Biomedical subjects

J Beuth

Publications and source records attributed to J Beuth.

143 records · Page 8Linked to original sources

PubMedDate not supplied

Intratumoral application of standardized mistletoe extracts down regulates tumor weight via decreased cell proliferation, increased apoptosis and necrosis in a murine model.

The cytotoxic in vitro activity of standardized mistletoe extracts (ME) was examined by established assays towards the human ductal breast carcinoma cell line BT474. A dose-dependent (optimum 25 mg/mL medium) and significantly (p < 0.05) enhanced cytotoxic activity towards the BT474 cells was demonstrated. In vivo experiments on the antitumor activity of ME-A and ME-M were performed in a BALB/c-mouse / BT474 ductal breast carcinoma model. ME-A and ME-M were intratumorally administered according to an application schedule which was found to be optimal concerning dosage and time of administration. Standardized intratumoral application of ME-A and ME-M induced a significantly (p < 0.05) decreased tumor weight in experimental mice. Histological investigations were performed comprising analysis of mitosis and proliferation rates (Ki67 expression), as well as necrosis and apoptosis induction (ssDNA detection). As compared to tumors of control mice with intratumoral phosphate-buffered saline (PBS) injections, tumors of the ME-A and ME-M treated groups showed a decreased cell proliferation rate, as well as an increased cell necrosis and apoptosis rate. Standardized mistletoe extracts, interfering with defined tumor cell functions, e.g., proliferation, necrosis and apoptosis, may have an impact on local cancer treatment.

Animals↗

PubMedDate not supplied

Influence of treatment with the immunomodulatory effective dose of the beta-galactoside-specific lectin from mistletoe on tumor colonization in BALB/c-mice for two experimental model systems.

Mistletoe extracts have approval for clinical application. This warrants the quest for the definition of the active substances to optimize their application. Thus, the extent of immunomodulating and antimetastatic activity of the beta-galactoside-specific lectin from mistletoe extract (ML I) was investigated. In BALB/c-mice regular subcutaneous (s.c.) injections of small nontoxic doses of ML I yielded significant enhancement of peritoneal macrophage activity, as measured in chemiluminescence assays, as well as significant weight gain of thymus. Spleen weight, however, increased without statistical significance. To evaluate the anti-metastatic activity of ML I we intravenously (i.v.) inoculated sarcoma L-1 and fibrosarcoma RAW 117-H 10 cells which cause tumor colonization of lungs and livers in BALB/c-mice, respectively. After regular s.c. administration of ML I, the number of lung and liver tumor colonies significantly decreased in both experimental tumor models as compared to control mice which received injections of saline solution. Accordingly, ML I can be regarded as a potent immunomodulating and antimetastatic substance, which seems to be promising for clinical trials in human oncology.

Adjuvants, Immunologic↗

PubMedDate not supplied

Immunoprotective activity of the galactoside-specific mistletoe lectin in cortisone-treated BALB/c-mice.

Hydrocortisone-acetate (HA)-treatment of BALB/c-mice induced a profound suppression of the lymphatic immune system with statistically significant decreases of thymocyte proliferation and maturation rates as well as peripheral blood lymphocyte (PBL) counts. To check its putative immunoprotective/immunorestoring activity, the optimal immunomodulating dosage of commercially available mistletoe extract standardized for the galactoside-specific mistletoe lectin (ML-1) was regularly administered (1 ng ML-1 per kg body weight; subcutaneously). As compared to counts of thymic lymphatic subsets of HA-treated mice, a considerable up regulation of mature cells expressing helper/inducer (L3T4+) as well as cytotoxic/suppressor (Lyt-2+) phenotypes and immature cells expressing both antigens (L3T4+/Lyt-2+) could be found after ML-1 co-administration. Counts of BALB/c-mouse peripheral blood mononuclear cells also revealed statistically significant increases after ML-1 co-administration, as compared to HA-treated animals. Accordingly, ML-1 treatment may be supposed to restore the lymphatic system after immunosuppressive corticoid treatment and thus this treatment may be of great benefit to patients.

Adjuvants, Immunologic↗

PubMedDate not supplied

Enhancement of immune responses to suramin correlates with antineoplastic activity in BALB/c-mice.

