Using a novel hemostatic peptide solution to prevent bleeding after endoscopic submucosal dissection of a gastric tumor

BACKGROUND Endoscopic mucosal dissection has become the standard treatment for early gastric cancer.However,post-endoscopic submucosal dissection(ESD)ulcer occurs in 4.4%of patients.This study hypothesized whether applying PuraStat,a novel hemostatic peptide solution,prevents post-ESD bleeding.AIM To investigate the preventive potential of PuraStat,a hemostatic formulation,against bleeding in post-ESD gastric ulcers.METHODS Between May 2022 and March 2023,101 patients(Group P)underwent ESD for gastric diseases at our hospital and received PuraStat(2 mL)for post-ESD ulcers.We retrospectively compared this group with a control group(Group C)com-prising 297 patients who underwent ESD for gastric diseases at our hospital between April 2017 and March 2021.P values<0.05 on two-sided tests indicated significance.RESULTS Post-ESD bleeding occurred in 6(5.9%)(95%CI:2.8-12.4)and 20(6.7%)(95%CI:4.4-10.2)patients in Groups P and C,respectively,with no significant between-group difference.The relative risk was 1.01(95%CI:0.95-1.07).The lesser curvature or anterior wall was the bleeding site in all 6 patients who experienced postoperative bleeding in Group P.In multivariate analysis,the odds ratios for resection diameter≥50 mm and oral anticoagulant use were 6.63(95%CI:2.52-14.47;P=0.0001)and 4.04(1.26-0.69;P=0.0164),respectively.The adjusted odds ratio of post-ESD bleeding and PuraStat was 1.28(95%CI:0.28-2.15).CONCLUSION PuraStat application is not associated with post-ESD bleeding.However,the study suggests that gravitational forces may affect the effectiveness of applied PuraStat.

HPV16 E5 Peptide Vaccine in Treatment of Cervical Cancer In Vitro and In Vivo

Human papillomavirus （HPV）-induced cervical cancer is the second most common cancer among women worldwide. Despite the encouraging development of the preventive vaccine for HPV, a vaccine for both prevention and therapy or pre-cancerous lesions remains in high priority. Thus far, most of the HPV therapeutic vaccines are focused on HPV E6 and E7 oncogene. However these vaccines could not completely eradicate the lesions. Recently, HPV E5, which is considered as an oncogene, is getting more and more attention. In this study, we predicted the epitopes of HPV16 E5 by bioinformat- ics as candidate peptide, then, evaluated the efficacy and chose an effective one to do the further test. To evaluate the effect of vaccine, rTC-1 （TC-1 cells infected by rAAV-HPV16E5） served as cell tumor model and rTC-1 loading mice as an ectopic tumor model. We prepared vaccine by muscle injection. The vaccine effects were determined by evaluating the function of tumor-specific T cells by cell prolif- eration assay and ELISPOT, calculating the tumor volume in mice and estimating the survival time of mice. Our in vitro and in vivo studies revealed that injection of E5 peptide＋CpG resulted in strong cell-mediated immunity （CMI） and protected mice from tumor growth, meanwhile, prolonged the sur- vival time after tumor cell loading. This study provides new insights into HPV16 E5 as a possible target on the therapeutic strategies about cervical cancer.

Affinity peptide developed by phage display selection for targeting gastric cancer

AIM:To develop an affinity peptide that binds to gastric cancer used for the detection of early gastric cancer.METHODS:A peptide screen was performed by biopanning the PhD-12 phage display library,clearing non-specific binders against tumor-adjacent normal appearing gastric mucosa and obtaining selective binding against freshly harvested gastric cancer tissues.Tumortargeted binding of selected peptides was confirmed by bound phage counts,enzyme-linked immunosorbent assay,competitive inhibition,fluorescence microscopy and semi-quantitative analysis on immunohistochemistry using different types of cancer tissues.RESULTS:Approximately 92.8% of the non-specific phage clones were subtracted from the original phage library after two rounds of biopanning against normal-appearing gastric mucosa.After the third round of positive screening,the peptide sequence AADNAKTKSFPV(AAD) appeared in 25%(12/48) of the analyzed phages.For the control peptide,these values were 6.8 ± 2.3,5.1 ± 1.7,3.5 ± 2.1,4.6 ± 1.9 and 1.1 ± 0.5,respectively.The values for AAD peptide were statistically signif icant(P < 0.01) for gastric cancer as compared with other histological classif ications and control peptide.CONCLUSION:A novel peptide is discovered to have a specific binding activity to gastric cancer,and can be used to distinguish neoplastic from normal gastric mucosa,demonstrating the potential for early cancer detection on endoscopy.

