摘要:

The importance of age as a prognostic factor in aggressive non-Hodgkin’s malignant lymphoma (NHL) remains controversial. It is not clear whether age is an independent factor, reflecting the limited physiologic reserves of the patient, and leading in any treatment conditions to the poorer treatment outcome. This study was aimed at assessing the influence of age on treatment results in NHL patients. Therefore, the records of 40 patients with histologically confirmed NHL of intermediate and high-grade malignancy, according to the Working Formulation, who were treated by Adriamycin-containing chemotherapy, were retrospectively reviewed. There were 25 patients above 60 years of age and 15 patients below this age. Myelotoxicity was observed in 60% of the patients in the younger and in 48% patients in the older age group. The median time to dose-limiting toxicity, average percentage of projected dose intensity for all drugs, and percentage of projected dose intensity did not differ significantly in the two groups. Complete remissions (CR) were obtained in 67 and 64% of the younger and older groups, respectively. Progressive disease was observed during the treatment in 20% of the patients in each age group. Median survival was 36.5 and 32 months in the younger and older group, respectively. In conclusion, age alone is not an absolute predictor of survival of treated elderly patients with aggressive NHL. Dose rate, tolerance of treatment and achievement of CR are additional important prognostic factors. Dose intensity should not be automatically reduced at the beginning of the treatment, especially now that growth factors are availabl

ISSN:0030-2414    

DOI:10.1159/000227617

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The overexpression of two members of the erbB oncogene family – the epidermal growth factor receptor protein (EGF-R) and the HER-2/neu protein – in breast cancer has been investigated by numerous authors. Their exact role in breast cancer is still not defined. The simultaneous investigation of EGF-R and HER-2/neu in the same study population has only rarely been performed in breast cancer. Therefore, we analyzed the EGF-R and the HER-2/neu protein expression in 142 breast cancer specimens and 12 benign breast samples by immunohistochemistry. Results of the different expression analyses were compared with established clinicopathological parameters including estrogen and progesterone receptor status. In our study group EGF-R expression correlated with advanced tumor stage, axillary lymph node status and histological grade. HER-2/neu expression correlated with larger tumor size. Neither the evaluation of a single parameter of the erbB family nor the combination of both parameters showed a significant correlation with the disease-free and the overall survival of the individual patient with breast cancer. Only the expression of the progesterone receptor correlated with a better overall survival. Steroid hormone receptor expression and the expression of EGF-R and HER-2/neu seem to be two independent phenomena in our samples of breast cancer. The simultaneous evaluation of EGF-R and HER-2/neu expression did not lead to new information of prognostic releva

ISSN:0030-2414    

DOI:10.1159/000227618

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Overexpression and amplification of the c-myc oncogene occur in approximately 70 and 10% of human primary colorectal carcinomas, respectively, indicating the importance of this gene in colorectal tumorigenesis. Little, however, is known about the involvement of c-myc in the progression of colorectal cancer. We therefore determined c-myc gene expression and amplification in a group of primary tumors and metastases from patients with colorectal cancer using quantitative PCR-based tests. While the percentage of metastases over-expressing c-myc (13/26 =50%) was in the same range as reported for primary tumors by others, gene amplification of c-myc was significantly (p = 0.001) more frequent in metastases (16/27 = 59%) compared to primary tumors (1/23 = 4%) in our series. Interestingly, in 23 metastases where both expression and amplification of c-myc could be determined, there was no correlation between gene copy number and expression level (p = 0.18; r = 0.19). We conclude that amplification but not overexpression of c-myc is related to metastatic progression of colorectal cancer and that overexpression of c-myc is driven by mechanisms other than the number of c-myc copies in the tumors studied.

ISSN:0030-2414    

DOI:10.1159/000227619

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

In patients affected with different tumours, disorders concerning clotting are frequently observed. The biological processes leading to coagulation are probably involved in the mechanisms of metastasis. We studied plasma levels of thrombin-antithrombin III complexes (TAT) in 90 patients affected with lung tumours subgrouped in small cell and non-small cell (NSC) lung cancer: 17 patients had no evidence of disease after surgery (NE); the remaining 73 patients were divided according to the absence (LOC) or the presence (META) of metastases. All the patients were followed up for several months. In all the lung cancer patient groups, at the beginning of the study we detected TAT levels that were higher than in controls. During the follow-up period, the NSC-NE patients with no recurrence of the disease as well as the NSC-LOC patients responding to the treatment had a decrease in TAT levels (p < 0.01 and p < 0.05, respectively). The NSC-META patients with progression of their disease had, in contrast, an increase in TAT levels (p < 0.01). Our data reveal the presence of ‘latent coagulation disorders’ as assessed by the presence of high TAT levels in the majority of lung cancer patients. The follow-up study indicates that in the NSC group, a relation exists between coagulation activation and rate of tumour progression and/or response to treatment. In cancer patients the early detection of coagulation disorders could also allow, therefore, the prevention of thromboembolism and/or haemorrhage by administration of appropriate treatm

