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MELANOMA

The sensitivity of melanoma to Rigvir was achieved by adaptation of ECHO-7 viruses in melanoma tissue.

Вирус Ригвир

"Ригвир" готов атаковать меланому

В Риге открылся первый в мире Центр виротерапии. Латвийские иммунологи и онкологи готовы консультировать врачей и пациентов о возможностях лечения меланомы местной вакциной "Ригвир", или "рижским вирусом".

Препарат был разработан профессором Айной Муцениеце еще в советские годы, но его внедрению помешали сначала развал Союза, а затем вступление Латвии в Евросоюз. Только сейчас "Ригвир" удалось провести через европейский регистр и выпустить в продажу.

Недавно почетному консультанту Центра виротерапии Айне Муцениеце исполнилось 85 лет. Свою медицинскую карьеру она посвятила поиску вакцины от рака. Ей удалось найти вирус, способный распознавать клетки меланомы, внедряться в них и разрушать злокачественную опухоль.

Около сорока лет ушло на исследование вирусного препарата — розовой жидкости, которая облегчает протекание болезни и повышает сопротивляемость организма. Меланома подавляет производство лейкоцитов и лимфоцитов — клеток-"борцов", а "Ригвир", наоборот, их мобилизует.

Введение препарата до и после хирургического удаления злокачественной опухоли защищает от метастазов и рецидивов и продлевает жизнь больным с третьей-четвертой стадией рака.

Сначала были опыты на животных, затем "Ригвир" испытывали на людях — добровольцах, которым уже нечего было терять. Никто не знал, как может повести себя вирус, но его таки удалось заставить служить человеку. Этот был прорыв в медицине, ведь меланома, в отличие от других онкологических заболеваний, устойчива к химиотерапии и лучевой терапии.


Автор: Оксана ДОНИЧ
Источник текст: www.telegraf.lv

Medicine is love

Medicine is love

Scientist Anna Muceniece discovered how to treat cancer with a virus 40 years ago. Now her discoveries have been confirmed by the world’s latest research. It was as early as the 60’s that Muceniece discovered that an inestinal virus from young children was able to destroy cancer cells. By using the methods of selection and adaptation, the live gastrointestinal virus was obtained and its preparation was called Rigvir.

“Unlike chemotherapy and radiation therapy Rigvir doesn’t have a damaging affect on inner organs. And the long lives of patients who have used Rigvir testify about this” explains the scientist. Her discovery is described in the book “ Oncotropism of viruses and the problem of virotherapy of malignant tumours, “ that was published in 1972 in Russian. For now Rigvir is the only virus that has the ability to mobilize the innate antigen and to destroy malignant cells.

Muceniece admits that she came to these discoveries accidentally. “In the 50’s I was working in Latvian Microbiology Institute. That was the time when the poliomyelitis was a major calamity in the world. While looking for the viruses of the poliomyelitis I isolated many intestinal viruses, but soon medicine for the poliomyelitis was discovered and I had to toss out my investigations, but before that I decided to check how “my viruses” treat cancer cells. The results were surprising- it turned out that only inestinal viruses from young children can mobilize in human cells and destroy them”

It has been proven that Rigvir is harmless and does not proliferate in adult’s organism.
None of her patients have complained of side-effects or an inability to accept the preparation. The main result is extending patient’s life time.

Anna Muceniece says that cancer represents many different diseases and her preparation can help with some but not with others. “I have managed to find some who can be helped.”

“I have no business gene and I have never had a passion to make money either. I don’t think that medicine is business. Medicine is love. You have to love humans if you want to help them.”

Even at the age of 85 the scientist doesn’t refuse consultations to doctors in virotherapy and immunology. Last year together with her daughter she wrote a book how to value immunity. “I have been thinking for a very long time whether we are guided by destiny or our will. I decided that it is destiny and I think I have had a very good one.”

http://www.li.lv/index.php?option=com_content&task=view&id=421&Itemid=1105 Medicine is love

Melanoma-associated Antigens as Markers for Melanoma Progression and the Efficiency of Immunotherapy

INTRODUCTION

Human melanoma, being an extremely malignant tumour, at the same time is known to have immunologically provocative features and is capable of inducing a specific immune response. It is supposed that the immunogenicity is determined by melano­ma-associated antigens (MAA) which have been classified into two main groups:

* tissue differentiation antigens (tyrosinase, MART/Melan, gp 100, gp 75) present also in nor­ mai melanocytes, and
* tumour-specific antigens (MAGE, BAGE, GAGE gene groups) present only in malignant celis (1).



Several strategies are being employed to construct vaccines to fight against melanoŗna. A key element is identification of the structures on melanoma celis which play an important role in the immune res­ponse against growing melanoma (2, 3).

A promising approach for melanoma immunotherapies is the design and the use for the immunisation of the viral/tumour celi vaccines. An immuno(bio)modulator of virai origin (Rigvir) which is potentially usable for melanoma treatment has beert elaborated in Latvia (4). In experimental tumour systems and in clinical trials its antitumoural and immunomodulating action was well established, but modulatory effects on specific melanoma surface components of immune rejection must be investi-gated.