Glycosylated and non-glycosylated quantum dot-displayed peptides trafficked indiscriminately inside lung cancer cells but discriminately sorted in normal lung cells: An indispensable part in nanoparticle-based intracellular drug delivery

Difference in sub-cellular trafficking of glycosylated and naked peptides, between normal and lung cancer cells, was established. Normal lung tissue discriminately sorted glycosylated from non-glycosylated peptides by allowing golgi localization of the glycosylated peptides while restricting golgi entry of the naked peptides. This mechanism was surprisingly not observed in its cancer cell counterpart. Lung cancer cells tend to allow unrestricted localization of both glycosylated and naked peptides in the golgi apparatus. This newly discovered difference in sub-cellular trafficking between normal and lung cancer cells could potentially be used as an effective strategy in targeted intracellular delivery, especially targeting golgi-resident enzymes for possible treatment of diseases associated with glycans and glycoproteins, such as, congenital disease of glycosylation(CDG). This very important detail in intracellular trafficking inside normal and cancer cells is an indispensable part in nanoparticle-based intracellular drug delivery.

Identifying peptides that specifically bind to MDA-MB-468 breast cancer cells

Objective To use phage display technique to screen for small polypeptides that specifically bind to MDA-MB-468 cells.Methods A random heptapeptide phage display library was used for in vitro screening against target MDA-MB-468 cells.SC1180 cells were used for subtractive selection.High-affinity phage DNA was extracted,and peptides were sequenced.Results(1)The original library capacity of the polypeptide library was 2×10^13 pfu/mL,and phage titer was determined over 4 rounds.The average library capacity was 1.8×10^13 pfu/mL.(2)Subtractive screening showed that the phage library volume of each round was 1.8×10^12 pfu/mL,and that there was an enrichment effect in each subsequent round.Screening was stopped after the fourth round.(3)PCR results showed that the size of 39 products(78.0%)and 11 products(22%),were 300 bp and 258 bp,respectively.Thirty positive phages were selected for DNA extraction and sequencing,and the corresponding amino acid sequence was LMTRXSK.The sequence had no homology with known genes or proteins.Conclusion Using the phage display technique,we identified that the short polypeptide,LMTRXSK,specifically binds MDA-MB-468 human breast cancer cells.

Novel Anti-Cancer Peptides Comprising Three Amino Acids

Background: The NPxY motif common to all β integrin cytoplasmic domains forms part of a canonical recognition sequence for phosphotyrosine-binding domains which are protein modules present in a wide variety of signaling and cytoskeletal proteins. We have recently reported that a non-naturally occurring peptide, RSKAKNPLYR, derived from the β6 integrin cytoplasmic domain inhibits cancer cell growth in vitro and proposed that this may be due, at least in part, to the inhibition of c-Src activity [1]. In the present study we examined the role of the NPLY motif within RSKAKNPLYR in terms of its requirement for inhibition of cancer cell growth. Materials and Methods: The effects of peptide modifications to RSKAKNPLYR on in vitro proliferation of human cancer cell lines (colorectal HT29, prostate DU145, breast MCF-7 and ovarian A2780) were evaluated using the MTT cell growth assay. Passage of peptide across the plasma membrane was assessed by means of confocal microscopy using FITC-labelled peptide. The effect of peptide on kinase activity was assessed in cell-free in vitro kinase assays. Results: The NPLY motif within RSKAKNPLYR was found to be essential for the growth inhibitory effect of this peptide. However, modified forms of this peptide in which all amino acids except the charged residues arginine and lysine were replaced by single non-polar amino acids such as alanine or valine were equally effective at inhibiting cancer cell proliferation. Moreover, these peptides inhibited not only c-Src activity as seen for RSKAKNPLYR but also the activity of members of the PKB/Akt kinase family. Conclusion: Novel decapeptides comprising only three amino acids have anti-cancer effects without the requirement for an integrin-based NPLY motif. These peptides inhibit the activity of not only c-Src but also members of the Akt family of kinases and may be useful as potential anti-cancer agents when used either alone or in combination with compounds previously reported to inhibit c-Src kinase activity.

