ISSN:0378-584X    

DOI:10.1159/000218436

出版商:S. Karger GmbH    

年代:1994

数据来源: Karger

ISSN:0378-584X    

DOI:10.1159/000218437

出版商:S. Karger GmbH    

年代:1994

数据来源: Karger

摘要:

This review considers the latest achievements in c-erbB-related research, which is dominated by the recent identification of a series of related membrane receptors and corresponding ligands. The family of c-erbB receptors and epidermal growth fac-tor(EGF)-like ligands is increasingly recognized as an important cross-connected signal transduction system that controls normal cell development. Perturbation of the homeostatic balance of this system frequently causes malignant transformation. The family currently comprises four closely related receptors [EGF receptor (EGFR), c-erbB-2, c-erbB-3 and c-erbB-4]. Various ligands have been described for EGFR, c-erbB-2 and c-erbB-4, but not for c-erbB-3. Amplification and/or over-expression of EGFR and c-erbB-2 are well-known markers for a poor clinical prognosis in some malignant diseases. Apart from its role in the pathogenesis of human cancer, c-erbB-specific signaling was found to exert crucial functions in neural development and in neuropathology. Unraveling of the complicated transregulatory network between the c-erbB system and other growth-controlling receptor pathways yields the rational basis for the design of novel forms of antitumor therapy. In this review we are going to discuss the recent advances and future avenues for basic and clinical investigations.

ISSN:0378-584X    

DOI:10.1159/000218438

出版商:S. Karger GmbH    

年代:1994

数据来源: Karger

摘要:

The capacity of solid tumors to invade surrounding tissue and to metastasize is correlated with the formation and degradation of structural elements in the vicinity of the tumor cells. Evidence has accumulated that proteases play a crucial role in tumor cell invasion and metastasis. Four different classes of proteases are involved: 1. serine proteases, 2. metalloproteases, 3. cysteine proteases, and 4. aspartyl proteases. It has been shown that the content of some tumor-associated proteolytic factors in tumor extracts have a strong prognostic value. Especially the urokinase-type plasminogen activator (uPA) and the plasminogen activator inhibitor type-1 (PAI-1), predicting relapse-free and overall survival of patients with breast, gastric and ovarian cancer, allow to classify high-risk cancer patients. A prospective clinical study currently investigates whether lymph-node-negative breast cancer patients with either high uPA and/or PAI-1 level will benefit from adjuvant chemotherapy. Based on the present knowledge of basic and clinical aspects of tumor-associated proteases, new potential therapeutic strategies have emerged targeting these proteolytic enzyme systems.

ISSN:0378-584X    

DOI:10.1159/000218439

出版商:S. Karger GmbH    

年代:1994

数据来源: Karger

摘要:

The saying ‘you can teach an old drug new tricks’ has been proven to be useful in the case of 5-fluorouracil (5-FU), when its ability to be modulated by non-cytotoxic drugs was discovered. This review summarises experimental preclinical and clinical data on the biochemical modulation of 5-FU, focusing on the pharmacology of 5-FU and the stereoselective pharmacokinetic behaviour of tetrahydrofolates. Several drugs such as interferon, N-(phosphonacetyl)-L-aspartate, and methotrexate share common modes of action with reduced folates. These substances interact mainly with the pyrimidine network responsible for the activation of 5-FU Preclinical studies have largely contributed to our understanding of resistance to modulated 5-FU, e. g. enhanced synthesis of the target enzyme thymidylate synthase. The feasibility of pharmacokinetic in vivo studies in humans, using new techniques such as nuclear magnetic resonance spectroscopy, enables us to translate preclinical investigations into clinical knowledge. Significant progress in the palliative treatment of colorectal cancer will depend on our ability to predict therapeutic success or therapeutic failure on the basis of experimental parameters. Thus, individualisation of anti-neoplastic treatment is the main challenge for the coming ye

ISSN:0378-584X    

DOI:10.1159/000218440

出版商:S. Karger GmbH    

年代:1994

数据来源: Karger

摘要:

This review summarizes encouraging data concerning pathophysiology and systemic treatment of desmoid tumours, which are a rare tumour entity with an incidence of 0.3 per 100,000 persons per year. Therapy of choice for primary desmoid tumours remains surgery. Extensive surgical procedureí lave to be accepted. Recent data concerning the mode of action of hormonal treatment indicate the presence of oestrogen receptors in about one third of the tumours. Casuistic contributions reported on 22 patients treated with tamoxifen, of whom 9 (41%) responded to therapy. Experience in treatment with other hormonally active drugs (toremifen and progesterone) is limited. It is interesting to note that non-steroidal anti-inflammatory drugs show antiproliferative activity of a similar range

ISSN:0378-584X    

DOI:10.1159/000218441

出版商:S. Karger GmbH    

年代:1994

数据来源: Karger

ISSN:0378-584X    

DOI:10.1159/000218442

出版商:S. Karger GmbH    

年代:1994

数据来源: Karger

摘要:

Primary gastrointestinal lymphomas represent a specific entity which must be differentiated from nodal non-Hodgkin’s lymphomas due to its significantly different biological behavior, prognosis and treatment. In localized disease (stages IE and IIE) surgery can yield curative results. While adjuvant therapy is not necessarily required in stage-IEl tumors, postoperative chemotherapy or radiation are mandatory in the other stages or in residual disease. Multimodal therapy in stages IE and HE results in favorable prognosis as indicated by a 5-year survival rate of 75-90 %. In disseminated disease (stages IIIE and IVE) primary intensive combination chemotherapy (CHOP) is the therapy of first choice. Additional radiotherapy may be beneficial to eradicate localized tumors. Surgical resection of the tumor may eliminate hazardous sequelae of this therapy, e.g. hemorrhage, perforation. Inspite of intensive therapy, the prognosis of advanced gastrointestinal (GI) lymphoma remains poor, resulting in a 5-year survival rate of 10-30

ISSN:0378-584X    

DOI:10.1159/000218443

出版商:S. Karger GmbH    

年代:1994

数据来源: Karger

摘要:

Gastric sarcoma is rare, accounting for no more than 1-3% of all gastric malignancies. Approximately one half of all gastrointestinal sarcomas develop in the stomach. Upper GI series and endoscopy can identify the presence of a gastric lesion, but endoscopic biopsy usually fails to establish a histological diagnosis. The vast majority of gastric sarcomas are of myogenic origin. It may be difficult to determine the benign or malignant character of a stromal tumor, even if intraoperative frozen section is performed. Surgical treatment should be aimed at complete removal of the tumor with at least a 2-cm margin. Systematic lymphadenectomy is not indicated. Tumor grading and size are independent predictors of prognosis. Tumor biology varies widely and 5-year recurrence-free survival has been reported from 20-68%. Chemotherapy or radiotherapy in an adjuvant setting or for treatment of recurrence are largely ineffective.

ISSN:0378-584X    

DOI:10.1159/000218444

出版商:S. Karger GmbH    

年代:1994

数据来源: Karger

摘要:

The primary noninvasive treatment of anal carcinoma by simultaneous radio-chemotherapy is generally accepted, although prospective randomized studies have not been finished yet. The predominantly used cytotoxic agents are 5-fluorouracil and mitomycin C. Further optimizing improvement to tumor response might depend on developing more effective schedules of chemotherapy. Much is to be expected of treatment with cisplatin. Quality criteria for total- and single-dosage radiotherapy are well established in spite of different techniques. Brachytherapy requires special experience. Prophylactic radiation of the inguinal lymphatic pathways is widely used for all anal canal carcinomas as well as for anal margin carcinomas, except for Tl-carcinomas with superficial infiltration. Because of slow tumor regression, restaging should be done 3 months after completion of radio-chemotherapy. The need for control biopsy is discussed more and more controversially and greater importance is given to clinical reevaluation. In case of good tumor regression with only minimal microscopical residual tumor load, local boost radiation should be applied. If tumor regression is insufficient, however, ab-domino-perineal resection must be performed. Anal margin carcinomas require -according to their histopathologic type and tumor stage – a differentiated therapy combining surgery and radio-chemotherap

ISSN:0378-584X    

DOI:10.1159/000218445

出版商:S. Karger GmbH    

年代:1994

数据来源: Karger