Avance de la ciencia israelí en la lucha contra el cáncer: primera bio-impresión en 3D de un tumor viable

Prof. Ronit Satchi-Fainaro-impresión-tumor-en-3D
Prof. Ronit Satchi-Fainaro-impresión-tumor-en-3D

Un logro científico para los investigadores en la Universidad de Tel Aviv: la impresión de un tumor completo, activo y viable de tipo glioblastoma utilizando una impresora 3D. El tumor bio-impreso en 3D incluye un complejo sistema de tubos que asemejan los vasos sanguíneos a través de los cuales pueden fluir células sanguíneas y medicamentos, simulando un tumor real.

El estudio fue liderado por Prof. Ronit Satchi-Fainaro, Facultad Sackler de Medicina y Escuela Sagol de Neurociencia. Además es Directora del Centro de Investigación Biológica de Cáncer. Jefa del Laboratorio de Investigación de Cáncer y Nanomedicina y Directora de la Iniciativa Morris Kahn de Bio-impresión 3D para la investigación del cáncer, en la Universidad de Tel Aviv.

La nueva tecnología fue desarrollada por la estudiante de PhD Lena Neufeld junto a otros investigadores en el laboratorio de la Prof. Satchi-Fainaro: Eilam Yeini, Noa Reisman, Yael Shtilerman, Dr. Dikla Ben-Shushan, Sabina Pozzi, Dr. Galia Tiram, Dr. Anat Eldar-Boock y Dr. Shiran Farber.

Los modelos bio-impresos en 3D están basados en muestras de pacientes extraídas directamente de los quirófanos del departamento de neurocirugía del Centro Médico Sourasky de Tel Aviv. Los resultados del nuevo estudio fueron publicados en la prestigiosa revista Science Advances.

“Glioblastoma es el cáncer más letal del sistema nervioso central, y es responsable de la mayoría de las neoplasias malignas del cerebro”, dijo Prof. Satchi-Fainaro. “En un estudio previo identificamos una proteína llamada P-Selectin, que se produce cuando células cancerosas del glioblastoma se encuentra con microglía – células del sistema inmune cerebral.

Leer más: Dispositivo israelí detecta cáncer de cuello uterino

Nosotros descubrimos que esta proteína es responsable de una falla en la microglía, que hace que apoyen a las células cancerosas en lugar de atacarlas, ayudando a que el cáncer se propague. Sin embargo, identificamos esta proteína en tumores extraídos durante cirugías, pero no en células de glioblastoma que fueron cultivadas en placas de Petri 2D en nuestro laboratorio. Esto debido a que el cáncer, al igual que todos los tejidos, se comporta muy diferente en una superficie plástica que en el cuerpo humano. Aproximadamente 90% de todas las medicinas experimentales fallan en las etapas clínica porque los éxitos alcanzados en el laboratorio no se replican en los pacientes”.

Para abordar este problema, el equipo de investigación liderado por Prof. Satchi-Fainaro y la estudiante de PhD Lena Neufeld, receptora de la prestigiosa beca Dan David Fellowship, creó el primer modelo bio-impreso en 3D de un tumor de glioblastoma, que incluye tejido canceroso en 3D rodeado de matriz extracelular, que se comunica con su microambiente y vasos sanguíneos funcionales.

Leer más: Un estudio en Israel señala que el Covid-19 afecta emocionalmente más a las mujeres que a los hombres

«No son solo las células cancerosas”, explica Prof. Satchi-Fainaro. “Son también las células del microambiente en el cerebro; los astrocitos, microglía, y los vasos sanguíneos conectados a un sistema de microfluidos. Es decir, un sistema que nos permite administrar sustancias como células sanguíneas y medicinas a la réplica del tumor. Cada modelo es impreso en un biorreactor que diseñamos en el laboratorio. Utilizando un hidrogel muestreado y reproducido de la matriz extracelular tomada del paciente, simulando así el propio tejido.

Las propiedades físicas y mecánicas del cerebro son diferentes que las de otros órganos como la piel, los senos, o huesos. El tejido mamario se compone principalmente de grasa, el tejido óseo es más que nada calcio; cada tejido tiene sus propias propiedades que afectan el comportamiento de las células cancerosas y cómo responden a los medicamentos. Cultivar todos los tipos de cáncer en superficies de plástico idénticas no es una simulación óptima del entorno clínico”.

Tras imprimir exitosamente el tumor en 3D, la Prof. Satchi-Fainaro y sus colegas demostraron que, a diferencia de células cancerosas que crecen en placas de Petri, el modelo bio-impreso en 3D tiene el potencial de ser efectivo en la predicción rápida, sólida y reproducible del tratamiento más adecuado para un paciente específico.

Leer más: Infiltraciones: ¿si o no?. Por Dr. David Sznajderhaus

“Demostramos que nuestro modelo 3D es más adecuado para predecir la eficacia de un tratamiento, el descubrimiento de objetivos y el desarrollo de fármacos en tres formas diferentes. Primero, probamos una sustancia que inhibió la proteína que acabábamos de descubrir, P-Selectin, en cultivos de células de glioblastoma cultivadas en placas de Petri 2D, y no encontraron diferencias en la división celular y la migración entre las células tratadas y las células de control que no recibieron tratamiento.

Por el contrario, tanto en los modelos animales como en modelos bio-impresos en 3D, que sobreexpresan la proteína, pudimos retrasar el crecimiento e invasión de glioblastoma al bloquear la proteína P-Selectin. Este experimento nos mostró por qué los medicamentos potencialmente efectivos pocas veces llegan a la etapa clínica, simplemente porque fallan en modelos 2D, y viceversa: por qué fármacos considerados un gran éxito en el laboratorio, terminan fallando en ensayos clínicos”.

“Adicionalmente, colaborando con el laboratorio del Dr. Asaf Madi del Departamento de Patología de la Facultad de Medicina de la Univ. de Tel Aviv, realizamos la secuenciación genética de las células cancerosas cultivadas en el modelo bio-impreso en 3D y lo comparamos tanto con las células cancerosas cultivas en plástico 2D como con células cancerosas tomadas de pacientes. De esta forma demostramos una semejanza mucho mayor entre los tumores bio-impresos en 3D y las células de glioblastoma. Son derivadas del paciente que crecieron junto con las células del estroma cerebral en su entorno natural.

