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

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  • Kölby, Lars, 1963-, et al. (författare)
  • Histidine decarboxylase expression and histamine metabolism in gastric oxyntic mucosa during hypergastrinemia and carcinoid tumor formation.
  • 1996
  • Ingår i: Endocrinology. - 0013-7227. ; 137:10, s. 4435-42
  • Tidskriftsartikel (refereegranskat)abstract
    • Histamine is an important stimulator of gastric acid secretion. In experimental animals, inhibition of acid secretion by long term histamine2 receptor blockade causes hypergastrinemia, proliferation of enterochromaffin-like (ECL) cells, and formation of histamine-producing gastric carcinoids. The aim of this study was to examine the role of gastrin in histamine synthesis and metabolism of the oxyntic mucosa of normal, hyperplastic, and carcinoid-bearing Mastomys natalensis. Administration of exogenous gastrin to normal animals increased histidine decarboxylase (HDC) messenger RNA (mRNA) expression in the oxyntic mucosa within 30 min, indicating that gastrin stimulates histamine synthesis by regulating HDC mRNA abundance. Endogenous hypergastrinemia, induced by short term histamine2 receptor blockade (loxtidine) for 3-29 days, did not induce tumors, but enhanced the expression of HDC mRNA (2- to 4-fold elevated) and histamine contents (2-fold elevated) in the oxyntic mucosa. Long term histamine2 receptor blockade (7-21 months) resulted in sustained hypergastrinemia and ECL tumor formation. Tumor-bearing animals had a 4-fold increase in HDC mRNA expression and histamine contents of the oxyntic mucosa. Urinary excretion of the histamine metabolite methyl-imidazole-acetic acid was 2-fold elevated. Tumor-bearing animals recovering from histamine2 receptor blockade were normogastrinemic and had normal levels of HDC mRNA and histamine in the oxyntic mucosa as well as normal excretion of methyl-imidazole-acetic acid. The results indicate that ECL cell carcinoids developing during hypergastrinemia are well differentiated tumors that respond to high gastrin levels with increased histamine synthesis and secretion.
  • Eklund, Johan (författare)
  • Searching for genetical cancer risks using a database of familial cancer : part I
  • 1999
  • Rapport (övrigt vetenskapligt)abstract
    • <p>A method to estimate cancer risks, when a recessive genetic defect is assumed to influence the risk to develop cancer, is presented. The proportion of the recessive defect is also estimated. The method uses cancer diagnosis data from a large sample of biological families. A family is here parents and two children. The information used is the frequencies of cancer diagnoses among siblings. Estimations are performed with the method of moments. The work is methodological, meaning that no specific type of cancer is considered.</p>
  • Karunaratne, P M, et al. (författare)
  • Analysis of Swedish male breast cancer family data : a simple way to incorporate a common sibling effect
  • 1998
  • Ingår i: Genetic Epidemiology. - John Wiley and Sons Inc.. - 0741-0395. ; 15:2, s. 12-201
  • Tidskriftsartikel (refereegranskat)abstract
    • Based on a population-based cohort study, Olsson et al. [1993] found significant evidence for elevated incidence of breast and ovarian cancers among female first-degree relatives of men with breast cancer. Using an extension of logistic regressive models we investigate whether, after allowing for multifactorial familial correlations, single locus segregation could be the cause of the elevated incidence in these families. The logit for a given sib in the class D logistic regressive model depends on the order in which affected sibs occur in a sibship. That makes the model less appropriate for the situation where a polygenic component or a common sibling environment may be present, as well as being computationally cumbersome. In this paper, we propose to use the proportion of siblings in a sibship who are affected to quantify a sibling correlation. That not only relaxes the interchangeability problem but also makes the model computationally efficient. We then use this modified class D logistic regressive model for our segregation analysis. Using the proportion of siblings in a sibship who are affected as a covariate resulted in a significantly higher likelihoods in all the models we investigated. We found evidence for a dominant Mendelian gene leading to early age of onset of breast and/or ovarian cancer. This could either be a germline mutation of BRCA2 or a mutation in a gene different from BRCA2.
