Research Progress on Anti-tumor Mechanism of Clearing Heat-Toxin Intervention of Apoptosis-related Proteins

Apoptosis is a spontaneous programmed cell death process,which is closely related to the occurrence and development of tumors.Inducing apoptosis of tumor cells has become an important way of anti-tumor therapy.Studies have found that clearing heat-toxin Chinese medicine has a significant effect on inducing apoptosis,which may be the key mechanism of anti-tumor of Chinese medicine.By reviewing the theoretical origin of anti-tumor TCM of clearing heat-toxin Chinese herbs and the pharmacological research progress of intervening apoptosis-related proteins to promote apoptosis of tumor cells,this paper provides a basis for TCM to induce apoptosis of tumor cells to prevent and treat malignant tumors.

Radiofrequency ablation,heat shock protein 70 and potential anti-tumor immunity in hepatic and pancreatic cancers:a minireview

BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive surgical procedure which has widespread popularity in the treatment of hepatic and pancreatic cancers. Increased evidence indicates that RFA stimulates anti-tumor immunity, possibly through the induction heat shock protein 70 (HSP70) expression. HSP70 has the capacity to affect the immunogenicity of tumor cells, to chaperone antigenic peptides and deliver these into antigen presentation pathways within antigen-presenting cells, and to activate and regulate innate and adaptive immunity, which makes it useful in immunotherapeutic strategies for the treatment of cancers. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1991-2010) on anti-tumor immunity, heat shock protein 70, radiofrequency ablation, hepatic cancer, pancreatic cancer, and other related subjects. RESULTS: RFA has an increasing application in the surgical treatment of hepatic and pancreatic cancers. Increased evidence indicates that RFA can induce the expression of HSP70 which possesses properties that enable it to influence a variety of immunological processes. Tumor-derived HSP70 is regarded as a potent adjuvant facilitating presentation of tumor antigens and induction of anti-tumor immunity. CONCLUSIONS: This review addresses the potential association of RFA, HSP70, and anti-tumor immunity in treatment of hepatic and pancreatic cancers. To establish direct evidence of a potential association of RFA, HSP70, and anti-tumor immunity in hepatic and pancreatic cancers, further investigations should be conducted.

Enhanced Anti-tumor Effect of an IFN-γ-EGF Fusion Protein

The novel fusion proteins harbering human or mouse interferon combined with epidermalgrowth factor receptor binding domain were constructed using methods of genetic and proteinengineering. The fusion proteins were assayed to retain complete antiviral activities. The EGFreceptor binding moiety of the fusion proteins exhibited competitive binding saainst 125 I-EGFfor EGF receptbrs on A431 cells. The fusion proteins were shown to be more potent in in-hibiting the growth of cultured target carcinoma cells than interferon-y alone. Experimentaldata derived from rnouse Bl6 malignant melanoma models indicates that the weight of tumorin mice treated with IFN fusion proteins was significantly smaller than that of mice treatedwith interferon-y alone. The work here is unprecedented in the world and provides a reliableevidence to supPOrt the upcoming clinical employment of a class of interferons that specificallytarget tumor cell

Dioscin-induced Apoptosis of Human LNCaP Prostate Carcinoma Cells through Activation of Caspase-3 and Modulation of Bcl-2 Protein Family

Dioscin is a natural steroid saponin derived from several plants, showing potent anti-cancer effect against a variety of tumor cell lines. In the present study, we investigated the anti-cancer activity of dioscin against human LNCaP cells, and evaluated the possible mechanism involved in its antineoplastic action. It was found that dioscin（1, 2 and 4 μmol/L） could significantly inhibit the viability of LNCaP cells in a time- and concentration-dependent manner. Flow cytometry revealed that the apoptosis rate was increased after treatment of LNCaP cells with dioscin for 24 h, indicating that apoptosis was an important mechanism by which dioscin inhibited cancer. Western blotting was employed to detect the expression of caspase-3, Bcl-2 and Bax in LNCaP cells. The expression of cleaved caspase-3 was significantly increased, and meanwhile procaspase-3 was markedly decreased. The expression of anti-apoptotic protein Bcl-2 was down-regulated, whereas the pro-apoptotic protein Bax was up-regulated. Moreover, the Bcl-2/Bax ratio was drastically decreased. These results suggested that dioscin possessed potential anti-tumor activity in human LNCaP cells through the apoptosis pathway, which might be associated with caspase-3 and Bcl-2 protein family.