Con el tiempo, las células cancerosas cultivadas en plástico cambiaron considerablemente. Perdiendo cualquier semejanza a las células cancerosas en la muestra del tumor cerebral del paciente”.

Leer más: La tecnología israelí que permite chequear signos vitales con ver el celular

“La tercera prueba fue obtenida al medir la tasa de crecimiento del tumor. El glioblastoma es una enfermedad agresiva en parte porque es impredecible: cuando las células cancerosas heterogéneas se inyectan separadamente a modelos animales, el cáncer permanece latente en algunos, mientras que en otros se desarrolla un tumor activo rápidamente.

Esto tiene sentido ya que nosotros, como humanos, podemos morir pacíficamente de vejez sin siquiera saber que estábamos albergando tales tumores latentes. Sin embargo, en las placas en el laboratorio, todos los tumores crecen y se propagan al mismo ritmo. En nuestro tumor bio-impreso en 3D se mantiene la heterogeneidad y el desarrollo es similar al amplio espectro que vemos en pacientes o en modelos animales”.

Según Prof. Satchi-Fainaro, este enfoque innovador también permitirá el desarrollo de nuevos fármacos, así como el descubrimiento de nuevos objetivos farmacológicos – a un ritmo mucho mayor que hoy en día. Ojalá en el futuro esta tecnología pueda facilitar la medicina personalizada para los pacientes.

Leer más: COVID-19: Israel es el primer país del mundo en vacunar con la tercera dosis a mayores de 50 años

“Si tomamos una muestra del tejido del paciente, junto con su matriz extracelular, podemos bio-imprimir en 3D de esta muestra, 100 tumores pequeños y probar muchos fármacos diferentes en combinaciones variadas para descubrir el tratamiento óptimo para este tumor específico. Alternativamente, podemos probar varios compuestos en un tumor bio-impreso en 3D y decidir cuál es el más prometedor para seguir desarrollando e invertir en él como fármaco potencial.

Pero tal vez el aspecto más emocionante es encontrar nuevas proteínas y genes diana farmacológicos en las células cancerosas. Es una tarea muy difícil cuando el tumor está dentro del cerebro del paciente humano o el modelo animal. Nuestra innovación nos brinda acceso sin precedentes, sin límite de tiempo, a tumores 3D. Imitan mejor el escenario clínico permitiendo investigación óptima”.

El estudio fue financiado por la Morris Kahn Foundation, el Consejo Europeo de Investigación (ERC), el Fondo Israelí de Investigación del Cáncer (ICRF), la Asociación Israelí de Cáncer y la Fundación Israelí de Ciencia (ISF), y Check Point Software Technologies LTD.  

avance-de-la-ciencia-israeli-en-la-lucha-contra-el-cancer-primera-bio-impresion-en-3d-de-un-tumor-viable
avance-de-la-ciencia-israeli-en-la-lucha-contra-el-cancer-primera-bio-impresion-en-3d-de-un-tumor-viable
Equipo de investigación - Eilam Yeini- Prof. Satchi-Fainaro y Lena Neufeld.
Equipo de investigación – Eilam Yeini- Prof. Satchi-Fainaro y Lena Neufeld.

Crédito fotos: Universidad de Tel Aviv

979 COMENTARIOS

  1. Ԍreat web site. A lot of սseful informatіon here.
    I am sending it to some ƅuddies ans additionally sharing in delicious.
    Аnd naturally, thаnk yoᥙ to your effort!

  2. magnificent publish, very informative. I ponder why the
    other experts of this sector do not notice this. You must
    continue your writing. I’m sure, you’ve a great readers’ base already!

  3. Good day very cool blog!! Man .. Beautiful ..
    Amazing .. I’ll bookmark your blog and take the feeds also?
    I’m happy to seek out a lot of useful info right here within the post, we’d like work out
    more techniques on this regard, thank you for sharing.
    . . . . .

  4. Hi there! I know this is kinda off topic nevertheless I’d figured I’d ask.
    Would you be interested in trading links or maybe guest authoring a blog
    article or vice-versa? My site goes over a lot of the same
    subjects as yours and I feel we could greatly benefit from each other.
    If you happen to be interested feel free to send me an e-mail.
    I look forward to hearing from you! Awesome blog by the way!

  5. Thanks , I’ve recently been looking for info about this subject
    for ages and yours is the greatest I have discovered so far.

    But, what in regards to the bottom line? Are you certain in regards to the source?

  6. I am really loving the theme/design of your website.
    Do you ever run into any browser compatibility issues? A couple of my blog readers have complained about my site not operating
    correctly in Explorer but looks great in Chrome.
    Do you have any solutions to help fix this issue?

  7. I think that everything published was very logical.

    However, think on this, what if you added
    a little information? I ain’t saying your content is not good., however suppose you
    added something to possibly get a person’s attention? I mean Otro avance de la ciencia
    israelí en la lucha contra el cáncer is kinda plain. You
    could glance at Yahoo’s home page and see how they create
    news titles to grab viewers to click. You
    might add a related video or a picture or two to grab people excited about what you’ve written. In my opinion, it would bring your posts a little livelier.

  8. Hello There. I found your blog using msn. This is a very well written article. I will be sure to bookmark it and come back to read more of your useful information. Thanks for the post. I’ll definitely return.

  9. Hi! This is my first visit to your blog! We are a team of volunteers and starting a new
    initiative in a community in the same niche. Your blog provided us useful information to work on. You
    have done a marvellous job!

  10. Hello there, just became alert to your blog
    through Google, and found that it is really informative.
    I am going to watch out for brussels. I’ll be grateful if you continue this in future.
    A lot of people will be benefited from your writing.
    Cheers!

  11. Excellent post. I was checking continuously
    this blog and I am impressed! Very helpful information specially the last part 🙂 I care for such info much.

    I was seeking this certain info for a long time. Thank you and best of luck.

  12. Having read this I thought it was extremely informative.
    I appreciate you taking the time and energy to put this short article together.

    I once again find myself spending a significant amount of
    time both reading and leaving comments. But so what, it was still worth
    it!

  13. My developer is trying to convince me to move to .net from PHP.
    I have always disliked the idea because of the costs.
    But he’s tryiong none the less. I’ve been using WordPress on several websites for about
    a year and am nervous about switching to another platform.
    I have heard very good things about blogengine.net. Is there a way I can transfer all my wordpress posts into it?
    Any help would be greatly appreciated!

