Tutkimuksen moninaisuutta

Kirja-arvioLaitinen, Lea & Nuolijärvi, Pirkko & Saari, Mirja (toim.): (Leikkauspiste. Kirjoituksia kielestä ja ihmisestä

BRCA1 mislocalization leads to aberrant DNA damage response in heterozygous ABRAXAS1 mutation carrier cells

Peer reviewe

Cationic tantalum oxide nanoparticle contrast agent for micro computed tomography reveals articular cartilage proteoglycan distribution and collagen architecture alterations

Objective: Cationic tantalum oxide nanoparticles (Ta2O5-cNPs), as a newly introduced contrast agent for computed tomography of cartilage, offer quantitative evaluation of proteoglycan (PG) content and biomechanical properties. However, knowledge on the depth-wise impact of cartilage constituents on nanoparticle diffusion, particularly the influence of the collagen network, is lacking. In this study, we aim to establish the depth-dependent relationship between Ta2O5-cNP diffusion and cartilage constituents (PG content, collagen content and network architecture). Methods: Osteochondral samples (n = 30) were harvested from healthy equine stifle joints (N = 15) and the diffusion of 2.55 nm diameter cationic Ta2O5-cNPs into the cartilage was followed with micro computed tomography (µCT) imaging for up to 96 hours. The diffusion-related parameters, Ta2O5-cNP maximum partition (Pmax) and diffusion time constant, were compared against biomechanical and depth-wise structural properties. Biomechanics were assessed using stress-relaxation and sinusoidal loading protocols, whereas PG content, collagen content and collagen network architecture were determined using digital densitometry, Fourier-transform infrared spectroscopy and polarized light microscopy, respectively. Results: The Pmax correlates with the depth-wise distribution of PGs (bulk Spearman's ρ = 0.87, p < 0.001). More open collagen network architecture at the superficial zone enhances intake of Ta2O5-cNPs, but collagen content overall decreases the intake. The Pmax values correlate with the equilibrium modulus (ρ = 0.80, p < 0.001) of articular cartilage. Conclusion: This study establishes the feasibility of Ta2O5-cNPs for the precise and comprehensive identification of biomechanical and structural changes in articular cartilage via contrast-enhanced µCT

"Mammat kuntoon" - toiminnallisen elämäntaparyhmän suunnittelu ja toteuttaminen Kuopion kansalaisopistossa

