ISSN:0378-584X    

DOI:10.1159/000218886

出版商:S. Karger GmbH    

年代:1996

数据来源: Karger

ISSN:0378-584X    

DOI:10.1159/000218774

出版商:S. Karger GmbH    

年代:1996

数据来源: Karger

ISSN:0378-584X    

DOI:10.1159/000218775

出版商:S. Karger GmbH    

年代:1996

数据来源: Karger

摘要:

Bispecific monoclonal antibodies (Bi-MAb) which recognize a tumor-associated antigen (TAA) with one arm and bind to a trigger molecule on an immunologic effector cell with the second arm, open the potential for specific activation of cytotoxic effector cells of the immune system (NK cells, T lymphocytes, macrophages) at the tumor site. SCID mice bearing hetero-transplanted Hodgkin’s tumors were cured even at the stage of disseminated disease by treatment with the appropriate Bi-MAbs and human lymphocytes, establishing this approach as one of the most effective models of immunotherapy for human tumors. Several clinical trials employing different target and effector cells for the evaluation of the feasibility, toxicity, and efficacy of Bi-MAb therapy have recently been started. The low toxicity and surprising efficacy of the systemic application of an NK-cell-activating Bi-MAb in patients with refractory Hodgkin’s disease encourage further clinical trials of this novel immunotherapy in patients with malignant tumors refractory to standard treatm

ISSN:0378-584X    

DOI:10.1159/000218776

出版商:S. Karger GmbH    

年代:1996

数据来源: Karger

摘要:

Neuroendocrine tumors of the gastroenteropancreatic system present both a diagnostic and therapeutic challenge. Even in a patient presenting with a clinical hypersecretion syndrome such as the carcinoid syndrome, the Zollinger-Ellison syndrome or the hypoglycemia syndrome the primary tumor is often difficult to localize. Recently, tumor imaging has been improved by two new powerful techniques, the endosonography and the somatostatin-receptor scintigraphy. In addition, the new arterial secretin or calcium injection tests may guide surgery in patients with gastrinoma or insulinoma, respectively. The recently introduced positron emission tomography with nC-5-hydroxytryptophan can provide information about biochemical and metabolic changes in neuroendocrine tumors. Patients with the hereditary form of neuroendocrine tumor disease of the foregut suffer from the multiple endocrine neoplasia type 1 syndrome. The genetic defect of this autosomal dominant disease has been assigned to chromosomal region 11 q13. Current investigations aim to detect the multiple endocrine neoplasia 1 gene and thus to allow early diagnosis of hereditary neuroendocrine tumor disease of the foregut.

ISSN:0378-584X    

DOI:10.1159/000218777

出版商:S. Karger GmbH    

年代:1996

数据来源: Karger

摘要:

The integrity of the skeleton is maintained by two tightly coupled processes: bone resorption and bone formation. Osteoclasts are responsible for bone degradation, osteoblasts for synthesis of the bone matrix. Mature bone consists of a mineral phase (hydroxyapatite crystals) and the organic bone matrix (predominantly type I collagen). In metabolic and malignant bone disease, the balance between bone formation and bone resorption processes is disturbed. Biochemical markers of bone metabolism fall in two categories: enzymes reflecting the activity of osteoblasts (e.g., bone alkaline phosphatase), and osteoclasts (e. g., tartrate-resistant acid phosphatase), and markers of the organic bone matrix. Osteocalcin is established as a bone formation parameter, whereas pyridinium cross-links (a specific breakdown product of type I collagen) can be recommended as a bone resorption parameter. The urinary calcium excretion rate cannot be considered as a specific marker for bone resorption, as it reflects overall mineralization/demineralization rather than bone matrix resorption. Thus, assessment of pyridinium cross-links and urinary calcium excretion are reflecting different aspects of bone turnover. The different biochemical markers of bone metabolism are reviewed in this report, and their applications in states of altered bone metabolism (e.g., malignant osteolysis) are discussed.

ISSN:0378-584X    

DOI:10.1159/000218778

出版商:S. Karger GmbH    

年代:1996

数据来源: Karger

摘要:

Both hereditary and nutritional factors contribute to the development of colorectal cancer – a slow, stepwise process driven by the accumulation of genetic changes in the tumor cells and by progressive deregulation of growth. Dietary factors can both cause somatic mutations and stimulate tumor growth. This review explores the mechanisms of growth regulation in colonic tumors and the interaction between genetic changes and growth modulators derived from our diet. Most of the genetic defects observed in colon carcinogenesis have a potency of affecting growth control, creating a premalignant cell population that is highly susceptible to regulatory signals. Growth stimulators are bile acids, 1,2-diglycerides, and prostaglandins stemming from fat consumption, while fruits and vegetables contain various substances that might inhibit growth – like carotinoids, flavonoids and of course fiber. Similar protective effects may be caused by Ca2+ and the vitamins A and D. Diet is a complex mixture of all these tumor-enhancing and tumor-inhibiting constituents, whose effects and interactions have to be understood to develop cancer-protective dietary patte

ISSN:0378-584X    

DOI:10.1159/000218779

出版商:S. Karger GmbH    

年代:1996

数据来源: Karger

摘要:

Background: An American National Intergroup has shown that the risk of cancer recurrence could be reduced by 41% in a group of patients who had undergone a curative resection of colon carcinoma Dukes’ stage C (regional nodal involvement) if they were subsequently treated with levamisole and 5-Fluorouracil (5-FU) in comparison to a group of patients who had undergone surgery only. The mortality rate was reduced by 33%. The study carried out by the Oncological Center of Stuttgart aimed to reproduce these results. Patients and Methods: Having had a curative resection of a colon carcinoma stage TNM III (Dukes’ C), 62 patients were then treated with levamisole and 5-FU for 1 year. Inclusion criteria and levels of dosage of levamisole and 5-FU were the same as those in the study carried out by the National Intergroup. Due to the extremely positive results shown in the National Intergroup study it was considered unethical to include in the Stuttgart study a control group of patients who had undergone surgery only. Results: As severe side effects were observed in the study of the Oncological Center of Stuttgart, the study was already discontinued after a median follow-up time of 15 months (range 1 month to 3.5 years) and the patient data were evaluated. The prognostically relevant characteristics of the levamisole and the 5-FU patient groups in both studies were very nearly identical. This would allow a direct comparison between the two studies. 3.5 years after the beginning of the treatment, 63% of the levamisole and 5-FU patients in the Intergroup study had no cancer recurrence in comparison to 39% of patients in the Stuttgart study. This difference is statistically highly significant. Severe neurotoxic side effects were observed in patients in the Stuttgart study. 2 patients developed multifocal leucencephalopathy, 2 patients fell into coma. Conclusions: As the Stuttgart study could not include a control group of patients who had undergone surgery only, the study is not able to proof the possible ineffectiveness of an adjuvant therapy with levamisole and 5-FU. Considering the study results, however, it would be a sensible and justifiable decision to include a control group in future randomized studies to examine the effectiveness of this adjuvant therapy. We recommend that those patients treated with levamisole and 5-FU should be watched very carefully for neurotoxic side eff

ISSN:0378-584X    

DOI:10.1159/000218780

出版商:S. Karger GmbH    

年代:1996

数据来源: Karger

摘要:

Background: Patients with stage T3-4 and/or N-positive rectal cancer have a high risk for local recurrence with or without distant metastases. Despite a failure rate of approximately 50%, no standard adjuvant therapy has been defined until recently. Patients and Methods: Between May 1988 and December 1990, 62 patients who underwent potential curative surgery for adenocarcinoma of the rectum were randomly assigned to observation or adjuvant treatment, consisting of perioperative instillation of 20 mg mitoxantrone into the sacral cavity followed by 6 intravenous treatment cycles of leucovorin (200 mg/m2) plus 5-fluorouraciJ (370 mg/m2) on days 1-5 every 4 weeks. Results: After a median follow-up time of 4.5 years, a comparison between the two groups of patients, 57 of whom were eligible, suggested both an improvement in disease-free survival (68% vs. 46%) and a survival advantage (70% vs. 54%) in favor of the adjuvant chemotherapy group. The benefit appears to be greatest in patients with stage II rectal cancer. Particularly striking was the advantage of chemotherapy in decreasing the incidence of locoregional failure: The pelvis with or without distant metastases was the first site of treatment failure in 9 of 15 (60%) patients with documented recurrences in the control group and in 3 of 9 (33%) patients who received additional treatment. Tolerance of chemotherapy in the treatment arm was remarkable, with no evidence of interference with wound healing. Conclusions: Although, due to the small number of patients in this pilot study, no definite conclusions can be drawn, combined local and systemic intravenous chemotherapy seems to represent a potentially effective adjuvant regimen in stage II/III rectal cancer.

ISSN:0378-584X    

DOI:10.1159/000218781

出版商:S. Karger GmbH    

年代:1996

数据来源: Karger

摘要:

Background: Treosulfan (Ovastat®), a bifunctional alkylating cytostatic, indicated for the treatment of advanced ovarian carcinoma, was recently found to be active in human lung and breast carcinoma xenografts. Moreover, toxicological evaluation as well as clinical experience revealed the lack of significant nonhematological toxicity which makes treosulfan a promising candidate for high-dose chemotherapy combined with autol-ogous blood stem-cell reinfusion. As a prerequisite for clinical high-dose studies, a formal phase I dose escalation without stem-cell reinfusion was conducted to reassess the maximum tolerated dose and dose-limiting toxicity of treosulfan after intravenous short-term infusion. Patients: A total of 12 patients with chemotherapy-refractory advanced cancer were entered at 3 dose levels (8 g; 10 and 12.5 g/m2 treosulfan i.v). Most patients suffered from advanced small-cell lung cancer (5 patients) or ovarian carcinoma (3 patients). Results: The maximum tolerated dose of treosulfan in this group of heavily pretreated patients was 10 g/m2. The dose-limiting toxicity was reversible thrombocytopenia. There were no nonhematological side effects exceeding WHO grade 2. Conclusions: This phase I dose escalation trial confirmed the lack of significant nonhematologic side effects of treosulfan although a dose of 12.5 g/m2 was infused. A subsequent phase I study of high-dose treosulfan followed by peripheral blood progenitor cells has therefore been initiated

ISSN:0378-584X    

DOI:10.1159/000218782

出版商:S. Karger GmbH    

年代:1996

数据来源: Karger