  14. naturally like your web site however you have to take a look at the spelling
    on quite a few of your posts. A number of them are rife with
    spelling problems and I to find it very troublesome
    to tell the reality however I’ll certainly come again again.

  15. Its such as you read my mind! You appear to understand a lot about this, such as you wrote the e-book in it or something.
    I believe that you simply can do with some % to force the message
    home a bit, but other than that, this is fantastic blog.
    An excellent read. I will certainly be back.

  16. My brother suggested I might like this web site. He used to be entirely right.
    This put up actually made my day. You can not consider just how a lot time I had
    spent for this information! Thank you!

  17. Hey there! I know this is kinda off topic but I was wondering which blog platform are you
    using for this site? I’m getting sick and tired of
    Wordpress because I’ve had problems with hackers and I’m looking at options for
    another platform. I would be great if you could point
    me in the direction of a good platform.

  18. Superb post however , I was wondering if you could write a litte more on this subject?
    I’d be very grateful if you could elaborate a little bit more.
    Kudos!

  19. Excellent goods from you, man. I have understand your stuff previous
    to and you’re just too excellent. I actually like what you’ve acquired here, certainly
    like what you’re stating and the way in which you say it.
    You make it enjoyable and you still care for to keep it sensible.
    I can not wait to read far more from you. This is really a
    terrific website.

  20. I really love your site.. Great colors & theme. Did you make this web
    site yourself? Please reply back as I’m looking
    to create my own personal blog and would love to learn where you got this from or just what the theme is named.
    Thank you!

  21. I am extremely inspired together with your writing skills and also with
    the layout on your weblog. Is this a paid subject matter
    or did you modify it yourself? Either way stay up the excellent quality writing,
    it’s uncommon to look a great weblog like this one today..

  22. I was extremely pleased to find this page.
    I wanted to thank you for ones time for this wonderful read!!
    I definitely liked every bit of it and i also have you
    saved as a favorite to look at new things on your blog.

  23. I’m pretty pleased to find this site. I wanted to thank
    you for your time just for this fantastic read!! I definitely appreciated every bit of it and i also have you bookmarked to check out new things in your web site.

  24. Hi! I could have sworn I’ve visited this website before
    but after browsing through a few of the posts I realized it’s new
    to me. Regardless, I’m certainly delighted I
    came across it and I’ll be book-marking it and checking back frequently!

  25. Hey There. I found your blog using msn. This is an extremely well written article.

    I will make sure to bookmark it and come back to read more of your useful information. Thanks for the post.
    I will certainly comeback.

  26. Hello, Neat post. There is a problem along with your website
    in web explorer, would test this? IE nonetheless is the marketplace chief and a big component of folks will pass over
    your fantastic writing because of this problem.

  27. Hmm it seems like your blog ate my first comment (it was extremely long)
    so I guess I’ll just sum it up what I wrote and say, I’m thoroughly enjoying your blog.
    I too am an aspiring blog writer but I’m still new to everything.
    Do you have any points for inexperienced blog writers?
    I’d definitely appreciate it.

  28. First off I would like to say excellent blog!

    I had a quick question which I’d like to ask if you don’t mind.
    I was curious to know how you center yourself and clear your head before writing.
    I’ve had trouble clearing my mind in getting my thoughts out.
    I truly do take pleasure in writing but it just seems like the first 10 to
    15 minutes are generally wasted simply just trying to figure out how to begin. Any suggestions or hints?
    Appreciate it!

  29. Hello i am kavin, its my first occasion to commenting anyplace,
    when i read this article i thought i could also make comment due to this sensible paragraph.

  30. Hmm is anyone else experiencing problems with the
    images on this blog loading? I’m trying to determine if its a problem on my end or if it’s the blog.
    Any feedback would be greatly appreciated.

  31. What’s Taking place i am new to this, I stumbled upon this I have found It positively useful and
    it has aided me out loads. I hope to give a contribution & assist different users like its
    helped me. Great job.

  32. I got this web page from my pal who shared with
    me about this web page and at the moment this time I am browsing this website and reading very informative articles or reviews here.

  33. I am extremely impressed with your writing skills and also with the layout on your blog.

    Is this a paid theme or did you customize it yourself?
    Anyway keep up the excellent quality writing, it’s rare to see a nice blog
    like this one today.

  34. Hello there! This article couldn’t be written any better!
    Looking at this article reminds me of my previous roommate!
    He always kept talking about this. I most certainly will forward this post to him.
    Fairly certain he will have a very good read. Thanks for sharing!

  35. Thanks for some other excellent post. Where else could anyone get that kind of info in such an ideal way of writing?
    I’ve a presentation subsequent week, and I am at the look for such information.

  36. I was wondering if you ever considered changing the page layout of your site?

    Its very well written; I love what youve got to
    say. But maybe you could a little more in the
    way of content so people could connect with it better.

    Youve got an awful lot of text for only having 1 or two images.

    Maybe you could space it out better?

  37. Hey I am so grateful I found your site, I really found you by
    accident, while I was browsing on Google for something
    else, Nonetheless I am here now and would just like to say kudos for a marvelous post
    and a all round thrilling blog (I also love the theme/design), I don’t
    have time to read through it all at the moment but I have
    bookmarked it and also included your RSS feeds, so when I have time I will be back to read
    a great deal more, Please do keep up the great b.

  38. You really make it seem so easy with your presentation but I find this matter to be actually something which I think I
    would never understand. It seems too complicated and extremely broad for me.

    I’m looking forward for your next post, I will try to get the
    hang of it!

  39. We’re a bunch of volunteers and starting a new scheme in our community.
    Your website offered us with valuable information to work on. You have performed a formidable
    activity and our entire group will probably be grateful to you.

  40. This is the right blog for anyone who hopes to find out about this topic.
    You know a whole lot its almost tough to argue with you
    (not that I personally would want to…HaHa). You definitely put a brand new spin on a topic
    which has been written about for ages. Great stuff, just wonderful!

  41. Howdy very cool blog!! Guy .. Excellent .. Wonderful ..

    I will bookmark your site and take the feeds additionally?
    I am glad to seek out numerous useful information right here in the post, we want
    work out more strategies in this regard, thank you for
    sharing. . . . . .