The antiparasitic naphthylurea suramin (SUR) could be shown to exert immunomodulating and antimetastatic activity in BALB/c-mice. Regular intraperitoneal administration of SUR yielded significant weight gain of spleen and significant enhancement of peritoneal macrophage activity in chemiluminescence assays. The number of thymocytes per mg organ weight did not show evident differences in control and SUR treated groups; however, determinations of lymphocyte subsets revealed up-regulation of mature cells expressing helper/inducer (L3T4) or cytotoxic/suppressor (Lyt-2) phenotypes but down-regulation of immature cells presenting both L3T4/Lyt-2 antigens. Accordingly, administration of SUR obviously accelerated murine thymocyte maturation. Counts of BALB/c-mice peripheral blood lymphocytes (PBL) revealed evident (but statistically non-significant) increases after SUR administration. The determination of activated T-cells expressing interleukin (Il-2) receptors further proved that SUR induced a potent immunostimulation since these cells were significantly enhanced after treatment. To evaluate the antimetastatic activity of SUR, sarcoma L-1 cells were intravenously inoculated into BALB/c-mice. In this model system the number of experimental lung metastases significantly decreased, as compared to control mice which received injections of saline solution. Accordingly, SUR can be regarded as an immunomodulating and antimetastatic substance which seems to be promising for clinical trials in oncology.

Animals↗

PubMedDate not supplied

Mistletoe extract standardized for the galactoside-specific lectin (ML-1) induces beta-endorphin release and immunopotentiation in breast cancer patients.

The ability of immunomodulating mistletoe extract standardized for the galactoside-specific lectin (ML-1) to affect immunological parameters (peripheral blood lymphocyte counts, cytokine release) as well as neuroendocrinological parameters (beta-endorphin release) was investigated in breast cancer patients (n = 36). Regular subcutaneous injections of the optimal immunomodulating ML-1 dosage (1ng/kg body weight, twice a week) for 12 weeks induced 1) a significant increase (p < 0.005) of beta-endorphin plasma levels, 2) a reduced decrease (respectively moderate increase) of defined peripheral blood lymphatic subsets after standard chemotherapy, 3) an evidently increased in vitro cytokine release by mononuclear immune cells after adequate stimulation. The increased levels of plasma beta-endorphin after ML-1 administration obviously correlate with an improved quality of life in this group of patients; however, increased in vitro cytokine release and stabilization of peripheral blood lymphocyte counts after chemotherapy demonstrate the immunoactive potency of ML-1.

Adjuvants, Immunologic↗

PubMedDate not supplied

Thymocyte proliferation and maturation in response to galactoside-specific mistletoe lectin-1.

Commercially available mistletoe extract standardized for the galactoside-specific mistletoe lectin-1 (ML-1) could be shown to induce thymocyte proliferation and maturation in BALB/c-mice after regular subcutaneous administration of the optimal immunomodulating dosage (1ng lectin/kg body weight). The increase in thymocyte numbers per mg organ weight was statistically significant. Determinations of thymic lymphatic subsets revealed considerable up-regulation of mature cells expressing helper/inducer (L3T4) or cytotoxic/suppressor (Lyt-2) phenotype and immature cells presenting both (L3T4/Lyt-2) antigens. Thus, administration of ML-1 accelerated murine thymocyte proliferation and maturation. Counts of BALB/c-mouse peripheral blood lymphocytes (PBL) revealed evident (but statistically non-significant) increases after ML-1 administration. The determination of activated PBL expressing interleukin (Il)-2 receptors proved, however, that ML-1 induced a potent immunostimulation since these cells were significantly enhanced after ML-1 administration.

Adjuvants, Immunologic↗

PubMedDate not supplied

Immunostimulation by propionibacteria--effects on immune status and antineoplastic treatment.

Experimental studies were performed to investigate further the effects of immunotherapy with Propionibacterium avidum KP-40 on thymocyte proliferation, maturation and emigration in BALB/c-mice. Thymus weight and thymocyte counts, especially cells presenting the immature or cytotoxic/suppressor phenotype were significantly increased. Due to enhanced emigration, peripheral blood lymphocyte and monocyte counts as well as expression of activation markers were significantly upregulated. The antimetastatic effect of Propionibacterium avidum KP-40 was demonstrated in BALB/c-mice, where RAW 117-H10 lymphosarcoma liver colonization was significantly reduced after immunostimulation. Clinical investigations proved that surgical treatment of colorectal carcinoma induced an evident decrease of peripheral blood lymphocytes as compared with preoperative counts. However, single preoperative Propionibacterium avidum KP-40 administration induced a considerable increase of peripheral white blood cell counts, especially lymphocytes. Clinical effects of preoperative immunostimulation by Propionibacterium granulosum KP-45 were investigated in a prospective randomized trial in colorectal carcinoma patients. Positive effects on survival time, local tumor recurrence and distant metastasis could be demonstrated in stages I and II, whereas no advantage of immunotherapy was found in advanced stages III and IV. A recent prospective randomized clinical trial was initiated on the quality of life of colorectal carcinoma patients. Three months after surgical treatment negative effects could not be determined after immunotherapy. Quality of life even proved to be better in patients with abdominoperineal resection as compared to non Propionibacterium avidum KP-40 treated control patients.

