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Methionine free amino acid imbalance using total parenteral nutrition as an adjunct of cancer chemotherapy
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METHIONINE FREE AMINO ACI~n~~~~C~ USING TOTAL PARBNTEfi NUTRITION AS AN ADJUNCT OF CANCER CHEMOTHERAPY. , Goseki N.**, Kosaki G.*, Kuwahata T.*** and Hibino Y.*** (*Surgical Department, Tokyo Metropolitan Komagome Hospital, **SWgical Department I, School of Medicine Tokyo Medical and Dental University, *** Otsuka Pharmaceutical Factory, Incorporated, Tokushima, JAPAN) In recent years, methionine has been reported to be essential for the growth of most of malignant tumor cells in tissue culture studies and animal experiments. Methionine free amino acid imbalance (MF-AAI) was produced by total parenteral nutrition using a specially devised amino acids made by removing methionine and cystine from an ordinary amino acids of Vuj-N type (Panamin S:PAS) in tumor bearing rats and beagle dogs. Antitumor effect of MF-AA1 by itself was recognized but not strong enough for cancer therapy. However, when anticancer agents were qiven to the animals during the development of MF-AAI, prominent inhibitions of tumor growth and metastasis were observed resulting significant prolongations of the survival periods in most of the experiments using different combinations of tumor cells and anticancer agents. For example,in an experiment using rats inoculated with Yoshida sarcoma subcutaneously, the survival period was significantly prolonged to 45.2i17.6 days (n=6) in the group of MF-AA1 plus 5-Fluorouracil (S-FU) while it was 15.9+3.8 days (n=7) in PAS only, 21.3t8.4 days (n=6) in PAS plus 5-FU and 30.4tlS.O days (n=5) in MF-AA1 only. Autopsy-of the experimental animals revealed that the metastasis was a single in the liver of 1 out of 6 rats of MF-AA1 plus 5-FU while it was multiple in many organs of all 6 rats of PAS plus 5-FU. The studies by methods of "fraction of la&led mitosis", "Puck's collection function" and "flow cytometry" showed that duration of cancer cell cycle was siqnificantly prolonged by MF-AAI. On the basis of the animal experiments, MF-AA1 has been clinically applied as an adjunct of cancer chemotherapy demonstrating favorable results.
0.72
EFFECT OF THE TUMOR UN PLASMA FREE TRYPTOPHAN LEVELS IN CANCER PATIENTS C. Cangiano, A. Cascino, F. Ceci, A. Avella, M. Muscaritoli, F. Rossi Fanelli. Lab. of Clin. Nutr., III Dept. of Intern. Med., Univ. of Rome "La Sapienza", Rome, IT. Increased plasma free tryptophan (F-TRP) levels without the related modification of circulating albumin (ALB), its natural carrier, or of serum free fatty acid (FFA), which competitively share the same binding sites for serum ALB with TRP, have been These findings suggested that the tumor previously reported in cancer patients (CP). may per se play a role in the rise of plasma F-TRP levels. To verify this hypothesis, into two groups of 12 lung CP (1CP) and 16 breast CP 28 untreated CP, subdivided (bCP), all eligible for radical surgery, the levels of plasma F-TRP (pmol/l), serum FFA (mEq/l) and serum ALB (g/dl) were measured before and 15 days after surgery. CONTROLS
1CP
bCP
POST-OP PRE-OP POST-OP PRE-OP 0.46+0.1+ 0.66+0.3* 0.72+0.:"+ 1.i)9+0.5* F-TRP 0.4820.1 0.58+0.3+ 1.08+0.3* 0.47+0.2+ 0.71;0.3 0.59to.2 FFA 3.19?0.6+ 3.50+0.5* 3.76$8+ 4.31zo.9 ALB 4.45~0.6 __________________________-___________-_________________________--___-----___--__-__-Mean + S.D.;
* vs controls;
+ vs PRE-OP, Min. sign: p
After tumor removal, plasma F-TRP levels decreased significantly in both groups of These data patients without any significant correlation to serum ALB or FFA levels. support the hypothesis that the tumor may cause, either directly or indirectly, a rise in plasma F-TRP levels in CP.
