TY - JOUR
T1 - Anti-tumor and differentiation-inducing activity of N,N-dimethylformamide (DMF) in head-and-neck cancer xenografts
AU - van Dongen, G. A.
AU - Braakhuis, B. J.
AU - Leyva, A.
AU - Hendriks, H. R.
AU - Kipp, B. B.
AU - Bagnay, M.
AU - Snow, G. B.
PY - 1989/1/1
Y1 - 1989/1/1
N2 - The anti-tumor activity of the putative differentiation-inducing agent dimethylformamide (DMF) was assessed in 7 head-and-neck xenograft (HNX) lines transplanted into nude mice. The drug was administered intra-peritoneally at the maximum tolerated dose. A significant growth-inhibitory effect was observed in 3 out of 7 tumor lines tested. When compared with 5 conventional drugs active in patients with squamous-cell carcinoma of the head and neck (HNSCC), DMF was as effective as the most active drugs (cisplatin and bleomycin). The most sensitive xenograft line, the poorly differentiated tumor HNX-14C, was used to test the hypothesis that differentiation induction might play a role in the anti-tumor activity of DMF. Light microscopic examination did not show clear-cut alteration of differentiation characteristics such as keratin and keratin pearl formation. Furthermore, we used a monoclonal antibody to study the expression of cytokeratin 10 which is useful as a differentiation marker of human HNSCC tumors. Keratin 10, not present in HNX-14C tumors grown under control conditions, became expressed in some cells upon DMF treatment. Further evidence for a differentiation-inducing activity of DMF was found in electron-microscopic studies. In treated HNX-14C tumors, in addition to cells with normal ultrastructural features, better-differentiated cells were observed, as manifested by an increase in the number of tonofilaments and desmosomes. The results show that DMF has a potential value for the treatment of patients with head-and-neck cancer, and that differentiation induction might play a role in the anti-tumor action of the drug
AB - The anti-tumor activity of the putative differentiation-inducing agent dimethylformamide (DMF) was assessed in 7 head-and-neck xenograft (HNX) lines transplanted into nude mice. The drug was administered intra-peritoneally at the maximum tolerated dose. A significant growth-inhibitory effect was observed in 3 out of 7 tumor lines tested. When compared with 5 conventional drugs active in patients with squamous-cell carcinoma of the head and neck (HNSCC), DMF was as effective as the most active drugs (cisplatin and bleomycin). The most sensitive xenograft line, the poorly differentiated tumor HNX-14C, was used to test the hypothesis that differentiation induction might play a role in the anti-tumor activity of DMF. Light microscopic examination did not show clear-cut alteration of differentiation characteristics such as keratin and keratin pearl formation. Furthermore, we used a monoclonal antibody to study the expression of cytokeratin 10 which is useful as a differentiation marker of human HNSCC tumors. Keratin 10, not present in HNX-14C tumors grown under control conditions, became expressed in some cells upon DMF treatment. Further evidence for a differentiation-inducing activity of DMF was found in electron-microscopic studies. In treated HNX-14C tumors, in addition to cells with normal ultrastructural features, better-differentiated cells were observed, as manifested by an increase in the number of tonofilaments and desmosomes. The results show that DMF has a potential value for the treatment of patients with head-and-neck cancer, and that differentiation induction might play a role in the anti-tumor action of the drug
UR - http://www.scopus.com/inward/record.url?scp=0024551363&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ijc.2910430221
DO - https://doi.org/10.1002/ijc.2910430221
M3 - Article
C2 - 2465278
SN - 0020-7136
VL - 43
SP - 285
EP - 292
JO - International journal of cancer. Journal international du cancer
JF - International journal of cancer. Journal international du cancer
IS - 2
ER -