摘要:

There are numerous data on the immunostimulative and antitumorous activity of various Viscum album tissue extracts. Isorel (Novipharm, Austria) is one of these compounds. We found that in mice an increased number of plaque-forming cells to sheep red blood cells (SRBC) followed the injection of Isorel together with SRBC. Further, survival time of a foreign skin graft was shortened if Isorel was applied at the correct time. Finally, suppressed immune reactivity in tumorous mice recovered following Isorel injection. Isorel was further shown to be cytotoxic to tumor cells in vitro. Its application to tumor-bearing mice could prolong their life but without any therapeutic effect. However, a combination of local irradiation and Isorel was very effective: following 43 Gy of local irradiation to a transplanted methylcholanthrene-induced fibrosarcoma (volume about 240 mm3) growing in syngeneic CB A/HZgr mice, the tumor disappeared in about 25% of the animals; the addition of Isorel increased the incidence of cured animals to over 65%. The combined action of Isorel, influencing tumor viability on the one hand and the host’s immune reactivity on the other, seems to be favorable for its antitumor action in viv

ISSN:0030-2414    

DOI:10.1159/000227217

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The mechanisms responsible for the immunostimulatory role of the pineal hormone melatonin (MLT) are still obscure. To investigate the influence of MLT on interleukin-2 (IL-2)-induced immune effects in cancer, we compared the results obtained in 14 cancer patients treated with IL-2 (6 x 106 IU/day s.c. for 5 days/week for 4 weeks) plus MLT (10 mg/day orally) with those seen in 14 patients treated with IL-2 alone and with those obtained from 14 other patients treated with MLT only. All patients were affected by metastatic solid neoplasms. The increase in the mean number of lymphocytes, T lymphocytes, natural killer cells, CD25-positive cells and eosinophils was significantly higher in patients treated with IL-2 plus MLT than in those receiving IL-2 alone. On the contrary, the increase in mean serum levels of the macrophage marker neo-pterin was significantly higher in patients treated with IL-2 alone than in those treated with IL-2 plus MLT. Finally, MLT alone has no significant effect on immune cell mean number and on neopterin secretion. These results would suggest that the immunostimulatory action of M LT requires the concomitant presence of IL-2 and that two of the main target cells for MLT activity in humans are represented by T helper lymphocytes of type 2, which are involved in IL-2-induced eosinophilia by the release of IL-5, and macrophages, which may inhibit IL-2-dependent immune functions.

ISSN:0030-2414    

DOI:10.1159/000227218

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Pharmaceutical preparations containing mixtures of various proteolytic and nonproteolytic enzymes have been suggested for use in the treatment of malignant diseases. However, the mode of action of such preparations was not clear. We have shown before that intact bromelain, papain or amylase, which are components of a commercial polyenzyme preparation, induce cytokine production in peripheral blood mononuclear cells in vitro. IFN-α and IFN-γ which had no effect alone, synergistically increased TNF production when applied together with the enzymes. Here we show that trypsin alone had only a small inducing effect. The tryptic but not the autolytic fragments of papain and bromelain have a higher (10- to 40-fold) inducing capacity for TNF production than the untreated enzyme. Additionally we demonstrate that after ingestion of milligram doses of the polyenzyme preparation (as recommended for clinical use), PBMNC of healthy donors acquire the ability to produce TNF-α, IL-1β and IL-6 when incubated ex vivo with IFN-γ. Our results indicate that the biological effects observed after oral administration of polyenzyme preparations are realted to their ability to induce cytokine production. This may explain the antitumor effects of such enzymes. Our results also suggest that polyenzyme preparations may have a stronger immunomodulary effect when used in combination with I

ISSN:0030-2414    

DOI:10.1159/000227219

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Increase of gene activity of the proto-oncogene erbB2 which codes for the transmembrane kinase receptor p185erbB230% of female breast and gynecological carcinomas. This overexpression was shown to be correlated with poor prognosis. We have investigated 38 samples of carcinomas of the male breast for p185erbB2 expression by using tumor thin sections and a monoclonal antibody. The immunostaining was compared to clinical data to assess a possible prognostic value of this parameter. Although most cases were immunopositive (36/38), no correlation to tumor grading and survival spans was notable. Therefore, erbB2 activity fails to add a new prognostic parameter in male breast carcinomas.