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METHIONINE FREE AMINO ACI~n~~~~C~ USING TOTAL PARBNTEfi NUTRITION AS AN ADJUNCT OF CANCER CHEMOTHERAPY. , Goseki N.**, Kosaki G.*, Kuwahata T.*** and Hibino Y.*** (*Surgical Department, Tokyo Metropolitan Komagome Hospital, **SWgical Department I, School of Medicine Tokyo Medical and Dental University, *** Otsuka Pharmaceutical Factory, Incorporated, Tokushima, JAPAN) In recent years, methionine has been reported to be essential for the growth of most of malignant tumor cells in tissue culture studies and animal experiments. Methionine free amino acid imbalance (MF-AAI) was produced by total parenteral nutrition using a specially devised amino acids made by removing methionine and cystine from an ordinary amino acids of Vuj-N type (Panamin S:PAS) in tumor bearing rats and beagle dogs. Antitumor effect of MF-AA1 by itself was recognized but not strong enough for cancer therapy. However, when anticancer agents were qiven to the animals during the development of MF-AAI, prominent inhibitions of tumor growth and metastasis were observed resulting significant prolongations of the survival periods in most of the experiments using different combinations of tumor cells and anticancer agents. For example,in an experiment using rats inoculated with Yoshida sarcoma subcutaneously, the survival period was significantly prolonged to 45.2i17.6 days (n=6) in the group of MF-AA1 plus 5-Fluorouracil (S-FU) while it was 15.9+3.8 days (n=7) in PAS only, 21.3t8.4 days (n=6) in PAS plus 5-FU and 30.4tlS.O days (n=5) in MF-AA1 only. Autopsy-of the experimental animals revealed that the metastasis was a single in the liver of 1 out of 6 rats of MF-AA1 plus 5-FU while it was multiple in many organs of all 6 rats of PAS plus 5-FU. The studies by methods of "fraction of la&led mitosis", "Puck's collection function" and "flow cytometry" showed that duration of cancer cell cycle was siqnificantly prolonged by MF-AAI. On the basis of the animal experiments, MF-AA1 has been clinically applied as an adjunct of cancer chemotherapy demonstrating favorable results.
0.72
EFFECT OF THE TUMOR UN PLASMA FREE TRYPTOPHAN LEVELS IN CANCER PATIENTS C. Cangiano, A. Cascino, F. Ceci, A. Avella, M. Muscaritoli, F. Rossi Fanelli. Lab. of Clin. Nutr., III Dept. of Intern. Med., Univ. of Rome "La Sapienza", Rome, IT. Increased plasma free tryptophan (F-TRP) levels without the related modification of circulating albumin (ALB), its natural carrier, or of serum free fatty acid (FFA), which competitively share the same binding sites for serum ALB with TRP, have been These findings suggested that the tumor previously reported in cancer patients (CP). may per se play a role in the rise of plasma F-TRP levels. To verify this hypothesis, into two groups of 12 lung CP (1CP) and 16 breast CP 28 untreated CP, subdivided (bCP), all eligible for radical surgery, the levels of plasma F-TRP (pmol/l), serum FFA (mEq/l) and serum ALB (g/dl) were measured before and 15 days after surgery. CONTROLS
1CP
bCP
POST-OP PRE-OP POST-OP PRE-OP 0.46+0.1+ 0.66+0.3* 0.72+0.:"+ 1.i)9+0.5* F-TRP 0.4820.1 0.58+0.3+ 1.08+0.3* 0.47+0.2+ 0.71;0.3 0.59to.2 FFA 3.19?0.6+ 3.50+0.5* 3.76$8+ 4.31zo.9 ALB 4.45~0.6 __________________________-___________-_________________________--___-----___--__-__-Mean + S.D.;
* vs controls;
+ vs PRE-OP, Min. sign: p
After tumor removal, plasma F-TRP levels decreased significantly in both groups of These data patients without any significant correlation to serum ALB or FFA levels. support the hypothesis that the tumor may cause, either directly or indirectly, a rise in plasma F-TRP levels in CP.
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