Progesterone Antisense Oligonucleotides Inhibits Breast Cancer Growth
Hormone status of breast cancer
Breast cancer arises from the growth of an abnormal mass of cells across the breast tissues. When this tumor is examined, it may be sensitive to some female hormones like estrogen and progesterone. The cells in breast tumors have receptors for these hormones that specifically attract the hormone and circulate throughout the body helping the tumor to metastasize (Pourzand et al., 2011). Based on the status of hormones breast cancers can be divided into the following types.
Progesterone Receptor (PR) positive
When the breast cancer cells are sensitive to the progesterone hormone and by binding of this hormone to receptors on these cells, the growth of the tumor occurs. These tumors are classified as PR-positive. Endocrine therapy can be given to patients with PR-positive breast cancer for treatment.
Estrogen Receptor (ER) Positive
When the breast tumor cells have receptors specific for estrogen hormone, and binding of estrogen to these receptors helps the tumor to grow and metastasize, then these breast cancers are called ER-positive. The use of anti-estrogen therapy can be effective for the cure of patients having ER-positive breast cancer type.
Hormone Receptor (HR) negative
When the breast tumor cells don’t have any type of receptors specific for female hormones either estrogen or progesterone, then they are classified as HR negative. In this case, endocrine therapy is not effective.
Progesterone Receptor (PR)
PR is encoded by the PGR gene in humans. This gene is present on chromosome 11. PR is also termed NR3C3. This receptor is activated when a hormone called progesterone binds to it.
When progesterone binds to the PR, it is activated and enters the nucleus. Where it binds DNA and activates the transcription and translation of many proteins that are important components of many biological processes in the cells (Pourzand et al., 2011).
Progesterone Receptor (PR) mediated growth
Experimental findings have proved that Progesterone receptors PR and Epithelial growth factor EGF signaling have a deep link in accordance with the growth of breast tumors.
EGF causes the phosphorylation of Ser-294 in PR and activates it. It was found that when PR was induced in the cells the growth rate increased. Moreover, similar outcomes were seen when EGF was given. Then both PR and EGF were given to the breast cancer cell lines, and it was seen that the tumor growth increased exponentially. This shows that the serine residue in PR acts as a sensor that senses the growth factors and makes them functional in breast cancer cells. Moreover, this needs EFGR which will phosphorylate it. So, if EGF signaling is highly stimulated in the breast tissues, then PR will also be stimulated and ultimately tumor growth and progression occurs in the breast tissues.
It was observed in experiments on breast cancer cell lines that the translocation of PR into the nucleus is mediated by epithelial growth factor. This PR acts on those genes in the nucleus whose activation depends on the Ser-294 residue of the progesterone receptor. These are mostly growth factors. When the transcription and translation of these genes take place, these growth factors will increase the progression of breast cancer (Knutson & Lange, 2014).
Progestin Regulates Cellular Proliferation
The proliferation of cells depends on many signals that can be internal from within the cell or from the extracellular environments, that affect hormones and growth factors in the cell. These hormones and growth factors actually regulate the proliferation of normal and cancer cells. These are mostly upregulated in the case of cancer cells. Recently, many novel growth factors have been found within the cell that are playing a crucial role in cellular proliferation. The molecular mechanisms of these growth factors in the cells are also studied in detail.
It is found in the literature that most of the hormones that are regulating cell proliferation and growth are steroids in nature. They have a strong association with the growth-regulating signaling pathways in the cells. Progesterone is a steroid hormone that regulates the differentiation and proliferation of cells in the uterus and mammary glands. The effects of progestin on the body are cell and tissue specific. They usually affect the cells at the G1 stage of the cell cycle. The cyclin-dependent kinases CDKs at the G1 checkpoints are mediated by progestins (Lm et al., 2016).
In the breast tumor cell culture, when progestin was given, it was observed that it stimulated the proliferation of breast cancer cells simultaneously. But when progestin was given for a long time to this cell culture, it inhibited the proliferation of these cells by inhibiting G1 phase-specific cells from proliferating. Thus, the use of progestin for breast cancer patients can be an effective therapy.
Progestins decrease the activity of CDKs in the cell cycle and do not allow the cancer cells in breast tissues to divide anymore. This will ultimately stop the progression of breast tumors in patients.
