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 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 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 (, identifier CRD42020157144.
  • 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.
  • 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.
  • 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.