  • Bjartell, Anders, et al. (författare)
  • Distribution and tissue expression of semenogelin I and II in man as demonstrated by in situ hybridization and immunocytochemistry
  • 1996
  • Ingår i: Journal of Andrology. - American Society of Andrology. - 0196-3635. ; 17, s. 17-26
  • Tidskriftsartikel (refereegranskat)abstract
    • Semenogelin I and II (Sgl, Sgll) are two separate gene products of chromosome 20 with extensive (80%) identity in primary structure. They are mainly responsible for immediate gel formation of freshly ejaculated semen. Degradation of Sgl and Sgll is due to the proteolytic action of prostate-specific antigen (PSA); it results within 5-15 minutes in liquefaction of semen and release of progressively motile spermatozoa. By means of cDNA cloning and Northern blots, Sgl and Sgll transcripts have previously been shown to be abundant in human seminal vesicles, but Sgll alone is suggested to be expressed at low levels in the epididymis. To characterize the expression and tissue distribution of Sgl and Sgll in greater detail, we produced monoclonal immunoglobulin Gs (lgGs for immunocytochemistry (lCC) and specific [35S]-, digoxigenin-, or alkaline phosphatase-labeled 30-mer antisense probes to Sgl and Sgll for in situ hybridization (lSH). Immunocytochemical staining for both Sgl and Sgll, and lSH detection of both Sgl and Sgll transcripts, were demonstrated in the cytoplasm of seminal vesicle epithelium. lSH showed Sgll alone to be expressed in the epithelium of the epididymal cauda. Neither lCC nor lSH yielded any evidence of Sgl or Sgll expression in caput or corpus epithelium or in any stromal cells of the epididymis. Consistent with our previous findings using polyclonal lgG, monoclonal anti-Sgll Sgll lgGs identified epitopes on the posterior head, midpiece, and tail of ejaculated spermatozoa. Spermatozoa in the epididymal cauda were also immunoreactive, but those in the caput or corpus region of the epididymis as well as those in the testis were negative. As shown by lCC, neither Sgl nor Sgll were expressed in the testis, the prostate, the female genital tract, or other normal human tissue specimens. Although the significance of Sg attachment to epididymal and ejaculated spermatozoa remains to be established, monoclonal anti-Sg lgG might prove useful in establishing the origin of seminal vesicle tissue components in prostate core biopsies or other biopsy specimens.
  • Fulda, S., et al. (författare)
  • Betulinic acid triggers CD95 (APO-1/Fas)- and p53-independent apoptosis via activation of caspases in neuroectodermal tumors
  • 1997
  • Ingår i: Cancer Research. - American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 57:21, s. 4956-4964
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Betulinic acid CBA), a melanoma-specific cytotoxic agent, induced apoptosis in neuroectodermal tumors, such as neuroblastoma, medulloblastoma, and Ewing's sarcoma, representing the most common solid tumors of childhood. BA triggered an apoptosis pathway different from the one previously identified for standard chemotherapeutic drugs. BA-induced apoptosis was independent of CD95-ligand/receptor interaction and accumulation of wild-type p53 protein, but it critically depended on activation of caspases (interleukin 1 beta-converting enzyme/Ced-3-like proteases), FLICE/MACH (caspase-8), considered to be an upstream protease in the caspase cascade, and the downstream caspase CPP32/YAMA/Apopain (caspase-3) were activated, resulting in cleavage of the prototype substrate of caspases PARP. The broad-spectrum peptide inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, which blocked cleavage of FLICE and PARP, also completely abrogated BA-triggered apoptosis. Cleavage of caspases was preceded by disturbance of mitochondrial membrane potential and by generation of reactive oxygen species. Overexpression of Bcl-2 and Bcl-x(L) conferred resistance to BA at the level of mitochondrial dysfunction, protease activation, and nuclear fragmentation. This suggested that mitochondrial alterations were involved in BA-induced activation of caspases. Furthermore, pax and Bcl-x(s), two death-promoting proteins of the Bcl-2 family, were up-regulated following BA treatment. Most importantly, neuroblastoma cells resistant to CD95- and doxorubicin-mediated apoptosis were sensitive to treatment with BA, suggesting that BA may bypass some forms of drug resistance. Because BA exhibited significant antitumor activity on patients' derived neuroblastoma cells ex vivo, BA may be a promising new agent for the treatment of neuroectodermal tumors in vivo.</p>
