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Иммунопотент - ТФ при онкологии (на английском)

Antiangiogenic and antitumor effects of IMMUNEPOTENT CRP in murine melanoma.

Moisés A Franco-Molina, Edgar Mendoza-Gamboa, Pablo Zapata-Benavides, Paloma Castillo-Tello, Clara E Isaza-Brando, Diana Zamora-Avila, Lydia G Rivera-Morales, Diana F Miranda-Hernández, Crystel A Sierra-Rivera, Magda E Vera-García, Reyes S Tamez-Guerra and Cristina Rodríguez-Padilla

Laboratorio de Inmunología y Virología. Departamento de Microbiología e Inmunología. Facultad de Ciencias Biológicas de la Universidad Autónoma de Nuevo León, San Nicolás de los Garza, N. L. México.

Background: Skin cancers are common, and there has recently been a dramatic increase in their incidence, particularly in the occurrence of melanoma. Furthermore, relapse after curative surgical treatment of melanoma remains a significant clinical challenge and accounts for most of the mortality of this disease. Objective: The aim of this study was to determine whether IMMUNEPOTENT CRP affects B16F10 melanoma cells and tumors growth and vascular endothelial growth factor (VEGF) production in vivo and in vitro. Methods: B16F10 cells and B16F10-inoculated mice were treated with different concentrations of IMMUNEPOTENT CRP. Outcomes were then evaluated using MTT, TUNEL, Caspase-3, senescence, ELISA and colorimetric assays. Parameters related to survival and tumor weight were also assessed. Results: IMMUNEPOTENT CRP decreased the viability of B16F10 cells by increasing apoptosis of the treated cells, and VEGF production was decreased both in vitro and in vivo. Furthermore, treatment prevented metastasis, delayed the appearance of tumors, decreased tumor weight and improved the survival of tumor-bearing mice. Discussion: These observations suggest that IMMUNEPOTENT CRP can be used to suppress growth and metastasis by using targeting proteins such as VEGF. DOI: 10.3109/08923971003663253

Immunopharmacol Immunotoxicol. 2010 Mar 5. [Epub ahead of print]

Antiangiogenic and antitumor effects of IMMUNEPOTENT CRP in murine melanoma.

Franco-Molina MA, Mendoza-Gamboa E, Zapata-Benavides P, Castillo-Tello P, Isaza-Brando CE, Zamora-Avila D,Rivera-Morales LG, Miranda-Hernández DF, Sierra-Rivera CA, Vera-García ME, Tamez-Guerra RS, Rodríguez-Padilla C.

Laboratorio de Inmunología y Virología. Departamento de Microbiología e Inmunología. Facultad de Ciencias Biológicas de la Universidad Autónoma de Nuevo León, San Nicolás de los Garza, N. L. México.

Abstract

Background: Skin cancers are common, and there has recently been a dramatic increase in their incidence, particularly in the occurrence of melanoma. Furthermore, relapse after curative surgical treatment of melanoma remains a significant clinical challenge and accounts for most of the mortality of this disease. Objective: The aim of this study was to determine whether IMMUNEPOTENT CRP affects B16F10 melanoma cells and tumors growth and vascular endothelial growth factor (VEGF) production in vivo and in vitro. Methods: B16F10 cells and B16F10-inoculated mice were treated with different concentrations of IMMUNEPOTENT CRP. Outcomes were then evaluated using MTT, TUNEL, Caspase-3, senescence, ELISA and colorimetric assays. Parameters related to survival and tumor weight were also assessed. Results: IMMUNEPOTENT CRP decreased the viability of B16F10 cells by increasing apoptosis of the treated cells, and VEGF production was decreased both in vitro and in vivo. Furthermore, treatment prevented metastasis, delayed the appearance of tumors, decreased tumor weight and improved the survival of tumor-bearing mice. Discussion: These observations suggest that IMMUNEPOTENT CRP can be used to suppress growth and metastasis by using targeting proteins such as VEGF.

PMID: 20205507 [PubMed - as supplied by publisher]

Cytotherapy. 2008;10(5):490-6.

IMMUNEPOTENT CRP (bovine dialyzable leukocyte extract) adjuvant immunotherapy: a phase I study in non-small cell lung cancer patients.

Franco-Molina MA, Mendoza-Gamboa E, Zapata-Benavides P, Vera-García ME, Castillo-Tello P, García de la Fuente A,Mendoza RD, Garza RG, Támez-Guerra RS, Rodríguez-Padilla C.

