Inhibitory Effect of Bupleuri Radix Saponins on Adhesion of Some Solid Tumor Cells and Relation to Hemolytic Action: Screening of 232 Herbal Drugs for Anti-Cell Adhesion

Abstract Background Glomus tumors are subcutaneous tumors arising from glomus bodies, thermoregulatory components of the skin. These tumors could occur in visceral organs where glomus bodies are not normally present. Herein, we report a case of primary pancreatic glomus tumor with aggressive direct invasion into the superior mesenteric vein (SMV). To the best of our knowledge, this is the second case report of a glomus tumor arising in the pancreas. Case presentation A 46-year-old woman was referred to our hospital due to vomiting with epigastric and back pain. Dynamic-CT revealed a well-circumscribed hypervascular mass, measuring 37 mm in its maximal diameter involving the pancreatic head. Both CT and endoscopic ultrasonography (EUS) revealed direct invasion into the SMV and radiologically suspected tumor thrombus. Biopsy sample obtained by EUS-guided fine needle aspiration revealed proliferation of small cells, round-to-oval tumor cells with round nuclei and scant cytoplasm. A histological diagnosis of pancreatic neuroendocrine tumor, G1 was initially considered. Therefore, subtotal stomach-preserving pancreatoduodenectomy using Child-II reconstruction was subsequently performed. Her SMV was resected and reconstructed due to extensive tumor involvement. Subsequent histopathological analysis revealed solid tumor cells proliferation that comprised oval-shaped nuclei and scant cytoplasm around disorganized or slit-shaped vessels in hematoxylin–eosin-stained slides. Immunohistochemical analysis then demonstrated positive immunoreactivity for smooth muscle actin, vimentin, and CD34, but negative for chromogranin A, synaptophysin, CD56, and signal transducer and activator of transcription 6. Based on these histological findings of resected specimens, the lesion was subsequently diagnosed as a primary pancreatic glomus tumor harboring direct invasion into the SMV. Her postoperative course was uneventful and annual surveys for the following 4 years post-op detected no clinical signs of recurrence. Conclusions We report a very rare case of glomus tumor of the pancreas accompanied by venous invasion. Curative surgical resection is the best treatment option for pancreatic glomus tumors. Although pancreatic glomus tumor is rare, it should be taken into consideration in the differential diagnosis of a pancreatic solid tumor with hypervascularity.

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RGD4C peptide mediates anti-p21Ras scFv entry into tumor cells and produces an inhibitory effect on the human colon cancer cell line SW480

BMC Cancer ◽

10.1186/s12885-021-08056-4 ◽

2021 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Chen-Chen Huang ◽

Fang-Rui Liu ◽

Qiang Feng ◽

Xin-Yan Pan ◽

Shu-Ling Song ◽

...

Keyword(s):

