Browsing by Subject "Oncology"

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  • Kallio, Pauliina; Jokinen, Elina; Das, Suvendu; Högström, Jenny; Heino, Sarika; Lähde, Marianne; Alitalo, Kari (Helsingin yliopisto, 2018)
    Radiation induced tumor cell death is strongly dependent on oxygen. As abnormal tumor vasculature promotes tumor hypoxia, drugs that induce vascular normalization, such as the anti-vascular endothelial growth factor (VEGF) antibody, have been tested as radiation sensitizers in preclinical and clinical settings. The insufficient benefit obtained with anti-VEGF therapy prompted us to test if antibodies blocking the endothelial growth factor angiopoietin-2 (Ang2) could improve the effect of radiation in mouse tumor allografts and human tumor xenografts. Mouse or human tumor cells were injected subcutaneously in isogenic immunocompetent or immunodeficient (NSG) mice, respectively, and tumors were allowed to form. The mice were injected with anti-Ang2 or control antibodies every three or four days starting three days before 3x2 Gy or 4x0.5 Gy whole-body radiation, followed by analysis of tumor growth, histology, vasculature, hypoxia and necrosis. Combination treatment with anti-Ang2 and radiation improved tumor growth inhibition and extended the survival of mice with melanoma or colorectal carcinoma allografts. A similar anti-Ang2 plus radiation response was also obtained in immunodeficient mice implanted with a human colorectal carcinoma xenograft, indicating that the adaptive immune response was not essential for the effect. Histological and immunohistochemical analysis of the tumors showed that the combination treatment decreased tumor vasculature, and increased tumor hypoxia and tumor necrosis in comparison with control tumors and tumors treated with the monotherapies. Our results suggest that a combination of Ang2 blocking antibodies and radiation increases tumor growth inhibition and extends the survival of tumor-bearing mice. Significance: These findings offer a preclinical rationale for further testing of the use of Ang2 blocking antibodies in combination with radiation to improve the overall outcome of cancer treatment.
  • Baltscheffsky, Daniela (Helsingfors universitet, 2014)
    Melanom är den mest maligna formen av hudcancer. De viktigaste prognosfaktorerna för lokalt melanom är tumörtjockleken (Breslow), eventuell ulceration, mitosindexet samt eventuella metastaser i de lokala lymfknutarna (stadium III). Vid behandlingen av stadium III melanom med hög recidivrisk ges adjuvant strålbehandling efter lymfadenektomi för att minska lokalrecidivrisken. I denna retrospektiva studie analyserades ifall den adjuvanta strålbehandlingen förbättrar patienternas lokalkontroll samt helhetsöverlevnad i jämförelse med hittills rapporterade studier. I studien analyserades 92 stadium III melanompatienter som behandlats med adjuvant strålbehandling vid HUCS' klinik för cancersjukdomar åren 1989-2009. Recidivmönster samt överlevnad analyserades skilt för tre patientgrupper baserat på ifall de fått lymfknutsmetastaser eller satellitmetastaser samt ifall de fått den adjuvanta strålbehandlingen före eller efter år 2000, då man infört biopsi av portvaktskörteln (SNB) till behandlingen. Resultaten är jämförbara med resultat från tidigare publicerade studier där adjuvant strålbehandling efter lymfknutsresektion anses förbättra den lokala kontrollen, medan helhetsöverlevnaden inte nämnvärt påverkas.
