Oncolytic virotherapy has been investigated for several decades and is emerging as a plausible biological therapy with several ongoing clinical trials and two viruses are now approved for cancer treatment in humans. The direct cytotoxicity and immune-stimulatory effects make oncolytic viruses an interesting strategy for cancer treatment. In this review, we summarize the results of in vitro and in vivo published studies of oncolytic viruses in different phases of evaluation in dogs, using PubMed and Google scholar as search platforms, without time restrictions (to date). Natural and genetically modified oncolytic viruses were evaluated with some encouraging results. The most studied viruses to date are the reovirus, myxoma virus, and vaccinia, tested mostly in solid tumors such as osteosarcomas, mammary gland tumors, soft tissue sarcomas, and mastocytomas. Although the results are promising, there are issues that need addressing such as ensuring tumor specificity, developing optimal dosing, circumventing preexisting antibodies from previous exposure or the development of antibodies during treatment, and assuring a reasonable safety profile, all of which are required in order to make this approach a successful therapy in dogs.
Research on oncolytic viruses has mostly been directed towards the treatment of solid tumors, which has yielded limited information regarding their activity in hematological cancer. It has also been directed towards the treatment of humans, yet veterinary medicine may also benefit. Several strains of the Newcastle disease virus (NDV) have been used as oncolytics in vitro and in a number of in vivo experiments. We studied the cytolytic effect of NDV-MLS, a low virulence attenuated lentogenic strain, on a human large B-cell lymphoma cell line (SU-DHL-4), as well as on primary canine-derived B-cell lymphoma cells, and compared them to healthy peripheral blood mononuclear cells (PBMC) from both humans and dogs. NDV-MLS reduced cell survival in both human (42% ± 5%) and dog (34% ± 12%) lymphoma cells as compared to untreated controls. No significant effect on PBMC was seen. Cell death involved apoptosis as documented by flow-cytometry. NDV-MLS infections of malignant lymphoma tumors in vivo in dogs were confirmed by electron microscopy. Early (24 h) biodistribution of intravenous injection of 1 × 1012 TCID50 (tissue culture infective dose) in a dog with T-cell lymphoma showed viral localization only in the kidney, the salivary gland, the lung and the stomach by immunohistochemistry and/or endpoint PCR. We conclude that NDV-MLS may be a promising agent for the treatment of lymphomas. Future research is needed to elucidate the optimal therapeutic regimen and establish appropriate biosafety measures.
Medical imaging techniques play a central role in clinical oncology, helping to obtain important information about the extent of disease, and plan treatment. Advanced imaging modalities such as Positron Emission Tomography–Computed Tomography (PET/CT), may help in the whole-body staging in a single procedure, although the lesions should be carefully interpreted. PET/CT is becoming commonly used in canine cancer patients, but there is still limited information available on specific tumors such as mammary cancer. We evaluated the utility of fluorine-18 fluorodeoxyglucose ( 18 F-FDG)-PET/CT to detect malignant lesions in eight female dogs with naturally occurring mammary tumors. A whole-body scan was performed prior to surgery, and mammary and non-mammary lesions detected either on PET/CT or during pre-surgical physical exam were resected when possible and submitted for histopathological examination. Multiple mammary lesions involving different mammary glands were detected in 5/8 dogs, for a total of 23 lesions; there were 11 non-mammary-located lesions in 6/8 dogs, three of these were lung or lymph node metastasis. A total of 34 lesions were analyzed: 22 malignant (19 mammary tumors and three metastatic lesions), and 12 benign (four mammary lesions and eight of non-mammary tissues). Glucose uptake by maximum standardized uptake value (SUVmax) was analyzed and correlated with tumor size, and benign vs. malignant pathology. We found that the minimum tumor size needed to distinguish malignant lesions according to the SUVmax was 1.5 cm; benign and malignant lesions <1.5 cm did not differ in glucose uptake (mean SUVmax = 1.1). In addition, a SUVmax value >2 was 100% sensitive for malignancy. Combining these data, lesions >1.5 cm with a SUVmax >2 had a positive predictive value of 100%. Finally, we did not find an association between SUVmax and histologic subtype or grade, which may be present in a larger sample. Thus, 18 F-FDG PET/CT is useful for distinguishing malignant from benign lesion but further imaging of dogs with diverse tumors, should establish characteristic SUV value cutoffs for detecting primary and metastatic disease, and distinguishing them from benign lesions.
