Patent Description:
The discovery of oncogenes and tumor suppressor genes (TSGs) revealed the biochemical basis of the impact of some metabolic pathways of tumor cells on some peculiar features of tumors, including e.g. uncontrolled proliferation, nondependence from stimulation of growth factors and resistance to apoptosis.

The metabolism is the assemble of biochemical transformations that take place inside the cells and which include, e.g., the catabolic processes of energy unit production (in the form of ATP or reducing equivalents) and the anabolic processes of complex biomolecule synthesis, such as proteins, lipids and DNA. The metabolic pathway that has been most studied and successfully used in anticancer treatments is the synthesis of nucleotides and deoxynucleotides. Other metabolic pathways have only recently become research focus, based on new discoveries and by virtue of the plateau reached in terms of improving efficacy with traditional therapies.

Similar to highly proliferative healthy cells, cancer cells need a constant supply of ATP and anabolic precursors to support crucial biochemical processes, such as DNA synthesis and repair, protein and lipid synthesis, protein post-translational modifications, formation and re-assembly of membranes and organelles, vesicular transport of intracellular cargo and endocytosis.

It has been observed that many tumors are characterized by reprogramming mechanisms of oncogene-dependent metabolic pathways, e.g., while the mitochondrial oxidation of pyruvate deriving from glucose represents the main source of ATP for healthy proliferative cells, in cancer cells the synthesis of pyruvate is diverted to lactate synthesis metabolism from the mitochondrial oxidation one.

Recent studies have shown that not only glycolysis, but also other metabolic pathways can be regulated differently in cancer cells than in the cells of the corresponding normal tissues. Furthermore, the relationship between oncogenes/TSGs and metabolic reprogramming suggests that the altered regulation of metabolisms crucially contributes to the uncontrolled proliferation of the neoplastic cell.

Therefore, diet changes could have an impact on tumor growth by changing the plasma concentration of different biomolecules and metabolites that support the proliferation and other biological functions of cancer cells. Given the great variety of possible approaches and their unpredictable and complex impact on the multiplicity of blood metabolites, it is not obvious or immediate to be able to design the "ideal" anticancer diet which is safe, well tolerated and accepted by patients and, at the same time, biologically active and effective. Diets to be used as adjuvants for cancer therapy are known from e.g., <CIT> and <CIT>.

Since moderate chronic calorie restriction significantly reduces tumor incidence in primates and other mammal species, many anti-cancer dietary approaches currently under study are based on the assumption that restriction/modulation of nutrient intake can reduce the cancer cell uptake of metabolites (<NPL>).

The Applicant has now identified a specific combination of nutrients, suitable for preparing low-calorie, low-carbohydrate and low-protein meals, useful in patients suffering from different types of neoplasias.

The object of the present invention is a kit comprising food preparations according to claim <NUM> for use as therapeutic adjuvants in the daily diet of patients affected by neoplasias.

The present invention relates to a kit for use as a therapeutic adjuvant in the daily diet of patients suffering from neoplasia, comprising a plurality of daily food preparations, wherein:.

wherein the components of the nutritional combinations (A1, A2, A3) and the dietary fibre (B <NUM>, B2, B3) are foods of vegetable origin. According to the scope of the present invention, by food preparation (or nutrition plan) is meant a combination of foods suitable for the arrangement of one or more meals.

By daily food preparation, is meant a combination of foods intended to provide sufficient caloric content for one day; in other words, the food preparation of the invention is intended for daily use, as a therapeutic adjuvant in the diet of patients suffering from neoplasias.

By therapeutic adjuvant is meant a biologically active substance or a set of biologically active substances, to be taken in combination with anticancer therapies, to enhance their therapeutic effects. In the present case, such biologically active substances are taken through the diet, with the food preparations of the present invention.