Pharmacological Activities and Molecular Mechanisms of Arctigenin

Arctigenin has a variety of pharmacological effects,such as anti-inflammatory,anti-tumor,antiviral and hypoglycemic.In this paper,the pharmacological effects and mechanisms of arctigenin were reviewed,in order to provide a theoretical basis for further research and development of arctigenin.

Research Progress on Pharmacological Effects of Lycorine Hydrochloride

Lycoris radiata,a Chinese herbal medicine,is a plant of Amaryllidaceae family,which has the antidotal,expectorant,diuretic,emetic and insecticidal effects.Lycorine hydrochloride is an alkaloid extracted from the bulb of L.radiata.Studies have shown that lycorine hydrochloride has many pharmacological effects(anti-fungal,anti-viral and anti-tumor).In this paper,the related research on pharmacological effects and mechanism of lycorine hydrochloride is systematically summarized in order to provide a theoretical basis for further research and application of lycorine hydrochloride.

Complex structure of human Hsp90~N and a novel small inhibitor FS5

Heat shock proteins(Hsps)are a family of abundantly expressed ATP-dependent chaperone proteins.Hsp90 is an eminent member of Hsp family.Thus far,two primary functions have been described for Hsp90:first,as a regulator of conformational change of some protein kinases and nuclear hormone receptors,and the other as an indispensable factor in cellular stress response.Hsp90 has an essential number of interaction proteins since it participates in almost every biological process and its importance is self-evident.Hsp90 has an inextricable relationship in the pathogenesis of cancer,especially in the proliferation and irradiation of cancer cells,thus being a notable cancer target.Since the discovery of geldanamycin,the first inhibitor of Hsp90,from the bacterial species Streptomyces hygroscopicus,even more attention has been focused toward Hsp90.Many structure-based inhibitors of Hsp90 have been designed to develop an innovative method to defeat cancer.However,already designed inhibitors have various deficiencies,such as hepatotoxicity,poor aqueous solubility,instability,and non-ideal oral bioavailability.Based on the aforementioned reasons and to achieve an optimal performance and fewer side effects,we designed a novel inhibitor of Hsp90,called FS5,and resolved the crystal structure of the Hsp90^N-FS5 complex(1.65 A°,PDB code 5XRB).Furthermore,we compared the complexes Hsp90^N,Hsp90^N-GDM,and Hsp90^N-ATP and suggest that the inhibitor FS5 may compete with ATP for binding to Hsp90,which can be regarded as a potential strategy for the development of novel cancer drugs in the future.

Combined evaluation of biomarkers as predictor of maintained remission in Crohn's disease

