Metastasis and recurrence of tumors is the chief cause of death for such patients. Therefore, researches on the mechanism of its metastasis, prevention and treatment are the focal points in the field of traditional Ch...Metastasis and recurrence of tumors is the chief cause of death for such patients. Therefore, researches on the mechanism of its metastasis, prevention and treatment are the focal points in the field of traditional Chinese medicine (TCM) and Western medicine (WM) at present. WM practitioners" study on tumor metastasis involved its occurrence and development including every detail and process, and now it even has developed into the molecular biological field. py is used as the main means, but the efficacy is not n treatment surgical operation and radio- chemotheratoo optimistic. In recent years, TOM, as part of the comprehensive therapy, has been gradually gaining attention of oncologists. Aimed at solving the difficult problems in metastasis of tumor, many TOM practitioners on the basis of syndrome differentiation have raised theories about the cause of tumor metastasis. On the basis of these theories, some TOM recipes against tumor metastasis have been developed to serve as an effective supplement to surgical operation, radio- and chemotherapy. The present article summarizes research results in recent years about the cause of formation of tumor and its metastasis by TOM and WM, so as to offer some theoretical clues to the study of tumors metastasis.展开更多
BACKGROUND The totally implantable venous access port(TIVAP)is an important device in patients for injecting blood products,parenteral nutrition or antineoplastic chemotherapy.Metastatic spread at the site of the inse...BACKGROUND The totally implantable venous access port(TIVAP)is an important device in patients for injecting blood products,parenteral nutrition or antineoplastic chemotherapy.Metastatic spread at the site of the insertion of a TIVAP is extremely rare.CASE SUMMARY We report the case of 33-year-old male with advanced gastrointestinal stromal tumor(GIST)who underwent radical tumor resection after neoadjuvant imatinib therapy.However,a solitary GIST metastasis at the site of a TIVAP insertion developed during adjuvant imatinib treatment.Mutational analysis showed secondary mutation in KIT exon 13(V564 A),which is resistant to imatinib treatment.To our knowledge,this is the first case report of a patient with advanced GIST developing GIST metastasis at the site of a TIVAP insertion.CONCLUSION This case highlights that when a patient with advanced,high metastatic GIST requires TIVAP insertion,we should realize that there is a risk of developing tumor metastasis at the site of a TIVAP insertion.展开更多
Bladder tumor is the most common malignant tumor in urinary system and always com- panied with lymph node metastasis. The accurate staging plays a significant role in treatment for bladder tumor and prognostic evaluat...Bladder tumor is the most common malignant tumor in urinary system and always com- panied with lymph node metastasis. The accurate staging plays a significant role in treatment for bladder tumor and prognostic evaluation, and the distant metastasis predicts worse prognosis. The objective of this study was to assess the clinical significance of 18F-FDG PET/CT imaging in diagnosing bladder tumor metastasis lesions. A retrospective analysis of 60 patients with bladder tumor from October 2008 to May 2010 was done. The patients were stratified based on the imaging technique. Among all 60 cases, besides the primary lesion, 81 suspected lesions were spotted and 73 confirmed as metastasis, including 50 lymph node metastases, 22 distant metastases, and 1 bone metastasis. For PET/CT imaging, its sensitivity was 94.5%, specificity 87.5%, positive predictive value 98.6%, negative predictive value 63.6% and accuracy 93.8% respectively. For CT, its sensitivity was 82.2%, specificity 50%, positive predictive value 93.8%, negative predictive value 23.5% and accuracy 79% respectively. PET/CT im- aging was superior to CT in sensitivity, specificity and accuracy. In conclusion, 18F-FDG PET/CT imaging is more significant in diagnosing bladder tumor metastasis lesions.展开更多
Pyroptosis is a type of programmed cell death mediated by gasdermines(GSDMs).The N-terminal domain of GSDMs forms pores in the plasma membrane,causing cell membrane rupture and the release of cell contents,leading to ...Pyroptosis is a type of programmed cell death mediated by gasdermines(GSDMs).The N-terminal domain of GSDMs forms pores in the plasma membrane,causing cell membrane rupture and the release of cell contents,leading to an inflammatory response and mediating pyrodeath.Pyroptosis plays an important role in inflammatory diseases and malignant tumors.With the further study of pyroptosis,an increasing number of studies have shown that the pyroptosis pathway can regulate the tumor microenvironment and antitumor immunity of colorectal cancer and is closely related to the occurrence,development,treatment and prognosis of colorectal cancer.This review aimed to explore the molecular mechanism of pyroptosis and the role of pyroptosis in the occurrence,development,treatment and prognosis of colorectal cancer(CRC)and to provide ideas for the clinical diagnosis and treatment of CRC.展开更多
BACKGROUND Our study investigated the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma(PDAC)metastasis.AIM To further investigate the r...BACKGROUND Our study investigated the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma(PDAC)metastasis.AIM To further investigate the role of FAM53B in regulating macrophage M2 polarization and its potential mechanism in promoting PDAC metastasis.Our goal is to determine how FAM53B affects macrophage M2 polarization and to define its underlying mechanism in PDAC metastasis.METHODS Cell culture and various experiments,including protein analysis,immunohisto-chemistry,and animal model experiments,were conducted.We compared FAM53B expression between PDAC tissues and healthy tissues and assessed the correlation of FAM53B expression with clinical features.Our study analyzed the role of FAM53B in macrophage M2 polarization in vitro by examining the expression of relevant markers.Finally,we used a murine model to study the role of FAM53B in PDAC metastasis and analyzed the potential underlying mechanisms.RESULTS Our research showed that there was a significant increase in FAM53B levels in PDAC tissues,which was linked to adverse tumor features.Experimental findings indicated that FAM53B can enhance macrophage M2 polarization,leading to increased anti-inflammatory factor release.The results from the mouse model further supported the role of FAM53B in PDAC metastasis,as blocking FAM53B prevented tumor cell invasion and metastasis.CONCLUSION FAM53B promotes PDAC metastasis by regulating macrophage M2 polarization.This discovery could lead to the development of new strategies for treating PDAC.For example,interfering with the FAM53B signaling pathway may prevent cancer spread.Our research findings also provide important information for expanding our understanding of PDAC pathogenesis.展开更多
BACKGROUND Colorectal cancer(CRC)is a common malignant tumor,and liver metastasis is one of the main recurrence and metastasis modes that seriously affect patients’survival rate and quality of life.Indicators such as...BACKGROUND Colorectal cancer(CRC)is a common malignant tumor,and liver metastasis is one of the main recurrence and metastasis modes that seriously affect patients’survival rate and quality of life.Indicators such as albumin bilirubin(ALBI)score,liver function index,and carcinoembryonic antigen(CEA)have shown some potential in the prediction of liver metastasis but have not been fully explored.AIM To evaluate its predictive value for liver metastasis of CRC by conducting the combined analysis of ALBI,liver function index,and CEA,and to provide a more accurate liver metastasis risk assessment tool for clinical treatment guidance.METHODS This study retrospectively analyzed the clinical data of patients with CRC who received surgical treatment in our hospital from January 2018 to July 2023 and were followed up for 24 months.According to the follow-up results,the enrolled patients were divided into a liver metastasis group and a nonliver metastasis group and randomly divided into a modeling group and a verification group at a ratio of 2:1.The risk factors for liver metastasis in patients with CRC were analyzed,a prediction model was constructed by least absolute shrinkage and selection operator(LASSO)logistic regression,internal validation was performed by the bootstrap method,the reliability of the prediction model was evaluated by subject-work characteristic curves,calibration curves,and