By patients suffering from neoplasias is meant subjects who have been diagnosed by a medical specialist with a malignant tumor of any type, at any stage of growth; examples of neoplasias in subjects suitable for the diet with the food preparation of the invention are breast cancer, colorectal cancer, lung cancer, prostate cancer, melanoma, chronic lymphatic leukemia.

As indicated above, the daily caloric content of the food preparation is between <NUM> Kcal and <NUM> Kcal, preferably between <NUM> and <NUM> Kcal, more preferably between <NUM> and <NUM> Kcal. This daily calorie content is low enough to induce specific metabolic effects, including a reduction in the blood concentration of glucose, insulin and insulin-like growth factor (IGF-<NUM>), which constitute the metabolic prerequisite for the expected immunomodulatory and anticancer effects to occur.

It should be noted that the maximum calorie content during each diet day is the same for each patient, regardless of weight or other anthropometric parameters (height, body mass index, body composition). The minimum caloric content, on the other hand, is potentially different from patient to patient, as it depends on the ability of each patient to consume the maximum amount of food intended by the schedule or, alternatively, only a part of it.

It should be noted that, according to an embodiment of the invention which is not the subject of the present patent application, the patient suffering from neoplasm can also be subjected to a fasting regime (<NUM> Kcal/day) for a maximum duration of <NUM> consecutive days.

Generally, by food we mean a substance that, introduced into the animal organism, compensates for its expenditure in living force, provides for the reintegration matter, necessary for any growth, and such factors (proteins, fats, carbohydrates, vitamins, minerals) which are essential for the normal performance of fundamental functions for the individual and the species. In the science of nutrition, simple foodstuff, i.e., proteins, carbohydrates or carbohydrates, lipids or fats, vitamins and minerals, and compound foodstuff, consisting in various proportions of simple foods (milk, meat, fruit, etc.) are distinguished. More generally, by foodstuff is meant food (http://www. it/vocabolario/alimento/).

In view of the above-mentioned definitions, according to the scope of the invention, by foodstuff is meant a compound food which, for the purposes of carrying out the food preparation of the invention, is of vegetable origin.

By food of vegetable origin is meant a food consisting of vegetables or which is obtained from the vegetable (such as vegetable oils) by chemical/physical treatment of the source plant.

The daily food preparations which are present in the kit of the invention comprises nutritional preparations containing.

dietary fiber (B) in an amount comprised between <NUM> and <NUM>, preferably between <NUM> and <NUM>, preferably between <NUM> and <NUM>, preferably between <NUM> and <NUM>. Foodstuffs containing vegetable fiber are included in the daily food preparation as "bulking agents", which are capable to increase the diet bulk without causing a significant increase in its calorie content.

It should be noted that the percentages of each nutrient (carbohydrates, proteins, lipids) are percentages by weight calculated on the total weight of the nutritional combination (A).

The carbohydrates of the daily food preparation preferably comprise between <NUM>% and <NUM>% (w/w) by weight of starches; between <NUM>% and <NUM>% (w/w) by weight of soluble carbohydrates.

The lipids of the daily food preparation preferably comprise between <NUM>% and <NUM>% (w/w) by weight of saturated fat; between <NUM>% and <NUM>% (w/w) by weight of monounsaturated fats; between <NUM>% and <NUM>% (w/w) by weight of polyunsaturated fats.

The proteins of the daily food preparation preferably consist of <NUM>% vegetable proteins.

The dietary fiber of the daily food preparation preferably comprises between <NUM>% and <NUM>% (w/w) by weight of soluble fiber; between <NUM>% and <NUM>% (w/w) by weight of insoluble fiber.

The caloric content of each of the foods contained in the daily food preparation was calculated on the basis of data available on the website www. it (website of "Consiglio per la Ricerca in Agricoltura e per l'analisi dell'economia agraria"), based on the INRAN data set (nut.

The carbohydrates contained in the daily food preparation preferably and mostly originate from bread and fruit.

The proteins of the daily food preparation preferably originate from whole wheat bread, vegetables, plant seeds and combinations thereof.

