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Rigvir Research Paper

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RIGVIR explained

RIGVIR explained

RIGVIR is a virotherapy medication approved by the State Agency of Medicines of the Republic of Latvia. [1] It was developed in the 1960s and 1970s by the team of Aina Muceniece (1924–2010) and patented in 2002. [2]

Rigvir is a drug that contains live, natural virus, which has cytolytic and immunomodulating effects. Cytolytic action – finding and destroying malignant cells, applies only to the cancer cells without affecting the normal tissue cells.Regarding immunomodulation, because of its structure Rigvir selectively affects cells in sensitive tumors. Rigvir activates cells of the immune system due to what causes specific immune response against itself. It is not genetically modified and not pathogenic virus, it is not able to replicate in human body. It is issued in oncology for the prevention of secondary immunodeficiency. In 2015 RIGVIR was registered in Georgia [3] and included in the Latvian national guidelines for skin cancer and melanoma treatment.

Recent retrospective study published in Melanoma Research showed that IB-IIC melanoma patients treated with oncolytic virus Rigvir were 4.39–6.57-fold lower mortality than those, who according to melanoma treatment guidelines did not receive virotherapy and were only observed. [4]

Passed all phases of clinical trials and registered in Latvia (Reg. No. 04-0229) and is used as a prescription drug for the treatment of cancer. Rigvir – 7 strain ECHO-virus, a solution for intramuscular injection. Code: ATX: L03AX. Must be stored and transported at a temperature of -20 °C ± 2 °C.

  • In 1960 unknown phenomenon was discovered: when human enteric viruses (enteroviruses of group ECHO), which were isolated from the gastrointestinal tract of young children and grafted into hamster buccal bags showed oncotropic and oncolytic properties [5]
  • In 1965, cancer virotherapy laboratory was founded in the Institute of Microbiology (Latvian Academy of Sciences) to explore this phenomenon. 60 different types of enteric viruses were tested, 5 of them were identified as the most effective viruses capable of destroying cancer cells. One of them was named Rigvir (Riga virus). It was found that Rigvir is safe for adults and not able to replicate in the human body. [6]
  • In 1968 scientists received permission from the Ministry of Health of the Latvian SSR to study and use Rigvir on patients, with the participation of 415 patients. It has been proven that Rigvir was safe for cancer patients and can not cause epidemics. Successful adaptation of the virus in the tissues of cutaneous melanoma (not sensitive to chemotherapy and radiotherapy) was produced, and the therapeutic effect was ascertained. [7]
  • In 1985, received approval from the All-Union Cancer Center in Moscow to begin an extensive clinical research of Rigvir treatment on melanoma patients (study involved 1063 patients).
  • In 1987 clinical studies also took place in the All-Union Cancer Center in Moscow and Saratov oncology clinic. It was acknowledged that Rigvir is not dangerous even for very severe and incurable patients.
  • In 1990–1995, Rigvir used to treat patients with various kinds of cancer in the P. Stradina clinic and Latvian Oncology Center.
  • On October 20, 2002 granted a patent for Rigvir.
  • On April 29, 2004 Rigvir was approved by the State Agency of Medicines of the Republic of Latvia.
  • On August 22, 2005 Rigvir became available for residents of Latvia.
  • Since 2011 Rigvir is included in the list of state compensated drugs to the diagnosis of malignant melanoma of the skin (the exception – ocular melanoma) for residents of Latvia.
  • In February 2015 registered in Georgia. [3]
  • Since 2015 Rigvir is included in the Latvian National guidelines for treatment of skin cancer and melanoma.
Side effects

Like other medicines, Rigvir may cause side effects. The side effects are short-term and do not require special therapy, the most common side effects are subfebrile temperature, pain in the tumor, fatigue, drowsiness, dyspepsia (diarrhea). [8]