clinical decision curves,and a column graph was drawn to show the prediction results.RESULTS Of 130 patients were enrolled in the modeling group and 65 patients were enrolled in the verification group out of the 195 patients with CRC who fulfilled the inclusion and exclusion criteria.Through LASSO regression variable screening and logistic regression analysis.The ALBI score,alanine aminotransferase(ALT),and CEA were found to be independent predictors of liver metastases in CRC patients[odds ratio(OR)=8.062,95%confidence interval(CI):2.545-25.540],(OR=1.037,95%CI:1.004-1.071)and(OR=1.025,95%CI:1.008-1.043).The area under the receiver operating characteristic curve(AUC)for the combined prediction of CRLM in the modeling group was 0.921,with a sensitivity of 78.0%and a specificity of 95.0%.The H-index was 0.921,and the H-L fit curve hadχ^(2)=0.851,a P value of 0.654,and a slope of the calibration curve approaching 1.This indicates that the model is extremely accurate,and the clinical decision curve demonstrates that it can be applied effectively in the real world.We conducted internal verification of one thousand resamplings of the modeling group data using the bootstrap method.The AUC was 0.913,while the accuracy was 0.869 and the kappa consistency was 0.709.The combination prediction of liver metastasis in patients with CRC in the verification group had an AUC of 0.918,sensitivity of 85.0%,specificity of 95.6%,C-index of 0.918,and an H-L fitting curve withχ^(2)=0.586,P=0.746.CONCLUSION The ALBI score,ALT level,and CEA level have a certain value in predicting liver metastasis in patients with CRC.These three criteria exhibit a high level of efficacy in forecasting liver metastases in patients diagnosed with CRC.The risk prediction model developed in this work shows great potential for practical application.展开更多
As one of the most serious threats to human being,cancer is hard to be treated when metastasis happens.What’s worse,there are few identified targets of metastasis for drug development.Therefore,it is important to dev...As one of the most serious threats to human being,cancer is hard to be treated when metastasis happens.What’s worse,there are few identified targets of metastasis for drug development.Therefore,it is important to develop strategies to prevent metastasis or treat existed metastasis.This review focuses on the procedure of metastasis,and first summarizes the targeting delivery strategies,including primary tumor targeting drug delivery,tumor metastasis targeting drug delivery and hijacking circulation cells.Then,as a promising treatment,the application of immunotherapy in tumor metastasis treatment is introduced,and strategies that stimulating immune response are reviewed,including chemotherapy,photothermal therapy,photodynamic therapy,ferroptosis,sonodynamic therapy,and nanovaccines.Finally,the challenges and perspective about nanoparticle-enabled tumor metastasis treatment are discussed.展开更多
Rosa rugosa Thunb.is recognized as both medicine and edible in China.The article investigated the antitumor activity of rose flavonoids.Water-extracted rose flavonoids(RFW)and ethanol-extracted rose flavonoids(RFE)wer...Rosa rugosa Thunb.is recognized as both medicine and edible in China.The article investigated the antitumor activity of rose flavonoids.Water-extracted rose flavonoids(RFW)and ethanol-extracted rose flavonoids(RFE)were achieved by extracting with distilled water and 70%ethanol,respectively.The effects of the two extracts on proliferation inhibition,apoptosis inducement and metastasis prevention of human HepG2 hepatocellular carcinoma cell lines were tested,via optical/fluorescence microscopy,MTT detection,Transwell assay,flow cytometry and Western blot,etc.The results indicated that rose flavonoids at low concentration(10-40μg/mL)had a better inhibitory effect on migration and invasion of HepG2 cells in a dose-dependent manner,while rose flavonoids at high concentration(80-160μg/mL)could induce apoptosis of HepG2 cells by up-regulating the expression of pro-apoptotic proteins p53 and Bax,and down-regulating the expression of anti-apoptotic proteins Bcl-2,leading to the functioning of caspase-3 and caspase-9.The effect of RFE at the same concentration was significantly better than that of RFW.Conclusion,this study found that rose flavonoids had a certain inhibitory effect on proliferation and metastasis of human liver cancer cells HepG2,indicating the application of rose flavonoids in preventing and treating of liver cancer.展开更多
Background:Fascin is crucial for cancer cell filopodium formation and tumor metastasis,and is functionally regulated by post-translational modifications.However,whether and how Fascin is regulated by acetylation remai...Background:Fascin is crucial for cancer cell filopodium formation and tumor metastasis,and is functionally regulated by post-translational modifications.However,whether and how Fascin is regulated by acetylation remains unclear.This study explored the regulation of Fascin acetylation and its corresponding roles in filopodium formation and tumor metastasis.Methods:Immunoprecipitation and glutathione-S-transferase pull-down assays were performed to examine the interaction between Fascin and acetyltransferase P300/CBP-associated factor(PCAF),and immunofluorescence was used to investigate their colocalization.An in vitro acetylation assay was performed to identify Fascin acetylation sites by using mass spectrometry.A specific antibody against acetylated Fascin was generated and used to detect the PCAF-mediated Fascin acetylation in esophageal squamous cell carcinoma(ESCC)cells using Western blotting by overexpressing and knocking down PCAF expression.An in vitro cell migration assay was performed,and a xenograft model was established to study in vivo tumor metastasis.Live-cell imaging and fluorescence recovery after photobleaching were used to evaluate the function and dynamics of acetylated Fascin in filopodium formation.The clinical significance of acetylated Fascin and PCAF in ESCC was evaluated using immunohistochemistry.Results:Fascin directly interacted and colocalized with PCAF in the cytoplasm and was acetylated at lysine 471(K471)by PCAF.Using the specific antiAcK471-Fascin antibody,Fascin was found to be acetylated in ESCC cells,and the acetylation level was consequently increased after PCAF overexpression and decreased after PCAF knockdown.Functionally,Fascin-K471 acetylation markedly suppressed in vitro ESCC cell migration and in vivo tumor metastasis,whereas Fascin-K471 deacetylation exhibited a potent oncogenic function.Moreover,Fascin-K471 acetylation reduced filopodial length and density,and lifespan of ESCC cells,while its deacetylation produced the opposite effect.In the filipodium shaft,K471-acetylated Fascin displayed rapid dynamic exchange,suggesting that it remained in its monomeric form owing to its weakened actinbundling activity.Clinically,high levels of AcK471-Fascin in ESCC tissues were strongly associated with prolonged overall survival and disease-free survival of ESCC patients.Conclusions:Fascin interacts directly with PCAF and is acetylated at lysine 471 in ESCC cells.Fascin-K471 acetylation suppressed ESCC cell migration and tumor metastasis by reducing filopodium formation through the impairment of its actin-bundling activity.展开更多
Objective:rupture of liver metasta-ses with disturbance of consciousness accompanied by aggravation of hemiplegia is very rare.We describe the clinical features of a case of spontaneous rupture of liver metastasis tum...Objective:rupture of liver metasta-ses with disturbance of consciousness accompanied by aggravation of hemiplegia is very rare.We describe the clinical features of a case of spontaneous rupture of liver metastasis tumors with disturbance of consciousness and progression of right limb hemiplegia.Methods:collect the patient's medical history,conduct a detailed physi-cal examination,timely improve the relevant laboratory and imaging examination,formulate a comprehensive treatment plan,and track the changes of the disease and the treatment effect.Results:the patient presented with blurred consciousness,hemiplegia of the right limb,and epigastric tenderness when admitted to the hospital.No evident new lesions were found on cranial computed to-mography(CT).Blood routine examination showed that hemoglobin decreased significantly compared with be-fore.Abdominal CT showed tumor rupture and bleeding.The patient in critical condition did not have operation conditions,but improved after conservative treatment.Conclusion:when patients with liver metastasis tumors suddenly have a disturbance of consciousness and prog-ress of hemiplegia,they should not only be considered to have acute cerebrovascular diseases,but also the possi-bility of rupture of liver metastasis tumors.If only treated according to acute stroke,it will endanger their lives.For the liver metastasis tumor rupture,if there is no oppor-tunity for embolotherapy,timely conservative treatment with drugs can also achieve good results.展开更多
