Spontaneous regression: a hidden treasure buried in time
Authors: S A Hoption Cann, J P van Netten, C van Netten, D W Glover
Spontaneous tumor regression is a phenomenon that has been observed for hundreds, if not thousands of years. Although the term spontaneous implies 'without apparent cause', a review of case reports over the last several hundred years demonstrates that regression generally coincides with acute infections. Observations of this non-specific effect led to the emergence of active cancer immunotherapies by the 1700s. By the 1890s, William Coley refined this approach with a bacterial vaccine which, when administered properly, could induce complete regression of extensive metastatic disease. Unfortunately, after Coley's death, his vaccine and technique fell into obscurity. Modern approaches to treatment have reduced the occurrence of spontaneous regressions. Aseptic techniques and antibiotics significantly reduce postoperative infections, while chemotherapy and radiation impair immune activation even when an infection does occur. More than a century after its inception, Coley's vaccine and aggressive approach to treatment may still be one of most effective immunotherapies for cancer.
Medical hypotheses. 01/03/2002; 58(2):115-9.
ISSN: 0306-9877
DOI: 10.1054/mehy.2001.1469

The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas
Authors: Edward F McCarthy
In 1891, William B. Coley injected streptococcal organisms into a patient with inoperable cancer. He thought that the infection he produced would have the side effect of shrinking the malignant tumor. He was successful, and this was one of the first examples of immunotherapy. Over the next forty years, as head of the Bone Tumor Service at Memorial Hospital in New York, Coley injected more than 1000 cancer patients with bacteria or bacterial products. These products became known as Coley's Toxins. He and other doctors who used them reported excellent results, especially in bone and soft-tissue sarcomas. Despite his reported good results, Coley's Toxins came under a great deal of criticism because many doctors did not believe his results. This criticism, along with the development of radiation therapy and chemotherapy, caused Coley's Toxins to gradually disappear from use. However, the modern science of immunology has shown that Coley's principles were correct and that some cancers are sensitive to an enhanced immune system. Because research is very active in this field, William B. Coley, a bone sarcoma surgeon, deserves the title "Father of Immunotherapy".
The Iowa orthopaedic journal. 01/02/2006; 26:154-8.
ISSN: 1541-5457I like this!You like this publication

Fever and cancer in perspective
Authors: U Hobohm
CONTEXT: A relationship between feverish infection and concurrent remission from cancer has been known about for a very long time. However, a systematic investigation of the phenomenon has not yet been made. OBJECTIVE: To bring together the isolated observations about the coincidence of spontaneous remissions with feverish infections and William Coley's seminal work, as a basis for devising an immunological hypothesis about the putative anti-cancer effect of fever. CONCLUSION: Fever induction under medical guidance may be considered as part of a therapy regimen for cancers of mesodermal origin.
Cancer immunology, immunotherapy : CII. 01/11/2001; 50(8):391-6.
ISSN: 0340-7004

Coley's toxins, tumor necrosis factor and cancer research: a historical perspective
Authors: B Wiemann, C O Starnes
As far back as the 1700s, it was recorded that certain infectious disease processes could exert a beneficial therapeutic effect upon malignancy. Most prominent among the numerous deliberate efforts made to take advantage of these observations was that of a pioneering New York surgeon, William B. Coley, active career 1891-1936. Using a bacterial vaccine to treat primarily inoperable sarcoma. Coley accomplished a cure rate of better than 10%. This review examines the history of these efforts and presents a discussion of their corresponding relevance to present day immunotherapy.
Pharmacology & therapeutics. 01/02/1994; 64(3):529-64.
ISSN: 0163-7258

