Differentiation therapy

We see some similarities between the major life processes in plants (growth and differentiation) and the major life processes in animals and humans (proliferation and differentiation). We expect in future to relate this concept to animal production and to human health, to be able to cross the bridge from soil to plant to animal and finally human health. For example, the development in medicine of differentiation therapy in which vitamin A-derivates are used to treat human cancer cells in vitro (De Luca el al., 1995). Cancer is defined by too much uncontrolled growth of cells without enough differentiation. Using treatment with vitamin A-derivatives - a product of differentiation processes in the plant - undifferentiated cancer cells change into differentiated more healthy ones. 

There has been some concern expressed regarding the use of CSFs to treat MDS patients. Because these cytokines have proliferative activity, they have the potential to induce a leukaemic transformation in the malignant clone. However, the combined use of CSFs with cytotoxic drugs such as cytosine arabinoside (ara-C) appears promising. If leukaemic clones are induced to proliferate by the cytokine, then they are killed by ara-C as they enter the cell cycle. Other forms of differentiation therapy, such as treatment with retinoids, 1,25-dihydroxyvitamin D3 and interferons, have also been tested, but results have been variable. 

SARS Is a federally man- Headache differential Therapy is largely supportive. 

P. Fenaux and L. Degos Differentiation therapy for acute promyelocytic leukemia. New England Journal of Medicine 337, 1076 (1997). 

Butyrate has potential for use in differentiation therapy but is limited by the requirement of millimolar concentrations and short metabolic half-life for efficacy. In order to overcome these problems BA derivatives (prodrugs) have been synthesized and screened. Among them, pivaloyloxymethyl butyrate (named AN-9) has demonstrated impressive anticancer activity in preclinical and clinical studies [23, 24, 28]. AN-9, metabolized intracellularly to acids and aldehyde, affects and penetrates cancer cells about 100-fold faster than BA [25]. 

In this work we chose HT-29 human colon cancer cells (ATCC) as a model system for high throughput screening of human cancer cells response to differentiation therapy. 

HT-29 cells are sensitive to differentiation therapy agents such as BA and its derivatives (AN-7 and AN-9) by enhancement of the alkaline phosphatase activity [25, 29]. According to the enzymatic activity level of the treated cancer cells, the efficiency of the particular drug treatment was evaluated. In general, normal enzymatic activity denotes that the cells differentiate properly as a consequence of the particular drug treatment, whilst lack of enzymatic activity denotes ineffectual drug treatment for the particular cancer tumor and for the particular patient. 

In this study, we have demonstrated a new electrochemical method for highly sensitive, accurate, and rapid multiplex detection of colon cancer cells response to differentiation therapy. The development of an electronic biochip array system, adjusted to biological experiments can help tailor cancer treatment to individual patients. Human colon cancer cells, HT-29, were treated with the differentiation therapy drag agents BA, AN-7, and AN-9, and the cells response was simultaneously measured on hue and compared. This microarray technology provides the ability to test on line the affect of multi-drag agents, and to tailor effective therapy to the individual. 

Cao T, Heng BC (2005) Differentiation therapy of cancer. Potential advantages over conventional therapeutic approaches targeting death of cancer/tumor cells. Med Hypotheses 65(6) 1202-1203... 

Sell, S. (2004). Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol 51(1), 1-28. 

Although differentiation therapy does not kill cancer cells, it does have the potential to restrain their self-renewal capacity and perhaps increase the efficacy of conventional therapies, which are often most effective on differentiated cells. Furthermore, differentiation agents often have less toxidty than conventional... 

MRl is also the first-line modality for excluding or demonstrating local tumor recurrence. In particular, MRl enables differentiation of postoperative or radiation-induced scars from recurrent tumor. Additional contrast-enhanced dynamic Tl-weighted studies are helpful to differentiate therapy-related changes from tumor tissue. In contrast, CT demonstrates most local recurrences only when they produce a mass effect or infiltrate adjacent structures or organs [80,81]. 

Although recent years have seen an explosion of interest in the identification and development of small molecule modulators of stem cell fate, early observations in this area were made over 30 years ago describing the effects of naturally derived molecules on cell fate. In 1978, two independent reports demonstrated embryonal carcinoma (EC) cells could be differentiated towards parietal endo-derm-like cells with either all-trans-vtiinoic acid (ATRA) or hexamethylenebis-acetamide. ATRA has since been shown to exhibit pleiotropic effects and to promote differentiation to multiple cell types, and has been used in the clinic for the differentiation therapy of acute promyelogenous leukaemia. ... 

The application of the method for symptomatic patients with a high pretest probability is not indicated for two reasons. A patient with an acute coronary syndrome should be taken to the catheterization laboratory directly in order to offer a timely and direct possibility of transluminal interventions. But for patient with stable angina and high probability, increasing evidence indicates that transluminal intervention does not reduce the rate of future cardiac events in comparison to medical therapy. This has fueled a quest for a noninvasive accurate luminogram to stratify differential therapy options. The demand could be served by CT if the above-outlined restrictions could be overcome. 

Castaigne, S., Chomienne, C, Daniel, M, T, Ballerim, P, Berger, R Fenaux, P, and Degos, L. (1990) All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia I Clinical results. Blood 76, 1704-1709... 

Chomienne, C., Fenaux, P., and Degos, L. (1996) Retinoid differentiation therapy in promyelocytic leukemia, FASEB J. 10, 1025-1030. 

Chao W, Rudd CJ, Costa E, Jong L, Hobbs PD, Lehmann JM, Pfahl M, Lombardo A, Ely KA, Quick T et al (1995) Effects of receptor-selective retinoids on epidermal cells in the presence of the tumor promoter 12-0-tetradecanoylphorbol-13-acetate. American Association of Cancer Research Special Conference, Mechanism of Action of Retinoids, Vitamin D and Steroid Hormones. Whistler, British Columbia, Canada Bollag W, Apfel C, LeMotte P (1995) Retinoids Achievements, prospectives and future goals. In S Waxman (ed.) Challenges in Modem Medicine, VoL 10. Proceedings of the 6th Conference on Differentiation Therapy. Ares Serono Symposia Publications, Rome, 285-302... 

In recent years, discovery of the in vitro and in vivo differentiation of APL blasts by dX -trans retinoic acid (ATRA) has modified the therapeutic approach of APL [23-25] but also lead to important advances in the biology of APL and opened new perspectives for differentiation therapy in cancer [26]. 

Castaigne S, Chomienne C, Daniel MT, Berger R, Fenaux P, Degos L (1990) AVi-trans retinoic acid as a differentiating therapy for acute promyelocytic leukemias. I. Clinical results. Blood 76 1704-1709... 

Warrel RP, Frankel SR, Miller WH, Scheinberg DA, Itri IM, Hittelman WN, Vyas R, Andreeff M, Tafiiri A, Jakubowski A et al (1991) Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-tram retinoic acid). New EnglJ Med 324 1385-1395... 

---