External links Notes and References
  1. For an freely accessible English version see page 642 of Chumakov PM, Morozova VV, Babkin IV, Baikov IK, Netesov SV, Tikunova NV. Oncolytic enteroviruses. Molecular Biology. 2012. 46. 5. 639–50. 10.1134/S0026893312050032.
    For the original version in Russian see Chumakov PM, Morozova VV, Babkin IV, Baĭkov IK, Netesov SV, Tikunova NV. [Oncolytic enteroviruses] (Russian). Molekulyarnaya Biologiya. 2012. 46. 5. 712–25. 23156670.
  2. Web site: Inventions and Inventors of Latvia. 8 April 2013.
  3. Web site: Georgia Today .
  4. 10.1097/CMR.0000000000000180. Adapted ECHO-7 virus Rigvir immunotherapy (oncolytic virotherapy) prolongs survival in melanoma patients after surgical excision of the tumour in a retrospective study. 2015. Doniņa. Simona. Strēle. Ieva. Proboka. Guna. Auziņš. Jurģis. Alberts. Pēteris. Jonsson. Björn. Venskus. Dite. Muceniece. Aina. Melanoma Research. 25. 5. 421–426.
  5. . Muceniece A.J. 1978. Analysis of sensitivity of human melanomas to enteroviruses adaptred to these tumors.In: Virusy v terapii opukholei (Viruses in Antitumor Therapy), Riga: Zinatne, pp. 175–189.
  6. Muceniece A.J. Bumbieris J.V. 1982. Transplantation antigens and their changes in carcinogenesis and viral infection. In: Virusnyi onkoliz i iskusstvennaya geterogenizatsiya opukholei (Viral Oncolysis and Artificial Heterogenization of Tumors). Riga, pp. 217–234.
  7. Muceniece A.J. Bumbieris J.V. 1982. Transplantation antigens and their changes in carcinogenesis and viral infection. In: Virusnyi onkoliz i iskusstvennaya geterogenizatsiya opukholei (Viral Oncolysis and Artificial Heterogenization of Tumors). Riga, pp. 217–234
  8. Web site: RIGVIR side effects .

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Adapted ECHO-7 virus Rigvir immunotherapy (oncolytic virotherapy) prolongs survival in melanoma patients after surgical excision of the tumour in a re

Adapted ECHO-7 virus Rigvir immunotherapy (oncolytic virotherapy) prolongs survival in melanoma patients after surgical excision of the tumour in a retrospective study

An oncolytic, nonpathogenic ECHO-7 virus adapted for melanoma that has not been genetically modified (Rigvir) is approved and registered for virotherapy, an active and specific immunotherapy, in Latvia since 2004. The present retrospective study was carried out to determine the effectiveness of Rigvir in substage IB, IIA, IIB and IIC melanoma patients on time to progression and overall survival. White patients (N =79) who had undergone surgical excision of the primary melanoma tumour were included in this study. All patients were free from disease after surgery and classified into substages IB, IIA, IIB and IIC. Circulating levels of clinical chemistry parameters were recorded. Survival was analysed by Cox regression. Rigvir significantly (P

1: Outpatient Department, Riga Eastern Clinical University Hospital, Institute of Microbiology and Virology 2: Department of Public Health and Epidemiology, Riga Stradiņš University 3: Outpatient Department, Riga Eastern Clinical University Hospital 4: Latvian Virotherapy Center, Riga, Latvia 5: Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden

Virotherapy Consultations

Você sabe para que serve a Viroterapia?

O câncer é uma das doenças mais letais já descobertas e que tomaram conta da vida de muitas pessoas nas últimas décadas.

De acordo com a Organização Mundial da Saúde (OMS), a previsão é que em até 2025 ocorra uma evolução nos óbitos provocados pela doença e também nos novos casos.

No entanto, para os pacientes que já enfrentam o problema, surgiu uma nova forma de tratamento, a Viroterapia.

Mas você sabe para que serve a Viroterapia? Preste atenção em nosso post e fique por dentro do assunto!

O que é a Viroterapia?

A Viroterapia é uma nova direção para o tratamento do câncer. Ela é um ramo de ciências medidas que explora o uso do vírus para que ele possa destruir as células cancerosas. E a Viroterapia Oncológica tem o objetivo de se concentrar na eliminação das células cancerígenas por invasão viral em tumores malignos.

Isso acontece porque a maioria dos vírus mostra um alto tropismo para as células cancerosas, e, portanto, os cientistas pensaram que esses vírus poderiam ser usados no tratamento de cancros. Como os vírus atingem as células normais do corpo e causam danos, os cientistas tiveram a ideia de direcioná-los para tumores para que fossem destruídas as células com problemas.

Depois de muitas pesquisas, foi descoberto que daria para implementar a ideia e que esses vírus, considerados especiais, mataram de maneira eficaz as células cancerígenas. Pois, normalmente, o próprio corpo reage a infecções virais e retarda o metabolismo celular cessando as funções celulares, de modo assim que a replicação viral será impedida.

Porém, as células que contém tumores não demonstram tais alterações durante uma infecção viral, o que as fazem atrair vírus para suas células e isso leva a uma oncolise – destruição de células malignas – bem sucedida.

Quem pode se submeter ao tratamento de Viroterapia?

Por ser considerado um método eficaz e seguro, a Viroterapia é recomendada para o tratamento de quaisquer tipos de câncer, pois ela não tem efeitos colaterais negativos sobre o corpo humano.

