Clinical Oncology

[EMT (Epithelial-Mesenchymal transition) – CSC (Cancer Stem Cells)]

KOPPER László

FEBRUARY 10, 2018

Clinical Oncology - 2018;5(01)

[The effi cacy of the antitumor therapy is usually limited due to the resistance against the chemotherapy. One of the most important reason of the secunder resistance is the intratumoral heterogeneity, which is the consequence of the variety tumor phenotypes in the same tumor. Such clonal heterogeneity develops during the tumor growth or tumor therapy. The cancer stem cells (CSC), according to the concept, can determine the progression of the tumor, including metastatization, which probably the major enemy for clinical oncology. This activity of CSC, in tumors with epithelial origin, is supported by a change from epithelial to mesenchymal phenotype (epithelial-mesenchymal transition); but not entirely. The CSC phenotype is very similar to characteristic of the normal stem cells, as resistance, self-renewal etc. The mechanisms of these concepts is known only partially, but the technical advances contribute to the identifi cation of key genetic and epigenetic regulatory pathways. If such improvement becomes real, we can be much ahead both with markers and therapeutic targets.]

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Further articles in this publication

Clinical Oncology

[Foreword]

A szerkesztők

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[News from the World]

KLINIKAI Onkológia

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[New results from San Antonio Breast Cancer Symposium, 2017]

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[SABCS 2017 has been a 40-year jubilee conference with festive appearance and content. The anniversary provides possibility to look back: today we fi nd the knowledge and practice as of twenty years ago schematic and rough while the changes are overwhelming. Therapy became colorful and personally. There is need for precisious care which means consideration all patient and tumor features when surgical or medical therapy, radiotherapy or even diagnostic issues are decided - this has been the most important message of the conference this year. The Symposium always provides the most modern and breakthrough approaches and attitude that support advancement in patient care.]

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[Treatment of hepatocellular carcinoma - an update]

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[Last time we have described about the modern treatment of hepatocellular carcinoma (HCC) in „Klinikai Onkológia” in 2014 (1) and a detailed guideline regarding epidemiology, treatment according to BCLC staging system has been published as well in a special edition in this year (2). Here, we discuss mainly the fi rst- and second line systemic treatment of HCC according to our experience and the new results of clinical trials. 203 patients were treated in our Department between 2010 and 2016. These results have been presented already on the MKOT conference in 2016. In this year we have started second line systemic therapy with regorafenib in 9 cases.]

Clinical Oncology

[Solid organ transplantation and malignancies]

VÉGSŐ Gyula, MÁTHÉ Zoltán

[Recent breakthroughs in the fi eld of organ transplantation and oncology have challenged existing views, and necessitate the revision of several tumor-related issues in transplantation. The need for expanding the donor pool raises the question of how and when it is plausible to transplant the organs of a donor with a history of cancer, such that the risk of tumor inoculation and manifestation due to the graft would be minimal for the recipient. Another point to consider is whether it is acceptable to transplant a recipient with a history of a malignant tumor, and if yes, how much tumor-free survival time is required as a minimum before the transplant. Transplanted patients live longer as a result of modern immunosuppressive therapy. However, the risk of malignant tumors increases proportionally to the length of the immunosuppressed state: their incidence may be as much as 20-30% in the long term. The signifi cance of „de novo” posttransplant tumors is highlighted by the fact that they are among the leading causes of death in transplant patients. Taken together, malignant diseases pose a serious problem from several aspects, the solution for which requires close teamwork of experts in oncology and transplantation, and the integration of up-to-date knowledge in the process of making a therapeutic decision, tailored individually for the patient.]

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[Risk estimates of advanced chronic kidney disease and predicting mortality in dialyzed patients]

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[In mostly the second part of the last decade lots of epidemiological study have been released about the progression of the chronic kidney disease (CKD) and theirs connection with the risk of death. The fact that lots of nephrologist from all over the world (from Canada to New-Zealand) are pretty much interested in this topic is absolutely proved by national (REIN Study – French Registry) and international (KDIGO Controversies Conference, DOPPS 1-5, or the European AROII Study) researchers with these epidemiological questions in their focus. The risk estimation facts that are able to show the life expectancy of patients with CKD 3-5 (expected time to dialysis or mortality risk before renal replacement therapy – RRT) and the early or hopefully longer survival odds of the dialyzed ones could be very useful not only for the medical stuff but also for the patients. In case of the predialyzed patients the focus has to be on the Bansal score and also on the Kidney Failure Risk Equation (KFRE) scores (with 4 and 8 variable); on the other hand in dialyzed patients the REIN score that prognose a short-term survival and the Cohen model (both are easy calculated with webcalculators) are in the highlight of importance. There is not a big difference (2- 7%) in validated researches between the prognosed and the real survival dates. Despite of this prediction has to always be evaluated individually in favour of the best decision we can make for the patients and in order to choose the right treatment: conservative therapy, dialysis or transplantation.]