Bacterial targeted tumour therapy-dawn of a new era
Authors: Ming Q Wei, Asferd Mengesha, David Good, Jozef Anné
Original observation of patients' spontaneous recovery from advanced tumours after an infection or a "fever" inspired extensive research. As a result, Coley's toxin for the therapy of sarcomas and live Bacillus Calmette-Guerin (BCG) for bladder cancer were born. In addition, three genera of anaerobic bacteria have been shown to specifically and preferentially target solid tumours and cause significant tumour lyses. Initial research had focused on determining the best tumour colonizing bacteria, and assessing the therapeutic efficacy of different strategies either as a single or combination treatment modalities. However, although clinical trials were carried out as early as the 1960s, lack of complete tumour lyses with injection of Clostridial spores had limited their further use. Recent progress in the field has highlighted the rapid development of new tools for genetic manipulation of Clostridia which have otherwise been a hurdle for a long time, such as plasmid transformation using electroporation that bore the problems of inefficiency, instability and plasmid loss. A new Clostridium strain, C. novyi-NT made apathogenic by genetic modification, is under clinical trials. New genetic engineering tools, such as the group II intron has shown promise for genetic manipulation of bacteria and forecast the dawn of a new era for a tumour-targeted bacterial vector system for gene therapy of solid tumours. In this review we will discuss the potential of genetically manipulated bacteria that will usher in the new era of bacterial therapy for solid tumours, and highlight strategies and tools used to improve the bacterial oncolytic capability.
Cancer letters. 01/02/2008; 259(1):16-27.
ISSN: 0304-3835
DOI: 10.1016/j.canlet.2007.10.034I like this!You like this publication


Coley toxins immunotherapy: a retrospective review
Authors: M A Richardson, T Ramirez, N C Russell, L A Moye
OBJECTIVE: Coley toxins are administered to cancer patients worldwide, though clinical studies assessing efficacy either alone or in combination with conventional cancer therapy are limited. This article provides an overview of Coley toxins immunotherapy and compares the survival experience of cancer patients who received Coley toxins for renal, ovarian, breast cancer, or soft-tissue sarcomas with patients who received conventional treatment other than radiation. DATA SOURCES: Cases were compiled from 5 of 18 monographs by Helen Coley Nauts. STUDY SELECTION: Using a retrospective cohort design with external controls, 128 Coley cases treated in New York from 1890 to 1960 were compared with 1675 controls from the Surveillance Epidemiology End Result (SEER) population-based cancer registry who received a cancer diagnosis in 1983. DATA EXTRACTION: Groups were matched on age, sex, ethnicity, site, stage, and treatment status (i.e., no radiotherapy). DATA SYNTHESIS: The Cox proportional hazards model controlled for stage and menopausal status (when applicable) and the hazard ratio and 95% CI defined the odds of site-specific survival from date of diagnosis to last follow-up. Compared to the SEER population, risk of death within 10 years was not significantly different in Coley patients treated for renal, ovarian, breast cancer, or soft-tissue sarcomas. CONCLUSIONS: This study suggests that patients treated with surgery and Coley toxins between 1890 and 1960 experienced survival rates comparable to those of patients diagnosed in 1983 and treated with nonradiotherapeutic conventional approaches. The study is limited by small sample sizes, possibly inaccurate technology for staging during Coley time, and potential selection bias with Coley patients.
Alternative therapies in health and medicine. 01/06/1999; 5(3):42-7.
ISSN: 1078-6791I like this!You like this publication

The impact of immune responses on lung cancer and the development of new treatment modalities
Authors: E Pluygers, A Sadowska, L Chyczewski, J Nikliński, W Niklińska, E Chyczewska
OBJECTIVE: This presentation covers predominantly review data in relation with immune responses initiating and accompanying lung carcinogenesis or- on the contrary-contributing to novel therapeutic developments. Occasionally, personal findings will be considered. RESULTS 1 OF IMMUNE DEFICIENCY: It is known for several decades that cancer incidence (several sites) is increased in subjects receiving immunosuppressive therapy, e.g. to avoid transplant rejection, or suffering from AIDS. We have observed that in areas heavily polluted by industrial activities, resulting in immune deficiency, cancer incidence is increased, notably for lung cancer. On the other hand, neoplastic cells are able to escape the host's immune responses by inducing apoptosis of the effector T lymphocytes. Apoptosis in T-cells is triggered by the interaction of the membrane receptor Fas with its normal ligand Fas L, or an activating antibody. Now lung carcinoma cells have been shown to express Fas L, enabling them to destroy cytolytic T cells. RESULTS 2 OF IMMUNE TREATMENT: It is well over a century ago that interest in the immunotherapy of cancer was aroused by the observation of tumour regressions concomitant with bacterial infection, an observation leading to the development of 'Coley's toxin', a mixture of killed bacteria (presently known to act through the presence of TNF-alpha). Since these long-standing empirical attempts, a lasting search for immune control of cancer has been initiated, comprising such different approaches as active non-specific immunotherapy, active specific immunotherapy, approaches based on the use of monoclonal antibodies, as well as those depending on cellular immunity and the development of adoptive immunotherapy, and the use of peptide vaccines. These different approaches will be described and their results presented. CONCLUSION: Present state-of-the-art will be discussed and new pathways for development evoked; better understanding of immune mechanisms is opening new avenues for improved treatment efficacy.
Lung cancer (Amsterdam, Netherlands). 01/01/2002; 34 Suppl 2:S71-7.
ISSN: 0169-5002I like this!You like this publication