  • Zhao, Yue (Helsingfors universitet, 2017)
    Background: 5-year survival rate of oral tongue squamous cell carcinoma (OTSCC) has been low (less than 60%) despite developing treatment modalities. A previous research revealed that different populations of inflammatory cells infiltration in OTSCC were associated with different clinical outcomes. On the other hand, extracellular vesicles (EVs) secreted by OTSCC cells suggested crosstalk between OTSCC cells and tumor infiltrating inflammatory cells. Study aims: This study aims to investigate the interaction between OTSCC cells and inflammatory cells and answer 3 questions: (1) Can human peripheral blood mononuclear cells (MNCs) affect activities of OTSCC cells such as proliferation, migration and invasion? (2) Can EVs of OTSCC cells affect polarization of macrophages? (3) Can EVs of OTSCC cells affect cytotoxic activity of CD8+ T cells and NK cells? Materials and methods: Two OTSCC cell lines (HSC-3 and SCC-25) were used. OTSCC cells and human peripheral blood MNCs were co-cultured using a 3D organotypic myoma model. Proliferation and invasion into myoma tissue of OTSCC cells were detected by Immunohistochemical staining of pan-cytokeratin and Ki67. Invasion area and depth of OTSCC cells were measured using ImageJ software. Migration of OTSCC cells in the presence of MNCs was monitored using a scratch wound healing assay with IncuCyte™ system. OTSCC EVs were isolated with ultracentrifugation and characterized with NTA and Immuno-EM. Human primary monocytes, CD8+ T cells and NK cells were isolated using MACS, and their purity was checked using FACS. Expression of macrophage phenotypic markers was checked with qPCR. Cytotoxic activity was evaluated using an IncyCyte™ cell killing assay. Results: Activated human peripheral blood MNCs significantly reduced proliferation of both OTSCC cell lines, and invasion area of only HSC-3. None of the inflammatory cells in the experiment had any effect on invasion depth and migration of OTSCC cells. On the other hand, OTSCC cell-derived EVs didn't influence macrophage polarization, but had heterogeneous modulating effects on cytotoxic activity of CD8+ T cells and NK cells. Conclusion: We detected effects of OTSCC cells and inflammatory cells on each other by secreted molecule mediators or EVs, but the results were not uniform and varied in different OTSCC cell lines or inflammatory cell populations and sources. The outcome of the study emphasizes the importance of a personalized design of cancer treatment, which takes other components in tumor microenvironment such as inflammatory cells and EVs into consideration.
  • Jaatinen, Hannakaisa (Helsingfors universitet, 2016)
    This thesis work was carried out in Biology Section of Experimental Therapeutics Programme in Spanish National Cancer Research Center in Madrid. The aim of this work was to carry out characterization of ADME profile of novel protein kinase inhibitors synthesized by the Medicinal Chemistry Section of Experimental Therapeutics Programme. ADME refers to absorption, distribution, metabolism and excretion. ADME screening provides crucial information when choosing new chemical entities (NCEs) and lead compounds with desirable properties for further development and for clinical studies. ADME screening is carried out in the early discovery phase in order to avoid costly failures in the later stages. The protein kinase inhibitors used in this work were designed against three different targets. However, the targets cannot be disclosed in this work due to confidentiality reasons and thus they will be referred to as X, Y, and Z. The ADME characterization was performed in a high-throughput format to screen fast compounds with desired properties. To carry out ADME characterization for the novel compounds, several in vitro assays and in vivo pharmacokinetic studies were carried out. The work was started by setting up an LC-MS/MS detection method for each compound. All in all, LC-MS/MS detection method was set up for 63 new compounds. The detection method was used to analyze the results of different in vitro and in vivo studies. In vitro assays included kinetic solubility assay, parallel artificial membrane permeability assay (PAMPA), microsomal metabolic stability assay, plasma protein binding assay, and solubility in biological fluids. The solubility in biological fluids assay was performed only for the two compounds that were selected for the pharmacokinetic (PK) study. Pharmacokinetic properties of the compounds selected for the pharmacokinetic study using the Balb/C mice were further analyzed by their pharmacokinetic parameters. These parameters were calculated by applying non-compartmental model in the WinNonlin software. One compound, ETP-871, showed promising results in the pharmacokinetic study. Another compound ETP-827 was cleared too fast from the body. Too fast excretion is undesirable since low plasma concentration of the drug is insufficient to reach the therapeutic effect. For the compound ETP-827 a new PK study with higher dose was carried out. Due to the confidentiality reasons, these further studies are not presented in this work.