BACKGROUND The individual performances and the complementarity of Crohn's disease(CD)activity index(CDAI), C-reactive protein(CRP) and faecal calprotectin(Fcal) to monitor patients with CD remain poorly inves-tigated in the era of "tight control"and "treat to target" strategies.AIM To assess CDAI, CRP and Fcal variation, alone or combined, after 12 wk(W12) of anti-tumor necrosis factor(TNF) therapy to predict corticosteroids-free remission(CFREM = CDAI < 150, CRP < 2.9 mg/L and Fcal < 250 μg/g with no therapeutic intensification and no surgery) at W52.METHODS CD adult patients needing anti-TNF therapy with CDAI > 150 and either CRP >2.9 mg/L or Fcal > 250 μg/g were prospectively enrolled.RESULTS Among the 40 included patients, 13 patients(32.5%) achieved CFREM at W52. In univariable analysis, CDAI < 150 at W12(P = 0.012), CRP level < 2.9 mg/L at W12(P = 0.001) and Fcal improvement at W12(Fcal < 300 μg/g; or, for patients with initial Fcal < 300 μg/g, at least 50% decrease of Fcal or normalization of Fcal(< 100 μg/g)(P = 0.001) were predictive of CFREM at W52. Combined endpoint(CDAI < 150 and CRP ≤ 2.9 mg/L and FCal improvement) at W12 was the best predictor of CFREM at W52 with positive predictive value = 100.0%(100.0-100.0)and negative predictive value = 87.1%(75.3-98.9). In multivariable analysis, Fcal improvement at W12 [odd ratio(OR) = 45.1(2.96-687.9); P = 0.03] was a better predictor of CFREM at W52 than CDAI < 150 [OR = 9.3(0.36-237.1); P = 0.145]and CRP < 2.9 mg/L(0.77-278.0; P = 0.073).CONCLUSION The combined monitoring of CDAI, CRP and Fcal after anti-TNF induction therapy is able to predict favorable outcome within one year in patients with CD.

Research Progress on Pharmacological Action of 5-O-methylvisammioside

5-O-methylvisammioside is a chemical derived from the dry root of Saposhnikovia divaricata,which has the functions of expelling pathogenic wind from body surface,removing dampness to relieve pain,and relieving convulsion.Recent studies have found that 5-O-methylvisammioside can play a variety of pharmacological effects such as anti-tumor,anti-inflammation,anti-virus and anti-depression through a variety of ways.The paper reviews the pharmacological action and mechanism of 5-O-methylvisammioside in recent years.

<i>Lactobacillus</i>sp.—A Threat to Pathogenic Microorganisms and Tumor Cells

Beneficial bacteria, often used as probiotics, play efficient role in providing protection against pathogenic microorganisms in humans. Probiotic bacteria like many Lactobacillus sp. (L. acidophilus, L. casei etc.), Bafidobacterium sp. Streptococcus thermophiles, Bacillus coagulans, etc. are beneficial and nowadays are used as supportive therapeutics. Even Lactobacillus is highlighted for showing the anticancer effects on some human cancer cells (cervical, gastric, colon, breast cancer). Some specific antibiotics like peptide antibiotic, Acidolin;some specific bacteriocins and some metabolites like H2O2, acetic acid, lactic acid produced by Lactobacillus sp. kill or inhibit other microorganisms mainly gram positive and gram negative bacteria, including both enteropathogens and spore formers. Proteins like Enterolisin A, Labyrintho peptin A2, etc. show promising anti-cancer activities. Lactobacillus has effective role in clinical and industrial fields. Clinically it is used to manufacture medicines, some hormones and industrially used for broad fermentations, etc. Studies are going on to use Lactobacillus in more broad ways, by improving strains, increasing specificity, making more effective and to find out some other characteristics to prepare them as more natural therapeutic modality.

Type XIX collagen: a promising biomarker from the basement membranes

Among collagen members in the collagen superfamily,type XIX collagen has raised increasing interest in relation to its structural and biological roles.Type XIX collagen is a Fibril-Associated Collagen with Interrupted Triple helices member,one main subclass of collagens in this superfamily.This collagen contains a triple helix composed of three polypeptide segments aligned in parallel and it is associated with the basement membrane zone in different tissues.The molecular structure of type XIX collagen consists of five collagenous domains,COL1 to COL5,interrupted by six non-collagenous domains,NCI to NC6.The most relevant domain by which this collagen exerts its biological roles is NCI domain that can be cleavage enzymatically to release matricryptins,exerting anti-tumor and anti-angiogenic effect in murine and human models of cancer.Under physiological conditions,type XIX collagen expression decreases after birth in different tissues although it is necessary to keep its basal levels,mainly in skeletal muscle and hippocampal and telencephalic interneurons in brain.Notwithstanding,in amyotrophic lateral sclerosis,altered transcript expression levels show a novel biological effect of this collagen beyond its structural role in basement membranes and its anti-tumor and anti-angiogenic properties.Type XIX collagen can exert a compensatory effect to ameliorate the disease progression under neurodegenerative conditions specific to amyotrophic lateral sclerosis in transgenic SOD1 G93 A mice and amyotrophic lateral sclerosis patients.This novel biological role highlights its nature as prognostic biomarker of disease progression in and as promising therapeutic target,paving the way to a more precise prognosis of amyotrophic lateral sclerosis.