To study the effect of IL-18 and nitric oxide(NO) on the growth and metastasis of non-small cell lung cancer (NSCLC).Methods Serum IL-18 and nitrate and nitrite levels in 82 patients with NSCLC and 20 healthy control ...To study the effect of IL-18 and nitric oxide(NO) on the growth and metastasis of non-small cell lung cancer (NSCLC).Methods Serum IL-18 and nitrate and nitrite levels in 82 patients with NSCLC and 20 healthy control subjects were measured by using ELISA and Griess.Results The levels of serum IL-18 were (334.2±31.0)ng/L in NSCLC patients and (151.3±22.0)ng/L in control subjects,respectively.The levels of nitrate and nitrite were (237.1±21.0)μmol/L in NSCLC patients and (44.2±15.0)μmol/L in control subjects.The levels of serum IL-18 and nitrate and nitrite were not related with age,gender,histological types in patients with NSCLC.The levels of serum IL-18 was closely associated with TNM stage,lymph node metastasis and distal metastasis,but not with its degree and organ types of metastasis.There was a negative correlation between the levels of serum IL-18 and nitrate and nitrite.Conclusion Serum IL-18 and nitrate and nitrite levels may be useful to evaluate the prognosis of the patients with NSCLC.16 refs,2 tabs.展开更多
BACKGROUND: FasL expression was reported to be asso- ciated with hepatic metastasis of colorectal cancer. The aim of this study was to study FasL gene expression in colorectal carcinoma and its influences on biologica...BACKGROUND: FasL expression was reported to be asso- ciated with hepatic metastasis of colorectal cancer. The aim of this study was to study FasL gene expression in colorectal carcinoma and its influences on biological behavior and he- patic metastasis of colorectal carcinoma. METHODS: FasL gene expressions were examined with re- verse transcriptase-polymerase chain reaction (RT-PCR) in the primary focus of colorectal carcinoma, adjacent can- cerous mucosae, and metastasized liver focus from colorec- tal cancer. HR-8348 cells of human rectal cancer cell line were transfected with FasL cDNA. Cell growth suppression rate and response to 5-FU and carboplatin were observed and analyzed with the MTT method. RESULTS: FasL gene expression was detected in the prima- ry focus of colorectal cancer ( n = 58), adjacent cancerous mucosae ( n = 58), and metastasized hepatic tumor tissues (n =28). The positive rate of FasL expression was 24% (14/ 58), 8% (5/58), and 100% (58/58) in the primary focus, adjacent cancerous mucosae and metastasized hepatic tumor tissues respectively. FasL expression rate in the me- tastasized hepatic tumor tissues was higher than that in the primary focus (χ2 = 43.49, P<0. 01) and adjacent cance- rous mucosae (χ2=57.66, P<0.01). In a group of patients with hepatic metastasis, the FasL expression rate in primary focus was higher than that in patients without hepatic me- tastasis (χ2=3.96, P <0.05). In vitro study positive expres- sion of FasL was shown in transfected HR-8348 cells. When 5-FU or carboplatin was added, there was a significant difference in growth suppression rate between FasL positive and controlled cancer cells (t=9.02, t = 11.93, P<0.01). Under the same concentration of chemotherapeutic agents, the survival rate of FasL positive HR-8348 cells was higher than that of controlled cells. CONCLUSIONS: FasL positive cancer cells are powerfullyresistant to chemotherapeutic agents. The expression of the FasL gene in colorectal cancer cells is related to immune evasion to escape from being killed by immune cells, show- ing stronger drug-resistance, and it facilitates hepatic me- tastasis.展开更多
TMTP1, a 5-amino acid peptide NVVRQ, obtained by using the flagella peptide library screening in our previous studies, can be used for the labeling of malignant in situ and metastatic lesions, and even micro-metastase...TMTP1, a 5-amino acid peptide NVVRQ, obtained by using the flagella peptide library screening in our previous studies, can be used for the labeling of malignant in situ and metastatic lesions, and even micro-metastases. In this study, TMTP1 was assessed for its ability to specifically target the malignant hematopoietic cells and metastatic lesions of hematological malignancies. FITC-TMTP1 was chemically synthesized. Immunofluorescence assay and competitive test were carried out to determine the specific binding capacity of TMTPl to hematological malignant cell lines, including HL60, k562, SHI-1, Jurkat, Raji, El-4 and umbilical cord blood mononuclear cells. Mononuclear cells were isolated from the bone marrow of healthy subjects and patients with chronic myeloid leukemia. Then the cells were co-clutured with TMTP1 or scrambled peptides and the binding and affinity of TMTP1 peptide to the primary cells of hematological malignancies were flow cytometrically analyzed. The binding speci-ficity of TMTP1 to target hematological malignancies was measured in vivo by intravenous injection of FITC-conjugated TMTP1 into El-4 lymphoma-bearing mice. The results showed that TMTP1 specifi-cally bound to the cells of a series of hematological malignancies, including HL60, k562, Jurkat, Raji , El-4 and chronic myeloid leukemia primary cells but not to bone marrow mononuclear cells from healthy subjects. By contrast, TMTP1 could bind to the metastatic foci of lymphoma originating from the EL-4 cell line while the scrambled peptide failed to do so. Moreover, the occult metastases could be identified, with high specificity, by detecting FITC-TMTP1. We are led to conclude that TMTP1, as a novel tumor-homing peptide, can serve as a marker for primary malignant and metastatic lesions for the early diagnosis of hematological malignances and a carrier of anticancer drugs for cancer treatment.展开更多
On the basis of preparation of anti-metastatic recombinant FN polypeptides, CH50 and CH56, we further studied the function of these polypeptides.The capacity of CH50 binding with melanoma cells (ED50 30 mM) was higher...On the basis of preparation of anti-metastatic recombinant FN polypeptides, CH50 and CH56, we further studied the function of these polypeptides.The capacity of CH50 binding with melanoma cells (ED50 30 mM) was higher than that of CH56 (ED50 45 mM). Both of the polypeptides could significantly suppress the binding of melanoma B16 cells to laminin. There was no significant difference in the inhibitory effect between two polypeptides. In the experimental metastasis of melanoma cells, both of CH50 and CH56 could significantly inhibit the metastasis of the tumor cells, and reduce the number of lung metastasis by about 80%. Our results suggest that Ⅲ-11 and ED-A repeats influenced, to some extent, the binding capacity of bifunctional-domain polypeptide to cells, but did not affect the inhibition of the polypeptide on the metastasis of melanoma cells. The presence and connection of cell Ⅰ and Hep Ⅱ domains are the elements which determine the ability of recoinbinant FN polypeptides to inhibit the metastasis of tumor cells.展开更多
Background: Ankyrin repeat and SOCS box protein 3(ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradatio...Background: Ankyrin repeat and SOCS box protein 3(ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradation of tumor necrosis factor receptor 2 and is likely involved in inflammatory responses. However, its effects on oncogenesis are unclear. This study aimed to investigate the effects of ASB3 on the growth and metastasis of colorectal cancer(CRC).Methods: We used next?generation sequencing or Sanger sequencing to detect ASB3 mutations in CRC specimens or cell lines, and used real?time quantitative polymerase chain reaction, Western blotting, and immunohistochemical or immunofluorescence assay to determine gene expression. We evaluated cell proliferation by MTT and colony for?mation assays, tested cell cycle distribution by flow cytometry, and assessed cell migration and invasion by transwell and wound healing assays. We also performed nude mouse experiments to evaluate tumorigenicity and hepatic metastasis potential of tumor cells.Results: We found that ASB3 gene was frequently mutated(5.3%) and down?regulated(70.4%) in CRC cases. Knock?down of endogenous ASB3 expression promoted CRC cell proliferation, migration, and invasion in vitro and facilitated tumorigenicity and hepatic metastasis in vivo. Conversely, the ectopic overexpression of wild?type ASB3, but not that of ASB3 mutants that occurred in clinical CRC tissues, inhibited tumor growth and metastasis. Further analysis showed that ASB3 inhibited CRC metastasis likely by retarding epithelial?mesenchymal transition, which was characterized by the up?regulation of β?catenin and E?cadherin and the down?regulation of transcription factor 8, N?cadherin, and vimentin.Conclusion: ASB3 dysfunction resulted from gene mutations or down?regulated expression frequently exists in CRC and likely plays a key role in the pathogenesis and progression of CRC.展开更多