Pessoas com câncer de pele, de pulmão e câncer ósseo são alguns dos exemplos que podem ser tratados com a Oncolytic virotherapy (Viroterapia Oncológica).

O que é utilizado para o tratamento?

Até o momento, a Viroterapia é feita com apenas um medicamento aprovado, que contém o vírus, que mostrou durante pesquisas realizadas, uma redução significante em relação a mortalidade provocada pelo câncer.

O vírus é uma solução que contém 2ml do vírus ECHO-7 adaptado e selecionado. Ele é administrado por via intramuscular.

Agora que você já sabe o que é Viroterapia e que existe um novo tipo de tratamento eficaz e seguro para o câncer, é importante cuidar cada vez mais da sua saúde, não é mesmo? Por isso, não perca tempo, agende uma consulta em uma clínica especializada no assunto.

Você tem mais alguma dúvida sobre a Viroterapia? Entre em contato com nossa clínica e saiba como podemos ajudá-lo!

# câncer #Viroterapia #cancerosas

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As the world leaders in the field of oncology are offering new methods and drugs for cancer treatment, ordinary people face difficulties to get things straight; understand, what is going on with them, and, what is more important, what will happen, if certain treatment method is applied; what will be the response of the body; will it be possible to stop the destructive process or at least pause it for some time. At the certain point you need to undertake all the responsibility and make the decision. It is the question of life, and you are not able to take something back or change something. Affected cells are multiplying really quickly, and the body is virtually destroying itself. The immune system is not functioning; it is not able to operate normally, because it does not distinguish the „good” cells from the „bad” ones. This is a well-known situation for the patients. It develops especially fast, if the diagnosis is melanoma. But the desire to live is so strong. However, if there is a problem, then the solution will also come. Our civilization managed to overcome various epidemics, which took more lives, than all the wars together. It will also be possible to overcome cancer. Moreover, we already have the necessary medicine. It is only left to inform the people about it.


More than half of the century ago, already in Soviet times, the virus, which is able to affect the malignant cells, was found. The brilliance of this method is that this virus is live, completely safe for healthy cells and the human body in general, namely, it cures, and is taken out of the body really quick. But it is not all. This virus is also an immunomodulator, which helps to boost the person’s own immune system. The medicine of the future, like nano-technologies. The patient during the therapy is able to maintain his usual daily routine – being home, doing ordinary things, perhaps, even working. No side-effects, no complex manipulations, no invasive procedures. The process of the treatment is almost not felt by the patient. The injections maybe implemented by any nurse, as no special preparation is needed. Doctors may handle the monitoring of the patient’s condition distantly. Just regular examinations to compare the results and choose the individual treatment scheme and rare consultations. It sounds too easy and simple, doesn’t it? But the rest depends on the patient himself, because such disease as oncology requires a lot of inner strength, the desire to live and fight. Not everyone can win this fight, not everyone can harness all of his willpower and say „I can and I will overcome cancer”.

Latvian doctors have big experience in treatment of various kinds of oncological diseases at different stages. The medicine has undergone clinical studies, is licensed and certified. Patients from more than 50 countries already are using this medicine. This small vial is prolonging live, improving the body’s condition and not harming it. This medicine has no analogues and is not very much known yet. However, the most important is to start the therapy on time the earlier possible to increase the chances for winning the battle against cancer. Latvian doctors, which are, by the way, the most experienced virotherapy specialists in the world, are doing their best to make virotherapy with Riga virus available for all the patients.

It is possible to receive consultation online – just send your clinical record and the lab tests. It is completely free of charge. To start the treatment it is necessary to come to Riga for some days, undergo the complex examination and make the necessary blood work. The following treatment process is very individual and depends on the stage of the disease and the condition of the patient. Currently, this treatment method, which has almost no counterindications, but, in turn, many positive outcomes, is becoming more popular in the world and increasing chances for survival.

If you or your loved ones are facing this disease, use this information. It may help to save someone’s life.

Virotherapy Consultation Division

Address: 13. janvāra Street 3, Riga, Latvia, LV-1050

Phone: +371 25532281;

The only medications in the Virotherapy industry compared read the article on Ask Wonder.


Text from web site:

  • Oyedele A.
Reviewer
  • Ally
Support
  • Kiersten M.

INSIGHTS
  • RIGVIR has up to 48% survival rate, but is geographically constrained,
  • T-VEC also passed clinical trials and is more accepted in the global community.
  • It has been proven that both virotherapy drugs work.
OVERVIEW
Hello, thank you very much for your question. In the research I have done, these two virotherapy drugs are very different in their derivation, their uses, their respective regions and even the opinions about them, although they are both mainly used as treatments for melanoma.