Adjuvants, Immunologic↗

PubMedDate not supplied

Effect of keyhole limpet hemocyanin (KLH) and bacillus Calmette-Guérin (BCG) instillation on carcinoma in situ of the urinary bladder.

Patients with histologically verified carcinoma in situ (CIS) of the urinary bladder (13 primary and 8 secondary CIS) were treated with intravesical instillations of Keyhole Limpet Hemocyanin (KLH) (20 mg KLH weekly for 6 weeks, then monthly for 1 year or bimonthly for 2 subsequent years. Patients, non-responding to 2 courses of KLH were then treated with regular Bacillus Calmette-Guerin instillations (120 mg BCG-Connaught strain). The follow-up period ranged from 10 to 54 months (mean 23.5 months). 7 patients (33%) were free of tumor after the first therapeutical KLH course and 4 patients (19%) presented a complete-remission after the second KLH course (total primary response: 52%). 5 patients (24%) remained free of tumor during the established follow-up period (mean 31.7 months) and no evidence of further tumor progression occurred in patients after two courses of KLH treatment. However, 2 patients (9.5%) had to be cystectomized after KLH instillations because of progressive disease or tumor recurrence. 8 patients (38%) had to be radically cystectomized because of CIS persistence or progression after KLH and subsequent BCG treatment. Altogether 9 patients (42.8%) presented long-term remissions, with a mean duration of 31.3 months. Instillations of KLH did not induce major side effects; however, instillations of BCG caused severe dysuria in 60% and fever in 40% of patients.

Adjuvants, Immunologic↗

PubMedDate not supplied

Antibody response to keyhole limpet hemocyanin (KLH) treatment in patients with superficial bladder carcinoma.

The dynamics of specific KLH-antibody production after intracutaneous and intravesical instillation was analysed. Nine patients (male, n = 7; female, n = 2, mean age 68.6 years, range 47-75) with primary superficial carcinomas of the bladder were intracutaneously immunized with 1 mg Keyhole limpet hemocyanin (KLH) after the complete resection of the tumors. Treatment was continued for 6 consecutive weeks, monthly for one year and thereafter bimonthly for 2 subsequent years, consisting of 20 mg KLH in 20 ml saline introduced intravesically. The antibodies against KLH in patient sera were determined by means of a specially developed direct enzyme-linked immunosorbent assay (ELISA; according to H. von der Kammer, Max Planck Institute for Biophysical Chemistry, Goettingen, Germany). Blood was taken for antibody-titer examination before treatment and 8 weeks after treatment. The KLH-antibody titer increased significantly (Mann-Whitney-Test P = 0.02) after KLH therapy in bladder cancer patients, however the level varied considerably from patient to patient. 6 of 9 patients (67%) presented increased serum antibody titers to KLH after immunotherapy. 4 patients (44.4%) remained free of tumor during the established follow-up period of 10-45 months (median 30.7 months). One patient without increased antibody titer to KLH was free of tumor, 2 patients however, suffered from tumor recurrence after the KLH course. 2 patients presented with tumor recurrence in spite of increased antibody titers. No evidence of tumor progression occurred in patients with recurrence after KLH therapy. 4 of 5 patients (80%) without tumor recurrence presented with a positive skin test. Of patients with tumor recurrence, 50% had a negative skin test. 44.4% KLH-treated patients had tumor recurrence The recurrence rate was 1.6. The time to recurrence was 8.75 months. KLH instillation did not induce major side effects. Positive skin test reactivity and KLH antibody response were more commonly seen in responding patients (i.e. those who remained tumor free after therapy) than in non-responders. The production of KLH antibodies, apparently is the biological response to the antigen stimulus of KLH.

Adjuvants, Immunologic↗

PubMedDate not supplied

Immunoprotective activity of the galactoside-specific lectin from mistletoe after tumor destructive therapy in glioma patients.

