Clinical Oncology

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


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.]



Further articles in this publication

Clinical Oncology

[News from the World]

KLINIKAI Onkológia

Clinical Oncology

[Treatment of hepatocellular carcinoma - an update]


[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

[Treatment of locally advanced rectum cancer]

FRÖBE Ana, JURETIC Antonio, BROZIC Marić Jasmina, SOLDIC Zeljko, ZOVAK Mario

[Over the last several decades, local control (LC) for rectal cancer has markedly improved because of advances in surgical technique and the adoption of adjuvant or neoadjuvant chemoradiotherapy (CRT). Total mesorectal excision (TME) during surgical resection of localized rectal cancer, which involves removal of the entire circumferential perirectal tissue envelope, decreases rates of both involved surgical margins and local recurrences. Similarly, for patients with locally advanced rectal cancer (LARC), including T3 and T4 tumors and lymph node-positive disease, adjuvant and more preferably neoadjuvant CRT has exhibited the ability to both improve disease-free survival (DFS) and LC. Some patients undergoing neoadjuvant CRT achieve a complete pathologic response (pCR) to CRT and the oncologic outcomes are particularly favourable in this group. In contrast to improved local control, patients’ overall survival rates are in need of improvement, and the major factor limiting the outcome is the appearance of metachronous distant metastases. The main approach to overcome this issue is the escalation of systemic therapy in the neoadjuvant setting, e.g. by addition of induction or consolidation chemotherapy before or after neoadjuvant chemoradiotherapy (the so-called total neoadjuvant treatment, TNT, approach). The aim was to present a short overview of the role of radiotherapy and radiochemotherapy in the management of rectal cancer with a focus on current treatment stand wasards for locally advanced rectal cancer.]

Clinical Oncology

[The role of early clinical studies in oncology]


[Although the basic theory of the early development of different drug groups is identical, due to their various pharmacological characteristics the design of the studies, the starting safe dose and the selection of the pharmacologic and therapeutic end-points show signifi cant differences. The development process of drugs is usually divided into two functionally different parts, the learning and the confi rming phases, respectively. The aim of the fi rst part is the description of the suggested targets, the mechanism of action in humans and the characterization of the drug-linked biomarkers. This section contains the microdose (phase 0), phase I and II studies. The end-point of this part is the proof of the underlying concept which was developed on the basis of the non-clinical studies. According to the internationally accepted terminology, this strategically important point is called the Proof of Concept (POC). Upon POC it has to be decided whether the drug-candidate possesses those qualities which make it worthwhile to perform human phase III studies, treating the statistically required number of patients for proving the good therapeutic effi cacy and safety of the drug. This section of the drug development is called the confi rmatory phase. The use of highly sophisticated technology opened the possibility to apply microdoses in humans for studying the pharmacokinetics and pharmacodynamics of new drugs as well as the characteristics of human biomarkers at very low, harmless drug doses. This approach made possible to draw important conclusions on the usefulness of biomarkers for the clinical practice even following the fi rst drug-application. The planning of phases I and II studies, the calculation of the applicable doses, the selection of the pharmacologic and therapeutic end-points, the use of biomarkers, are all based on the concept of translational medicine and are essentially dependent on the results obtained both in animal experiments and human microdose studies.]

Clinical Oncology


A szerkesztők

All articles in the issue

Related contents

Clinical Oncology

[Resistancy and/or progression - Failure or only a short stop]


[Nowadays, with the continuously in creasing demand for targeted diagnostics and therapy, we are approaching an ideal stage when the most effective treat ment for a given patient could be selected. However, some basic problems are still waiting to be solved. One major hurdle is the heterogeneity, the formation of subclones with different signifi cance during progression, but with the capacity to overgrow after the failure of the initial therapy. The importance of this phenomenon is refl ected in the daily practice where targeted therapy is allowed to treat only locally extended or metastatizing tumors. Therefore, it is not as to nishing, that the clinical success is usually tem po rary, the disease in spite of the good response at the beginning will progress. The main reason is the resistancy against the carefully analysed and applied therapeutic drugs, which has several options (e.g. new mutations, crosstalks between pathways, faults of feed-backs, etc.). This review focuses on the acquired resistancy with some relevant examples. Among the open questions we can recall e.g. the resistancy in combination therapy, or the suggested link between resistancy and progression including the potential use of drug rechallenge.]

Lege Artis Medicinae

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

SZAPÁRY László, FEHÉR Gergely

[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.]

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]


[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.]

Clinical Oncology

[Fusions in solid tumors]


[Genetic fusions are the cosequence of genomic rearrangement including chromosomal inversion, interstitial deletion, duplication, amplifi cation, translocation. Fusions can influence tumor development and progression. Fusions fi rst discovered in hematological malignances (e.g. BCR-ABL), butlater more and more were identified dueto the higly sensitive NGS. It has been found that the oncogenic fusions are in minority in a given tumor. Today, some fusions were apprevedas targets (ALK, ROS1, PDGFB) by FDA. Asino ther targeted therapy resistance is in evitable, which is a very important challenge for newly designed drugs.]

Lege Artis Medicinae

[Change of resistance among Gram-positive bacteria]


[Physicians are faced with increasingly rapid emergence and spread of antibiotic resistant Gram-negative bacilli and, in particular, Gram-positive bacteria. It poses a major problem for hospitals and general practice as well. The article focuses on the change of resistance of four important and frequently occurring Gram-positive bacteria (Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus spp. and Streptococcus pneumoniae). Among the therapeutic choices recently introduced fluoroquinolones, oxazolidinones, streptogramins and ketolids are reviewed.]