EpCAM- AN OLD CANCER ANTIGEN, TURNED ONCOGENIC RECEPTOR AND ITS TAGETING IMMUNOTHERAPY

Zhu, George

doi:10.22270/ujpr.v3i2.140

Cited by 6 publications

(5 citation statements)

References 48 publications

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“… 38 Anti-EpCAM antibody conjugated with alpha-amanitin has the potential to be a highly effective therapeutic agent for pancreatic carcinoma and various EpCAM-expressing malignancies. 39 Since 1970s, the method of MD simulation has gained popularity in biochemistry and biophysics. 40 The aim of this study was to offer a reasonable pattern of anti-EpCAM IT model to design the novel generation of recombinant IT.…”

Section: Discussionmentioning

confidence: 99%

Simulation and Stability Assessment of Anti-EpCAM Immunotoxin for Cancer Therapy

Hosseinian¹,

Haddad-Mashadrizeh²,

Dolatabadi³

2018

Adv Pharm Bull

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Purpose: Epithelial cell adhesion molecule (EpCAM) is a dominant antigen in human colon carcinoma tissue. Topology features of this antigen are different in normal and malignant conditions; for instance, EpCAM is much less accessible to antibodies in normal cells than in cancerous tissues. Hence, EpCAM has been considered as a suitable candidate for cancer target therapy via immunotoxins (ITs) development. In this study, attention was focused on the stability assessment of anti-EpCAM-IT (anti-Ep-IT) to design a novel IT.Methods: The 3D structures of the antibody template and the toxin segment of anti-Ep-IT were retrieved from PDB. Discovery Studio3.0 was used to separate the ligands and water molecules. The antibody (Ab) fragment of anti-Ep-IT was aligned using protein blast (BLAST-p), and SWISS-MODEL database was used for Ab modeling. IT modeling was accomplished using MODELLER 9.15. Also, GROMACS 5.07 was used for molecular dynamic (MD) simulation step. Moreover, ERRAT and RAMPAGE databases were used for quality assessment of the structures.Results: BLAST-p results indicated that antibody moiety of IT has the highest E-value and query coverage scores to the monoclonal antibody (mAb) 4D5MOC-B. Modeling by SWISS-MODEL provided a reasonable template for Ab portion compared to MODELLER. The best modeled full-length IT with the lowest RMSD values was selected. Finally, RMSD plot for MD stage demonstrated constant values from 7000ps to 20000ps.Conclusion: In general, both modeling results and their quality evaluations were satisfactory for designing IT. Moreover, RMSD plot revealed that IT stability was preserved during the simulation. Overall, our findings led to modeling and simulation of the anti-Ep-IT with more structural stability.

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Section: Discussionmentioning

confidence: 99%

Simulation and Stability Assessment of Anti-EpCAM Immunotoxin for Cancer Therapy

Hosseinian¹,

Haddad-Mashadrizeh²,

Dolatabadi³

2018

Adv Pharm Bull

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“…Aberrant activation of RTKs often leads to malignant transformation, whereas PI3K/ Axl is required for this oncogenic receptor signaling [13]. Targeting against a deregulated dominant oncogenic receptor such as the oncogenic estrogen receptor (ER) pathway (tamoxifen), and blocking oncogenic receptor HER3/HER2 agent trastuzumab is enough to slow tumor progression [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32].…”

Section: Short Communicationmentioning

confidence: 99%

“…At present,the oncogenic receptors and their target antibodies (Abs) [33]strategies have been widely extended to CD44 oncogenic receptor of hyaluronic acid(HA) [34], RAGE oncogenic receptor [35][36][37][38], the oncogenic receptor platelet-derived growth factor receptor-β (PDGFRβ) or PDGFRa linked to the pathogenesis of myeloproliferative neoplasm or chronic leukemia [26,39,40], cytokine IL-3/oncogenic receptor IL3R, IL-6/IL6R-STAT3-ADAR1 (P150) oncogenic transcription factors [41], oncogenic IL7R [42], IL-11/IL-11 gp130 receptor pro-oncogenic signaling [24,[43][44][45] and oncogenic receptor IL17rb [46,47]. Intriguing, in Wilmes' article [48,49], homodimeric class I cytokine receptors TpoR, EpoR and GHR are normally dimerized by their ligands.…”

Section: Short Communicationmentioning

confidence: 99%

A Mini-Review Towards the Assessment of two Natural Anticoagulants Protein C And Antithrombin III

