Livet för en patient med hjärntumör förändras drastiskt. Patienter med hjärntumör upplever att sjukdomen tar deras självständighet och mening med livet. Syftet var att beskriva vårdarens upplevelser av att vårda en närstående med hjärntumör. En strukturerad litteraturstudie genomfördes, där tio artiklar analyserades med induktiv ansats. Litteraturstudiens resultat resulterade i en huvudkategori; ensamhet följt av fem underkategorier; vilsenhet, ovisshet, motvilligt maktövertagande, frustration samt längtan efter stöd. Vårdare till närstående med hjärntumör visade en stor påfrestning när de antog den vårdande rollen. Ett stort behov av stöd från vänner, familj och sjukvårdspersonal fanns. Den vårdande rollen innefattade inte enbart omvårdnad av den sjuke, utan även att axla ytterligare ansvar i vardagen så som att ta hand om ekonomin, hushållet och familjen. Denna litteraturstudie visar att när en anhörig blir vårdare till en familjemedlem med hjärntumör kan det vara en tillvaro av ensamhet. Denna ensamhet visade sig på flera olika sätt, såsom att känna sig vilsen, leva i ovisshet, hamna i ett motvilligt maktövertagande, känna sig frustrerad och känna en längtan efter stöd. För att hjälpa vårdarna i denna situation behöver vårdpersonalens rutiner och riktlinjer kring anhörigvård förbättras. / The life of a patient with brain tumor changes drastically. Patients with brain tumors experience that the illness robs them of their independence and life-meaning. The aim of this study was to describe the experiences of the caregiver. The study was conducted as a structured literature study in which ten articles were analyzed with an inductive approach. The literature study resulted in one main category; loneliness, and five subcategories; disorientation, uncertainty, reluctant takeover of power, frustration and longing for support. Caregivers of families with brain tumors showed a great strain when they accepted the caregiving role along with a need for support from friends, family and healthcare professionals. The caregiving role meant not only caring for the sick one, but also shouldering additional responsibility, such as the financials, the household and the family. This literature study shows that when a relative becomes a caregiver to a family member with a brain tumor there could be an existence of loneliness. This loneliness showed itself in many different ways, such as disorientation, uncertainty, reluctant takeover of power, frustration and longing for support. To help caregivers in this situation, care providers’ routines and guidelines on caregiving needs to be improved.

Introducción: El cáncer de estómago, posee una de las más altas incidencias a nivel mundial. En el Perú, no existe un adecuado registro y reporte de casos, que permita una evaluación de los clásicos y nuevos factores descritos en la literatura, así como de factores propios del carcinoma. Objetivo: Determinar la asociación entre el desarrollo de metástasis en pacientes con adenocarcinoma gástrico y el patrón en anillo de sello. Materiales y Métodos: Ejecutamos un estudio de casos y controles en el Instituto Nacional de Enfermedades Neoplásicas (INEN) en pacientes con diagnóstico de cáncer de estómago. Se definió como caso, a todo paciente que desarrolló metástasis y como control, aquel paciente que no desarrolló metástasis, nuestra exposición de interés fue el tipo de adenocarcinoma. Resultados: Evaluamos 174 casos y 93 controles. La edad promedio en los casos y controles fue de 58,8 y 58,6, respectivamente. El 86,78% de casos y 61,29% de controles fueron diagnosticados en estadios avanzados. Además, se evidenció que los casos presentaron una mayor posibilidad 5,57 veces (IC95%: 1,76 – 17,62) de haber presentado los subtipos anillo de sello en conjunto con otros subtipos histológicos en comparación a los controles. Conclusiones: En pacientes con cáncer gástrico que desarrollaron metástasis, el hallazgo del patrón en anillo de sello no es un factor asociado al pronóstico negativo. Por el contrario, podemos afirmar que en las personas con cáncer gástrico que desarrollaron metástasis es probable que hayan presentado algún patrón histológico que haya co-existido con el subtipo adenocarcinoma en anillo de sello. / Background: Stomach cancer has one of the highest incidences worldwide. In Peru, there is no adequate record and report of cases, which allows an evaluation of the classic and new factors described in the literature, as well as factors typical of carcinoma. Objective: To determine the association between the development of metastasis in patients with gastric adenocarcinoma and the histopathological pattern in signet ring cell. Materials and Methods: We conducted a case-control study at the National Institute of Neoplastic Diseases (INEN) in patients diagnosed with stomach cancer. It was defined as case, to any patient who developed metastases and as a control, that patient who did not develop metastases, our exposure of interest was the type of adenocarcinoma. Results: We evaluated a total of 174 cases and 93 controls. The average age in cases and controls was 58.8 and 58.6, respectively. The majority of cases (86,78%) and controls (61,29%) were diagnosed in advanced stages (greater than 2). Likewise, it was evidenced that the cases presented a greater possibility 5.57 times (IC 95%: 1.76 - 17.62) of having presented the seal ring subtypes in conjunction with other histological subtypes compare to the controls. Conclusions: In patients with gastric cancer who developed metastases, the finding of the signet ring pattern is not a factor associated with the negative prognosis. On the contrary, we can affirm that in people with gastric cancer who developed metastases it is likely that they have presented some histological pattern that has co-existed with the adenocarcinoma subtype in the seal ring. / Tesis