Laboratorio de Inmunología y Virología, Departamento de Microbiología e Inmunología, Facultad de Ciencias Biológicas de la Universidad Autónoma de Nuevo León, San Nicolás de los Garza, México.

Abstract

BACKGROUND: IMMUNEPOTENT CRP is a mixture of low molecular weight substances, some of which have been shown to be capable of modifying the immune response. We evaluated the response and adjuvant effect of IMMUNEPOTENT CRP on non-small cell lung cancer (NSCLC) patients in a phase I clinical trial.

METHODS: Twenty-four NSCLC patients were included in the study and divided into two groups. Group 1 received a conventional treatment of 5400 cGy external radiotherapy in 28 fractions and chemotherapy consisting of intravenous cisplatin (40 mg/m(2)) delivered weekly for 6 weeks. Group 2 received the conventional treatment plus IMMUNEPOTENT CRP (5 U) administered daily. We performed clinical evaluation by CT scan and radiography analysis, and determined the quality of life of the patients with the Karnofsky performance scale. A complete blood count (red and white blood cell tests), including flow cytometry analysis, blood work (alkaline phosphatase test) and a delayed-type hypersensitivity (DTH) skin test for PPD, Varidase and Candida were performed.

RESULTS: The administration of IMMUNEPOTENT CRP induced immunomodulatory activity (increasing the total leukocytes and T-lymphocyte subpopulations CD4(+), CD8(+), CD16(+) and CD56(+), and maintaining DHT) and increased the quality of the patients' lives, suggesting immunologic protection against chemotherapeutic side-effects in NSCLC patients.

DISCUSSION: Our results suggest the possibility of using IMMUNEPOTENT CRP alongside radiation and chemotherapy for maintaining the immune system and increasing the quality of life of the patients.

PMID: 18821359 [PubMed - indexed for MEDLINE]

Cytotherapy. 2008;10(2):212-9.

Bovine dialyzable leukocyte extract modulates AP-1 DNA-binding activity and nuclear transcription factor expression in MCF-7 breast cancer cells.

Mendoza-Gamboa E, Franco-Molina MA, Zapata-Benavides P, Castillo-Tello P, Vera-García ME, Tamez-Guerra RS,Rodríguez-Padilla C.

Laboratorio de Inmunología y Virología, Departamento de Microbiología e Inmunología, Facultad de Ciencias Biológicas de la Universidad Autónoma de Nuevo León, San Nicolás de los Garza, N. L, México.

Abstract

BACKGROUND: We have previously demonstrated that bovine dialyzable leukocyte extract (bDLE) induces death through an apoptosis mechanism in MCF-7 breast cancer cells. Depending on the cell type and stimulus, activating protein-1 (AP-1) has been shown to regulate cell proliferation and differentiation, the stress response, apoptosis and survival. It remains unknown whether AP-1 and other transcription factors are mechanisms by which bDLE induces cell death.

METHODS: To determine whether bDLE modulates the AP-1 DNA binding and gene expression, MCF-7 breast cancer cells were treated with bDLE (0, 1, 5, 10 U) for 72 h and evaluated by electrophoretic mobility shift assay, reverse transcriptase-polymerase chain reaction and Western blot assays.

RESULTS: bDLE induced inhibition of cell growth, suppressed the AP-1 DNA-binding activity, decreased c-Jun protein expression and modulated NFATx, NFATc, NFkappaB, c-Jun and c-Fos transcription factor gene expression in MCF-7 breast cancer cells.

DISCUSSION: The present data indicate that bDLE can block the AP-1 DNA-binding activity and expression of several transcriptions factors in breast cancer cells, which will have great potential in improving cancer therapy.

PMID: 18368600 [PubMed - indexed for MEDLINE]

Cytotherapy. 2006;8(4):408-14.

In vitro effects of bovine dialyzable leukocyte extract (bDLE) in cancer cells.

Franco-Molina MA, Mendoza-Gamboa E, Miranda-Hernández D, Zapata-Benavides P, Castillo-León L, Isaza-Brando C,Tamez-Guerra RS, Rodríguez-Padilla C.

Departamento de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, México.

Abstract

BACKGROUND: Bovine dialyzable leukocyte extract (bDLE) is a dialyzate of a heterogeneous mixture of low molecular weight substances released from disintegrated blood leukocytes or lymphoid tissue obtained from homogenized bovine spleen. The purpose of this study was to determine if bDLE had cytotoxic effects and modulated apoptosis gene expression in breast cancer cells.