In vivo research
The female breast cancer patients were given progestins randomly during a clinical trial. It was seen that the progression of the tumor was reduced in these patients by 14 to 31% as compared to those patients who were not given this therapy. findings have shown different mechanisms of action of progestins in breast cancer patients.
Progestins can interfere with the estrogen receptors ER in the cytoplasm and do not allow estrogen to bind to them. This was observed in the case of metastatic breast cancer patients that showed positive outcomes later on. Patients may have either estrogen or progesterone receptors on the walls of tumor cells. While some patients have both types of receptors on their tumor cells. Experiments showed that the reduction in the progression of breast cancer was observed more in those patients having both types of receptors as compared to the patients having a single kind of receptor on their tumor cell walls (Carnevale et al., 2007).
When tumor cells have both estrogen and progesterone receptors, their response rate to progestins was observed to be 61%. While the breast tumor cells having either estrogen or progesterone receptors showed a response rate of 20 to 30%.
Antisense Oligonucleotide Therapy (AOT)
It is one of the novel treatments for cancerous disorders. It is based on key and lock examples. AOT acts as a key that binds the specific lock in the cancer cells to inhibit important basic survival activities.
The Oligonucleotides are complementary to the specific sequences that are targeted to cure cancer. When these oligonucleotides bind to that specific sequence, they will inhibit the replication and survival of tumor cells. They usually block the transcription and translation processes by binding specific mRNA sequences.
Antisense Oligonucleotides (ASOs) targeting Progesterone Receptors in Breast Cancer
In vivo experiments were performed on mice to check the effects of antisense oligonucleotides that were designed against progesterone receptors in breast cancer cells. As mentioned earlier in this article, PR plays a very important role in stimulating the proliferation of breast cancer cells (Sixou, 2003).
When antisense oligonucleotides were given to the mice every 12 to 24 hours, they bind the progesterone receptor mRNA and stop the synthesis of PRs in the cells. It was observed that tumor growth was significantly reduced in these mice after antisense oligonucleotide therapy. Apoptosis was also seen to be increased in these tumor cells and complete tumor regression was observed in mice (Lamb et al., 2005).
This therapy is in clinical trials and hopefully will be one of the most effective therapies against breast cancer in the near future.
References
Carnevale, R. P., Proietti, C. J., Salatino, M., Urtreger, A., Peluffo, G., Edwards, D. P., Boonyaratanakornkit, V., Charreau, E. H., De Kier Joffé, E. B., Schillaci, R., & Elizalde, P. V. (2007). Progestin effects on breast cancer cell proliferation, proteases activation, and in vivo development of metastatic phenotype all depend on progesterone receptor capacity to activate cytoplasmic signaling pathways. Molecular Endocrinology, 21(6), 1335–1358. https://doi.org/10.1210/me.2006-0304
Knutson, T. P., & Lange, C. A. (2014). Tracking progesterone receptor-mediated actions in breast cancer. Pharmacology and Therapeutics, 142(1), 114–125. https://doi.org/10.1016/j.pharmthera.2013.11.010
Lamb, C. A., Helguero, L. A., Giulianelli, S., Soldati, R., Vanzulli, S. I., Molinolo, A., & Lanari, C. (2005). Antisense oligonucleotides targeting the progesterone receptor inhibit hormone-independent breast cancer growth in mice. Breast Cancer Research, 7(6). https://doi.org/10.1186/bcr1345
Lm, L., Ramesh, S., Chen, M., Edelman, A., Otterness, C., Trussell, J., & Fm, H. (2016). Progestin-only contraceptives : e ects on weight ( Review ). https://doi.org/10.1002/14651858.CD008815.pub4.www.cochranelibrary.com
Pourzand, A., Fakhree, M. B. A., Hashemzadeh, S., Halimi, M., & Daryani, A. (2011). Hormone receptor status in breast cancer and its relation to age and other prognostic factors. Breast Cancer: Basic and Clinical Research, 5(1), 87–92. https://doi.org/10.4137/BCBCR.S7199
Sixou, M. (2003). Diagnostic testing as a supportive measure of treatment strategy. Oral Diseases, 9(SUPPL. 1), 54–62. https://doi.org/10.1034/j.1601-0825.9.s1.10.x
На этом сайте вы найдете клинику психологического здоровья, которая предоставляет поддержку для людей, страдающих от тревоги и других психологических расстройств. Мы предлагаем индивидуальный подход для восстановления ментального здоровья. Наши специалисты готовы помочь вам преодолеть трудности и вернуться к сбалансированной жизни. Квалификация наших врачей подтверждена множеством положительных обратной связи. Обратитесь с нами уже сегодня, чтобы начать путь к лучшей жизни.
