La terapia farmacológica contra el cáncer está registrando grandes avances. La última novedad en este campo son unas nanopartículas que portan fármacos antitumorales y que pueden ser dirigidas a voluntad del médico a través del torrente circulatorio.

Los responsables de este hallazgo han sido científicos del Instituto de Tecnología de Massachusetts (MIT), dirigidos por la doctora Sangeeta Bhatia. Estos expertos explican en la revista “Advanded Materials” que las nanopartículas se dirigen por “control remoto” hacia el tejido tumoral para liberar, una vez allí y en el momento elegido por los médicos, los fármacos que portan, de forma que actúan en el lugar preciso y en la dosis elegida, minimizando los efectos adversos para el resto del organismo.

Anteriormente, el equipo de la doctora Bathia había desarrollado nanopartículas con propiedades magnéticas que, una vez inyectadas en el caudal circulatorio, podían ser dirigidas a voluntad hasta concentrarse en torno a las células tumorales. Estas nanopartículas, cargadas con iones de hierro, facilitaban la visualización del tumor con imágenes de resonancia magnética.

Ahora, los científicos estadounidenses han ido un poco más allá y han logrado que estas mismas nanopartículas lleven incorporados fármacos antitumorales -en forma de moléculas activas- por medio de dos “hebras” de ADN unidas por enlaces de hidrógeno. Una vez que se han concentrado en el tejido tumoral, las nanopartículas son expuestas a un campo magnético de baja frecuencia generado en el exterior del cuerpo, de entre 350 y 400 kilohercios. Estas ondas atraviesan los tejidos sin causar daño, y el calor generado en las nanopartículas provoca la rotura por fusión del enlace de hidrógeno que mantenía unidas las dos “hebras” de ADN, de manera que una de ellas queda adherida a la nanopartícula, mientras que la otra es liberada junto con las moléculas que actúan como fármacos.

Este hallazgo todavía está lejos de ser utilizado en humanos, pero en roedores ya ha sido probada su eficacia. El equipo del MIT implantó en un ratón de laboratorio un gen con las propiedades de un tumor. Luego hizo llegar hasta él un torrente de nanopartículas cargadas con fármacos anticancerígenos y aplicó, mediante una bobina eléctrica, impulsos magnéticos sobre la zona de actuación. Las medicinas quedaron liberadas y actuaron eficazmente sobre el tejido tumoral.

Un informe de la Academia de Ciencias Médicas de Reino Unido celebra la llegada de las nuevas terapias para la prevención y el tratamiento de las enfermedades mentales, y elige a sus favoritas entre las candidatas actuales. Los investigadores también encomiendan al Gobierno y a las compañías farmacéuticas la tarea de acelerar el proceso de descubrimiento de nuevos fármacos para la salud mental.

“El Gobierno británico gasta más de 15 millones de libras anuales (algo más de 19 millones de euros) en compensar los daños sociales y económicos relacionados con el abuso de sustancias y, sin embargo, hay muy pocos fármacos en desarrollo para tratar la adicción. Hay que animar tanto a los investigadores como a la industria farmacéutica a ver las “adicciones como un área terapéutica prioritaria y desarrollar más medicamentos innovadores”, recomienda.
 
La Academia de Ciencias Médicas de Gran Bretaña encomendó a un investigador de Cambridge, Gabriel Horn, la elaboración de un informe sobre los medicamentos psicoactivos. En este documento se señalan los candidatos “más prometedores” y se pide al Gobierno que facilite la innovación en esta área y que prevenga los malos usos. Asimismo, insta a la industria a descubrir pronto nuevos medicamentos en este campo.

El informe incluye lo que llama “un rápido repaso a las terapias actuales”, y recuerda que este tipo de tratamiento “cambia vidas” y que ampliar el abanico terapéutico lograría alcanzar a más pacientes. Con todo, también señala las limitaciones de los medicamentos actuales como barreras a superar. Por otro lado, según manifiesta el autor de este informe, las terapias moduladoras de las emociones son un buen ejemplo del prometedor enfoque cognitivo en el desarrollo de nuevos medicamentos.

Dos diferentes clases de antidepresivos comparten la habilidad de reducir la respuesta cerebral a las emociones. Al menos dos trabajos al respecto prueban que existen funciones cognitivas independientes de neurotransmisores concretos. Lo que esto significa, razona, es que “ahora es posible la aparición de nuevos antidepresivos, con efectos neuroquímicos completamente nuevos”. “El enfoque cognitivo puede ser particularmente útil para el desarrollo de fármacos para el control de la impulsividad”, se asegura en el informe.