Fever therapy revisited
Authors: U Hobohm
The phenomenon of spontaneous regression and remission from cancer has been observed by many physicians and was described in hundreds of publications. However, suggestive clues on cause or trigger are sparse and not substantiated by much experimental evidence. In this review, literature is surveyed and summarised and possible causes are discussed. At least in a larger fraction of cases a hefty feverish infection is linked with spontaneous regression in time and is investigated as putative trigger. Epidemiological and immunological evidence is put into perspective. An online forum to discuss the possible application of fever therapy in the future can be accessed at http://bioinfo.tg.fh-giessen.de/fever-and-cancer.
British journal of cancer. 01/03/2005; 92(3):421-5.
ISSN: 0007-0920
DOI: 10.1038/sj.bjc.6602386

Pathogen-associated molecular pattern in cancer immunotherapy
Authors: Uwe Hobohm, John L Stanford, John M Grange
Observations from different research frontiers--epidemiological data, case studies on spontaneous regressions from cancer, clinical studies, tumor immunology--indicate that exposure by vaccination or infection to pathogen-associated molecular patterns (PAMP) can have beneficial effects on neoplastic diseases, both prophylactically and therapeutically. These effects have not yet been harnessed to their full extent for the prophylaxis and therapy of cancer. Here, we summarize clinical, epidemiological, and experimental data and discuss the role of PAMP in cancer therapy.
Critical reviews in immunology. 01/02/2008; 28(2):95-107.
ISSN: 1040-8401I like this!You like this publication

Tumor necrosis factor
Authors: L J Old
A century ago it was noted that a bacterial infection sometimes causes the regression of cancer. In 1975 the author found an explanation: the infection stimulates the secretion of tumor necrosis factor (TNF), which has anticancer activity. Now TNF, an important regulator of inflammation and immunity, is in clinical trials as an anticancer drug.
Scientific American. 01/06/1988; 258(5):59-60, 69-75.
ISSN: 0036-8733I like this!You like this publication
--
Authors: S A Hoption Cann, J P van Netten, C van NettenPublishing researchers:
Victor Esepenok
Spontaneous tumour regression has followed bacterial, fungal, viral, and protozoal infections. This phenomenon inspired the development of numerous rudimentary cancer immunotherapies, with a history spanning thousands of years. Coley took advantage of this natural phenomenon, developing a killed bacterial vaccine for cancer in the late 1800s. He observed that inducing a fever was crucial for tumour regression. Unfortunately, at the present time little credence is given to the febrile response in fighting infections-no less cancer. Rapidly growing tumours contain large numbers of leucocytes. These cells play a part in both defence and repair; however, reparative functions can also support tumour growth. Intratumoural infections may reactivate defensive functions, causing tumour regression. Can it be a coincidence that this method of immunotherapy has been "rediscovered" repeatedly throughout the centuries? Clearly, Coley's approach to cancer treatment has a place in the past, present, and future. It offers a rare opportunity for the development of a broadly applicable, relatively inexpensive, yet effective treatment for cancer. Even in cases beyond the reach of conventional therapy, there is hope.
Postgraduate medical journal. 01/01/2004; 79(938):672-80.
ISSN: 0032-5473