Metastasis is closely related to the high mortality of cancer patients,which is regulated by multiple signaling pathways.Hence,multiphase blocking of this biological process is beneficial for cancer treatments.Herein,...Metastasis is closely related to the high mortality of cancer patients,which is regulated by multiple signaling pathways.Hence,multiphase blocking of this biological process is beneficial for cancer treatments.Herein,we establish a multifunctional self-delivering system by synthesizing D-α-tocopheryl succinates(TOS)-conjugated chondroitin sulfate(CS)(CT NPs),which both serve as nanocarrier and antimetastatic agent that affects different phases of the metastatic cascade.TOS as the hydrophobic segment of CT NPs can inhibit the secretion of matrix metalloproteinase-9,while the hydrophilic segment CS targets B16F10 cells through CD44 receptors and reduces the interaction between tumor cells and platelets.The results show that CT NPs are able to inhibit metastasis successfully both in vitro and in vivo by interfering the multiphase of the metastatic cascade.Following encapsulating chemotherapeutic drug doxorubicin(DOX),the obtained micelles CT/DOX efficiently suppress both primary-tumor growth and metastases in B16F10 bearing mice.As a result,the rationally designed multifunctional NPs composing of biocompatible materials provide excellent therapeutic effects on solid tumors and metastases。展开更多
BACKGROUND Secondary jejunal tumor from renal cell carcinoma(RCC)is extremely rare in clinical practice and is easily missed and misdiagnosed because of the low incidence and atypical symptoms.CASE SUMMARY A 38-year-o...BACKGROUND Secondary jejunal tumor from renal cell carcinoma(RCC)is extremely rare in clinical practice and is easily missed and misdiagnosed because of the low incidence and atypical symptoms.CASE SUMMARY A 38-year-old male patient was diagnosed pathologically with left RCC after radical nephrectomy in 2012.The patient then suffered multiple lung metastases 2 years later and was treated with oral sorafenib without progression for 6 years.In 2020,an emergency intestinal segmental resection due to intestinal obstruction was required,and postoperative pathology confirmed a jejunal secondary tumor from RCC.The patient had a smooth recovery following surgery.Three months after surgery,the patient was diagnosed with left adrenal metastasis,and subsequent sintilimab therapy has stabilized his condition.CONCLUSION This report is written to remind urologists and pathologists of the potential for small intestinal secondary tumors when a patient with a history of RCC seeks treatment for digestive symptoms.Enteroscopy and abdominal contrast-enhanced computed tomography are essential means of examination,but severe cases require immediate surgical intervention despite the lack of a preoperative examination to distinguish tumor attributes.展开更多
The tumor suppressor protein p53 is central to cancer biology,with its pathway reactivation emerging as a promising therapeutic strategy in oncology.This study introduced LZ22,a novel compound that selectively inhibit...The tumor suppressor protein p53 is central to cancer biology,with its pathway reactivation emerging as a promising therapeutic strategy in oncology.This study introduced LZ22,a novel compound that selectively inhibits the growth,migration,and metastasis of tumor cells expressing wild-type p53,demonstrating ineffectiveness in cells devoid of p53 or those expressing mutant p53.LZ22’s mechanism of action involves a high-affinity interaction with the histidine-96 pocket of the MDM2 protein.This interaction disrupted the MDM2-p53 binding,consequently stabilizing p53 by shielding it from proteasomal degradation.LZ22 impeded cell cycle progression and diminished cell proliferation by reinstating the p53-dependent suppression of the CDK2/Rb signaling pathway.Moreover,LZ22 alleviated the p53-dependent repression of Snail transcription factor expression and its consequent EMT,effectively reducing tumor cell migration and distal metastasis.Importantly,LZ22 administration in tumor-bearing mice did not manifest notable side effects.The findings position LZ22 as a structurally unique reactivator of p53,offering therapeutic promise for the management of human cancers with wild-type TP53.展开更多
To investigate the invasive ability of the residual tumor cells after immunotherapy and explore the feasible approach suppressing the invasion, mice were inoculated with B16 cells, and then treated by gene therapy wit...To investigate the invasive ability of the residual tumor cells after immunotherapy and explore the feasible approach suppressing the invasion, mice were inoculated with B16 cells, and then treated by gene therapy with p4-1BBL/psPD-1 or IFN-γ. The production and activities of MMP-9 and MMP-2 in residual tumor tissues were analyzed with gelatin zymography 1 day and 7 days after the termination of the immunotherapy. The production of MMP-9 and MMP-2 by B16 cells treated with IFN-γ was also analyzed. IFN-γ-treated B16 cells were inoculated to mice via subcutaneous injection. The invasion of tumor to muscular tissue was analyzed. Gene therapy with CH50 was used to suppress the invasive growth of tumor. The results showed that the expression and the activities of MMP-9 and MMP-2 were significantly increased 7 days after the end of immunotherapy. The re- sponse of tumor cells to ECM molecules was intensified after the removal of IFN-γ, resulting in significant increase of both the production and activities of MMP-9 and MMP-2, and the increased invasion of tumor. Gene therapy with CH50 effectively suppressed the invasive growth of tumor. It is concluded that the termination of immunotherapy may result in a higher metastatic potential of residual tumor cells. Suppressing tumor invasion by suitable treatment will improve the efficacy of immunotherapy..展开更多
γ-Interferon (IFN-Y) was detected by ELISA assayin ascitic fluid from a number of ovarian cancer patients.To study its clinical significance, the effect of IFN-Y on the metastatic potential of a mouse mammary adenoca...γ-Interferon (IFN-Y) was detected by ELISA assayin ascitic fluid from a number of ovarian cancer patients.To study its clinical significance, the effect of IFN-Y on the metastatic potential of a mouse mammary adenocarcinoma, MA-891, was explored. Pretreatment of the tumor cells in vitro for 48 hr with recombinant IFN-γ significantly increased the number of lung tumor nodules after iv. or sc. inoculation into (TA2×615) F1 mice. In contrast, when recombinant IFN-αpretreated MA-891 cells were likewise injected into mice significant decrease in metastatic potential was seen. The study in vitro indicated that pretreatment of the tumor cells with IFN-γbut not IFN-αresulted in a decrease in susceptibility to NK cell cytotoxicity. Inasmuch as both IFN-αand IFN-γcan induce MHC class I expression on target cells, the increase in matastatic potential of IFN-γ-treated tumor cells can be explained only partially on the basis of their reduced NK cells susceptibility.展开更多
文摘Metastasis and recurrence of tumors is the chief cause of death for such patients. Therefore, researches on the mechanism of its metastasis, prevention and treatment are the focal points in the field of traditional Chinese medicine (TCM) and Western medicine (WM) at present. WM practitioners" study on tumor metastasis involved its occurrence and development including every detail and process, and now it even has developed into the molecular biological field. py is used as the main means, but the efficacy is not n treatment surgical operation and radio- chemotheratoo optimistic. In recent years, TOM, as part of the comprehensive therapy, has been gradually gaining attention of oncologists. Aimed at solving the difficult problems in metastasis of tumor, many TOM practitioners on the basis of syndrome differentiation have raised theories about the cause of tumor metastasis. On the basis of these theories, some TOM recipes against tumor metastasis have been developed to serve as an effective supplement to surgical operation, radio- and chemotherapy. The present article summarizes research results in recent years about the cause of formation of tumor and its metastasis by TOM and WM, so as to offer some theoretical clues to the study of tumors metastasis.