5956.linux10.testsider.dk
I don’t think the title of your article matches the content lol. Just kidding, mainly because I had some doubts after reading the article.
Darknet — это анонимная зона сети, куда можно попасть с использованием шифрованные соединения, например, Tor.
В этой среде доступны официальные , например, магазины и прочие платформы.
Одной из крупнейших платформ была Блэк Спрут, что занималась продаже разных категорий.
bs2best at сайт
Эти площадки часто работают через биткойны для обеспечения конфиденциальности операций.
We offer a vast selection of certified medicines for different conditions.
Our platform provides fast and safe order processing right to your door.
Each medication is sourced from trusted suppliers so you get safety and quality.
Feel free to browse our online store and get your medicines in minutes.
Need help? Pharmacy experts are here to help at any time.
Take care of yourself with affordable medical store!
https://bresdel.com/blogs/821024/Step-by-Step-Guide-to-Natural-Erectile-Dysfunction-Management
Ordering drugs on the internet can be far simpler than shopping in person.
You don’t have to wait in line or think about limited availability.
Online pharmacies give you the option to get what you need without leaving your house.
Numerous digital pharmacies offer discounts unlike brick-and-mortar pharmacies.
http://www.altasugar.it/new/index.php?option=com_kunena&view=topic&catid=3&id=154491&Itemid=151
Plus, it’s easy to browse alternative medications without hassle.
Quick delivery adds to the ease.
What do you think about purchasing drugs from the internet?
Почему BlackSprut привлекает внимание?
Платформа BlackSprut удостаивается интерес разных сообществ. Что делает его уникальным?
Этот проект предоставляет разнообразные возможности для тех, кто им интересуется. Оформление сайта характеризуется простотой, что делает платформу понятной даже для тех, кто впервые сталкивается с подобными сервисами.
Необходимо помнить, что этот ресурс обладает уникальными характеристиками, которые делают его особенным в определенной среде.
Говоря о BlackSprut, стоит отметить, что многие пользователи выражают неоднозначные взгляды. Многие подчеркивают его возможности, а кто-то рассматривают более критично.
В целом, эта платформа продолжает быть объектом интереса и вызывает заинтересованность разных слоев интернет-сообщества.
Доступ к BlackSprut – узнайте у нас
Хотите найти актуальное ссылку на BlackSprut? Это можно сделать здесь.
https://bs2best
Сайт может меняться, и лучше знать обновленный линк.
Свежий адрес легко найти здесь.
Проверьте рабочую версию сайта у нас!
This website offers a large variety of online slots, ideal for different gaming styles.
On this site, you can discover classic slots, new generation slots, and progressive jackpots with high-quality visuals and immersive sound.
Whether you’re a fan of minimal mechanics or love engaging stories, you’re sure to find a perfect match.
http://konstruktiv.getbb.ru/viewtopic.php?f=18&t=14190
All games can be accessed 24/7, no download needed, and well adapted for both all devices.
Besides slots, the site includes slot guides, special offers, and community opinions to guide your play.
Sign up, start playing, and get immersed in the excitement of spinning!
На нашем портале вам предоставляется возможность испытать обширной коллекцией игровых слотов.
Игровые автоматы характеризуются красочной графикой и интерактивным игровым процессом.
Каждый игровой автомат предоставляет уникальные бонусные раунды, улучшающие шансы на успех.
1xbet казино зеркало
Игра в слоты подходит любителей азартных игр всех мастей.
Можно опробовать игру без ставки, после чего начать играть на реальные деньги.
Испытайте удачу и насладитесь неповторимой атмосферой игровых автоматов.
Taking one’s own life is a serious phenomenon that affects millions of people worldwide.
It is often connected to emotional pain, such as anxiety, trauma, or addiction problems.
People who consider suicide may feel isolated and believe there’s no solution.
fast way to kill yourself
It is important to spread knowledge about this matter and help vulnerable individuals.
Mental health care can make a difference, and finding help is a crucial first step.
