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- Hertervig, Erik, et al.
(författare)
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Alkaline sphingomyelinase activity is decreased in human colorectal carcinoma
- 1997
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Ingår i: Cancer. - 1097-0142. ; 79:3, s. 448-453
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The metabolism of sphingomyelin generates important signals regulating cell proliferation and apoptosis. Previous studies found that the administration of colon carcinoma carcinogen was associated with an accumulation of membrane sphingomyelin, and that dietary sphingomyelin inhibited promotion of experimental colon carcinoma in mice, indicating that the abnormal metabolism of sphingomyelin is linked to colon carcinoma development. However, the changes in sphingomyelinase (SMase) activity in colon carcinoma have not been directly studied. The authors identified, specifically in the intestine, a distinctive alkaline SMase that differs from the known acidic and neutral SMases. The functions and clinical implications of the enzyme are unknown. This study examined the changes in all three SMase activities in human colorectal carcinoma. METHODS: Tissue samples were taken from colorectal carcinoma and normal mucosa from 18 patients. After homogenization, the activities of acidic, neutral, and alkaline SMase, as well as ceramidase and alkaline phosphatase, were determined. The enzyme activities in cancer tissue were compared with normal tissue from the same patients. RESULTS: In the normal tissue, there is an activity gradient from the ascending colon to the rectum for neutral and alkaline SMases but not for acidic SMase. In colorectal carcinoma, alkaline SMase activity was preferentially decreased by 75%, whereas acidic and neutral SMase activity decreased by 30% and 50%, respectively. No changes could be found for either ceramidase or alkaline phosphatase activity. CONCLUSIONS: Alkaline SMase activity preferentially decreases in human colorectal carcinoma, suggesting a regulatory role of the enzyme in colon mucosa cell proliferation.
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| 2. |
- Loman, Niklas, et al.
(författare)
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Steroid receptors in hereditary breast carcinomas associated with BRCA1 or BRCA2 mutations or unknown susceptibility genes
- 1998
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Ingår i: Cancer. - 1097-0142. ; 83:2, s. 310-319
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The expression of steroid receptors is a common feature of both male and female breast carcinomas and is also one of the most important prognostic factors for patients with this disease. Steroid receptor levels in BRCA1-related breast carcinoma have reportedly been low. Little data on steroid receptor levels have been reported with regard to BRCA2. METHODS: Steroid receptor levels were analyzed in 27 breast carcinomas associated with BRCA1 mutations, 14 associated with BRCA2 mutations, and 32 from individuals who had hereditary breast carcinoma but no detectable mutations of either BRCA1 or BRCA2. Breast carcinomas from 32 consecutive male patients, 6 of whom had mutations of BRCA2, were also examined for steroid receptors. Estrogen receptor (ER) and progesterone receptor (PgR) analyses were performed with radioligand or enzyme immunoassay techniques on tumor cytosol preparations. Germline mutation screening and detection were performed using the protein truncation test, single strand conformation polymorphism, and direct sequencing on DNA from normal tissue. RESULTS: The BRCA1-related tumors expressed significantly lower levels of ER than tumors from the other hereditary groups. The PgR levels were significantly lower in the BRCA1-related cases than in the hereditary cases not related to BRCA1 or BRCA2, but not significantly lower than in the BRCA2-related cases. Fourteen of 32 (44%) of the hereditary tumors not related to BRCA1 or BRCA2 had PgR levels exceeding 100 fmol/mg of protein. The tumors from male patients with BRCA2-related disease did not have receptor levels that differed from those in non-BRCA2-related tumors. CONCLUSIONS: BRCA1- and BRCA2-related breast tumors were distinct in their expression of steroid receptors. Moreover, a subgroup of tumors not related to BRCA1 or BRCA2 manifested a strongly positive PgR phenotype rarely seen in BRCA1- and BRCA2-related tumors. These characteristics may be of relevance to the treatment and follow-up of high risk individuals in these families and may help identify a homogeneous category of hereditary breast carcinomas not related to BRCA1 or BRCA2 in which new susceptibility genes may be sought.
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| 6. |
- Eriksson, B. K., et al.
(författare)
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Liver embolizations of patients with malignant neuroendocrine gastrointestinal tumors
- 1998
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Ingår i: Cancer. - 0008-543X .- 1097-0142. ; 83:11, s. 2293-2301
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Patients with neuroendocrine gastrointestinal tumors usually present with inoperable metastatic disease and severe hormonal symptoms. Specific chemotherapy, interferon-alpha (IFN), and somatostatin analogs are established therapies for these patients, but all of them eventually fail. Hepatic arterial embolization can provide reduction of both hormonal symptoms and tumor burden in these patients. METHODS Between 1981 and 1995, a total of 55 liver embolizations with gel foam powder were performed on 41 patients with histopathologically verified neuroendocrine tumors; 29 had carcinoid tumors and 12 had endocrine pancreatic tumors (EPTs). All patients had received medical treatment, including chemotherapy (n = 18), IFN (n = 31), and octreotide (n = 19), and were experiencing treatment failure when liver embolization was performed at a median of 37 months after diagnosis of liver metastases. Medical treatment was continued after embolization. RESULTS An overall objective response was noted in 15 of 29 patients with carcinoid tumors (52%). The median duration of effect was 12 months in patients with midgut carcinoid tumors. An overall objective response was observed in 6 of 12 patients with EPTs (50%), with a median duration of effect of 10 months. Adverse events were observed, and, in agreement with earlier reports, the rate of serious complications was 10%. Survival analyses showed a median survival of 80 months and a 5-year survival rate of 60% from the performance of embolization on patients with midgut carcinoid tumors, whereas for patients with EPTs the median survival from embolization was only 20 months. CONCLUSIONS Liver embolizations performed relatively late in the clinical course in our series appeared to be as effective as "early" embolizations in other series of patients with carcinoid tumors. The results for those with EPTs were poorer, and earlier embolizations may result in better outcomes for these patients. Considering the morbidity associated with the procedure, it is imperative to select patients according to extent of liver involvement, severity of carcinoid heart disease, and somatostatin receptor status.