  • Lindholm, C-E, et al. (författare)
  • Prognostic factors for tumour response and skin damage to combined radiotherapy and hyperthermia in superficial recurrent breast carcinomas
  • 1995
  • Ingår i: International Journal of Hyperthermia. - Taylor & Francis. - 0265-6736. ; 11:3, s. 337-355
  • Tidskriftsartikel (refereegranskat)abstract
    • Prognostic factors for complete tumour response and acute skin damage to combined hyperthermia and radiotherapy were analysed in material of patients with breast cancer, recurrent in previously irradiated areas. Radiotherapy was given daily to a total absorbed dose of 30.0 Gy in 2 weeks or 34.5 Gy in 3 weeks. The first radiotherapy schedule was combined with heat twice weekly, a total of four heat treatments (schedule A). The second radiotherapy schedule was combined with heat either once or twice a week resulting in a total of three (schedule B) or six (schedule C) heat treatments. Heat was induced with microwaves (2450, 915 or 434 MHz) via external applicators and always given after the radiotherapy fraction. The complete response (CR) rate in evaluable patients was 71% (49/69). There was no significant difference in CR rate between the three different hyperthermia schedules. The CR rates were 74% (14/19), 65% (15/23) and 74% (20/27) for schedules A, B and C respectively. The only factor predicting CR, evaluated both uni- and multivariately, was the CRE-value for the present radiotherapy dose (p = 0.02). If only tumours treated with 915 MHz were taken into account, however, then the highest minimum temperature at a given heat session predicted complete response (p = 0.03). This was true also in a multivariate analysis of this subgroup of tumours. A Kaplan-Meier analysis (log rank test) showed no significant difference in duration of CR between the different treatment schedules. Cox's proportional hazards method revealed three significant factors: tumour size (negatively correlated, p = 0.007), the time interval between the diagnosis of the primary tumour and the present treatment (p = 0.02) and the average temperature (0.03). Maximum acute skin reactions in the treatment field were scored according to an ordinal scale of 0-8, modified after WHO 1979. Twenty-six treatment areas (32%) expressed more severe skin damage (score > or = 5) in terms of desquamation with blisters (14%) and necrosis or ulceration (19%). Factors correlated with skin damage were the size of the lesion area (p = 0.011), the highest average maximum temperature during a given heat session (p = 0.03) and the fractionation schedule of hyperthermia (p = 0.05). The extent of previous radiotherapy absorbed dose, previous surgery in the treated area or previous chemotherapy had no significant influence on the acute skin reactions.
  • Karlsson, Mats G., 1960-, et al. (författare)
  • No association between immunohistochemical expression of p53, c-erbB-2, Ki-67, estrogen and progesterone receptors in female papillary thyroid cancer and ionizing radiation
  • 1997
  • Ingår i: Cancer Letters. - Clare, Ireland : Elsevier. - 0304-3835. ; 120:2, s. 173-177
  • Tidskriftsartikel (refereegranskat)abstract
    • An association has previously been reported between exposure to medical diagnostic ionizing radiation and papillary thyroid cancer in women. To further evaluate potential mechanisms in carcinogenesis, the expression of p53, c-erbB-2, as well as Ki-67, estrogen and progesterone receptors were analyzed by immunohistochemistry in 19 women exposed to X-rays and for comparison in nine women without such reported exposure. They all had papillary thyroid cancer. No difference was found between these groups. The results of this study showed that p53, c-erbB-2, Ki-67, estrogen and progesterone receptors are not involved in papillary thyroid cancer associated with exposure to medical diagnostic ionizing radiation.