Hypertension and nephrology

[Infections associated to vesicoureteral reflux disease in children below 1 year of age: the infulence of continuous antibiotic prophylactic therapy on the prevalence of resistant pathogenic bacteria]

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[Background: The primary goal when children with vesicoureteral reflux disease (VUR) are treated is the prevention of pyelonephritis and persisting renal damage. Continuous antibiotic prophylaxis (CAP) is usually applied to reach this aim. The selection of resisting pathogens is the major risk of CAP. The aim of our survey was to describe the patterns of pathogenic strains leading to pyelonephritis in patients treated with and without CAP. Patients and method: The pathogenic strains implicated in pyelonephritis were identified in 48 and 56 children below 1 year of age who were treated with or without CAP, respectively, between years 2006 and 2011. Results: Breakthrough urinary tract infections developing in the presence of CAP are more frequently (with about a double risk) caused by polyresistant bacteria compared to infections that emerged without CAP. Nevertheless, it should be noted that the prevalence of resistant pathogens was about 40% even in infants without CAP. Discussion: The pattern of pathogenic strains leading to pyelonephritis alters significantly even in the cohort of children below 1 year of age treated with CAP to prevent infections associated to VUR. The risk may be decreased through the rational use of antibiotics. To reach this goal national guidelines on VUR should be updated and the role of additional non-antibiotic treatment should be established.]

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KOPPER László

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[Mechanisms of metastasis formation as potential therapeutic targets]

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[The end-stage of the tumor progression is the development of the metastatic disease. The biological basis of this progression is well known, however the exact molecular background of it is not. In this process the metastatic cancer cells develop maximal adaptation to extreme environmental clues and collaborative potential with wide array of host cells, accordingly the metastatization takes place in an organ specific manner. The metastases are different from the primary tumor but from each other as well, and this true for their genetic background as well. The ultrasensitive monitoring of this process is possible with the use of liquid biopsy and molecular tests. Till we don’t have organ metastasis specific therapeutic modalities similarly to bone metastases, the available modalities must be fine-tuned for metastatic disease and not for the primary tumor. ]

Lege Artis Medicinae

[Examination of the efficacy of clopidogrel-hydrogen-sulphate in patients with cerebrovascular disease]

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[INTRODUCTION - On the basis of current guidelines, acetylsalicylic acid plus dipyridamole or clopidogrel monotherapy should be used for the long-term treatment of patients with cerebrovascular disease, whereas acetylsalicylic acid monotherapy is not recommended. The efficiency of recently introduced generic clopidogrels has not been assessed in patients with a history of acute stroke. PATIENTS AND METHODS - 100 patients with a history of acute stroke or transient ischaemic attack were involved in our study. The patients received acetylsalicylic acid monotherapy in the first 48 hours, followed by clopidogrel-hydrogen sulphate (Egitromb®) monotherapy. The efficiency of the therapy was assessed on day 7 and 28 of medical therapy. RESULTS - At the first measurement (day 7) after clopidrogel-hydrogen sulphate treatment, the therapy seemed to be inefficient in 11 patients (11%). A strong, clinically significant correlation was found between blood pressure values, blood glucose and lipid parameters, hsCRP levels and platelet aggregation values. At the second measurement (day 28), an aggressive secondary preventive threapy resulted in the normalisation of the above mentioned parameters, and the efficiency of platelet aggregation inhibtion therapy was also improed, whereas no patients proved to be resistant. No unwanted events or haemorrhagic complications were registered. CONCLUSIONS - On the basis of the result of our study, treatment with clopidogrel- hydrogen sulphate is safe and efficient both clinically and on the basis of optical aggregometry. The significance of an aggressive secondary preventive therapy should be considered as a factor that might influence the efficiency of thrombocyte aggregation inhibitory therapy.]