基金the National Natural Science Foundation of China,No.815729311.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University,No.ZYJC18034。
文摘BACKGROUND The totally implantable venous access port(TIVAP)is an important device in patients for injecting blood products,parenteral nutrition or antineoplastic chemotherapy.Metastatic spread at the site of the insertion of a TIVAP is extremely rare.CASE SUMMARY We report the case of 33-year-old male with advanced gastrointestinal stromal tumor(GIST)who underwent radical tumor resection after neoadjuvant imatinib therapy.However,a solitary GIST metastasis at the site of a TIVAP insertion developed during adjuvant imatinib treatment.Mutational analysis showed secondary mutation in KIT exon 13(V564 A),which is resistant to imatinib treatment.To our knowledge,this is the first case report of a patient with advanced GIST developing GIST metastasis at the site of a TIVAP insertion.CONCLUSION This case highlights that when a patient with advanced,high metastatic GIST requires TIVAP insertion,we should realize that there is a risk of developing tumor metastasis at the site of a TIVAP insertion.
文摘Bladder tumor is the most common malignant tumor in urinary system and always com- panied with lymph node metastasis. The accurate staging plays a significant role in treatment for bladder tumor and prognostic evaluation, and the distant metastasis predicts worse prognosis. The objective of this study was to assess the clinical significance of 18F-FDG PET/CT imaging in diagnosing bladder tumor metastasis lesions. A retrospective analysis of 60 patients with bladder tumor from October 2008 to May 2010 was done. The patients were stratified based on the imaging technique. Among all 60 cases, besides the primary lesion, 81 suspected lesions were spotted and 73 confirmed as metastasis, including 50 lymph node metastases, 22 distant metastases, and 1 bone metastasis. For PET/CT imaging, its sensitivity was 94.5%, specificity 87.5%, positive predictive value 98.6%, negative predictive value 63.6% and accuracy 93.8% respectively. For CT, its sensitivity was 82.2%, specificity 50%, positive predictive value 93.8%, negative predictive value 23.5% and accuracy 79% respectively. PET/CT im- aging was superior to CT in sensitivity, specificity and accuracy. In conclusion, 18F-FDG PET/CT imaging is more significant in diagnosing bladder tumor metastasis lesions.
文摘Pyroptosis is a type of programmed cell death mediated by gasdermines(GSDMs).The N-terminal domain of GSDMs forms pores in the plasma membrane,causing cell membrane rupture and the release of cell contents,leading to an inflammatory response and mediating pyrodeath.Pyroptosis plays an important role in inflammatory diseases and malignant tumors.With the further study of pyroptosis,an increasing number of studies have shown that the pyroptosis pathway can regulate the tumor microenvironment and antitumor immunity of colorectal cancer and is closely related to the occurrence,development,treatment and prognosis of colorectal cancer.This review aimed to explore the molecular mechanism of pyroptosis and the role of pyroptosis in the occurrence,development,treatment and prognosis of colorectal cancer(CRC)and to provide ideas for the clinical diagnosis and treatment of CRC.
文摘BACKGROUND Our study investigated the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma(PDAC)metastasis.AIM To further investigate the role of FAM53B in regulating macrophage M2 polarization and its potential mechanism in promoting PDAC metastasis.Our goal is to determine how FAM53B affects macrophage M2 polarization and to define its underlying mechanism in PDAC metastasis.METHODS Cell culture and various experiments,including protein analysis,immunohisto-chemistry,and animal model experiments,were conducted.We compared FAM53B expression between PDAC tissues and healthy tissues and assessed the correlation of FAM53B expression with clinical features.Our study analyzed the role of FAM53B in macrophage M2 polarization in vitro by examining the expression of relevant markers.Finally,we used a murine model to study the role of FAM53B in PDAC metastasis and analyzed the potential underlying mechanisms.RESULTS Our research showed that there was a significant increase in FAM53B levels in PDAC tissues,which was linked to adverse tumor features.Experimental findings indicated that FAM53B can enhance macrophage M2 polarization,leading to increased anti-inflammatory factor release.The results from the mouse model further supported the role of FAM53B in PDAC metastasis,as blocking FAM53B prevented tumor cell invasion and metastasis.CONCLUSION FAM53B promotes PDAC metastasis by regulating macrophage M2 polarization.This discovery could lead to the development of new strategies for treating PDAC.For example,interfering with the FAM53B signaling pathway may prevent cancer spread.Our research findings also provide important information for expanding our understanding of PDAC pathogenesis.