Por otro lado, se recoge también la consideración de que los mecanismos cerebrales del control del comportamiento se conocen razonablemente bien gracias a los modelos animales de experimentación, en los que se puede probar el funcionamiento de estos tratamientos. “Lo que se requiere ahora es capacidad de trasladar esos hallazgos de los modelos animales a los pacientes, para permitir el desarrollo de nuevos medicamentos”.

Según Horn, en la actualidad hay notables mejoras en la comprensión de las adicciones, “con pruebas científicas de que las drogas más adictivas —y algunas conductas de patrón similar, como las ludopatías— ‘secuestran’ los circuitos neuronales de una región cerebral particular. No obstante, también expresa preocupación porque estas investigaciones no han dado como resultado mejores terapias contra las adicciones.

They scrutinised the responses of 27,000 50 to 69-year-old healthy male smokers to a questionnaire and found “greater total flavonoid intake was associated with decreased pancreatic cancer risk in participants randomised during the trial to placebo…”.

The findings, published in the March edition of Cancer Epidemiol Biomarkers, are backed by at least three cited studies including a Finnish cohort study involving more than 10,000 people that found reduced rates of pancreatic cancer in both sexes.

But the researchers suggested the effect may be compromised by smokers who may have been consuming supplemental A-tocopherol and/or B-carotene.

Flavonoids are components of plants that are especially concentrated in fruits and vegetables such as broccoli and other cruciferous vegetables, apples, beans and onions. They have been shown to have various benefits including cancer reduction, heart health and free radical (oxidation) control.

Functional beverages such as superfruit juices have risen to prominence on the back of their boosted antioxidant levels and high-antioxidant food supplements derived from sources such as flax have also become popular with consumers.

Flavonoid effects

The study examined, “the association between dietary intakes of total flavonoids, three flavonoid subgroups (flavonols, flavan-3-ols, and flavones), seven individual flavonoids (kaempferol, myricetin, quercetin, catechin, epicatechin, apigenin, and luteolin), and flavonoid-rich foods and development of exocrine pancreatic cancer in a prospective cohort of male smokers in Finland.”

With such a large sample many variables had to be accounted for and these included age; height, weight, and body mass index; education; place of living; self-reported history of diabetes mellitus, pancreatitis, gallstones, or peptic or duodenal ulcers; measured blood pressure; serum cholesterol; smoking habits; occupational and leisure physical activity; energy and alcohol intake; and energy-adjusted fat, saturated fat, carbohydrate, free sugar, fibre, h-carotene, calcium, folic acid, vitamin C, and vitamin E intake.

The researchers acknowledged this variation “could cause inaccurate risk estimates” but noted “the monotonic decreasing hazard ratios across flavonoid intake quartiles and the consistency of the reduced pancreatic cancer risk across individual flavonols and flavan-3-ols among participants in the placebo group would support that subjects were ranked robustly enough to observe associations.”

After adjustments were made for the above factors it was demonstrated there was a 64 per cent reduced pancreatic cancer risk for those with high total flavonoid intake, relative to low intake, particularly for the flavonol kaempferol and the flavan-3-ol catechin.

Inverse trends were observed for three individual myricetin, quercetin, and epicatechin. In the case of quercetin these results supported an Argentinian study that found raised quercetin intake had led to an increased incidence of pancreatic dysplastic foci in rats.

But the researchers noted animal studies in pancreatic cancer models backed their conclusions that high dietary intake of flavonols and flavan-3-ols could inhibit human pancreatic carcinogenesis.

Modus operandi

The researchers suggested flavonols and flavan-3-ols inhibit pancreatic carcinogenesis via various actions including inhibition of proliferation, cell cycle arrest, induction of apoptosis, promotion of differentiation, antioxidative activity, and inhibition of angiogenesis.

But they cautioned: “Our results should be considered with caution given the relative small number of cases in the placebo group and the lack of an established biological mechanism for the interaction that we observed.”

“Most pertinent, flavonoids can inhibit the activity of phase I enzymes and increase the activity of phase II enzymes,” they stated.

The researchers pointed out their conclusions were related to men and not necessarily applicable to non-smokers, women, and populations with high consumption of food supplements.

