Cell growth regulator

#The present invention is generally in the field of human and veterinary medicine and concerns novel substances which effect growth and proliferation of cells. The present invention is also concerned with uses of the substances in prevention or therapy of diseases. The invention further concerns a method of diagnosis of diseases or screening for individuals which are prone to or which have a predisposition to develop a disease.

#For the purpose of streamlining the description herein, use will be made with several coined terms. Some of these terms and the manner in which they should be understood in the context of the present writing, are the following:

#"Cell Growth Regulator (G)"--an agent effecting growth or proliferation of cells. The effect of the GR on growth or proliferation may either be in promoting growth or proliferation of cells, or in inhibiting growth or proliferation of cells.

#In the drawings:

#FIGS. 1A, 1B, 2A, 2B, 3A, 3B, 4, 5, 6, 7, 8 and 9 show the effect of the MF or WBF as contained in the filtrate of a muscle cell CM or a white blood cell CM, filtered though a membrane having a molecular cut-off of 3,000 Daltons (such a filtrate will be referred to herein as f "3,000 Dalton MF ultrafiltrate" and "3,000 Dalton WBF ultrafiltrate", respectively). In the figures, cells were grown in 96 microwell plate and incubated with 3,000 Dalton MF filtrate, at several dilutions ("1"- undiluted, "2"- two-fold dilutions, etc.). In all the experiments a non-condition medium served as control. In FIGS. 1A, 1B, 2A, 2B, 3A, 3B, 4 6, 8 and 9, and partially in FIG. 7, the cell perforation was measured by .sup.3 H-thymidine incorporation, and the ordinate shows the radio activity count. In FIG. 5 and partially in FIG. 7, the proliferation was measured by cell count and the ordinate shows the cell number.

#FIGS. 1A and 1B show the effect of a 2,000 Dalton MF ultrafiltrate obtained from a primary culture of newborn rat striated muscle cells, on the proliferation of two tumor cell lines; B16, which is a murine melanoma cell line (FIG. 1A); HTB-38, which is a human adenocarcinoma cell line (FIG. 1B) In this figure, the activity of 3,000 Dalton MF ultrafiltrate is compared to that of the crude conditioned medium ("crude CM").

#In the following reference will at times be made to "MF" or "WBF" in discussing the activity of active fractions obtained from a muscle cell CM and a white blood cell CM. It should be understood, that it is possible that these two CMs contain more than one factor having the activities described below. In fact, the HPLC fractionation results obtained in accordance with the invention, some of which are shown below, may be explained in this manner (although other explanations axe also possible). Thus, for example, it is possible that the muscle cell CM contains more tan one factor which has a tumor growth inhibitory effect. Thus, for example, reference made at times to "the MF", etc., should not be construed as meaning the muscle CM contains only a single LMW-EGR, as the muscle cell CM could in fact contain more than one substance all of which could be termed "MF".

#MF

#MF was obtained from conditioned media (CM) of three types of muscle cell preparations: