Научные исследования по GcMAF

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1. Клинические случаи подтверждают гипотезу о том, что GcMAF может стать частью противоопухолевой схемы иммунотерапии

Опубликованные данные: онкоиммунология. 2013 Aug 1; 2 (8): e25769. Epub 2013 июля 29 PMID: 24179708
Дата публикации статьи: 31 июля 2013
Тип исследования: человеческое исследование
ВеществаGc protein-derived macrophage activating factor (GcMAF) : CK(42) : AC(7)
Болезнирак мочевого пузыря , рак молочной железы , фолликулярная лимфома , рак гортани , лимфома , рак яичников , рак простаты , язык ракаBladder Cancer : CK(349) : AC(100)Breast Cancer : CK(3592) : AC(1064)Follicular Lymphoma : CK(15) : AC(6)Laryngeal Cancer : CK(39) : AC(10)Lymphoma : CK(253) : AC(83)Ovarian Cancer : CK(363) : AC(129)Prostate Cancer : CK(1586) : AC(463)Tongue Cancer : CK(41) : AC(19)
Фармакологические действияиммуномодулирующее
Abstract Author(s): Lynda Thyer, Emma Ward, Rodney Smith, Jacopo Jv Branca, Gabriele Morucci, Massimo Gulisano, David Noakes, Robert Eslinger, Stefania Pacini
Автор статьи: Lynda Thyer

GC protein-derived macrophage-activating factor decreasesα-N-acetylgalactosaminidase levels in advanced cancer patients.

Аннотация:

α-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels ofnagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as»incurable»diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy.

2. После 14-25 еженедельных введений GcMAF у всех пациентов были очень низкие уровни сывороточной нагалазы, эквивалентные уровням здорового показателя, что указывает на то, что у этих пациентов нет опухолей

Опубликованные данные: Transl Oncol. 2008 июл; 1 (2): 65-72. PMID: 18633461
Дата публикации статьи: 30 июня 2008
Тип исследования: человеческое исследование
ВеществаGc protein-derived macrophage activating factor (GcMAF) : CK(42) : AC(7)
БолезниРак предстательной железы: CK (1586): AC (463)
Фармакологические действияиммуномодулирующее: CK (1287): AC (358)
Abstract Author(s): Nobuto Yamamoto, Hirofumi Suyama, Nobuyuki Yamamoto
Автор статьи: Nobuto Yamamoto

Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF.

Аннотация:

Serum Gc protein (known as vitamin D(3)-binding protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of prostate cancer patients was lost or reduced because Gc protein was deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Therefore, macrophages of prostate cancer patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent MAF (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages activated by GcMAF develop a considerable variation of receptors that recognize the abnormality in malignant cell surface and are highly tumoricidal. Sixteen nonanemic prostate cancer patients received weekly administration of 100 ng of GcMAF. As the MAF precursor activity increased, their serum Nagalase activity decreased. Because serum Nagalase activity is proportional to tumor burden, the entire time course analysis for GcMAF therapy was monitored by measuring the serum Nagalase activity. After 14 to 25 weekly administrations of GcMAF (100 ng/week), all 16 patients had very low serum Nagalase levels equivalent to those of healthy control values, indicating that these patients are tumor-free. No recurrence occurred for 7 years.

3. Олеиновая кислота, GcMAF и оксид азота могут быть объединены и использованы больными раком в качестве усиления стимуляции иммунной системы и уменьшение объема опухоли

Опубликованные данные: Anticancer Res. 2014 Jul ;34(7):3569-78. PMID: 24982371
Дата публикации статьи: 30 июня 2014
Тип исследования: человеческое исследование
ВеществаGc protein-derived macrophage activating factor (GcMAF) : CK(42) : AC(7)Oleic acid : CK(31) : AC(9)
БолезниРак — все виды : CK(14773) : AC(4596)
Фармакологические действия:  Immunomodulatory : CK(1287) : AC(358)
Abstract Author(s): Marco Ruggiero, Emma Ward, Rodney Smith, Jacopo J V Branca, David Noakes, Gabriele Morucci, Margit Taubmann, Lynda Thyer, Stefania Pacini
Автор статьи: Marco Ruggiero

Oleic Acid, deglycosylated vitamin D-binding protein, nitric oxide: a molecular triad made lethal to cancer.

Аннотация:

BACKGROUND: Oleic Acid (OA) has been shown to have anticancer properties mediated by interaction with proteins such asα-lactalbumin and lactoferrins. Therefore, we synthesized complexes of OA and Gc protein-derived macrophage activating factor (GcMAF) that inhibits per se cancer cell proliferation and metastatic potential. We hypothesised that OA-GcMAF complexes could exploit the anticancer properties of both OA and GcMAF in a synergistic manner. We postulated that the stimulating effects of GcMAF on macrophages might lead to release of nitric oxide (NO).

