Literaturquellen
Die nachfolgenden Literaturhinweise enthalten möglicherweise Informationen, die einer weiteren Erläuterung bedürfen.
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1.) Jurin, M. et al. (1997):
Chemotherapy and spleen peptides preparation, SP-1, (Polyerga®) in the treatment of experimental lung metastases of mammary carcinoma in mice. Croatian Medical Journal 38: 317-321
ABSTRACT:
Objective: To study the influence of chemotherapy with cyclophosphamide and/or spleen peptides preparation SP-1, Polyerga(R), on the incidence of experimental lung metastases of mammary carcinoma in mice.
Method: Mammary carcinoma cells were injected i.v. into CBA/HZgr mice to obtain experimental lung metastases. One day later, a single injection of cyclophosphamide (50 mg/kg) was given i.p., and/or different concentrations of Polyerga® were given perorally in drinking water until the end of the experiment. The mice were killed and the number of lung metastases nodules determined.
Results: Peroral application of Polyerga® was effective in reducing the number of experimental lung metastases. Even the smallest dose (0.05 mg/kg, 100-fold lower than the dose used in human practice) had a statistically significant effect (p = 0.042). By increasing the dose of Polyerga®, its effectiveness was more pronounced. The dose of 5.0 mg/kg was effective as a 100-fold higher dose, and was chosen for further experiments in combination with cyclophosphamide. Mice treated with the combined therapy were without tumor or the number of metastases was significantly reduced (p < 0.001).
Conclusion: Polyerga® preparation is active against tumor metastases, particularly if combined with the standard chemotherapy.
2.) Klingmüller, M. (1999):
Milzpeptide aktivieren natürliche Killer-Zellen. Erfahrungsheilkunde 12/1999: 756-759
ABSTRACT:
Mit Milzpeptiden (Polyerga®) läßt sich die spezifische Abwehr der natürlichen Killer-Zellen gegen Tumorzellen erhöhen. Daten aus der täglichen Praxis zeigen, daß die Aktivierung von der individuellen Konstitution der Patienten abhängt. Die Aktivierung der NK-Zellen läßt sich sowohl im Reagenzglasversuch als auch nach Behandlung von Tumorpatienten mit dem Milzpeptidpräparat nachweisen.
3.) Klose, G., Mertens, J. (1977):
Langzeitergebnisse der postoperativen Behandlung des Magenkarzinoms mit Polyerga®. Therapie Woche 27: 5359-5361
ABSTRACT:
Es wurde versucht, in einer randomisierten und prospektiven Studie das Ergebnis einer Polyerga®-Therapie des Magenkarzinoms statistisch abzusichern. Es wurden zwei Vergleichsgruppen gebildet, von denen die Gruppe II zu klein war, so daß sie den statistischen Anforderungen nicht mehr entsprach. Deshalb wurde auf Anraten Prof. Kollers eine analoge Gruppe gebildet, die den statistischen Anforderungen gerecht wurde. Die Studie erforderte eine Zeit von 71/2 Jahren ohne die anschließend vorgenommenen Beurteilung. Die Arbeit erscheint uns deswegen besonders wertvoll, weil als hartes Prüfkriterium ausschließlich das 5-Jahres-Überleben der Patienten gewählt wurde. Als Ergebnis fanden wir: Mit Polyerga® behandelte Magenkarzinompatienten der Stadium T3 und T4 überleben wesentlich länger als unbehandelte Patienten. 38% überschreiten die 5-Jahres-Überlebenszeit im Vergleich mit 9% in der Bundesrepublik Deutschland und in den USA. Das Ergebnis der prospektiven und randomisierten Studie rechtfertigt die Empfehlung einer Polyerga®-Behandlung des Magenkarzinoms, die sofort nach Diagnosestellung beginnen sollte. Dies um so mehr, als das Präparat keinerlei Nebenerscheinungen zeigt und mit allen anderen Medikamenten einschließlich Zytostatika kombiniert werden kann.
