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Träfflista för sökning "AMNE:(MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology) srt2:(1995-1999)"

Sökning: AMNE:(MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology) > (1995-1999)

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  • Jernström, Helena (författare)
  • Effects of Oral Contraceptives on Endogenous Hormones, Body Constitution, and Breast Epithelium in Healthy, Young Women
  • 1996
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • This thesis concerns the effects of low-dose oral contraceptives (OCs) on endogenous hormones, insulin-like growth-factor-1 (IGF-1), sexual hormone binding globulin (SHBG), and body constitution in two groups of healthy women aged 19­25 who had never been pregnant. Prolactin concentrations were elevated in a subgroup of present and former users. IGF-1 concentrations were significantly decreased during menstrual cycle days 18­23 in present OC users compared with never users, while no effect was seen during cycle days 5­10. Former users had significantly higher follicle-stimulating hormone (FSH) concentrations than never users. This rebound-like phenomenon peaked one year after cessation of use. High FSH concentrations could increase the number of ovulations and thereby the ovarian cancer risk, especially among intermittent users who may experience repeated rebound peaks. Among present and former users SHBG concentrations were significantly correlated with reported weight gain in connection with OC start. SHBG was not related to the same hormonal and constitutional parameters in former users as in never users. Breast size was significantly larger in present users than in former and never users, and approximately half of the ever users reported breast tenderness or enlargement in connection with OC start. Breast epithelial proliferation rate was studied by means of a new monoclonal antibody, Ki-S5, in 58 women who had undergone reduction mammoplasties and who were born 1940 or later. There was no significant difference in breast tissue proliferation between present, former and never users. Women who had used OCs before the first full-term pregnancy had a significantly higher proliferation rate in the breast tissue than other women, regardless of present OC status. Women who used exogenous hormones and who had a first and/or second degree relative relative with breast cancer had a significantly higher proliferation rate in the breast tissue than other women. A high proliferation rate may increase the risk of developing breast cancer.
  • Johansson, Maria C (författare)
  • Improvements of the Bromodeoxyuridine-DNA Flow Cytometry Method for the Study of Cell Proliferation
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Potential doubling time (Tpot), DNA synthesis time (TS), and labelling index (LI) are fundamental growth kinetics parameters in clinical and experimental cancer research, which may be of further practical importance regarding prognosis and treatment prediction of cancer. They can be measured by bromodeoxyuridine(BrdUrd)/flow cytometry (FCM) methods, where BrdUrd, an analogue of thymidine, is incorporated into DNA and quantified simultaneously with the DNA content. However, this method requires improvements. Since in many applications only a single sample is available, the method must be reproducible, accurate, and independent of the time of sample collection in relation to BrdUrd pulse-labelling. With the modifications we describe, growth kinetic data could be obtained in response to the demands, both in vitro and in vivo and they were in agreement with those obtained with the [3H]thymidine/autoradiography method. Thus, the BrdUrd/FCM method can replace traditional [3H]thymidine-based methods. The modifications included new mathematic formulas for the calculation of LI and TS. They were compared with various other formulas, in several cell lines and experimental tumours. Our formulas did show sampling time independence in several cell lines studied. The labelling time should be kept as short as possible. The proposed TS formula is used preferable in more slowly growing cell populations. Tpot values based on our formulas did not depend on sampling time. In conclusion, with our modified BrdUrd/FCM method for growth kinetic studies, experimentally and/or clinically, it is possible to obtain reproducible and sampling time independent data from only one sampling, an advantage of great importance when clinical applications are concerned.