文摘BACKGROUND Colorectal cancer(CRC)is a common malignant tumor,and liver metastasis is one of the main recurrence and metastasis modes that seriously affect patients’survival rate and quality of life.Indicators such as albumin bilirubin(ALBI)score,liver function index,and carcinoembryonic antigen(CEA)have shown some potential in the prediction of liver metastasis but have not been fully explored.AIM To evaluate its predictive value for liver metastasis of CRC by conducting the combined analysis of ALBI,liver function index,and CEA,and to provide a more accurate liver metastasis risk assessment tool for clinical treatment guidance.METHODS This study retrospectively analyzed the clinical data of patients with CRC who received surgical treatment in our hospital from January 2018 to July 2023 and were followed up for 24 months.According to the follow-up results,the enrolled patients were divided into a liver metastasis group and a nonliver metastasis group and randomly divided into a modeling group and a verification group at a ratio of 2:1.The risk factors for liver metastasis in patients with CRC were analyzed,a prediction model was constructed by least absolute shrinkage and selection operator(LASSO)logistic regression,internal validation was performed by the bootstrap method,the reliability of the prediction model was evaluated by subject-work characteristic curves,calibration curves,and clinical decision curves,and a column graph was drawn to show the prediction results.RESULTS Of 130 patients were enrolled in the modeling group and 65 patients were enrolled in the verification group out of the 195 patients with CRC who fulfilled the inclusion and exclusion criteria.Through LASSO regression variable screening and logistic regression analysis.The ALBI score,alanine aminotransferase(ALT),and CEA were found to be independent predictors of liver metastases in CRC patients[odds ratio(OR)=8.062,95%confidence interval(CI):2.545-25.540],(OR=1.037,95%CI:1.004-1.071)and(OR=1.025,95%CI:1.008-1.043).The area under the receiver operating characteristic curve(AUC)for the combined prediction of CRLM in the modeling group was 0.921,with a sensitivity of 78.0%and a specificity of 95.0%.The H-index was 0.921,and the H-L fit curve hadχ^(2)=0.851,a P value of 0.654,and a slope of the calibration curve approaching 1.This indicates that the model is extremely accurate,and the clinical decision curve demonstrates that it can be applied effectively in the real world.We conducted internal verification of one thousand resamplings of the modeling group data using the bootstrap method.The AUC was 0.913,while the accuracy was 0.869 and the kappa consistency was 0.709.The combination prediction of liver metastasis in patients with CRC in the verification group had an AUC of 0.918,sensitivity of 85.0%,specificity of 95.6%,C-index of 0.918,and an H-L fitting curve withχ^(2)=0.586,P=0.746.CONCLUSION The ALBI score,ALT level,and CEA level have a certain value in predicting liver metastasis in patients with CRC.These three criteria exhibit a high level of efficacy in forecasting liver metastases in patients diagnosed with CRC.The risk prediction model developed in this work shows great potential for practical application.
基金supported by National Natural Science Foundation of China(81961138009)111 Project(B18035,China)
文摘As one of the most serious threats to human being,cancer is hard to be treated when metastasis happens.What’s worse,there are few identified targets of metastasis for drug development.Therefore,it is important to develop strategies to prevent metastasis or treat existed metastasis.This review focuses on the procedure of metastasis,and first summarizes the targeting delivery strategies,including primary tumor targeting drug delivery,tumor metastasis targeting drug delivery and hijacking circulation cells.Then,as a promising treatment,the application of immunotherapy in tumor metastasis treatment is introduced,and strategies that stimulating immune response are reviewed,including chemotherapy,photothermal therapy,photodynamic therapy,ferroptosis,sonodynamic therapy,and nanovaccines.Finally,the challenges and perspective about nanoparticle-enabled tumor metastasis treatment are discussed.
基金supported by the natural science foundation of Shandong province ZR2017BH053the youth doctor cooperation foundation of Qilu University of Technology(Shandong Academy of Sciences)2017BSH2017。
文摘Rosa rugosa Thunb.is recognized as both medicine and edible in China.The article investigated the antitumor activity of rose flavonoids.Water-extracted rose flavonoids(RFW)and ethanol-extracted rose flavonoids(RFE)were achieved by extracting with distilled water and 70%ethanol,respectively.The effects of the two extracts on proliferation inhibition,apoptosis inducement and metastasis prevention of human HepG2 hepatocellular carcinoma cell lines were tested,via optical/fluorescence microscopy,MTT detection,Transwell assay,flow cytometry and Western blot,etc.The results indicated that rose flavonoids at low concentration(10-40μg/mL)had a better inhibitory effect on migration and invasion of HepG2 cells in a dose-dependent manner,while rose flavonoids at high concentration(80-160μg/mL)could induce apoptosis of HepG2 cells by up-regulating the expression of pro-apoptotic proteins p53 and Bax,and down-regulating the expression of anti-apoptotic proteins Bcl-2,leading to the functioning of caspase-3 and caspase-9.The effect of RFE at the same concentration was significantly better than that of RFW.Conclusion,this study found that rose flavonoids had a certain inhibitory effect on proliferation and metastasis of human liver cancer cells HepG2,indicating the application of rose flavonoids in preventing and treating of liver cancer.
基金National Natural Science Foundation of China,Grant/Award Numbers:81872372,81902469Natural Science Foundation of China-Guangdong Joint Fund,Grant/Award Number:U0932001+2 种基金National Cohort of Esophageal Cancer of China,Grant/Award Number:2016YFC0901400China Postdoctoral Science Foundation,Grant/Award Number:2018M6431342020 Li Ka Shing Foundation Cross-Disciplinary Research Grant,Grant/Award Number:2020LKSFG07B。
文摘Background:Fascin is crucial for cancer cell filopodium formation and tumor metastasis,and is functionally regulated by post-translational modifications.However,whether and how Fascin is regulated by acetylation remains unclear.This study explored the regulation of Fascin acetylation and its corresponding roles in filopodium formation and tumor metastasis.Methods:Immunoprecipitation and glutathione-S-transferase pull-down assays were performed to examine the interaction between Fascin and acetyltransferase P300/CBP-associated factor(PCAF),and immunofluorescence was used to investigate their colocalization.An in vitro acetylation assay was performed to identify Fascin acetylation sites by using mass spectrometry.A specific antibody against acetylated Fascin was generated and used to detect the PCAF-mediated Fascin acetylation in esophageal squamous cell carcinoma(ESCC)cells using Western blotting by overexpressing and knocking down PCAF expression.An in vitro cell migration assay was performed,and a xenograft model was established to study in vivo tumor metastasis.Live-cell imaging and fluorescence recovery after photobleaching were used to evaluate the function and dynamics of acetylated Fascin in filopodium formation.The clinical significance of acetylated Fascin and PCAF in ESCC was evaluated using immunohistochemistry.Results:Fascin directly interacted and colocalized with PCAF in the cytoplasm and was acetylated at lysine 471(K471)by PCAF.Using the specific antiAcK471-Fascin antibody,Fascin was found to be acetylated in ESCC cells,and the acetylation level was consequently increased after PCAF overexpression and decreased after PCAF knockdown.Functionally,Fascin-K471 acetylation markedly suppressed in vitro ESCC cell migration and in vivo tumor metastasis,whereas Fascin-K471 deacetylation exhibited a potent oncogenic function.Moreover,Fascin-K471 acetylation reduced filopodial length and density,and lifespan of ESCC cells,while its deacetylation produced the opposite effect.In the filipodium shaft,K471-acetylated Fascin displayed rapid dynamic exchange,suggesting that it remained in its monomeric form owing to its weakened actinbundling activity.Clinically,high levels of AcK471-Fascin in ESCC tissues were strongly associated with prolonged overall survival and disease-free survival of ESCC patients.Conclusions:Fascin interacts directly with PCAF and is acetylated at lysine 471 in ESCC cells.Fascin-K471 acetylation suppressed ESCC cell migration and tumor metastasis by reducing filopodium formation through the impairment of its actin-bundling activity.
基金Scientific Research Program of Hubei Provincial Department of Education in 2019(Q20192103).
文摘Objective:rupture of liver metasta-ses with disturbance of consciousness accompanied by aggravation of hemiplegia is very rare.We describe the clinical features of a case of spontaneous rupture of liver metastasis tumors with disturbance of consciousness and progression of right limb hemiplegia.Methods:collect the patient's medical history,conduct a detailed physi-cal examination,timely improve the relevant laboratory and imaging examination,formulate a comprehensive treatment plan,and track the changes of the disease and the treatment effect.Results:the patient presented with blurred consciousness,hemiplegia of the right limb,and epigastric tenderness when admitted to the hospital.No evident new lesions were found on cranial computed to-mography(CT).Blood routine examination showed that hemoglobin decreased significantly compared with be-fore.Abdominal CT showed tumor rupture and bleeding.The patient in critical condition did not have operation conditions,but improved after conservative treatment.Conclusion:when patients with liver metastasis tumors suddenly have a disturbance of consciousness and prog-ress of hemiplegia,they should not only be considered to have acute cerebrovascular diseases,but also the possi-bility of rupture of liver metastasis tumors.If only treated according to acute stroke,it will endanger their lives.For the liver metastasis tumor rupture,if there is no oppor-tunity for embolotherapy,timely conservative treatment with drugs can also achieve good results.