Anti-tumor effect of CTLs activated by dendritic cells pulsed with K-ras mutant peptide and whole tumor antigen on pancreatic cancer

Objective： We studied the role of specific cytotoxic T lymphocytes （CTLs） activated by dendritic cells （DCs） presenting cationic nanoparticles with the K-ras （12-Val） mutant peptide and whole tumor antigen in the killing of different pancreatic cancer cell lines in vitro and in vitro. Methods： Peripheral blood DCs were induced by rhGM-CSF and IL-4 and cultured. DCs were sensitized by whole antigen of a pancreatic cancer cell line （PANC-1） with expression of K-ras mutant, K-ras mutant peptide （K-ras＋peptide） and cationic nanoparticles with K-ras mutant peptide （K-ras＋peptide-CNP）, respectively. Cell surface markers were measured by flow cytometry. Lymphocyte proliferation was detected by the 3H-TdR test, and ELISAwas performed to detect IFN-y secretion. 125I-UdR was used to measure the killing effect of CTLs. We also evaluated the antitumor activity of CTLs in vivo in a tumor-bearing nude mouse model prepared with the PANC-1 （K-ras＋） and SW1990 （K-ras-） cell lines. Results： Compared with K-ras＋peptide, low concentration K-ras＋pepUde-CNP can be effectively presented by DCs （P 〈 0.05）. CTLs induced by DCs pulsed with whole tumor antigen had significant greater killing effect （P 〈 0.05） on PANC-1 and SW1990 pancreatic cancer cells compared with K-ras＋peptide and K-ras＋peptide-CNP-induced CTLs. CTLs induced by DCs pulsed with K-ras＋peptide and K-ras＋peptide-CNP had a specific killing effect （P 〈 0.05） for PANC-1 and no effect （P 〉 0.05） on SW1990 cell lines （P 〉 0.05）. Conclusion： Cationic nanoparticles with K-ras （12-Val） mutant peptide can be effectively presented by DCs at a low concentration in a short time. CTLs induced by K-ras＋peptide-CNP had specific killing activity for the pancreatic cancer cell line with the K-ras （12-Val） mutant and could significantly inhibit tumor growth and increase the survival time of tumor-bearing nude mice.

Anti-tumor effects of p53N15-based fusion peptide in the transfected H1299 lung cancer cells

Objective Loss-of-function mutation of p53,a tumor suppressor gene,is an important mechanism for the development of human cancers. In this study we tried to transfect p53N15-based fusion peptide into H1299,a lung cancer cell line,and evaluate the anti-tumor effects of the fusion peptide. Methods Adeno-associated virus (AAV) vectors were used for transfecting p53N15 fusion peptide into p53-null lung adenocarcinoma H1299 cells.

噬菌体多肽peptide 20抗胃癌细胞肝转移作用的实验研究

目的:探讨噬菌体多肽peptide 20对胃癌肝高转移潜能细胞XGC9811-L肝转移能力的影响。方法:细胞体外生长实验观察噬菌体多肽peptide 20是否可影响胃癌肝高转移潜能细胞XGC9811-L的生长能力;侵袭、运动实验检测peptide 20对XGC9811-L细胞的侵袭和运动能力的影响;体外黏附试验检测peptide 20是否可抑制XGC9811-L对不同细胞外基质的黏附能力。结果:噬菌体多肽peptide 20对细胞的生长无影响,但可减弱XGC9811-L的侵袭、运动、及对collagen Ⅳ的黏附能力。结论:噬菌体多肽peptide 20可抑制胃癌肝高转移潜能细胞的侵袭、运动和对collagen Ⅳ的黏附能力。