  • Johnsson, Anders (författare)
  • Pharmacokinetic and pharmacodynamic studies on cisplatin in mice and men
  • 1996
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Methodological tools for studies of the cytostatic agen cisplatin (CDDP) were explored and applied to elucidate various aspects of pharmacokinetics, drug distribution, chemomodulation and pharmacodynamics. An immunohistochemical assay for analysis of CDDP-DNA adducts, i.e. the drug in its probable target position, was modified to allow quantitation with computerized image analysis. The methodological sources of error were estimated. We found the method to be feasible for comparing samples of the same tissue type, stained in the same batch and preferrably measured by one observer on one occasion. The pharmacokinetics were studied as platinum (Pt) and CDDP-DNA adducts in nude mice. The highest tissue concentration was noted in kidney at 15 min. A biphasic elimination of Pt was observed in most sample types and the terminal half-life was similar (55h-76h) in whole-blood, serum, kidney, liver and testis. In brain the pharmacokinetics differed with a gradual accumulation during the study period of 7 days. Peak adduct levels were reached between 30 min and 4h. Each tissue type had its specific adduct staining pattern. With escalating CDDP doses there was a linear increase in both Pt concentrations and CDDP-DNA adducts including tumor. There were also good correlations between serum-Pt, tissue levels of Pt and adducts, respectively. Heterogeneities in the intratumoral drug distribution were described and a model was presented for investigating the potential influence of vascularization and cell proliferation on intratumoral adduct distribution by using different immunohistochemical stainings of parallel sections. A weak correlation was found between adducts and proliferation, which might indicate that drug uptake and adduct formation is increased in proliferating cells. The antifungal agent amphotericin B was given to glioma-bearing rats with the purpose of enhancing the cytotoxicity of CDDP. The combined treatment resulted in excessive nephrotoxicity and in increase levels of CDDP-DNA adducts on kidneys. This indicates that nephrotoxicity is related to adduct formation in kidneys. It also shows that adduct analysis can be a valuable tool for assessing the mechanisms of interaction between CDDP and modulation agents. Ten patients were studies during the first cycle of CDDP-based chemotherapy. With limited-sampling and a population approach useful pharmacokinetic information was obtained. CDDP-DNA adducts in lymphocytes and buccal cells showed different kinetic profiles, possibly due to differences in cell turn-over. Renal damage, studied in terms of urinary protein excretion, was first displayed as tubular damge and later as impaired glomerular barrier function. Significant correlations were found between tubular dysfunction and pharmacokinetic parameters. These results could be the basis for further pharmacodynamic studies aiming towards individualized dose adaptation for cancer chemotherapy.
  • Sriplakich, S., et al. (författare)
  • Epidermal growth factor receptor expression : predictive value for the outcome after cystectomy for bladder cancer?
  • 1999
  • Ingår i: BJU International. - Oxon, United Kingdom : Blackwell Publishing. - 1464-4096 .- 1464-410X. ; 83:4, s. 498-503
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Objective: To determine whether epidermal growth factor receptor (EGFR) immunostaining of tumour cells is associated with cancer-specific death after cystectomy for locally advanced bladder cancer.</p><p>Patients and Methods: The hospital records of all patients treated with cystectomy for urothelial cancer of the urinary bladder between 1967 and 1992 were reviewed retrospectively. The paraffin-embedded specimens obtained before treatment from 173 patients were processed for immunohistochemical staining, using the monoclonal antibody NCL-EGFR (Novocastra, UK). EGFR immunostaining was considered positive if membrane staining was found in at &gt; or = 20% of tumour cells in one or more fields at &gt; or = 200 (area 0.59 mm2).</p><p>Results: Most patients (149) received preoperative irradiation and one had neoadjuvant chemotherapy. The mean observation time was 81.3 months; 63 patients (36%) had tumour recurrence within 1-80 months (mean 18.3). Positive EGFR immunostaining was found in 100 patients (58%). The proportion of T2-4 tumours was higher in those EGFR-positive than in those EGFR-negative. Proportional-hazards analysis revealed that clinical stage was significantly associated with cancer-specific death, but EGFR expression was not.</p><p>Conclusion: Although positive immunostaining for EGFR was more frequent in higher stages of locally advanced bladder cancer, this variable was not an independent predictor of outcome after cystectomy.</p>