  • Toppila, Iiro; Kysenius, Kai; Miettinen, Tatu; Lassenius, Mariann Ida; Lievonen, Juha; Anttila, Pekka (2022)
    Multiple myeloma (MM) patients are predominantly elderly with comorbidities that have an impact on patient mortality and treatment decisions. We previously reported the patient characteristics and overall survival outcomes of the Finnish MM cohort diagnosed between 2005 and 2016 in a nationwide retrospective registry study comprising 3,851 adults. Here, we report detailed comorbidity characteristics for this real-world Finnish MM population at cohort entry and during follow-up. Data on diagnoses and causes of death were obtained from Finnish healthcare data registries and interrogated using various multistate time-to-event models. In the year preceding MM diagnosis, comorbidities (as per Charlson Comorbidity Index definition) were recorded in 38.0% of the cohort, of which 27.9% presented with pre-existing cardiovascular disease (CVD) and 4.8% had suffered a major adverse cardiac event (MACE). At 2 years post-MM diagnosis, cumulative incidence for CVD and MACE more than doubled to 57.1% and 11.4%, respectively, and only 31.9% of the cohort remained CVD-free. Prevalent secondary malignancies were recorded in 16.8% of the patient population at MM diagnosis, with cumulative incidence increasing steadily to 27.5% at 2 years and 33% at 5 years post-diagnosis. The main cause of mortality attributed to MM, CVD, secondary malignancy, or other causes remained stable throughout the follow-up, at an average of 74.2%, 9.4%, 9.8%, and 6.5%, respectively. Prevalence of CVDs and secondary malignancies is high in Finnish patients at MM diagnosis, with older male patients suffering from higher MACE and mortality risk. Proper recording and management of comorbidities alongside novel treatments remain crucial for optimal MM management.
  • Tupasela, Aaro; Di Nucci, Ezio (2020)
    Machine learning platforms have emerged as a new promissory technology that some argue will revolutionize work practices across a broad range of professions, including medical care. During the past few years, IBM has been testing its Watson for Oncology platform at several oncology departments around the world. Published reports, news stories, as well as our own empirical research show that in some cases, the levels of concordance over recommended treatment protocols between the platform and human oncologists have been quite low. Other studies supported by IBM claim concordance rates as high as 96%. We use the Watson for Oncology case to examine the practice of using concordance levels between tumor boards and a machine learning decision-support system as a form of evidence. We address a challenge related to the epistemic authority between oncologists on tumor boards and the Watson Oncology platform by arguing that the use of concordance levels as a form of evidence of quality or trustworthiness is problematic. Although the platform provides links to the literature from which it draws its conclusion, it obfuscates the scoring criteria that it uses to value some studies over others. In other words, the platform "black boxes" the values that are coded into its scoring system.
  • Chattopadhyay, Subhayan; Hemminki, Akseli; Försti, Asta; Sundquist, Kristina; Sundquist, Jan; Hemminki, Kari (2018)
    Background: Malignant melanoma (MM) patients are at increasing risk of developing second primary cancers (SPCs). We assessed mortality and risk of SPCs in MM patients with siblings or parents affected with same cancer compared with that of the general population. Methods: We used the Swedish Family-Cancer Database to assess relative risks (RRs) and causes of death in SPCs until 2015 in patients with a MM diagnosis between 1958 and 2015. We identified 35 451patients with MM among whom 3212 received a subsequent diagnosis of SPC. RRs of SPCs after MM diagnosis were calculated stratifying over concordant family history of cancer in first-degree relatives. Results: Familial RRs were increased for second melanoma (RR = 19.28, 95% CI = 16.71 to 22.25), squamous cell skin cancer (RR = 7.58, 95% CI = 5.57 to 10.29), leukemia (RR = 5.69, 95% CI = 2.96 to 10.94), bladder (RR = 4.15, 95% CI = 2.50 to 6.89), ovarian (RR = 3.89, 95% CI = 1.46 to 10.37), kidney cancer (RR = 3.77, 95% CI = 1.57 to 9.06), cancer of unknown primary (RR = 3.67, 95% CI = 1.65 to 8.16), nervous system (RR = 2.88, 95% CI = 1.20 to 6.93), breast (RR = 2.34, 95% CI = 1.92 to 2.84), lung (RR = 2.24, 95% CI = 1.50 to 3.35), and prostate cancer (RR = 2.22, 95% CI = 1.89 to 2.61) with statistical significance. For all cancers, familial RR was in excess (2.09, 95% CI = 2.02 to 2.16 vs 1.78, 95% CI = 1.69 to 1.87; P-trend <.0001). Cause of death in MM patients with SPC is shown to be dependent on the cancer site though SPCs contributed to majority of deaths. Conclusions: SPCs appear higher with prior family history of cancer and contribute to mortality. SPC was the most common cause of death in patients with SPC and is almost uniformly the major contributing cause of death for all cancer sites. For improved survival in MM patients, prevention and early detection of SPCs would be important.