1.PRESCRIPT
onanatoxins vaccine usage to prevent
streptococcusisof farm, carnivorous and gnawing
animalsand of avifauna.
STREPTOEVAK
1.General Terms
1.1. Anatoxinsvaccine against streptococcusis among
farm, carnivorous and gnawing animals as well as
avifauna has been producedof streptococcus germ
culture belonging to serogroup С inactivated in
formaline and depositedin aluminum hydroxine.
1.2.In outwardappearance it is a coarse dispersion of
yellowish-grey color with batting residual matter
which is formingat the bottom of bottle when stored
and such sedimentation easily restores itshomogenous
condition when shaking the bottle.
1.3.As abiopharmaceutical product this vaccine appears
on the market measured out indoses of 0.5, 1.0, 2.0,
3.0, 50 and 200 ml. The bottle of anatoxins
vaccineshould be hermetically sealed with rubber cork
aluminum rolled capping. Each bottle must be labeled
and provide the followinginformation, namely:
denomination of themanufacture and its trade mark,
name of vaccine, the quantity of vaccine in thebottle
(in ml), number of series, control number,
manufacturing date (month andyear), expiration date,
storing conditions, specifications and
cautionarywarning For Animal Beings Only.
1.4. Thebottle which does not carry any labeling or
marking, and/or contains mold, extraneousbodies,
flakes which remain even when shaking the bottle,
having broken ordefective capping as well as remaining
anatoxinsvaccine which was opened and not used within
the same day should be rejected. Thevaccine is
normally destructed by boiling it within 10 minutes.
1.5. Anatoxinsvaccine is suitable for usage within the
two years from the date ofmanufacturing subject it is
stored in a dry dark place under the temperatures of
environment from 2 to 100 degreesCentigrade.
2. Biological Properties
2.1. Anatoxinsvaccine ensures active imunity of
vaccinated animals against streptococcusis. Anatoxins
vaccine is quite safe and arectogenious.
2.2. Vaccinatedanimal beings start having such imunity
after 11-13 days following the first injectionof this
vaccine and remain immune overthe next 6 months and
longer.
2.3. Anatoxinsvaccine has also a curative effect when
streptococcusisafflicts farm, carnivorous and gnawing
animals and avifauna fighting such diseases as blue
bag, endometritis, cystitis, nefritis, eye mucositis,
ear auricleinflammation, arthritis, gastric and
intestinal mucosa, respiratory organdiseases, derma
inflations and abscesses, as well as reduces
surgicalcomplications. Anatoxins vaccine neutralizes
immunologic attack of own body'stissue, affected by
pathogetic streptococcus.
2.4. Anatoxinsvaccine neutralizes exotoxin of
biological agent and prevents tissue injury anddamage.
2.5. Anatoxinsvaccine is an immunostimulant of immune-
evocation which generates polyclonal agitation B-
поликлональной активации В - lymphocytes and
normalizeequilibrium in sub-components ofT-lymphoid
cells.
3. VaccineTreatment Prescription
3.1. Anatoxinsvaccine is used to provide immunity to
farm,carnivorous and gnawing animals as wellas
avifauna in the farms and animalretainers where there
is a risk of streptococcus disease.