4.) Landgraf, G. (1992):
Krebstherapie in der täglichen Praxis. Zeitschrift für Allgemeinmedizin 68: 764-7
ABSTRACT:
Im Rahmen einer umfangreichen Anwendungsbeobachtung wurde die Wirksamkeit und Verträglichkeit von Polyerga® Ampullen und Dragées an insgesamt 1302 Tumorpatienten untersucht. Die Mehrzahl der Patienten war vor der Therapie mit Polyerga® operiert und anschließend mit Zytostatika und/oder Bestrahlung behandelt worden. Unter der im Durchschnitt sieben-wöchigen Therapie mit Polyerga® kam es zu einer Gewichtszunahme in 49,6% der Fälle. Die Schmerzintensität verringerte sich in den meisten Fällen deutlich. Eine Verbesserung des Allgemeinbefindens konnte in ca. 44,6% der Patienten gemessen werden. Über unerwünschte Arzneimittelwirkungen wurde in nur einem Fall berichtet. Bei 74 Patienten wurde zusätzlich der zellvermittelte Immunstatus mittels Merieux-Stempel-Test (Antigen-Stempeltest) erhoben. Bei 38,1% der untersuchten Patienten verbesserten sich die Immunreaktionen, bei 48,6% blieben sie unverändert, in 16.2% der Fälle kam es zu einer Verschlechterung.
5.) Maar, K. (1998):
Verbesserung des Allgemeinzustandes von Tumorpatienten. Erfahrungsheilkunde 47: 60-4
ABSTRACT:
In einer prospektiven Anwendungsbeobachtung wurden 248 vorbehandelte Tumorpatienten über eine Zeitraum von vier Monaten mit einem oralen Milzpeptidpräparat (Polyerga®) behandelt. Während des Untersuchungszeitraums erhielten die Patienten keine weitere tumorspezifische Therapie. Im Laufe der Untersuchung wurde eine signifikante Verbesserung des Appetits vermerkt, wobei das Körpergewicht nahezu unverändert blieb. Es kam zu einer signifikanten Reduktion der Schmerzen, einer Erhöhung des Aktivitätsstatus und zu einer Verbesserung des allgemeinen Wohlbefindens. Weiterhin wurde von den Ärzten eine Verringerung des Schweregrads der Erkrankung mit deutlicher Zustandsverbesserung dokumentiert, die auf die Wirksamkeit des Peptidpräparates zurückgeführt wurde. Die besten Ergebnisse zeigten Brustkrebspatientinnen und Patienten mit Kolon- und sonstigen Karzinomen, während die Bronchialkarzinompatienten und Patienten mit schon vorhandenen Metastasen teilweise zu einer Zustandsverschlechterung neigten. Zusammenfassend läßt sich feststellen, daß die orale Therapie mit dem Peptidpräparat zu einer deutlichen Verbesserung des Allgemeinzustandes der vorbehandelten Tumorpatienten führte.
6.) Ojeda, G., Diez-Orejas, R., Portoles, P., Ronda, M., Del Pozo, M.L., Feito, M.J., Hartleb, M., Rojo, J.M. (1994):
Polyerga®, a biological response modifier enhancing T-lymphocyte dependent responses. Res Exp Med 94: 261-7
ABSTRACT:
Cancer patients are often treated with biological response modifiers to enhance immunological functions. However, little is known about the actual mechanism of action of many of these substances. Therefore, we were interested in the effect of i.p. treatment with porcine low-molecular-weight spleen peptides, which are used during supportive cancer therapy, on lymphoid cell populations and function in mice. After treatment with 0.5 µg peptides/kg body weight for 14 consecutive days, lymphokine secretion and the generation of cytotoxic T-cells were significantly enhanced as compared with controls. However, there was no effect on the number of cells or the percentage of cells expressing functional surface markers in secondary lymphoid organs.