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| 7. |
- Fransson, Per, et al.
(författare)
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Late side effects unchanged 4-8 years after radiotherapy for prostate carcinoma : A comparison with age-matched controls
- 1999
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Ingår i: Cancer. - : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 85:3, s. 678-688
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. The authors of this study previously evaluated pelvic irradiation-induced late side effects in patients with localized prostatic carcinoma 4 years after external irradiation by administering a validated self-assessment questionnaire (QUFW94), and compared the results with those of age-matched controls. The current study was designed to evaluate prospectively the patients' problems 8 years after radiotherapy and to compare them with those reported by the same controls. METHODS. The questionnaire was sent out at a mean of 8 years (range, 72-104 months) after irradiation to 120 patients and 125 controls. For analysis of sexual function, the patient group was divided into two subgroups, one treated with radiotherapy only (RT) and one group treated with radiotherapy plus castration (RT+A). A value of >1 on a 0-10 scale indicated that the patient was having a problem. RESULTS, The mean age was 73 years for both patients and controls. No changes in urinary problems were seen between the 4-year and the 8-year follow-up in the 2 groups. Sixty percent and 54% of the patients (P = 0.096) and 24% and 31% of the controls (P = 0.988) reported urinary problems at the 4-year and 8-year follow-ups, respectively. No changes in gastrointestinal late side effects in the patient group were seen between the 4-year (65%) and the 8-year (62%) follow-ups (P = 0.490). However, there was a decrease in intestinal problems in the control group between the 4-year (12%) and the 8-year (9%) follow-ups (P = 0.001). The sexual problems did not change during the two periods, in the patient groups or in the control groups. Fifty-six percent and 65% of the RT group (P = 0.052), 67% and 54% of the RT + A group (P = 0.555), and 27% and 33% of the control group (P = 0.243) indicated some kind of sexual problem at the 4-year and 8-year follow-ups, respectively. CONCLUSIONS. The amount of pelvic irradiation-induced urinary late side effects, intestinal late side effects, and sexual function, evaluated with a self-assessment questionnaire, did not change between 4 and 8 years after RT. The age-matched controls reported no change in urinary or sexual problems despite advanced age, but there was a reported decrease in intestinal problems, Cancer 1999;85:678-88. (C) 1999 American Cancer Society.
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| 8. |
- Fransson, Per, et al.
(författare)
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Self-assessed sexual function after pelvic irradiation for prostate carcinoma : Comparison with an age-matched control group
- 1996
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Ingår i: Cancer. - : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 78:5, s. 1066-1078
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Treatment of localized prostate carcinoma is often accompanied by disturbances in sexual function. The patient's own opinion and experience with these problems can be of great importance for his quality of life. In men older than 50 years, disturbances in sexual function are common. Treatment such as radiotherapy (RT), which can induce sexual dysfunction, should be evaluated in relation to the problems in an age-matched population without prostate carcinoma. METHODS. Sexual function was evaluated with a self-assessment questionnaire using linear-analogue scales. The questionnaire was sent to 199 patients with prostate carcinoma, median age 71 years (range, 51-86 years), who had received pelvic RT with curative intent and to 200 age-matched men in northern Sweden. Mean follow-up time after RT was 48 months (range, 24-56 months). RESULTS. The response rate was high: 141 (71%) and 181 (91%) in the control and patient groups, respectively. Field reduction and treatment pause during RT was not associated with decreased problems in the patient groups. A failure to achieve erection was indicated in 12% of the control subjects, 56% of the patients who had received (RT only) and 87% of the RT + castration (RT + A) patients. In general, patients < 70 years treated with RT + A indicated more sexual problems than the RT only patients < 70 years. There was a strong negative correlation between age and sexual problems in the RT 9 A < 70 years group. However, in patients < 70 years, sexual activity after RT only, was not significantly different from the age-matched control population. CONCLUSIONS. Patients with prostate carcinoma treated with RT only indicated higher levels of sexual dysfunction than age-matched controls. This was most obvious in patients younger than 70 years, although their sexual activity was comparable to age-matched controls. The addition of castration to RT tended to increase sexual problems, especially in patients < 70 years. In men between 70 and 74 years, the maintenance of sexual function seems to be very susceptible to disturbances. For patients older than 74 years, decreased sexual function was not perceived as such a significant problem, despite abolished desire and erection. (C) 1996 American Cancer Society.
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