scholarly journals Human amniotic membrane-derived epithelial stem cells display anticancer activity in BALB/c female nude mice bearing disseminated breast cancer xenografts

Author(s):  
Kyung-Chul Choi
2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1049-1049 ◽  
Author(s):  
T. A. Traina ◽  
B. Higgins ◽  
M. Theodoulou ◽  
U. Dugan ◽  
K. Kolinsky ◽  
...  

1049 Background: Mathematical methods applied to xenograft breast cancer models have determined that the maximum impact of C therapy occurs after ∼7 days (7d) of treatment (Norton AACR 2005). The model predicts that doses of C beyond 7d will contribute to toxicity without additional antitumor benefit. The tolerability and anti-tumor activity of C 7d on/7d off (7/7) in female nude mice bearing KPL-4 breast cancer xenografts has been established (SABCS 2006). We now report preclinical models of C7/7 with targeted therapies. Methods: We evaluated the tumor growth inhibition (TGI%) and increase in life span (ILS%) of C7/7 and B with or without T in female nude mice bearing KPL-4, HER2+ breast cancer xenografts. C at maximum tolerated dose (MTD) and ½MTD were tested in combination with conventional doses of the antibodies. Results: C7/7 at MTD is well tolerated in combination with conventional dose B + T. No toxicity was observed at any dose level. The addition of B ± T to C7/7 monotherapy significantly improves TGI%. Survival is significantly prolonged for the combination of C7/7 MTD with B ± T. Comparative results for C7/7 at MTD and ½ MTD are shown in the Table . Additional comparative data will be shown at the meeting. Assessment of ILS% is ongoing for the triplet C7/7 + B + T but has exceeded 463% and >152 days. Conclusions: The improvement in response and survival shown here supports the study of combination C7/7 with B and T. Combinations with B and anti-HER2 therapy will be tested in the clinical, Phase II program at MSKCC. [Table: see text] [Table: see text]


2019 ◽  
Vol 12 (6) ◽  
pp. 599-613 ◽  
Author(s):  
Siti Nurnasihah Md Hashim ◽  
Muhammad Fuad Hilmi Yusof ◽  
Wafa’ Zahari ◽  
Hamshawagini Chandra ◽  
Khairul Bariah Ahmad Amin Noordin ◽  
...  

2018 ◽  
Vol 7 (12) ◽  
pp. 906-917 ◽  
Author(s):  
Alejandro Navas ◽  
Fátima Sofía Magaña-Guerrero ◽  
Alfredo Domínguez-López ◽  
César Chávez-García ◽  
Graciela Partido ◽  
...  

2010 ◽  
Vol 22 (1) ◽  
pp. 349 ◽  
Author(s):  
A. Lange Consiglio ◽  
B. Corradetti ◽  
D. Bizzaro ◽  
M. Cassano ◽  
F. Cremonesi

According to the developmental stage from which they are obtained, stem cells are classified as being embryonic, fetal, or adult. Embryonic stem cells have unlimited self-renewing capacity and multilineage differentiation potential, but the separation of these cells requires destruction of the embryo. Moreover, their clinical application seems to be hindered by the high tumorigenic rate after transplantation. Stem cells derived from adult tissues are considered to be more limited in their potential; although, they are currently the more versatile cells in the clinical field. However, the risk of the immunological rejection of the transplanted stem cells by the recipient is an important limiting factor. In human medicine, stem cells isolated from term placenta are the ideal candidates for disease treatment, specifically because of their plasticity and reduced immunogenicity. The aim of this work was to provide, for the first time, an isolation protocol and the characteristics of the stem cells from horse amniotic membrane, which hold potential uses in equine clinical regenerative medicine. Minimal criteria for stemness definition are adherence to plastic culture dish, formation of fibroblast colony forming units (CFU-F), specific pattern of surface antigen expression, and differentiation potential toward one or more lineages. The amnion is a thin, avascular membrane composed of an epithelial layer and an outer layer of connective tissue. From 3 samples of allantoamnion retrieved at delivery, each amniotic membrane was stripped from the overlying allantois and, for isolation of the epithelial cells, digested with trypsin. After removal of epithelial cells, the AMSC population was obtained by digestion with collagenase and DNase. The cellular yield from term amnion was 10-fold more epithelial cells than AMSC. Isolated cells readily attached to plastic culture dishes. Culture was established in DMEM-HG medium, supplemented with 10% serum and EGF, where the cells proliferated robustly. Epithelial cells displayed typical cuboidal morphology, whereas AMSC were fibroblast-like. Normally, 5 to 6 passages were achieved before proliferation decreased, with a mean of 13.08 and 26.5 cell population doublings after 31 days, respectively, for epithelial cells and AMSC. The mean frequency of CFU-F was, respectively, 1 : 283 and 1:111 for epithelial cells and AMSC. The 2 cellular lines expressed MSC mRNA markers (CD29, CD105, CD44) and were negative for CD34, which was expressed at the fifth passage in both cellular types. Osteogenic differentiation of epithelial stem cells and AMSC was confirmed by von Kossa stain and by an increased expression of osteocalcin and osteopontin. Our preliminary data showed that equine amnion holds apparent potential as a source of presumptive stem cells, which might have widespread clinical applications, but aspects including immunohistochemical study, preclinical experimentation, and immunological properties must be studied.


2015 ◽  
Vol 4 (10) ◽  
pp. 1144-1154 ◽  
Author(s):  
Dajeong Kim ◽  
Jangbeen Kyung ◽  
Dongsun Park ◽  
Ehn-Kyoung Choi ◽  
Kwang Sei Kim ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document