ISSN:0030-2414    

DOI:10.1159/000227220

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

c-erbB-2 DNA amplification and mRNA expression were analyzed by dot and Southern blots in 65 human primary breast tumors. Gene amplification was observed in 21 of 65 (32.3%) and elevated levels of c-erbB-2 transcript in 14 of 60 (23.3%) of the tumors analyzed. Only 55% of the tumors with c-erbB-2 gene amplification presented gene overexpression, showing an incomplete correlation between gene amplification and overexpression. No statistically significant correlation was observed between c-erbB-2 genetic alterations and other prognostic factors in breast cancer. However, patients with tumors presenting c-erbB-2 gene amplification and/or overexpression appeared to have a shorter disease-free interval than patients without c-erbB-2 genetic alterations. High levels of c-erbB-2 gene amplification were more powerful predictors of risk of recurrence than was overexpression of the gene. Cox univariate-bivariate analyses suggested that gene amplification was independent of nodal status to predict recurrence in breast cancer.

ISSN:0030-2414    

DOI:10.1159/000227221

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

c-erbB-2 gene amplification was examined by slot blot hybridization using DNAs extracted from formalin-fixed and paraffin-embedded tissues of primary gastric carcinomas. Eleven of the 82 carcinomas (13.4%) exhibited amplification. Twenty-eight carcinomas (34.1%) expressed c-erbB-2 protein immunohistochemically. All of the tumors with amplified c-erbB-2 genes had expression of c-erbB-2 protein. The incidence of diploid and aneuploid tumors with c-erbB-2 gene amplification was similar. The survival rate was significantly lower in cases with c-erbB-2 gene amplification. Furthermore, patients with tumors showing a combination of c-erbB-2 gene amplification and DNA aneuploidy had the poorest prognosis. c-erbB-2 gene amplification may be an important prognostic indicator in gastric carcinomas.

ISSN:0030-2414    

DOI:10.1159/000227222

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Forty oral squamous cell carcinomas and 20 leukoplakias were examined for expression of p53 oncoprotein using an immunohistochemical technique with BP53-12 monoclonal antibody. Positive staining was found in 21/40 (52%) of the carcinomas and 2/20 (10%) of the leukoplakias. Furthermore, comparison of p53 expression with binding of PC 10 monoclonal antibody to proliferating cell nuclear antigen (PCNA) and degree of histological malignancy in terms of invasion and histological differentiation of carcinomas demonstrated a positive correlation in both cases.

ISSN:0030-2414    

DOI:10.1159/000227223

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The objective of this study was to evaluate the diagnostic utility of the measurement of the serum activity of angiotensin-converting enzyme (SACE) as a cancer marker. This case-control study included 135 patients with cancer of different sites, confirmed histologically, and 145 controls (107 normal individuals plus 38 chronically ill patients with nontumoral diseases). Determination of SACE activity was done by a spectophotometric method using as substrate the synthetic tripeptide N-(3-[2-furyl]acryloyl)-L-phenylalanyl-glycine. There were no sex- or age-related variations in SACE activity. Mean SACE activity in 107 normal controls was 51.6 U/l (95% C.I., 50.1-53.1); in 145 nontumoral individuals, including 38 chronic nonmalignant diseases plus 107 normal controls, 51.5 (50.1–53.1) and in malignant tumors 35.7 (32.8–38.5). There was no statistically significant difference between chronic diseases and normal controls (p > 0.05); but there was one between cancer patients and nontumoral individuals, normals and chronic nontumoral diseases. The mean of SACE activity values by tumoral site are (U/l; 95% C.I.): breast, 41.3 (36.2–46.5); gastrointestinal, 31.5 (24.3–38.8); head and neck, 32.3 (26.7–37.8), and lung 27.6 (21.6-33.6) (p < 0.001). The means by clinical stage are: complete remission, 58.0 (53.7–62.3), significantly higher than in normal controls (p < 0.001); local disease, 40.56 (34.5–46.5); locoregional disease, 35.09 (30.7-39.4); metastatic disease, 23.04 (19.5–26.5), and in relapse at diverse stages, 30.86 (25.1–36.5). In clinical active cases, there is a statistically significant decrease of SACE activity, especially in metastatic disease (p < 0.001). The calculated cutoff value, excluding complete remission cases, is 40.7 U/l, with sensitivity of 69.5% and specificity of 91.6%. We conclude that there is a decrease of SACE activity in cases of clinically active cancer and an increase in clinical complete remission.