文摘To study the effect of IL-18 and nitric oxide(NO) on the growth and metastasis of non-small cell lung cancer (NSCLC).Methods Serum IL-18 and nitrate and nitrite levels in 82 patients with NSCLC and 20 healthy control subjects were measured by using ELISA and Griess.Results The levels of serum IL-18 were (334.2±31.0)ng/L in NSCLC patients and (151.3±22.0)ng/L in control subjects,respectively.The levels of nitrate and nitrite were (237.1±21.0)μmol/L in NSCLC patients and (44.2±15.0)μmol/L in control subjects.The levels of serum IL-18 and nitrate and nitrite were not related with age,gender,histological types in patients with NSCLC.The levels of serum IL-18 was closely associated with TNM stage,lymph node metastasis and distal metastasis,but not with its degree and organ types of metastasis.There was a negative correlation between the levels of serum IL-18 and nitrate and nitrite.Conclusion Serum IL-18 and nitrate and nitrite levels may be useful to evaluate the prognosis of the patients with NSCLC.16 refs,2 tabs.
基金This study was supported by grants from the " Fifteenth" Military MedicalKey Projects of China (01Z006) and the National Natural Science Founda-tion of China (30271279 and 30070747 ).
文摘BACKGROUND: FasL expression was reported to be asso- ciated with hepatic metastasis of colorectal cancer. The aim of this study was to study FasL gene expression in colorectal carcinoma and its influences on biological behavior and he- patic metastasis of colorectal carcinoma. METHODS: FasL gene expressions were examined with re- verse transcriptase-polymerase chain reaction (RT-PCR) in the primary focus of colorectal carcinoma, adjacent can- cerous mucosae, and metastasized liver focus from colorec- tal cancer. HR-8348 cells of human rectal cancer cell line were transfected with FasL cDNA. Cell growth suppression rate and response to 5-FU and carboplatin were observed and analyzed with the MTT method. RESULTS: FasL gene expression was detected in the prima- ry focus of colorectal cancer ( n = 58), adjacent cancerous mucosae ( n = 58), and metastasized hepatic tumor tissues (n =28). The positive rate of FasL expression was 24% (14/ 58), 8% (5/58), and 100% (58/58) in the primary focus, adjacent cancerous mucosae and metastasized hepatic tumor tissues respectively. FasL expression rate in the me- tastasized hepatic tumor tissues was higher than that in the primary focus (χ2 = 43.49, P<0. 01) and adjacent cance- rous mucosae (χ2=57.66, P<0.01). In a group of patients with hepatic metastasis, the FasL expression rate in primary focus was higher than that in patients without hepatic me- tastasis (χ2=3.96, P <0.05). In vitro study positive expres- sion of FasL was shown in transfected HR-8348 cells. When 5-FU or carboplatin was added, there was a significant difference in growth suppression rate between FasL positive and controlled cancer cells (t=9.02, t = 11.93, P<0.01). Under the same concentration of chemotherapeutic agents, the survival rate of FasL positive HR-8348 cells was higher than that of controlled cells. CONCLUSIONS: FasL positive cancer cells are powerfullyresistant to chemotherapeutic agents. The expression of the FasL gene in colorectal cancer cells is related to immune evasion to escape from being killed by immune cells, show- ing stronger drug-resistance, and it facilitates hepatic me- tastasis.
基金supported by the National Science Foundation of China (No. 30800402)
文摘TMTP1, a 5-amino acid peptide NVVRQ, obtained by using the flagella peptide library screening in our previous studies, can be used for the labeling of malignant in situ and metastatic lesions, and even micro-metastases. In this study, TMTP1 was assessed for its ability to specifically target the malignant hematopoietic cells and metastatic lesions of hematological malignancies. FITC-TMTP1 was chemically synthesized. Immunofluorescence assay and competitive test were carried out to determine the specific binding capacity of TMTPl to hematological malignant cell lines, including HL60, k562, SHI-1, Jurkat, Raji, El-4 and umbilical cord blood mononuclear cells. Mononuclear cells were isolated from the bone marrow of healthy subjects and patients with chronic myeloid leukemia. Then the cells were co-clutured with TMTP1 or scrambled peptides and the binding and affinity of TMTP1 peptide to the primary cells of hematological malignancies were flow cytometrically analyzed. The binding speci-ficity of TMTP1 to target hematological malignancies was measured in vivo by intravenous injection of FITC-conjugated TMTP1 into El-4 lymphoma-bearing mice. The results showed that TMTP1 specifi-cally bound to the cells of a series of hematological malignancies, including HL60, k562, Jurkat, Raji , El-4 and chronic myeloid leukemia primary cells but not to bone marrow mononuclear cells from healthy subjects. By contrast, TMTP1 could bind to the metastatic foci of lymphoma originating from the EL-4 cell line while the scrambled peptide failed to do so. Moreover, the occult metastases could be identified, with high specificity, by detecting FITC-TMTP1. We are led to conclude that TMTP1, as a novel tumor-homing peptide, can serve as a marker for primary malignant and metastatic lesions for the early diagnosis of hematological malignances and a carrier of anticancer drugs for cancer treatment.
文摘On the basis of preparation of anti-metastatic recombinant FN polypeptides, CH50 and CH56, we further studied the function of these polypeptides.The capacity of CH50 binding with melanoma cells (ED50 30 mM) was higher than that of CH56 (ED50 45 mM). Both of the polypeptides could significantly suppress the binding of melanoma B16 cells to laminin. There was no significant difference in the inhibitory effect between two polypeptides. In the experimental metastasis of melanoma cells, both of CH50 and CH56 could significantly inhibit the metastasis of the tumor cells, and reduce the number of lung metastasis by about 80%. Our results suggest that Ⅲ-11 and ED-A repeats influenced, to some extent, the binding capacity of bifunctional-domain polypeptide to cells, but did not affect the inhibition of the polypeptide on the metastasis of melanoma cells. The presence and connection of cell Ⅰ and Hep Ⅱ domains are the elements which determine the ability of recoinbinant FN polypeptides to inhibit the metastasis of tumor cells.