  • Heikkinen, Sanna; Miettinen, Joonas; Pukkala, Eero; Koskenvuo, Markku; Malila, Nea; Pitkaniemi, Janne (2017)
    Background: It has been suggested that long-term activation of the body's stress-response system and subsequent overexposure to stress hormones may be associated with increased morbidity. However, evidence on the impact of major life events on mortality from breast cancer (BC) remains inconclusive. The main aim of this study is to investigate whether major negatively or positively experienced life events before or after diagnosis have an effect on BC-specific mortality in women who have survived with BC for at least 2 years. Methods: We conducted a case fatality study with data on life events from a self-administered survey and data on BC from the Finnish Cancer Registry. Cox models were fitted to estimate BC mortality hazard ratios (MRs) between those who have undergone major life events and those who haven't. Results: None of the pre-diagnostic negative life events had any effect on BC-specific mortality. Regarding post-diagnostic events, the effect was greatest in women with moderate scores of events. As for event-specific scores, increased BC mortality was observed with spouse unemployment, relationship problems, and death of a close friend. By contrast, falling in love and positive developments in hobbies were shown to be associated with lower BC mortality (MRs 0.67, 95% CI: 0.49-0.92 and 0.74, 95% CI: 0.57-0.96, respectively). In an analysis restricted to recently diagnosed cases (2007), also death of a child and of a mother was associated with increased BC mortality. Conclusions: Some major life events regarding close personal relationships may play a role in BC-specific mortality, with certain negative life events increasing BC mortality and positive events decreasing it. The observed favorable associations between positive developments in romantic relationships and hobbies and BC mortality are likely to reflect the importance of social interaction and support. (C) 2017 Elsevier Ltd. All rights reserved.
  • Ilola, Jaakko (Helsingfors universitet, 2016)
    Kolesteroli on solukalvojen välttämätön rakennemolekyyli ja sen pitoisuus solukalvolla vaikuttaa muun muassa kasvutekijäsignalointiin. MLN64 (STARD3) on proteiini, joka kykenee siirtämään kolesterolia solun eri kalvojen välillä ja jonka yli-ilmentyminen soluissa muuttaa solukalvon kolesterolipitoisuutta ja voi siten vaikuttaa solukalvon signaalireitteihin. HER2 (erbB-2) on tyrosiinikinaasireseptoreihin kuuluva HER-ryhmän solukalvoreseptori. HER2-positiivisuus rintasyövässä on syövän ennustetta huonontava tekijä. HER2-positiiviset rintasyövät ilmentävät lähes poikkeuksetta voimakkaasti myös MLN64:ä. Tutkielmani tarkoituksena oli selvittää, vaikuttaako rintasyövän MLN64-proteiinin ilmentyminen kolesterolisynteesin avainentsyymin, HMG-CoA-reduktaasin (HMGCR), tai steroidisynteesin pullonkaulaentsyymin, CYP11A1:n, lähetti-RNA-määriin (mRNA-määriin). CYP11A1 ei fysiologisena ilmenny rintarauhaskudoksessa ja sen ilmeneminen voisi mahdollistaa rintasyövän oman steroidisynteesin. Materiaalina oli FinHer-aineiston formaliinifiksoiduista ja parafiiniin valetuista rintasyöpänäytteistä eristetty RNA. RNA käännettiin cDNA:ksi kvantitatiivista PCR-reaktiota varten, jolla tutkittiin näytteiden HMGCR:n ja CYP11A1:n lähetti-RNA-tasot. Tutkielman mukaan MLN64:n voimakas ilmentyminen korreloi positiivisesti HMGCR:n mRNA-määrään. CYP11A1 ilmentyi 16 % näytteistä, mutta korrelaatiota MLN64:n määrään ei havaittu. Tutkimus tukee näkemystä, jonka mukaan voimakas MLN64:n ilmentyminen vaikuttaa syöpäsolujen kolesterolituotantoon.