3.2. Maleand female animals are being
vaccinatedbetween 30 and 50 days prior service for
breeding. Springer cows are being vaccinatedtwice 50-
60 days prior calving with the doses 2.0 and 3.0 ml
the interval between thevaccinations being from 10 to
14 days. Stud bulls get vaccinated between 30 and 50
days prior service forbreeding with the same doses.
Calves are vaccinated when they reach 18-21 daysof
life with the doses of 2.0 and 3.0 mland the interval
between the vaccinations should be from 10 to 14 days.
3.3.Breedingsows are being vaccinated within theperiod
of 30 and 50 days prior farrowing with the doses of
2.0 and 3.0 ml theinterval between the vaccinations
being from 10 to 14 days. Male pigs get vaccinated
between 30 and 50 days prior service forbreeding with
the same doses. Young pigs are vaccinated twice prior
breakinginto milk with the doses of 0.5 and 1.0 ml the
interval between thevaccinations being from 10 to 14
days.
3.4.Fur animals,gnawers, dogs and cats (male and
female) are vaccinated 20-30 days before service,
growing stock -twice after breaking into milk with
thefollowing doses: the weight of animal being less
than 5 kgs - 0.3 and 0.5 ml,over 5 kgs respectively
0.5 and 1.5 ml and over 35 kgs - 1.0 and 1.5 ml andthe
interval between the vaccinationsbeing from 10 to 14
days.
3.5. Householdand fancy poultry is vaccinated starting
from 2 months of age when under 3 kgsof weight with
the dose: 0.2 and 0.3ml, and over 3 kgs of weight with
the dosesof 0.3 and 0.5 ml.
3.6.For treatmentpurposes the doses of this biological
product should be increased in 2 or 3times and used in
accordance with the prescription. The third dose is
normallyinjected following one month after the the
first one and the forth dose - after2 months following
the first injection.
3.7.Everybottle of Anatoxins vaccine should be shaked
well before usage to get ahomogeneous substance. In a
very coldenvironment it ie required to warm the bottle
with vaccine on steam up to thetemperature of 30-36
degrees Centigrades.
3.8. Anatoxinsvaccine injection is made
intramuscularly to a hip zone, which has to
bepreviously desinfected, syringe and needles should
be asepticized in bolingwater for 10 minutes. At the
point of injection a small concretion may appear
whichwill resolve in 3-5 days after vaccination.
4. Claiming Procedures
4.1. In caseof complications after vaccination or non-
effectiveness the usage of products ofthe same series
should be stopped and inaccordance with the
instructions of Head Veterinary Department on claiming
proceduresdated 19/09/1987 such cases should be
reported to the All-Union State Science andResearch
Institute for veterinary medicines standards and
certifications (5,Zvenigorodskoie shosse, Moscow,
123022). At the same time two bottles of vaccine as
minimumshould be sent to the institute of those which
caused such complications. Theduplicate of the letter
should be sent to the manufacturer.
Vaccine havingits term expired should not be
accepted.See http://www.saberespoder.sitecity.ru
http://picasaweb.google.com/suegra111/CCTREPTOKOKKOZYAn
dComplications# http://www.streptoevak.com

