Turkiye Klinikleri Journal of Medical Sciences

.: ORIGINAL RESEARCH
Creation of Myeloma Model in BALB/c Mice: Experimental Study
BALB/c Farelerde Miyeloma Modelinin Oluşturulması: Deneysel Çalışma
Selda TAŞDEMİRa, Zuhal HAMURCUb, Kemal DENİZc, Nesrin DELİBAŞI KÖKÇÜa, Özlem CANÖZc, Mustafa ÇETİNd
aErciyes University Betül Ziya Eren Genome and Stem Cell Center, Kayseri, TURKEY
bDepartment of Medical Biology, Erciyes University Faculty of Medicine, Kayseri, TURKEY
cDepartment of Pathology, Erciyes University Faculty of Medicine, Kayseri, TURKEY
dDepartment of Hematology Oncology, Erciyes University Faculty of Medicine, Kayseri, TURKEY
Turkiye Klinikleri J Med Sci. 2021;41(3):250-7
doi: 10.5336/medsci.2020-78693
Article Language: EN
ABSTRACT
Objective: Multiple myeloma (MM) disease is characterized by clonal proliferation of malignant plasma cells in the bone marrow. It represents approximately 1% of all cancers in the world. Individual dissolution foci or diffuse osteopenia are common in the bones. In approximately 3% of the cases, non-bone marrow (extramedullary) involvement may occur and this solid involvement outside the bone marrow is defined as plasmacytoma. Experimental animal studies are widely used to elucidate metabolic and physiological mechanisms. It is more advantageous to use experimental animal models since there are many systemic organ involvement, especially in hematological cancers. We aimed to create a standard animal model for MM which is suitable for new experiments and drug trials. Seven experimental animal groups were created apart from the control group. Different amount of MOPC315 cells (1-2-5x106 /200-500 µL) applied to three different regions (subcutaneous right abdominal, intravenous to the tail vessel, intraperitoneal right abdominal), in male (n=10) and female (n=7) BALB/c mice. Insulin injection should not be used. Different waiting times were applied for tumor development (20-30 days). Material and Methods: The control group consisted of 1 male and 1 female mouse. Pathological examination was performed after hematoxylin and eosin staining of organs and suspicious tissues of mice killed by cervical dislocation. Results: According to our study, after cells were injected, pneumonia, which is one of the late symptoms of MM, developed in females, but no tumor was formed. Whereas, after the cell was injected, tumor formation was observed in males. Conclusion: According to our results, we suggest that the standard MM animal model can be created by intraperitoneally injecting of 2x106 /500 µL MOPC315 cells into male BALB/c mouse. Our work has been a pioneer in the use of animal experiments in MM disease in Turkey.

Keywords: Multiple myeloma; animal model
ÖZET
Amaç: Multipl miyelom (MM) hastalığı, kemik iliğindeki malign plazma hücrelerinin klonal çoğalması ile karakterizedir. Dünyadaki tüm kanserlerin yaklaşık %1'ini temsil eder. Kemiklerde, tek tek erime odakları ya da diffüz osteopeni sık görülür. Olguların yaklaşık %3'ünde kemik dışı (ekstramedüller) tutulum olabilir ve kemik iliği dışındaki bu katı tutulum, plazmasitom olarak tanımlanır. Deneysel hayvan çalışmaları, metabolik ve fizyolojik mekanizmaları aydınlatmak için yaygın olarak kullanılmaktadır. Özellikle hematolojik kanserlerde, çok sayıda sistemik organ tutulumu olduğu için deneysel hayvan modellerinin kullanılması daha avantajlıdır. MM için yeni deneyler ve ilaç denemelerine uygun standart bir hayvan modeli oluşturmayı amaçladık. Kontrol grubunun dışında, 7 deneysel hayvan grubu oluşturuldu. Farklı sayıda erkek (n=10) ve dişi (n=7) BALB/c farelere, 3 farklı bölgeden (subkütan sağ karın, kuyruk damarına intravenöz, intraperitoneal sağ karın) farklı miktarda MOPC315 hücresi (1-2-5x106 /200-500 µL) uygulandı. İnsülin enjektörü kullanılmamalıdır. Tümör gelişimi için farklı bekleme süreleri uygulandı (20-30 gün). Gereç ve Yöntemler: Kontrol grubu, 1 erkek ve 1 dişi fareden oluşmaktaydı. Servikal dislokasyonla öldürülen farelerin organları ve şüpheli dokuların, hematoksilen-eozin boyanması sonucunda patolojik incelemesi yapıldı. Bulgular: Çalışmamıza göre hücreler enjekte edildikten sonra MM'nin geç semptomlarından biri olan pnömoni, dişi farelerde gelişti, ancak tümör oluşmadı. Oysa hücre enjekte edildikten sonra erkek farelerde tümör oluşumu gözlendi. Sonuç: Sonuçlarımıza göre standart MM hayvan modelinin, 2x106 /500 µL MOPC315 hücresinin erkek BALB/c fareye intraperitoneal yoldan enjekte edilmesi ile oluşturulabileceğini önermekteyiz. Çalışmamız, Türkiye'de MM hastalığında deney hayvanı kullanılması konusunda öncü olmuştur.