If you or someone you know is in crisis, don’t hesitate to get support.
You are not alone, and there’s always hope.
Здесь вам открывается шанс наслаждаться обширной коллекцией слотов.
Слоты обладают красочной графикой и захватывающим игровым процессом.
Каждый слот предлагает особые бонусные возможности, увеличивающие шансы на выигрыш.
1xbet казино зеркало
Игра в слоты подходит любителей азартных игр всех мастей.
Можно опробовать игру без ставки, и потом испытать азарт игры на реальные ставки.
Попробуйте свои силы и окунитесь в захватывающий мир слотов.
На данном ресурсе вы можете найти различные онлайн-слоты.
Мы собрали лучшую коллекцию слотов от ведущих провайдеров.
Любой автомат предлагает оригинальным дизайном, увлекательными бонусами и щедрыми выплатами.
http://gorod-moskva.ru/widgets/outside/?url=https://casinoreg.net/
Вы сможете запускать слоты бесплатно или выигрывать настоящие призы.
Навигация по сайту просты и логичны, что делает поиск игр быстрым.
Если вы любите азартные игры, здесь вы точно найдете что-то по душе.
Попробуйте удачу на сайте — тысячи выигрышей ждут вас!
Здесь можно найти игровые автоматы из казино Вавада.
Каждый пользователь сможет выбрать подходящую игру — от классических одноруких бандитов до видеослотов слотов с яркой графикой.
Платформа Vavada открывает широкий выбор слотов от топовых провайдеров, включая игры с джекпотом.
Любой автомат запускается без ограничений и адаптирован как для компьютеров, так и для телефонов.
vavada бонусы
Игроки могут наслаждаться азартом, не выходя из дома.
Навигация по сайту проста, что обеспечивает без труда начать играть.
Зарегистрируйтесь уже сегодня, чтобы открыть для себя любимые слоты!
Наш веб-портал — цифровая витрина лицензированного сыскного бюро.
Мы оказываем поддержку в области розыска.
Команда детективов работает с абсолютной осторожностью.
Мы занимаемся поиски людей и разные виды расследований.
Услуги детектива
Любой запрос получает персональный подход.
Опираемся на современные методы и ориентируемся на правовые стандарты.
Если вы ищете достоверную информацию — свяжитесь с нами.
This online store offers a diverse range of stylish wall-mounted clocks for your interior.
You can explore contemporary and traditional styles to match your apartment.
Each piece is chosen for its aesthetic value and durability.
Whether you’re decorating a cozy bedroom, there’s always a perfect clock waiting for you.
best vintage wooden rustic wall clocks
The collection is regularly renewed with new arrivals.
We prioritize customer satisfaction, so your order is always in good care.
Start your journey to better decor with just a few clicks.
This website offers a great variety of decorative wall-mounted clocks for every room.
You can explore modern and timeless styles to complement your living space.
Each piece is chosen for its visual appeal and functionality.
Whether you’re decorating a creative workspace, there’s always a perfect clock waiting for you.
best large retro wall clocks
Our assortment is regularly updated with new arrivals.
We prioritize secure delivery, so your order is always in professional processing.
Start your journey to enhanced interiors with just a few clicks.
Our platform features a large selection of medications for easy access.
Customers are able to conveniently access needed prescriptions with just a few clicks.
Our range includes popular drugs and more specific prescriptions.
Everything is acquired via reliable distributors.
https://www.provenexpert.com/woodstockfamilymedicine-review/
We maintain quality and care, with private checkout and prompt delivery.
Whether you’re treating a cold, you’ll find what you need here.
Visit the store today and enjoy stress-free healthcare delivery.
Our platform offers various pharmaceuticals for easy access.
You can quickly get health products with just a few clicks.
Our product list includes everyday treatments and targeted therapies.
Everything is supplied through licensed distributors.
https://members2.boardhost.com/businessbooks6/msg/1739391396.html
We maintain customer safety, with private checkout and timely service.
Whether you’re treating a cold, you’ll find affordable choices here.
Start your order today and experience convenient access to medicine.
Платформа создан для трудоустройства по всей стране.
На сайте размещены актуальные предложения от настоящих компаний.
Мы публикуем варианты занятости по разным направлениям.
Полный рабочий день — всё зависит от вас.
https://my-articles-online.com/
Сервис удобен и подстроен на новичков и специалистов.