基金supported by the National Natural Science Foundation of China (No. 81472256, 81272638)the Guangdong Provincial Science and Technology Project (No. 2016A020215081, 2016A020217007)the National High Technology Research and Development Program of China (863 Program, No. 2012AA02A204)
文摘Background: Ankyrin repeat and SOCS box protein 3(ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradation of tumor necrosis factor receptor 2 and is likely involved in inflammatory responses. However, its effects on oncogenesis are unclear. This study aimed to investigate the effects of ASB3 on the growth and metastasis of colorectal cancer(CRC).Methods: We used next?generation sequencing or Sanger sequencing to detect ASB3 mutations in CRC specimens or cell lines, and used real?time quantitative polymerase chain reaction, Western blotting, and immunohistochemical or immunofluorescence assay to determine gene expression. We evaluated cell proliferation by MTT and colony for?mation assays, tested cell cycle distribution by flow cytometry, and assessed cell migration and invasion by transwell and wound healing assays. We also performed nude mouse experiments to evaluate tumorigenicity and hepatic metastasis potential of tumor cells.Results: We found that ASB3 gene was frequently mutated(5.3%) and down?regulated(70.4%) in CRC cases. Knock?down of endogenous ASB3 expression promoted CRC cell proliferation, migration, and invasion in vitro and facilitated tumorigenicity and hepatic metastasis in vivo. Conversely, the ectopic overexpression of wild?type ASB3, but not that of ASB3 mutants that occurred in clinical CRC tissues, inhibited tumor growth and metastasis. Further analysis showed that ASB3 inhibited CRC metastasis likely by retarding epithelial?mesenchymal transition, which was characterized by the up?regulation of β?catenin and E?cadherin and the down?regulation of transcription factor 8, N?cadherin, and vimentin.Conclusion: ASB3 dysfunction resulted from gene mutations or down?regulated expression frequently exists in CRC and likely plays a key role in the pathogenesis and progression of CRC.
基金supported by Major Projects of the National Natural Science Foundation of China(81974499)Sichuan Science and Technology Program(2018RZ0136)Sichuan Veterinary Medicine and Drug innovation Group of China Agricultural Research System(SCCXTD-2020-18).
文摘Metastasis is closely related to the high mortality of cancer patients,which is regulated by multiple signaling pathways.Hence,multiphase blocking of this biological process is beneficial for cancer treatments.Herein,we establish a multifunctional self-delivering system by synthesizing D-α-tocopheryl succinates(TOS)-conjugated chondroitin sulfate(CS)(CT NPs),which both serve as nanocarrier and antimetastatic agent that affects different phases of the metastatic cascade.TOS as the hydrophobic segment of CT NPs can inhibit the secretion of matrix metalloproteinase-9,while the hydrophilic segment CS targets B16F10 cells through CD44 receptors and reduces the interaction between tumor cells and platelets.The results show that CT NPs are able to inhibit metastasis successfully both in vitro and in vivo by interfering the multiphase of the metastatic cascade.Following encapsulating chemotherapeutic drug doxorubicin(DOX),the obtained micelles CT/DOX efficiently suppress both primary-tumor growth and metastases in B16F10 bearing mice.As a result,the rationally designed multifunctional NPs composing of biocompatible materials provide excellent therapeutic effects on solid tumors and metastases。
文摘BACKGROUND Secondary jejunal tumor from renal cell carcinoma(RCC)is extremely rare in clinical practice and is easily missed and misdiagnosed because of the low incidence and atypical symptoms.CASE SUMMARY A 38-year-old male patient was diagnosed pathologically with left RCC after radical nephrectomy in 2012.The patient then suffered multiple lung metastases 2 years later and was treated with oral sorafenib without progression for 6 years.In 2020,an emergency intestinal segmental resection due to intestinal obstruction was required,and postoperative pathology confirmed a jejunal secondary tumor from RCC.The patient had a smooth recovery following surgery.Three months after surgery,the patient was diagnosed with left adrenal metastasis,and subsequent sintilimab therapy has stabilized his condition.CONCLUSION This report is written to remind urologists and pathologists of the potential for small intestinal secondary tumors when a patient with a history of RCC seeks treatment for digestive symptoms.Enteroscopy and abdominal contrast-enhanced computed tomography are essential means of examination,but severe cases require immediate surgical intervention despite the lack of a preoperative examination to distinguish tumor attributes.
基金supported by the National Natural Science Foundation of China(Nos.82125036,82273964,81973363,82304538,81973188)the State Key Laboratory of Natural Medicines of CPU(No.SKLNMZZ202207)+3 种基金the“Double-First Class”Program of CPU,the National Key Research and Development Program of China(No.2017YFA0503900)the Jiangsu Provincial Natural Science Fund for Distinguished Young Scholar(No.BK20230042)the Jiangsu Funding Program for Excellent Postdoctoral Talent(No.2023ZB171)the Shenzhen Fundamental Research Program(No.JCYJ20200109114225087).
文摘The tumor suppressor protein p53 is central to cancer biology,with its pathway reactivation emerging as a promising therapeutic strategy in oncology.This study introduced LZ22,a novel compound that selectively inhibits the growth,migration,and metastasis of tumor cells expressing wild-type p53,demonstrating ineffectiveness in cells devoid of p53 or those expressing mutant p53.LZ22’s mechanism of action involves a high-affinity interaction with the histidine-96 pocket of the MDM2 protein.This interaction disrupted the MDM2-p53 binding,consequently stabilizing p53 by shielding it from proteasomal degradation.LZ22 impeded cell cycle progression and diminished cell proliferation by reinstating the p53-dependent suppression of the CDK2/Rb signaling pathway.Moreover,LZ22 alleviated the p53-dependent repression of Snail transcription factor expression and its consequent EMT,effectively reducing tumor cell migration and distal metastasis.Importantly,LZ22 administration in tumor-bearing mice did not manifest notable side effects.The findings position LZ22 as a structurally unique reactivator of p53,offering therapeutic promise for the management of human cancers with wild-type TP53.
基金the National Natural Science Foundation of China (No. 30772589)
文摘To investigate the invasive ability of the residual tumor cells after immunotherapy and explore the feasible approach suppressing the invasion, mice were inoculated with B16 cells, and then treated by gene therapy with p4-1BBL/psPD-1 or IFN-γ. The production and activities of MMP-9 and MMP-2 in residual tumor tissues were analyzed with gelatin zymography 1 day and 7 days after the termination of the immunotherapy. The production of MMP-9 and MMP-2 by B16 cells treated with IFN-γ was also analyzed. IFN-γ-treated B16 cells were inoculated to mice via subcutaneous injection. The invasion of tumor to muscular tissue was analyzed. Gene therapy with CH50 was used to suppress the invasive growth of tumor. The results showed that the expression and the activities of MMP-9 and MMP-2 were significantly increased 7 days after the end of immunotherapy. The re- sponse of tumor cells to ECM molecules was intensified after the removal of IFN-γ, resulting in significant increase of both the production and activities of MMP-9 and MMP-2, and the increased invasion of tumor. Gene therapy with CH50 effectively suppressed the invasive growth of tumor. It is concluded that the termination of immunotherapy may result in a higher metastatic potential of residual tumor cells. Suppressing tumor invasion by suitable treatment will improve the efficacy of immunotherapy..
文摘γ-Interferon (IFN-Y) was detected by ELISA assayin ascitic fluid from a number of ovarian cancer patients.To study its clinical significance, the effect of IFN-Y on the metastatic potential of a mouse mammary adenocarcinoma, MA-891, was explored. Pretreatment of the tumor cells in vitro for 48 hr with recombinant IFN-γ significantly increased the number of lung tumor nodules after iv. or sc. inoculation into (TA2×615) F1 mice. In contrast, when recombinant IFN-αpretreated MA-891 cells were likewise injected into mice significant decrease in metastatic potential was seen. The study in vitro indicated that pretreatment of the tumor cells with IFN-γbut not IFN-αresulted in a decrease in susceptibility to NK cell cytotoxicity. Inasmuch as both IFN-αand IFN-γcan induce MHC class I expression on target cells, the increase in matastatic potential of IFN-γ-treated tumor cells can be explained only partially on the basis of their reduced NK cells susceptibility.