摘要:

Recently, many studies have reported on the relationship between malignant potential of neoplasms and cell proliferation. Proliferating cell nuclear antigen (PCNA) is an auxiliary protein of DNA polymerase δ and is considered to correlate with the cell’s proliferative state. In this study, we investigated the correlation between tumor cell proliferation and nodal status of early gastric carcinoma. One hundred two endoscopically biopsied specimens from patients with early gastric carcinoma prior to operation were investigated by an immunohistochemical study, using anti-PCNA monoclonal antibody. Correlation of PCNA labeling index (percentage of postitive cells per over 500 tumor cells) with nodal status were studied. PCNA labeling index in patients with lymph node metastasis was significantly higher in those without metastasis. Moreover, multivariate analysis indicated that PCNA labeling index is an independent significant factor for lymph node metastasis. As a result of this study, PCNA labeling index was suggested to be effective as one of the predictors of lymph node metastasis.

ISSN:0030-2414    

DOI:10.1159/000227525

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Anticipatory nausea and vomiting (ANV) are learned responses to chemotherapy that develop in up to 25% of patients by the fourth treatment cycle. Post-treatment nausea and emesis must occur before development of ANV can take place. Certain patient characteristics and other responses to chemotherapy can also be used to predict their occurrence. Once they develop, ANV cannot be controlled by pharmacologic means including use of new 5-HT3 receptor antagonists. By contrast, behavioral therapies involving relaxation, most notably systematic desensitization, can be used to effectively treat ANV. Clinic personnel including oncologists and oncology nurses as well as behavioral psychologists can effectively administer systematic desensitization to chemotherapy patients.

ISSN:0030-2414    

DOI:10.1159/000227633

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The expression of Bcl-2 protein in 29 small cell carcinomas (SCCs; 6 surgical and 15 biopsy specimens obtained from various organs, 7 metastatic lymph nodes, and 1 metastatic liver tissue) was investigated by immunohistochemical technique. Negative staining was observed in only two cases (7%). The majority of Bcl-2-positive tumors had > 95% positive cells, with a moderate staining intensity. A combined small-cell lung cancer showed discordant staining results between two different histology types. No correlations of Bcl-2 immunoreactivity with p53 expression and clinical staging were found. Our findings suggest that Bcl-2 expression may play a certain role in the early phases of SCC tumorigenesis, or that it may solely be a succeeding property directly derived from the tumor progenitor cells. As the Bcl-2 protein was present in most cases, it is not a useful prognostic or treatment marker for the cancer.

ISSN:0030-2414    

DOI:10.1159/000227526

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Animal models of chemotherapy/radiotherapy-induced emesis successfully predicted the clinical efficacy of the 5-HT3 receptor antagonists for the control of acute emesis. Further studies in animals have provided valuable information relating to the pathophysiology of emesis and the mechanism of action of 5-HT3 receptor antagonists. These agents inhibit emesis by blocking the action of 5-HT at 5-HT3 receptors on the vagus nerve in the gastrointestinal tract and in the hindbrain vomiting system. 5-HT is hypothesized to be released from enterochromaffin cells following cytotoxic therapy or radiation. The mechanism by which 5-HT is released from enterochromaffin cells is unknown and, although various mechanisms have been proposed, none of these have provided convincing supportive evidence. In collaboration with scientists at Glaxo we have pioneered two models of cisplatin-induced acute and delayed emesis [Rudd et al., 1994]. In the first model, ferrets are given a low dose of cisplatin (5 mg/kg i.p.) and observed for 3 days. A pattern of emesis similar to that seen in the clinic has been observed with two distinct phases of emesis. Ondansetron, and particularly ondansetron plus high-dose dexamethasone, are effective in reducing the emetic response over days 1–3. The second model uses a higher dose of cisplatin (10 mg/kg i.p.) and an observation period of 24 h. Part of the emetic response over this time is resistant to 5-HT3 receptor antagonism. Studies into the mechanism of the emesis induced in both models may give an insight into cisplatin-induced emesis in man that is not controlled with 5-HT3 receptor antagonist

ISSN:0030-2414    

DOI:10.1159/000227634

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The expression of pS2 estrogen-inducible protein was investigated using formalin-fixed, paraffin-embedded sections from 210 primary breast cancers. One hundred and three (49%) out of 210 cases were positive for pS2. A significant correlation existed between pS2 expression and hormone receptor status. Patients with pS2 expression had better overall survival and a longer survival time after the first recurrence than those without pS2 expression. By multivariate analysis, pS2 was not an independent prognostic indicator, but pS2 expression was a possible indicator for responsiveness to treatment in relapsed breast cancer patients.

