Browsing by Subject " therapy"

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  • Hyytiäinen, Aini (Helsingin yliopisto, 2021)
    Pään ja kaulan alueen syöpäpotilaiden ennuste on huono siitä huolimatta, että syöpähoidot ovat kehittyneet viime vuosina. Angiogeneesi, eli verisuonten uudismuodostus, on edellytys syövän kasvulle ja leviämiselle ja tämän takia useita angiogeeneesiä estäviä lääkkeitä on kehitetty syövän hoitoon. Tässä tutkimuksessa tehtiin systemaattinen kirjallisuuskatsaus, jossa kerättiin tiedot kliinisistä tutkimuksista, joissa käytettiin angiogeenesi-inhibiittoreita pään ja kaulan alueen syöpäpotilailla. Kirjallisuushaku tehtiin Ovid MEDLINE, Cochrane Library, Scopus sekä ClinicalTrials.gov tietokannoissa. Tutkimus rajattiin kolmeen kategoriaan angiogeneesiä estäviä lääkkeitä: bevacizumab, tyrosiinikinaasin estäjät sekä endostatin. Kirjallisuuskatsaukseen sisällytettiin 38 kliinistä tutkimusta, jotka olivat vaiheissa I, II tai III. Angiogeneesi-inhibiittoreita käytettiin tutkimuksissa yksinään sekä yhdistettynä sädehoitoon, kemoterapiaan, kohdennettuun syöpähoitoon tai immunoterapiaan. Tutkimuksissa esiintyi 12 erilaista angiogeneesi-inhibiittoria ja näistä bevacizumab oli yleisimmin tutkittu lääke. Bevacizumab osoittautui tehokkaaksi useissa eri kombinaatioissa, mutta siihen liittyi paljon haittavaikutuksia. Endostatin sekä lenvatinib olivat hyvin siedettyjä ja niiden teho oli lupaava. Useimmat kliiniset tutkimukset angiogeneesi-inhibiittoreista eivät osoittautuneet hyödyllisiksi pään ja kaulan alueen syöpäpotilaiden hoidossa ja lisäksi useisiin lääkkeisiin liitettiin paljon haittavaikutuksia. Jotkin tulokset olivat kuitenkin lupaavia, varsinkin yhdistelmähoitoina, joten lisätutkimukset angiogeeneesi-inhibiittoreista pään ja kaulan alueen syöpäpotilaiden hoidossa ovat perusteltuja.
  • Hyytiäinen, Aini; Wahbi, Wafa; Väyrynen, Otto; Saarilahti, Kauko; Karihtala, Peeter; Salo, Tuula; Al-Samadi, Ahmed (2021)
    Background Head and neck squamous cell carcinoma (HNSCC) carries poor survival outcomes despite recent progress in cancer treatment in general. Angiogenesis is crucial for tumour survival and progression. Therefore, several agents targeting the pathways that mediate angiogenesis have been developed. We conducted a systematic review to summarise the current clinical trial data examining angiogenesis inhibitors in HNSCC. Methods We carried out a literature search on three angiogenesis inhibitor categories-bevacizumab, tyrosine kinase inhibitors and endostatin-from Ovid MEDLINE, Cochrane Library, Scopus and ClinicalTrials.gov database. Results Here, we analysed 38 clinical trials, total of 1670 patients, investigating 12 angiogenesis inhibitors. All trials were in phase I or II, except one study in phase III on bevacizumab. Angiogenesis inhibitors were used as mono- and combination therapies together with radio-, chemo-, targeted- or immunotherapy. Among 12 angiogenesis inhibitors, bevacizumab was the most studied drug, included in 13 trials. Although bevacizumab appeared effective in various combinations, it associated with high toxicity levels. Endostatin and lenvatinib were well-tolerated and their anticancer effects appeared promising. Conclusions Most studies did not show benefit of angiogenesis inhibitors in HNSCC treatment. Additionally, angiogenesis inhibitors were associated with considerable toxicity. However, some results appear encouraging, suggesting that further investigations of angiogenesis inhibitors, particularly in combination therapies, for HNSCC patients are warranted. Systematic Review Registration PROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42020157144.