ISSN:0030-2414    

DOI:10.1159/000227620

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The objective of this review is to make physicians aware of new radionuclide methods to detect cardiac effects of chemotherapeutic drugs. This knowledge is important because of the limitations of the physical examination and the electrocardiogram for detecting early reversible cardiac damage. Presently left ventricular ejection fraction (LVEF) is routinely used to screen for cardiotoxicity. Since LVEF obtained by radionuclide angiocardiography is more accurate than the LVEF estimated by echocardiography, serial radionuclide LVEF monitoring is most commonly used to monitor cardiotoxicity. Diastolic measurements of left ventricular function (such as peak filling rate) are now being added to routine LVEF measurements to enhance standard radionuclide evaluation. This screening test should be done prior to beginning therapy and at appropriate points based on the baseline study, therapy scheme and the patient’s clinical status. At some centers, exercise LVEF methods are being used to determine if cardiac reserve is adequate for the patient to tolerate additional chemotherapy when cardiac injury may be present. Previously, endomyocardial biopsy was needed to detect and confirm early anthracycline cardiotoxicity. This invasive test may be replaced by a new noninvasive in vivo method using radioactive monoclonal antibodies against cardiac muscle (indium-lll-antimyosin). Because cardiac failure has been associated with adrenergic neuron injury, it has been proposed that radioactive methyliodo-benzylguanine may detect the adrenergic abnormality which may predict future development of congestive heart failure or sudden death months after therapy is discontinued. Advantages and disadvantages of these methods in evaluating cardiotoxicity, and an algorithm to optimally monitor antitumor therapy-induced cardiomyopathy are discusse

ISSN:0030-2414    

DOI:10.1159/000227621

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The objective of this study was to investigate the influence of pregnancy in breast cancer prognosis of women under the age of 35 years. Two hundred and forty-three women with breast cancer, from three oncology departments in Athens, were investigated. Twenty-one got pregnant (7.91%) 7–100 months after breast cancer diagnosis and in a median time period of 31 months. All women had mastectomy apart from 2 who had only lumpectomy as surgical procedure. Thirteen of 21 were treated with radiotherapy and 17 of 21 had also adjuvant chemotherapy mainly with CMF for 6 cycles. Sixteen children from 14 mothers were born and the rest of the patients underwent an abortion between the 2nd and 5th month of pregnancy. All children were healthy and grew up normally up to the age of 12–142 months (end of the study) and their median age of 51 months. Only 2 patients had stage III disease at diagnosis while the remaining 19 had stage I–IIb. Three cancer recurrences were observed (14.3%) after 7–84 months. One patient had a second primary-ovarian cancer 60 months after mastectomy. Recurrence rate and survival compared with those of nonpregnant women of the same age and the stages of disease were not different. To conclude: the present study indicates that healthy offsprings can be delivered from breast cancer patients, and pregnancy does not seem to play any role in tumor rec

ISSN:0030-2414    

DOI:10.1159/000227622

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Preclinical and clinical studies have been performed to evaluate the efficacy of gemcitabine (2′,2′-difluorodeoxycytidine; dFdC) in human renal cell carcinoma. Experimental data corroborated dFdC as an effective drug against cell lines from renal cell carcinomas (ACHN, A-498, SN12C) at concentrations much below clinically achievable doses. ACHN-bearing nude mice showed an overall response rate of 27% to dFdC (3 mice with complete response, 1 with partial response, 3 with stable and 8 with progressive disease). Objective response from 37 evaluable patients was 8.1% (1 patient with complete response and 2 patients with partial response). Gemcitabine was well tolerated thus, although gemcitabine at the dosage and schedule chosen had only small activity, the observed toxicity may permit further dose escalation or a more frequent administration of the d

ISSN:0030-2414    

DOI:10.1159/000227623

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Forty-one patients with acute non-lymphoblastic leukemia were treated between March 1990 and November 1993 with mitoxantrone, cytarabine, etoposide and granulocyte-macrophage-colony-stimulating factor (GM-CSF) started on day 1. This was given as induction, consolidation and intensification treatment. A complete response was obtained in 26 of 41 (63%) patients. The median survival of the 25 evaluable patients in complete remission was 18 months. The median duration to neutropenia < 500/ul was 20 days during induction, 15 days during consolidation, 21 days during first intensification and 25 days during second intensification. Mitoxantrone, cytarabine and etoposide given with GM-CSF gave a complete response rate and median survival similar to other combination treatments but there was no definite evidence that the duration of neutropenia was reduced by the addition of GM-CSF from the start of treatment.