ISSN:0030-2414    

DOI:10.1159/000227527

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

At present, there is no satisfactory treatment for advanced breast cancer patients who have become refractory to anthracyclines. Vinca alkaloids and mitomycin C (MMC) are among the drugs most frequently used in this setting. Recently, vinorelbine (VNR) has been reported to be highly active in advanced breast cancer. Sixty advanced breast cancer patients previously treated with anthracyclines have been exposed to VNR 25 mg/m2 i.v. on days 1 and 8, and MMC 10 mg/m2 i.v. on day 1, with cycles repeated every 4 weeks. There were 3 complete and 21 partial responses for an overall response rate of 40% (CI 95%: 28–52%). Median duration of response and median survival were 7 and 10 months, respectively. Myelosuppression was the dose-limiting toxicity, but it was generally mild to moderate. Although this combination appears to be effective and well tolerated, every effort should be made to further improve treatment results in anthracycline-pretreated advanced breast cance

ISSN:0030-2414    

DOI:10.1159/000227528

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Emesis is a common side effect of chemotherapeutic drugs. Cisplatin, nitrogen mustard and dacarbazine induce increases in urinary 5-hydroxyindoleacetic acid (5-HIAA) in parallel with the development of the period of emesis which is sensitive to 5-HT3 receptor antagonists (‘acute emesis’). It is suggested that these cytotoxics release serotonin from enterochromaffin cells, which then acts on 5-HT3 receptors to trigger the emetic response. Cyclophosphamide, on the other hand, induces a modest emetic response, partly sensitive to 5-HT3 receptor antagonists, but not associated with increases in urinary 5-HIAA. It is suggested that cyclophosphamide-induced emesis is not mediated by the release of serotonin from enterochromaffin cells. Although after high-dose cisplatin most emesis is sensitive to 5-HT3 receptor antagonists, patients often present a milder, although more prolonged form of emesis which is mostly resistant to 5-HT3 receptor antagonists (also known as ‘delayed emesis’)- This form of emesis is not associated with increases in urinary 5-HIAA (not due to serotonin released from the enterochromaffin cells). Treatment with p-chlorophe-nylalanine (a serotonin synthesis inhibitor) inhibited cisplatin-induced emesis and cisplatin-induced increases in urinary 5-HIAA excretion. In summary, these results indicate that in human patients, serotonin plays a fundamental role in chemotherapy-induced emesis. Serotonin released from enterochromaffin cells seems to mediate emesis sensitive to 5-HT3 receptor antagonists induced by cisplatin, dacarbazine and nitrogen mustard. Emesis sensitive to 5-HT3 receptor antagonists associated with cyclophosphamide treatment, is not mediated by the release of serotonin from enterochromaffin cells by the cytotoxic. Therefore, cyclophosphamide could induce serotonin release either from enteric serotonin nerves or from the CNS. Cisplatin-induced emesis resistant to 5-HT3 receptor antagonists (‘delayed emesis’) is not mediated by serotonin released from enterochrom

ISSN:0030-2414    

DOI:10.1159/000227636

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We evaluated the effects of cisplatin on the cell kinetics, cytomorphological changes, and cleavage patterns of DNA in two lines of human ovarian carcinoma cells. KF-1 cells displayed a cell cycle arrest in the G2M phase, while HMG cells displayed a transient cell accumulation in the S phase, without obvious G2M arrest. Morphological changes characterized by condensation and fragmentation of chromatin, and DNA cleavage by oligonucleosome-sized DNA fragments were observed in the HMG cells but not in the KF-1 cells. The pattern of cell death in HMG cells was considered to be apoptosis, but that of KF-1 cells necrosis. These findings showed the different mechanisms of antitumor effect of cisplatin on human ovarian carcinoma cell lines, including cell kinetics and pattern of cell death.

ISSN:0030-2414    

DOI:10.1159/000227529

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Different cytotoxic drugs induce different patterns of emesis. This is relevant to clinical practice since we often see in the medical literature oversimplifications in the recommendation for management of chemotherapy-induced emesis, so that the same guidelines are given for cisplatin and non-cisplatin-containing chemotherapy. In particular, cisplatin induces a biphasic pattern of emesis which is characterized by an acute immediate phase and a delayed phase. These two phases are clearly different, especially when cisplatin is given in short i.v. administration (e.g. over 20 min to 1 h) and in high doses (100–120 mg/m2). On the other hand, cyclophosphamide and carboplatin induce a quite different pattern of emesis, characterized by a monophasic curve which, although more intense in the first 24 h, may continue for a number of days. The antiemetic response to 5-HT3 receptor antagonists on days 2–5 is good in the case of carboplatin and cyclophosphamide and poor in the case of cisplatin (delayed emesis after cisplatin). This firmly suggests that the pathogenesis of cisplatin-induced emesis may differ from that induced by other cytotoxic drugs, especially in the delayed phase of emesis. We think that we should reserve the term ‘delayed emesis’ for the late emesis induced by cisplatin, while ‘prolonged emesis’ could be a better denomination for the late emesis induced by cyclophosphamide and carboplatin. The main clinical implication of these observations is that 5-HT3 receptor antagonists should be administered over 3–5 days in the case of carboplatin and cyclophosphamide, while a short treatment during the first day could be sufficient to control the acute phase of cisplatin-i

ISSN:0030-2414    

DOI:10.1159/000227637

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Methotrexate (MTX) suppressed the growth of Ehrlich ascites tumor (EAT) cells in vitro. The intracellular level of phosphoribosyl 5-pyrophosphate (PRPP) of EAT cells increased in a dose-dependent manner in response to MTX treatment. At the same time, the rate of glucose transport was lowered. Hypoxanthine reversed both these effects of MTX and partially rescued EAT cell growth. Under all conditions tested, changes in rate of glucose transport were shown to be the result of alterations in the number of glucose transporter (Vmax) rather than ligand affinity (Km). The dual action of MTX as a chemotherapeutic agent is discussed in this light.

ISSN:0030-2414    

DOI:10.1159/000227530

出版商:S. Karger AG    

年代:1996

数据来源: Karger