RigVir, a derivative of Riga Virus was developed, tested and approved by Latvia, and after a series of successful experiments carried out it was discovered that there was a significant and positive change in the patients, recording a survival rate of 48% compared to the 24% recorded in the control group. At face value, this a positive and believable result. But RigVir has found no success in America as it has not been approved by the FDA, so RigVir has gained little popularity in the general market.

T-VEC on the other hand involves the injection of the virus Talimogene Laherparepvec into the tumor. T-VEC has found success in mainstream media as it has passed clinical trials in the USA and has been approved by the FDA, recording a positive result when tested. The FDA approved T-VEC for patients with advanced melanoma (Stage IIIB, IIIC or IV) that cannot be completely removed with surgery. It was concluded that T-VEC was effective in shrinking these inoperable tumors.

Both drugs performed excellently well.

More than 540 melanoma patients were involved in the RigVir efficacy studies. It showed that the 3-year survival for patients that had been treated with surgery only was 46-58%, while patients that had also been treated with RigVir had a 3-year survival of 84% and a 5-year survival of 44-66%. The 3- and 5-year survival for eye melanoma patients were 90% and 70%. 486 people made it past the 3-year stage and 378 people made it past the 5-year stage. This information was provided on an academic paper published by the medical institute of Latvia. Another experiment was carried out with 67 patients in the Riga Eastern Clinical University Hospital in Latvia, 79 White patients who had undergone surgical excision of the primary melanoma tumour were included in this study. It was concluded that RigVir significantly prolongs survival in early-stage melanoma patients without any side effects. The number of dropouts in this experiment were not included in the research paper. Side effect, which is high temperature were said to be general in all patients.

T-VEC went through a more thorough testing period than RigVir, going through 3 stages of clinical trials with hundreds of patients in each stage. Its clinical trials were also more particular and specific than RigVir. T-VEC resulted in a decrease in size by greater than 50% in 64% of injected lesions with a total test number pf 2116 people, calculated, this means 1355 people out of 2116 had obvious and positive effect from the drug. This is a good testimony for T-VEC.

SIDE EFFECTS

Both drugs have also been found to have side effects, T-VEC has numerous side-effects. ranging from fatigue, herpes to flu-like symptoms and therefore is not suitable for the pregnant and those with a weakened immune sysytem. The only side-effect for RigVir is said to be a high temperature.

AVAILABILITY

Availability is also a huge factor when juxtaposing these two drugs together, T-VEC has more mainstream success and is very much more available than RigVir in the market right now, and this is because of approval and sponsor problems that RigVir is facing currently.

DO THE DRUGS WORK?

To answer your questions, yes, the two drugs work, according to the results from these studies and research. Both drugs, according to research performed well when tested but the environment they stemmed from differs a lot and it will surely influence judgement when you pitch them against each other. The goal, it seems, of the RigVir drug is to extend the lives of cancer patients taking a 3-5 year period as a threshold while that of the T-VEC is to shrink the tumour in hopes of a remission.

Due to the 3-phase clinical trial method. the sheer number of patients and the specificity of the experiments, it has also been proven that T-VEC is a more trusted, reliable and accountable drug than its counterpart, RigVir. This is so, because of the rigorous clinical trial T-VEC passed through before it could be certified and these tests, as research has shown are superior to the ones performed on RigVir.

Thank you for contacting us with this very educating question, and thanks for using Wonder!


On 1st December International Virotherapy Center issued accreditation certificate to the outpatient clinic "Virotherapy consultations", which is established as a completely new concept of medical institution that offers virotherapy services to foreign economic segment's patients. Clinic will be led by former head of Aina Muceniece Virotherapy Foundation Diana Otisone.

Today we with Dr. Guna Proboka visiting PET/CT diagnostic center Medvision.

PET/CT is one the most innovative and most accurate methods for diagnostics of cancer, that combines two radiological methods – positron emission tomography (PET) and computed tomography (CT).

The most frequently PET/CT is used for Hodgkin’s and non-Hodgkin lymphomas, breast cancer, colorectal and lung cancer, as well as prostate, uterine, cervical and ovarian cancer, stomach and esophageal cancer, pancreatic cancer, melanoma and sarcoma cases, as well as diagnosing the tumor of unknown location.

PET/CT in oncology has no competitors that could equally well:

  • determine the stage of cancer
  • evaluate tumor growth
  • provide timely diagnostics for recurrent tumors
  • determine the effectiveness of the prescribed treatment.

PET/CT examination is possible with a doctor’s referral.