35 patients suffering from malignant stage III/IV glioma were enrolled into a prospectively randomized clinical trial. All patients were provided with standard oncologic treatment (neurosurgery, radiation, basic clinical care according to protocol and indication) and randomly divided into a) treatment group: receiving subcutaneous injections of a ML (a galactoside-specific lectin from mistletoe) standardized mistletoe extract, 1 ng ML-1/kg BW, twice a week for 3 months, starting on day 1 post surgery, b) control group: without additional complementary treatment. Immunophenotyping of peripheral blood leukocytes was done by flow cytometry (pre surgery; day 1, week 1, month 3 and 6 post surgery) to evaluate the immunomodulating capacity of ML-1 standardized mistletoe extract. Standard tumor destructive treatment of glioma proved to be suppressive for peripheral blood lymphocytes, since all subsets tested revealed statistically significant down regulation. Unlike the lymphocyte counts and activities of patients from the control group who gave preoperative values after 3-6 months), mistletoe treatment induced a statistically significant up regulation of cell counts (CD-3, CD4, CD-8 cells) and activities (CD-25, HLA/DR positive cells) after 3 months, as compared to preoperative values. Obviously, a strong immunoprotective/immunostimulatory effect was induced by the treatment of glioma patients with ML-1 standardized mistletoe extract which correlated with an improved quality of life, as determined by a standard questionnaire (Spitzer).

Brain Neoplasms↗

PubMedDate not supplied

Prevention of hepatic metastases by liver lectin blocking with D-galactose in colon cancer patients. A prospectively randomized clinical trial.

76 colon adenocarcinoma patients (stages 1-3, NO, MO) were enrolled into a prospectively randomized clinical trial, 39 patients were perioperatively treated with D-galactose-(therapy group: 1.9 g/kg BW and day) or D-glucose-containing electrolyte infusions (control group: n = 37). There were no cases of perioperative mortality. The complication rate was 17.1% (therapy group: 15.3%; control group: 18.9%). Since tumor staging and grading were equally distributed for therapy and control groups, a non-stratified statistical analysis yielded a) significantly reduced hepatic metastases and b) improved overall survival for patients of the therapy group. Stage-dependent analysis demonstrated that stage 3 carcinoma patients of the treatment group developed significantly less hepatic metastases as compared to patients of the control group.

Adenocarcinoma↗

PubMedDate not supplied

Prevention of hepatic metastases by liver lectin blocking with D-galactose in stomach cancer patients. A prospectively randomized clinical trial.

80 stomach adenocarcinoma patients (T1-3, NO, MO) were enrolled into a prospectively randomized clinical study. 40 patients were perioperatively treated with D-galactose (treatment group: 1.9 g/kg BW and per day) or D-glucose-containing electrolyte infusions (control group: n = 40). Perioperative mortality was low (3.7%), complication rate was 11.2% (treatment group: 12.5%; control group: 10%). Since tumor staging and grading were similarly distributed for treatment and control groups, a non-stratified statistical analysis yielded a) significantly reduced hepatic metastases b) significantly improved overall survival for patients of the treatment group. A statistically significant effect on survival free of hepatic metastases and overall survival could be demonstrated for stage T3 patients of the verum group, as compared to patients of the control group.

Aged↗

PubMedDate not supplied

Immunomodulating efficacy of combined administration of galactoside-specific lectin standardized mistletoe extract and sodium selenite in BALB/c-mice.

The immunomodulating abilities of commercially available mistletoe extract standardized for the galactoside-specific lectin (mistletoe lectin-1, ML-1) and sodium selenite (Se) were evaluated in BALB/c-mice and compared to non-treated control animals. Following the optimal schedule of administration (ML-1: 1ng/kg BW; days 1, 2, 3, 5 and Se: 3,5 micrograms/kg BW for 7 subsequent days before evaluation) yielded enhanced counts (thymocytes; peritoneal macrophages, MO; peripheral blood leukocytes; lymphocytes, PBL; monocytes, PBM) and activities (CD-25 positive PBL, MAC-3 positive PBM) of desired immune cells reaching statistical significance for most parameters. However, combined administration of ML-1 and Se proved to be superior to monotherapy since immune cell counts (thymocytes, leukocytes, PBL, PBM) and activities (CD-25 positive PBL) exceeded values obtained after monotherapy. These data are in favour of therapeutical strategies in complementary oncology and suggest that the combination of defined immunomodulating substances might positively enhance the efficacy.

Animals↗

PubMedDate not supplied

Liver lectin blocking with D-galactose to prevent hepatic metastases in colorectal carcinoma patients.

