ONCOBIOLOGY

ONCOBIOLOGY : OSTEOPOROSIS

ONCOBIOLOGY : AIDS & CANCER

ONCOBIOLOGY

EXPERIMENTAL SCHEMES EXAMPLES

FIRST SCHEME :

Experimental study of the fight against osteoporosis in mammary neoplasms :

AIMS :

  • To bring advance to the knowledge of physiopathological datas of osteoporosis appearing during the mammary carcinomas evolution.
  • To bring advance to the knowledge of biological datas in order to improve osteoporosis detection and assessment of osteoporotic risk.
  • To bring advance to preventive and curative osteoporosis therapy and specifically to classical oestrogenic treatments replacement.

    MEANS :

    Collect and correlate all general datas of osteoporosis complicated breast cancers :

    Gather, collect and correlate all datas intended to study metabolic deviations and their relationship to the endocrine system in the osteoporosis genesis and evolution :

    Thyroid - Parathyroid - Hypophysis - Cortico-suprarenal - Pancreas

    Study the bone metabolism evolution under an adapted oncobiological treatment effect.

    DEFINITIONS :

    Osteoporosis is a bone tissue rarefaction such as all skeleton elements end up not being able to ensure their supporting mechanical function.

    Amongst the various types of types of osteoporosis defined according to their physiological and anatomical differences, we are only keeping, on the anatomical level, the type affecting mainly women after menopause aged between 55 and 70.

    It predominates on spongy or trabecular bone and express itself through vertebral compression. Oestrogenic deficiency seems to play a major part as it appears 6 times more often in women than in men.

    On the physiological level, 3 sub-types can be distinguished according to the activity differences of the trabecular bone remodeling :
    In 50% of the cases, the diagnosis is confirmed only upon the bone biopsy motivated by a recent compression of the spine without any previously detected trabecular bone remodeling abnormality .
    Amongst 30% of osteoporotic women of this type, it is found an increased osteocalcine seric level with extended resorption and osteoformation surfaces showing a high remodeling level.
    The last 20% of these vertebral compression women have a low circulating osteocalcine level because of a reduced osteoblastic apposition speed.

    BIOLOGICAL FOLLOW UP (Days 0, 30, 90, 180) :

    It is meant to establish the type of osteoporosis in order to apply the best adapted treatment and then to follow up the bone metabolism and endocrine distorsions evolution under the treatment's influence.
    It is planned to try to refine the biological detection of the osteoporotic risk, in particular in the type called "without a bone remodeling detectable abnormality".

    I) Bone metabolism evaluation :

    a) osteoblastic activity :

    b) osteoclastic activity :

    c) global remodeling activity

    II) Mammary metabolism evaluation :

    RADIOLOGICAL FOLLOW UP (Day 0-180) :

  • Bone to modensitometry by biphotonic absorptiometry :
    It is meant to confirm the osteoporosis type on the anatomical level and is most valuable in the type "without a biologically detected bone remodeling" and to follow up the bone structure evolution under the treatment's influence.

    THERAPEUTICS :

    Osteoporosis with confirmed high remodeling level

    COMMENTARIES

    1) Brassica napus :
    Turnip is chosen here for its specific blocking action of thyroxine which is reactionnally elevated in these patients, spontaneously or under the violent effect of a induced and therefore unprepared menopause In fact, thyroxine elevates the bone turn over through favouring resorption and so reducing calcitonine activity as much the physiological and residual calcitonine as the medicinal one.
    Turnip also offers the advantage to present none anti-TSH activity. So TSH will be able to go on stimulating the thyroid and to participate to the permanent and necessary thyrocalcitonin boosting.

    2) Vitex agnus castus :
    The hemp tree is chosen here not so much for its anti-oestrogenic action that remains a not inconsiderable contribution to the breast cancer specific treatment (supposedly otherwise correctly led) neither for its anti-FSH activity very important in this double context, but for its primordial activity of lowering the alpha sympathetic function level and its noxious part over the ACTH-prolactine stimulation.

    3) Mercurialis annua :
    Mercurial is chosen here for its very efficient prolactine and GH secretions inhibitory action.

    4) Zea maïs :
    Corn radicle is chosen here for its anti-TRH action. It has a triple grounding, two of them complement the associated treatment's anticarcinological action : oestrogenic stimulation reducing and prolactine secretion rising, the third one concerns the osteoporosis treatment itself and allows to keep a preference for thyrocalcitonine stimulation in the reactional mode chosen for this treatment.

    5) Sequoia gigantea :
    Sequoia is chosen here for its androgene stimulating effect which holds a not inconsiderable contribution to breast cancer specific treatment and brings a direct bone apposition boosting element.

