Downloadable publications

Cancer Biotherapy And Radiopharmaceuticals (2014)
Safety, Tolerability and Effect on Quality of Life of a Mixture of Amino Acids and Other Small Molecules in Cancer Patients

Publikáció típusa:Type: Scientific article
Év:Year: 2014
Szerző:Author: Tamás Czömpöly, Zoltán Langmár, Mária Bors, Csilla Zsákai, Mária Géczy and gyula Kulcsár
Szaklap:Magazine: Cancer biotherapy and radiopharmaceuticals
Évfolyam:Grade: Volume 29, Number 4 (2014)
Terjedelem (oldal):Number of pages: 11
Oldalszám:Page: 124-134
Nyelv:Language: English
Teljes cím:Full title: Safety, Tolerability, and Effect on Quality of Life of a Mixture of Amino Acids and Other Small Molecules in Cancer Patients
Összefoglaló:Abstract: We performed two clinical studies to evaluate the safety, tolerabolity, and effect on quality of life a product containing a mixture of amino acods, vitamins and other small molecules. In the first period, open-label, multiple-dose study, the safety and tolerability of a 1-week administration was evaluated in 24 healthy volunteers. In the second one period, open-label, multiple-dose, single-arm study, we investigated the safety, tolerability and effect on quality of life of a 4-week administration in 50 cancer patients. The safety assessment included the monitoring of adverse events, changes in physical status, and clinical laboratory tests. Changes in quality of life were measured with the European Organization for Research and Treatment of Cancer Qualit of Life Questionnaire Core 30 version 3.0 (EORTC QLQ-C30). We have found that administration of the investigated product is safe and well tolerated in healthy individuals and in cancer parients. Administration of the product to cancer patients significally improved their qulaity of life (EORTC QLQ-C30 global health status score: baseline: 24.17 ± 9.2; end of treatment: 47.08 ± 14.56, p<0.001). To evaluate the anticancer activity of the investigated product in humans, a randomized, blinded, combination clinical trial should be conducted.
Kulcsszavak:Keywords: amino acids, cancer, chemotherapy, quality of life, vitamins
Teljes cikk letöltése:Download full article: http://www.culevit.com/wp-content/uploads/2015/01/cancer-biotherapy-czompoly-langmar-bors-zsakai-geczy-kulcsar-safety-tolerability-and-effect-on-quality-of-life.pdf

 

 

International Journal Of Cancer (2013)
A mixture of amino acids and other small molecules present in the serum suppresses the growth of murine and human tumors in vivo

Publikáció típusa:Type: Scientific article
Év:Year: 2013
Szerző:Author: Gyula Kulcsár, Dezső Gaál, Péter I. Kulcsár, Ákos Schulcz and Tamás Czömpöly
Szaklap:Magazine: International Journal Of Cancer
Évfolyam:Grade: Volume 132, Issue 5, 1 March 2013
Terjedelem (oldal):Number of pages: 9
Oldalszám:Page: 1223-1231
Nyelv:Language: English
Teljes cím:Full title: A mixture of amino acids and other small molecules present in the serum suppresses the growth of murine and human tumors in vivo
Összefoglaló:Abstract: Previously we have hypothesized that the small molecules which are selectively accumulated in cancer cells might participate in a non-immunological antitumor surveillance mechanism. We demonstrated earlier that a mixture of experimentally selected substances (‘‘active mixture’’, AM: L-arginine, L-histidine, L-methionine, L-phenylalanine, L-tyrosine, L-tryptophan, L-ascorbate, D-biotin, pyridoxine, riboflavin, adenine, L(-)malate) possesses a selective toxic effect in vitro on a variety of tumor cell lines, and we have shown that the AM selectively induces apoptosis of cancer cells in vitro. To explore the in vivo significance of our earlier findings we examined the antitumor effect of AM in Colon 26 murine colorectal adenocarcinoma, B16 murine melanoma, MXT murine mammary carcinoma, S180 murine sarcoma, P388 murine lymphoid leukemia, HL-60 human promyeloid leukemia, PC-3 human prostate carcinoma, and HT-29 human colon carcinoma tumor models. Treatment of tumor bearing mice with AM inhibited the growth of the tumors investigated, with an inhibitory effect ranging from 40 to 69%. The AM had a comparable antitumor effect with 5-fluorouracil and cisplatin in the Colon-26 tumor model, and combined treatment with AM and 5-fluorouracil or cisplatin resulted in an enhanced tumor growth inhibitory effect. The AM induced apoptosis through the mitochondrial pathway and induced G1 arrest in PC-3 cells and increased the number of apoptotic cells in PC-3 xenografts. These findings suggest that the AM might offer an interesting perspective in the treatment of cancer and in combination with other treatments may offer hope for a more effective cancer therapy.
Kulcsszavak:Keywords: antitumor effect, amino acids, vitamins, apoptosis, chemotherapy
Teljes cikk letöltése:Download full article: http://www.culevit.com/downloads/2012-international-journal-of-cancer-kulcsar-czompoly-gaal-schulcz-a-mixture-of-amino-acids.pdf