METHODS: The MCF-7, BT-474, MDA-MB-453, A-427, Calu-1, U937 and L5178Y cancer cell lines and PBMC human cells were treated with bDLE (0-0.66 U/mL) for 72 h. The bDLE effect on cell growth proliferation was evaluated by MTT assay, and the MCF-7 was evaluated by ethidium bromide-acridine orange staining; total DNA was evaluated for DNA fragmentation, and total RNA was isolated for p53, bag-1, c-myc, bim, bax, bcl-2 and bad mRNA expression.

RESULTS: The bDLE had dose-dependent cytotoxic effects and demonstrated an IC50 at a dosage of 0.06 U/mL (P<0.05). The bDLE did not affect the viability of normal human PBMC. The bDLE induced DNA fragmentation at doses of 0.06 and 0.13 U/mL in MCF-7 breast cancer cells. The bDLE induced cytotoxic effects and suppressed the p53, bag-1, c-myc, bax, bcl-2, and bad mRNA expression that influences apoptosis in MCF-7 breast cancer cells. Bim mRNA expression was not detected.

DISCUSSION: This may open up interesting prospects for the treatment of human breast cancer.

PMID: 16923617 [PubMed - indexed for MEDLINE]

Cytotherapy. 2007;9(4):379-85.

Bovine dialyzable leukocyte extract modulates cytokines and nitric oxide production in lipopolysaccharide-stimulated human blood cells.

Franco-Molina MA, Mendoza-Gamboa E, Castillo-Tello P, Isaza-Brando CE, García ME, Castillo-León L, Tamez-Guerra RS, Rodríguez-Padilla C.

Departamento de Inmunología y Virología, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, México.

Abstract

BACKGROUND: In the current study, we determined whether bovine dialyzable leukocyte extract (bDLE) modulates lipopolysaccharide (LPS)-induced nitric oxide and cytokine overproduction.

METHODS: Human whole blood cells were treated with LPS (50 ng) + bDLE (1 U).

RESULTS: The bDLE treatment decreased nitric oxide as well as TNF-alpha, IL-6 and IL-10 (P <0.01) cytokine production. In addition, it decreased TNF-alpha, IL-1beta and IL-6 mRNA expression and suppressed IL-10 and IL-12p40 mRNA expression, but did not modulate IL-8 mRNA expression in LPS-stimulated human blood cells.

DISCUSSION: Our results suggest that bDLE may effectively modulate the fatal symptoms of hypotensive shock associated with endotoxin (LPS)-induced nitric oxide and cytokine production, and this may offer therapeutic potential for the treatment of endotoxic shock.

PMID: 17573613 [PubMed - indexed for MEDLINE]

Cytotherapy. 2006;8(4):408-14.

In vitro effects of bovine dialyzable leukocyte extract (bDLE) in cancer cells.

Franco-Molina MA, Mendoza-Gamboa E, Miranda-Hernández D, Zapata-Benavides P, Castillo-León L, Isaza-Brando C,Tamez-Guerra RS, Rodríguez-Padilla C.

Departamento de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, México.

Abstract

BACKGROUND: Bovine dialyzable leukocyte extract (bDLE) is a dialyzate of a heterogeneous mixture of low molecular weight substances released from disintegrated blood leukocytes or lymphoid tissue obtained from homogenized bovine spleen. The purpose of this study was to determine if bDLE had cytotoxic effects and modulated apoptosis gene expression in breast cancer cells.

METHODS: The MCF-7, BT-474, MDA-MB-453, A-427, Calu-1, U937 and L5178Y cancer cell lines and PBMC human cells were treated with bDLE (0-0.66 U/mL) for 72 h. The bDLE effect on cell growth proliferation was evaluated by MTT assay, and the MCF-7 was evaluated by ethidium bromide-acridine orange staining; total DNA was evaluated for DNA fragmentation, and total RNA was isolated for p53, bag-1, c-myc, bim, bax, bcl-2 and bad mRNA expression.

RESULTS: The bDLE had dose-dependent cytotoxic effects and demonstrated an IC50 at a dosage of 0.06 U/mL (P<0.05). The bDLE did not affect the viability of normal human PBMC. The bDLE induced DNA fragmentation at doses of 0.06 and 0.13 U/mL in MCF-7 breast cancer cells. The bDLE induced cytotoxic effects and suppressed the p53, bag-1, c-myc, bax, bcl-2, and bad mRNA expression that influences apoptosis in MCF-7 breast cancer cells. Bim mRNA expression was not detected.

DISCUSSION: This may open up interesting prospects for the treatment of human breast cancer.