  42. What’s Taking place i am new to this, I stumbled upon this I’ve discovered
    It absolutely helpful and it has aided me out loads.
    I hope to contribute & help different customers like its helped me.
    Great job.

  43. Hey I am so delighted I found your website, I really found you by error, while I was researching on Bing for something else, Anyways I am here now and would just like to say thank you for a incredible post and
    a all round interesting blog (I also love the
    theme/design), I don’t have time to look over it all at the moment but I have bookmarked it and also added in your RSS feeds, so when I have time I will be back to read much more, Please do keep up the fantastic work.

  44. I got this web site from my buddy who shared with me regarding this website and at the moment this time I am visiting this website and reading very informative articles or reviews at this
    place.

  45. Hey There. I discovered your weblog the usage of msn. That is a really neatly written article.
    I will be sure to bookmark it and return to
    learn more of your helpful info. Thanks for the post.
    I will definitely return.

  46. I’m really enjoying the design and layout of your
    site. It’s a very easy on the eyes which makes it much more
    enjoyable for me to come here and visit more often. Did you hire out a designer to create your theme?
    Exceptional work!

  47. I am really loving the theme/design of your website.
    Do you ever run into any web browser compatibility problems?
    A small number of my blog audience have complained about my site not
    operating correctly in Explorer but looks great in Opera.
    Do you have any recommendations to help fix this problem?

  48. Hey I know this is off topic but I was wondering
    if you knew of any widgets I could add to my blog
    that automatically tweet my newest twitter updates.

    I’ve been looking for a plug-in like this for quite some time and was hoping maybe you would have some experience with something like this.
    Please let me know if you run into anything.
    I truly enjoy reading your blog and I look forward to
    your new updates.

  49. I was wondering if you ever considered changing the page layout of your site?
    Its very well written; I love what youve got to say.

    But maybe you could a little more in the way of content
    so people could connect with it better. Youve got an awful
    lot of text for only having 1 or two images. Maybe you could space
    it out better?

  50. Somebody necessarily lend a hand to make significantly
    articles I’d state. This is the first time I frequented your website page and
    thus far? I surprised with the analysis you made to make this
    actual submit amazing. Fantastic task!

  51. Very nice post. I just stumbled upon your blog and wanted to
    say that I have really enjoyed surfing around your blog posts.

    In any case I’ll be subscribing to your feed and I hope you write again soon!

  52. Hi there! Quick question that’s entirely off topic.

    Do you know how to make your site mobile friendly? My web site looks weird when viewing
    from my iphone. I’m trying to find a template or plugin that might
    be able to fix this issue. If you have any suggestions, please share.
    Thanks!

  53. Hi there! I just would like to give you a huge thumbs up for your great information you’ve got right here on this post. I am returning to your blog for more soon.

  54. Hello my family member! I want to say that this post is amazing, nice written and include almost all important infos. I’d like to peer more posts like this .

  55. Though, only these who have Canadian on-line financial institution accounts can be eligible. One should maintain on his excitement and not show it to others. It’s very best to try and make this as conversational as possible.

  56. Nice post. I was checking constantly this blog and I am impressed! Extremely helpful info specifically the last part I care for such information a lot. I was seeking this particular information for a very long time. Thank you and best of luck.

  57. Thanks, I’ve just been searching for info about this subject for a long time and yours is the best I’ve found out till now. However, what about the conclusion? Are you sure in regards to the source?

  58. Hello there, just became alert to your blog through Google, andfound that it’s truly informative. I’m going to watchout for brussels. I will be grateful if you continue this in future.Numerous people will be benefited from your writing. Cheers!

  59. I do trust all of the ideas you have presented in your post. They’re really convincing and will definitely work. Nonetheless, the posts are very brief for newbies. May you please extend them a little from next time? Thanks for the post.

  60. I will immediately grab your rss feed as I can not to find your email subscription link or e-newsletter service. Do you have any? Kindly allow me realize in order that I may just subscribe. Thanks.

  61. Wie konfiguriere ich einen Grid Trading Bot? 1. Wählen Jeneeine Münze aus, die Sie via Grid-Bot verwenden möchten. 2.Ändern Sie den Parameter manuell oder mit Hilfestellungeines KI-Beraters. 4.

  62. Hi there! I just wanted to ask if you ever have any problems with hackers? My last blog (wordpress) was hacked and I ended up losing many months of hard work due to no backup. Do you have any solutions to stop hackers?

  63. Very interesting topic , thankyou for posting . «The maxim of the British people is ‘Business as Usual.'» by Sir Winston Leonard Spenser Churchill.

  64. I like the valuable info you provide in your articles. I will bookmark your blog and check again here regularly. I’m quite sure I will learn many new stuff right here! Good luck for the next!

  65. When I initially commented I clicked the « Notify me when new comments are added » checkbox and now each time a comment is added I get three e-mails with the same comment. Is there any way you can remove me from that service? Appreciate it!

  66. Asking questions are actually nice thing if you are notunderstanding something entirely, except this piece of writing providespleasant understanding yet.

  67. Good way of describing, and fastidious piece ofwriting to take information concerning my presentation topic, which i am goingto convey in school.

  68. I enjoy what you guys are up too. This type of clever work and coverage! Keep up the good works guys I’ve added you guys to our blogroll.

  69. Thanks for another magnificent post. Where else could anybody get that kind of information in such a perfect way of writing? I have a presentation next week, and I’m on the look for such info.

  70. Heya! I just wanted to ask if you ever have any trouble withhackers? My last blog (wordpress) was hacked andI ended up losing many months of hard work due to no backup.Do you have any solutions to protect against hackers?

  71. Thank you, I’ve just been looking for information approximately this subject for a long time and yours is the greatest I have came upon so far. But, what about the bottom line? Are you positive about the source?

  72. Hello my friend! I wish to say that this post is amazing,great written and come with almost all vital infos.I would like to look more posts like this .

  73. I will right away grasp your rss feed as I can not find your email subscription hyperlink or e-newsletter service. Do you’ve any? Kindly let me recognize in order that I could subscribe. Thanks.

  74. Awesome issues here. I am very satisfied to look your article.Thanks a lot and I’m taking a look forward to touch you.Will you kindly drop me a e-mail?