  • Heinonen, Antti Tuomas (Helsingfors universitet, 2015)
    Tavoitteet: Kuvata lapsuusiän kiinteästä syöpäkasvaimesta selvinneiden potilaiden saama hoito ja hoidon jälkeen ilmenneet haitat. Testata aikaisemmissa tutkimuksissa osoitettujen hoitojen ja haittojen välisten yhteyksien toimivuutta uudempia syöpähoito-ohjelmia läpikäyneillä potilailla. Menetelmät: Retrospektiivisesti kerättiin potilaskertomuksista tiedot annetuista syöpähoidoista ja hoidon jälkeen ilmenneistä haitoista vuosina 1995-2005 syntyneiltä potilailta, jotka olivat saaneet HYKS Lastenklinikalla solusalpaajia tai sädehoitoa kiinteään syöpäkasvaimeen. Tulokset: Aineistoon kertyi potilaita 110 ja heidän keskimääräinen seuranta-aika oli noin 8 vuotta. Osalla potilaista ei ilmennyt haittoja pitkässäkään seurannassa, mutta toisilla haittoja ilmeni runsaasti jo varhain hoitojen jälkeen. Sisplatiinin käyttö altisti kuulohaitoille. Alkyloivien aineiden suuri kumulatiivinen annos altisti hedelmällisyyshaitoille. Sädehoitoa saaneilla potilailla ilmeni enemmän vakavia haittoja. Päätelmät: Hoitojen ja haittojen väliset yhteydet, jotka on osoitettu vanhempia syöpähoito-ohjelmia läpikäyneillä potilailla, toteutuvat ainakin osittain tuoreempia syöpähoito-ohjelmia läpikäyneillä potilailla alle 10 vuoden seurannassa.
  • Suni, Silja (Helsingfors universitet, 2016)
    Miesten rintasyöpä on hyvin harvinainen sairaus, ja sen syyt tunnetaan huonosti. Perinnöllisillä tekijöillä saattaa olla miesten rintasyövän synnyssä tärkeä rooli, ja perheen syöpähistoria on havaittu epidemiologisissa tutkimuksissa merkittäväksi riskitekijäksi. Perinnölliset mutaatiot BRCA1- ja etenkin BRCA2-geeneissä aiheuttavat myös miehille kohonneen riskin. Myös muita, pienemmän riskin aiheuttavia alleeleja on tunnistettu viime vuosina. Niiden kliininen merkitys eri populaatioissa vaihtelee suuresti. Tässä tutkimuksessa genotyypitettiin 72 miespuolisen rintasyöpäpotilaan sekä yhdeksän perheen, joissa esiintyy miesten rintasyöpää, perimä kiinnostuksen kohteina olleiden mutaatioiden suhteen CHEK2-, PALB2-, RAD51C-, RAD51D- ja FANCM-geeneissä.
