Hypoxia,angiogenesis and liver fibrogenesis in the progression of chronic liver diseases

Angiogenesis is a dynamic,hypoxia-stimulated and growth factor-dependent process,and is currently referred to as the formation of new vessels from preexisting blood vessels.Experimental and clinical studies have unequivocally reported that hepatic angiogenesis,irrespective of aetiology,occurs in conditions of chronic liver diseases(CLDs) characterized by perpetuation of cell injury and death,inflammatory response and progressive fibrogenesis.Angiogenesis and related changes in liver vascular architecture,that in turn concur to increase vascular resistance and portal hypertension and to decrease parenchymal perfusion,have been proposed to favour fibrogenic progression of the disease towards the end-point of cirrhosis.Moreover,hepatic angiogenesis has also been proposed to modulate the genesis of portal-systemic shunts and increase splanchnic blood flow,thus potentially affecting complications of cirrhosis.Hepatic angiogenesis is also crucial for the growth and progression of hepatocellular carcinoma.Recent literature has identified a number of cellular and molecular mechanisms governing the cross-talk between angiogenesis and fibrogenesis,with a specifi c emphasis on the crucial role of hypoxic conditions and hepatic stellate cells,particularly when activated to the myofibroblast-like pro-fibrogenic.Experimental anti-angiogenic therapy has been proven to be effective in limiting the progression of CLDs in animal models.From a clinical point of view,anti-angiogenic therapy is currently emerging as a new pharmacologic intervention in patients with advanced fibrosis and cirrhosis.

Plexiform angiomyxoid myofi broblastic tumor of the stomach

Plexiform angiomyxoid myofibroblastic tumor of the stomach is a unique mesenchymal tumor that we first described in 2007.The tumor is very rare,and to date,only 18 cases confirmed by immunohistochemistry have been reported in the literature.The patients' ages ranged from 7 to 75 years(mean,43 years),and the male-to-female ratio was approximately 1:1.Representative clinical symptoms are ulceration,associated upper gastrointestinal bleeding(hematemesis),and anemia.The tumors are located at the antrum in all cases,and grossly,the tumor is whitish to brownish or reddish,and forms a lobulated submucosal or transmural mass.Microscopically,the tumor is characterized by a plexiform growth pattern,the proliferation of cytologically bland spindle cells,and a myxoid stroma that is rich in small vessels and positive for Alcian blue stain.Immunohistochemically,the tumor cells are positive for α-smooth muscle actin and negative for KIT and CD34.Differential diagnoses include gastrointestinal stromal tumor and other mesenchymal tumors of the gastrointestinal tract.Some authors proposed that this tumor should be designated as "plexiform fibromyxoma",but this designation might cause confusion.The tumor is probably benign and thus far,neither recurrence nor metastasis has been reported.

Inflammatory myofibroblastic tumor from molecular diagnostics to current treatment

Inflammatory myofibroblastic tumor(IMT)is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic rate.Diagnostic challenges arise from the diverse pathological presentation,variable symptomatology,and lack of different imaging features.However,IMT is identified by the fusion of the anaplastic lymphoma kinase(ALK)gene,which is present in approximately 70%of cases,with various fusion partners,including ran-binding protein 2(RANBP2),which allows confirmation of the diagnosis.While surgery is the preferred approach for localized tumors,the optimal long-term treatment for advanced or metastatic disease is difficult to define.Targeted therapies are crucial for achieving sustained response to treatment within the context of genetic alteration in IMT.Crizotinib,an ALK tyrosine kinase inhibitor(TKI),was officially approved by the US Food and Drug Administration(FDA)in 2020 to treat IMT with ALK rearrangement.However,most patients face resistance and disease progression,requiring consideration of sequential treatments.Combining radiotherapy with targeted therapy appears to be beneficial in this indication.Early promising results have also been achieved with immunotherapy,indicating potential for combined therapy approaches.However,defined recommendations are still lacking.This review analyzes the available research on IMT,including genetic disorders and their impact on the course of the disease,data on the latest targeted therapy regimens and the possibility of developing immunotherapy in this indication,as well as summarizing general knowledge about prognostic and predictive factors,also in terms of resistance to systemic therapy.

Regulation of exogenous bFGF gene mediated by recombinant adeno-associated virus in vitro

The regulatory effect of basicfibroblast growth factor(bFGF)mediated by recombinant adeno-associated virus(AAV)in vitro was investigated.Recombinant plasmid pAAV-S3-bFGF,and pSVneo were co-transfected into BHK-21 cells,then the recombinant AAV genome was replicated and packaged with the helper virus HSV1-rc/ΔUL2.The titer of the recombinant rAAV2-tet-off-bFGF was determined by dot-blot assay.MC3T3-E1 cells were infected with rAAV2-tet-off-bFGF.Regulatory effects of Doxycycline(Dox)on bFGF and osteogenic factors were assayed quantitatively by real-time reverse transcription-polymerase chain reaction(RT-PCR)and Western blot.The physical particle titer of rAAV2-tet-off-bFGF successfully constructed was 1.8�1012 vector genomes/mL,and the virus could infect MC3T3-E1 cells effectively.In MC3T3-E1 cells treated with Dox,the expression levels of exogenous bFGF and osteogenic factors declined to varying degrees.It was concluded that rAAV2-tet-off-bFGF could infect MC3T3 cells efficiently,and this recombinant system could be regulated success-fully by Dox in vitro.

Relative expression of PTTG and bFGF in oral squamous cellcarcinoma and Tca8113

The purpose of this study was to investigate the expression of pituitary tumor transforming gene(PTTG)and basicfibroblast growth factor(bFGF)in oral squamous cell carcinoma(OSCC)and tongue cancer cell line Tca8113,as well as their effects on each other.We detected PTTG protein and bFGF in OSCC tissues from 56 cases using the streptavidin-biotin peroxidase(S-P)method;additionally,after being treated with different concentrations of anti bFGF or PTTG antibody,PTTG or bFGF expression in Tca8113 was examined by immuno-cytochemistry.The results were as follows:(1)Positive rates of PTTG protein and bFGF were 78.2%and 67.3%in OSCC,respectively,which were significantly higher than those in normal mucosal tissues(P<0.05).PTTG protein was significantly up-regulated in poorly and moderately differentiated tumors compared to well differentiated tumors(P<0.05),and there was also a significant difference between tumors with lymph node metastasis and tumors without lymph node metastasis(P<0.05).PTTG protein expression was positively correlated with bFGF(r=0.382,P<0.05);(2)PTTG protein emitted strongfluorescence in Tca8113,and it decreased after being treated with anti-bFGF antibody.Anti-PTTG anti-body also had an inhibitive effect on bFGF expression.In summary,the overexpression of PTTG protein is closely related with OSCC differentiation and lymph node metastasis.PTTG protein expression conforms to bFGF in OSCC tissues and Tca8113 cells.Detection of both PTTG and bFGF may help to judge the degree of malignancy and prognosis of patients with OSCC.