  75. always i used to read smaller content which as well clear their motive, and that is also happening with this paragraph which I am reading at this time. emma hardie sverige greas.wommmewt.com/decorations/emma-hardie-sverige.php

  76. Wow loads of very good advice.essay help sydney dissertations writing help for students

  77. Touche. Sound arguments. Keep up the great spirit.Feel free to surf to my blog post: 888ad.cn

  78. Hello. magnificent job. I did not imagine this. This is a excellent story. Thanks!

  79. whoah this blog is great i like reading your posts.Keep up the great work! You know, many individuals are searching round for this info, you can help them greatly.

  80. ผมถูกอกถูกใจเล่นกับ UFABET ระบบเยี่ยม ถูกอกถูกใจสุดน่าจะเป็นระบบฝากถอนแบบอัตโนมัติ ไม่มีขั้นต่ำ เนื่องจากคราวที่ผ่านมาผมเคยเล่นเว็บไซต์อื่นเวลาฝากก็จำเป็นต้องแจ้งพนักงานตอนถอนก็จำต้องแจ้งบุคลากร ถ่วงเวลาเสียอารมณ์ จริงๆครับ

  81. submit is just great and that i can suppose you are a professional on this subject.

  82. wonderful points altogether, you just won a new reader. What would you recommend about your post that you made some days ago? Any sure?

  83. I’m really impressed with your writing skills as well as with the layout on your blog. Is this a paid theme or did you customize it yourself? Either way keep up the excellent quality writing, it is rare to see a great blog like this one today..

  84. Howdy! I could have sworn Iíve been to your blog before but after looking at some of the articles I realized itís new to me. Nonetheless, Iím certainly pleased I found it and Iíll be book-marking it and checking back often!

  85. I like what you guys are up too. Such clever work and exposure! Keep up the great works guys I’ve added you guys to our blogroll.

  86. It’s going to be finish of mine day, except before finish I am reading this great post to increase my experience.

  87. An interesting discussion is worth comment. I think that you should publish more on this subject, it may not be a taboo subject but typically people do not talkabout these issues. To the next! Kind regards!!

  88. It’s actually a great and useful piece of information. I’m satisfied that you shared this useful information with us. Please keep us up to date like this. Thanks for sharing.

  89. Thanks on your marvelous posting! I genuinely enjoyed reading it, you can be a great author.I will remember to bookmark your blog and will often come back later in life. I want to encourage continue your great posts, have a nice morning!

  90. Hi there mates, how is everything, and what you would like to sayregarding this piece of writing, in my view its genuinely amazing in favor of me.0mniartist asmr

  91. Now I am going to do my breakfast, after having my breakfast coming yet again to read further news.Feel free to visit my blog post :: Keto Total BHB Review

  92. Thank you, I have recently been searching for info approximately this subject for ages and yours is the best I’ve found out till now. But, what about the bottom line? Are you certain in regards to the source?

  93. Hi, I do believe this is a great blog. I stumbledupon it I’m going to return yet again since I bookmarked it. Money and freedom is the greatest way to change, may you be rich and continue to help other people.

  94. Yes, I play the guitar tally ho playing cards near me The move has been welcomed by the Irish Cancer Society (ICS), which has been campaigning for this for several years

  95. Everyone loves what you guys tend to be up too. This sort of clever work and reporting!Keep up the excellent works guys I’ve added youguys to my own blogroll.

  96. Excellent post. I was checking constantly this blog andI’m impressed! Extremely useful information specially the last part Icare for such information a lot. I was looking for thiscertain information for a long time. Thank you andgood luck.

  97. Heya! I’m at work surfing around your blog from my new iphone 3gs!Just wanted to say I love reading through your blog and look forward to all your posts!Keep up the superb work!

  98. That is a really good tip particularly to those new to the blogosphere. Short but very accurate infoÖ Thanks for sharing this one. A must read article!

  99. magnificent post, very informative. I wonder why the otherexperts of this sector don’t realize this. Youshould proceed your writing. I’m confident, you have agreat readers’ base already!

  100. Hmm is anyone else experiencing problems with the pictures on this blog loading?I’m trying to figure out if its a problem on myend or if it’s the blog. Any suggestions would be greatly appreciated.

  101. fantastic points altogether, you simply gained a new reader. What may you suggest in regards to your publish that you simply made some days ago? Any sure?

  102. I simply want to say I am just newbie to blogging and site-building and definitely savored this website. Very likely I’m planning to bookmark your site .
    You surely come with outstanding well written articles.«밤부» Thanks a bunch for revealing your website page.
    I really enjoy reading through on this site, it has got fantastic articles .
    Literature is the orchestration of platitudes

  103. It’s going to be ending of mine day, but before ending I amreading this impressive piece of writing to increase my experience.My blog post: cleveland clinic diet

  104. I do not even know the way I stopped up right here, however I believedthis submit was once great. I do not understandwho you’re however certainly you’re going to a well-known blogger ifyou happen to are not already. Cheers!

  105. Where do you study? levothyroxine 88 mcg side effects We’re more than capable of being the best defensive team in the league, but we’ve got to focus on it every game.»

  106. I’ll right away clutch your rss as I can’t to find your email subscription hyperlink or e-newsletterservice. Do you have any? Kindly let me know in order that I could subscribe.Thanks.

  107. It’s an awesome paragraph in support of all the internet viewers; they will take advantage from it I am sure.

  108. Aw, this was an exceptionally good post. Spending some time and actual effort to generate a top notch article… but what can I say… I put things off a lot and never seem to get anything done.

  109. A fascinating discussion is definitely worth comment. I do believe that you should publish more about this subject matter, it might not be a taboo subject but typically people don’t discuss these issues. To the next! Many thanks.

  110. Right now it appears like WordPress is the top blogging platform out there right now.(from what I’ve read) Is that what you are using on your blog?

  111. Riot Games, RP fiyatları konusunda sahip olduğu sayfadan satış gerçekleştirirken fiyatları bir hayli pahalı tutuyor.lol codes free rp 2021 League of Legends Riot Pointslol codes free rp

  112. I do not even know how I ended up right here, but I thought this post used to be good. I do not understand who you’re but definitely you are going to a well-known blogger if you happen to aren’t already. Cheers!

  113. When I originally commented I clicked the «Notify me when new comments are added» checkbox and now each time a comment is added I get three e-mails with the same comment. Is there any way you can remove me from that service? Appreciate it!