7.) Vassilev, M., Antnonov, K., Tcheocharov, P., Krastev, Z. (1996):
Effects of Low Molecular Weight Glycoproteins in Chronic Hepatitis B. Hepato-Gastroenerology 43, 882 - 886
ABSTRACT:
Background/Aims: We evaluated the effect of low molecular weight glycoproteins isolated from animal spleen (Polyerga®) in ten patients with biopsy proven chronic HBV infection with ongoing replication. Material and Methods: Polyerga® was given intramusculary trice weekly and orally 3 tablets daily for 24 weeks. The effect on viral replication was evaluated by measuring HBV-DNA and HBeAg in serum. Results: In three out to ten, HBV-DNA became undetectable and ALT decreased (mean pre-treatment ALT 87.2 ( 55.38 SD, mean post-treatment ALT 62.6 ( 41.86 SD p = 0.026 t-test and Wilcoxon test p = 0.014). During the first month of Polyerga( application transient increase of serum ALT was observed in 50%. In HBeAg negative patients and in patients with low pre-treatment level of HBV-DNA (below 250 pg/ml) there was significant decrease of ALT by t-test (p = 0.022), Wilcoxon (p = 0.028) and Sign test (p = 0.041) in contrast to those with HBV-DNA above 250 pg/ml. Conclusion: The effect of increasing the cytolysis shows that these drugs are active, probably by increasing the lymphokine secretion and the generation of cytotoxic T-cells. The absence of side effects, its ability to reduce viral replication and lower ALT activity even in patients with liver cirrhosis warrants further studies as a "second drug" or as a drug of choice when IFN is contraindicated.
8.) Veen, A. van't, Ruyter, H.A. de, Mouton, J.W., Hartleb, M., Lachmann, B. (1995):
Pretreatment with spleen extracts enhances survival in influenza A infected mice. Forsch Komplementärmed 3, 218 - 221
ABSTRACT:
Background: Preclinical experiments showed a positive influence of Polyerga®, a low molecular weight spleen peptide preparation, on T-cell-dependent immunoreactions (cytokine release, CTL activity), which are important for antiviral defense mechanisms. This effect may lead to an improved resistance against virus infections, which can offer an additional treatment of immunosuppressed patients during complementary therapy.
Objective: Approval of the effect of low molecular weight spleen peptides on survival rate of influenza A infected mice.
Methods: Mice were pretreated orally with 3 different dosages of Polyerga® drug substance (0.5, 50, 250 microg/kg) or with saline for 6 days and then subsequently infected by inhalation with influenza A virus suspension. Survival rate of mice was observed during the following 16 days.
Results: The survival rate of mice was significantly increased in a dose-dependent manner after oral pretreatment with 50 microg (p < 0.02) and 250 microg (p < 0.001) in comparison with saline.
Conclusion: Taken together the results of previous immunological experiments, we conclude that pretreatment of mice with low molecular weight spleen peptides enhances the T-lymphocyte-dependent defense mechanisms against influenza A virus. This result is indicative for a supportive therapy with low molecular weight spleen peptides in immunosuppressed patients.
9.) Zarkovic N., Hartleb,M., Zarkovic K., Borovic S., Golubic J., Kalisnik T., Frech S., Klingmüller M., Loncaric I., Bosnjak B., Jurin M., Kuhlmey J. (1998):
Spleen peptides (Polyerga®) inhibit development of artificial lung metastases of murine mammary carcinoma and increase efficiency of chemotherapy in mice. Cancer Biotherapy & Radiopharmaceuticals 13: 25-32
ABSTRACT:
There are numerous attempts to find novel anticancer drugs or to improve therapeutic protocols based on application of chemotherapeutic agents and immunomodulators (biological response modifiers, cytokines, various plant or bacterial products). Among the preparations that have beneficial effects for the cancer bearing organism are preparations of spleen peptides (Polyerga®). Hence, we analyzed if treatment with spleen oligopeptides GP-1 (active substance for the manufacture of Polyerga® ampoules' solution injected as 0.5 µg/kg every second day) if given alone or combined with chemotherapy (Endoxan 50 mg/kg single i.p. dose) of mice bearing artificial lung metastases of mammary carcinoma will have an impact on the metastases count and survival of the animals. The results obtained have shown that chemotherapy reduced metastases count and increased survival of the tumor bearing mice, while the use of GP-1 alone did not affect metastases development. However, combined GP-1 treatment and chemotherapy were more efficient in prevention of the metastases development than chemotherapy alone. Thus, in mice treated with GP-1 and Endoxan, the average metastases count was four times lower than in the mice treated by chemotherapy only, while 2/12 animals were without tumor nodules in the lungs. Finally, the animals treated by chemotherapy alone died until the 42nd day after tumor transplantation, while at the same time, only 5/10 animals died receiving combined therapy. Thus, these results give an experimental support for the use of the spleen peptides in biotherapy (or combined therapy) of cancer.