Insights into therapeutic peptides in the cancerimmunity cycle:Update and challenges

Immunotherapies hold immense potential for achieving durable potency and long-term survival opportunities in cancer therapy.As vital biological mediators,peptides with high tissue penetration and superior selectivity offer significant promise for enhancing cancer immunotherapies(CITs).However,physicochemical peptide features such as conformation and stability pose challenges to their on-target efficacy.This review provides a comprehensive overview of recent advancements in therapeutic peptides targeting key steps of the cancer-immunity cycle(CIC),including tumor antigen presentation,immune cell regulation,and immune checkpoint signaling.Particular attention is given to the opportunities and challenges associated with these peptides in boosting CIC within the context of clinical progress.Furthermore,possible future developments in this field are also discussed to provide insights into emerging CITs with robust efficacy and safety profiles.

Development of LAG-3/FGL1 blocking peptide and combination with radiotherapy for cancer immunotherapy

Aside from antibodies,peptides show great potential as immune checkpoint inhibitors(ICIs)due to several advantages,such as better tumor penetration and lower cost.Lymphocyte-activation gene 3(LAG-3)is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1(FGL1).Here,we found that LAG-3 expression was higher than programmed cell death protein 1(PD-1)in multiple human cancers by TCGA databases,and successfully identified a LAG-3 binding peptide LFP-6 by phage display bio-panning,which specifically blocks the interaction of LAG-3/FGL1 but not LAG-3/MHC-II.Subsequently,D-amino acids were introduced to substitute the N-and C-terminus of LFP-6 to obtain the proteolysis-resistant peptide LFP-D1,which restores T cell function in vitro and inhibits tumor growth in vivo.Further,a bispecific peptide LFOP targeting both PD-1/PD-L1 and LAG-3/FGL1 was designed by conjugating LFP-D1 with PD-1/PD-L1blocking peptide OPBP-1(8-12),which activates T cell with enhanced proliferation and IFN-γ production.More importantly,LFOP combined with radiotherapy significantly improve the T cell infiltration in tumor and elevate systemic antitumor immune response.In conclusion,we developed a novel peptide blocking LAG-3/FGL1 which can restore T cell function,and the bispecific peptide synergizes with radiotherapy to further enhance the antitumor immune response.

Identification of LRG1 targeting peptide and its application in targeted imaging for breast cancer

Breast cancer remains a leading cause of morbidity and mortality among women worldwide,emphasizing the urgent need for enhanced diagnostic and therapeutic approaches.Leucine-rich-alpha-2-glycoprotein 1(LRG1)has emerged as a notable target due to its markedly elevated expression in breast tumors,suggesting the viability of LRG1 as a theranostic target.In our study,we employed phage display technology to identify a peptide,termed ET,that binds to LRG1 with a dissociation constant of 48.4μM.After modified with fluorescent cyanine dye,the ET peptide showcased effective tumor-targeting imaging across three different primary breast tumor models and a metastatic breast tumor model.We also undertook a comprehensive safety evaluation,which verified the good biosafety credentials of ET peptide.In summary,the ET peptide identified in this study shows effective LRG1-targeting ability both in vitro and in vivo,thus exhibiting immense potential for clinical translation.