Nueva susstancia bioespeciaica para reacciones auto inmunes de etiologia estreptococia.

V.A.Esepyonok,doctor en citncias de veterinaria.

La estreptococosis:enfermedad infeccisa en el homre,de todos los tipos de animales domesticos y de granfa,animales salvafes y de laboratorio, aves y peces,ocasionada por la bacteria gram positiva estreptococo.La gran incidencia de portadores entre personal y los animales ya gue el estreptococo hemolitico es id
entico para todos los animales.
La enfermedad se caracterisa por la presensia de abscesos en diferentes tefidos y organos de todo el cuerpo gue puedo ser letal.
El estreptococo patogeno-es un complefo sistema biologico con enzimas internas y externas,las cuales en el proceso de la evolucion biologica adguirieron la capacidad de convertirse en fagositos defenderse delcompleto,formar mutantas en la celula madre y desarrollar la enfermedad del huesped en ausensia de inmuno deficit.
La importancia de la etiologнa estreptocтcica en la patologia de los animales y del hombre esta disminuida ya que son exigentes para su cultivo y necesitan material especial. La respuesta inmune de huesped se desarrolla sin la eliminaciуn de la bacteria del organismo.
La agresiуn interna del estreptococo patуgeno dana los tejidos del huesped lo que garantiza la penetracion del estreptococo y de otras bacterias, condicionando el desarrollo de enfermedades infecciosas.
Estudiando la biologia de los estreptococos patogenos y el desarrollo de la enfermedad en el organismo, nosotros hemos preparado una anatoxina vacuna STREPTOEVACK a nivel de polimetros biologicos ( 1 . )
Esta Biosustancia no es danina y tiene efecto antitoxico y profilactico contra el estreptococo hemolitico, esto se ha demostrado en experimentos realizados en miles de animales afectados ( 2 . )
En la actualidad practicamente los especialistas del mundo entero no cuentan con medios confiables para combatir al estreptococo. Segun datos de L.V. Lvovoy ( ano 2000 ), no hay medicamento que pueda evitar que el hombre desarrolle la glomerulo nefritis. Ni siquiera el transplante renal ya que el rinon transplantado presenta tambien glomerulo nefritis. Cientificos del centro nacional de Virologia y Biotecnologia VEKTOR ( 2006 ) ( 4 ) , presentaron una hipуtesis “ Causas del desarrollo de enfermedades cardiovasculares y oncolуgocas “, que habla de la importancia etiologica del estreptococo.
Nosotros entendemos y demostramos la teorнa.
La enfermedad auto inmune del ojo constituye un problema de la medicina veterinaria ya que con frecuencia presentan cambios irreversibles en los tejidos oculares. La Queratoconjuntivitis seca y como consecuencia la queratitis ulcerosa profunda que conlleva a la ceguedad de los animales.
La vacuna antitoxina ESTREPTOVAK se utiliza para el tratamiento de gatos en estadio inicial de un absceso corneal . Los criterios diagnostico para su uso son: blefaroespasmo, lagrimeo, blefaroptosis. Con la aplicacion en la lesion de la sustancia ocurre una coloracion verde de todos los tejidos comprometidos. ESTREPTOVAK se emplea 0.5 ml. intramuscular con intervalos de 15 – 20 dнas por tres veces. Conjuntamente se usa antovegin en del para uso ocular y antimicrobianos. Con el uso oportuno se consigue la epitelializacion de toda la cornea sin pigmentaciуn de la misma.
La biosustancia es efectiva por su alta especificidad ,transformando celulas semejantes a los fibroblastos en celulas epiteliales del parpado en los ojos caninos .En las fotos presentadas de los perros antes del tratamiento(1,2) y despues del tratamiento(3,4).El tratamiento consiste en la aplicacion de 4 inyecciones de la vacunantitoxina. Los resultados del tratamiento con STREPTOEVAC de caninos y felinos de las complicaciones de la estreptococcosis ,por primera vez muestran una curacion sin intervenciones quirurgicas .
La siguiente etapa del trabajo, muestra el estudio de la influencia de ESTREPTOEVAC en el cancer hepatocelular en ratones .El experimento se llevo a cabo en ratones ROVR. Para el transplante subcutaneo en animales de laboratorio se uso 16 pasajes de tumores de higado que se recibieron en PONX im. N.n.brojina RAMN .La vacunacion se llevo a cabo 2 veces con intervalos de 12 dias intrabdominal en dosis de 0.1 y 0.3ml. el estudio del tumor se realizo a la semana de la vacunacion ,el control fueron ratones no vacunados y que si recibieron el tumor. El efecto de la vacunacion se califico con la aparicion de los primeros nodulos cancerнgenos ,velocidad de crecimiento y tiempo de vida. Los primeros nodulos en los ratones vacunados aparecieron mas tarde ,(porcentaje de incremento en el tiempo 5%) pero la diferencia no tiene significado estadistico El volumen del tumor en ratones vacunados fue menor en comparacion con los no vacunados. Una diferencia significativa se noto en 8 de 11 mediciones en el experimento .Entre lo s vacunados se observo un menor tiempo de vida (8%), sin embargo esta diferencia en comparacion con los no vacunados ,no tiene significado estadistico.
Analizando los resultados positivos en los gatos y perros (mas de 100),y en los animales de laboratorio se puede llegar a la conclusion de que la vacuna anatoxina ESTREPTOEVAC constituye una biosustancia especifica para el tratamiento de reacciones auto inmunes de etiologia estreptocуcica.

1.-V:A:Ecepenok. Estreptococcosis en las nutrias. Diagnуstico como combatir y profilaxis especifica .Disertaciуn tesis de investigacion para lograr el doctorado en ciencias veterinarias.
2.- V:A: Ecepenok, J:C:Gorbatova. Etiologia , patogenesis ,tratamiento y profilaxis de la estreptococosis Consultor veterinario N 10 (125) mayo 2006
3.-L:V:Lvova. El estreptococo golpea .RR:Drjiv.2000 n8.
4.-Cientificos del Centro Cientifico de Virologia y Biotecnologia VECTOR.(2006
Hipotesis “Motivos del desarrollo de enfermedades oncologicas y cardiovasculares”.

Protocolo.......

