Rat xenograft chondrosarcoma development by human tissue fragment
Aim: We conducted this study to develop a chondrosarcoma on rat by graft of human chondrosarcoma tumor tissue. Methods: Fourteen male Sprague-Dawley rats equally divided in xenograft-implanted and control groups. On the lateral side of the right femur distal 1/3, 5 mm incision was done on the skin a...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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| Zitieren: | Rat xenograft chondrosarcoma development by human tissue fragment / M. Hemmati, A. Abbaspour, A.M. Alizadeh, M. Khaniki, A. Amanzadeh, M.A. Mohagheghi, M.S. Mousavi // Experimental Oncology. — 2011. — Т. 33, № 1. — С. 52–54. — Біліогр.: 16 назв. — англ. |
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irk-123456789-323192012-04-17T12:25:16Z Rat xenograft chondrosarcoma development by human tissue fragment Hemmati, M. Abbaspour, A. Alizadeh, A.M. Khaniki, M. Amanzadeh, A. Mohagheghi, M.A. Mousavi, M.S. Short communications Aim: We conducted this study to develop a chondrosarcoma on rat by graft of human chondrosarcoma tumor tissue. Methods: Fourteen male Sprague-Dawley rats equally divided in xenograft-implanted and control groups. On the lateral side of the right femur distal 1/3, 5 mm incision was done on the skin after animal anesthesia. Then, was drilled 3 mm on the bone and implanted the xenograft in the bone. Radiography was taken from the operated femur weekly until the fourth week and monthly for 3 months. Four animals of each group were sacrificed after 4 weeks of operation; femur was harvested for histopathological study. 2011 Article Rat xenograft chondrosarcoma development by human tissue fragment / M. Hemmati, A. Abbaspour, A.M. Alizadeh, M. Khaniki, A. Amanzadeh, M.A. Mohagheghi, M.S. Mousavi // Experimental Oncology. — 2011. — Т. 33, № 1. — С. 52–54. — Біліогр.: 16 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/32319 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Short communications Short communications Hemmati, M. Abbaspour, A. Alizadeh, A.M. Khaniki, M. Amanzadeh, A. Mohagheghi, M.A. Mousavi, M.S. Rat xenograft chondrosarcoma development by human tissue fragment Experimental Oncology |
| description |
Aim: We conducted this study to develop a chondrosarcoma on rat by graft of human chondrosarcoma tumor tissue. Methods: Fourteen male Sprague-Dawley rats equally divided in xenograft-implanted and control groups. On the lateral side of the right femur distal 1/3, 5 mm incision was done on the skin after animal anesthesia. Then, was drilled 3 mm on the bone and implanted the xenograft in the bone. Radiography was taken from the operated femur weekly until the fourth week and monthly for 3 months. Four animals of each group were sacrificed after 4 weeks of operation; femur was harvested for histopathological study. |
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Article |
| author |
Hemmati, M. Abbaspour, A. Alizadeh, A.M. Khaniki, M. Amanzadeh, A. Mohagheghi, M.A. Mousavi, M.S. |
| author_facet |
Hemmati, M. Abbaspour, A. Alizadeh, A.M. Khaniki, M. Amanzadeh, A. Mohagheghi, M.A. Mousavi, M.S. |
| author_sort |
Hemmati, M. |
| title |
Rat xenograft chondrosarcoma development by human tissue fragment |
| title_short |
Rat xenograft chondrosarcoma development by human tissue fragment |
| title_full |
Rat xenograft chondrosarcoma development by human tissue fragment |
| title_fullStr |
Rat xenograft chondrosarcoma development by human tissue fragment |
| title_full_unstemmed |
Rat xenograft chondrosarcoma development by human tissue fragment |
| title_sort |
rat xenograft chondrosarcoma development by human tissue fragment |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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2011 |
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Short communications |
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http://dspace.nbuv.gov.ua/handle/123456789/32319 |
| citation_txt |
Rat xenograft chondrosarcoma development by human tissue fragment / M. Hemmati, A. Abbaspour, A.M. Alizadeh, M. Khaniki, A. Amanzadeh, M.A. Mohagheghi, M.S. Mousavi // Experimental Oncology. — 2011. — Т. 33, № 1. — С. 52–54. — Біліогр.: 16 назв. — англ. |
| series |
Experimental Oncology |
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2025-07-03T12:50:03Z |
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2025-07-03T12:50:03Z |
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| fulltext |
52 Experimental Oncology 33, 52–54, 2011 (March)
Chondrosarcoma is the second most frequent
malignant primary bone tumor in human. Orthopedic
oncologists believe that chondrosarcoma is one of the
most difficult types of cancer to diagnose and treat-
ment; it is also highly resistant to ionizing radiation
action and chemotherapy. In experimental musculo-
skeletal oncology animal models are routinely used to
assess the efficacy of new and innovative treatment
methodologies for these tumors [1–3].