  • Woock, Malin; Martinez-Majander, Nicolas; Seiffge, David J.; Selvik, Henriette Aurora; Nordanstig, Annika; Redfors, Petra; Lindgren, Erik; Sanchez van Kammen, Mayte; Rentzos, Alexandros; Coutinho, Jonathan M.; Doyle, Karen; Naess, Halvor; Putaala, Jukka; Jood, Katarina; Tatlisumak, Turgut (2022)
    The association between stroke and cancer is well-established. Because of an aging population and longer survival rates, the frequency of synchronous stroke and cancer will become even more common. Different pathophysiologic mechanisms have been proposed how cancer or cancer treatment directly or via coagulation disturbances can mediate stroke. Increased serum levels of D-dimer, fibrin degradation products, and CRP are more often seen in stroke with concomitant cancer, and the clot retrieved during thrombectomy has a more fibrin- and platelet-rich constitution compared with that of atherosclerotic etiology. Multiple infarctions are more common in patients with active cancer compared with those without a cancer diagnosis. New MRI techniques may help in detecting typical patterns seen in the presence of a concomitant cancer. In ischemic stroke patients, a newly published cancer probability score can help clinicians in their decision-making when to suspect an underlying malignancy in a stroke patient and to start cancer-screening studies. Treating stroke patients with synchronous cancer can be a delicate matter. Limited evidence suggests that administration of intravenous thrombolysis appears safe in non-axial intracranial and non-metastatic cancer patients. Endovascular thrombectomy is probably rather safe in these patients, but probably futile in most patients placed on palliative care due to their advanced disease. In this topical review, we discuss the epidemiology, pathophysiology, and prognosis of ischemic and hemorrhagic strokes as well as cerebral venous thrombosis and concomitant cancer. We further summarize the current evidence on acute management and secondary preventive therapy.
  • Niemelä, Nea (Helsingin yliopisto, 2022)
    B-solulymfoomien nykyisistä tehokkaista hoidoista huolimatta osalla potilaista lymfooma uusiutuu toistuvasti tai hidaskasvuinen lymfooma muuntuu aggressiivisemmaksi, jolloin ennuste on huono. Yksi uusimmista hoitokeinoista on CAR T-soluterapia. Tämän rekisteritutkimuksen tavoitteena oli selvittää CAR T-soluterapian hoitotuloksia sekä haittavaikutuksia HUS syöpäkeskuksessa hoidetuilla aikuispotilailla. Aineisto koostui 17 potilaasta, jotka sairastivat diffuusia suurisoluista B-solulymfoomaa, primaarista välikarsinan B-solulymfoomaa, transformoitunutta follikulaarista lymfoomaa tai gradus 3B follikulaarista lymfoomaa. CAR T-soluhoitoa annettiin ensimmäisen tai toisen systeemihoitoa sisältäneen hoitolinjan jälkeen uusiutuneeseen tai hoitoon reagoimattomaan tautiin. CAR T-soluterapian sai 14 potilasta. Mediaani seuranta-aika oli 9 kuukautta. Kokonaisvasteiden osuus oli 86 %. Täydellisen vasteen sai 64 % ja osittaisen vasteen sai 21 %. Pysyviä hoitovasteita havaittiin jopa yli 3,5 vuotta hoidon jälkeen. Taudittoman ajan mediaania ei saavutettu ja 9 kuukauden kohdalla remissiossa olevien osuus oli 51 %. Tapahtumavapaan elinajan osuus oli 47 % yhdeksän kuukauden kohdalla. Potilaiden mediaani elinaika oli 9,8 kuukautta ja 9 kuukauden kohdalla elossa oli 53 % potilaista. Seuranta-aikana kuoli kahdeksan potilasta. Heistä kuusi menehtyi taudin etenemisen vuoksi. Sytokiinien vapautumisoireyhtymä todettiin haittavaikutuksena kaikilla, 13 potilaalla (93 %) lievänä ja yhdellä (7 %) henkeä uhkaavana (gradus 4). Neurologinen haittavaikutus esiintyi 12 potilaalla (86 %), suurimmalla osalla lievänä ja neljällä (29 %) merkittävänä (gradus 3-4). Näiden haittavaikutusten hoitoon kymmenen (71 %) potilasta sai tosilitsumabia ja yhdeksän (64 %) deksametasonia. Gradus 3-4 neutropeniaa esiintyi 14 (100 %), trombosytopeniaa 7 (50 %) sekä anemiaa 7 (50 %) potilaalla. Pitkittyneitä, yli 28 vuorokautta kestäviä, sytopenioita esiintyi 10-11 potilaalla (71-79 %). Tämän tutkimuksen perusteella CAR T-soluterapia soveltuu B-solulymfoomien hoitoon toisessa tai kolmannessa linjassa. Tutkimuksen heikkous oli aineiston pieni koko sekä lyhyt seuranta-aika, minkä vuoksi tulevaisuudessa tarvitaan lisää tutkimuksia aiheesta.