Skin exams are a visual inspection of the entire body for suspicious growths, moles or lesions using a bright light and sometimes a magnifying glass for a closer look. Even the scalp is checked out by parting sections of hair to get a good look.

You should have a skin exam if you have:
  • Suspicious moles or skin lesions
  • Symptoms of early skin cancer
  • A history of previous skin cancer
  • 50 or more moles
  • Atypical (unusual) or large moles
  • A family history of skin cancer
Early detection

Early signs of skin cancer are a change in the skin, such as a growth, an irritation or a sore that does not heal, or a change in a wart or a mole. Recognition of changes in the skin is the best way to detect early melanoma. They most frequently appear on the upper back, torso, lower legs, head and neck. In females 15-29 years old, the torso is the most common location for developing melanoma which may be due to high-risk tanning behaviors. If you have a changing mole, a new mole, or a mole that is different, contact us to schedule a skin exam as soon as possible.

Follow the ABCDE rule

If you notice a mole on your skin, you should follow the simple ABCDE rule which outlines the warning signs of melanoma:

  • A stands for ASYMMETRY; one half unlike the other half.
  • B stands for BORDER; irregular, scalloped or poorly defined border.
  • C stands for COLOR; varied from one area to another; shades of tan and brown, black; sometimes white, red or blue.
  • D stands for DIAMETER; while melanomas are usually greater than 6mm/1/4Inch (the size of a pencil eraser) when diagnosed, they can be smaller.
  • E stands for EVOLVING; a mole or skin lesion that looks different from the rest or is changing in size, shape, or color.


Other signs of melanoma in a mole include changes in:
  • Elevation, such as thickening or raising of a previously flat mole.
  • Surface, such as scaling, erosion, oozing, bleeding, or crusting.
  • Surrounding skin, such as redness, swelling, or small new patches of color around a larger lesion (satellite pigmentations).
  • Sensation, such as itching, tingling, or burning.
  • Consistency, such as softening or small pieces that break off easily (friability).

Rigvir research paper

Virions of enteroviruses in Rigvir

Rigvir is a drug containing a live and natural virus (ECHO-7 [1] ) which has cytolytic and immunomodulating effects. Cytolytic action – finding and destroying malignant cells, applies only to the cancer cells without affecting the normal tissue cells. Regarding immunomodulation, because of its structure Rigvir selectively affects cells in sensitive tumors. Rigvir activates cells of the immune system due to what causes specific immune response against itself. It is not genetically modified and not a pathogenic virus It is not able to be replicated in the human body. It is issued in oncology for the prevention of secondary immunodeficiency.

RIGVIR was registered in Latvia on 29 April 2004, a few days before Latvia joined the European Union. [4] Since Rigvir was registered via a national registration procedure, it has not been tested in the standard clinical trials required for central registration in the European Union. [5]

History [ edit ]