    6) Equisetum arvense :
    Horsetail is chosen here for its silicium and other minerals contents. Silicium elevates bone trabecular volume through a direct osteoblastic stimulation. It has a great usefulness in those high remodeling level osteoporosis where the necesary formation-resorption coupling is very unfavourable to formation.

    7) Calcitonine :
    Calcitonine is chosen here for its depressive action over all remodeling multicellular unit by inhibitating new units activation. In a first move, it directly reduces the osteoclastic bone resorption and therefore immediatly reduces osteoblastic population. This activity endows it with a great advantage for high remodeling level osteoporosis.
    On another hand, because it does not elevate the bone calcium deposit, although its global effect lowers calcemia by reducing intestine absorption and calcium tubular reabsorption, it provokes a secondary hyperparathyroïdism. The latter is all the more pronounced since it leads to a urinary phosphorus loss by inhibitating also its tubular reabsorption.
    It is used as a spine osteoporosis curative treatment, although in a limited manner because of the necesary administrating way - IM or SC - with visible and undesirable side effects (skin flushes, nausea) but its limits should be mainly set by not immediatly visible but much more disturbing side effects, and firstly by the final inhibition of all remodeling effect.

    That is the reason why it is here nothing more than an useful element of the therapeutic strategy whose efficiency and durability are real and trustworthy only within the treatment's entirety. That is also why it has been replaced by a synthetic substitute holding the same properties with much less drawbacks : most of its hormonal type actions in relation to the rest of the endocrine system, oral administrating way possible for a longer time. That is finally why it is only proposed at low doses.

    8) Vitamin D2 :
    Vitamin D2 is chosen here in order to allow an instant accretion of the calcium circulating in excess because of the patient's present balance, and to extend the therapeutic calcitonine action without forcing the organism to resort to GH whose misfunctions effects are fearsome in all proliferative syndromes . Its posology is stricly low (chosen dose here : 100 units) in order to retain pharmacologically active its two first actions only, important in these osteoporosis, the osteoblastic type (osteocalcine synthesis stimulation ) and the bone calcium deposit activating type.

    9) Magnesium :
    Magnesium is chosen here to maintain a sufficient magnesemia level essential to the calcium movements necesary to the efficiency of the therapy in use in front of the biological drift of this particularly troubled time in the patient's life. The mere fact that more than half the magnesium capital is situated inside the skeleton is another argument for this supplementation. Actually the magnesemia decrease provokes an bone magnesium mobilisation hormonal reactivity in many points analogous to the calcium releasing points, particularly a PTH rise and calcitonine decline, whereas on the opposite a magnesemia excess provokes a sorely felt calcitonine rising Its posology is strickly strong (chosen dose here : 4,8 mmol/24 hours) all the more so since the extra daily deficiency is known to be aggravated by the physiopathological troubles generally specific to this patients type.

    Its importance here is even more enhanced by its synergy with other elements from the treatment. Thus the association with silicium, i.e. with horsetail, increases even more the calcitonine secretion's stimulation, reducing accordingly the osteoclastic activity in excess in these high level remodeling forms. The association with vitamin D2 allows an increase of the bone receptivity to this vitamin's action that logically increases itself the magnesium intestinal absorption and diminishes its urinary elimination. Action analogous to the turnip' fighting the thyroid hormones reverse effect.

    10) Potassium :
    Potassium is chosen here to reduce the secondary hyperaldosteronism inevitably accompanying the hormonal disorder of these women life time and the unfavourable consequences over an already faulty and noxious mineral balance.Its posology is simply compensation, i.e. average (chosen dose here 0,52 mmol/24 hours).

    Preserved or low remodeling level osteoporosis

    COMMENTARIES

    1) Lycopus europaeus :
    Lycopus is chosen here in order to favor the osteoclastic time stimulation essential to the bone remodeling stimulation and stopped here by the calcitonine/tri-iodothyronine couple relative excess, result of a hypothalamo-hypophysary functional overactivity. The resulting effect is an excessive osteoclasis blocage that does not allow the osteoblastic production. By blocking the TRH-TSH axis, lycopus will restore, with an improved thyroxinian expression level, a better osteoclastic activity and therefore a bone remodeling resumption through a possible calcium accretion.

    2) Medicago sativa :
    Alfafa is chosen here for - apart from its very specific anti-LH action and its remineralizing properties - its bioavailable supply of vitamin K physiologically essential to osteocalcine synthesis and necessary to an improved vitamin D activity. This galenic form and this extract's constitution general balance, the recommended posologies make almost nil the risk of hypercoagulability manifestation.

    3) Lithospermum arvense :
    It is chosen here to complement the anticancerous treatment hormonal action by inhibitating very efficiently the hypophysary gonadotrophine activity and the lycopus hormonal action, doubling its anti-TSH activity.