 

Cancer biotherapy and radiopharmaceuticals (2009)
Experimental Evidence for Killing the Resistant Cells and Raising the Efficacy and Decreasing the Toxicity of Cytostatics and Irradiation by Mixtures of the Agents of the Passive Antitumor Defense System in the Case of Various Tumor and Normal Cell Lines in Vitro

Publikáció típusa:Type: Scientific article
Év:Year: 2009
Szerző:Author: Dr. Gyula Kulcsár
Szaklap:Magazine: Cancer biotherapy and radiopharmaceuticals – A journal of new cancer treatment and imaging
Évfolyam:Grade: 24
Terjedelem (oldal):Number of pages: 13
Oldalszám:Page: 67-79
Nyelv:Language: English
Teljes cím:Full title: Experimental Evidence for Killing the Resistant Cells and Raising the Efficacy and Decreasing the Toxicity of Cytostatics and Irradiation by Mixtures of the Agents of the Passive Antitumor Defense System in the Case of Various Tumor and Normal Cell Lines in Vitro
Összefoglaló:Abstract: Despite the substantial decline of the immune system in AIDS, only a few kinds of tumors increase in incidence. This shows that the immune system has no absolute role in the prevention of tumors. Therefore, the fact that tumors do not develop in the majority of the population during their lifetime indicates the existence of other defense system(s). According to our hypothesis, the defense is made by certain substances of the circulatory system. Earlier, on the basis of this hypothesis, we experimentally selected 16 substances of the circulatory system and demonstrated that the mixture of them (called active mixture) had a cytotoxic effect (inducing apoptosis) in vitro and in vivo on different tumor cell lines, but not on normal cells and animals. In this paper, we provide evidence that different cytostatic drugs or irradiation in combination with the active mixture killed significantly more cancer cells, compared with either treatments alone. The active mixture decreased, to a certain extent, the toxicity of cytostatics and irradiation on normal cells, but the most important result was that the active mixture destroyed the multidrug-resistant cells. Our results provide the possibility to improve the efficacy and reduce the side-effects of chemotherapy and radiation therapy and to prevent the relapse by killing the resistant cells.
Kulcsszavak:Keywords: chemotherapy, radiation therapy, passive antitumor defense system, increasing the efficacy of cytostatics and irradiation, protection of normal cells against toxicity of cytostatics and irradiation, killing multidrug resistant cells, Culevit
Teljes cikk letöltése:Download full article: http://www.culevit.com/downloads/2009-cancer-biotherapy-kulcsar-experimental-evidence.pdf

 

 

Cancer biotherapy and radiopharmaceuticals (2003)
Experimental Evidence for the Existence of the Passive Antitumor Defense System Formed by the Synergistic Action of Certain Small Substances of the Circulatory System

Publikáció típusa:Type: Scientific article
Év:Year: 2003
Szerző:Author: Dr. Gyula Kulcsár
Szaklap:Magazine: Cancer biotherapy and radiopharmaceuticals – A journal of new cancer treatment and imaging
Évfolyam:Grade: 18
Terjedelem (oldal):Number of pages: 14
Oldalszám:Page: 949–962
Nyelv:Language: English
Teljes cím:Full title: Experimental Evidence for the Existence of the Passive Antitumor Defense System Formed by the Synergistic Action of Certain Small Substances of the Circulatory System
Összefoglaló:Abstract: In AIDS, only a few types of tumors (mainly Kaposi’s sarcoma and non-Hodgkin’s lymphoma) increase in incidence despite global abnormalities in the immune system. In addition, the reason for the higher incidence of these tumors is not immunosuppression but other agents. This shows that the immune system has no absolute role in the prevention of tumors. Consequently, the fact that tumors do not develop in the majority of the population during their lifetime, indicates the existence of other defense system(s). We demonstrated previously that a mixture of 16 substances (selected experimentally out of 89 compounds of the circulatory system using the synergistic tumor cell-killing effect as criteria) had a cytotoxic effect (inducing apoptosis) in vitro and in vivo on tumor cell lines, but not on normal cells in vitro or animals. In our hypothesis these substances (L-tryptophan, L-tyrosine, L-methionine, L(–)malate, L-ascorbate, L-arginine, L-phenylalanine, L-histidine, 2-deoxy-D-ribose, d-biotin, pyridoxine, adenine, riboflavin, D(1)-mannose, orotate, and hippurate) are the active agents of a passive antitumor defense system (PADS). On the basis of the results, a tablet and a cream were developed, and an infusion is in preclinical phase. In this study we demonstrate that the above-mentioned substances can kill tumor cells when the experimental protocols, concentrations, and cell numbers are chosen to be comparable to the physiological conditions that exist in the living system when these substances fight against arising cancer cells. The results of our experiments demonstrate that the PADS really works in the human body.
Kulcsszavak:Keywords: apoptosis, immune system in AIDS, passive antitumor defense system (PADS), human and murine cancer cell lines, in vitro and in vivo, cytotoxic effect, DNA fragmentation, gel electrophoresis
Teljes cikk letöltése:Download full article: http://www.culevit.com/downloads/2003-cancer-biotherapy-kulcsar-experimental-evidence.pdf