  • Lundin, Catarina (författare)
  • Cytogenetic studies of benign breast lesions
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Popular Abstract in Swedish Vår arvsmassa (DNA) finns packad i cellkärnan i de flesta kroppsceller i form av 46 kromosomer (23 par). Könscellerna innehåller ett halverat antal kromosomer. Det korrekta kromosomtalet hos människa beskrevs i Lund 1956, av Tjio och Levan. Kromosomerna innehåller tillsammans 50000-100000 gener, vilka är de delar av DNA-strängen som kan avläsas till proteiner. Cancer är på cellnivå en genetisk sjukdom, såtillvida att det är förändringar i DNA, som ger upphov till bl. a. den okontrollerade delning som är typisk för tumörceller. Den första tumörkarakteristiska kromosomförändringen rapporterades 1960, och sedan dess har ett stort antal avvikelser identifierats både i elakartade och godartade tumörer. En del av dessa avvikelser är typiska för en viss tumörtyp och kan därför användas som diagnostiskt och prognostiskt hjälpmedel. Bröstcancer är den vanligaste tumörformen hos kvinnor, med en livstidsrisk på ungefär 10%. I de flesta fall är det ännu okänt vad som orsakar bröstcancer, men man har identifierat några riskfaktorer, såsom förekomst av godartad bröstförändring, ålder över 30 år vid första graviditet, tidig pubertet och sent inträde i klimakteriet. Den viktigaste riskfaktorn är dock förekomst av flera fall av bröstcancer i familjen. För kvinnor med tre förstagradssläktingar (föräldrar, syskon, barn) med bröstcancer, varav minst en insjuknat före 50 års ålder, är risken mellan 40-50% att själv drabbas. På senare år har det klarlagts att 5-10% av alla som utvecklar bröstcancer tillhör familjer där sjukdomsrisken nedärvs autosomalt dominant. Man har också under 1990-talet kunnat lokalisera två gener som är ansvariga för bröstcanceransamlingen i en del av dessa släkter. Det innebär att den enskilda individens risk i en sådan familj, om genförändringen är känd, kan fastställas med större säkerhet. De vanligaste typerna av godartade bröstknutor är sk fibrocystiska förändringar och fibroadenom. Fibrocystiska förändringar kan i sin tur indelas i tre olika grupper, där två av dem innebär en viss ökad risk för kvinnan att senare utveckla bröstcancer. Fibroadenom är den vanligaste godartade tumören i bröstet, och har rapporterats medföra en lätt ökad risk för bröstcancer, jämfört med kvinnor utan fibroadenom. Andra exempel på bröstknutor är papillom och phyllodestumörer. Den senare är mycket ovanlig, och kan uppvisa alla svårighetsgrader från godartad till elakartad. Kromosomundersökningar av bröstcancer har avslöjat ett flertal återkommande avvikelser, där de vanligaste förändringarna leder till för mycket material från den långa armen på kromosom nummer 1. En annan återkommande förändring är en förlust, deletion, av en bit av den korta armen på kromosomen 3. När vi inledde den aktuella studien av kromosomavvikelser i godartade bröstsjukdomar, fanns publicerade data från endast 18 fall, att jämföra med över 300 fall av bröstcancer med kromosomförändringar. Syftet med studien var att försöka få en bild av avvikelsemönstret vid olika godartade bröståkommor, och jämföra det eventuella mönstret med det vid bröstcancer. Likheter skulle i så fall kunna peka på avvikelser som är viktiga för uppkomsten av bröstcancer. Totalt analyserades 266 vävnadsbitar från 230 kvinnor. De generella slutsatserna av de studier som ligger till grund för avhandlingen är att även godartade bröstförändringar karakteriseras av kromosom- avvikelser, och att dessa avvikelser i många fall liknar de som beskrivits vid bröstcancer. Förändringarna vid de godartade tillstånden tycks dock mestadels vara av en enklare natur. I fråga om phyllodestumörer verkar kromosom- avvikelsemönstrets komplexitet följa tumörens svårighetsgrad. För att kunna säga något om den eventuella betydelsen av kromosomförändringar för en senare cancerutveckling, behövs kliniska uppföljningsstudier av kvinnor med avvikelser/utan avvikelser i godartade bröstsjukdomar.