The expression of particular MAA during the course of tumour growth and progression may serve as a molecular marker for the prognosis of disease as well a key for new strategies of immunotherapy.
The purpose of our work was to detect the ex-pression of MAA

* in association with histological markērs
* during different stages of disease
* during disease progression or stabilization
* in samples of patients treated with Rigvir.

MATERIALS AND METHODS

The expression of differentiation (tyrosinase, MART, gp 100) and tumour-specific (MAGE group, MAGE-1, MAGE-3) antigens was detected by RT-PCR in:

* 62 melanoma samples of different malignancy benign melanocytic tissues (keratoma, nevi, n = 7) primary malignant melanoma (n = 48) melanoma metastases (n = 7)
* a small group of melanoma samples after immunotherapy with Rigvir (n = 12) placebo (n = 10).


RT-PCR reaction and primer sequences were the same as in the publication of O. Heisele et. al (5).
Histological characterization of tumours (ulceration, tumour thickness by Breslow (mm), level of invasion by Clark (I-V), cell growth type) was examined.
Melanoma patients received Rigvir - a biomodulator of viral origin, whose active part is an apathogenic strain of ECHO-7 virus specifically selected and adapted in melanoma tissues (4), or placebo 3 days prior to surgical treatment.

RESULTS - results table, you can see on the website

http://www.viroterapija.lv/publikacijas.html

The sensitivity of melanoma to Rigvir was achieved by adaptation of ECHO-7 viruses in melanoma tissue.

Virotherapy

The biotherapy is a kind of therapy which, by means of the preparations of natural origin mobilizes the innate antigen specific adaptive immune cells and system against foreign genetical information, genetically modified cells and tissue of the organism including malignant cells.
Since 1980-s in oncological science has been established conviction, that the immune defense against the tumour fails not due to the lack of surface antigens in the tumour, but due to the fact, that the tumour successfully avoids immune control and inhibits/blocks all immune reactions targeted to the tumour.
Modern oncology is using the protective activities of the immune mechanisms, promotors of stabilization and preparations to change the surface structures of the tumour cells and make them visible target to the natural immune defense. Such properties are possessed by oncotropic viruses and cytokines, including interferons.
The application of oncotropic/oncolytic viruses in oncology is called virotherapy and it is a kind of biotherapy.
Virotherapy in the tissue susceptible to the respective virus like radio- and chemotherapy causes cell death (cytolysis). In comparison with chemotherapy and radiotherapy virotherapy has several advantages:

* Very high therapeutical index, sometimes even 10000:1 (10.000 tumour cells are killed against 1 normal cell).
* More rapid elimination of virotherapy caused cell destruction products (in case of radio- and chemotherapy elimination is protracted due to immunosuppression caused by these therapies).
* The combination of virotherapy and chemotherapy increases the antitumoral effect. This conclusion made in Latvia in1972, has been proved in experimental and clinical investigations of Australian and Canadian virotherapeutists in 1990.
* In the susceptible tumours virotherapy due to the oncotropism, i.e. induced by the viral infection of cancer cell, modifies the surface structures of cancer cell, thus submitting just these cells to specific cytotoxic immune mechanisms.

* Apoptosis is a natural process of the liquidation of old, damaged and foreign cells.

Therefore virotherapy is also the method for the activation of antigen-specific mechanisms of immune protection.

The best results were achieved in the early stages of the tumour, using biotherapy after surgery for the prevention of metastases. Biothrerapy is not a silver bullet, good results can not be promised in the late stages of cancer, when all possible treatments have been exhausted.
Application of virotherapy treatment shall be local and systemic. Virotherapy can be combined with other methods used in oncology, such as surgery, radiotherapy, chemotherapy and hormonal therapy. In such combinations the suppression of immunity (the effect of immunosuppression) is reduced due to the above methods of treatment effect. Virotherapy currently is probably the only option to cure tumours, which are not sensitive to radiotherapy and chemotherapy (melanoma, hipernefroma, etc.).

The effect of virotherapy to a higher extent depends on the condition of patient’s immune system as well as progression of cancer process before the treatment. During virotherapy course, which could last several years, it is highly recommended to monitor patient's immune status and consult immunologist.

Guidelines for the practical application of virotherapy have been developed by Latvian scientists and practicing immunologists,led by Professor Aina Muceniece. These guidelines, according to the principle of regional administration, and depending on tumour progression and patient's immune system status, recommend frequency and duration of virotherapy course, as well as the virus injection site to reach the higher therapeutic effect.

World experience:
http://www.isracast.com/tech_news/260106_tech.aspx
http://www.bioline.org.br/request?mj03002
http://discoverysedge.mayo.edu/measles/
http://www.mayoclinic.org/news2007-rst/3954.html
http://www.collegiatetimes.com/news/1/ARTICLE/8949/2007-04-12.html
http://www.epeiusbiotech.com

You may acquaint yourself with the information of Rigvir only if you are health care professional!!!