TCP-1,a novel peptide to diagnose early colon cancer

A nine cyclic peptide(TCP-1)showed excellent specificity for colon cancer.TCP-1 binds with human tumor tissues at early stages and mice tumor with diameters of 1-4 mm,suggesting that TCP-1 may be used for early diagnosis of colon cancer.The mechanism of the targeted binding of TCP-1 to colon cancer was also studied using immunoprecipitation,LC-MS and bioinformatics.After screening and identifying of the possible binding target proteins of TCP-1,keratin,typeⅡcytoskeletal 5 was speculated to be the specific binding target protein of TCP-1 in human tumor tissue.Pharmacokinetics studies were conducted to investigate the target-mediated drug disposition of the new tumor-specific peptide by LC-MS/MS.The tissue distribution study showed that TCP-1 was found only in colon tumors(the target site)in tumor mice did not bind to any other tissues.Conjugating TCP-1 to tumor markedly increased its removal rate from blood circulation but mildly extended its staying time in vivo.In tumor mice,a lower AUC of TCP-1(reduced by almost 35%)and 2-fold higher clearance were found compared to that of normal mice.The proposed metabolic pathway of TCP-1 in the kidney was also determined using LC-MS^(n)-IT-TOF.The high specificity and low toxicity of the peptide may be caused by its extremely tight binding to the targets.Potential applications for future clinical use,including MRI and PET/CT were also explored,and this research may promote the development of colon cancer diagnostic technology research and provide new ideas and technical routes for tumor diagnostic technology.

Role of gastrin-peptides in Barrett's and colorectal carcinogenesis

Gastrin is the main hormone responsible for the stimulation of gastric acid secretion;in addition,gastrin and its derivatives exert proliferative and antiapoptotic effects on several cell types.Gastrin synthesis and secretion are increased in certain situations,for example,when proton pump inhibitors are used.The impact of sustained hypergastrinemia is currently being investigated.In vitro experiments and animal models have shown that prolonged hypergastrinemia may be related with higher cancer rates;although,this relationship is less clear in human beings.Higher gastrin levels have been shown to cause hyperplasia of several cell types;yet,the risk for developing cancer seems to be the same in normo-and hypergastrinemic patients.Some tumors also produce their own gastrin,which can act in an autocrine manner promoting tumor growth.Certain cancers are extremely dependent on gastrin to proliferate.Initial research focused only on the effects of amidated gastrins,but there has been an interest in intermediates of gastrin in the last few decades.These intermediates aren't biologically inactive;in fact,they may exert greater effects on proliferation and apoptosis than the completely processed forms.In certain gastrin overproduction states,they are the most abundant gastrin peptides secreted.The purpose of this review is to examine the gastrin biosynthesis process and to summarize the results from different studies evaluating the production,levels,and effects of the main forms of gastrin in different overexpression states and their possible relationship with Barrett's and colorectal carcinogenesis.

POTENTIATION OF BOANMYCIN ANTITUMOR ACTIVITY BY CHEMOTACTIC PEPTIDE

Objective: Chemotactic peptide may interfere with the process of tumor growth, invasion and metastasis by activating and attracting leukocytes containing macrophages. fMLP (CHO-Met-II e-Phe) is one of the chemotactic peptides. Boanmycin (BAM), a single A6 component from the bleomycin complex, is effective against a panel of cancers in clinical trials. This study was set to investigate the antitumor activity of BAM in combination with chemotactic peptide fMLP. Methods: Cytotoxicity of BAM and fMLP to cancer cells was determined by MTT assay. Therapeutic effect was evaluated by using the model of subcutaneously transplanted hepatoma 22 in mice. Results were judged as that a CDI less than 0.85 was considered as synergism and one less than 0.75 as significant synergism. Results: BAM and fMLP showed no synergism in cytotoxicity to cancer cells. In all in vivo experiments, fMLP was administered peritumorally at the dose of 1 mg/mouse; no significant inhibition by fMLP alone on the growth of hepatoma 22 was found. Different settings of BAM and fMLP combination included: (1) BAM, administered peritumorally×3, was started 24 h after tumor inoculation. BAM (0.5 mg/kg) alone and BAM-fMLP combination inhibited the growth of hepatoma 22 by 26.6% and 64.7%, respectively (P<0.05, CDI=0.36) on day 13. (2) BAM, administered ip×3, was started 24 h after tumor inoculation. The growth of tumor in BAM (1 mg/kg) group was faster than that in BAM-fMLP combination group. On day 14, BAM (1 mg/kg) alone and BAM-fMLP combination suppressed the growth of tumor by 11% and 70.6%, respectively (P<0.05), CDI=0.42). (3) BAM, administered ip×3, was started 96 h after tumor inoculation. The growth of tumor in BAM (1 mg/kg) group was faster than that in BAM-fMLP combination group. On day 13, BAM (1 mg/kg) alone and BAM-fMLP combination suppressed tumor growth by 38.2% and 77.1%, respectively (P<0.05, CDI=0.51). As shown in all in vivo experimental settings, antitumor effect of BAM in combination with fMLP was much more potent than that of BAM alone. Conclusion: This experiment shows that chemotactic peptide fMLP may enhance the antitumor effect of BAM, which indicates that chemotactic modulation may play a positive role in cancer chemotherapy.