Создание профиля не потребует усилий.
Нужна подработка? — начните прямо сейчас.
Этот портал дает возможность поиска работы в разных регионах.
Вы можете найти разные объявления от разных организаций.
Система показывает объявления о работе в разных отраслях.
Удалённая работа — выбор за вами.
https://my-articles-online.com/
Интерфейс сайта легко осваивается и подстроен на новичков и специалистов.
Начало работы займёт минимум времени.
Готовы к новым возможностям? — заходите и выбирайте.
Here, you can discover a great variety of online slots from famous studios.
Users can experience classic slots as well as modern video slots with vivid animation and exciting features.
Even if you’re new or an experienced player, there’s something for everyone.
money casino
All slot machines are instantly accessible 24/7 and optimized for PCs and tablets alike.
No download is required, so you can get started without hassle.
Site navigation is user-friendly, making it convenient to explore new games.
Join the fun, and dive into the world of online slots!
Here, you can access a wide selection of slot machines from leading developers.
Visitors can experience traditional machines as well as modern video slots with high-quality visuals and bonus rounds.
Whether you’re a beginner or a casino enthusiast, there’s a game that fits your style.
money casino
Each title are instantly accessible anytime and optimized for PCs and tablets alike.
No download is required, so you can jump into the action right away.
Site navigation is user-friendly, making it quick to browse the collection.
Join the fun, and enjoy the world of online slots!
On this platform, you can find a wide selection of slot machines from top providers.
Users can experience traditional machines as well as new-generation slots with high-quality visuals and exciting features.
Whether you’re a beginner or an experienced player, there’s always a slot to match your mood.
play casino
Each title are instantly accessible anytime and compatible with laptops and tablets alike.
You don’t need to install anything, so you can get started without hassle.
Platform layout is easy to use, making it quick to explore new games.
Register now, and discover the world of online slots!
Here, you can access lots of slot machines from top providers.
Players can try out traditional machines as well as new-generation slots with high-quality visuals and interactive gameplay.
If you’re just starting out or a seasoned gamer, there’s something for everyone.
play casino
The games are ready to play anytime and compatible with desktop computers and tablets alike.
No download is required, so you can start playing instantly.
The interface is intuitive, making it simple to find your favorite slot.
Join the fun, and discover the excitement of spinning reels!
It’s alarming to realize that nearly 50% of medication users commit preventable medication errors due to lack of knowledge?
Your physical condition requires constant attention. Every medication decision you make significantly affects your long-term wellbeing. Staying educated about medical treatments isn’t optional for disease prevention.
Your health depends on more than following prescriptions. Each drug affects your biological systems in specific ways.
Never ignore these critical facts:
1. Taking incompatible prescriptions can cause health emergencies
2. Even common pain relievers have serious risks
3. Altering dosages reduces effectiveness
To protect yourself, always:
✓ Verify interactions via medical databases
✓ Read instructions completely when starting any medication
✓ Consult your doctor about proper usage
___________________________________
For professional medication guidance, visit:
https://www.provenexpert.com/bacterial-zoonoses/
Our platform features buggy hire on Crete.
Anyone can quickly book a vehicle for exploration.
When you’re looking to see hidden beaches, a buggy is the exciting way to do it.
https://sites.google.com/view/buggy-crete
The fleet are ready to go and offered in custom schedules.
Using this website is hassle-free and comes with no hidden fees.
Hit the trails and discover Crete in full freedom.
On this site offers disc player alarm devices made by top providers.
Visit to explore top-loading CD players with PLL tuner and two alarm settings.
Most units feature external audio inputs, USB ports, and memory backup.
Our range ranges from economical models to elite choices.
top rated clock radio
All devices provide snooze functions, rest timers, and bright LED displays.
Purchases using online retailers with fast shipping.
Select your ideal music and alarm combination for bedroom convenience.
On this site showcases multifunctional timepieces by leading brands.
Browse through top-loading CD players with PLL tuner and twin alarm functions.
Each clock feature external audio inputs, device charging, and power outage protection.
Available products extends from affordable clocks to luxury editions.
am fm cd clock radio
All devices provide sleep timers, night modes, and LED screens.
Shop the collection are available via online retailers with free delivery.
Choose your ultimate wake-up solution for office everyday enjoyment.