Quite a few animal models of chondrosarcoma have
been developed and described in literature, such as (i)
inoculation chondrosarcoma cell line (MCS-1) [4–5],
(ii) allograft tumor tissue fragments on rats [6], (iii)
human tumor xenograft implanted cell line into the
nude mice [7–8]. In 1960’s allograft chondrosarcoma
models were developed based on rat tumor implanta-
tion [9]. The chondrosarcoma model was established
with repeated transplantation. However, these models
could not show the human tumor behavior. Therefore,
the development of a reliable animal model for chon-
drosarcoma would be a helpful tool to study tumor
growth and progression.
To have a more similar experimental human tumor,
human chondrosarcoma development on animal
cases is needed. Yet, such a tumor may not be entirely
representative of spontaneously developing chondro-
sarcoma [10]. Since animal model of human xenograft
would be feasible and reproducible. We conducted
this study to develop a chondrosarcoma model on
Sprague-Dawley rat by fresh human chondrosarcoma
tissue fragments.
Animals. Fourteen, four-week-old male Sprague-
Dawley rats (weighing 90±5 g) were taken from Razi
Vaccine and Serum Research Institute of Iran, kept in
separated cages at 21–23 °C, humidity 50% and 12 h light-
dark cycle. They had free access to rat chow and water.
Animals were equally divided in xenograft-implanted and
control groups. The implanted group received tumoral
fresh tissue fragments. The human chondrosarcoma tis-
sue was obtained from a 37 year-old female diagnosed
with left leg chondrosarcoma (Tumor bank number 328,
File number 822585, Cancer Institute, Emam Khomeini
Hospital, Tehran, Iran). The fresh sample had atypical
and anaplastic cells as a low-grade type of tumor. All
experimental procedures were in accordance with the
guidelines of the animal and human ethical committee of
Tehran university of Medical Sciences.
Surgical procedure. Animals were anesthetized
by a mixture of ketamine (60 mg/kg i.p) and xylazine
(10 mg/kg i.p). First the lateral skin of the right femur
distal 1/3 was incised 5 mm and then drilled 3 mm on
the bone. Fresh chondrosarcoma tumoral segments
were taken from operation room, immersed in normal
saline immediately. The segments were divided into
very small fragments less than 0.5 mm and inoculated
with gage 14 needle into femoral intramedullary space
[11]. The control group was injected normal saline.
Cyclosporine A (10 mg/kg i.p) has been given for 4
weeks from implantation day (day 0) to suppress graft
versus host reactions [12]. Animals were weighted
once a week throughout the experiment.
Radiological study. Post operative AP X-rays were
taken every week for one month to assess the implan-
tation site. X-rays were obtained monthly for three
months after immunosuppressive discontinuation.
Histopathological study. Four weeks after the
operation, four rats were sacrificed of each group
to harvest their femur bones and tumoral samples
immediately fixed in a 10% formalin solution for 24 h
and then put in a nitric acid solution (10%) for five days
to decalcify bone mass. Samples were embedded in
RAT XENOGRAFT CHONDROSARCOMA DEVELOPMENT BY HUMAN
TISSUE FRAGMENT
M. Hemmati1, A. Abbaspour2, A.M. Alizadeh1,*, M. Khaniki, A. Amanzadeh3, M.A. Mohagheghi1, M.S. Mousavi1
1Cancer Research Center, Tehran University of Medical Science, Keshavarz str., Tehran 1419733141, Iran
2Department of Orthopedics, Baghiatallah University of Medical Science, Shiraz str., Tehran 1435915371, Iran
3Pasteur Institute of Iran, National Cell Bank, Davazdeh farvardin str., Tehran 1316943551, Iran
Chondrosarcoma is one of the most difficult types of cancers to diagnose and treatment. Therefore, the development of a reliable
animal model for chondrosarcoma would be a helpful tool to study of the tumor’s growth and progression. Aim: We conducted this
study to develop a chondrosarcoma on rat by graft of human chondrosarcoma tumor tissue. Methods: Fourteen male Sprague-Dawley
rats equally divided in xenograft-implanted and control groups. On the lateral side of the right femur distal 1/3, 5 mm incision was
done on the skin after animal anesthesia. Then, was drilled 3 mm on the bone and implanted the xenograft in the bone. Radiography
was taken from the operated femur weekly until the fourth week and monthly for 3 months. Four animals of each group were sacrificed
after 4 weeks of operation; femur was harvested for histopathological study. Results: Radiological images showed sclerotic area on
the implanted bone after 4 weeks of operation. Sections from tumoral areas reveal cartilage forming hypercellular neoplastic tissue
with lobular pattern of growth and foci of adjacent tissue invasion such as bone trabeculas and bone marrow. Conclusion: the present
study showed that rat xenograft chondrosarcoma can develop by human chondrosarcoma fresh tissue fragments.
Key Words: human chondrosarcoma, xenograft, rat.
Received: September 8, 2010.