 

 

Cancer Detection and Prevention (2000)
Synergistic Potentiating Effect of D(+)- Mannose, Orotic, and Hippuric Acid Sodium Salt on Selective Toxicity of a Mixture of 13 Substances of the Circulatory System in Culture for Various Tumor Cell Lines

Publikáció típusa:Type: Scientific article
Év:Year: 2000
Szerző:Author: Dr. Gyula Kulcsár
Szaklap:Magazine: Cancer Detection and Prevention
Évfolyam:Grade: 24
Terjedelem (oldal):Number of pages: 11
Oldalszám:Page: 485-495
Nyelv:Language: English
Teljes cím:Full title: Synergistic Potentiating Effect of D(+)- Mannose, Orotic, and Hippuric Acid Sodium Salt on Selective Toxicity of a Mixture of 13 Substances of the Circulatory System in Culture for Various Tumor Cell Lines
Összefoglaló: Abstract: Despite global immune system abnormalities in the autoimmune deficiency syndrome, the incidence of only a few tumor types increases; and the degree of immunosuppression does not seem to be critical in the development of these tumors, indicating that the immune system does not prevent tumor development. Consequently because tumors do not develop in most individuals, other defense systems Inay exist. We demonstrated previously that 13 substances in the circulatory system acting synergistically induced apoptosis in vitro and in vivo in different tumor cell lines. but not in normal cells and animals. We investigated another 17 compounds and five ions in the circulatory system to determine their participation in the defense provided by the 13 substances. Three of the 17 substances but no ions had a potentiating effect on the mixture of substances used previously. The new 16-component mixture suppressed in vitro growth of six human and murine tumor cell lines, including multidrug- resistant tumor cells, without cytotoxic effects in two normal cell lines. The selectivity also was demonstrated hy investigating the mixture’s effect over time on tumor and normal cell growth.
Kulcsszavak:Keywords: immune system in AIDS, Passive Antitumor Defense System (PADS), human and murine cell lines, normal and tumor cells, multidrug resistance, in vitro.
Teljes cikk letöltése:Download full article: http://www.culevit.com/downloads/2000-cancer-detection-kulcsar-synergistic-potentiating-effect.pdf

 

 

Cancer biotherapy and radiopharmaceuticals (1997)
Theoretical and Literary Evidence for the Existence of the Passive Antitumor Defence System

Publikáció típusa:Type: Scientific article
Év:Year: 1997
Szerző:Author: Dr. Gyula Kulcsár
Szaklap:Magazine: Cancer biotherapy and radiopharmaceuticals – A journal of new cancer treatment and imaging
Évfolyam:Grade: 12
Terjedelem (oldal):Number of pages: 6
Oldalszám:Page: 281-286
Nyelv:Language: English
Teljes cím:Full title: Theoretical and Literary Evidence for the Existence of the Passive Antitumor Defence System
Összefoglaló:Abstract: It is well documented that despite global abnormalities of the immune system in AIDS and other immune dejciency dseases or in immunosuppressedpatients the incidence of only a few kinds of tumour increases and even in the development of tumours in question the degree of immunosuppression seems not to be a critical factor. It resultsfiom this that the known immune system has no significant role in the mechanism that prevents the development of tumours. Consequently, the fact that tumours do not develop in the majority of the population during their lifetime, indicates the existence of other defence systems. We assumed that the defence is made by small substances of the circulatory system. Substantial evidence exists that the uptake of the majority of these substances is increased and unregulated by tumour cells and proportional to their availabiliry. This feature of tumour cells may be fatal when the number of cells is still low and there are abundant substances in their environment because some substances may be toxic iftheir concentrations can reach high level in the cells. Thus, the arising cancer cells die in the majority of the population during their lrfetime if the number of cells arisen is not too high, or the concentrations of the required substances are not too low. To our hypothesis, the above effects of thephysiological mixture of the given molecules in the blood form the Passive Antitumor Defence System (PADS). This hypothesis is confirmed by our experiments and supported by epidemiological, clinical observations and other literary data.
Kulcsszavak:Keywords: Immune response in AIDS; immune system; small substances of the circulatory system; synergistic tumour cell killing effect; passive antitumor defence system; PADS
Teljes cikk letöltése:Download full article: http://www.culevit.com/downloads/1997-cancer-biotherapy-kulcsar-theoretical-and-literary-evidence.pdf