Virus RIGVIR

Virotherapeutical preparation with antitumoral activity, immunomodulator with philogenetically determined pleiotropic specific and nonspecific immunemodulating activities. Due to the structural functional formation selectively affects cells of susceptible tumour and inducing specific immunity to itself, activises cells of immune system (the active compound is ECHO group enterovirus, non-pathogen to humans and not causing immunesuppression, as influenza virus, e.g.).
The direct antitumoral effect of Rigvir is associated with oncotropism and oncolysis.
The cytolytic effect is selective – affects only malignant cells completely „ignoring” normal tissue cells. Very important is a fact that on the surface of non-lysated malignant cells Rigvir induce expression of tumor-associated differentiation antigens and subdues the expression of MAGE group antigens which are associated with progressive growth of melanoma. The altered surface structures of malignant cells makes them the target structures of cytotoxic mechanisms of the immune system.

The immunmodulating effect of Rigvir is associated with activation of lymphnodes, lymphoid tissue and immune cells. Inducing the immune response to itself, Rigvir stimulates normal primary and secondary immunogenesis and cancels tumour-caused block of local immunity. By activation of the immune response to the expressed tumor-associated antigens the apoptosis-like process of immune rejection of the tumour is realized. Repeated application of the preparation in the course of eficiently managed virotherapy with Rigvir allows to achieve gradual and complete regression of lymphnode micrometastases and subcutaneous metastases. During the mentioned processes it is possible to trace how Rigvir stimulates humoral immunity – the activation of B-cells, antibody production, induction of interferon simultaneously with activation of cellular, T-system immunity processes – in peripheral blood there is increasement of cytotoxic CD8+ cells and helper – CD4+ cells. As well activation of the cells of nonspecific immunity: natural killers (NK) and macrophages is present. The function of lymphnode is activated and lymphocyte infiltration in tumour focus increases, which indicates to the activation of local immunity processes.

It had been convicingly proved that Rigvir do not multiply in other human organs, tissue and blood and is not excreted in the environment.
Virotherapy studies, either early – (before World War I and after World War II) or investigations in Latvia as well as conclusions of australian, german, japanese, US investigators in recent decades witnessed that oncotropism of viruses from different groups differs, and this phenomenon was called virus spectrum in regard to tumours and tumour spectrum in regard to viruses. The most sensitive to Rigvir are tumours of those organs and tissue which during the embryogenesis had originated fom endoplastum. We had determined that the tumours sensitive to Rigvir are:

* melanoma,
* gastric cancer,
* cancer of rectum and large intestine,
* cancer of pancreas,
* cancer of uterus,
* kidney tumours,
* cancer of bladder,
* different kinds of sarcoma:
o lymphosarcoma,
o angiosarcoma,
o rhabdomyosarcoma.


The sensitivity of melanoma to Rigvir was achieved by adaptation of ECHO-7 viruses in melanoma tissue.
Long term observations witnessed that cancer patients treated with Rigvir seldom are caught ill with viral diseases, including influenza.


Rigvir influence on the progress of melanoma

There are several goals of Rigvir systemic and local use before and after the surgery for the melanoma patients:

* To fullfil Rigvir potential oncotropic and oncolytic qualities against the tumour cells;
* To induce tumor cell tissue differentiation antigen genes, and reduction of tumor progression of gene expression, stimulate the immune rejection mechanism
* To delay and correct the immune deficit caused by surgery;
* For prevention of metastases process to activeate the regional lymph nodes after the primary focal surgery treatment to prevent the metastases process.

The history of investigation of Rigvir

In 1960 the scientists detected that the human intestinal viruses, obtained from young children, can destroy the human tumors which are engrafted to hamsters (Human heterograft of angiosarcoma in the cheek pouches of Syrian hamsters).
In 1965 laboratory of cancer virotherapy was established in Latvian Microbiology Institute to investigate this phenomenon. Under the guidance of Professor Aina Muceniece 60 different types of the enteroviruses were estimated.
In 1968 Ministry of Health of Latvian Republic accepted the first stage of clinical trial of 5 viruses with the the highest anti-tumour ability. EHCO-7 group virus with the highest anti-tumour activity, which was also proven as non-pathogen and epidemiologically safe, not able to replicate in healthy tissues, was named – Rigvir (Riga virus). RIGVIR was also successfully adopted in the skin melanoma tissues to test is against the most aggressive tumour, not sensitive to radiation and chemical therapy.


In 1985 the positive conclusion from the Scientific Council of Soviet Cancer Centre (Moscow) was received for the extensive clinical trials of using RIGVIR in the treatment of melanoma patients.

Since 1987, under permission of the Pharmacology Committee of Soviet Union, third stage of clinical trials were carried out in the Soviet Oncology Centre in Moscow and Saratov Oncology Hospital, where effectiveness and safety of RIGVIR was proven.

In April 29, 2004 the Rigvir preparation was registered in the State Agency of Medicines of Republic of Latvia.

Since 2008 Rigvir (as prescription drug) is available in pharmacy stores in Latvia.

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