The lipids of the daily food preparation preferably originate from wholemeal bread, extra virgin olive oil, plant seeds and combinations thereof.

The fibers contained in the daily food preparation preferably originate from whole wheat bread, vegetables, fruit, and combinations thereof.

The daily food preparation is particularly advantageous as is extremely versatile; in order to improve the efficacy of anticancer therapies, the patient suffering from neoplasia who intends to be on a diet with the preparation of the invention, can make prepare various dishes and choose to consume the foodstuffs both cooked and raw, in liquid form (e.g. smoothies) or in solid form, depending on the preference.

The form in which the patient intends to take the foodstuffs of the preparation, in fact, does not affect the diet biological (immunological or metabolic) effects, which are attributable to the calorie, carbohydrate and protein restriction that characterizes the food preparation of the invention.

Preferably, the daily food preparation of the invention further comprises aqueous drinks in a total amount of between <NUM> and <NUM>, more preferably between <NUM> and <NUM>.

According to a preferred embodiment, the daily food preparation according to the invention provides for the intake of at least <NUM> liters of liquids per day during the autumn/winter season and at least <NUM> liters of liquids per day during the spring/summer season. The intake of liquids in such quantities is important to ensure adequate hydration, in order to dispose of the organic acids (e.g. acetoacetic acid, beta-hydroxybutyric acid and uric acid) that accumulate in the blood during the diet, and also as a remedy for decreased sense of thirst that can be associated with calorie restriction. In order to stimulate thirst, and therefore to guarantee a sufficient intake of liquids to the patient, the food preparation provides for the possibility of intaking various non-caloric, water-based drinks.

By non-caloric drink is meant a drink having an average caloric content lower than <NUM> Kcal/liter.

Preferably, the non-caloric aqueous drink is selected from the group consisting of water, green or black tea, non-caloric herbal teas, and combinations thereof.

It should be noted that, despite the calorie content per liter, the daily food preparation allows the intake of coffee (espresso); preferably, the coffee (espresso) is taken in quantities not exceeding two cups a day (about <NUM> cl, equivalent to about <NUM> Kcal).

According to a preferred embodiment, the daily food preparation further includes a non-caloric aqueous drink, selected from the group consisting of water, green or black tea, non-caloric herbal teas, and combinations thereof, and/or coffee.

It should be noted that the daily food preparation is suitable for use as a therapeutic adjuvant in the diet of subjects suffering from neoplasias for a maximum of <NUM> consecutive days, and can be repeated on a three-week or four-week basis. Preferably, the daily food preparation is suitable for use as a therapeutic adjuvant in the diet of subjects suffering from neoplasias for a period of between <NUM> and <NUM> days, preferably between <NUM> and <NUM> days, preferably between <NUM> and <NUM> days, preferably between <NUM> and <NUM> days.

It should be noted that, according to a preferred embodiment, the daily food preparation contains about <NUM>-<NUM> Kcal during the first day, and about <NUM>-<NUM> Kcal, each day, in the following four (second, third, fourth and fifth) days.

The patients who take the daily food preparation of the present invention are preferably subjects suffering from neoplasias.

Preferably, in cases of radiotherapy and/or chemotherapy anticancer treatments, non-radio/chemotherapy anticancer treatments, the food preparation according to the invention is taken before (neo-adjuvant), during (co-adjuvant) and after (adjuvant) the administration of the treatment.

More preferably, in the case of anticancer radiotherapy and/or chemotherapy, immunotherapy, endocrine treatment or anticancer treatment with molecularly targeted biological drugs, the food preparation according to the invention is taken starting from two days before the start of the administration of the treatment and until completion of the five-day diet (i.e. up to about <NUM> hours after starting the anticancer treatment).