*Correspondence: Fax: +98 21 66581638;
E-mail: aalizadeh@razi.tums.ac.ir
Exp Oncol 2011
33, 1, 52–54
SHORT COMMUNICATIONS
53 Experimental Oncology 33, 52–54, 2011 (March)
paraffin and sliced into 5 μm serial sections for stain-
ing Hematoxylin and Eosin (H & E). For the pathologic
classification of chondrosarcoma, cellularity, nuclear
format cells and necrosis were examined.
Statistical analysis. Nonparametric fisher exact test
was used to compare between two groups (p < 0.05).
The radiological image showed sclerotic area on
the implanted group (Fig. 1 a). The cortical bone
presents signs of invasion and thickening of the
periosteum. A low-grade chondrosarcoma showed
by disruption of trabeculae, intralesional calcification
and periosteal reaction. Around the implantation area
was seen more opacity compared to control group
(Fig. 1 b, c).
a b c
Fig. 1. Radiographies after chondrosarcoma tissue fragments
implantation: a, period of the immunosuppressive treatment
with abnormalities and bone resorption in implanted group; b,
immunosuppressive agent discontinue showing bone formation
improvement; c, control group
Typical signs of chondrosarcoma were observed
four weeks after operation implanted group (Fig. 2 a,
c, d). Sections from tumoral areas reveal cartilage form-
ing hypercellular neoplastic tissue with lobular pattern
of growth and foci of adjacent tissue invasion. Invasion
occurred in bone trabeculas and bone marrow tissue as
well as cellular criteria of chondrosarcoma (see Fig. 2
c, d). Section from implanted area of femur in control
group showed normal pattern of tissue (Fig. 2 b).
In the present study, xenograft chondrosarcoma
induction was established in rat femoral bone by fresh
human chondrosarcoma fragments.
Poor prognosis of chondrosarcoma demands new
therapeutic options to improve the overall rate of sur-
vival, especially in high-risk groups. Animal models of
accurately reproduced human pathology, physiology
and histology are needed to experience a new thera-
peutic strategy. Accordingly, animal xenograft cell line
inoculation was done in nude mice, rats and hamsters
during the last century [4–5, 13–15]. It will be more use-
ful to have animal tumoral models behave very similar to
the human cancerous cells with minimal manipulation.
A number of xenograft implantable human tumors
including chondrosarcoma were prepared by treat-
ing the animals with radiation and cortisone. With the
advent of athymic nude mice, animal immunosuppres-
sant free cancerous cell models were adopted xeno-
graft implantation [16]. In 1990’s, chondrosarcoma
cells of human were implanted in nude mice. Since,
this technique has become popular, so that, most of
chondrosarcoma models used during the last two
decades involve human chondrosarcoma tissue or cell
lines as ectopically implanted (within subcutaneous
tissue) in various strains of immunocompromised mice
[10]. However, transgenic mouse chondrosarcoma
have been observed with unpredictability of tumor
location, multiple tumors forming and varying pheno-
types that makes this approach difficult to control as
a function assessment model [10, 12].
a b
c d
Fig. 2. Chondrosarcoma implantations after 28 days stain with
hematoxylin and eosin: a — bone infiltration was seen obviously,
40X; b — control group, 40X; c, d — hyper cellularity, bone mar-
row and trabeculae infiltration in implanted group, 100X
In present study, radiographic findings show more
opacity at the implantation region (Fig. 1 a) compared
to control group (Fig. 1 c). Implanted region lag growth
may result immunosuppressive agent discontinuation
(Fig. 1 b, see Fig. 2 a, c, d). Cellular criteria of chon-
drosarcoma include lacunar spaces with more than
one nucleus, atypical hyperchromatic nuclei and bone
infiltration [10]. Note that penetration into the bone,
hypercellularity and irregularity are characteristics of
chondrosarcoma tumor. This investigation showed
chondroid cell infiltration into the bone marrow and
trabeculae (see Fig. 2 a), also irregularity and hyper-
cellularity were seen in histopathological images of
treated group (see Fig. 2 c, d).
In our study it seems the ectopic chondroid cells at
the intramedullary bone region may be related to well-
differentiated chondroid cells or benign tumor in focal
site. Thus, the present study shows that animal xenograft
chondrosarcoma can be produced from fresh human
54 Experimental Oncology 33, 52–54, 2011 (March)
fragments. The advantages of this kind of method are
reproducibility, feasibility and cost effectiveness. Based
on, chondrosarcoma xenograft can be a helpful model
in human cancer studies and may be a good adjuvant
to assess the efficacy of new and innovative treatment
methodologies for chondrosarcoma tumors.
CONCLUSION
The present study showed that xenograft chondro-
sarcoma in rat can be developed by human chondro-
sarcoma tissue fragments.
ACKNOWLEDGMENTS
The present research was supported by Tehran
University of Medical Sciences and health services,
a grant of Cancer Research Center of Emam Kho-
meini Hospital. We thank Dr. Faezipour for handling
the patient in the operation room in Cancer Research
Center of Cancer Institute. Also, we thank Dr. Akbari
for histopathological consultance in the Department
of Pathology, Baghiyatallah Hospital.
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