  • Åström, Max (Helsingfors universitet, 2016)
    INTRODUCTION: Differentiating atypical lipomatous tumours (ALT) and well-differentiated liposarcomas (WDLS), also known as grade 1 liposarcomas (G1LS), from benign lipomas is a common diagnostic problem for pathologists. ALT/WDLS are characterised by amplification of the murine double minute 2 (MDM2) gene and our aim was to investigate if immunohistochemistry for MDM2 can be used to diagnose ALT/WDLS. We also reported treatment and calculated survival rates for patients with grade 1 liposarcomas (G1LS) at Helsinki University Central Hospital (HUCH). METHODS: 25 lipomas, 17 ALT and 21 G1LS were reviewed and initiated for MDM2 immunohistochemistry. For the clinical cohort we included 53 patients with a final diagnosis of G1LS during 1995-2007. RESULTS: The sensitivity of MDM2 immunohistochemistry for ALT and G1LS was 35% and 86%, respectively. The specificity in distinguishing ALT and G1LS from lipomas was 100%. The 5-year local-recurrence free survival (LRFS) for G1LS was 80%, and the 10-year LRFS was 68%. Local recurrence occurred in 16/53 patients. Retroperitoneal and intra-abdominal tumours had a 4.224 times greater risk of local recurrence compared to tumours in the extremities or trunk wall. Only one patient died due to G1LS. DISCUSSION: MDM2 immunohistochemistry is a good supportive method when diagnosing lipomatous tumours. It was highly specific in differentiating ALT and G1LS from lipomas and also relatively sensitive in recognising ALT and G1LS. We reported that G1LS are recurring tumours with tumour site strongly affecting the risk of local recurrence. Despite the high risk of local recurrence, the mortality of G1LS is low.
  • Lindell, Rony (Helsingfors universitet, 2016)
    Next-generation sequencing has evolved during the past 10 years to become the go-to method for genome-wide analysis projects. Based on parallelizable PCR methods adopted from the traditional Sanger sequencing, NGS platforms can produce massive amounts of genetic information in a single run and read an entire DNA molecule within a day. The immense amount of nucleotide sequence data produced by a single sample has brought us to an era of algorithmic optimization for analysis and guring out parallelization schema. For cohort projects generally cloud based systems are used due to vast computing power requirements. Anduril is an integration and parallelization framework well suited for NGS analysis, as is shown in this study. After a brief review of the golden standard methods of NGS analysis, we describe the incorporation of the main tools into the new sequencing bundle for Anduril. Tools for alignment (BWA, Bowtie), recalibration (GATK, Picard-tools) and variant calling (GATK, Samtools, VarScan) are in main focus. The Best Practice of Broad Institute, creators of The Genome Analysis Toolkit (GATK), has been a big inspiration in the creation of our sequencing pipeline. The evolution of sequencing bundle tools into a pipeline is discussed through three separate project examples. First, a small group of 8 chronic myeloid leukemia patient samples were analysed after implementation of the main tools of the pipeline. The results were consistent with previous results, but no novel relevant mutations were found. Second, exome sequencing data from 180 breast cancers with controls available in TCGA (The Cancer Genome Atlas) were processed for use in various projects in our lab. The example showed the power of Anduril in gross cohort analysis projects, enabling automatic parallelization and intelligent work ow management system. Third, we analysed exome data from 330 TCGA ovarian cancers with controls and created a prototypical set of database components for creation of a database of annotated variants for use in analytical queries. Compared to other integration frameworks (e.g. GATK, Crossbow and Hadoop), Anduril is a robust contender for the programming oriented scientist. As cloud computing is becoming at an increasing rate a requirement in large genome-wide analysis projects, Anduril provides an e ective generalizable framework for adding tools, creating pipelines and executing entire work ows on multi-nodal computing servers. As technology advances and available computational resources grow, fast multi-processor analysis can be incorporated into health care more and more for detection of disease causing genes, medication kinetics altering polymorphisms and cancer driving mutations in an everyday setting.