For example, in patients receiving intravenous treatments (e.g. chemotherapy, immunotherapy) the diet is started two days before the administration of the treatment, ending on the third day after the start of the administration thereof; in patients receiving oral chemotherapy treatment, the diet is preferably started two days before the start of therapy, and continued until the completion of the five days, regardless of the chemotherapy schedule; in patients receiving radiotherapy treatment, the experimental diet is preferably started two days before the start of radiation therapy, and continued for <NUM> days; in patients receiving non-chemotherapy oral therapies, the diet is preferably started at the beginning of oral therapy, or during the course thereof, and continued until the completion of the five days.

Preferably, in cases where the patient does not receive any anticancer treatment, the food preparation is administered on a three- or four-week basis for a duration of five consecutive days.

The present invention relates to a kit for use as a therapeutic adjuvant in the daily diet of patients suffering from neoplasia, comprising a plurality of daily food preparations hereafter called first, second and third daily food preparations.

dietary fiber (B1) in an amount comprised between <NUM> and <NUM>, preferably between <NUM> and <NUM>, preferably between <NUM> and <NUM>, preferably of <NUM>, the first embodiment of the daily food preparation being characterized by a average caloric content between <NUM>-<NUM> KCal, in which the nutritional combination (A1) and dietary fiber (B1) consist of foods of vegetable origin.

Preferably, the first daily food preparation is characterized by an average caloric content of about <NUM> Kcal.

Preferably, such first daily food preparation is intended for use as an adjuvant for the diet of patients suffering from neoplasia for a period of <NUM> day.

More preferably, said first daily food preparation is intended for use as an adjuvant the diet of patients suffering from neoplasia on day one of the diet.

According to a preferred embodiment, at least <NUM>% by weight of the nutritional combination (A1) consists of carbohydrates and lipids. More preferably, the nutritional combination (A1) consists of between <NUM>% and <NUM>% by weight (w/w) of carbohydrates and lipids.

The lipids of the daily food preparation preferably comprise between <NUM>% and <NUM>% (w/w) by weight of saturated fat; between <NUM>% and <NUM>% (w/w) by weight of monounsaturated fats; between <NUM>% and <NUM>% (w/w) by weight of polyunsaturated fats.

The dietary fiber (B1) of the daily food preparation preferably comprises between <NUM>% and <NUM>% (w/w) by weight of soluble fiber; between <NUM>% and <NUM>% (w/w) by weight of insoluble fiber.

The carbohydrates (carbohydrates) contained in the first embodiment of the daily food preparation preferably originate from bread and fruit.

The proteins of the daily food preparation preferably originate from whole wheat bread, vegetables, and combinations thereof.

The lipids of the daily food preparation preferably originate from wholemeal bread, extra virgin olive oil and combinations thereof.

Preferably, the daily food preparation further comprises aqueous drinks in a total amount of between <NUM> and <NUM>, more preferably between <NUM> and <NUM>.

According to a preferred embodiment, the daily food preparation according to the invention provides for the intake of at least <NUM> liters of liquids during the autumn/winter season and at least <NUM> liters of liquids during the spring/summer season. The daily intake of liquids in such quantities is important to ensure adequate hydration, in order to dispose of the organic acids (e.g. acetoacetic acid and beta-hydroxybutyric) that accumulate in the blood during the diet, and also as a remedy for decreased sense of thirst that can he associated with calorie restriction In order to stimulate thirst, and therefore to guarantee a sufficient intake of liquids to the patient, the daily food preparation provides for the possibility of intaking non-caloric, water-based drinks.

Preferably, the non-caloric aqueous drink is selected from the group consisting of water, green or black tea, coffee, non-caloric herbal teas, and combinations thereof. Preferably, the coffee (espresso) is taken in quantities not exceeding two cups a day (about <NUM> cl, equivalent to about <NUM> Kcal).

The second daily food preparation which is part of the kit of the invention comprises a nutritional combination (A2) containing.

dietary fiber (B2) in an amount comprised between <NUM> and <NUM>, preferably between <NUM> and <NUM>, preferably between <NUM> and <NUM>, preferably of <NUM>, the second embodiment of the daily food preparation being characterized by a average caloric content between <NUM> and <NUM> Kcal, in which the nutritional combination (A2) and dietary fiber (B2) consist of foods of vegetable origin.