  • Pålsson, Maj-Britt, 1936- (författare)
  • Support for women with breast cancer, and for the district and hospital nurses involved an intervention study
  • 1995
  • Ingår i: digitalisering@umu. - Umeå : Umeå universitet. - 91-7191-082-4
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>The purpose of this study was to investigate breast cancer patients’ experiences of their illness and of traditional nursing care (TNC) or supportive nursing care (SNC) respectively, as well as nurses' experiences of support and of caring for cancer patients. An intervention including extended co-operation between the surgical ward and primary health care, shorter waiting times, and changed routines concerning the information about the diagnosis, as well as training and systematic clinical supervision for the nurses, was implemented. Newly diagnosed breast cancer patients (n=47) from two county councils in the south-east of Sweden were interviewed (IV, V). Thirty-four of them completed scales about well-being, burnout, hopelessness, anxiety and depression (VII). The women who had TNC reported lack of professional support during the initial phase of the disease and suggested changes in the care similar to those implemented in the SNC. In the SNC group the women expressed feelings of safety and security after the professional support and the organizational changes in the care. There were significantly more single women and women who had had breast conserving surgery in the SNC group than in the TNC (VII). The hopelessness scores in the SNC group were significantly higher than in the TNC group.</p><p>Thirty-nine district nurses (DNs) were interviewed at baseline (I), and thirty-three of them completed scales about burnout, empathy, and sense of coherence (SOC) before and after systematic clinical supervision (VI). Twenty-three of the 39 DNs, as well as 9 hospital nurses (HNs) who participated in the clinical supervision, were interviewed about their experiences of this intervention (III). Twenty-nine tape-recorded supervision sessions in three groups of DNs (n=23) were analysed (II). Baseline interviews and analyses of the content of the supervisory sessions strongly emphasized that DNs experienced problems in the home care of seriously ill cancer patients. Deep human contacts were a source of both strain and enrichment. The clinical supervision was said to provide relief from undesirable thoughts and feelings, confirmation of themselves both as individuals and in their professional role, a broader and deeper knowledge and increased self-confidence. There were no significant differences in the burnout, empathy, and SOC scores between the supervisory group (n=21) and a comparison group (n=12) at the first and second measures, nor over time within the groups. There were some correlations between these phenomena and the Karolinska scales of personality, as well as cor­relations between burnout, empathy and SOC.</p><p>The groups of women were not entirely similar as regards demographic and medical characteristics, and the sample size of patients and nurses was small. It is obvious that patients in the TNC missed those factors that were implemented in the SNC, at the same time the latter women expressed hopelessness more often than those who had received TNC. This result may be due to the fact that support from nurses had made the women more prepared to express their feelings, that support had not been provided to an adequate extent or in the right way, or that the applied scales were not appropriate. The finding that the nurses experienced the clinical supervision as very positive but that, despite this, there were no significant differences in attitudes measured by scales within or between the groups, can be interpreted in a similar way. Consequently, further research is needed to judge the effects of intervention. The study has, above all, produced qualitative descriptions of patients' experiences of the nursing care after discharge from hospital, and of DNs’ experiences of the care of cancer patients in their homes, and of systematic clinical supervision.</p>
  • Elfving, Peter (författare)
  • Cytogenetic studies of normal kidney tissue and renal cell carcinoma
  • 1996
