T.J. Martell Memorial Laboratories at Mt. Sinai Medical Center
New York City, NY

Dr. James Holland,
Principal Investigator

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The T.J. Martell Memorial Laboratories for  Leukemia, Cancer, and AIDS Research at Mount Sinai Medical Center has substantially improved the treatment for MDS (myelodysplastic syndrome), a precursor of acute leukemia.  We previously had discovered the first successful chemotherapy for this condition with AzaC (azacytidine).  AzaC works on DNA in leukemic cells to allow it to express more normal genes.  Now we have added to the treatment plan another new drug that works on the proteins that are in DNA.  The combination causes more rapid and more frequent responses, and more effectively prevents the development of leukemia.

We have shown over many years that a virus is present in more than 35% of American womens’ breast cancers.  The human mammary tumor virus (HMTV) is 95% identical to the mouse MTV (MMTV) known to cause breast cancer in mice.  We now know some of the places where the human virus inserts into DNA, which will help in determining exactly which genes are important in causing cancer.  We have already shown that HMTV in human breast cancer cells can be transmitted to normal breast cells, and are actively engaged in experiments to show that these cells acquire all the characteristics of cancer cells.

We have discovered a new protein hormone from the pituitary, called the master gland.  This hormone converts breast cancer cells into a more benign type of cell by causing cells to follow patterns of differentiation closer to normal.  For this reason we call this hormone tumor differentiating factor (TDF).  Breast cancer cells, for example, change their appearance toward that or normal cells, and make the message for enzymes that create milk, which untreated cancer cells do not do.  We have isolated a much smaller molecule that is a segment of TDF.  TDF-small effectively shares all the activity of TDF, and is small enough to make synthetically in the laboratory.  Recently, changing TDF-small by a single carbon atom has increased its activity ten-fold.  Remarkably, this differentiating effect occurs also on prostate cancer cells known to be insensitive to ordinary hormone treatments.  When human breast cancers or hormone refractory  prostate cancers are grown in special mice, TDF-small markedly slows the cancer growth.  Since we already have improved TDF-small by one simple chemical change, we believe further improvements are possible.  And since this is a new hormone, we expect it will have a role in the therapy of human breast cancer and prostate cancer.

We have pursued studies in how muscle cells differentiate from primitive cells in the embryo.  Systems that portray how genes control proteins that bring about differentiation of tissues may light the way toward understanding how cancer cells fail in that respect.  Several newly-discovered protein interactions illustrate the complexity of this problem.

We continue to study new drugs in cell cultures, animal experiments and in human trials.  One drug in wide clinical use for many types of human cancers is doxorubicin.  Its value is limited by its chief toxicity: destruction of heart muscle.  We have identified a new drug that substantially blocks this in mice, while simultaneously improving the anti-tumor effect of doxorubicin on the tumor.  This win-win type effect is being prepared for human trial.

Another new drug is not really new, since it comes from ancient Chinese herbal medicine.  The drug has been purified from the herb, however, and shows significant decrease in human prostate cancer growth in cell cultures and in mice.  Its effectiveness against other cancers has not yet been tested.  Since the herb is taken by mouth in its native form in Chinese medicine, the possibility that the prepared purified drug could be taken by mouth will be explored in tumor-bearing mice.

None of these unique experiments, decidedly not run-of-the-mill, would have been possible without the extraordinary support of the T.J. Martell Foundation.  The vision of the Martell Foundation is funding new concepts before they become popular is exemplary.  The scientists, doctors, nurses and support staff of the T.J. Martell Memorial Laboratories at Mount Sinai join in expressing our deep appreciation and profound thanks.