摘要:

Mitomycin, ifosfamide, and cisplatin have demonstrated the best single-agent activity thus far in patients with non-small cell lung cancer (NSCLC), the most common malignant disease in the western world. For this reason, we initiated a phase II study, giving these three agents in combination (designated MIC) to 74 patients with inoperable NSCLC. Sixty-six patients were evaluable for response, of whom 30 (45%) demonstrated a partial response and 7 (11%) a complete response. These results, along with those obtained in two other phase II trials of MIC in NSCLC, prompted us to begin a large-scale, multicen-ter, phase III study of MIC in patients with inoperable limited-stage NSCLC. In this ongoing study, patients have been randomized to receive treatment with MIC and radiotherapy or radiotherapy alone. We hope to resolve the issue of whether a survival advantage is conferred on NSCLC patients treated with radiotherapy in combination with this promising chemotherapeutic regimen.

ISSN:0030-2414    

DOI:10.1159/000227245

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

We studied the potential of alpha-interferon(IFN-α) to enhance alpha-feto-protein (AFP) and thus alter the localization of 125I-labeled antibody to the human hepatoma xenograft in athymic mice using monoclonal antibody (M Ab) 19F12, which recognized AFP on the surface of human hepatoma cells. Treatment of the human hepatoma cell NuE with IFN-α increased the surface expression of AFP 2.4-fold in an IFN-dose-dependent manner. The IFN-α treatment substantially increased (2.7-fold) the localization of 125I-labeled 19F12 to NuE xenografts in athymic mice. The increase in localization of 125I-labeled 19F12 was dependent on the circulating plasma IFN levels. Our experimental results suggested that IFN-α could act as a potent modulator of the cellular antigen AFP, and be used to enhance the targeting of a conjugated MAb to hepatoma cell populations.

ISSN:0030-2414    

DOI:10.1159/000227144

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

DNA ploidy was analysed by flow cytometer from frozen samples of 205 colorectal carcinomas. Sixty-two percent of the tumours had an abnormal DNA stemline. Forty-eight percent of carcinomas in the right colon, 62% of carcinomas in the left colon and 74% of carcinomas in the rectum were aneuploid (p = 0.007). Sixty-nine percent of tumours in males and 55% of tumours in females were aneuploid (p = 0.029). The difference in frequency of aneuploidy between females and males was greatest in tumours of the right colon, where 37% of the tumours in females and 62% of the tumours in males were aneuploid (p = 0.047). The percentage of diploid colorectal carcinomas was higher (55%) in patients with a history of noncolorectal malignancy than in others (34%, p = 0.031). These results suggest that flow cytometry may be helpful in understanding the development of colorectal carcinomas.

ISSN:0030-2414    

DOI:10.1159/000227145

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

This study was performed to clarify the promoting effects of primary or secondary bile acid load on the occurrence of cholangiocarcinoma, using Syrian golden hamsters. These hamsters received subcutaneously diisopropanolnitrosamine (DIPN) once weekly for 10 weeks, and simultaneously were given a standard pellet diet (control group) containing taurocholic acid (TCA group) or deoxycholic acid (DCA group). The rates of cholangiocarcinoma at 20 weeks were 23% in the control group, 60% in the TCA group and 59% in the DCA group. There were significant differences between the control and the TCA or DCA groups (p < 0.05). The rates of proliferation of bile ductules or hyperplasia of the bile duct epithelium and the bromodeoxyuridine labeling indices of bile duct epithelial cells were high in both groups treated with bile acids, compared with those in the control group. Regarding the composition of bile acids in the intraductal bile, the TCA and DCA groups revealed a decrease in primary bile acids and an increase in DCA. These results suggest that both TCA and DCA given orally promote the occurrence of DIPN-induced cholangiocarcinoma.

ISSN:0030-2414    

DOI:10.1159/000227146

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

A silver-staining technique to identify nucleolar organizer region-associated proteins (Ag-NOR) was applied to 55 gastric myogenic tumors. The mean numbers of Ag-NOR in the nucleus were: leiomyoma (30 cases), 2.0 + 0.6 (mean + SD); low-grade leiomyosarcoma (11 cases), 3.0 + 0.7; and high-grade leiomyosarcoma (14 cases), 3.9 + 0.7. The Ag-NOR counts were compared with DNA ploidy as determined by flow cytometry in 46 tumors. The Ag-NOR counts were significantly different in the aneuploid leiomyosarcomas (4.1 + 0.6: mean + SD) and diploid leiomyosarcomas (2.9 + 0.6: mean + SD). Thus, this parameter may serve as an objective histological discriminant for malignancy.