Rigvir antigen in tumor cells

  • In 1960 unknown phenomenon was discovered: when human enteric viruses (enteroviruses of group ECHO), which were isolated from the gastrointestinal tract of young children and grafted into hamster buccal bags showed oncotropic and oncolytic properties. [6]
  • In 1965, cancer virotherapy laboratory was founded in the Institute of Microbiology (Latvian Academy of Sciences) to explore this phenomenon. 60 different types of enteric viruses were tested, 5 of them were identified as the most effective viruses capable of destroying cancer cells. One of them, ECHO-7, was named Rigvir (Riga virus). It was found that Rigvir is safe for adults and not able to replicate in the human body. [7]
  • In 1968 scientists received permission from the Ministry of Health of the Latvian SSR to study and use Rigvir on patients, with the participation of 415 patients. It has been proven that Rigvir was safe for cancer patients and can not cause epidemics. Successful adaptation of the virus in the tissues of cutaneous melanoma (not sensitive to chemotherapy and radiotherapy) was produced, and the therapeutic effect was ascertained. [7]
  • In 1985, received approval from the All-Union Cancer Center in Moscow to begin an extensive clinical research of Rigvir treatment on melanoma patients (study involved 1063 patients). [ citation needed ]
  • In 1987 clinical studies also took place in the All-Union Cancer Center in Moscow and Saratov oncology clinic. It was acknowledged that Rigvir is not dangerous even for very severe and incurable patients. [ citation needed ]
  • In 1990–1995, Rigvir used to treat patients with various kinds of cancer in the P. Stradina clinic and Latvian Oncology Center. [ citation needed ]
  • On October 20, 2002 a patent was granted for Rigvir [3]
  • On April 29, 2004 Rigvir was approved by the State Agency of Medicines of the Republic of Latvia. [4]
  • Since 2011 Rigvir is included in the list of state compensated drugs to the diagnosis of malignant melanoma of the skin (the exception – ocular melanoma) for residents of Latvia. [ citation needed ]
  • In February 2015 registered in Georgia. [8]
  • In 2015 Rigvir was included in Latvian clinical guidelines for skin cancer and melanoma, published by National Health Service of Latvia. Page 11 specifies that, according to the criteria of European Society for Medical Oncology outlined in pages 7–8, evidence level for Rigvir even in the case of skin melanoma (which is the only indication Rigvir is registered for) is III/C, meaning: "insufficient evidence of efficacy, or benefits do not exceed disadvantages (negative outcomes, cost of treatment and other risks); optional use". Clinical guidelines were developed under the management of professor Dace Baltiņa (page 2 ), who later became the medical director of Global Virotherapy Cancer Clinic. the main treatment center in Latvia providing Rigvir and part of Rigvir holding.
  • In 2016 RIGVIR was approved in Armenia. [9]
  • In July 2016, the European Commission's Horizon 2020 program awarded a grant to Latima for the commercialisation of Rigvir in EU markets. [10] [11]
  • On August 29, 2016 National Health Inspectorate of Latvia published a decision to apply a fine to SIA Latima, manufacturer of Rigvir, according to the Law on the Prohibition of Unfair Commercial Practices. After investigating the advertisements of prescription medicine Rigvir on the Internet and a magazine, Health Inspectorate decided that SIA Latima, the marketing authorization holder of Rigvir, has engaged in misleading commercial practice without due professional care, as the advertisements violate the requirements of Cabinet of Ministers regulation No.378. which specify that advertising prescription medicine to the general public is forbidden and that the information contained in advertisement has to match the information provided in the product characteristics. While Rigvir was only registered for treatment of cutaneous melanoma, it is being advertised for various cancers without any evidence of efficacy by International Virotherapy Centre in Latvia, the main institution providing treatment with Rigvir, as well as its accredited partners. e.g. exclusive partner in Mexico, Hope 4 Cancer Institute. known for its use of unproven "natural" cancer treatments .

Since Latvia is a member of European Union, according to Article 88 (DIRECTIVE 2001/83/EC on the Community code relating to medicinal products for human use), Member States shall prohibit the advertising to general public of medicinal products which are available on medical prescription only (page 26).

Side effects [ edit ]

The most commonly reported side effects are subfebrile temperature, pain in the tumor, fatigue, drowsiness, and dyspepsia (diarrhea). [12] [4]

See also [ edit ] References [ edit ]
  1. ^ ab For a freely accessible English version see page 642 of Chumakov PM, Morozova VV, Babkin IV, Baikov IK, Netesov SV, Tikunova NV (2012). "Oncolytic enteroviruses" (PDF). Molecular Biology. 46 (5): 639–50. doi :10.1134/S0026893312050032.  
    For the original version in Russian see Chumakov PM, Morozova VV, Babkin IV, Baĭkov IK, Netesov SV, Tikunova NV (2012). "[Oncolytic enteroviruses] (Russian).". Molekulyarnaya Biologiya. 46 (5): 712–25. PMID  23156670.  
  2. ^ "Inventions and Inventors of Latvia". Retrieved 8 April 2013.  
  3. ^ ab EP application 1537872. Aina Muceniece, "Immunostimulator having antineoplastic action and method for producing said immunostimulator", published 2005-06-08  
  4. ^ abc "Rigvir šķīdums injekcijām" [Rigvir solution for injection]. Medicinal product register of the Republic of Latvia. 2004-04-29. Retrieved 2016-11-02.  
  5. ^ "Feasibility study for registration of medicine RIGVIR with the European Medicine Agency". European Commission. 2016-01-08. Archived from the original on 2016-11-02. Retrieved 2016-11-02. However,further use and commercialisation in the EU is prevented as EU regulations require cancer medicines to be registered centrally through the European Medicine Agency (EMA). National registrations are not considered.  
  6. ^ Muceniece A.J. 1978. Analysis of sensitivity of human melanomas to enteroviruses adaptred to these tumors.In: Virusy v terapii opukholei (Viruses in Antitumor Therapy), Riga: Zinatne, pp. 175–189.
  7. ^ ab Muceniece A.J. Bumbieris J.V. 1982. Transplantation antigens and their changes in carcinogenesis and viral infection. In: Virusnyi onkoliz i iskusstvennaya geterogenizatsiya opukholei (Viral Oncolysis and Artificial Heterogenization of Tumors). Riga, pp. 217–234.
  8. ^ Karsaulidze, Eka (2015). "Georgia's Aversi Now Selling Riga Virus Cancer Treatment". Georgia Today. Archived from the original on 2016-03-12. Retrieved 2016-11-03. Rigvir was officially registered by the Ministry of Labor, Health and Social Affairs of Georgia on February 15, 2015.  
  9. ^ "Latvian Rigvir anti-cancer medicine registered in Armenia".  
  10. ^ Petrán, Leide (12 July 2016). "Rigvir saņem Eiropas Komisijas grantu medikamenta komercializācijai ES tirgū" [Rigvir receives European Commission grant for the commercialization of the medicine in the EU market]. Dienas Bizness (in Latvian). Retrieved 2017-01-09.  
  11. ^ "EC awards grant to commercialise Latima's cancer virotherapy medicine". Pharmaceutical Technology. 22 July 2016. Retrieved 2017-01-09.  
  12. ^ "RIGVIR Side Effects". RIGVIR. Archived from the original on 2016-11-13.  

