,results in 20(35.7%) were excellent,11(19.6%) were good,8(14.3%) were fair,17 (30%) were poor. The satisfactory rate was 70%.Thirty-eight patients survived for two years without tumor.Thirty patients survived for 5 years with the survival rate of 55%. Except local relapsed, the major complications were infection (4 cases), fracture (3 cases),collapse of articular facet (1 cases), and arthrocleisis (5 cases),with the infection rate of 7%.No internal fixation was broken.[Conclusion]For extremity malignant tumor, effective tissue repairing and functional reconstruction not only offer a limb-sparing effect, but also keep the limb in good function. This is an effective method for bone malignant tumor.
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Objective:To established a modified implanting model of VX2 liver tumor in rabbit on the base of the classic implanting method, and compared the results within the two methods. Methods:30 rabbits with the mean weight of (2.65?0.29)kg were divided randomly into two groups with 15 rabbits each. The rabbits in Group A received classic implantation for induction of the liver tumor model, and Group B were inducted by injecting a piece of tumor tissue into the left anterior lobes of liver. Implanting time of each group was recorded and compared, and spiral CT scan was performed at 8th day, 15th day, 22nd day, 29th day postoperatively. The manifestation of tumors in CT scan was observed and tumor volume was calculated simultaneously with formula V=1/2ab2 (a=the shortest diameter and b=the longest diameter).Each tumor was confirmed through pathology. Results:The implanting time of Group A and Group B were (9.47?2.85)min and (5.85?1.62)min, respectively, with significant difference between them. Besides, there was statistical difference of the achievement ratio between two groups, as it was 53.3% for Group A and 86.7% for Group B. No significant difference was found for the tumor growth between two groups. Conclusion:Modified implanting method for induction of the rabbit liver tumor model was superior to the classic implanting method.
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PURPOSE: Current pediatric cancer research requires an organized pediatric tumor tissue bank with standardized guidelines for preparation and storage of human tumor tissue samples, white cells, serum, genomic DNA, RNA, cDNA and proteins.. Our institution established and managed pediatric tumor tissue bank for the last one year, and we want to present an overview of our experiences and guidelines. METHODS: From leukemia patients, peripheral blood and bone marrow aspirates were collected at initial diagnosis. Leukemic cells were prepared by Ficoll density-gradient centrifugation and stored at 196oC liquid nitrogen. For solid tumors, tissue cultures were performed as soon as possible after surgical excision or needle biopsy. Serum free media and primary cultured cells were collected and stored at 20degrees C and at 196degrees C, respectively. Genomic DNA, RNA and cDNA were isolated from leukemic cells and cultured solid tumor cells, and stored at 20degrees C. We also isolated genomic DNA from white blood cells of solid tumor patients and stored at 20degrees C. Finally we collected serum samples from all pediatric cancer patients at diagnosis and stored at 20degrees C. RESULTS: Among the 41 cases of leukemia and 100 cases of solid tumor patients who were diagnosed at department of pediatrics, Samsung Medical Center, from August 2000 to July 2001, 26 cases (63%) of leukemia and 59 cases (59%) of solid tumor patients were registered to Pediatric Tumor Tissue Bank. Primary cell cultures were performed in 21 cases of solid tumors and were successful in 19 cases (90%). The isolated genomic DNA, RNA and cDNA were all in high quality confirmed by electrophoresis in agarose gel. CONCLUSION: The problem of tissue sample size obtained by needle biopsy could be overcome by primary cell cultures. For the effective management of pediatric tumor tissue bank, fresh tissue collection with active cooperation of surgeons, organized personnel structure, and multidisciplinary standardized guidelines are necessary.
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Humans , Biopsy, Needle , Bone Marrow , Cell Culture Techniques , Cells, Cultured , Centrifugation , Culture Media, Serum-Free , Diagnosis , DNA , DNA, Complementary , Electrophoresis , Ficoll , Leukemia , Leukocytes , Nitrogen , Pediatrics , Primary Cell Culture , RNA , Sample Size , Sepharose , Tissue BanksABSTRACT
OBJECTIVE: To determine the content of lomustine in mouse tumor tissue. METHODS: Lomustine was separated and determined on a reverse-phase C18 5um column with a mobile phase of acetonitrile-H2O(54 : 46), detected at 254nm and no internal standard. RESULTS: The ca[ibration curve was 1ineaI(r = 0. 9 999) within the range of 0. 98- 15. 68ug/ml for lomus tine. The recovery ratio of lomustine was 68. 64% (n = 9). The relative standard deviation(RSD) was 0. 32%. CONCLUSION: This method is simple and accurate
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Objective:Tumor common antigen of an extract of plant and applying in early stage diagnosis for tumor were studied.Methods:Tumor cells and lymphocytes proliferate responses were determined by 3H-TdR intervening.Fresh tumor tissue from human transplant to mice,the survival rate of transplanted tumor was observed.DNA content of tumor cells was measured by flowcytometery.The chemical nature was analyzed by chromatography and measured by ultraviolet-spectrometer.Results:The extract of plant markedly stimulated the lymphocytes from tumor patients and atypical hyperplasia patient to proliferate,but failed to health persons(P