PMID- 18188568
OWN - NLM
STAT- MEDLINE
DCOM- 20081216
LR  - 20131121
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 62
IP  - 5
DP  - 2008 Oct
TI  - Toxicity and antitumor activity of the vitamin D analogs PRI-1906 and PRI-1907 in 
      combined treatment with cyclophosphamide in a mouse mammary cancer model.
PG  - 787-97
LID - 10.1007/s00280-007-0666-6 [doi]
AB  - PURPOSE: Active and less toxic vitamin D analogs could be useful for clinical 
      applications. In the present study, we evaluated the toxicity and antitumor 
      effect of two new synthetic analogs of vitamin D, namely PRI-1906 
      [(24E)-24a-Homo-(1S)-1,25-dihydroxyergocalciferol] and its side-chain unsaturated 
      homo analog PRI-1907. METHODS: The toxicity and calcemic activity, as well as 
      antitumor effect of calcitriol analogs was investigated in vivo. The studies were 
      performed in a mouse mammary 16/C cancer model. Since calcitriol and its analogs 
      inhibited 16/C tumor growth only slightly, we applied them in the combined 
      therapy with cyclophosphamide (CY). Moreover, cell cycle analysis and VDR and p27 
      expression were investigated. RESULTS: The LD50 values after five daily 
      subcutaneous (s.c.) injections were 7.8, 10.0 and 2.4 microg/kg per day for 
      calcitriol, PRI-1906 and PRI-1907, respectively. The serum calcium level 
      increased to 40, 23 and 63% over the control for these compounds. We also compare 
      the antitumor activity of the PRI-1906 with the calcitriol and previously studied 
      PRI-2191 (1,24-dihydroxyvitamin D3, tacalcitol). Statistically significant 
      inhibition of tumor growth by calcitriol up to the eighth day was observed in all 
      schedules applied. PRI-1906 inhibited the tumor growth at doses 1 and 5 microg/kg 
      per day, and PRI-2191 only at the dose 5 microg/kg per day. CONCLUSION: Addition 
      of vitamin D analogs increased the antitumor effect of CY. PRI-1906 exhibited 
      toxicity higher than PRI-2191 but lower than calcitriol and antitumor activity 
      similar to both PRI-2191 and calcitriol. This new analog seems to be a good 
      candidate for the combined treatment of mammary cancer.
FAU - Wietrzyk, Joanna
AU  - Wietrzyk J
AD  - Department of Experimental Oncology, Institute of Immunology and Experimental 
      Therapy, 12 R. Weigla St., 53-114, Wroclaw, Poland, wietrzyk@iitd.pan.wroc.pl.
FAU - Nevozhay, Dmitry
AU  - Nevozhay D
FAU - Milczarek, Magdalena
AU  - Milczarek M
FAU - Filip, Beata
AU  - Filip B
FAU - Kutner, Andrzej
AU  - Kutner A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080110
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (24a-homo-1,15-dihydroxyergocalciferol)
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Dihydroxycholecalciferols)
RN  - 0 (Ergocalciferols)
RN  - 0 (Vitamins)
RN  - 55248-15-2 (1,25-dihydroxyergocalciferol)
RN  - 60965-80-2 (1 alpha,24-dihydroxyvitamin D3)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - FXC9231JVH (Calcitriol)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Alkylating/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use/*toxicity
MH  - Body Weight
MH  - Calcitriol/blood
MH  - Calcium/blood
MH  - Cell Cycle/drug effects
MH  - Cyclophosphamide/administration & dosage
MH  - Dihydroxycholecalciferols/administration & dosage
MH  - Ergocalciferols/administration & dosage
MH  - Female
MH  - Lethal Dose 50
MH  - Male
MH  - Mammary Neoplasms, Animal/*drug therapy
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred DBA
MH  - Vitamins/blood
EDAT- 2008/01/12 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/01/12 09:00
PHST- 2007/06/25 00:00 [received]
PHST- 2007/12/17 00:00 [accepted]
PHST- 2008/01/12 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/01/12 09:00 [entrez]
AID - 10.1007/s00280-007-0666-6 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2008 Oct;62(5):787-97. doi: 
      10.1007/s00280-007-0666-6. Epub 2008 Jan 10.