Anahtar Kelimeler: Multipl miyelom; hayvan modeli
REFERENCES:
  1. Ovayolu Ö, Ovayolu N. Multipl miyelom tanısı alan geriatrik hastalarda ağrı ve yönetimi [Pain and its management in geriatric patients diagnosed with multiple myeloma]. Journal of Hacettepe University Faculty of Nursing. 2018;5(3):260-7. [Crossref] 
  2. Morvan L, Carlier T, Jamet B, Bailly C, Bodet-Milin C, Moreau P, et al. Leveraging RSF and PET images for prognosis of multiple mye loma at diagnosis. Int J Comput Assist Radiol Surg. 2020;15(1):129-39. [Crossref] [PubMed] 
  3. Curado MP, Oliveira MM, Silva DRM, Souza DLB. Epidemiology of multiple myeloma in 17 Latin American countries: an update. Cancer Med. 2018;7(5):2101-8. [Crossref] [PubMed] [PMC] 
  4. Gassiot S, González Y, Morgades M, Motlló C, Clapés V, Maluquer C, et al. Response to first cycle is the major predictor of long-term response to lenalidomide and dexamethasone therapy in relapsed and refractory multiple myeloma: can we spare patients the toxicity and costs of additional agents? Clin Lymphoma Myeloma Leuk. 2019;19(9):585-92.e1. [Crossref] [PubMed] 
  5. Vo MC, Jung SH, Chu TH, Lee HJ, Lakshmi TJ, Park HS, et al. Lenalidomide and programmed death-1 blockade synergistically enhances the effects of dendritic cell vaccination in a model of murine myeloma. Front Immunol. 2018;9:1370. [Crossref] [PubMed] [PMC] 
  6. Kaya M, Çevik A. Hayvan deneylerinde planlanma ve model seçimi [Planning in animal experiments and choosing model]. Deneysel Tıp Araştırma Enstitüsü Dergisi. 2011;1(2):36-9. [Link] 
  7. Winter WE. Chapter 5. Monoclonal Gammopathies. Herris NS, Winter WE, eds. Multiple Myeloma And Related Serum Protein Disorders An Electrophoretic Guide. 1st ed. New York, NY: Demos Medical Pub.; 2012. p.72.
  8. Chen JH, Chung CH, Wang YC, Hsu SN, Huang WY, Chien WC. Prevalence and mortality-related factors of multiple myeloma in Taiwan. PLoS One. 2016;11(12):e0167227. [Crossref] [PubMed] [PMC] 
  9. Wang LH, Yang XY, Mihalic K, Xiao W, Li D, Farrar WL. Activation of estrogen receptor blocks interleukin-6-inducible cell growth of human multiple myeloma involving molecular cross-talk between estrogen receptor and STAT3 mediated by co-regulator PIAS3. J Biol Chem. 2001;276(34):31839-44. [Crossref] [PubMed] 
  10. Riedel SS, Mottok A, Brede C, Bäuerlein CA, Jordán Garrote AL, Ritz M, et al. Non-invasive imaging provides spatiotemporal information on disease progression and response to therapy in a murine model of multiple myeloma. PLoS One. 2012;7(12):e52398. [Crossref] [PubMed] [PMC] 
  11. Ahn JH, Lee BH, Kim SE, Kwon BE, Jeong H, Choi JR, et al. A novel anti-PD-L1 antibody exhibits antitumor effects on multiple myeloma in murine models via antibody-dependent cellular cytotoxicity. Biomol Ther (Seoul). 2021;29(2):166-74. [Crossref] [PubMed] [PMC] 
  12. Rummler M, Ziouti F, Bouchard AL, Brandl A, Duda GN, Bogen B, et al. Mechanical loading prevents bone destruction and exerts anti-tumor effects in the MOPC315.BM.Luc model of myeloma bone disease. Acta Biomater. 2021;119:247-58. [Crossref] [PubMed] 
  13. Röhner L, Ng YLD, Scheffold A, Lindner S, Köpff S, Brandl A, et al. Generation of a lenalidomide-sensitive syngeneic murine in vivo multiple myeloma model by expression of CrbnI391V. Exp Hematol. 2021;93:61-9.e4. [Crossref] [PubMed] 
  14. Everaus H, Lehtmaa J. Sex hormones and immune dysregulation in multiple myeloma. Cancer Immunol Immunother. 1993;36(3):205-9. [Crossref] [PubMed] 
  15. Landgren O, Zhang Y, Zahm SH, Inskip P, Zheng T, Baris D. Risk of multiple myeloma following medication use and medical conditions: a case-control study in Connecticut women. Cancer Epidemiol Biomarkers Prev. 2006;15(12):2342-7. [Crossref] [PubMed] 