  114. Hey There. I found your blog using msn. This is a very well written article. I?ll make sure to bookmark it and return to read more of your useful information. Thanks for the post. I will certainly comeback.

  115. An intriguing discussion is worth comment. There’s no doubt that that youshould write more about this subject matter, it maynot be a taboo matter but generally people don’t discuss these issues.To the next! All the best!!

  116. Hey just wanted to give you a quick heads up and let you know afew of the pictures aren’t loading correctly. I’m not sure why but I think its alinking issue. I’ve tried it in two different browsers and both show the same outcome.

  117. Hello! I’ve been following your blog for some time now and finally got the bravery to go ahead and give you a shout out from Humble Tx! Just wanted to tell you keep up the good work!

  118. I wanted to thank you for this wonderful read!! I certainly enjoyed every little bit of it.I’ve got you saved as a favorite to look at new stuff you

  119. hello!,I love your writing very so much! percentage we keep up a correspondence extra approximately your article on AOL? I need an expert in this house to solve my problem. Maybe that is you! Looking forward to see you.

  120. Thank you, I have just been looking for information approximately this subject for a while and yours is the greatest I have discovered so far. However, what concerning the bottom line? Are you sure concerning the source?

  121. Good day! This post could not be written any better! Reading through this post reminds me of my good old room mate!He always kept talking about this. I will forward this write-up to him.Fairly certain he will have a good read. Thank youfor sharing!

  122. Hey there! I’m at work browsing your blog from my newapple iphone! Just wanted to say I love reading through your blog and look forward to all your posts!Carry on the great work!

  123. Wonderful blog! I found it while browsing on Yahoo News. Do you have any tips on how to get listed in Yahoo News? I ave been trying for a while but I never seem to get there! Appreciate it

  124. Hi, I do believe this is an excellent blog. I stumbledupon it I am going to return once again since i have book-marked it. Money and freedom is the greatest way to change, may you be rich and continue to guide other people.

  125. Thanks for your personal marvelous posting!I truly enjoyed reading it, you could be a great author.I will make certain to bookmark your blog and may come back sometime soon.I want to encourage one to continue your great work, have a nice day!

  126. Arguably the most effective OnlyFans to obtain, Hannah knows howFree Onlyfans Accounts 2021 Account Login And Passwordonlyfans free account

  127. Pretty section of content. I just stumbled upon your blog and in accession capital to assert that I acquire actually enjoyed account your blog posts. Any way I’ll be subscribing to your feeds and even I achievement you access consistently fast.

  128. Hey! I know this is somewhat off topic but I was wondering if you knew where I could geta captcha plugin for my comment form? I’m using the same blog platformas yours and I’m having problems finding one? Thanks a lot!

  129. This is a good tip particularly to those new to the blogosphere. Short but very accurate infoÖ Thank you for sharing this one. A must read article!

  130. fantastic issues altogether, you simply receiveda logo new reader. What could you recommend in regards to your post that you simply made some days in the past?Any positive?

  131. That is a really good tip especially to those new to the blogosphere. Simple but very accurate info… Appreciate your sharing this one. A must read post!

  132. Your style is really unique compared to other people I have read stuff from. Thank you for posting when you have the opportunity, Guess I will just bookmark this blog.

  133. แทงบอลยังไงให้ได้เงิน พนันบอลชนะยังไงไม่ถูกฉ้อโกง UFABET จ่ายจริงจ่ายไม่ยั้งระบบเข้าใจง่าย แค่เพียงคลิกสมัครก็ทำเงินได้ไม่ยากกับคาสิโนออนไลน์ สบายสุดๆชีวิตชิวๆชีวิตคลูๆทำเงิน สร้างกำไรสบายๆจำเป็นต้องที่ UFABET

  134. It is truly a great and useful piece of info. I am satisfied that you just shared this useful info with us. Please stay us informed like this. Thank you for sharing.

  135. I’ll immediately grasp your rss as I can not in finding your email subscription hyperlink or e-newsletter service. Do you have any? Kindly permit me recognise in order that I may just subscribe. Thanks.

  136. Excellent read, I just passed this onto a friend who was doing a little research on that. And he actually bought me lunch since I found it for him smile Thus let me rephrase that: Thank you for lunch!

  137. These are genuinely great ideas in concerning blogging. You have touched some nice things here. Any way keep up wrinting.

  138. Nice post. I was checking constantly this blog and I’m impressed! Extremely helpful information specifically the last part I care for such information a lot. I was seeking this certain info for a very long time. Thank you and good luck.

  139. essay helper online – help writing a research paper purchase essay online

  140. I do not even know how I ended up here, but I thought this post wasgreat. I do not know who you are but definitely you are going to a famous blogger if you are not already Cheers!

  141. Greetings! Veryy useful advvice inn thhis particular post!It iss tthe little changes thazt make thee greatesst changes.Thankms forr sharing!

  142. I wanted to thank you for this excellent read!! I definitely enjoyed every bit of it. I’ve got you bookmarked to look at new stuff you postÖ

  143. Thanks for picking out the time to discuss this, I feel great about it and love studying more on this topic. It is extremely helpful for me. Thanks for such a valuable help again.

  144. Hi! I’ve been following your blog for a longtime now and finally got the courage to go ahead and give you a shout outfrom Kingwood Tx! Just wanted to say keep up the fantastic work!

  145. I am now not sure where you’re getting your information, however great topic. I must spend some time studying much more or figuring out more. Thank you for magnificent info I used to be looking for this info for my mission.

  146. Eloisa Caughron says:Cheers for this excellent. I was wondering whether you were planning of publishing similar posts to this. .Keep up the excellent articles!Reply 04/09/2020 at 6:42 pm

  147. fantastic points altogether, you just received a new reader. What might you suggest about your post that you made a few days ago? Any sure?

  148. This very blog is really cool as well as amusing. I have discovered a bunch of helpful things out of it. I ad love to visit it every once in a while. Thanks a lot!

  149. An intriguing discussion is definitely worth comment. There’s no doubt that that you ought to write more about this topic, it may not be a taboo matter but usually people do not speak about such subjects. To the next! All the best!!

  150. It’s really a great and helpful piece of info. I’m glad that you shared this helpful info with us. Please keep us informed like this. Thanks for sharing.

  151. 33983 26025my English teacher hate me cause i keep writing about somebody from The WANTED called Jay, she gives me evils and low 960730

  152. This is a good tip especially to those new to the blogosphere. Simple but very precise informationÖ Thank you for sharing this one. A must read article!

