Compositions, methods, kits and systems for cancer treatment and metabolic intervention therapy

Abstract

The present disclosure provides compositions and methods for treating cancer with nutritionally modified diets and/or dialysis treatment, such as through amino acid depletion of one or more nonessential amino acids. In some aspects, the present disclosure provides compositions and methods for treating obesity with such modified diets and/or dialysis treatment. Furthermore, in some aspects, the present disclosure provides compositions and methods for treating renal disease with such modified diets and/or dialysis treatment.

1 .- 30 . (canceled) 
     
     
         31 . A composition comprising a mixture of amino acids, wherein the mixture comprises:
 (a) one or more of histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, or valine; and   (b) none, or one or more nonessential amino acids selected from alanine, asparagine, aspartate, cysteine or cystine, glutamine, glycine, serine, tyrosine or proline, and wherein when one or more nonessential amino acids are present in the mixture, the amount and ratio of nonessential amino acids to methionine present is in an amount wherein the composition is substantially free of at least one nonessential amino acid and wherein the composition is effective to treat cancer, renal disease, metabolic disease or obesity.   
     
     
         32 . The composition of  claim 31 , wherein when the one or more nonessential amino acids are present in the mixture of amino acids, at least one of the nonessential amino acid is present in the mixture in an amount that provides a molar ratio of methionine of:
 (i) a molar ratio of methionine to alanine that is greater than about 0.06;   (ii) a molar ratio of methionine to asparagine that is greater than about 0.3;   (iii) a molar ratio of methionine to aspartate that is greater than about 2;   (iv) a molar ratio of methionine to cysteine or cystine that is greater than about 0.5;   (v) a molar ratio of methionine to glutamine that is greater than about 0.04;   (vi) a molar ratio of methionine to glycine that is greater than about 0.1;   (vii) a molar ratio of methionine to serine that is greater than about 0.2;   (viii) a molar ratio of methionine to tyrosine that is greater than about 0.3; or   (viiii) a molar ratio of methionine to proline that is greater than about 0.1.   
     
     
         33 . The composition of  claim 31 , wherein the composition decreases the level of plasma cysteine in a subject after consumption of the composition compared to the level of plasma cysteine in the subject before consumption of the composition. 
     
     
         34 . The composition of  claim 33 , wherein the level of plasma cysteine is reduced by at least 30%. 
     
     
         35 . The composition of  claim 31 , wherein the mixture of amino acids further comprises arginine. 
     
     
         36 . The composition of  claim 35 , wherein the amount of methionine is in a molar ratio of methionine to arginine that is greater than about 0.3. 
     
     
         37 . The composition of  claim 31 , wherein the mixture of amino acids further comprises glutamate. 
     
     
         38 . The composition of  claim 37 , when the amount of methionine is in a molar ratio of methionine to glutamate that is greater than about 0.3. 
     
     
         39 . The composition of  claim 31 , further comprising gelatin. 
     
     
         40 . The composition of  claim 31 , further comprising at least one vitamin selected from the group consisting of vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, vitamin K, and choline. 
     
     
         41 . The composition of  claim 40 , wherein the at least one vitamin comprises vitamin B or vitamin C. 
     
     
         42 . The composition of  claim 31 , further comprising at least one ion selected from a group consisting of sodium, calcium, magnesium, chloride, and lactate. 
     
     
         43 . The composition of  claim 31 , further comprising maltodextrin. 
     
     
         44 . The composition of  claim 31 , further comprising at least one mineral selected from the group consisting of iron, copper, chromium, fluoride, iodine, manganese, molybdenum, selenium, and zinc. 
     
     
         45 . The composition of  claim 31 , further comprising one or more preservatives. 
     
     
         46 . The composition of  claim 45 , wherein the one or more preservatives is a citric acid ester of mono- and di-glycerides, lecithin citrate, monoglyceride citrate, or monoisopropyl citrate. 
     
     
         47 . The composition of  claim 31 , further comprising a fatty acid. 
     
     
         48 . The composition of  claim 47 , wherein the fatty acid is omega-3 fatty acid. 
     
     
         49 . The composition of  claim 31 , comprising at least one or more nonessential amino acids selected from the group consisting of alanine, asparagine, aspartate, cysteine or cystine, glutamine, glycine, serine, tyrosine or proline. 
     