Investigation on the effect of peptides mixture from tumor cells inducing anti-tumor specific immune response

The peptides mixture was prepared from tumor cells by freezing-thawing cells, precipitation by heating, followed by acidification of the solution. The activation and proliferation of mouse splenocytes by HSP70-peptide complex, formed by the binding of HSP70 and peptides in vitro, were observed, so was the specific cytotoxicity of the proliferative lymphocytes to tumor cells. The phenotypes of the proliferative lymphocytes were analyzed by a flow cytometer. BALB/c mice inoculated with H22 hepatocarcinoma cells in peritoneal cavity or hind thigh were immunized by injection with HSP70-peptides complex to observe the inhibitory effect of the immunization on tumor and lifetime of tumor-bearing mice. On the other hand, blood samples were collected from the immunized mice to check the functions of liver and kidney. The results showed that the peptides mixture from tumor cells contained tumor-specific antigen peptides which could be presented by HSP70 to activate lymphocytes in vitro, the proliferative lymphocytes were T cells which were specifically cytotoxic to tumor cells, the in vivo growth of both ascitic and solid carcinoma could be suppressed by immunization with HSP70-peptides and the lifetime of tumor-bearing mice was prolonged, the in vivo immunization with HSP70-H22-peptides had no impact on the function of mouse liver and kidney, suggesting that there was no occurrence of autoimmunity in vivo after immunization.

The morphology of hydroxyapatite nanoparticles regulates clathrinmediated endocytosis in melanoma cells and resultant anti-tumor efficiency

Clathrin-mediated endocytosis plays a critical role for hydroxyapatite nanoparticles(HANPs)to enter tumor cells,induce mitochondrial apoptosis,and inhibit tumor growth.This study was aimed to investigate how the morphology of HANPs impacts the endocytosis of the particles in melanoma cells,and their anti-tumor effect by using in vitro cell experiments and in vivo tumor animal model.Three shapes of HANPs,including granular HANPs(G-HANPs),rod-like HANPs(R-HANPs),and needle-like HANPs(N-HANPs),were successfully prepared by wet chemical method.All the three HANPs could be internalized into A375 melanoma cells as indicated by cellular transmission electron microscopy images.Among these HANPs,only G-HANPs induced morphological change of mitochondria and loss of mitochondrial membrane potential(Δψm),and exhibited the greatest intracellular internalization efficiency in the tumor cells.Furthermore,the results of immunofluorescence staining and western blotting indicated that the level of adaptin-2(AP2)protein was up-regulated by all the HANPs,and highest in G-HANPs treated A375 cells.Moreover,in the tumor-bearing mouse model,we found that tumor growth was delayed by all the three HANPs,of which,G-HANPs delayed tumor growth most efficiently and presented a highest expression level of AP2 protein in tumor tissues.Therefore,this study suggested that the morphology of HANPs regulated their endocytosis efficiency and their effect to inhibit tumor growth.This work facilitates to direct the rational design of nano-materials for tumor therapy.

Unraveling the Mystery of γδ T Cell Recognizing Lipid A

Traditionally, the materials which are regarded as antigens recognized by γδ T lymphocytes are protein and carbohydrate, not nucleic acid or lipid. Recently, it has been demonstrated that γδ T cells can recognize lipid A and directly induce immune responses that involve CD1 （cluster of differentiation type 1） family and Toll like receptors （TLRs）. This is a review about the interacting-mechanism, immunological effect and clinical application of them.