Zhu

2022

AJBSR

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“…Chemotherapy is a major skillful of cancer therapy. One of the most important advances in oncology has been increased acceptance of evidence that most patients with disseminated tumors were setted to the protocol of chemotherapy in conjunction with recent targeting oncogenic receptor [1][2][3][4][5][6][7][8][9][10][11][12][13][14],traditional medicine(TCM)and/or adoptive immunotherapy(LAK cells, TIL therapy) [15,16].The experience in Ugandan children with Hodgkin's disease has been excellent [17] and in a study of 14 adults with stage I and II Hodgkin's disease, mostly clinically staged,13 patients (93%) achieved CR with combination chemotherapy and all were in CR 11 to 94 months after the completion of treatment [18]. Another, a disease-free survivors of 5 years (56.5-59.3% versus 22-24.3%) and 10 years (48.9%) was remarkedly higher rate in those breast cancers with stage III following surgery plus chemotherapy than only surgery.…”

Section: Introductionmentioning

confidence: 99%

Clinical prolonged follow up of patients with advanced cancers after chemotherapy with traditional medicine (78 cases)

Zhu¹

2018

Trends Cancer Res Chemother

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Objective: Traditional systems of medicine all over the world even traditional medicine and cancer have been using plants and plants products for therapeutic intention. The purpose of this retrospective trials is to assesses the clinical efficacy of chemotherapy in conjunction with TCM for a broad variety of cancers.Methods: 78 patients with available cancers were concluded in the study during September1993 -May2018.The sex ratio of male: female was 53:25 respectively. The mean age at onset was 46.9 years (range 10-79 years). All patients were treated with different dosage of various chemotherapy in combination with TCM or traditional medicine alone. The basic chemotherapeutic regimen consisted of vincristine (VCR,1-2mg/week), cyclophosphamide (CTX, 200-1,000mg / week), mitomycin C (MMC, 2-4mg/week) and 5-fluorouracil (5-Fu,250-500mg/day). In addition, according to patient condition, the additional drug doxorubicin (ADM,20mg/week) in lymphoma and metastatic breast cancer, demethylcantharidin in liver cancer and cisplatin (DDP) or interleukin-2(PHA) or gefitinib in lung cancer. The detail prescription of TCM varied among a broad variety of carcinomas (see full text case reports). The criteria of complete remission (CR) and/or partial remission (PR)is according to the rules where physicians have in common with in clinics. Results:In 78 cases, the CR was obtained in 33(42.3%) advanced cancers, a short CR in 12(15.4%) cases, PR in 27 (34.6%) cancers, Stable disease in 6 cases. In differential types of 20 patients over ten years, lymphoma occupied 8 cases (40%). As to approach to the schedule of drug administration,16 lymphoma obtained CR via COMA (CTX, VCR, MMC, ADM) regimen and TCM or antibiotics and immunotherapy. Five advanced gastric cancer were successfully treated using MFC and cinobufacini/cantharidin,and TCM. In follow up, one HCC accompanied with colon polyps obtained CR via hepatectomy and targeting oncogenic receptor tyrosine kinase inhibitor sorafenib. Among two lung cancer, one female with metastatic lung cancer was given targeting oncogenic receptor EGFR gefitinib therapy after the combination chemotherapy, which was stable disease for 8+months.CR can also be achieved in one advanced cholangicarcinoma and one advanced gallbladder cancer through major protocol of TCM and the addition of small dosage of chemotherapy. Thyroid cancer was placed on the primary use of TCM. The crude herbs consisted of sargassum, tangle, Oyster (mussels), Poria cocos, Ophiopogon japonicus, Prunella vulgaris, Taraxacum, Scrophularia ningpoensis, Cremastra appendiculata, Trichosanthes Kirilowii, Sophora subprostrata, Houttuynia cordata, Scutellaria barbata d. don and Oldenlandia diffusa roxb. Among those long-term survivors,31 carcinomas obtained in disease-free survival over 5years,20 cancers were survival over 10years, the longest four patients over 25 years. Conclusion:In this study, I experienced that a CR was a pivotal influencing factor in those longest survival patients, and traditional medicine was also recommended. Do...

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EpCAM- AN OLD CANCER ANTIGEN, TURNED ONCOGENIC RECEPTOR AND ITS TAGETING IMMUNOTHERAPY

Cited by 6 publications

References 48 publications

Simulation and Stability Assessment of Anti-EpCAM Immunotoxin for Cancer Therapy

Simulation and Stability Assessment of Anti-EpCAM Immunotoxin for Cancer Therapy

A Mini-Review Towards the Assessment of two Natural Anticoagulants Protein C And Antithrombin III

Clinical prolonged follow up of patients with advanced cancers after chemotherapy with traditional medicine (78 cases)

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