    4) Equisetum arvense :
    Horsetail is chosen here for its silicium and other minerals contents. Silicium elevates bone trabecular volume through a direct osteoblastic stimulation. It is always useful even in the low remodeling level osteoporosis cases where resorption stimulation within the formation-resorption coupling is not necessarely sufficient to formation stimulation.

    5) Fluor :
    Fluor is chosen here for its ability to increase the bone trabecular mass. It acts directly upon the osteoblasts of which it increases activity and lifetime. It is recommended exclusively in low remodeling level osteoporosis and totally contraindicated for the high remodeling level cases. Its posology must be rigoureous as an overdose brings osteosclerosis. Its ill-driven or overextended therapeutic use might generate a general bone condensation of the skeleton and particularly of the spine as well as a long bones hypertrophic periostose (fluorose). Apart from the high remodeling level there are two formal contraindication to the fluor treatment. First even a light osteomalacia when associated to osteoporosis would aggravate the fracture risk under the fluor treatment. Then, a renal insufficiency is a formal prohibition to this treatment. Finally some current studies show a sodium fluoride antimitotic activity.

    6) Vitamin D2 :
    Vitamin D2 is chosen here in order to fight the physiological calcitonine action and to allow, because of the patient's present balance, a resumption of calcium mobilization for bone accretion Its posology is stricly average (chosen dose here : 1000 units) in order to retain pharmacologically active the osteoblastic action (stimulation of osteocalcine synthesis), and the action activating bone calcium deposit while stimulating osteolysis to some degree.

    7) Calcium :
    Calcium is chosen here in order to maintain a calcemia level necessary to vitamin D and fluor direct action, and sufficient to avoid any extra parathyroid reactivity that would only hamper the bone density progressive improvement. It should be absorbed away from magnesium and fluor not to hinder their own absorptions.

    8) Magnesium :
    Magnesium is chosen here to maintain a sufficient magnesemia level, parallel to the calcium level, essential to the therapy's efficiency. Magnesium directely activates osteoclasts and osteoblasts allowing to restore a certain modeling level, main drawback of this form. Its posology is strickly strong (chosen dose here : 7,87 mmol/24 hours) all the more so since the extra daily deficiency is known to be aggravated by the physiopathological troubles generally specific to this running pathology. Its level here is even more elevated because of the calcium presence and of the need to maintain some harmony between both ions.

    Its importance is even more valuable because of its synergy with other elements from the treatment over the remodeling resumption and in particular with vitamin D and phosphorus. The association with silicium, i.e. with horsetail, is maintained on order to favour the osteoblastic formation at the osteoclastic resorption's expense, as it is asked by these unsufficient or incomplete remodeling level forms.

    9) Phosphorus :
    Phosphorus is chosen here in order to globally stimulate the bone remodeling thanks to its direct activity over osteoblasts and indirect activity over osteoclasis. Its posology is strictly moderate (chosen dose here : 2,34 mmol/24 hours) in order to pharmacologically favour its osteoblastic action

    SECOND SCHEME

    General evaluation of a medico-surgical oncology department's oncobiological activity :

    AIMS :

  • To bring advance to the protection of patients under anti- cancer chimiotherapy
  • To precise the part and efficiency of oncobiological treatments.

    MEANS :

    Gather, collect and correlate all general, local and biological datas on cancer patients following a chimiotherapy :

    THERAPEUTICS :

  • General catalytic complementation
  • Constitutional and specific catalytic compensation
  • Constitutional and specific nutritional compensation
  • Etiological functional induction

    THIRD SCHEME :

    Experimental study of a treatment against repermeation nodules of mammary neoplasms :

    AIMS :

  • To bring advance to the knowledge of physiopathological datas of the mammary adenocarcinoma repermeation nodules etiology.
  • To bring advance to the adjuvant therapeutics by an in-situ anti-tumoral complementary action.

    MEANS :

    Collect and correlate all general datas on breast cancers complicated with repermeation nodules :

    Gather, collect and correlate all datas intended to study metabolic deviations and their relationship to the endocrine system in the genesis and evolution of a tumors cutaneous and nodular expression :

    Thyroid - Parathyroid - Hypophyse - Cortico-adrenal - Pancreas

    BIOLOGICAL FOLLOW-UP (Days 0, 30, 90, 180) :

    ICONOGRAPHIC FOLLOW UP (Days 0, 30, 90, 180) :

    THERAPEUTICS :

  • Firstly : Bring in situ in overconcentration the main chimiotherapeutic agent presently used in the treatment.
  • Secondly : even use this way exclusively,
  • Thirdly : add the treatment element specific to the hormonal factors underlying the repermeation nodules onset.

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