PMID: 16923617 [PubMed - indexed for MEDLINE]

Cytotherapy. 2008;10(5):490-6.

IMMUNEPOTENT CRP (bovine dialyzable leukocyte extract) adjuvant immunotherapy: a phase I study in non-small cell lung cancer patients.

Franco-Molina MA, Mendoza-Gamboa E, Zapata-Benavides P, Vera-García ME, Castillo-Tello P, García de la Fuente A,Mendoza RD, Garza RG, Támez-Guerra RS, Rodríguez-Padilla C.

Laboratorio de Inmunología y Virología, Departamento de Microbiología e Inmunología, Facultad de Ciencias Biológicas de la Universidad Autónoma de Nuevo León, San Nicolás de los Garza, México.

Abstract

BACKGROUND: IMMUNEPOTENT CRP is a mixture of low molecular weight substances, some of which have been shown to be capable of modifying the immune response. We evaluated the response and adjuvant effect of IMMUNEPOTENT CRP on non-small cell lung cancer (NSCLC) patients in a phase I clinical trial.

METHODS: Twenty-four NSCLC patients were included in the study and divided into two groups. Group 1 received a conventional treatment of 5400 cGy external radiotherapy in 28 fractions and chemotherapy consisting of intravenous cisplatin (40 mg/m(2)) delivered weekly for 6 weeks. Group 2 received the conventional treatment plus IMMUNEPOTENT CRP (5 U) administered daily. We performed clinical evaluation by CT scan and radiography analysis, and determined the quality of life of the patients with the Karnofsky performance scale. A complete blood count (red and white blood cell tests), including flow cytometry analysis, blood work (alkaline phosphatase test) and a delayed-type hypersensitivity (DTH) skin test for PPD, Varidase and Candida were performed.

RESULTS: The administration of IMMUNEPOTENT CRP induced immunomodulatory activity (increasing the total leukocytes and T-lymphocyte subpopulations CD4(+), CD8(+), CD16(+) and CD56(+), and maintaining DHT) and increased the quality of the patients' lives, suggesting immunologic protection against chemotherapeutic side-effects in NSCLC patients.

DISCUSSION: Our results suggest the possibility of using IMMUNEPOTENT CRP alongside radiation and chemotherapy for maintaining the immune system and increasing the quality of life of the patients.

PMID: 18821359 [PubMed - indexed for MEDLINE]

Anticancer Res. 2008 Nov-Dec;28(6B):3997-4002.

Prospective study of chemotherapy in combination with cytokine-induced killer cells in patients suffering from advanced non-small cell lung cancer.

Wu C, Jiang J, Shi L, Xu N.

The Third Affiliated Hospital of Suzhou University, Changzhou 213003, PR China.

Abstract

The present study evaluated the clinical efficacy of chemotherapy in combination with cytokine-induced killer (CIK) biotherapy compared to the chemotherapy alone. Fifty-nine advanced non-small cell lung cancer (NSCLC) patients were randomly divided into two groups, group A (chemotherapy alone, including docetaxel 75 mg/m2, day 1; cisplatin, 25 mg/m2, days 1-4, tri-weekly) and group B (chemotherapy plus CIK cell transfusion). Autologous CIK cells were induced from the patients'peripheral mononuclear cells in vitro and separated by cytometry and then transfused back the patients. The host cellular immune function, clinical curative effects and quality of life (QOL) were examined and were compared between the two groups. The host immune function was enhanced and QOL was improved in the patients treated by chemotherapy plus CIK biotherapy compared to the patients treated by chemotherapy alone. The overall response rate (ORR) was 43.3% and 44.8% in groups A and B, respectively. The disease control rate (DCR) was higher in group B than in group A (89.7% vs. 65.5%, p = 0.030). The time to progression was 4.67 months (95% CI 3.98-6.02 months) in group A and 6.65 months (95% CI 4.70-7.30 months) in group B and the median survival time was 11.0 months (95% CI 7.88-14.1 months) in group A and 15.0 months (95% CI 11.04-18.96 months) in group B. Compared to patients in group A, the patients in group B had significantly longer progression-free survival (p = 0.042) and overall survival (p = 0.029). No severe side-effects occurred in the CIK cell transfusion patients. It was concluded that chemotherapy plus CIK cells has potential benefits compared to chemotherapy alone in patients suffering from advanced NSCLC and autologous CIK cell transfusion has no obvious side-effects.

PMID: 19192663 [PubMed - indexed for MEDLINE]

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