ISSN:0030-2414    

DOI:10.1159/000227624

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

A retrospective review of 130 patients with peripheral-type cholangiocarcinomas (PTCC), hilar-type cholangiocarcinomas (HTCC), extrahepatic cholan-giocarcinomas (EHCC), gallbladder cancers (GBCA), and periampullary cancers (PACA), seen at National Cheng Kung University Hospital and Tainan Municipal Hospital from June 1987 to July 1993 was performed. There were 47 (36%) HTCC, 32 (25%) PACA, 24 (19%) PTCC, 17 (13%) GBCA, and 10 (8%) EHCC patients. The distribution is completely different from that reported in western countries. These cancers mainly occur in elderly patients. HTCC and GBCA were predominantly noted in female patients. Biliary cancers in Taiwan were not related to liver fluke infestation, inflammatory bowel disease or hepatitis B virus infection. However, a close association with biliary lithiasis was found. The incidence of gallstones was 67, 39,20,29 and 19% for PTCC, HTCC, EHCC, GBCA and PACA, respectively. The most common presentation for PTCC and GBCA was abdominal pain, or jaundice for HTCC, EHCC and PACA. These symptoms correlate well with the location of the tumors. Among serum tumor markers, the elevation of CA19-9 was most frequent, occurring in 86% of the patients while CA125 and CEA occurred in 47% and 30% of the patients, respectively. During the course of disease, infection developed in 61 % of the patients and was the main cause of death in 25%. Biliary tract infection and sepsis were the two leading manifestations and occurred in 49% and 32% of the patients, respectively. Overall survival was poor except in patients whose tumor could be completely resected.

ISSN:0030-2414    

DOI:10.1159/000227625

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The retinoblastoma gene product (RB protein) plays a key role in the progression of the cell cycle from G1 to S phase in normal and neoplastic cells. The activity of RB is regulated by phosphorylation and dephosphorylation with cell-cycle-dependent protein kinases. We investigated the effect of the protein kinase inhibitors, staurosporine and 7-hydroxy-staurosporine (UCN-01), on RB protein expression of N417 small cell lung cancer cells (absent RB), H209 small cell lung cancer cells (mutant RB), and Ma-31 non-small cell lung cancer cells (wild-type RB), using immunologic blotting. Staurosporine and UCN-01 each suppressed the growth of N417, H209 and Ma-31 cells in a dose-dependent manner in MTT assay. IC50 values of staurosporine for N417, H209 and Ma-31 cells were 54, 29 and 602 nM, respectively. IC50 values of UCN-01 for N417, H209 and Ma-31 cells were 737,181 and 2,197 nM, respectively. Exposure to staurosporine and UCN-01 for 72 h each suppressed the level of expression and altered the ratio of phosphorylated/dephosphorylated RB protein (ppRB/pRB) of Ma-31 cells. Conversely, these agents increased the expression level of RB protein at concentrations less than IC50, and did not change phosphorylation status of mutant RB protein of H209 cells at the concentrations studied. A time course study demonstrated that exposure to the IC50 concentration of staurosporine for 48–72 h increased the ratio of ppRB/ pRB of Ma-31 cells, while exposure to the IC50 concentration of UCN-01 decreased that ratio. UCN-01 increased % cells in G2+M phase and decreased % cells in S phase, while staurosporine increased % cells in G1 phase and decreased % cells in G2+M phase. UCN-01 did not induce apoptosis (DNA content < 2N) of Ma-31 cells, but staurosporine induced it. These findings suggest that the differing effects of staurosporine and UCN-01 on RB protein expression and cell cycle phases of lung cancer cells may explain their differing in vivo antitumor effect of staurosporine and UCN-01 despite their similar chemical structure

ISSN:0030-2414    

DOI:10.1159/000227626

出版商:S. Karger AG    

年代:1996

数据来源: Karger