  • Varkila, Nora (Helsingfors universitet, 2016)
    Syövän ja veren hyytymisen välillä on useita yhteyksiä. Erityisesti haimasyöpä, kuten duktaalinen adenokarsinooma (PDAC), lisää merkittävästi hyytymisaktiviteettia. Tutkimuksemme tavoitteena oli selvittää syövän levinneisyyden, hoitojen ja preoperatiivisten biomarkkereiden yhteyttä haimasyövässä, verraten sitä hyvänlaatuiseen intraduktaaliseen papillaariseen musinoottiseen neoplasiaan (IPMN). Tutkimukseen otettiin 158 haimatuumorin vuoksi leikattua potilasta, joiden kasvain diagnosoitiin joko PDAC:ksi tai IPMN:ksi. Verenkuvaa, hyytymis- ja tuumorimarkkereita analysoitiin preoperatiivisesti. Potilaat jaettiin ryhmiin riippuen syövän levinneisyydestä ja neoadjuvanttihoidoista (NT). Hyytymistekijä VIII (FVIII:C) oli aktiivisempi PDAC potilailla kuin IPMN potilailla (p<0.05), paitsi paikallisilla NT-hoidetuilla PDAC potilailla. D-dimeeripitoisuus oli suurempi paikallista hoitamatonta PDAC:ta ja metastasoinutta NT-hoidettua PDAC:ta sairastavilla kuin IPMN potilailla (p<0.02). Tuumorimarkkeri CA 19-9 oli koholla PDAC potilailla, lukuun ottamatta paikallista NT-hoidettua PDAC:ta. Yhdistämällä FVIII:C, D-dimeeri ja CA 19-9-tulokset aikaansaimme paneelipisteytyksen, joka erotti kaikki PDAC ryhmät IPMN potilaista (p<0.05). Tutkimuksessamme CA 19-9 ei yksinään erottanut kaikkia PDAC ryhmiä IPMN:stä. Yhdistämällä CA 19-9:ään hyytymistä kuvaavat FVIII:C:n ja D-dimeerin syntyy paneelipisteytys, joka preoperatiivisesti ennustaa PDAC:a.
  • Danielsson, Oscar (Helsingfors universitet, 2016)
    Hudmelanom är en malign sjukdom som afficierar huden. Tumören infiltrerar kringliggande vävnader och sprids genom metastasering, främst via lymfkärl till lymfknutor. Vid utredning av melanom är det viktigt att utreda om sjukdomen spridit sig till de närmaste lymfknutorna, portvaktskörtlarna. Ifall metastaser konstateras i portvaktskörtel utförs körtelutrymning av det lymfknutområde där metastaser konstaterats. Målet med studien är att granska metastasfynd i portvaktskörtel från åren 2012 och 2013 för att utreda hur metastasfyndet påverkar patientens prognos samt hur ofta ytterligare metastaser konstateras i körtelutrymning. I studien konstaterades metastaser i portvaktskörtel hos 16,7 % av patienterna. Hos 16,7 % av patienterna konstaterades metastaser i körtelutrymning. Överlevnadsprognosen för patienter med metastaser i portvaktskörtel motsvarade resultat i tidigare studier. Övriga faktorer som försämrade prognosen bland patientmaterialet var hög ålder, stor metastas och lokalrecidiv. Studiens material bestod av 42 patienter, för att kunna fatta nya vårdbeslut om melanom krävs studier med större patientmaterial.