PATIENTS AND METHODS: Patients with advanced cancer were treated at the Immuno Biotech Treatment Centre with OA-GcMAF-based integrative immunotherapy in combination with a low-carbohydrate, high-protein diet, fermented milk products containing naturally-produced GcMAF, Vitamin D3, omega-3 fatty acids and low-dose acetylsalicylic acid.

RESULTS: Measuring the tumour by ultrasonographic techniques, we observed a decrease of tumour volume of about 25%.

CONCLUSION: These observations demonstrate that OA, GcMAF and NO can be properly combined and specifically delivered to advanced cancer patients with significant effects on immune system stimulation and tumour volume reduction avoiding harmful side-effects.

4. Это исследование демонстрирует биомолекулярный эффект GcMAF в BMDMs от пациентов с аутизмом, предоставляя дополнительные доказательства положительного использования этой молекулы в лечении аутизма

Опубликованные данные: J Neuroinflammation. 2014 ;11:78. Epub 2014 Apr 17. PMID: 24739187
Дата публикации статьи: 31 декабря 2013 г.
Тип исследования: Human In Vitro
ВеществаGc protein-derived macrophage activating factor (GcMAF) : CK(42) : AC(7)
Болезнирасстройства аутистического спектра Autism Spectrum Disorders : CK(1493) : AC(159)
Фармакологические действияImmunomodulatory : CK(1287) : AC(358)
Abstract Author(s): Dario Siniscalco, James Jeffrey Bradstreet, Alessandra Cirillo, Nicola Antonucci
Автор статьи: Dario Siniscalco

The in vitro GcMAF effects on endocannabinoid system transcriptionomics, receptor formation, and cell activity of autism-derived macrophages.

Аннотация:

BACKGROUND: Immune system dysregulation is well-recognized in autism and thought to be part of the etiology of this disorder. The endocannabinoid system is a key regulator of the immune system via the cannabinoid receptor type 2 (CB2R) which is highly expressed on macrophages and microglial cells. We have previously published significant differences in peripheral blood mononuclear cell CB2R gene expression in the autism population. The use of the Gc protein-derived Macrophage Activating Factor (GcMAF), an endogenous glycosylated vitamin D binding protein responsible for macrophage cell activation has demonstrated positive effects in the treatment of autistic children. In this current study, we investigated the in vitro effects of GcMAF treatment on the endocannabinoid system gene expression, as well as cellular activation in blood monocyte-derived macrophages (BMDMs) from autistic patients compared to age-matched healthy developing controls.

METHODS: To achieve these goals, we used biomolecular, biochemical and immunocytochemical methods.

RESULTS: GcMAF treatment was able to normalize the observed differences in dysregulated gene expression of the endocannabinoid system of the autism group. GcMAF also down-regulated the over-activation of BMDMs from autistic children.

CONCLUSIONS: This study presents the first observations of GcMAF effects on the transcriptionomics of the endocannabinoid system and expression of CB2R protein. These data point to a potential nexus between endocannabinoids, vitamin D and its transporter proteins, and the immune dysregulations observed with autism.

5. GcMAF показывает терапевтические результаты при лечении рассеянного склероза

Опубликованные данные: Anticancer Res. 2016 Jul ;36(7):3771-4. PMID: 27354653
Дата публикации статьи: 30 июня 2016
Тип исследования: Human: Case Report
ВеществаGc protein-derived macrophage activating factor (GcMAF) : CK(42) : AC(7)
Болезнирассеянный склероз Multiple Sclerosis : CK(964) : AC(184)
Фармакологические действияImmunomodulatory : CK(1287) : AC(358)
Abstract Author(s): Toshio Inui, Goro Katsuura, Kentaro Kubo, Daisuke Kuchiike, Leslye Chenery, Yoshihiro Uto, Takahito Nishikata, Martin Mette
Автор статьи: Toshio Inui

Case Report: GcMAF Treatment in a Patient with Multiple Sclerosis.

Аннотация:

BACKGROUND/AIM: Gc protein-derived macrophage-activating factor (GcMAF) has various functions as an immune modulator, such as macrophage activation, anti-angiogenic activity and anti-tumor activity. Clinical trials of second-generation GcMAF demonstrated remarkable clinical effects in several types of cancers. Thus, GcMAF-based immunotherapy has a wide application for use in the treatment of many diseases via macrophage activation that can be used as a supportive therapy. Multiple sclerosis (MS) is considered to be an autoimmune disorder that affects the myelinated axons in the central nervous system (CNS). This study was undertaken to examine the effects of second-generation GcMAF in a patient with MS.

RESULTS: This case study demonstrated that treatments of GcMAF in a patient with MS have potent therapeutic actions with early beneficial responses, especially improvement of motor dysfunction.

CONCLUSION: GcMAF shows therapeutic potency in the treatment of MS.