Äitiys muuttaa suuresti naisen elämää. Uusi elämäntilanne asettaa haasteita äidin hyvinvoinnille ja synnytyksestä palautumiselle. Hyvä terveys lisää äidin voimavaroja ja jaksamista, sekä edistää vauvan hyvinvointia. Tuoreen äidin hyvinvointiin ja terveyteen vaikuttavat merkittävästi riittävä ja monipuolinen ravitsemus ja liikunta. Opinnäytetyö toteutettiin kehittämistyönä, jonka tarkoituksena oli suunnitella ja toteuttaa Mammat Kuntoon -niminen elämäntaparyhmä kuopiolaisille äideille ja heidän alle 1- vuotiaille lapsilleen yhteistyössä Kuopion kansalaisopiston kanssa. Kehittämistyön tavoitteena oli edistää kuopiolaisten äitien terveyttä ja hyvinvointia suuntaamalla elämäntapaohjausta kliinisten ja hoitavien palveluiden ulkopuolelle sekä tuoda Kansalaisopiston kurssitarjontaan äitien elämäntaparyhmä. Ryhmän tavoitteena oli kasvattaa ryhmään osallistuneiden äitien tietoja ja taitoja terveyttä ja hyvinvointia edistävistä elämäntavoista sekä ohjata ryhmäläisiä omaksumaan sellaisia liikunnan ja ravitsemuksen toimintamalleja, jotka tukevat heitä synnytyksestä palautumisessa. Ryhmä kokoontui viisi kertaa keväällä 2014 Kuopion kansalaisopiston tiloissa. Ryhmään osallistui eri kerralla eri määrä äiteja ja heidän vauvojaan. Yhteensä ryhmään osallistui 9 äitiä ja 9 vauvaa. Jokaisella ryhmäkerralla oli oma teemansa ja tapaamiset koostuivat aihepiiriin liittyvistä tietoiskuista, liikunta- ja ravitsemusohjauksesta, liikuntaharjoituksista ja ruokapäiväkirjan pitämisestä. Palautetta saatiin ryhmäläisiltä suullisesti jokaisen ryhmäkerran yhteydessä ja viimeisellä kerralla kirjallisesti. Äidit kokivat ryhmän tarpeelliseksi ja aiheiltaan tärkeiksi. Kaiken kaikkiaan palautteessa koettiin liikuntaohjaus monipuolisena ja kattavana, kun taas ravitsemusohjaukseen sekä keskustelulle olisi toivottu lisää aikaa. Ryhmän toteutuksen myötä kävi ilmi, että äskettäin synnyttäneiden äitien asiakaslähtöiselle elämäntapaohjaukselle on tarvetta Kuopiossa. Ryhmään osallistuvat äidit toivoivat ryhmän jatkuvan. Yhteistyökumppanin ehdotuksen mukaan Savonia-ammattikorkeakoulun opiskelijat voisivat jatkossakin pitää edellä kuvatun kurssin ja kehittää sitä esimerkiksi hanketyönä. Tällä hetkellä kurssi ei jatku Kuopion kansalaisopistolla.Becoming a mother changes a woman’s life. A new situation of life sets challenges to the mother’s welfare and recovering from delivery. Maternal health increases resources and energy, and it also improves the baby’s wellbeing. Sufficient, diversified nutrition and exercises are a big part of the new mother’s health. This thesis was conducted as a product development project. The function was to plan and execute a functional course in cooperation with Kuopio’s Community College. The course included information of healthy nutrition and exercises after delivery. A target group was the mothers of babies under one year from Kuopio. The aim of this thesis was to promote health and wellbeing of mothers from Kuopio and give a new lifestyle group to Kuopio Community College. Another objective was also to have a health promotional approach vis-à-vis nutrition and sports to support mothers recovering from delivery. One more objective was also to add to mothers’ knowledge of the combined effects of nutrition and sports and promote mothers’ energy and wellbeing with early intervention. The course included five meetings with the group in the spring of 2014. Meetings were in Kuopio Community College’s building and there were in total 9 mothers and 9 babies. Each meeting had an own theme. Themes included fact sheets, sport- and nutrition counselling, different exercises and writing a food diary. We collected feedback from mothers on every meeting. We used spoken- and written feedback. Mothers thought the group was important and necessary. Mothers told that sport counselling was diverse and comprehensive but nutrition counselling could have been more extensive. During this project it turned out that mothers’ customer- oriented lifestyle counselling is necessary in Kuopio. Mothers who took part in the course hoped that the course may continue in the future. Kuopio Community College proposed that students of Savonia University of Applied Sciences could organize the same group again in the future for example as a part of project studies. At the moment the group is not continuing in Kuopio Community College

Tumor suppressor MCPH1 regulates gene expression profiles related to malignant conversion and chromosomal assembly

Abstract Strong inherited predisposition to breast cancer is estimated to cause about 5–10% of all breast cancer cases. As the known susceptibility genes, such as BRCA1 and BRCA2, explain only a fraction of this, additional predisposing genes and related biological mechanisms are actively being searched for. We have recently identified a recurrent MCPH1 germline mutation, p.Arg304ValfsTer3, as a breast cancer susceptibility allele. MCPH1 encodes a multifunctional protein involved in maintenance of genomic integrity and it is also somatically altered in various cancer types, including breast cancer. Additionally, biallelic MCPH1 mutations are causative for microcephaly and at cellular level premature chromosome condensation. To study the molecular mechanisms leading to cancer predisposition and malignant conversion, here we have modeled the effect of MCPH1 p.Arg304ValfsTer3 mutation using gene‐edited MCF10A breast epithelial cells. As a complementary approach, we also sought for additional potential cancer driver mutations in MCPH1 p.Arg304ValfsTer3 carrier breast tumors. We show that mutated MCPH1 de‐regulates transcriptional programs related to invasion and metastasis and leads to downregulation of histone genes. These global transcriptional changes are mirrored by significantly increased migration and invasion potential of the cells as well as abnormal chromosomal condensation both before and after mitosis. These findings provide novel molecular insights to MCPH1 tumor suppressor functions and establish a role in regulation of transcriptional programs related to malignant conversion and chromosomal assembly. The MCPH1 p.Arg304ValfsTer3 carrier breast tumors showed recurrent tumor suppressor gene TP53 mutations, which were also significantly over‐represented in breast tumors with somatically inactivated MCPH1