     
         50 . The composition of  claim 31 , comprising at least two or more nonessential amino acids selected from the group consisting of alanine, asparagine, aspartate, cysteine or cystine, glutamine, glycine, serine, tyrosine or proline. 
     
     
         51 . The composition of  claim 31 , comprising at least three or more nonessential amino acids selected from the group consisting of alanine, asparagine, aspartate, cysteine or cystine, glutamine, glycine, serine, tyrosine or proline. 
     
     
         52 . The composition of  claim 31 , comprising at least four or more nonessential amino acids selected from the group consisting of alanine, asparagine, aspartate, cysteine or cystine, glutamine, glycine, serine, tyrosine or proline. 
     
     
         53 . The composition of  claim 31 , comprising at least five or more nonessential amino acids selected from the group consisting of alanine, asparagine, aspartate, cysteine or cystine, glutamine, glycine, serine, tyrosine or proline. 
     
     
         54 . The composition of  claim 31 , comprising at least six or more nonessential amino acids selected from the group consisting of alanine, asparagine, aspartate, cysteine or cystine, glutamine, glycine, serine, tyrosine or proline. 
     
     
         55 . The composition of  claim 31 , comprising at least seven or more nonessential amino acids selected from the group consisting of alanine, asparagine, aspartate, cysteine or cystine, glutamine, glycine, serine, tyrosine or proline. 
     
     
         56 . The composition of  claim 31 , comprising at least eight or more nonessential amino acids selected from the group consisting of alanine, asparagine, aspartate, cysteine or cystine, glutamine, glycine, serine, tyrosine or proline. 
     
     
         57 . The composition of  claim 31 , comprising at least nine or more nonessential amino acids selected from the group consisting of alanine, asparagine, aspartate, cysteine or cystine, glutamine, glycine, serine, tyrosine or proline. 
     
     
         58 . The composition of  claim 31 , wherein the composition is a solid food, a semi-solid food, or a liquid. 
     
     
         59 . The composition of  claim 58 , wherein the composition is packaged as a food product, wherein the food product is a snack bar, a cereal product, a bakery product, a dairy product, or a nutritional shake. 
     
     
         60 . The composition of  claim 31 , wherein one or more of alanine, asparagine, aspartate, cysteine or cystine, glutamine glycine, serine, tyrosine or proline are not present in the composition. 
     
     
         61 . The composition of  claim 31 , wherein the one or more of histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, or valine are present in the composition in an amount sufficient to cause a reduction in tumor size in a subject with cancer. 
     
     
         62 . The composition of  claim 31 , further comprising a therapeutic agent. 
     
     
         63 . A method of treating cancer in a subject, the method comprising administering a therapeutically effective amount of the composition according to  claim 31  to a subject in need of said treatment. 
     
     
         64 . The method of treating cancer according to  claim 63 , wherein said treatment suppresses growth of a tumor in said subject. 
     
     
         65 . The method of suppressing growth of a tumor according to  claim 63 , wherein the method is effective for reducing the size of a tumor in the subject. 
     
     
         66 . The method of  claim 63 , wherein the subject has a genetic predisposition for cancer. 
     
     
         67 . The method of  claim 63 , wherein the size of the tumor is reduced by at least 10%. 
     
     
         68 . The method of  claim 63 , wherein the subject has liver cancer, breast cancer, lung cancer, leukemia, prostate, or colon cancer. 
     
     
         69 . The method of  claim 63 , wherein the tumor does not increase in size by at least 10% after administration of the composition compared to the size of the tumor before administration. 
     
     
         70 . A method of decreasing plasma cysteine levels in a subject, the method comprising administering to the subject the composition of  claim 31 , thereby decreasing plasma cysteine levels in the subject. 
     
     
         71 . The method of  claim 70 , wherein the plasma cysteine levels in the subject are decrease by at least 10%. 
     
     
         72 . The method of  claim 70 , wherein the subject has a genetic predisposition for cancer. 
     
     
         73 . The method of  claim 70 , wherein the subject has liver cancer, breast cancer, lung cancer, leukemia, prostate, or colon cancer.