Antitumor Activity ◽

Cell Membrane ◽

Fusion Protein ◽

Tumor Cell ◽

Tumor Cells ◽

Fusion Proteins ◽

Inhibitory Effect ◽

Endosomal Escape ◽

Antitumor Effects ◽

Sw480 Cells

Abstract Background We prepared an anti-p21Ras scFv which could specifically bind with mutant and wild-type p21Ras. However, it cannot penetrate the cell membrane, which prevents it from binding to p21Ras in the cytoplasm. Here, the RGD4C peptide was used to mediate the scFv penetration into tumor cells and produce antitumor effects. Methods RGD4C-EGFP and RGD4C-p21Ras-scFv recombinant expression plasmids were constructed to express fusion proteins in E. coli, then the fusion proteins were purified with HisPur Ni-NTA. RGD4C-EGFP was used as reporter to test the factors affecting RGD4C penetration into tumor cell. The immunoreactivity of RGD4C-p21Ras-scFv toward p21Ras was identified by ELISA and western blotting. The ability of RGD4C-p21Ras-scFv to penetrate SW480 cells and colocalization with Ras protein was detected by immunocytochemistry and immunofluorescence. The antitumor activity of the RGD4C-p21Ras-scFv was assessed with the MTT, TUNEL, colony formation and cell migration assays. Chloroquine (CQ) was used an endosomal escape enhancing agent to enhance endosomal escape of RGD4C-scFv. Results RGD4C-p21Ras-scFv fusion protein were successfully expressed and purified. We found that the RGD4C fusion protein could penetrate into tumor cells, but the tumor cell entry of was time and concentration dependent. Endocytosis inhibitors and a low temperature inhibited RGD4C fusion protein endocytosis into cells. The change of the cell membrane potential did not affect penetrability. RGD4C-p21Ras-scFv could penetrate SW480 cells, effectively inhibit the growth, proliferation and migration of SW480 cells and promote this cells apoptosis. In addition, chloroquine (CQ) could increase endosomal escape and improve antitumor activity of RGD4C-scFv in SW480 cells. Conclusion The RGD4C peptide can mediate anti-p21Ras scFv entry into SW480 cells and produce an inhibitory effect, which indicates that RGD4C-p21Ras-scFv may be a potential therapeutic antibody for the treatment of ras-driven cancers.

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Hsp90 inhibitors deplete key anti-apoptotic proteins in pediatric solid tumor cells and demonstrate synergistic anticancer activity with cisplatin

International Journal of Cancer ◽

10.1002/ijc.20611 ◽

2004 ◽

Vol 113 (2) ◽

pp. 179-188 ◽

Cited By ~ 55

Author(s):

Rochelle Bagatell ◽

Jason Beliakoff ◽

Cynthia L. David ◽

Marilyn T. Marron ◽

Luke Whitesell

Keyword(s):

Anticancer Activity ◽

Tumor Cells ◽

Solid Tumor ◽

Hsp90 Inhibitors ◽

Pediatric Solid Tumor ◽

Apoptotic Proteins

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Action inhibitrice des cellules irradiées sur la greffe des cellules actives dans la tumeur T8 de Guérin. (Inhibitory effect of irradiated tumor cells of Guérin T8 tumor on the growth of viable cells)

Plastic & Reconstructive Surgery ◽

10.1097/00006534-196204000-00055 ◽

1962 ◽

Vol 29 (4) ◽

pp. 489

Author(s):

&NA;

Keyword(s):

Tumor Cells ◽

Inhibitory Effect ◽

Viable Cells

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Cell adhesion and invasion during secondary tumor formation: interactions between tumor cells and host organs

Selected Aspects of Cancer Progression: Metastasis, Apoptosis and Immune Response ◽

10.1007/978-1-4020-6729-7_3 ◽

2008 ◽

pp. 21-32 ◽

Cited By ~ 1

Author(s):

Peter Gassmann ◽

Jörg Haier ◽

Garth L. Nicolson

Keyword(s):

Cell Adhesion ◽

Tumor Cells ◽

Tumor Formation ◽

Secondary Tumor ◽

Adhesion And Invasion

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EXPRESSION OF NEURAL CELL ADHESION MOLECULES IN THE MOUSE ANTERIOR PITUITARY GLAND AND PITUITARY TUMOR CELLS

Biomedical Research ◽

10.2220/biomedres.19.269 ◽

1998 ◽

Vol 19 (4) ◽

pp. 269-277

Author(s):

YOSHIHIRO YAYOI ◽

SUMIO TAKAHASHI ◽

SAKAE TAKEUCHI ◽

MAKOTO TAKEUCHI ◽

TATSUNORI SEKI ◽

...

Keyword(s):

Cell Adhesion ◽

Pituitary Gland ◽

Tumor Cells ◽

Adhesion Molecules ◽

Cell Adhesion Molecules ◽

Pituitary Tumor ◽

Anterior Pituitary ◽

Neural Cell ◽

Neural Cell Adhesion Molecules ◽

Neural Cell Adhesion

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163 Improved anti-tumor activity of next-generation TCR-engineered T cells through CD8 co-expression

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-sitc2021.163 ◽

2021 ◽

Vol 9 (Suppl 3) ◽

pp. A173-A173

Author(s):

Gagan Bajwa ◽

Justin Gunesch ◽

Inbar Azoulay-Alfaguter ◽

Melinda Mata ◽

Ali Mohamed ◽

...