  • Piccinini, Filippo; Balassa, Tamas; Carbonaro, Antonella; Diosdi, Akos; Toth, Timea; Moshkov, Nikita; Tasnadi, Ervin A.; Horvath, Peter (2020)
    Today, we are fully immersed into the era of 3D biology. It has been extensively demonstrated that 3D models: (a) better mimic the physiology of human tissues; (b) can effectively replace animal models; (c) often provide more reliable results than 2D ones. Accordingly, anti-cancer drug screenings and toxicology studies based on multicellular 3D biological models, the so-called "-oids" (e.g. spheroids, tumoroids, organoids), are blooming in the literature. However, the complex nature of these systems limit the manual quantitative analyses of single cells' behaviour in the culture. Accordingly, the demand for advanced software tools that are able to perform phenotypic analysis is fundamental. In this work, we describe the freely accessible tools that are currently available for biologists and researchers interested in analysing the effects of drugs/treatments on 3D multicellular-oids at a single-cell resolution level. In addition, using publicly available nuclear stained datasets we quantitatively compare the segmentation performance of 9 specific tools. (C) 2020 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
  • Kanerva, Anna; Lavilla-Alonso, Sergio; Raki, Mari; Kangasniemi, Lotta; Bauerschmitz, Gerd J; Takayama, Koichi; Ristimäki, Ari; Desmond, Renee A; Hemminki, Akseli (2008)
  • Salminen, Samuli (Helsingfors universitet, 2013)
    Sarkoomat ovat mesenkymaalisista kantasoluista lähtöisin olevia pahanlaatuisia kasvaimia, joiden yhtenä harvinaisena aiheuttavana tekijänä on sädehoito. Tämän tutkimuksen tavoitteena oli selvittää sädehoidon jälkeen todettujen sarkoomien ilmaantuvuutta Suomessa vuosina 1987-2009 ja määrittää kyseisten sarkoomapotilaiden tarkat sädehoitotiedot sekä ennusteet. Potilaiden ensimmäiselle syövälle ei asetettu vaatimuksia tyypin suhteen, mutta toisen tai myöhemmän syövän tuli olla sarkooma. Suomen Syöpärekisterin tietokantaan pohjautuvaa aineistoa analysoitiin luokittelemalla kukin syöpädiagnoosi anatomisesti pallean suhteen sekä määrittämällä myöhempien sarkoomien histologialuokkien yleisyys. Potilaita, joilla myöhempi sarkooma oli diagnosoitu vuonna 1987 tai myöhemmin, havaittiin yhteensä 1070. Yleisimmät myöhempien sarkoomien histologialuokat olivat leiomyosarkooma (179 kpl), maligni fibroosi histiosytooma (150 kpl) sekä muuten määrittelemätön sarkooma (123 kpl). Tämä tutkimus toimii pohjustavana tutkimuksena myöhemmän väitöskirjan osatutkimuksille, joissa käydään ensimmäisen syövän diagnoosin perusteella yksityiskohtaisesti läpi potilasasiakirjoja, sädehoitotietoja ja histologialuokituksia sekä määritetään sädehoidon jälkeen todettujen sarkoomien keskeisiä tunnuslukuja.
  • Bellou, Sofia; Karali, Evdoxia; Bagli, Eleni; Al-Maharik, Nawaf; Morbidelli, Lucia; Ziche, Marina; Adlercreutz, Herman; Murphy, Carol; Fotsis, Theodore (2012)
  • Virkunen, Ekaterina (Helsingin yliopisto, 2018)
    The majority of cancers, such as breast cancer, originate from epithelial structures. Highly organized epithelial tissues are comprised of cells which manifest apico-basal polarization. Factors regulating apico-basal polarity and epithelial integrity are often observed deregulated in cancer cells and loss of polarity is often observed in tumors. However, the importance and the specific role of epithelial integrity regulators in tumorigenesis are still not fully defined. This study shows that the key regulators of epithelial cell polarity Par6B and Par6G proteins have a role in the restriction of cell proliferation in mammary epithelial cell lines. Using the shRNA silencing approach, downregulation of PARD6B and PARD6G in the cells lead to the impediment of the cell-cycle exit, verified in proliferation suppressive conditions in which cells normally would enter quiescence. Par6 proteins were shown to regulate cell proliferation via the canonical PI3K/Akt pathway, which is one of the most commonly deregulated cell proliferation promoting pathways in cancer cells. The results demonstrate the unknown function of Par6B and Par6G proteins as cell proliferation regulators and a previously unrecognized relation between Par6 proteins and PI3K/Akt pathway. However, the detailed interaction between Par6 proteins and the PI3K/Akt pathway ought to be investigated further. In addition, the results revealed that Par6 proteins have different effects on cell proliferation suggesting biological differences between Par6 proteins and that certainly bears further investigation. In conclusion, the study presents a previously unknown connection between epithelial integrity regulators and cancer-relevant cell proliferation promoting pathways, which may provide new targets for therapeutic intervention in the future.