Preferably, the daily food preparation has an average calorie content of about <NUM> Kcal.

Preferably, such second daily food preparation is intended for use as an adjuvant for the diet of patients suffering from neoplasia for a period of time ranging from <NUM> to <NUM> consecutive days, more preferably <NUM> consecutive days.

More preferably, said second daily food preparation is intended for use as an adjuvant for the diet of patients suffering from neoplasia on the second, third and fourth day of the diet.

According to a preferred embodiment, at least <NUM>% by weight of the nutritional combination (A2) consists of carbohydrates and lipids. More preferably, the nutritional combination (A2) consists of between <NUM>% and <NUM>% by weight (w/w) of carbohydrates and lipids.

The dietary fiber (B2) of the daily food preparation preferably comprises between <NUM>% and <NUM>% (w/w) by weight of soluble fiber; between <NUM>% and <NUM>% (w/w) by weight of insoluble fiber.

The carbohydrates (carbohydrates) contained in the daily food preparation preferably originate from bread and fruit.

The proteins of the daily food preparation preferably originate from vegetables, dried fruit, and combinations thereof.

The lipids of the daily food preparation preferably originate from extra virgin olive oil, dried fruit, and combinations thereof.

According to a preferred embodiment, the daily food provides for the intake of at least <NUM> liters of liquids during the autumn/winter season and at least <NUM> liters of liquids during the spring/summer season. The intake of liquids in such quantities is important to ensure adequate hydration, in order to dispose of the organic acids (e.g. acetoacetic acid and beta-hydroxybutyric) that accumulate in the blood during the diet, and also as a remedy for decreased sense of thirst that can be associated with calorie restriction In order to stimulate thirst, and therefore to guarantee a sufficient intake of liquids to the patient, the daily food preparation provides for the possibility of intaking non-caloric, water-based drinks.

Preferably, the non-caloric aqueous drink is selected from the group consisting of water, green or black tea, coffee, non-caloric herbal teas, and combinations thereof.

Preferably, the coffee (espresso) is taken in quantities not exceeding two cups a day (about <NUM> cl, equivalent to about <NUM> Kcal).

The third daily food preparation which is part of the kit of the invention comprises a nutritional combination (A3) containing.

dietary fiber (B3) in an amount comprised between <NUM> and <NUM>, preferably between <NUM> and <NUM>, preferably between <NUM> and <NUM>, preferably of <NUM>, the third embodiment of the daily food preparation being characterized by a average caloric content between <NUM> and <NUM> KCal, in which the nutritional combination (A3) and dietary fiber (B3) consist of foods of vegetable origin.

Preferably, such third embodiment is intended for use as an adjuvant for the diet of patients suffering from neoplasia for a period of <NUM> day.

More preferably, said third daily food preparation is intended for use as an adjuvant the diet of patients suffering from neoplasia on day five of the diet.

According to a preferred embodiment, at least <NUM>% by weight of the nutritional combination (A3) consists of carbohydrates and lipids. More preferably, the nutritional combination (A3) consists of between <NUM>% and <NUM>% by weight (w/w) of carbohydrates and lipids.

The carbohydrates of the daily food preparation of the invention preferably comprise between <NUM>% and <NUM>% (w/w) by weight of starches; between <NUM>% and <NUM>% (w/w) by weight of soluble carbohydrates.

The proteins of the daily food preparation preferably originate from fruit, vegetables, and combinations thereof.

The lipids of the daily food preparation preferably originate from extra virgin olive oil.

The fibers contained in the daily food preparation preferably originate from vegetables, fruit, and combinations thereof.

Preferably, the daily food preparation of the invention further comprises aqueous drinks in am amount of between <NUM> and <NUM>, more preferably between <NUM> and <NUM>.