10.) Baier, J.E., Neumann, H.A., Taufighi-Chirazi, T., Gallati, H., Ricken, D. (1994):
Thymopentin, Factor AF2, and Polyerga® improve impaired mitogen induced interferon-g release of peripheral blood mononuclear cells derived from tumor patients. TumorDiagnostik&Therapie 15: 21-6
ABSTRACT:
The effect of three different biological response modifiers (BRM) Thymopentin (TP5), Factor AF2(R) and Polyerga® on mitogen induced interferon-gamma release by peripheral blood mononuclear cells (PBMC) was tested in 23 healthy humans and in 23 tumor patients. All patients were prior to surgery and had not yet received radio- or chemotherapy at the time of examination. The interferon-gamma concentration in the supernatants was measured by an enzyme-linked immunosorbent assay (ELISA). The cells were stimulated with PHA at 7.5 microg/ml. In the reference group, interferon-gamma concentration rose to a median of 2190 pg/ml and to 875 pg/ml in the tumor patients. The difference was statistically significant (p < 0.05). However, an addition of the three different BRM did not have any significant influences on interferon-gamma concentration in healthy references. In contrast, in tumor patients cocultivation with each BRM increased interferon-gamma release significantly. The most significant increases could be achieved with 100 microg/ml TP5 (median value 1300 pg/ml IFN-gamma, p < 0.001), 100 microg/ml factor AF2(R) (median value 1375 pg/ml IFN-gamma, p < 0.001), and 0.5 mg/ml Polyerga(R) (median value 1850 pg/ml IFN-gamma, p < 0.0001). At these concentrations the difference between the tumor patients and the reference group was no longer significant. Polyerga® and thymopentin showed slightly but not significantly higher increase than factor AF2(R) compared to the stimulation with mitogen alone. Flow cytometry analysis of CD3, CD4, CD8, CD16, CD19, CD56 and HLA-DR expression of the PBMC revealed slightly but not significantly higher values for CD16-positive cells and HLA-DR positive cells, respectively, in the tumor patients.
11.) Berressem, P., Frech, S., Hartleb, M. (1995):
Additional therapy with Polyerga® improve immune reactivity and quality of life in breast cancer patients during rehabilitation. TumorDiagnostik & Therapie 16: 45-48
ABSTRACT:
In a rehabilitation clinic 158 breast cancer patients received either 3x1ml/week Polyerga® ampoules, a low molecular weight glycopeptide extract derived from porcine spleen, or vitamins and minerals. Additional anti-cancer or immune medication was not applied. Inclusion criteria were reduced body weight, immunoreactivity (Merieux skin test), Karnofsky performance status and well-being (v. Zerssen scale). In both groups, almost all parameter improved after six weeks of therapy due to proper nursing. However, under Polyerga® the percentage of lymphocytes, Merieux skin test, performance status, and well-being increased significantly more compared to the control group. The results show, that Polyerga® therapy had an additional positive effect on immunoreactivity and quality of life.
12.) Borghardt JE, Rosien B, Görtelmeyer R, Lindemann S, Hartleb M, Klingmüller M (2000):
Effects of a spleen peptide preparation as supportive therapy in inoperable head and neck cancer patients. Arzneimittelforschung Drug Research. 50: 178-84
ABSTRACT:
Patienten mit inoperablen HNO-Tumoren wurden neben einer Chemotherapie (Cisplatin / Carboplatin, 5-Fluorouracil) supportiv mit einem Milzpeptidpräparat (Polyerga®) in einer randomisierten, doppelblinden, Placebo-kontrollierten Phase III - Studie behandelt. Das Ziel der Studie war es, die Wirksamkeit des Peptidpräparates als supportive Therapie bei chemotherapeutischer Behandlung hinsichtlich der Änderung immunologischer Parameter zu untersuchen, bzw. Verbesserungen in der Befindlichkeit der Patienten dokumentieren zu können. 40 Patienten nahmen an der Studie teil.