Login



Contact


Ortadoğu Reklam Tanıtım Yayıncılık Turizm Eğitim İnşaat Sanayi ve Ticaret A.Ş.

.: Address

Turkocagi Caddesi No:30 06520 Balgat / ANKARA
Phone: +90 312 286 56 56
Fax: +90 312 220 04 70
E-mail: info@turkiyeklinikleri.com

.: Manuscript Editing Department

Phone: +90 312 286 56 56/ 119 - 123
E-mail: yaziisleri@turkiyeklinikleri.com

.: English Language Redaction

Phone: +90 312 286 56 56/ 145
E-mail: tkyayindestek@turkiyeklinikleri.com

.: Marketing Sales-Project Department

Phone: +90 312 286 56 56/ 142
E-mail: reklam@turkiyeklinikleri.com

.: Subscription and Public Relations Department

Phone: +90 312 286 56 56/ 118
E-mail: abone@turkiyeklinikleri.com

.: Customer Services

Phone: +90 312 286 56 56/ 118
E-mail: satisdestek@turkiyeklinikleri.com

1. TERMS OF USE

1.1. To use the web pages with http://www.turkiyeklinikleri.com domain name or the websites reached through the sub domain names attached to the domain name (They will be collectively referred as "SITE"), please read the conditions below. If you do not accept these terms, please cease to use the "SITE." "SITE" owner reserves the right to change the information on the website, forms, contents, the "SITE," "SITE" terms of use anytime they want.

1.2. The owner of the "SITE" is Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. (From now on it is going to be referred as "Turkiye Klinikleri", shortly) and it resides at Turkocagi cad. No:30, 06520 Balgat Ankara. The services in the "SITE" are provided by "Turkiye Klinikleri."

1.3. Anyone accessing the "SITE" with or without a fee whether they are a natural person or a legal identity is considered to agree these terms of use. In this contract hereby, "Turkiye Klinikleri" may change the stated terms anytime. These changes will be published in the "SITE" periodically and they will be valid when they are published. Any natural person or legal identity benefiting from and reaching to the "SITE" are considered to be agreed to any change on hereby contract terms done by "Turkiye Klinikleri."

1.4. The "Terms of Use" hereby is published in the website with the last change on March 30th 2014 and the "SITE" is activated by enabling the access to everyone. The "Terms of Use" hereby is also a part of the any "USER Contract" was and/or will be done with the users using "Turkiye Klinikleri" services with or without a fee an inseparable.

2. DEFINITIONS

2.1. "SITE": A website offering different kind of services and context with a certain frame determined by "Turkiye Klinikleri" and it is accessible on-line on http://www.turkiyeklinikleri.com domain name and/or subdomains connected to the domain name.

2.2. USER: A natural person or a legal identity accessing to the "SITE" through online settings.

2.3. LINK: A link enabling to access to another website through the "SITE", the files, the context or through another website to the "SITE", the files and the context.

2.4. CONTEXT: Any visual, literary and auditory images published in the "Turkiye Klinikleri", "SITE" and/or any website or any accessible information, file, picture, number/figures, price, etc.

2.5. "USER CONTRACT": An electronically signed contract between a natural or a legal identity benefiting from special services "Turkiye Klinikleri" will provide and "Turkiye Klinikleri".

3. SCOPE OF THE SERVICES

3.1. "Turkiye Klinikleri" is completely free to determine the scope and quality of the services via the "SITE".

3.2. To benefit the services of "Turkiye Klinikleri" "SITE", the "USER" must deliver the features that will be specified by "Turkiye Klinikleri". "Turkiye Klinikleri" may change this necessity any time single-sided.

3.3. Not for a limited number, the services "Turkiye Klinikleri" will provide through the "SITE" for a certain price or for free are;

- Providing scientific articles, books and informative publications for health industry.

- Providing structural, statistical and editorial support to article preparation stage for scientific journals.

4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com