Chalones and Cancer: Melanoma Regression induced by “Chalone”: a New Tumour Inhibiting Principle acting in vivo

Möhr, U.; Althoff, J.; Kinzel, V.; Süß, R.; Volm, M

doi:10.1038/220138a0

Cited by 69 publications

(9 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…So far. for technical reasons, this has been possible with only 3 tumours (2 melanomata, Mohr et al, 1968;] granulocytic leukaemia, Ryt^maa andKivinienii, 1969. 1970), but in all eases the tumour growth was either retarded or reverse<l. In many animals a complete cure was obtained.…”

Section: Partmentioning

confidence: 99%

The Control of Epidermal Thickness*

Bullough¹

1972

Br J Dermatol

View full text Add to dashboard Cite

Summary.— Epidermal mass (thickness) is controlled by a complex mechanism in which the epidermal chalone plays a central role. The chalone inhibits epidermal mitotic activity by reducing the proportion of the basal cells that are in the mitotic cycle and the speed at which this cycle is completed. It also acts to reduce the speed at which the distal post‐mitotic cells age and die. The response of the epidermal mass (thickness) to a rising mitotic rate (falling chalone concentration) is divisible into 3 separate phases. In Phase 1 (e.g. normal mouse epidermis) the mitotic rate is low. Mitosis occurs in the basal layer in such a way that the 2 daughter cells remain basal; the pressure so generated is relieved by the extrusion of a neighbouring basal post‐mitotic cell. Any change in the mitotic rate is matched by an equivalent change in the rate of ageing of the extruded cells; thus no change in epidermal thickness occurs. In Phase 2 (e.g. normal human epidermis, hyperplastic mouse epidermis) the mitotic rate has increased beyond the point at which all the basal cells have entered the mitotic cycle; there are therefore no post‐mitotic basal cells available to be extruded. From this point onwards the greater the mitotic rate (the lower the chalone content), the higher the lateral pressure within the basal layer, the greater the folding (or doubling) of this layer, the higher the numbers of basal mitotic cells per unit area of skin, the higher in consequence the number of distal post‐mitotic cells (which are also ageing more quickly) per unit area of skin, and the thicker the epidermis. Thus epidermal mass (thickness) is a function of the degree of folding (or doubling) of the basal layer and of the increased rate of post‐mitotic ageing. Towards the top of Phase 2 (e.g. psoriasis, papillomata) the chalone content of the whole epidermis has fallen to a low level, but the rate of cell gain still equals the rate of cell loss. In Phase 3 (e.g. epidermal carcinomata) the average chalone content is very low, and the rate of cell gain exceeds the rate of cell loss. The normal balance can be restored by raising the chalone concentration artificially. The manner in which this mechanism operates during normal healing and tissue regeneration is examined, and reasons are given for considering that these epidermal reactions are typical of mitotic tissues and of tumours in general.

show abstract

Section: Partmentioning

confidence: 99%

The Control of Epidermal Thickness*

Bullough¹

1972

Br J Dermatol

View full text Add to dashboard Cite

show abstract

“…The antimitotie chalon [6,7,13] as well as adenosine 3'5'-cycliemonophosphate (cyclic AMP) [5,10,32,37] are capable to inhibit EAT in vitro and in vivo when injected into immature tumors [4,5,8,13,46,52]. In this case too, a correlation of these substances to normal serum factor seems not likely, because chalon is a tissue specific substance and needs adrenalin and hydrocortison for action, and cyclic AMP --if any sufficient amounts are present in normal sera --should prevent tumor growth without treatment.…”

Section: Discussionmentioning

confidence: 99%

Enhanced tumor defence against solid Ehrlich-Ascites tumor and sarcoma 180 mediated by a normal serum factor; comparison with tumor sera

1974

View full text Add to dashboard Cite

Summary. Normal sera of random bred NMRI mice of different provenience as well as those of BALB/c mice enhance tumor defence against Ehrlich-Ascites tumor (EAT) and sarcoma 180 when injected intraperitoneally. Sera of animals of different age, heparinized plasma or even autologous sera were equally active in this test system. However, the sera showed no effect at all when injected intravenously. Sera of C57 and AKR mice were inactive using the intraperitoneal way of application.In Sephadex G 200 chromatography, the normal serum factor of NMRI mice active in tumor defenee is located between the 7S and albumin peak; it is resistant to freezing (--70°C) and heating (30 min, 56°C) and to mercaptoethanol treatment. Its tumor inhibiting effect is demonstrable when injected intraperitoneally on the day of tumor transplantation but also when injected later up to day 5. --Intraperitoneal injection of thioglycollato or india ink had no effect.Presently, the normal serum factor seems not to be correlated with any of the known factors studied more in detail in respect to inhibition of tumor growth.As far as the mechanism is concerned, the normal serum factor is thought to activate peritoneal cells (PEC) resulting in facilitating transmigration of active cells, This was concluded from experiments with autologous PEC pretreated in vitro with normal serum factor.In contrast to sera of normal NMRI mice, the sera of tumor bearing animals of the same line had no effect when injected intraperitoneally. The reason for this was discussed in context with absorption experiments. However, no definite explanration can be given yet.

show abstract

“…So far this has been done with success in three animal tumours: two melanomata (mouse and hamster), [38] and one granulocytic leukaemia (rat) [33,39]. The fact that this may also be done in man has been shown by the inhibition of ten cases of human granuloeytic leukaemia in vitro [31].…”

Section: Treatment Of Tnmours With Chalonesmentioning

confidence: 98%

“…The first experiments were those of MOHR and his colleagues [38] who treated the HardingPassey melanoma of the mouse and an amelanotic melanoma of the hamsterwith the melanocyte chalone [12]. These tumours, which were fastgrowing, consisted of a peripheral mitotic zone, a medial zone of post-mitotic cells (pigmented in the Harding-Passey melanoma) which like normal post-mitotic cells were moving towards their death, and a central mass of dead cells [27].…”

Section: Treatment Of Tnmours With Chalonesmentioning

confidence: 99%

The actions of the chalones

Bullough

1971

Agents and Actions

View full text Add to dashboard Cite

In all the ten tissues so far examined it has been found that mitotic activity is controlled by a negative feedback mechanism in which a ehalone molecule acts as the messenger. A ehalone is synthesised within the same tissue on which it specifically acts to inhibit mitosis, it is not speciesspecific, and it has a prolein nature. The characteristics of a chalone mechanism and of its manner of action in a normal tissue are discussed. From studies of a wide range oftumours, both experimental and clinical, it now appears that their most important common characteristic is an abnormally low intracellular chalone concentration. When these tumoars, which include human tumours, are treated with the chalones of their tissues of origin, their mitotic activity is inhibited. The three tumours which have been repeatedly treated with the appropriate chalone have been destroyed. Thus the chalones are now emerging as potential therapeutic agents for the treatment of cancer. They have the great advantage of strict tissue and tumour-specificity so that the other body tissues remain unaffected by the treatment. The most important problem now concerns their preparation in pure enough form and in adequate quantities.

show abstract

Chalones and Cancer: Melanoma Regression induced by “Chalone”: a New Tumour Inhibiting Principle acting in vivo

Cited by 69 publications

References 6 publications

The Control of Epidermal Thickness*

The Control of Epidermal Thickness*

Enhanced tumor defence against solid Ehrlich-Ascites tumor and sarcoma 180 mediated by a normal serum factor; comparison with tumor sera

The actions of the chalones

Contact Info

Product

Resources

About