Evaluation of 64Cu-DOTA- and 64Cu-CBTE2A-Galectin-3 Peptide as a PET Radiotracer for breast Carcinoma

Galectin-3 (Gal-3) is a β-galactosidase binding protein that modulates various cellular processes including cell adhesion, and metastasis. We evaluated the tumor targeting and imaging properties of a galectin-3 binding peptide originally selected from bacteriophage display, in a mouse model of human breast carcinoma expressing galectin-3. A galectin-3 binding peptide, ANTPCGPYTHDCPVKR, was synthesized with a Gly-Ser-Gly (GSG) spacer and 1,4,7,10, tetraazacyclododecane-N,N’,N’’,N’’’-tetracetic acid (DOTA) or 4,11-bis(carboxymethyl)-1,4,8,11 tetrazabicyclo[6.6.2]hexadecane 4,11-diacetic acid (CB-TE2A), and radiolabeled with 64Cu. The synthesized peptides 64Cu-DO3A-(GSG)-ANTPCGPYTHDCPVKR (64Cu-DO3A- pep) and 64Cu-CB-TE2A-(GSG)-ANTPCGPYTHDCPVKR(64Cu-CB-TE2A-pep) demonstrated an IC50 value of 97 ± 6.7 nM and 130 ± 10.2 nM, respectively, to cultured MDA-MB-435 breast carcinoma cells in vitro in a competitive displacement binding study. The tumor tissue uptake in SCID mice bearing MDA-MB-435 tumors was 1.2 ± 0.18 %ID/g (64Cu-DO3A-pep) and 0.85 ± 0.0.9 %ID/g (64Cu-CB-TE2A-pep) at 30 min, respectively. While liver retention was moderate with both radiolabeled peptides the kidney retention was observed to be high. Radiation dose delivered to the tumor was estimated to be 42 mGy/mCi and 129 mGy/ mCi with CB-TE2A and DO3A peptides, respectively. Imaging studies demonstrated tumor uptake with both 64Cu-DO3A- and 64Cu-CB-TE2A-(GSG)-ANTPCGPYTHDCPVKR after 2 h post injection. These studies suggest that gal-3 binding peptide could be developed into a PET imaging agent for galectin-3-expressing breast tumors.

Synergistic Anti-Tumor Effect of Cisplatin When Combined with an Anti-Src Kinase Integrin-Based Peptide

Background: It is known that active Src kinase promotes survival of ovarian cancer cell lines and inhibition of c-Src has been shown to restore sensitivity of drug-resistant human ovarian cancer cells to cisplatin. In this study we examined the effects of a 10 mer peptide on proliferation of human colon and ovarian cancer cells when used alone and in combination with cisplatin. Materials and Methods: A 10 mer peptide, RSKAKNPLYR, derived from a 15 mer ERK2 binding sequence present on the cytoplasmic domain of the β6 integrin subunit was tested for its effect on proliferation of HT29 colon cancer cells under serum-free conditions by means of the MTT assay. Cell proliferation studies to examine the effects of cisplatin combined with peptide were conducted in serum-containing medium using the 10 mer peptide fused to a hydrophobic signal peptide sequence. Drug combination studies were performed on HT29 cells and a cisplatin-resistant cell line (ADDP) derived from an ovarian cancer cell line A2780. The effects of peptides on Src kinase activity were assessed in a cell-free in vitro kinase assay. Results: The 10 mer peptide was as effective as the 15 mer parent compound at inhibiting proliferation of HT29 cells. Exposure of HT29 and ADDP cells to a combination of cisplatin and the fusion peptide resulted in synergistic inhibition of cell growth. Both the 10 mer peptide alone and when fused to the signal peptide sequence inhibited Src kinase activity. Conclusion: Our findings raise the possibility of combination therapy comprising peptide and cisplatin for cisplatin-resistant ovarian cancers and other cancers that are high expressors of c-Src.