1. 2004 enlargement of the European Union – It occurred on 1 May 2004. The remaining two were former British colonies. The European Economic Community was created in 1957 between six countries within the Western Bloc and later expanded to twelve countries across Europe. European communist countries had a looser economic grouping with the USSR known as Comecon. To the south there was a federated country - Yugoslavia. In 1989, the Cold War between the two superpowers was coming to an end, with the USSR's influence over communist Europe collapsing. The Phare strategy was launched soon after to adapt more the structure of the Central and Eastern European countries to the European Economic Community. The Acquis Communautaire contained 3,000 directives and some 100,000 pages in the Official Journal of the European Union to be transposed. It raised cultural problems -- e.g. new legal concepts and language consistency problems. Copenhagen criteria Nuclear plants. The text also amended the main EU treaties, including the Qualified Majority Voting of the Council of the European Union. The treaty was ratified on time and entered into force on 1 May 2004 amid ceremonies around Europe. European leaders met at Áras an Uachtaráin, the Irish presidential palace. At the same time, citizens across Ireland enjoyed a nationwide celebration styled as the Day of Welcomes. 1 EU Association Agreement type: Europe Agreement for the states of the Fifth Enlargement.

2004 enlargement of the European Union – Celebration in the Parc du Cinquantenaire in Brussels
2004 enlargement of the European Union – Preexisting EU members in 2004
2004 enlargement of the European Union – Celebrations at Fort Saint Angelo commemorating Malta 's entry into the EU
2004 enlargement of the European Union – The "Polish Plumber" cliché adopted by Poland's tourism board to advertise Poland as a tourist destination on the French market. (English translation: "I am staying in Poland, come in large numbers")

2. Clinical trial – Clinical trials are experiments done in clinical research. Clinical trials generate data on safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. Clinical trials can vary in size and cost, they can involve a single research center or multiple centers, in one country or in multiple countries. Clinical study design aims to ensure the scientific validity and reproducibility of the results. Trials can be quite costly, depending on a number of factors. The sponsor may be a governmental organization or a pharmaceutical, biotechnology or medical device company. Only 10 percent of all drugs started in human clinical trials become an approved drug. Some clinical trials involve healthy subjects with no pre-existing medical conditions. Other clinical trials pertain to patients with specific health conditions who are willing to try an experimental treatment. When participants are healthy volunteers who receive financial incentives, the goals are different than when the participants are sick. During dosing periods, study subjects typically remain under supervision for one to 40 nights. Usually pilot experiments are conducted to gain insights for design of the clinical trial to follow. The benefits must outweigh the risks. In the US, the elderly constitute only 14 percent of the population, while they consume over one-third of drugs.

Clinical trial – Edward Jenner vaccinating James Phipps, a boy of eight, on 14 May 1796. Jenner failed to use a control group.
Clinical trial – Austin Bradford Hill was a pivotal figure in the modern development of clinical trials.
Clinical trial – Example of informed consent document from the PARAMOUNT trial
Clinical trial – Timeline of various approval tracks and research phases in the US

3. Prescription drug – A prescription drug is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. Different jurisdictions have different definitions of what constitutes a prescription drug. "Rx" is often used as a short form for prescription drug in North America- a contraction of the Latin word "recipe" meaning "take". Prescription drugs are often dispensed together with a monograph that gives detailed information about the drug. The use of prescription drugs has been increasing since the 1960s. In the U.S. 88% of older adults use at least 1 prescription drug, while 36% take at least 5 prescription medicines concurrently. Those covered by government entitlements and those covered under the Repatriation Pharmaceutical Benefits Scheme have a reduced co-payment, $6.00 in 2014. The table below indicates the changes in co-payments over the years. These co-payments are compulsory and cannot be discounted by pharmacies under any circumstances. Private prescriptions are issued for medicines not covered on the PBS, or being used off-label, for indications other than those covered by the PBS. The patient pays the pharmacy for medicines privately prescribed. Prescribing is also covered by this legislation. A patient visits a medical practitioner or dentist authorised to prescribe drugs and certain other medical items, such as blood glucose-testing equipment for diabetics. Also, suitably qualified and experienced nurses and pharmacists may be independent prescribers.