Image_1_AAV8-mediated sVEGFR2 and sVEGFR3 gene therapy combined with chemotherapy reduces the growth and microvasculature of human ovarian cancer and prolongs the survival in mice.pdf

BackgroundVascular endothelial growth factors (VEGFs) are major regulators of intratumoral angiogenesis in ovarian cancer (OVCA). Overexpression of VEGFs is associated with increased tumor growth and metastatic tendency and VEGF-targeting therapies are thus considered as potential treatments for OVCA. Here, we examined the antiangiogenic and antitumoral effects on OVCA of adeno-associated virus 8 (AAV8)-mediated expression of soluble VEGF receptors (sVEGFRs) sVEGFR2 and sVEGFR3 together with paclitaxel and carboplatin chemotherapy.Materials and methodsImmunodeficient mice were inoculated with human OVCA cell line SKOV-3m. Development of tumors was confirmed with magnetic resonance imaging (MRI) and mice were treated with gene therapy and paclitaxel and carboplatin chemotherapy. The study groups included (I) non-treated control group, (II) blank control vector AAV8-CMV, (III) AAV8-CMV with chemotherapy, (IV) AAV8-sVEGFR2, (V) AAV8-sVEGFR3, (VI) AAV8-sVEGFR2 and AAV8-sVEGFR3, and (VII) AAV8-sVEGFR2 and AAV8-sVEGFR3 with chemotherapy. Antiangiogenic and antitumoral effects were evaluated with immunohistochemical stainings and serial MRI.ResultsReduced intratumoral angiogenesis was observed in all antiangiogenic gene therapy groups. The combined use of AAV8-sVEGFR2 and AAV8-sVEGFR3 with chemotherapy suppressed ascites fluid formation and tumor growth, thus improving the overall survival of mice. Antitumoral effect was mainly caused by AAV8-sVEGFR2 while the benefits of AAV8-sVEGFR3 and chemotherapy were less prominent.ConclusionCombined use of the AAV8-sVEGFR2 and AAV8-sVEGFR3 with chemotherapy reduces intratumoral angiogenesis and tumor growth in OVCA mouse model. Results provide preclinical proof-of-concept for the use of soluble decoy VEGFRs and especially the AAV8-sVEGFR2 in the treatment of OVCA.</p

AAV8-mediated sVEGFR2 and sVEGFR3 gene therapy combined with chemotherapy reduces the growth and microvasculature of human ovarian cancer and prolongs the survival in mice

Abstract Background: Vascular endothelial growth factors (VEGFs) are major regulators of intratumoral angiogenesis in ovarian cancer (OVCA). Overexpression of VEGFs is associated with increased tumor growth and metastatic tendency and VEGF-targeting therapies are thus considered as potential treatments for OVCA. Here, we examined the antiangiogenic and antitumoral effects on OVCA of adeno-associated virus 8 (AAV8)-mediated expression of soluble VEGF receptors (sVEGFRs) sVEGFR2 and sVEGFR3 together with paclitaxel and carboplatin chemotherapy. Materials and methods: Immunodeficient mice were inoculated with human OVCA cell line SKOV-3m. Development of tumors was confirmed with magnetic resonance imaging (MRI) and mice were treated with gene therapy and paclitaxel and carboplatin chemotherapy. The study groups included (I) non-treated control group, (II) blank control vector AAV8-CMV, (III) AAV8-CMV with chemotherapy, (IV) AAV8-sVEGFR2, (V) AAV8-sVEGFR3, (VI) AAV8-sVEGFR2 and AAV8-sVEGFR3, and (VII) AAV8-sVEGFR2 and AAV8-sVEGFR3 with chemotherapy. Antiangiogenic and antitumoral effects were evaluated with immunohistochemical stainings and serial MRI. Results: Reduced intratumoral angiogenesis was observed in all antiangiogenic gene therapy groups. The combined use of AAV8-sVEGFR2 and AAV8-sVEGFR3 with chemotherapy suppressed ascites fluid formation and tumor growth, thus improving the overall survival of mice. Antitumoral effect was mainly caused by AAV8-sVEGFR2 while the benefits of AAV8-sVEGFR3 and chemotherapy were less prominent. Conclusions: Combined use of the AAV8-sVEGFR2 and AAV8-sVEGFR3 with chemotherapy reduces intratumoral angiogenesis and tumor growth in OVCA mouse model. Results provide preclinical proof-of-concept for the use of soluble decoy VEGFRs and especially the AAV8-sVEGFR2 in the treatment of OVCA