2.Protocolo
del uso de la vacuna anatoxina contra estreptococco de los animales
de granja, carnivoros, roedores, aves

STREPTOEVAK
Autor V.A.Esepyonok,doctor en siensias de veterinaria. Mosku.
1. Generalidades
1.La vacuna anatoxina contra estreptococco se usa para la inmunizacion de los animales de granja, los carnivoros, roedores y aves y esta preparada de los cultivos de estreptococo del grupo C e inactivada con formalina e hidroxido de aluminio.
1.2Tiene el aspecto de una suspension amarillenta con un presipitado en el fondo que se homogeniza rapidamente al agitarlo.
1.3La presentacion de los frascos es de 0,5,1,2,3,50,100 y 200 ml. Los frascos deben estar cerrados hermeticamente con una tapa de goma y aluminio. Cada frasco debe tener la etiqueta que tendra los siguientes datos: nombre de la industria productora, registro sanitario, nombre de la vacuna, cantidad (ml), serie, numero de control, fecha de produccion, fecha de caducidad, condiciones de conversacion, indicaciones para el uso.
1.4Frascos sin etiquetas ni marcado que no se homonicen al agitarse, los que contengan moho o mezclas extranas y los que no hayan sido usados el mismo dia , deben ser destruidos , hirviendolos por unos 10 min.
1.5 La vacuna anatoxina se puede usarla hasta 2 anos desde la fecha de su produccion, si esta ha estado guardada en un lugar seco, oscuro a la temperatura de 2- 10 grados .
2. Caracteristicas biologicas
2.1 La vacuna anatoxina produce una respuesta inmunitaria activa contra los estreptococos en los animales vacunados, sin efectos colaterales.
2.2.La respuesta inmunitaria en los animales se forma al dia 12- 14 despues de haber sido aplicada y continua hasta los 6 meses y mas.
2.3 La vacuna anatoxina tiene tambien el efecto terapeutico en los animales domesticos y los de granja y roedores en lo que se refiere a mastitis,endometritis, cistitis, arthritis, enfermedades de la piel y rinones,meningitis,inflamasion cordon umbilicalis, conyuctivitis, otitis, abscesos, disminuye tambien complicaciones despues de operaciones. La vacuna anatoxina neutraliza el ataque inmunologico en los tejidos del organismo del portador de estreptococo patogeno.
2.4 La vacuna anatoxina neutraliza las exotoxinas de la bacteria lo que evita el dano de los tejidos.
2.5 La vacuna anatoxina constituye un estimulante de la respuesta inmunitaria que conduce a la policlonacion y activacion de limfacitas B
3. Protocolo de uso de la vacuna
3.1 La vacuna anatoxina se la aplican para la inmunizacion de los animales de granja, carnivoros, roedores y aves que sean atacados por estreptococco en explotaciones agricolas, lugares cerrados desfavorables y los que estan bajo la amenaza del estreptococco.
3.2 A las vacas prenadas se las vacunan dos veces 50-60 dias antes la paridera en dosis de 2,0 y 3,0 ml con intervalos de 10-14 dias entre las inyecciones. A los toros sementales se les ponen la vacuna 30-50 dias antes de la cubricion en las mismas dosis. A los terneros se les vacunan a la edad de 18-21 dias en las dosis de 2,0 y 3,0 ml con intervalo de 10-14 dias entre las inyecciones.
3.3 A las cerdas se las vacunan dos veces 30-50 dias antes de la paridera en las dosis de 2,o y 3,0 ml con intervalo en 10-14 dias. A los verrones se les vacunan 30-50 dias antes de la cubricion en las mismas dosis. Antes de ser separados de las cerdas vacunan a los cerditos en las dosis de 0,5 y 1,0 ml con intervalo de 10-14 dias.
3.4 A los animales de piel fina, roedores, perros y gatos /machos y hembras/ se les vacunan 20-30 dias antes de la cubricion. Al ganado menudo despues de ser separado este de los “padres” se le vacunan dos veces con intervalo de 10-14 dias entre las inyecciones en las dosis siguientes con el peso hasta 5 kg-0,3 y 0,5 ml, mas de 5 kg-0,5 y 1,5 ml, mas de 35 kg-1,0 y 1,5.
3.5 A las aves del corral y decorativas se las vacunan desde 2 meses de edad . Los de 3 kg de peso con loa dosis de 0,3 y 0,5 ml y los de mas de 3 kg con la dosis de 0,3 y 0,5 ml.
3.6 Con los fines curativos aumentan las dosis del biomedicamento en dos o tres veces y las aplican segun las indicaciones. A la tercera dosis se la aplican despues de un mes de la aplicacion de la primera y la cuarta despues de dos meses de la primera.
3.7 Antes de la aplicacion de la vacuna anatoxina hay que agitar el frasco para que se forme una sustancia omogenea. Durante la temporada fria los frascos con la vacuna los hay que calentar al bano Maria a la temperatura de 30-36 grados.
3.8 La vacuna anatoxina se aplica via intramuscular en el muslo despues de haberlo desinfectado, las agujas y las jeringas las esterilizan por medio del hervor durante unos 10 minutos. En el lugar de la inyeccion puede aparecer una pequena compresion que se resuelve al tercer o quinto dia despues de la vacunacion.
4. Protocolo de reclamos
4.1 En al caso de presentar alguna complicacion despues de la vacunacion y su falta de efectividad, se suspende el uso de la vacuna de la misma serie y se informa segun las reglas de la veterenaria de 10-09-87 al instituto de la investigacion cientifica de centro y estandarizacion y certificacion de las sustancias veterinarias Moscu, 123022 Zvenigorodskoe shosse, 5/22. Al mismo tiempo se envia no menos de 2 frascos que presentaron complicaciones. El segundo ejemplar de la carta se lo envia a la industria farmaceutica.
No se puede usar la vacuna despues de la fecha de su vencimien