Prescription drug – Regulation of therapeutic goods in the United States

4. Oncolytic virus – An oncolytic virus is a virus that preferentially infects and kills cancer cells. As the infected cancer cells are destroyed by oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour. Oncolytic viruses are thought not only to cause direct destruction of the tumour cells, but also to stimulate host anti-tumour immune responses. The potential of viruses as anti-cancer agents was first realised in the early twentieth century, although coordinated research efforts did not begin until the 1960s. A number of viruses including adenovirus, reovirus, vaccinia have now been clinically tested as oncolytic agents. Most oncolytic viruses are engineered for selectivity, although there are naturally resulting in clinical trials. Later it was also approved in Georgia and Armenia. In 2005 Chinese company, Shanghai Sunway Biotech registered an oncolytic adenovirus, a genetically modified adenovirus named H101. It gained regulatory approval for the treatment of head and cancer. Efforts to treat cancer through immunisation or virotherapy, began in the mid-20th century. As the technology for creating a custom virus did not exist, all early efforts focused on finding natural oncolytic viruses. During the 1960s, promising research involved using poliovirus, others. Only certain cancers could be treated through virotherapy was also recognised very early. Even when a response was seen, these responses were neither complete nor durable. In a wide range of in vivo cancer models, the HSV1716 virus has induced tumour regression and increased survival times.

Oncolytic virus – Viral luciferase expression in a mouse tumour
Oncolytic virus – Vaccinia virus infected cells expressing beta-glucuronidase (blue colour)
Oncolytic virus – Adenoviral NIS gene expression in a mouse tumour (Located at the crosshairs) following intravenous delivery of virus (Left) compared to an uninfected control mouse (Right)

5. PubMed Identifier – PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine at the National Institutes of Health maintains the database as part of the Entrez system of information retrieval. From 1971 to 1997, MEDLINE online access to the MEDLARS Online computerized database had been primarily through institutional facilities, such as university libraries. PubMed, first released in January 1996, ushered in the era of private, free, home- and office-based MEDLINE searching. Information about the journals indexed in MEDLINE and available through PubMed is found in the NLM Catalog. As of the same date, 13.1 million of PubMed's records are listed with their abstracts, 14.2 million articles have links to full-text. In 2016, NLM changed the indexing system so that publishers will be able to directly correct typos and errors in PubMed indexed articles. Simple searches on PubMed can be carried out by entering key aspects of a subject into PubMed's search window. When a journal article is indexed, numerous article parameters are extracted and stored as structured information. Such parameters are: Article Type, publication history. Publication type parameter enables many special features. Since July 2005, the MEDLINE process puts those in a field called Secondary Identifier. The secondary field is to store accession numbers to various databases of clinical trial IDs. For clinical trials, PubMed extracts trial IDs for the two largest trial registries: ClinicalTrials.gov and the International Standard Randomized Controlled Trial Number Register. A reference, judged particularly relevant can be marked and "related articles" can be identified.

PubMed Identifier – PubMed

6. RIGVIR – RIGVIR is a virotherapy medication approved by the State Agency of Medicines of the Republic of Latvia. It was patented in 2002. Rigvir is a drug containing a natural virus which has cytolytic and immunomodulating effects. Cytolytic action -- finding and destroying malignant cells, applies only without affecting the normal tissue cells. Regarding immunomodulation, because of its structure Rigvir selectively affects cells in sensitive tumors. Rigvir activates cells of the immune system due to what causes immune response against itself. Not a pathogenic virus It is not able to be replicated in the human body. It is issued in oncology for the prevention of secondary immunodeficiency. RIGVIR was registered on 29 April 2004, a few days before Latvia joined the European Union. In 1965, cancer laboratory was founded in the Institute of Microbiology to explore this phenomenon. 60 different types of enteric viruses were tested, 5 of them were identified as the most effective viruses capable of destroying cancer cells. ECHO-7, was named Rigvir. It was found that Rigvir is safe for adults and not able to replicate in the human body. It has been proven that Rigvir can not cause epidemics. The therapeutic effect was ascertained.

RIGVIR – Virions of enteroviruses in Rigvir
RIGVIR – Rigvir antigen in tumor cells