RESUMENPor efecto de la civilización industrial y del desarrollo tecnológico de nuestros tiempos, se origina la "lluvia ácida", que es la precipitación en forma de lluvia, nieve, aguanieve, granizo o niebla con altas concentraciones de ácido sulfúrico (H 2 SO 4 ), ácido nítrico (HNO 3 ) y ácido carbónico (H 2 CO 3 ). El aumento de la lluvia ácida ha tenido efectos considerables en los ecosistemas: los bosques del mundo se están muriendo y sus cuerpos de agua no pueden sostener a las poblaciones normales de peces. Asimismo, disminuye el rendimiento agrícola y se corroen el mármol, metal y piedra en las ciudades. ABSTRACTThe industrial civilization and technological development of our times has given birth to "acid rain," which is precipitation in the form of rain, snow, sleet, hail or fog with high concentrations of sulfuric acid (H 2 SO 4 ), nitric acid (HNO 3 ) and carbonic acid (H 2 CO 3 ). The increase in rain acid has had significant effects on ecosystems: the world's forests are dying and their water bodies cannot sustain normal fish populations. It also reduces crop yields and corrodes marble, metal and stone in cities.PALABRAS CLAVE: bosques, contaminación industrial, suelos forestales.KEy woRdS: forests, industrial pollution, forest soils. INTRODUCCIÓNEl término lluvia ácida fue utilizado por primera vez por Robert Angus Smith, quien investigaba la química del aire de las industrias británicas en 1850. Los molinos de algodón y las poderosas industrias pesadas que funcionaban gracias al carbón, vertían grandes cantidades de humo a la calle. Smith demostró que estas fábricas hacían emisiones directas al aire de hollín y sustancias que cambiaban la química de la lluvia haciéndola más ácida. Al final de 1950 fueron detectados los resultados de esta contaminación proveniente de las industrias por el incremento que presentó en la atmósfera, haciéndose evidente por el efecto adverso en los bosques. Aunque esta forma de contaminación es comúnmente conocida como lluvia ácida, el término más adecuado es deposición ácida, porque la acidez puede ser liberada como gas o como polvo, y estas partículas son arrastradas a la tierra por medio de la lluvia (Hendrey y Vertucii, 1980; Last y Nichoison, 1982; Torres y Galván, 1999).Por mucho tiempo se pensó que el problema de la lluvia ácida era consecuencia, en gran parte, de los gases ricos en azufre producidos por la quema de algunos combustibles fósiles (especialmente de carbones de pobre calidad) y por la fundición de minerales metálicos. Ahora
RESUMENCon el objetivo de conocer la respuesta de Quercus magnoliifolia al fuego en mortalidad y rebrotación, se aplicó una quema prescrita intensa, en fajas a favor de viento y pendiente, a una parcela de 0.5 ha en el estado de Guerrero, México, en abril de 2009. La quema inició a las 10:20 y duró 1 h 26 min. Se midieron las variables meteorológicas temperatura (25-28 °C), humedad relativa (33-24%), y velocidad del viento (7-25 km/h); y de comportamiento del fuego (largo de llama, de 0.5 a 3 m).Seis meses después se midieron variables de la estructura del arbolado y de severidad de la quema. El análisis de datos involucró regresión logarítmica y regresión logística. Los valores estructurales medios fueron: altura (11.2 m), diámetro normal (12. 2 cm) y altura de copas (6.8 m). Se halló relación logarítmica directa entre el largo de llama y la velocidad del viento (R2=0.65). No hubo mortalidad producto de la quema, pero 33 % de los árboles rebrotaron. Las variables explicativas de la probabilidad de rebrotación fueron: altura (p=0.0159), diámetro normal (p=0.0394)y altura a la base de copas (p=0.0487). La cicatriz sobre el tronco alcanzó 2.6 m y el chamuscado de copas 62 %, en promedio. La especie muestra resistencia a fuego poco severo, gracias a su corteza, y tolerancia a fuego más severo. Las quemas prescritas contribuirían a reducir impactos negativos de incendios en el arbolado.