Pancreatic cancer
Pancreatic cancer regression by intratumoural injection of live Streptococcus pyogenes in a syngeneic mouse model
C Maletzki1, M Linnebacher2, B Kreikemeyer3, J Emmrich1
+ Author Affiliations

1Division of Gastroenterology, Department of Internal Medicine, University of Rostock, Rostock, Germany
2Department of General, Thoracic, Vascular and Transplantation Surgery, University of Rostock, Rostock, Germany
3Department of Medical Microbiology and Hospital Hygiene, Institute of Medical Microbiology, Virology and Hygiene, University of Rostock, Rostock, Germany
C Maletzki, Division of Gastroenterology, Department of Internal Medicine, University of Rostock, Ernst-Heydemann-Str. 6, D-18055 Rostock, Germany; Claudia.Maletzki@uni-rostock.de
Revised 28 September 2007
Accepted 6 November 2007
Published Online First 19 November 2007
Abstract
Background: This study addressed the potential of bacteriolytic therapy using Streptococcus pyogenes in a syngeneic pancreatic carcinoma mouse model.

Methods: Panc02 tumours were either infected with S pyogenes or were treated with the equivalent volume of vehicle. In addition to assessment of tumour histology and immunohistochemistry, isolated splenocytes were analysed by flow cytometry. Interferon (IFN) γ secretion as a reaction of splenocytes against tumour cells was shown through the ELISpot technique. A cytotoxic effect of lymphocytes against tumour targets was detected by lactate dehydrogenase (LDH) release. Cytokine levels in serum were measured.

Results: A single application of live bacteria into established Panc02 tumours resulted in complete tumour regression. This antitumoural effect was accompanied by massive leucocyte infiltration into the tumours as well as a significant and sustained elevation of systemic levels of the proinflammatory cytokines IFNγ, tumour necrosis factor α and interleukin 6. Lymphocytes obtained from treated mice specifically recognised syngeneic tumour cells in IFNγ-ELISpot, and most importantly in cellular cytotoxicity assays, indicating a tumour-specific immune response.

Conclusions: We provide data that both the direct lytic activity of S pyogenes towards tumour cells and the infection-driven infiltration of tumours by cells of the innate immune system lead to damage of tumour cells followed by a dissemination of tumour components. This last outcome allows for the activation of tumour-specific effector cells, most probably in draining lymph nodes, promoted by the proinflammatory context. Taken together, these data indicate that the application of live S pyogenes may be a promising new treatment strategy for advanced pancreatic cancer patients that warrants further investigation.

http://gut.bmj.com/content/57/4/483.abstract