In the United States, pancreatic cancer is the fourth most common cause of cancer mortality. It led to 33,400 deaths among men and women in 2007.

 Researchers from Australia’s RMIT University and SGE International Pty Ltd, report that novel omega-3 polyunsaturated fatty acids extracts from the green-lipped mussel (Perna canaliculus) inhibited leukotriene and cyclo-oxygenase (COX) activity, both of which are involved in the inflammatory process.

Chronic inflammation, brought about by an over-expression or lack of control of the normal protective mechanism, has been linked to range of conditions linked to heart disease, osteoporosis, cognitive decline and Alzheimer’s, and type-2 diabetes.

The studies, published in consecutive issues of the journal Comparative Biochemistry and Physiology, Part B, looked at both commercial (Lyprinol) and super-critical carbon dioxide (CO2) extracts from the mussel, on both COX and leukotriene levels in vitro. 

The first study reports that lipid extracts from the green-lipped mussel and Mytilusedulis (blue mussel) moderately inhibited COX-1 and COX-2 pure enzymes in vitro. The Lyprinol commercial extract also exhibited strong inhibition of COX-1 and COX-2, wrote the researchers, with the free fatty acid and triglyceride fractions identified as the active anti-inflammatory compounds.

Hydrolysis of the extracts using potassium hydroxide or protease enzymes increased COX inhibition by up to ten-fold said the researchers.

“These results support the use of the commercial mussel extracts, in particular Lyprinol, as an alternative for conventional [non-steroidal anti-inflammatory drugs] NSAIDs and fish oil treatment in the relief of the symptoms of arthritis,” concluded the researchers.

The second study extracted and isolated the free fatty acid fraction from the mussel and identified novel omega 3 polyunsaturated fatty acids (ω-3 PUFA), thought to originate from the algae and other micro organisms unique to New Zealand waters.

Using supercritical CO2 extraction, followed by normal phase chromatography, followed by reversed-phase high performance liquid chromatography (RP-HPLC), the researchers identified the most bioactive fractions as C18:4, C19:4, C20:4, and C21:5.

“The C20:4 was the predominant PUFA in the extract, and was a structural isomer of arachidonic acid (AA),” wrote the researchers. “The novel compounds may be biologically significant as [anti-inflammatory] AI agents, as a result of their in vitro inhibition of lipoxygenase products of the AA pathway.“

The prostaglandins derived from omega-3 fatty acids are said to be anti-inflammatory, while prostaglandins derived from omega-6 fatty acids, like AA, are proposed to be pro-inflammatory.

“The inflammatory precursor AA is an ω-6 PUFA of 20 carbons in length and has 4 unsaturated double bonds (positions 5, 8, 11 and 14) with each double bond being separated by one methylene group,” explained the researchers.

“The predominant bioactive PUFA of P. canaliculus identified in this study is similar to AA in that it also possesses 20 carbons with four double bonds. However, the first double bond is located at the seventh position, and the second double bond is interrupted from the first by two methylene groups resulting in the double bonds at positions 7, 11, 14 and 17.

“The interrupted bond positioning of these structural analogues of AA may account for their AI behaviour, by competitively inhibiting the active site of enzymes which use AA as a substrate, i.e., LO and COX, thereby reducing the production of leukotriene (LT) and prostaglandin (PG) metabolites,” they said.

The NZ green lipped mussel, ranked among the top ‘eco-friendly seafoods’ according to the US environmental agency Blue Ocean Institute’s list, is already used a source of nutraceuticals.

The extract, a rich source of iron, betain, and glycoaminoglycans (including chondroitin sulphate) has gained a reputation amongst consumers as a natural product with anti-inflammatory properties – an effect that has been attributed to a body of science to its lipid factions.

The Greenshell, Green Lips and Greenback mussel trademarks are owned by the New Zealand Mussel Industry Council (NZMIC).

The majority of green-lipped mussel extract suppliers offer material that retains, to a greater or lesser degree of standardisation, the mussels’ natural nutrient profile.

There are also a small number of products that contain high levels of stabilised lipids, such as Lyprinol marketed by Pharmalink, which is said to be “125 times more potent than the original freeze dried mussel powder.”

However, a broad range of processes and different efficacies can be found amongst green lipped mussel extracts, and while the NZMIC is aware of this the onus is said to be very much on the industry to pull together and set standards.