 

Cancer biotherapy and radiopharmaceuticals (1997)
Apoptosis of Tumor Cells Induced by Substances of the Circulatory System

Publikáció típusa:Type: Scientific article
Év:Year: 1997
Szerző:Author: Dr. Gyula Kulcsár
Szaklap:Magazine: Cancer biotherapy and radiopharmaceuticals – A journal of new cancer treatment and imaging
Évfolyam:Grade: 12
Terjedelem (oldal):Number of pages: 8
Oldalszám:Page: 19-26
Nyelv:Language: English
Teljes cím:Full title: Apoptosis of Tumor Cells Induced by Substances of the Circulatory System
Összefoglaló:Abstract: Despite global abnormalities of’the immune system, such as in AIDS, the incidence of only a few kinds of tumor increases, and even in the development of these tumors the degree of immunosuppression seems not to be a crirical factor. This means rhot the known immune system has no significant role in the tumorprevenring mechanism. Thus, the fact that tumors do not develop in the majority of the population during their lifetime, indicates the existence of an additional defense mechanism of the immune system. We demonstrated previously that this defense is produced by the synergistic action of certain substances of the circulatory system. Here we report that the substances taking part in the defense induced. but only when they were used togelher, the apoptosis of tumor cells. but not normal cells as was detected by different methods. Other substances of the circulatory system did not show similar effects. These results futrther support the existence of the mentioned defense mechanism called by us the Passive Antitumor Defense System.
Kulcsszavak:Keywords: Small molecules of the circulatory system; Apoptosis; DNA fragmentation; Agarose gel electrophoresis; Flow-cytometric analysis; Passive Antitumor Defense System
Teljes cikk letöltése:Download full article: http://www.culevit.com/downloads/1997-cancer-biotherapy-kulcsar-apoptosis-of-tumor-cells.pdf

 

Cancer biotherapy and radiopharmaceuticals (1995)
Inhibition of the Growth of a Murine and Various Human Tumor Cell Lines in Culture and in Mice by Mixture of Certain Substances of the Circulatory System

Publikáció típusa:Type: Scientific article
Év:Year: 1995
Szerző:Author: Dr. Gyula Kulcsár
Szaklap: Magazine: Cancer biotherapy and radiopharmaceuticals – A journal of new cancer treatment and imaging
Évfolyam:Grade: 10
Terjedelem (oldal):Number of pages: 20
Oldalszám:Page: 157-176
Nyelv:Language: English
Teljes cím:Full title: Inhibition of the Growth of a Murine and Various Human Tumor Cell Lines in Culture and in Mice by Mixture of Certain Substances of the Circulatory System
Összefoglaló:Abstract: It is well documented that despite global abnormalities of the immune system in AIDS and other immune deficiency diseases or in immunosuppressed patients, the incidence of only a few kinds of tu,or increases, and that the degree of immunosuppression seems not to be a critical factor in the development of even these tumors. The fact that tumors do not develop in the majority of population during their lifetime, despite the ineffectiveness of the known immune system against the majority of tumors, can only be explained by hypothesizing that the living system has an additional defense mechanism against tumors. On the bases of literary data, it can be assumed that the effective agents of this defense mechanism are certain substances of the circulatory system. We proved this hypothesis by being able to select thirteen substances of the circulatory system from 71 compounds tested, using the synergistic tumor cell-killing effect as criteria. The mixture containing the thirteen substances (L-hyptophan, L-tyrosine, L-methionine, L(-)malate, L-ascorbate, L-arginine, L-phenylalanine, L-histidine, 2-deoxy-D-ribose, d-botin, pyridoxine, adenine and riboflavin) had a cytotoxic effect against Sp2/0-Ag14 mouse and K562, HEp-2, HeLa and Caco-2 human tumor cell lines in well-controlled conditions, but it was not cytotoxic against Vero normal cell line. The mixture of the above substances increased significantly the survival time of mice (T/C% 148.1) injected i.p. with Sp2/0-Agl4 mouse myeloma cells by killing more than 2 logs (99%) of the cells. Approximately the same 2 logs cell kill was found counting the Sp2/0-Ag14 cells in the ascitic fluid of control and treated animals after finishing treatment. The above mixture slowed down the growth of HeLa solid tumor significantly (T/C%, the least value 35.7). The weight loss of control and treated group during treatment did not differ significantly.
Kulcsszavak:Keywords: Small molecules of the circulatory system; Apoptosis; DNA fragmentation; Agarose gel electrophoresis; Flow-cytometric analysis; Passive Antitumor Defense System
Teljes cikk letöltése:Download full article: http://www.culevit.com/downloads/1995-cancer-biotherapy-kulcsar-inhibition-of-the-growth.pdf