Animal experiments in BALB/c-mice and in DBA/2-mice confirmed that lectin blockade with D-galactose containing receptor analogues can inhibit metastatic spread into the liver. The number of liver colonies of inoculated tumor cells was significantly reduced after D-galactose treatment as compared to animals of control group. Based on experimental investigations 193 colorectal carcinoma patients (UICC stages I-III) were enrolled in a prospectively randomized clinical trial. 93 patients were treated perioperatively with D-galactose- (treatment group: 1.5 g/kg body weight and per day) or D-glucose containing electrolyte infusions (control group: n = 100). Significant side effects were not observed. There were no cases of perioperative mortality. The overall complication rate was 7.3%. Since tumor stages were unequally distributed, analysis was performed in strata. Patients were observed for a total of 6237 months. Differences in overall survival and survival free of recurrence and hepatic metastases were negligible for stages I and II. For stage III carcinoma patients (n = 75) analysis of survival free of hepatic metastases revealed a shift to delayed events (i.e. hepatic metastases or death) after D-galactose treatment within 24 months following surgery. In patients with stage III carcinoma there was an indication for an overall benefit in survival after D-galactose treatment (p = 0.102).

Adult↗

PubMedDate not supplied

Correlation of immune cell activities and beta-endorphin release in breast carcinoma patients treated with galactose-specific lectin standardized mistletoe extract.

A prospectively randomized clinical study was performed with breast carcinoma patients to determine the correlation of defined parameters of the cellular immunity and beta-endorphin plasma levels after mistletoe lectin (ML-1) standardized therapy. The subcutaneous administration of optimal ML-1 dosages (0.5-1.0 ng ML-1/kg body weight; twice a week) induced an increased beta-endorphin plasma level, enhanced activity of peripheral blood natural killer (NK-)cells and T-lymphocytes (expression of CD-25/interleukin-2 receptors and HLA/DR-antigens). Statistical analysis of the data (Spearman correlation) revealed a significant correlation between NK- and T-cell activity and beta-endorphin plasma level. Thus, an obvious correlation between immune system and the neuroendocrine system may be anticipated which might gain therapeutical relevance.

Adult↗

PubMedDate not supplied

Efficiency of treatment with galactoside-specific lectin from mistletoe against rat glioma.

The cytotoxic activity of the galactoside-specific lectin from mistletoe (mistletoe lectin-1, ML-1) towards the anaplastic glioma cell line (F98) was investigated in vitro (three dimensional spheroid model) and in vivo (Fischer 344 rats). Both model systems demonstrated the dose dependent cytotoxicity of ML-1. F98 glioma cell spheroid growth was significantly inhibited after incubation with defined ML-1 concentrations of 10 and 100 ng/mL. To investigate the in vivo efficacy Fischer 344 rats were intracerebrally implanted with F98 glioma cells and assigned to local and systemic ML-1 treatment, respectively. Histological and immunohistochemical evaluations proved a reduction of tumor volume for both treatment modalities, most pronounced and statistically significant after systemic (immunomodulating) administration of the optimal ML-1 dosage (1 ng/kg BW, subcutaneously) and after low dose (10 ng ML-1 per application (10 microL) local treatment. High dose ML-1 administration (10 ng/kg BW; systemically; 100 ng/application, locally) was less effective than low (optimal) dose treatment and apparently the systemic/immunomodulating approach gained greater benefit for glioma bearing rats.

Animals↗

PubMedDate not supplied

Anti-infective catheters: novel strategies to prevent nosocomial infections in oncology.

Intravenous access contributes significantly to the therapeutical success and to the comfort of oncologic patients. The highest risk for bloodstream infections, however, is vascular catheter-mediated. In oncology high mortality is associated with Pseudomonas aeruginosa, Candida albicans and Staphylococcus aureus sepsis. Besides established hygienic measures, the coupling or incorporation of antimicrobial substances to or into catheter materials may be a suitable way to prevent the development of catheter-associated infections. Here we present a risk- benefit evaluation of different models of antimicrobial catheter coated with silver, antiseptics or antibiotics. The controversial reports on clinical efficacy and the potential of adverse reactions due to silver and antiseptic coated catheters are discussed. The microbiological, pharmaceutical and physicochemical backgrounds of different types of coating are discussed in detail. Incorporation of antimicrobial agents into long-term silicon catheters providing a slow release of those substances through the external and internal surfaces of catheters may be the most effective technological innovation for reducing biomaterial-mediated nosocomial infections.

Anti-Infective Agents↗