ISSN:0030-2414    

DOI:10.1159/000227147

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Concurrent administration of chemotherapeutic agents and radiation with or without surgery has yielded better local disease control and more prolonged survival than has standard radiation therapy or surgery alone in patients with esophageal cancer. Combinations of 5-fluorouracil (5-FU) and either cisplatin or mitomycin have proven most effective in this setting. As a single agent, mitomycin has generated response rates of 14–42% in patients with squamous cell carcinoma of the esophagus. The response of patients with esophageal adenocarcinoma to single-agent mitomycin is unknown. The clinical use of mitomycin concurrent with 5-FU and radiation is well established in esophageal cancer. There is some experimental evidence to suggest that synergy may occur between 5-FU and mitomycin. Mitomycin is preferentially cytotoxic to hypoxic cells, which are relatively radioresistant. It is not clear whether use of mitomycin with radiation is additive or supra-additive as experimental evidence exists to support both types of interaction. Nonrandomized clinical trials suggest that using either cisplatin or mitomycin concurrently with 5-FU and relatively low-dose radiation (30 Gy) prior to esophagectomy can result in comparable rates of pathologic complete response (20–30%) and median survival (12–19 months). Hematologic toxicity is frequently severe if all 3 drugs are used concurrently in combination with radiation. In patients with advanced disease (stage III or IV), combination chemotherapy/radiation therapy can result in significant palliation with tolerable morbidity. The use of concurrent chemotherapy and radiation has changed the pattern of failure in esophageal cancer from one dominated by inability to control local disease to one where systemic failure predominates. Current and proposed trials in esophageal cancer have changed their focus accordingly to meet this new treatment chal

ISSN:0030-2414    

DOI:10.1159/000227247

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Survival data of the patients were correlated to tumour size, axillary lymph node (pN) status, mitotic frequency and morphometric prognostic index (MPI) in a series of 611 women with a primary breast carcinoma treated and followed-up for over 12 years in Kuopio University Hospital. The pN status, tumour size, mitotic activity index (MAI), volume-corrected mitotic index (M/V index) and MPI all predicted recurrence-free survival and cancer survival (p < 0.001). In pN(––) patients, the MPI was the most important predictor of recurrence-free survival and cancer survival (p < 0.001) followed by the mitotic frequency. In pN( + ) patients, tumour diameter and MPI were equal predictors (p < 0.001) of survival followed by M/V index. In Cox’s analysis, MPI, pN status and mitotic frequency independently predicted survival in the whole series. In the separate analysis of pN(––) and in pN( + ) tumours, the MPI and MAI independently predicted survival. The M/V index was independently related to recurrence-free survival in pN( + ) tumours. In multivariate analysis, MPI was an independent predictor although it does not include all the prognostic information. The results suggest that the decisions on adjuvant therapy in breast cancer can be based on the MPI, particularly in pN(–

ISSN:0030-2414    

DOI:10.1159/000227148

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

A sulfur-containing amino acid compound, S-allyl cysteine (SAC), derived from garlic extract inhibited proliferation of nine human and a murine melanoma cell line in a dose-dependent manner (1.2–10 mM) assessed by a [3H]thy-midine incorporation assay. Three control human lymphoblastoid cell lines were not inhibited by SAC concentrations < 5 mM. Four human melanoma cell lines in a soft-agar assay also showed dose-dependent inhibition of colony formation by SAC. Melanin content was increased up to 95% compared to the same untreated cell lines in these four human melanoma and two B16 murine melanoma sublines. Expression of cell surface gangliosides, cellular-differentiation and transformation markers, decreased after SAC treatment. Significant morphological changes including ‘flattening and/or dendritic-like elongations’ were also observed. Thus SAC inhibited cellular growth and proliferation and modulated major cell differentiation markers of mel

ISSN:0030-2414    

DOI:10.1159/000227149

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The Ki-ras proto-oncogene is converted into an active oncogene by mutations in codon 12, 13, or 61. The incidence of mutations in the Ki-ras oncogene in colorectal adenomas and primary colorectal carcinomas has been shown to be 50-75 and 40-65%, respectively. To determine the role activation of the Ki-ras oncogene plays in the progression of colorectal carcinoma, we analyzed DNA from 11 nude-mouse xenografts and from 24 metastases of 22 patients with colorectal carcinoma, using the polymerase chain reaction technique and hybridization with labeled mutation-specific oligomers. Eleven of the 24 metastases (46%) carried mutations, 7 in codon 12 and 4 in codon 13, whereas only 1 nude-mouse tumor (9%) harbored a Ki-ras codon-12 mutation. Eleven of these 12 mutations in advanced stages of colorectal cancer were localized to the second position of either codon 12 or codon 13, whereas a majority of published ras mutations in earlier stages are in the first position of codon 12 of the Ki-ras oncogene. We conclude that there is a position specificity of Ki-ras oncogene mutations in advanced stages of colorectal carcinoma. In general, however, these mutations do not seem to play an important role in the progression of this cancer.

ISSN:0030-2414    

DOI:10.1159/000227150

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

In a randomized trial we compared single-agent epirubicin with the FEM (5-fluorouracil/epirubicin/mitomycin) combination in patients with locally advanced and/or metastatic adenocarcinoma of the pancreas. Sixty patients previously untreated with radiotherapy or chemotherapy were randomly assigned to receive either 100 mg/m2 epirubicin or FEM in the following doses: 5-fluorouracil, 600 mg/m2 to a maximum of lg; epirubicin, 50 mg/m2; mitomycin, 6 mg/m2 to a maximum of 10 mg. Treatment was given every 28 days via intravenous bolus; because of its association with delayed myelotoxicity, mitomycin was given every other cycle. A total of 47 patients are evaluable for toxicity and survival, 22 who received FEM and 25 epirubicin. Preliminary results of this ongoing study show no difference in survival between the two arms. Toxicity has been easily managed. A similar number of patients in each arm had elevated serum bilirubin levels, but dose reductions of 50% allowed all these patients to continue treatment.

ISSN:0030-2414    

DOI:10.1159/000227250

出版商:S. Karger AG    

年代:1993

数据来源: Karger