  • Larsson, Gunnel, et al. (författare)
  • Importance-satisfaction discrepancies are associated with health-related quality of life in five-year survivors of endocrine gastrointestinal tumours
  • 1999
  • Ingår i: Annals of Oncology. - 0923-7534 .- 1569-8041. ; 10:11, s. 1321-1327
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><em>Background:</em> Little is known about the health-related-quality of life (HRQoL) of patients with endocrine gastrointestinal tumours. In this study, HRQoL was investigated in long-term survivors of endocrine GI tumours.</p> <p><em>Patients and methods:</em> A questionnaire including the EORTC QLQ-C30 and ratings of importance of and satisfaction with a variety of HRQoL aspects was mailed to patients with carci-noid tumours (<em>n</em> = 64), or endocrine pancreatic tumours (EPT, <em>n</em> = 55). Median time since diagnosis was 120 months (range 60–360). The majority of patients (77 of 119) had ongoing treatment.</p> <p><em>Results:</em> The EORTC QLQ-C30 ratings suggest that in spite of a long disease duration and treatment, patients perceived their HRQoL as relatively good. There were no major differences in HRQoL ratings between patients with carcinoid tumours and those with EPT. Patients whose ratings of importance was higher than their ratings of satisfaction with a specific HRQoL aspect also evidenced a low HRQoL for that aspect.</p> <p><em>Conclusions:</em> The results indicate that survivors of endocrine GI tumours enjoy a relatively good HRQoL and suggest that importance &lt; satisfaction discrepancies identify patients with a low quality of life.</p>
  • Johannsson, Oskar, et al. (författare)
  • Incidence of malignant tumours in relatives of BRCA1 and BRCA2 germline mutation carriers
  • 1999
  • Ingår i: European Journal of Cancer. - Elsevier. - 1879-0852. ; 35:8, s. 1248-1257
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated cancer incidence between 1958 and 1995 in 1873 individuals belonging to 29 consecutively identified BRCA1 and 20 BRCA2 associated families from Southern Sweden using data from parish and local tax authorities, as well as the Swedish Cancer Registry, Cause of Death Registry and Census Registry. 150 malignant tumours were analysed from 1145 relatives in the BRCA1 families and 87 tumours were analysed from 728 relatives in the BRCA2 families. After excluding index cases which led to the mutation analysis, the incidence for all malignant tumours was significantly increased for both BRCA1- standardised morbidity rate, SMR, 1.98, 95% confidence interval (CI) 1.59-2.45; P < 0.0001 and BRCA2- (SMR 1.79, 95% CI 1.35-2.31; P < 0.0001) associated family members. For women in BRCA1-associated families, the incidence of breast cancer (SMR 3.76, 95% CI 2.29-5.80, P < 0.0001), ovarian cancer (SMR 15.49, 95% CI 9.46-23.92, P < 0.0001), stomach cancer (SMR 5.86, 95% CI 1.60-15.01, P = 0.005) were significantly increased. Amongst men only invasive squamous cell cancer of the skin was significantly increased (SMR 6.02, 95% CI 1.96-14.05, P = 0.002). In BRCA2 associated families, female breast cancer (SMR 3.03, 95% CI 1.61-5.18, P = 0.0005) was increased after exclusion of index cases. If these were included, ovarian cancer (SMR 5.16, 95% CI 1.89-11.24, P = 0.001), invasive cervical cancer (SMR 4.21, 95% CI 1.15-10.79, P = 0.016), male breast cancer (SMR 290.52, 95% CI 125.42-572.43, P < 0.0001), and prostate cancer (SMR 2.21, 95% CI 0.89-4.56, P = 0.042) were significantly increased. The increased risk for ovarian cancer in BRCA2 related families were limited to the cases leading to mutation analysis. Our data suggest that apart from breast and ovarian cancer, the incidence of other cancer types do not appear to be greatly increased in BRCA1- and BRCA2-associated families and does not warrant specific clinical follow-up in carriers.
  • Oohashi, T, et al. (författare)
  • Mouse ten-m/Odz is a new family of dimeric type II transmembrane proteins expressed in many tissues
  • 1999
  • Ingår i: Journal of Cell Biology. - Rockefeller University Press. - 0021-9525. ; 145:3, s. 563-577
  • Tidskriftsartikel (refereegranskat)abstract
    • The Drosophila gene ten-m/odz is the only pair rule gene identified to date which is not a transcription factor. In an attempt to analyze the structure and the function of ten-m/odz in mouse, we isolated four murine ten-m cDNAs which code for proteins of 2,700-2, 800 amino acids. All four proteins (Ten-m1-4) lack signal peptides at the NH2 terminus, but contain a short hydrophobic domain characteristic of transmembrane proteins, 300-400 amino acids after the NH2 terminus. About 200 amino acids COOH-terminal to this hydrophobic region are eight consecutive EGF-like domains. Cell transfection, biochemical, and electronmicroscopic studies suggest that Ten-m1 is a dimeric type II transmembrane protein. Expression of fusion proteins composed of the NH2-terminal and hydrophobic domain of ten-m1 attached to the alkaline phosphatase reporter gene resulted in membrane-associated staining of the alkaline phosphatase. Electronmicroscopic and electrophoretic analysis of a secreted form of the extracellular domain of Ten-m1 showed that Ten-m1 is a disulfide-linked dimer and that the dimerization is mediated by EGF-like modules 2 and 5 which contain an odd number of cysteines. Northern blot and immunohistochemical analyses revealed widespread expression of mouse ten-m genes, with most prominent expression in brain. All four ten-m genes can be expressed in variously spliced mRNA isoforms. The extracellular domain of Ten-m1 fused to an alkaline phosphatase reporter bound to specific regions in many tissues which were partially overlapping with the Ten-m1 immunostaining. Far Western assays and electronmicroscopy demonstrated that Ten-m1 can bind to itself.