ISSN:0030-2414    

DOI:10.1159/000227224

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The aims of this study were to (1) evaluate the diagnostic utility of a new tumor marker, TPS, with respect to TPA and CA 19-9 in patients with pancreatic cancer; (2) ascertain the reliability of the markers in predicting survival, and (3) evaluate the effect of liver dysfunction on the results. CA 19-9, TPA and TPS were measured in the serum of 19 control subjects, 42 patients with pancreatic cancer, 29 with chronic pancreatitis, and 52 with extrapancreatic diseases. CA 19-9 was confirmed to be the best serological indicator of pancreatic cancer, while TPA and TPS lacked both sensitivity and specificity. Pancreatic cancer patients with liver metastases had higher mean C A19-9 and TPA, but not TPS, values than pancreatic cancer patients without metastases. A shorter survival time was associated with the presence of liver metastases and with higher serum tumor marker levels. CA 19-9, TPA and TPS were found to be correlated with liver function test results (ALT, ALP and bilirubin). In conclusion: (1) TPS adds no significant information to that obtained using CA 19-9 in the diagnosis of pancreatic cancer; (2) CA 19-9 and TPA, but not TPS, are influenced by the presence of liver metastases; (3) the main factor to influence survival is advanced disease, which is in turn associated with higher tumor marker levels, and (4) liver dysfunction can influence not only CA 19-9 and TPA, as already described, but also TPS.

ISSN:0030-2414    

DOI:10.1159/000227225

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Cardiotoxicity with 5-fluorouracil (5-FU) therapy has been reported to range from asymptomatic EKG abnormalities to fatal myocardial infarction. We report a prospective study in 100 consecutive patients receiving 5-FU infusion in combination with other chemotherapeutic agents or alone for the treatment of different malignancies with the aim of identifying patients who develop symptomatic cardiotoxicity. Patients with a history of cardiac illness, abnormal EKG or cardiac enzyme levels were excluded. Patients were observed during the total period of infusion, daily EKG was performed on asymptomatic patients, those who developed cardiotoxicity were monitored till symptom-free for 24 h. Eight patients developed symptoms suggestive of cardiotoxicity. Pain was the commonest symptom (5/8), followed by palpitation and sweating. Three patients developed EKG abnormalities and 1 went into cardiogenic shock. Time to toxicity ranged from 18 to 30 h (mean 24 ± 3.7 h) and serial cardiac enzyme levels remained normal in all patients. The symptoms reversed immediately on cessation of the treatment in most of the patients (7/8). Time to recovery ranged from 5 to 60 min (mean 19.28 ± 19.6 min). There was no recorded death due to toxicity. We conclude that 5-Fu infusion is associated with a significant risk of symptomatic cardiotoxicity. Concomitant chemotherapeutic agents, received by all the affected patients, may have a contributory effect too. Cardiotoxicity seems to be completely reversible, particularly in patients without underlying cardiac disease. The patients should be informed about the symptoms and the condition recognised and managed immediatel

ISSN:0030-2414    

DOI:10.1159/000227226

出版商:S. Karger AG    

年代:1993

数据来源: Karger