Novel Immunogenic Epitopes in the NaPi-IIb Protein: Production of Monospecific Antibodies Using Synthetic Peptides Outlined on Isoform Specific Regions of the Type IIb Sodium-Dependent Phosphate Transporter (NaPi-IIb)

NaPi-IIb is a multiple passage protein membrane which is primarily responsible for phosphate uptake in the kidney and in the small intestine. Beyond its physiological functions, their involvement with carcinogenesis was initially described in mid-2003, due to its distinct level of expression in normal and tumor cells of the ovary. Although less common than cervical cancer, epithelial ovarian cancer is considered the most lethal gynecologic malignancy, which is mainly due to diagnosis in the advanced stages as a result of the absence of symptoms during the onset of the disease and the lack of tools for early detection. Here, we produce antibodies that are anti-synthetic peptides that are derived from the regions of second extracellular loop of NaPi-IIb, which is a non-overlapping portion of MX35 epitope. These two 15 distinct amino acid residue peptides, designated as Let#1 and Let#2, are engineered in a very thorough way to detect specific sites only in this isoform, thus excluding cross-reactivity with other carriers of the same family. The lack of immunogenicity of small peptides is surpassed by the conjugation with carrier proteins. Using immunochemical methods, we demonstrate that polyclonal antibodies that are mono-specific for the Let#1 and Let#2 peptides recognize proteins that express similar amino acid sequences during blood circulation. Additionally, using flow cytometry, we identify NaPi-IIb in NIH:OVCAR-3 cells. The clear identification of two shorter peptides on the extracellular loop of NaPi-IIb, which are far from the monoclonal antibody MX35-recognizing epitopes, adds new promising tools for ovarian cancer follow-up and staging.

马乳源性生物活性肽生物学信息及其抗肺癌作用靶点探索

在前期研究基础上通过在线软件对已知氨基酸组成的马乳源性活性肽生物学信息和关键靶蛋白进行分析并进行分子对接,探索马乳源性活性肽抗肺癌作用靶点。结果表明马乳源的活性肽为不稳定、带正电荷的亲水性多肽,是没有跨膜区和信号肽,也没有糖基化和磷酸化位点的细胞膜外多肽,二级结构主要以无规则卷曲为主,与肺癌相关的核心靶点即CTNNB1、FGFR2、FOXF1、KRAS、NKX2-1、TGFBR2具有很好的结合亲和力,为深入研究马乳源活性肽的生物学功能奠定了基础。

血清MMP-9、ProGRP及内皮素的水平与非小细胞肺癌分期的相关性分析

目的探究非小细胞肺癌患者中血清基质金属蛋白酶-9(MMP-9)、血清胃泌素释放肽前体(ProGRP)与肿瘤分期的相关性。方法选取非小细胞肺癌患者70例作为观察组,以同期健康体检者70例作为对照组,比较两组患者血清中MMP-9、ProGRP及内皮素水平,并采用ROC曲线分析上述指标的临床诊断价值。结果观察组患者MMP-9、ProGRP以及内皮素表达水平均显著高于对照组(P<0.05),MMP-9、ProGRP以及内皮素阳性表达率男性患者和Ⅲ、Ⅳ期患者显著高于女性患者和Ⅰ、Ⅱ期者,差异有统计学意义(P<0.05),MMP-9、ProGRP以及内皮素与肿瘤分期均具有显著相关性(P<0.05)。结论MMP-9、ProGRP以及内皮素均可作为非小细胞肺癌的检测指标,且其表达水平与肿瘤分期存在相关性,为临床诊断提供依据。