  153. What’s Taking place i’m new to this, I stumbled upon thisI’ve found It positively useful and it has helped me out loads.I hope to contribute & aid other users like its helped me.Good job.

  154. I will right away seize your rss as I can not findyour email subscription hyperlink or newsletter service. Do you have any?Kindly let me recognize in order that I may subscribe. Thanks.

  155. Aw, this was a very good post. Finding the time and actual effort to produce a top notch articleÖ but what can I sayÖ I put things off a lot and never manage to get anything done.

  156. Hey just wanted to give you a quick heads up and letyou know a few of the pictures aren’t loading properly.I’m not sure why but I think its a linking issue.I’ve tried it in two different browsers and both showthe same outcome.

  157. Hello my friend! I want to say that this post is amazing,great written and include approximately all significantinfos. I would like to look extra posts like this .

  158. What’s Going down i’m new to this, I stumbled upon this I have found It positively useful andit has helped me out loads. I’m hoping to give a contribution & help other customers like its helped me.Great job.

  159. Excellent blog you’ve got here.. It’s difficult to find excellent writing like yours nowadays. I truly appreciate individuals like you! Take care!!

  160. This is a good tip particularly to those fresh to the blogosphere. Simple but very accurate information… Many thanks for sharing this one. A must read post!

  161. I’ll without delay snatch your rss as I cannot to locate youre-mail membership connection or e-newsletter support. Does one’ve any?Kindly allow me to acknowledge as a way which i might subscribe.Thanks.

  162. When someone writes an piece of writing he/she retains the plan of a user in his/her brain that how a user can know it. Thus that’s why this article is outstdanding. Thanks!

  163. I’ll right away grab your rss as I can’t find your email subscription hyperlink or newsletter service. Do you have any? Kindly permit me recognise in order that I may just subscribe. Thanks.

  164. Generally I don’t read article on blogs, but I would like to say that this write-up verycompelled me to try and do so! Your writing taste has been surprised me.Thank you, very great article.

  165. Aw, this was an incredibly nice post. Finding the time and actual effort to make a very good article… but what can I say… I put things off a whole lot and don’t seem to get nearly anything done.

  166. Howdy! This is my first visit to your blog! We are a collection of volunteers and starting a new project in a community in the same niche.Your blog provided us valuable information to work on. You have done amarvellous job!

  167. That is a really good tip especially to those fresh to the blogosphere. Short but very precise informationÖ Thank you for sharing this one. A must read article!

  168. スーパーコピーブランドHydroxypropyl Methyl Cellulose for Mortar QuotationPortable Dental Chair

  169. Thanks for another informative blog. The place else could I get that typeof info written in such a perfect means? I have a undertakingthat I am just now working on, and I have been at the look out for such info.

  170. The American Gaming Association stated in June 2017,that a coalition will advocate for the repeal of the UnitedStates’ sports betting ban.

  171. Aw, this was an exceptionally nice post. Spending some time and actualeffort to generate a really good article… but what can I say…I procrastinate a whole lot and don’t seem to get anything done.Also visit my blog post; tanglewood.sh

  172. Excellent post. I was checking constantly this blog and I am impressed! Very useful info specifically the last part I care for such info a lot. I was seeking this certain info for a very long time. Thank you and best of luck.

  173. Its really a great and useful piece of info. I am happy that you simply shared this useful information with us. Please keep us informed like this. Thank you for sharing.

  174. I enjoy, cause I discovered just what I used to be having a look for. You’ve ended my four day lengthy hunt! God Bless you man. Have a great day. Bye

  175. This is a good tip especially to those new to the blogosphere.Simple but very precise information? Many thanks for sharing this one.A must read post!Feel free to visit my blog post :: foods rich in omega 3 fatty acids

  176. Thanks for one’s marvelous posting! I actually enjoyed readingit, you could be a great author.I will be sure to bookmark your blog anddefinitely will come back at some point. I want to encourageone to continue your great posts, have a nice day!

  177. Hi there, just became alert to your blog through Google, and found that it’s really informative.I’m gonna watch out for brussels. I will be grateful if youcontinue this in future. A lot of people will be benefited from your writing.Cheers!

  178. Having read this I believed it was rather enlightening. I appreciate you spending some time and energy to put this content together. I once again find myself spending a lot of time both reading and commenting. But so what, it was still worthwhile!

  179. I blog frequently and I really appreciate your content. Your article has really peaked my interest. I will book mark your blog and keep checking for new information about once per week. I opted in for your RSS feed too.

  180. An interesting discussion is definitely worth comment.I believe that you need to publish more aboutthis topic, it might not be a taboo subject but generally people donot speak about such issues. To the next! Cheers!!

  181. 703220 815961Enjoyed reading by means of this, really very good stuff, thankyou . 28365

  182. I like the valuable info you provide in your articles. I’ll bookmark your blogand check again here frequently. I am quite sure I will learn lots ofnew stuff right here! Good luck for the next!

  183. That is a very good tip especially to those new tothe blogosphere. Simple but very accurate info… Thank you forsharing this one. A must read article!My blog post: anapa-alrosa.com.ru

  184. Howdy! I’m at work surfing around your blog from my new iphone 3gs! Just wanted to say I love reading through your blog and look forward to all your posts! Keep up the superb work!

  185. It’s going to be end of mine day, but before finish I am reading this wonderful post to increase my knowledge.

  186. That is a really good tip especially to those fresh to the blogosphere. Brief but very precise informationÖ Appreciate your sharing this one. A must read article!

  187. My brother suggested I might like this blog. He was entirely right.This post actually made my day. You can not imagine simply howmuch time I had spent for this information! Thanks!My blog: fb88

  188. I love what you guys are up too. This sort of clever work and exposure! Keep up the superb works guys I’ve included you guys to my personal blogroll.Loading…

  189. Howdy! Would you mind if I share your blog with my myspace group?There’s a lot of folks that I think would really enjoy your content.Please let me know. Thanks

  190. great submit, very informative. I’m wondering why the other experts of this sector do not notice this. You must continue your writing. I am confident, you have a great readers’ base already!