Title Complex preoperative brain tumor imaging Abstract The differentiation of glioblastoma, metastases and brain lymphoma using modern diagnostic imaging methods has a major impact on the strategy of further diagnostic examinations and treatment. In a group of 67 patients with glioblastoma and 31 with cerebral metastasis, the ability to differentiate them according to the evaluation of perfusion parameters changes in peritumoral white matter by T1 dynamic post-contrast magnetic resonance imaging was verified, with the positive predictive value in glioblastoma detection up to 91%. In a group of 36 brain lymphoma patients the importance of imaging submodalities and contribution of a complex magnetic resonance imaging protocol to detect lymphoma up to 80% were evaluated. Key words brain, glioblastoma, lymphoma, magnetic resonance imaging, neoplasm metastasis

Integrin αvβ6 has emerged as a potential novel target for anticancer and plays a major role in promoting malignant tumor progression. Recent studies indicate that integrin αvβ6 occurs in many cancers. However, whether and how αvβ6 is regulated by genetic and epigenetic mechanisms in breast cancer remain unknown. In the present study, two different short hairpin RNAs (shRNAs) targeting the β6 gene were designed and constructed into pSUPER, respectively, which were transfected into the MCF-7 human breast adenocarcinoma cell line. The β6-shRNA stably transfected cells were successfully established, and significant lower levels of αvβ6 mRNA and protein expression were confirmed. Furthermore, inhibition of integrin αvβ6 markedly downregulated the expression of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-3 (MMP-3) and urokinase plasminogen activator (uPA) in tumor conditioned medium. Furthermore, β6-shRNA-mediated silencing of the αvβ6 gene obviously decreased the expression of ERK1/2. In particular, supression of integrin αvβ6 caused significant downregulation of the degradation of basement membrane type IV collagen secretion via modulation of the plasminogen activation cascade. Our results thus indicate that αvβ6 plays a fundamental role in promoting invasion and growth of breast adenocarcinoma cells. Taken together, this study revealed that targeting of the β6 gene by RNA interference (RNAi) could efficiently downregulate αvβ6 expression and suppress the ERK1/2-dependent extracellular matrix degradation in vitro, which is dependent upon inactivation of the mitogen-Activated protein kinase (MAPK) pathway. These findings may offer a useful therapeutic approach to block invasion and migration of breast cancer cells.