  • Athanasiou, Antonios; Veroniki, Areti Angeliki; Efthimiou, Orestis; Kalliala, Ilkka; Naci, Huseyin; Bowden, Sarah; Paraskevaidi, Maria; Martin-Hirsch, Pierre; Bennett, Philip; Paraskevaidis, Evangelos; Salanti, Georgia; Kyrgiou, Maria (2019)
    Introduction Local treatments for cervical intraepithelial neoplasia (CIN) and microinvasive disease remove or ablate a cone-shaped part of the uterine cervix containing the abnormal cells. A trend toward less radical techniques has raised concerns that this may adversely impact the rates of precancerous and cancerous recurrence. However, there has been no strong evidence to support such claims. We hereby describe a protocol of a systematic review and network meta-analysis that will update the evidence and compare all relevant treatments in terms of efficacy and complications. Methods and analysis Literature searches in electronic databases (CENTRAL, MEDLINE, EMBASE) or trial registries will identify published and unpublished randomised controlled trials (RCTs) and cohort studies comparing the efficacy and complications among different excisional and ablative techniques. The excisional techniques include cold knife, laser or Fischer cone, large loop or needle excision of the transformation zone and the ablative radical point diathermy, cryotherapy, cold coagulation or laser ablation. The primary outcome will be residual/recurrent disease defined as abnormal histology or cytology of any grade, while secondary outcomes will include treatment failure rates defined as high-grade histology or cytology, histologically confirmed CIN1+ or histologically confirmed CIN2+, human papillomavirus positivity rates, involved margins rates, bleeding and cervical stenosis rates. We will assess the risk of bias in RCTs and observational studies using tools developed by the Cochrane Collaboration. Two authors will independently assess study eligibility, abstract the data and assess the risk of bias. Random-effects meta-analyses and network meta-analyses will be conducted using the OR for dichotomous outcomes and the mean difference for continuous outcomes. The quality of the evidence for the primary outcome will be assessed using the CINeMA (Confidence In Network Meta-Analysis) tool. Ethics and dissemination Ethical approval is not required. We will disseminate findings to clinicians, policy-makers, patients and the public. PROSPERO registration number CRD42018115508.
  • Pihkala, Panu (2022)
    The environmental crisis is producing an increasing number of both physical and psychological impacts. This article studies the challenge of eco-anxiety for pastoral care, drawing from both interdisciplinary research and ecological theology. The aim is to help both practitioners and re-searchers to encounter eco-anxiety more constructively. The rapidly growing research about eco-anxiety and therapy is discussed in relation to pastoral care. The various forms of eco-anxiety are briefly analyzed. The role of the caregivers is discussed by using sources that study the challenges of therapists in relation to eco-anxiety. The existential depths of eco-anxiety are probed in the light of recent research and older existentialist theory. It is pointed out that the political character of ecological issues, especially climate change issues, causes many kinds of challenges for pastoral care. As the constructive conclusion of the article, various possibilities and resources for encountering eco-anxiety in pastoral care are discussed, along with the connections with wider pastoral theology. It is argued that pastoral care providers should engage in self-reflection about their own attitudes and emotions related to ecological issues, preferably with the support of trusted peers or mentors. Various organizational developments are also needed to support care-givers. Dialectical thinking is one tool that can help to navigate the complex dynamics related to environmental responsibility, eco-emotions, and questions of hope or hopelessness.