According to a preferred embodiment, the daily food preparation provides for the intake of at least <NUM> liters of liquids during the autumn/winter season and at least <NUM> liters of liquids during the spring/summer season. The intake of liquids in such quantities is important to ensure adequate hydration, in order to dispose of the organic acids (e.g. acetoacetic acid and beta-hydroxybutyric) that accumulate in the blood during the diet, and also as a remedy for decreased sense of thirst that can be associated with calorie restriction In order to stimulate thirst, and therefore to guarantee a sufficient intake of liquids to the patient, the daily food preparation provides for the possibility of intaking non-caloric, water-based drinks.

Preferably, the non-caloric aqueous drink is selected from the group consisting of water, green or black tea, coffee, non-caloric herbal teas, and combinations thereof. Preferably, the coffee is taken in quantities not exceeding two cups a day (one cup is equivalent to <NUM> of drink, with an average caffeine content of <NUM>/mL, obtained from roasted and ground coffee).

The present invention is a kit comprising daily food preparations <NUM>, <NUM>, and <NUM> defined above for use as a therapeutic adjuvant in the daily diet of patients suffering from neoplasias.

The kit comprises the first, second and third embodiments of the daily food preparation according to the invention, so as to supply the patient with the food preparations necessary to complete a diet cycle, preferably of <NUM> consecutive days. In this sense, what previously discussed in relation to the first, second and third embodiments of the daily food preparation according to the invention applies as it is to the kit.

According to the present invention, said kit comprises:.

wherein the components of the nutritional combinations (A1, A2, A3) and the dietary fibre (B1, B2, B3) are foods of vegetable origin.

The use of the daily food preparation according to the kit of the invention is associated with a series of significant immunoregulatory effects targeting the peripheral blood of the patients. These effects include:.

These immunoregulatory effects had never been previously described in patients suffering from different types of neoplasias. Our recent discoveries show that the experimental diet is able to stimulate the activation of anticancer immunity in patients suffering from different types of neoplasias, treated with different types of concomitant anticancer therapies.

For illustrative and non-limiting purposes, below are examples of the daily food preparation which are part of the kit according to the invention.

Example <NUM>: Experimental diet in a patient with breast cancer and treated with concomitant chemotherapy:.

Claim 1:
Kit for use as a therapeutic adjuvant in the daily diet of patients suffering from neoplasia, comprising a plurality of daily food preparations, wherein
- a first daily food preparation contains
A1) a nutritional combination comprising carbohydrates in an amount ranging from <NUM>% to <NUM>% (w/w), proteins in an amount ranging from <NUM>% to <NUM>% (w/w), lipids in an amount ranging from <NUM>% to <NUM>% (w/w); and
B1) dietary fibre in an amount ranging from <NUM> to <NUM>,
the first preparation being characterized by an average caloric content of between <NUM> and <NUM> Kcal;
- a plurality of a second daily food preparation which contains
A2) a nutritional combination comprising carbohydrates in an amount ranging from <NUM>% to <NUM>% (w/w), proteins in an amount ranging from <NUM>% to <NUM>% (w/w), lipids in an amount ranging from <NUM>% to <NUM>% (w/w); and
B2) dietary fibre in an amount ranging from <NUM> to <NUM>,
the second preparation being characterized by an average caloric content of between <NUM> and <NUM> Kcal; and
- a third daily food preparation which contains
A3) a nutritional combination comprising carbohydrates in an amount ranging from <NUM>% to <NUM>% (w/w), proteins in an amount ranging from <NUM>% to <NUM>% (w/w), lipids in an amount ranging from <NUM>% to <NUM>% (w/w); and
B3) dietary fibre in an amount ranging from <NUM> to <NUM>,
the third preparation being characterized by an average caloric content of between <NUM> and <NUM> Kcal, and
wherein the components of the nutritional combinations (A1, A2, A3) and the dietary fibre (B1, B2, B3) are foods of vegetable origin.