Keyword(s):

T Cells ◽

Tumor Cells ◽

Solid Tumor ◽

Cd4 T Cells ◽

Tumor Response ◽

Hla Class I ◽

Next Generation ◽

Engineered T Cells ◽

Anti Tumor Activity

BackgroundSuccessful targeting of solid tumors with TCR-engineered T cells (TCR-T) will require eliciting of antigen-specific, multi-dimensional, sustained anti-tumor immune response by infused T cells while overcoming the suppressive tumor microenvironment. First-generation TCR-T approaches have demonstrated clinical efficacy in some solid cancers. However, effective treatment across several solid tumor indications may require engineered T cells with enhanced anti-tumor activity. Here, we show pre-clinical data from one of the engineering approaches currently being developed for next-generation ACTengine® TCR-T product candidates. We evaluated the impact of co-expression of different CD8 co-receptors on functionality of CD4+ and CD8+ T cells genetically modified with an HLA class I-restricted TCR and determined the depth and durability of anti-tumor response in vitro.MethodsHere, we used a PRAME-specific TCR currently being tested in the ACTengine® IMA203 clinical trial. T cells expressing either the TCR alone or co-expressing the TCR and CD8α homodimer (TCR.CD8α) or CD8αβ heterodimer (TCR.CD8αβ) were characterized for transgene expression, antigen-recognition, and functional efficacy in vitro. Comprehensive evaluation of CD4+ T cells expressing TCR.CD8α or TCR.CD8αβ was performed focusing on cytotoxic potential and the breadth of cytokine response against target-positive tumor cell lines.ResultsIntroduction of CD8α or CD8αβ enabled detection of transgenic TCR on the surface of CD4+ T cells via HLA multimer-guided flow cytometry otherwise lacking in the TCR only transduced T cells. Co-expression of either form of CD8 co-receptor endowed CD4+ T cells with the ability to recognize and kill target positive tumor cells; however, genetic modification with TCR.CD8αβ led to more pronounced CD4+ T cell activation as compared to TCR.CD8α. Most distinct differences were observed in the breadth and magnitude of cytokine responses, less in cytotoxic activity against tumor cells. T cells expressing TCR.CD8αβ showed superior induction of Th1 cytokines e.g. IFNγ, TNFα, IL-2, GM-CSF in vitro upon antigen stimulation as compared to TCR.CD8α-T cells. Additionally, TCR.CD8αβ T cells demonstrated more efficient engagement with antigen-presenting cells and consequently, modulation of cytokine response than TCR.CD8α-T cells.ConclusionsOur findings illustrate that engaging CD4+ T cells via CD8 co-expression potentiates anti-tumor activity of HLA class I restricted TCR-T cells in vitro. The pleiotropic effects mediated by activated CD4+ T cells including acquired cytotoxicity may potentially improve outcomes in solid tumor patients when applied clinically. In addition, the differential functional profile of TCR-T cells co-expressing either CD8α or CD8αβ suggests that optimizing the type of co-receptor is relevant to maximize anti-tumor response.

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Antitumor activity of L-asparaginase from Erwinia Carotovora from against different leukemic and solid tumours cell lines

Biomeditsinskaya Khimiya ◽

10.18097/pbmc20135905498 ◽

2013 ◽

Vol 59 (5) ◽

pp. 498-513 ◽

Cited By ~ 9

Author(s):

O.Yu. Abakumova ◽

O.V. Podobed ◽

P.A. Karalkin ◽

L.I. Kondakova ◽

N.N. Sokolov

Keyword(s):