  • Vuorio, A.; Watts, G. F.; Schneider, W. J.; Tsimikas, S.; Kovanen, P. T. (2020)
    Vuorio A, Watts GF, Schneider WJ, Tsimikas S, Kovanen PT (Mehilainen Airport Health Centre, Vantaa; University of Helsinki, Helsinki, Finland; University of Western Australia, Perth, Australia; Royal Perth Hospital, Perth, Australia; Medical University of Vienna, Vienna, Austria; University of California San Diego, La Jolla, CA, USA; Wihuri Research Institute, Helsinki, Finland). Familial hypercholesterolemia and elevated lipoprotein(a): double heritable risk and new therapeutic opportunities (Review). J Intern Med 2020; 287: 2-18. There is compelling evidence that the elevated plasma lipoprotein(a) [Lp(a)] levels increase the risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. Like low-density lipoprotein (LDL) particles, Lp(a) particles contain cholesterol and promote atherosclerosis. In addition, Lp(a) particles contain strongly proinflammatory oxidized phospholipids and a unique apoprotein, apo(a), which promotes the growth of an arterial thrombus. At least one in 250 individuals worldwide suffer from the heterozygous form of familial hypercholesterolemia (HeFH), a condition in which LDL-cholesterol (LDL-C) is significantly elevated since birth. FH-causing mutations in the LDL receptor gene demonstrate a clear gene-dosage effect on Lp(a) plasma concentrations and elevated Lp(a) levels are present in 30-50% of patients with HeFH. The cumulative burden of two genetically determined pro-atherogenic lipoproteins, LDL and Lp(a), is a potent driver of ASCVD in HeFH patients. Statins are the cornerstone of treatment of HeFH, but they do not lower the plasma concentrations of Lp(a). Emerging therapies effectively lower Lp(a) by as much as 90% using RNA-based approaches that target the transcriptional product of the LPA gene. We are now approaching the dawn of an era, in which permanent and significant lowering of the high cholesterol burden of HeFH patients can be achieved. If outcome trials of novel Lp(a)-lowering therapies prove to be safe and cost-effective, they will provide additional risk reduction needed to effectively treat HeFH and potentially lower the CVD risk in these high-risk patients even more than currently achieved with LDL-C lowering alone.
  • Alkasalias, Twana; Moyano-Galceran, Lidia; Arsenian-Henriksson, Marie; Lehti, Kaisa (2018)
    Tumorigenesis is a complex process involving dynamic interactions between malignant cells and their surrounding stroma, including both the cellular and acellular components. Within the stroma, fibroblasts represent not only a predominant cell type, but also a major source of the acellular tissue microenvironment comprising the extracellular matrix (ECM) and soluble factors. Normal fibroblasts can exert diverse suppressive functions against cancer initiating and metastatic cells via direct cell-cell contact, paracrine signaling by soluble factors, and ECM integrity. The loss of such suppressive functions is an inherent step in tumor progression. A tumor cell-induced switch of normal fibroblasts into cancer-associated fibroblasts (CAFs), in turn, triggers a range of pro-tumorigenic signals accompanied by distraction of the normal tissue architecture, thus creating an optimal niche for cancer cells to grow extensively. To further support tumor progression and metastasis, CAFs secrete factors such as ECM remodeling enzymes that further modify the tumor microenvironment in combination with the altered adhesive forces and cell-cell interactions. These paradoxical tumor suppressive and promoting actions of fibroblasts are the focus of this review, highlighting the heterogenic molecular properties of both normal and cancer-associated fibroblasts, as well as their main mechanisms of action, including the emerging impact on immunomodulation and different therapy responses.
  • Seliger, Barbara; Al-Samadi, Ahmed; Yang, Bo; Salo, Tuula; Wickenhauser, Claudia (2022)
    Various in vitro models using primary and established 2- and 3-dimensional cultures, multicellular tumor spheroids, standardized tumor slice cultures, tumor organoids, and microfluidic systems obtained from tumor lesions/biopsies of head and neck cancer (HNC) have been employed for exploring and monitoring treatment options. All of these in vitro models are to a different degree able to capture the diversity of tumors, recapitulate the disease genetically, histologically, and functionally and retain their tumorigenic potential upon xenotransplantation. The models were used for the characterization of the malignant features of the tumors and for in vitro screens of drugs approved for the treatment of HNC, including chemotherapy and radiotherapy as well as recently developed targeted therapies and immunotherapies, or for novel treatments not yet licensed for these tumor entities. The implementation of the best suitable model will enlarge our knowledge of the oncogenic properties of HNC, expand the drug repertoire and help to develop individually tailored treatment strategies resulting in the translation of these findings into the clinic. This review summarizes the different approaches using preclinical in vitro systems with their advantages and disadvantages and their implementation as preclinical platforms to predict disease course, evaluate biomarkers and test therapy efficacy.