Das Peptidpräparat hatte eine signifikant stabilisierende Wirkung auf den Status der Lymphozyten während der Chemotherapiezyklen (Student t test, p = 0,05). Zudem zeigte sich ein tendenziell stabilisierender Effekt auf Veränderungen des Granulozytenstatus (Student t test, p = 0,18) unter Chemotherapie. Die typische Entwicklung einer zunehmenden Erschöpfung (Müdigkeit)während der Chemotherapiezyklen (Student t test, p = 0,01) wurde signifikant verringert, das Körpergewicht blieb in der Verumgruppe während der Chemotherapie im Gegensatz zur Placebogruppe stabil (Mann-Whitney U test, p = 0,17).
13.) Borghardt, JE., Rosien, B., Frech, S., Hartleb, M. (1995):
Polyerga® as a supportive therapy could improve quality of life in head and neck cancer patients during chemotherapy. Supportive Care in Cancer Vol. 3: 360
ABSTRACT:
Anti-cancer chemotherapy can often induce a severe reduction in quality of life. In a prospective, randomized double-blind study patients suffering from advanced head and neck cancer were treated with Polyerga®, a low molecular weight peptide preparation, or with placebo during and after finishing chemotherapy (5-FU, platin derivations). The study parameter were lymphocyte counts, quality of life (POMS), Karnofsky performance status, pain, body weight and survival. At the beginning of chemotherapy, Polyerga® showed in comparison to placebo a positive effect on nausea and vomiting. During chemotherapy Karnofsky performance status, activity and fatigue (POMS) remained stable for Polyerga® patients, while the corresponding data of the placebo group worsened. Furthermore, the body weight was stabilised in the verum group and decreased in the placebo group. Pain was reduced during chemotherapy and increased again after the chemotherapy was stopped. There was no difference between the two study groups. Polyerga® treated patients showed a tendency to higher T4- and lower T8-cell counts, while placebo patients had contrary data. There was no difference between the two study groups regarding tumor response and survival. As a summary, Polyerga® used as supportive treatment had positive effects on some parameter of quality of life in head and neck cancer patients during chemotherapy.
14. Jurin, M. et al. (1996):
Porcine splenic peptides (Polyerga®) decrease the number of experimental lung metastases in mice. Clin Exp Metastasis 15, 55-60
ABSTRACT:
Preparations of splenic peptides under the name of Polyerga® are being tested in numerous experimental immunomodulating and antitumorous models and are also used during supportive treatment of tumorous patients. Further, the incidence of experimental lung metastases of melanoma cells in mice was significantly reduced if we used Polyerga® preparations. The aim of our investigation was to determine whether Polyerga® is active directly against tumor cells or whether its activity is manifested by modulating immune and other possible abilities of the organism. To clarify the problem glycopeptides containing Polyerga® were incubated with melanoma B16F10 cells in vitro and the plating efficiency of these cells determined when cultivated in medium, or in medium with different doses of the same Polyerga® preparation. The cells preincubated in medium only reacted to the addition of increasing doses of Polyerga®. 150 pg or more, by raising colonies number. However, 24-h incubation of melanoma cells in the presence of 150 microg of Polyerga® per ml significantly reduced the number of tumor cell colonies in comparison to the corresponding cell cultures previously not exposed to Polyerga®. These in vitro studies were extended to in vivo application using C57B1/GoZgr mice injected i.v. with melanoma cells pretreated with Polyerga® in vitro or previously not treated. A group of the treated mice was further injected i.p. with Polyerga®. All the mice were killed at a particular time and the number of lung nodules determined. A significant difference to the control values was noticed in each group that used Polyerga®, regardless of the exposure of melanoma cells to Polyerga® in vitro, in vivo or to combined treatment. The efficiency of Polyerga® application 7 days following i.v. injection of control melanoma cells (cultivated in medium only) when the nodules already exist, was further evaluated in a combined treatment using DTIC, a drug of choice in melanomas. The smallest incidence of experimental lung metastases was observed in the group exposed to the combination of DTIC and Polyerga®. Polyerga® preparations is thus active against melanoma cells, particularly in vivo and if combined with chemotherapy.