  191. I have not checked in here for some time because I thought it was getting boring, but the last few posts are good quality so I guess I¡¦ll add you back to my everyday bloglist. You deserve it my friend

  192. Thank you, I have recently been looking for info approximately this topic for ages and yours is the greatest I’ve found out so far. But, what in regards to the conclusion? Are you sure concerning the source?

  193. I’m now not certain where you are getting your information, however great topic. I needs to spend some time studying more or figuring out more. Thank you for wonderful information I was on the lookout for this information for my mission. firmonet

  194. what are the long term effects of taking hydrochlorothiazide? how long does hydrochlorothiazide take to work

  195. Fuuuuuuck, she screamed, a few seconds later, as an obvious orgasm cascaded through her.

  196. Fine way of telling, and fastidious piece of writing to obtain information concerning my presentation focus, whichi am going to present in school.

  197. I’ll immediately snatch your rss as I can’t in findingyour e-mail subscription link or e-newsletter service.Do you’ve any? Kindly permit me recognize so thatI could subscribe. Thanks.

  198. magnificent issues altogether, you just won a logo new reader. What might you suggest about your put up that you just made some days in the past? Any positive?

  199. I read this article completely on the topic oof the difference of latest andprevious technologies, it’s awesome article.Read this, trust me its awesom: Slot Online

  200. wonderful points altogether, you simply gained a brand new reader. What would you recommend about your post that you made some days ago? Any positive?

  201. Tremendous write-up! I truly were pleased with all of the browsing. I’m hoping to view far more of you. I believe that you’ve fabulous information into together with idea. My group is exceptionally empowered utilizing this information and facts.

  202. I’ll right away clutch your rss feed as I can’t in findingyour e-mail subscription hyperlink or newsletter service.Do you have any? Please allow me understand so that I may just subscribe.Thanks.

  203. เกมส์สล็อตออนไลน์มีจุดเด่นในการเล่นที่ใช้เงินน้อยแต่ได้เยอะเพราะในการเล่นสล็อตออนไลน์นั้นถ้าแจ็คพ็อตแตกขึ้นมาก็จะได้รับเงินรางวัลอย่างมหาศาล

  204. ivermectin human dosage ivermectin mechanism of action in scabiesdoes ivermectin kill tapeworms in dogs scaly leg mite treatment ivermectin

  205. Pretty nice post. I just stumbled upon your blog and wanted to say that I have really enjoyed browsing your blog posts. In any case I will be subscribing to your rss feed and I hope you write again very soon!

  206. An interesting discussion is definitely worth comment. I think that you should publish more about this topic, it might not be a taboo matter but generally folks don’t talk about such issues. To the next! Cheers!!

  207. nature is definately not expensive. go on a hike with friends, or just explore a forest. there are always creeks to walk thru and all kinds of colorful plants and flowers. even frisbee golf is fun, free, and good exercise

  208. always i used to read smaller articles that as well clear theirmotive, and that is also happening with this paragraph which Iam reading now.

  209. Thanks for finally writing about > Interdiction ventenouveau format de pain: une grève des boulangers en vue. – LA VALLEÉ INFO

  210. Thanks so much for the article post.Really looking forward to read more. Want more.

  211. SightCare clears out inflammation and nourishes the eye and brain cells, improving communication between both organs. Consequently, you should expect to see results in as little as six months if you combine this with other healthy habits.

  212. Kelvin Kaemingk has over two decades of helping people make smarter decisions regarding their mortgage and money decisions. He began his career in financial planning and migrated into the mortgage space in 2002. He is passionate and committed to helping people throughout their lives, make the best financial decisions for themselves and their families. As a father of three, and now Papa K (grandpa) to one, a team builder and recruiter, Kelvin thrives on helping others realize their potential, often referenced as “Everyone’s biggest fan”. Kelvin Kaemingk is the Area Manager for loanDepot and Co-Host of the Real Estate Chalk Talk radio program based in the Minneapolis – St. Paul area. Kelvin Kaemingk, NMLS 251124 | Branch NMLS 1139048

  213. It’s Time To Say Goodbye To All Your Bedroom Troubles And Enjoy The Ultimate Satisfaction And Give Her The Leg-shaking Orgasms. The Endopeak Is Your True Partner To Build Those Monster Powers In Your Manhood You Ever Craved For.. https://endopeakbuynow.us/

  214. My brother recommended I would possibly like this blog. He used to be totally right. This put up truly made my day. You cann’t believe just how a lot time I had spent for this information! Thank you!|

  215. FlowForce Max is an innovative, natural and effective way to address your prostate problems, while addressing your energy, libido, and vitality.

  216. Great blog here! Also your site loads up fast! What host are you using? Can I get your affiliate link to your host? I wish my web site loaded up as quickly as yours lol|

  217. Are you seeking for a way to feel better? Unlock the trusted source for health and wellness right here! All of your health issues and difficulties must be addressed using the key.

  218. Hi this is somewhat of off topic but I was wanting to know if blogs use WYSIWYG editors or if you have to manually code with HTML. I’m starting a blog soon but have no coding experience so I wanted to get advice from someone with experience. Any help would be enormously appreciated!|

  219. Nice post. I was checking continuously this blog and I’m impressed! Extremely useful info specifically the last part 🙂 I care for such info much. I was looking for this particular information for a long time. Thank you and good luck.|

  220. Good day! This is kind of off topic but I need some advice from an established blog. Is it difficult to set up your own blog? I’m not very techincal but I can figure things out pretty fast. I’m thinking about making my own but I’m not sure where to start. Do you have any ideas or suggestions? Appreciate it|

  221. You ought to take part in a contest for one of the most useful sites on the net. I am going to recommend this site!|

  222. Fast Lean Pro is a herbal supplement that tricks your brain into imagining that you’re fasting and helps you maintain a healthy weight no matter when or what you eat. It offers a novel approach to reducing fat accumulation and promoting long-term weight management. https://fastleanpro-web.com/

  223. I was recommended this web site by my cousin. I’m not sure whether this post is written by him as no one else know such detailed about my difficulty. You are amazing! Thanks!|

  224. Greetings from Florida! I’m bored to death at work so I decided to browse your blog on my iphone during lunch break. I really like the information you present here and can’t wait to take a look when I get home. I’m shocked at how quick your blog loaded on my mobile .. I’m not even using WIFI, just 3G .. Anyhow, great site!|

DEJAR UN COMENTARIO

Por favor ingrese su comentario!
Por favor ingrese su nombre aquí