IMHCクリニック　コラム＆マスメディア：コラム1

コラム＆マスメディア　Dr. Column & Mass Media

コラム１

Apoptosis　inducing　treatment was applied to cancer prevention

Why systemic immunotthermochemotherapy( s-ITC) can promote the apoptosis of cancer.

ABSTRACT

The episodes of natural spontaneous regression of cancer sometimes happen in the case of high fever. So we have explored apoptosis inducing treatment using combination of artificial elevation of body temperature at 39～41 degree C, a small quantity of chemotherapy , high dose of vitamin C(20g～30g) and high level of cyclic AMP　 in the blood. We call this program as

systemicimmunotthermochemotherapy( s-ITC).　This therapy promotes apoptosis and redifferentiation of cancer cell.

Ninety nine percent of initial cancer can be prevented by using this s-ITC program. so this s-ITC program is easily applied to the high risk group of cancer as the last method.

INTRODUCTION

1) In 1866, a case in which a patient who had been suffering from facial sarcoma was cured ,after developing fever twice caused byerysipelas, was reported by W.Busch.MD

100 years ago, WB.Coley MD injected serratia and streptococous in around the tumor of 1000 inoperable cancer patients which resulted in remarkable data that 5 year- survival rate was 45%. Whereas in the case of the bone cancer, the 5 year survival rate was as high as 79%. However, historically, that was discarded and buried as the "poison of coley", without beingfollowed-up by anyone.

30 years ago, radiologists in order to resolve the bottle-neck of the radiotherapy, started to tacke the treatment method aiming at the necrosis of cancer by combining radio therapy with thermotherapy.

2) On the other hand, the biological characteristics of the cancer cell as neoplasm have been reported many times, for example, Folkman MD reported the fact that the cancer cell did not grow bigger than 2 mm diameter without cancer vessels.

Also professor Sato et al of the Tohoku University reported that the cancer vessel, having no muscle, did not react to angiotensin II and so it is a defective vessel. Figure 1 [below photo] shows electronmicroscopic photograph of the cancer vessel(Kumamoto University)

It may be clearly understood that considering the shaped of this cancer vessel which hinders the flow of blood, thus causing the build-up of heat, why the temperature of the cancer tissue elevated by 1～2 digreeC. higher than the normal tissue.

3) 30 years ago, Sutherland MD proved that cyclic AMP is the second messenger of the hormone and won the Noble prize. Later, An american scholar demonstrated that an addition of 1 mM cyclic AMP to ovary cancer cells enables them to differentiate into normal fibroblast 5～6 hours thereafter, in spite of the interesting data, it did not attract attention as this presentation was light after the award of the Nobel prize.

In December 1999, professor . Sato of the Tokyo Pharmaceutical University presented the fact that when they gave a heating treatment to the uterine cancer cell(HT-1080), the cyclic AMP within the cancer cell increased and doubled. This is the reason why the metastasis and invasion of the cancer cell are prevented.

In normal cell(HUCF), there was no response.

4) Role of the Heat Shock Protein (HSP)

Hiedenburger also reported the fact that cancer cell restored to the normal cell by heating treatment(2). It was known that HSP could be induced into the cell by heating treatment, but it was regarded as a side effect caused by heating treatment in the field of hyperthermia and what was happening within the cell was not known.

In 1987 Ellis, RJ et al reported that HSP played a role as a molecular chaperone. First it did not attract attension. However, in late 1980s, it suddenly became to attract attension, as the mystery of mitochondria became to attension(5).

The mitochondria existing within the cell possess the characterisitics of DNA in the red bacteria era which are totally different from those of nucleus thus, performing semi-autonomic replication like dual systems in one country(as in Hong Kong). Strangely, over 90% of the protein, which makes up the mitochondria DNA, also is produced by the nucleus and over 70% of the AMP synthetase is produced within the nucleus.

It may be considered that the reason why the mitochondria is attributable to the time of birth of the mitochondria. The fact that thermoacidophic bacteria and red bacteria started co-existence in a form like conception(red bacteria on their part, to avoid heat) 18 billion years ago, may be considered to be the birth of the current mitochondria.

Now, following the HSP molecule chaperone theory reported by many researchers, the autonomic replication of mitochondria becomes possible when the mitochondrial protein and ATP-ase produced by the nucleus are brought to mitochondria(Fig 4).

HSP 70 and HSP 60 are common with the red bacteria and with up to the higher animals. Therefore, there is a possibility that the HSP as a molecular chaperone was related to the control and differentiation of the cell structure. Mitochondrial nucleus, like bacteria and rickettsia keep on dividing by forming split ring-like nucleosome as shown in Figure5(Kuroiwa T)

When compared with the diversity and the polymorphism of the mitochondrial DNA, the fact that HSP is common with red bacteria and with up to the higher animals is presumed to suggest a cell regulation function destined since the early time of the birth of mitochondria 18 billion years ago.

The process whereby the HSP came to have a function as the molecule chaperone that red bacteria had a "rendez vous" with protobacteria to avoid heat and came to co-exist together.

5) Next, lets consider about the question of the mysterious mitochondrial DNA.

a) Mitochondria, having no supporting-stroma unlike that of nucleus, is susceptible to be damaged by substances such as carcinogenic substances 10 times more than nuclear DNA.

b) The amount of the protein produced by mitochondria diminishes with ages, reaching almost zero at age 100.

c) From above pheronomenon, with regard to the againg, the oxidative damage given to mitochondrial DNA and consequent accumulation of mutations are considered to be significant.

d) Dr.Tanaka of the International Bio-Center reported about the base arrangements of its mitochondrial DNA.

In the base arrangedments, 5178 variation (C-->A, changing of C to A causes leucin to change to methionine, C is called type C. When it changes to A, it is called the type A was found with 62% of 100 years aged people showing type A.

The result of the examination of the mucous membrance cell taken from the cheek of Kin-san (one of noted Japanese 100 years aged twin) showed the type A.