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Popular Abstract in Swedish Njurcancer är ungefär den 10:e vanligaste tumörformen i Sverige och diagnosticeras nästan dubbelt så ofta hos män som hos kvinnor. Tumörerna upptäcks vanligtvis i åldern mellan 50 och 70 år och de mest förekommande symtomen är blod i urinen och flanksmärtor. Varför man får njurcancer är inte känt, men det finns ett klart samband med rökning och asbest. Njurcancer kan upptäckas vid en vanlig njurröntgen och man kan med stor säkerhet särskilja en tumör ifrån en ofarlig cysta med hjälp av ultraljud, skikt- eller magnetröntgen. Den bästa behandlingsmetoden är kirurgi, dvs man opererar bort hela den njuren där tumören är belägen, vilket går bra eftersom man vid normal njurfunktion har en bra överkapacitet och kan klara sig med 1/2 - 1/3 njure. Ca hälften av patienterna blir botade med operation. Är sjukdomen spridd med dottertumörer redan vid upptäckten, eller om spridning upptäcks vid senare kontroller, finns det inte någon effektiv behandling, men patienterna kan leva i många år med sin sjukdom och ibland ser man en bra, men övergående, effekt av olika typer av hormonbehandlingar eller behandlingar som stimulerar kroppens eget immunförsvar. Olika faktorer hjälper oss att redan vid upptäckten att avgöra patientens prognos, dvs risken för att det redan finns spridd sjukdom vid diagnostillfället och för hur snabbt förloppet blir. Tumörens storlek är av betydelse men framför allt vid mikroskopisk undersökning av den bortopererade tumören kan man se tumörens malignitetsgrad (hur pass elakartad den är), om den växt igenom njurens kapsel eller ut i blodkärl och vilka celler den består av. Det vi önskar oss idag är mer information om olika tumörsjukdomars egenskaper, så att man hos de enskilda patienterna kan avgöra vilka som sannolikt är botade med enbart operation och vilka som behöver någon form av efterbehandling och då allra helst vilken sorts cellgifts- eller strålbehandling som just denna tumör är mest känslig för. Sedan mer än 10 år har man odlat tumörceller, undersökt deras kromosomer och funnit kromosomförändringar som är specifika för olika tumörtyper. I njurcancer är den vanligaste förändringen att den korta armen på kromosom 3 har förlorat sin yttersta del (deletion 3p). Man tror att detta kan vara den grundläggande förändringen för uppkomsten av njurcancer, där cellerna förlorat en gen som kontrollerar deras tillväxthastighet. Just okontrollerad tillväxt, där cellerna inte respekterar vävnadsgränser, är en av de egenskaper som gör att cancer sprider sig i kroppen och slutligen skadar livsviktiga funktioner så att organismen dör. En extra kromosom 7 (trisomi 7 eller +7) är den näst vanligaste kromosomförändringen vid njurcancer. Målet med denna studie var att studera förekomsten av +7 i njurcancer och i normal njurvävnad, om förändringen orsakades av cellodlingstekniken och om den hade prognostisk betydelse. I de tre första artiklarna visade vi att +7 förekom i drygt 5% av cellerna vid cellodling av normal njurvävnad, både från patienter med njurcancer och från patienter med andra icke tumör-relaterade sjukdomar. Frekvensen ökade inte vid långtidsodling. Vid odling av tumörvävnad förekom trisomi 7 både tillsammans med andra kromosomförändringar och som ensamt fenomen. Vid inmärkning av DNA hos t.ex. kromosom 7 med speciella molekyler får man en lysande prick för varje exemplar av kromosom 7 som finns i cellkärnan (se omslagsbilden). I artikel 4 har vi med denna metod visat att cellerna med +7 inte bara finns i cellodling utan även i icke odlad njurvävnad. Det har föreslagits att cellerna med +7 skulle vara vita blodkroppar, men vi fann genom en speciell färgningsteknik att de flesta cellerna med +7 var epitelceller, dvs av samma typ som de vanliga njurcellerna. I artikel 5 samarbetade vi med en grupp i Finland och visade på vävnadssnitt att +7 förekommer i njurtubuli, som är en viktig del av njuren ur funktionell synvinkel och den del där man visat att de flesta njurtumörer uppstår. I artikel 6, slutligen, har vi undersökt kromosomerna från 50 njurtumörer och följt patienterna under ett antal år för att se om vissa kromosomförändringar har någon betydelse för prognosen. De tumörer som har många kromosomförändringar har en klart sämre prognos än de som har få förändringar och vissa typer av förändringar var vanligare hos de patienter som som det går dåligt för. Vid jämförelse med andra prognostiska faktorer visade det sig dock att malignitetsgraden var den faktor som hade störst betydelse för hur det gick för patienterna. Det hade ingen betydelse om tumören hade trisomi 7 eller ej. Vår slutsats är att det finns njurceller med en extra kromosom 7, att dessa celler sannolikt inte är förstadier till cancer och att förekomsten av +7 i njurcancer inte är av prognostisk betydelse. Däremot har andra kromosomförändringar betydelse för prognosen och framför allt tyder ett stort antal kromosomförändringar i tumören på dålig prognos. Antalet tumörer som vi analyserat är hittills för litet för att bedöma de enskilda kromosomförändringars betydelse när det gäller val av terapi.
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