Oncolytic viruses, either naturally or genetically modified, possess the ability to kill cancer cells. Newcastle Disease Virus (NDV), a type I avian paramyxovirus, has demonstrated a selective ability to kill cancer cells directly as well as through immunostimulation. NDV is able to infect more than 250 species of birds, particularly poultry and is considered a zoonosis, primarily causing conjunctivitis. Importantly, no infections have been reported in mammalian species nor is there evidence of human to human transmission. We use the LaSota strain which is lentogenic (less pathogenic). We seek to study the in vitro oncolytic (lympholytic) potential of NDV on healthy mononuclear and malignant lymphocytes and the in vivo oncolytic therapeutic potential in dogs with lymphoma. LaSota vaccine strain (LSV) was propagated in pathogen –free 9 day old chicken embrios. Viral titers were reported as mean infective dose. Healthy human and canine mononuclear cells as well as a human diffuse large B cell lymphoma cell line (DHL4 cell line) were exposed to medium alone, LSV at a multiplicity of infection (MOI) of 0.1, 10 and 100 or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. Apoptosis was assessed by flow cytometry using annexin V/FITC/IT. Cell counts were carried out at 48 and 72 hs. Data was analyzed by FlowJo 9 and Prisma 6 Softwares. Interestingly, cells at the highest MOI (100) had the same rate of apoptosis as those exposed to chemotherapy, both significantly higher than negative controls. The in vivo response and toxicity to intravenous and intratumoral inyection of LSV in a dog with naturally occurring aggressive, multicentric cutaneous T-cell lymphoma is reported. The patient had a 4 week history of paraplegia due to lymphomatous infiltration of the spinal canal and a 3 week history of rapid development of multiple elevated cutaneous lesions ranging from (from 0.5 by 0.5 cm to 15 cm in diameter and 2 cm in thickness). After informed consent, LSV was given in a single occasion with 1x106 mean (50%) infective dose in tissue culture (TCDI 50) in only one lesion, as well as intravenously with a TCDI 50 of 1x1012 in order to assess response of distant non-virally infiltrated lesions. At four weeks of follow up, no new lesions have appeared. All tumors are responding with complete flattening of the lesions and decrease in diamenter of all lesions. Spontaneous bleeding from the lesions was seen from days 4 through 7 after treatment. All laboratory work up is within normal limits except for indirect hiperbilirrubinemia (2x above normal) in the 4th week (Coombs results are pending). Consecutive samples for histology, electron microscopy and viral load are being evaluated. The patient has had an excellent performance status with no evident clinical toxicity and has begun to wag his tail and show slow movement of the posterior limbs with gain in sensitivity. We have demonstrated the specific in vitro, oncolytic/lympholytic activity of NCV (LaSota) on human lymphoma- derived cells with minimal tropism towards healthy cells. Response to treatment of the first patient (dog) is encouraging. Longer follow up as well as histologic evaluation and viral shedding are being evaluated. Disclosures No relevant conflicts of interest to declare.
Pinus cembroides subsp. orizabensis es el pino piñonero con distribución más al sur en América, la mayoría de sus poblaciones se desarrollan dentro de los límites de la Cuenca Oriental, la única zona árida fría en México, donde se distribuyen en por lo menos cinco localidades aisladas. Los objetivos del presente estudio fueron realizar el inventario florístico y estructural de los bosques de pino piñonero de la Cuenca Oriental, cuyo dosel domina el taxón antes referido. El trabajo de campo consistió en la búsqueda y recolección de ejemplares de plantas vasculares mediante técnicas estándar, para su posterior identificación en laboratorio, y en el muestreo de los bosques para determinar la densidad, cobertura y valor de importancia de las especies. El análisis de agrupamiento permitió estimar la semejanza en la composición de especies entre bosques; mediante el análisis de correspondencia canónica se estimó la relación entre factores ambientales y edáficos, con respecto a la composición y distribución de las especies entre las localidades; y con los valores estructurales se realizó la caracterización fisionómica de los bosques. Los resultados indican que los bosques de pino piñonero se desarrollan en sustratos volcánicos, en suelos con pH neutro a ligeramente básico (7-8), en un intervalo altitudinal de entre 2300 m y 2700 m. Las asociaciones vegetales identificadas fueron: Piñón-Nolina, Piñón-Juniperus y Piñón-Pinus pseudostrobus; los taxones Pinus cembroides subsp. orizabensis y Nolina parviflora fueron constantes en todas las localidades. La composición florística de estos bosques se relacionó principalmente con los factores edáficos Ca y N.
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