  • Wängberg, Bo, 1953-, et al. (författare)
  • Survival of patients with disseminated midgut carcinoid tumors after aggressive tumor reduction.
  • 1996
  • Ingår i: World journal of surgery. - 0364-2313. ; 20:7, s. 892-9; discussion 899
  • Tidskriftsartikel (refereegranskat)abstract
    • Sixty-four consecutive patients with disseminated midgut carcinoids were treated during an 8-year period according to a single clinical protocol aimed at aggressive tumor reduction by surgery alone or with subsequent hepatic artery embolization. All patients had markedly elevated urinary 5-hydroxyindoleacetic acid (5-HIAA) levels (581 +/- 79 micromol/24 h) and hormonal symptoms. Fourteen patients (22%) reached anatomic and biochemical cure by surgery alone. At follow-up, the mean 5-HIAA levels were still normal after 69.0 +/- 6. 2 months; two patients had died from unrelated causes. With the introduction of somatostatin receptor scintigraphy, subclinical disease was diagnosed in 7 of these 14 patients. Forty patients with bilobar hepatic disease underwent embolization in combination with octreotide. In this group, 5-HIAA levels were still reduced by 55% after 71 +/- 11 months of follow-up, and the 5-year survival was 56%, estimated from the total death hazard function. After embolization, two subgroups could be identified with marked differences in their long-term response to treatment. Ten patients were not embolized owing to complicating diseases. The 5-year survival for the entire series was 58%. A significantly increased risk of cardiovascular deaths was seen, which underlines the importance of total survival analysis in a disease with multiple hormonal effects. It is concluded that an active surgical approach must be recommended to patients with the midgut carcinoid syndrome. In patients with bilobar hepatic disease, embolization combined with octreotide treatment markedly reduced the 5-HIAA excretion and suggested a prolonged 5-year survival.
  • Kölby, Lars, 1963-, et al. (författare)
  • Somatostatin receptor subtypes, octreotide scintigraphy, and clinical response to octreotide treatment in patients with neuroendocrine tumors.
  • 1998
  • Ingår i: World journal of surgery. - 0364-2313. ; 22:7, s. 679-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Several types of neuroendocrine tumor express high numbers of somatostatin receptors (sstr). We have compared the expression of sstr subtypes with the outcome of octreotide scintigraphy in patients with carcinoids and medullary thyroid carcinoma (MTC) in comparison with Hürthle cell tumors. The effect of sstr activation (octreotide treatment) on tumor markers was also studied in patients with disseminated carcinoid tumors. Six patients with carcinoid tumors (four midgut and two foregut), and three patients with thyroid tumors (one MTC, one Hürthle cell carcinoma, and one Hürthle cell adenoma) were studied. Octreotide scintigraphy visualized tumor sites in all nine patients. Macroscopic tumor was verified at these sites at subsequent surgical exploration. Using Northern blotting and subtype-specific riboprobes, sstr could be detected in all tumors examined. All five sstr subtypes were detected in most of the carcinoid tumors. All six carcinoids expressed sstr2. This was in contrast to the findings for the thyroid tumors analyzed, which also expressed several sstr subtypes but in some cases lacked expression of sstr2. This was also the case for normal thyroid tissue. Clinically, octreotide treatment of the patients with midgut carcinoid tumors resulted in palliation of hormonal symptoms accompanied by a significant reduction of urinary 5-HIAA levels (28-71%). These results indicate that carcinoid tumors frequently express all five sstr subtypes. The thyroid tumors also expressed multiple sstr but could lack expression of sstr2. Nevertheless, these tumors were visualized by octreotide scintigraphy, indicating that sstr2 expression is not a prerequisite for tumor imaging.
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