  • Thunnissen, Erik; Weynand, Birgit; Udovicic-Gagula, Dalma; Brcic, Luka; Szolkowska, Malgorzata; Hofman, Paul; Smojver-Jezek, Silvana; Anttila, Sisko; Calabrese, Fiorella; Kern, Izidor; Skov, Birgit; Perner, Sven; Dale, Vibeke G.; Eri, Zivka; Haragan, Alex; Leonte, Diana; Carvallo, Lina; Prince, Spasenja Savic; Nicholson, Siobhan; Sansano, Irene; Ryska, Ales (2020)
    A questionnaire on biomarker testing previously used in central European countries was extended and distributed in Western and Central European countries to the pathologists participating at the Pulmonary Pathology Society meeting 26-28 June 2019 in Dubrovnik, Croatia. Each country was represented by one responder. For recent biomarkers the availability and reimbursement of diagnoses of molecular alterations in non-small cell lung carcinoma varies widely between different, also western European, countries. Reimbursement of such assessments varies widely between unavailability and payments by the health care system or even pharmaceutical companies. The support for testing from alternative sources, such as the pharmaceutical industry, is no doubt partly compensating for the lack of public health system support, but it is not a viable or long-term solution. Ideally, a structured access to testing and reimbursement should be the aim in order to provide patients with appropriate therapeutic options. As biomarker enabled therapies deliver a 50% better probability of outcome success, improved and unbiased reimbursement remains a major challenge for the future.
  • Sarhadi, Virinder Kaur; Daddali, Ravindra; Seppänen-Kaijansinkko, Riitta (2021)
    Osteosarcoma (OS) is an aggressive bone tumor that mainly affects children and adolescents. OS has a strong tendency to relapse and metastasize, resulting in poor prognosis and survival. The high heterogeneity and genetic complexity of OS make it challenging to identify new therapeutic targets. Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into adipocytes, osteoblasts, or chondroblasts. OS is thought to originate at some stage in the differentiation process of MSC to pre-osteoblast or from osteoblast precursors. MSCs contribute to OS progression by interacting with tumor cells via paracrine signaling and affect tumor cell proliferation, invasion, angiogenesis, immune response, and metastasis. Extracellular vesicles (EVs), secreted by OS cells and MSCs in the tumor microenvironment, are crucial mediators of intercellular communication, driving OS progression by transferring miRNAs/RNA and proteins to other cells. MSC-derived EVs have both pro-tumor and anti-tumor effects on OS progression. MSC-EVs can be also engineered to deliver anti-tumor cargo to the tumor site, which offers potential applications in MSC-EV-based OS treatment. In this review, we highlight the role of MSCs in OS, with a focus on EV-mediated communication between OS cells and MSCs and their role in OS pathogenesis and therapy.
  • Rajala-Schultz, Päivi; Nødtvedt, Ane; Halasa, Tariq; Persson Waller, Karin (2021)
    Global concerns regarding bacterial antibiotic resistance demand prudent use of antibiotics in livestock production. Dairy production in the Nordic countries has a low consumption of antibiotics, while animal health, productivity and milk quality are at high levels. Here, we describe the basis of Nordic mastitis control and treatment strategies, as a model for production of high-quality milk with prudent use of antibiotics. We hope this will be beneficial for dairy producers and advisors in other countries and regions that consider limiting antibiotic use in cattle herds. In this perspectives paper we describe the dairy sector in the Nordic countries, and present regulatory aspects of antibiotic use, diagnostics and current guidelines for treatment of clinical mastitis as well as dry cow therapy. We also show summary statistics of udder health indicators in Denmark, Finland, Norway and Sweden, to illustrate the effects of the implemented udder health management practices.
  • Hemilä, Harri (1996)
    In 1971, Linus Pauling carried out a meta-analysis of four placebo-controlled trials and concluded that it was highly unlikely that the decrease in the "integrated morbidity of the common cold" in vitamin C groups was caused by chance alone (P < 0.00003). Studies carried out since then have consistently found that vitamin C (> or = 1 g/d) alleviates common cold symptoms, indicating that the vitamin does indeed have physiologic effects on colds. However, widespread conviction that the vitamin has no proven effects on the common cold still remains. Three of the most influential reviews drawing this conclusion are considered in the present article. Two of them are cited in the current edition of the RDA nutritional recommendations as evidence that vitamin C is ineffective against colds. In this article, these three reviews are shown to contain serious inaccuracies and shortcomings, making them unreliable sources on the topic. The second purpose is to suggest possible conceptual reasons for the persistent resistance to the notion that vitamin C might have effects on colds. Although placebo-controlled trials have shown that vitamin C does alleviate common cold symptoms, important questions still remain.