<p>Vitamin D ima antiproliferativno, proapoptotsko i prodiferencijaciono dejstvo. Dokazi o dejstvu na ćelije adenokarcinoma prostate su malobrojni i nekonzistentni. Cilj ispitivanja je određivanje stepena povezanosti između nivoa vitamina D, stadijuma adenokarcinoma prostate, prostata specifičnog antigena, Gleason grade i progresije oboljenja. Ispitivanje je prospektivno, sprovedeno na 120 ispitanika (90 pacijenata sa dijagnostikovanim karcinomom prostate i 30 kontrolnih, zdravih subjekata). Pacijenti sa dijagnostikovanim adenokarcinomom prostate podeljeni su prema stadijumu bolesti u dve grupe: lokalizovano (pT2cN0M0, prostata specifični antigen &le; 20 ng/ml, Gleason 2-7) i metastatsko oboljenje (pT3-4, N1, M 0,1(a,b,c), prostata specifični antigen &ge; 20 ng/ml, Gleason &ge; 8), dok su prema ordiniranoj terapiji podeljeni u tri grupe: pacijenti koji su hemijski kastrirani, hirur&scaron;ki kastrirani i grupa kod koje je urađena radikalna prostatektomija. Uzorci za analizu nivoa vitamina D i prostata specifičnog antigen uzeti pre ordinirane terapije a nakon toga posle 6 i 12 meseci. Kako ne postoje definisane vrednosti unosa vitamina D i kalcijuma za ispitivano podneblje formirani smo Upitnik kojim smo evaluirali dnevni unos kod 90 zdravih subjekata mu&scaron;kog pola starijih od 50 godina koji nisu učestvovali u ispitivanju. Da bismo uočili ispitanike koji su hranom ili životnim navikama drastično uticali na vrednost vitamina D isti Upitnik su ispunili svi ispitanici uključeni u ispitivanje. Ustanovljena je očuvana godi&scaron;nja oscilacija vitamina D kod ispitanika te smo statističkim modelom korigovali ovu varijablu. Rezultati pokazuju da grupa obolelih nema apsolutno niske vrednosti vitamina D i da su vrednosti kod obolelih niže u odnosu na kontrolne subjekte (64.12 nmol/l vs. 74.45 nmol/l). Nije uočena razlika u nivou vitamina D kod pacijenata sa lokalizovanim i metastatskim oboljenjem (62.90 nmol/l vs. 64,65 nmol/l). Odnos između prostata specifičnog antigena i vitamina D posmatran tokom perioda ispitivanja pokazuje da je kod obolelih pacijenata koji su hemijski ili hirur&scaron;ki kastrirani i kod pacijenata kod kojih je urađena radikalna prostektomija postoji pozitivna korelacija pre ordinirane terapije u sve tri grupe, nakon ordinirane terapije možemo uočiti inverznu korelaciju. Konrolna grupa ispitanika pokazuje stalnu pozitivnu korelaciju između nivoa vitamina D i prostata specifičnog antigena. Pacijenti kod kojih je do&scaron;lo do progresije imaju niže vrednosti nivoa vitamina D u odnosu na pacijente kod kojih nije do&scaron;lo do progresije. Nije ustanovljena korelacija između vremenskog intervala do progresije oboljenja i nivoa vitamina D.</p> / <p>Vitamin D has antiproliferative, proapoptotic and prodifferentiational actions. There is a limited number of studies asessing influence of vitamin D on prostate cancer. Results of those available studies are inconsistent. This study hypothesizes with correlation of vitamin D, prostate cancer stage, prostate specific antigen, Gleason grade, stage, and disease progression. This prospective study included 120 subjects (90 subjects with diagnosed prostate cancer and 30 healthy, age adjusted controls). Patients with diagnosed prostate cancer formed two groups by criterion of disease advancement: localized (&le;pT2cN0M0, prostate specific antigen &le; 20 ng/ml, Gleason 2-7) and metastatic (&ge;pT3-4, N1, M 0,1(a,b,c), prostate specific antigen &ge; 20 ng/ml, Gleason &ge; 8. According to applied therapy subjects were devided in three groups: surgicaly castrated, medicamentous castrated and radical prostatectomy treated. Samples were obtained before therapy and after 6 and 12 months. As no defined value for vitamin D and calcium intake could be found we formed Questionnaire for vitamin D and calcium intake. Data were obtained from 90 healthy, age adjusted subjects, not included in this study. All subjects included in this study filed the Questionnarie and subjects with unusual vitamin D and calcium intake were excluded. Annual oscilation of vitamin D was observed, so we applied statistical model that excluded this variable. Subjects with diagnosed prostate cancer didn&#39;t have absolutely low vitamin D level. This level was lower in group of subjects whith diagnosed prostate cancer comparing to controls (64.12 nmol/l vs. 74.45 nmol/l). No differences in vitamin D level was observed in groups of patients with localised and metastatic disease (62.90 nmol/l vs. 64,65 nmol/l).<br />Correlation of vitamin D and prostate specific antigen during 12 months period showed that castrated subjects and subjects in radical prostatectomy group showed possitive correlation before surgical treatment and inverse, negative correlation, after treatment. Control group showed possitive correlation of vitamin D and prostate specific antigen in all three measurements. Subjects with progression have significantly lower vitamin D level comparing to subjects without progression. No correlation between time to progression and vitamin D have been observed.</p>

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21420号 / 医博第4410号 / 京都大学大学院医学研究科医学専攻 / (主査)教授 羽賀 博典, 教授 武田 俊一, 教授 坂井 義治 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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