6. Текущее исследование показывает, что GcMAF и SDT можно использовать в сочетании с традиционными методами лечения у пациентов с метастатическим раком

Опубликованные данные: Anticancer Res. 2014 Aug ;34(8):4589-93. PMID: 25075104
Дата публикации статьи: 31 июля 2014
Тип исследования: Human: Case Report
ВеществаGc protein-derived macrophage activating factor (GcMAF) : CK(42) : AC(7)
Болезнирак молочной железы , рак молочной железы: метастазирование , рак метастазирование Breast Cancer : CK(3592) : AC(1064)Breast Cancer: Metastatic : CK(123) : AC(52)Cancer Metastasis : CK(442) : AC(206)
Фармакологические действияIntegrative Medicine : CK(312) : AC(45)Ultrasound therapy : CK(134) : AC(20)
Abstract Author(s): Toshio Inui, Kaori Makita, Hirona Miura, Akiko Matsuda, Daisuke Kuchiike, Kentaro Kubo, Martin Mette, Yoshihiro Uto, Takahito Nishikata, Hitoshi Hori, Norihiro Sakamoto
Автор статьи: Toshio Inui

Case report: A breast cancer patient treated with GcMAF, sonodynamic therapy and hormone therapy.

Аннотация:

Gc protein-derived macrophage-activating factor (GcMAF) occurs naturally in the human body. It has various functions, such as macrophage activation and antitumor activities. Recently, immunotherapy has become an attractive new strategy in the treatment of cancer. GcMAF-based immunotherapy can be combined with many other therapies. Sonodynamic therapy (SDT) using low-intensity ultrasound is a novel therapeutic modality. Ultrasound has been demonstrated to activate a number of sonosensitive agents allowing for the possibility of non-invasive targeted treatment for both superficial and deep-seated tumors. The current case study demonstrates that GcMAF and SDT can be used in combination with conventional therapies in patients with metastatic cancer, especially where treatment options are limited due to factors such as toxicity. This case study also suggests a new concept of cancer treatment using local destruction of cancer tissue, in this case conducted with SDT, to be used in combination with GcMAF immunotherapy as a systemic treatment.

7. OA-GcMAF, уже используемый в иммунотерапии распространенных видов рака, может значительно способствовать нейтрализации нейротоксичности, вызванной оксалиплатином

Опубликованные данные: Anticancer Drugs. 2015 Feb ;26(2):197-209. PMID: 25304987
Дата публикации статьи: 31 января 2015
Тип исследования: In Vitro Study
ВеществаGc protein-derived macrophage activating factor (GcMAF) : CK(42) : AC(7)
Болезнитоксичность, вызванная химиотерапией: оксалиплатин Chemotherapy-Induced Toxicity: Oxaliplatin : CK(27) : AC(5)
Фармакологические действияChemoprotective Agents : CK(356) : AC(146)Immunomodulatory : CK(1287) : AC(358)Neuroprotective Agents : CK(2360) : AC(1099)
Abstract Author(s): Gabriele Morucci, Jacopo J V Branca, Massimo Gulisano, Marco Ruggiero, Ferdinando Paternostro, Alessandra Pacini, Lorenzo Di Cesare Mannelli, Stefania Pacini
Автор статьи: Gabriele Morucci

Gc-protein-derived macrophage activating factor counteracts the neuronal damage induced by oxaliplatin.

Аннотация:

Oxaliplatin-based regimens are effective in metastasized advanced cancers. However, a major limitation to their widespread use is represented by neurotoxicity that leads to peripheral neuropathy. In this study we evaluated the roles of a proven immunotherapeutic agent [Gc-protein-derived macrophage activating factor (GcMAF)] in preventing or decreasing oxaliplatin-induced neuronal damage and in modulating microglia activation following oxaliplatin-induced damage. The effects of oxaliplatin and of a commercially available formula of GcMAF [oleic acid-GcMAF (OA-GcMAF)] were studied in human neurons (SH-SY5Y cells) and in human microglial cells (C13NJ). Cell density, morphology and viability, as well as production of cAMP and expression of vascular endothelial growth factor (VEGF), markers of neuron regeneration [neuromodulin or growth associated protein-43 (Gap-43)] and markers of microglia activation [ionized calcium binding adaptor molecule 1 (Iba1) and B7-2], were determined. OA-GcMAF reverted the damage inflicted by oxaliplatin on human neurons and preserved their viability. The neuroprotective effect was accompanied by increased intracellular cAMP production, as well as by increased expression of VEGF and neuromodulin. OA-GcMAF did not revert the effects of oxaliplatin on microglial cell viability. However, it increased microglial activation following oxaliplatin-induced damage, resulting in an increased expression of the markers Iba1 and B7-2 without any concomitant increase in cell number. When neurons and microglial cells were co-cultured, the presence of OA-GcMAF significantly counteracted the toxic effects of oxaliplatin. Our results demonstrate that OA-GcMAF, already used in the immunotherapy of advanced cancers, may significantly contribute to neutralizing the neurotoxicity induced by oxaliplatin, at the same time possibly concurring to an integrated anticancer effect. The association between these two powerful anticancer molecules would probably produce the dual effect of reduction of oxaliplatin-induced neurotoxicity, together with possible synergism in the overall anticancer effect.

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