Dna Synthesis ◽

Tumor Cells ◽

Solid Tumor ◽

Human Fibroblasts ◽

Erwinia Carotovora ◽

Cell Number ◽

Jurkat Cells ◽

Leukemic Cells ◽

Cycle Phase ◽

Tumor Cell Death

We have studied dose- and time-dependent antitumor and cytotoxic effects of Erwinia carotovora L-asparaginase (ECAR LANS) and Escherichia coli L-asparaginase (MEDAC) on human leukemic cells and human and animal solid tumor cells. We determined the sensitivity of tumor cells to L-asparaginases, as well the effect L-asparaginases on cell growth rate, protein and DNA synthesis per se and with addition of different cytostatics. The data obtained demonstrated that ECAR LANS L-asparaginase suppressed growth of all tested solid tumor cells. Evaluation of leukemic cell number after treatment with L-asparaginases for 24, 48 and 72 h demonstrated that asparagine deficiency did not kill cells but stopped normal cell division and had no effect on protein and DNA synthesis. Cytofluorometric study of solid and leukemic cells demonstrated that the treatment with L-asparaginase for 72 h did not change cell cycle phase distribution and did not increase the number of apoptotic cells. The HL-60 cell line was only exemption. At the same time, cells treatment with L-asparaginase and doxorubicin combination leaded to increase of apoptotypical cell number to 60% for MCF7 cells, to 40% for Jurkat cells and to 99% for HL-60 cells. We have excluded apoptosis as main reason for tumor cell death after asparaginase treatment because multi resistant Jurkat/A4 cells have been asparaginase sensitive. We have not found ECAR LANS L-asparaginase effect on normal human fibroblasts growth ability and we had come to conclusion that enzyme cytotoxcisity related only with asparagine deficiency.

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ANTITUMOR EFFECT OF ELECTROMAGNETIC FIELDS AND THEIR EFFECT ON PAIN IN EXPERIMENTAL AND CLINICAL ONCOLOGY

Research n Practical Medicine Journal ◽

10.17709/2409-2231-2019-6-2-9 ◽

2019 ◽

Vol 6 (2) ◽

pp. 86-99 ◽

Cited By ~ 2

Author(s):

E. M. Frantsiyants ◽

E. A. Sheiko

Keyword(s):

Tumor Cells ◽

Electromagnetic Fields ◽

Analgesic Effect ◽

Electromagnetic Waves ◽

Antitumor Effect ◽

Living Organism ◽

Inhibitory Effect ◽

Chemotherapeutic Agents ◽

Scientific Publications

The review examined and analyzed scientific publications on the effect of electromagnetic fields (EMF) on various systems of the human body and animals with tumors, as well as on pain in the experiment and the clinic. The theoretical foundations and practical results of the use of EMF in various modulations and modes in the goals and objectives of oncology, including how to optimize the process of anesthesia and correct the vital activity of the body's functional systems with a tumor, are consecrated. Information is given on possible physicochemical effects, features, and mechanisms of therapeutic influence at various levels of a living organism. The ability of electromagnetic waves to transfer information both within a single biosystem and at the level of a whole living organism with a tumor is shown. Studies of combined action of EMF and chemotherapy were analyzed. It has been established that there are experimental prerequisites for using this factor in order to induce changes in the permeability of the membranes of tumor cells by increasing the internalization of chemotherapeutic agents and, thus, enhance the antitumor effect. The role of EMF in the induction of apoptosis in tumor cells is shown. It has been shown that chemotherapy together with electromagnetic fields induces apoptosis and has an inhibitory effect on DNA synthesis in osteosarcoma cells, breast cancer, colon cancer, melanoma and other tumors. The role of magnetic fields in order to enhance the analgesic effect was investigated. The analgesic effect is due to the cessation or weakening of nerve impulses from the painful focus due to the elimination of hypoxia, the improvement of microcirculation, and the reduction of edema, it has been shown. Transcranial magnetic therapy is used as an analgesic tool in onconurology. The therapeutic anti-pain effect is associated with the stimulation of the antinociceptive system, an increase in the synthesis of natural analgesics — endorphins with their subsequent release into the cerebrospinal fluid and blood. As it has already been shown, with the increase in the intensity of pain and its duration, all indicators of the quality of life and the results of treatment of the patient deteriorate, so the search for ways to improve the antitumor effectiveness of specialized treatment and eliminate the causes that prevent their implementation continue to be relevant and in demand.

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