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Lege Artis Medicinae

DECEMBER 21, 2020

[History of vaccine production in Hungary ]

ÓCSAI Lajos

[This study presents the complete history of the Hungarian vaccine production, partly in association with the process of fighting vaccine-preventable infectious diseases, and underlines the fact that every government actively contributed to the age-adjusted mandatory vaccination schedule of the past 140 years. It demonstrates the various achievements from the smallpox lymph production through the launch of diphtheria serum production at Phylaxia and the establishment of the National Public Health Institute (OKI) with its vaccine production and the later institutional transformation of OKI into Humán as economic corporation to its closure. Among all OKI’s vaccine production activities, this study focuses on the production of influenza vaccines, due to its international importance in the 1960s and 1970s. The vaccine production against diphtheria tetanus and pertussis stands out from Humán’s activities, and the tetanus component of this vaccine is still used in the products of a multinational vaccine manufacturer. ]

Lege Artis Medicinae

DECEMBER 21, 2020

[Risk of nonsteroidal antiinflammatory drugs. Focus on aceclofenac]

FARSANG Csaba

[Nonsteroidal antiinflammatory drugs (NSAIDs) are among the most frequently used pharmaceuticals. Nevertheless, a number of studies emphasized that NSAIDs were damaging not only the gastrointestinal (GI), but also the cardiovascular (CV) system, could increase the blood pressure, the frequency of coronary events (angina, myocardial infarction) and stroke incidence, as well as they might deterio­rate renal functions. The National Institute for Health and Care Excellence (NICE) did not find evidence that administering NSAIDs could increase the risk of developing COVID-19 or worsened the condition of COVID-19 patients. However, unwanted effects of specific drugs differ substantially in their occurrence and seriousness as well. It seemed to be for a long time that the NSAIDs provoked higher GI-risk was closely related to the COX1/COX2 selectivity, like the cardiovascular (CV) risk to the COX2/COX1 selectivity, however, the recent data did not prove it clearly. Based on the available literature while pondering the gastrointestinal and cardiovascular adverse events, among all NSAIDs the aceclofenac profile seemed to be the most favourable.]

Clinical Oncology

APRIL 30, 2020

[Biological clock and cancer]

VELLAINÉ Takács Krisztina, SZTANKOVICS Dániel, HOFFMANN Gyula, KOPPER László, GÁLOSI Rita

[In the present paper, we are giving a review about the circadian rhythm of the biological rhythm, its regulation and relation to tumorigenesis. The circadian rhythm is an approximately 24-hour cycle in biochemical, physiological processes in organisms from unicellular to vertebrates. This biological rhythm is generated by the synchronization of our endogenous clocks and the light as the main “Zeitgeber”. The nucleus suprachiasmaticus (SCN) of the hypothalamus is the region, which is considered to be the circadian “main clock” of the organism and is responsible for coordinating peripheral clocks in different organ systems. At the cellular level, the regulation of the circadian rhythm is basically provided by the so-called “circadian locomotor output cycles kaput” the CLOCK genes. The discovery of those cellular mechanisms was awarded with Nobel Prize in 2017. The CLOCK genes, acting on other effector genes, regulate diurnal rhythm of protein synthesis. More and more data are available, which suggest that there is an association between circadian genes and tumor development. Furthermore, many studies show a link between the shift work and the development of breast and prostate cancer and between mutations in some circadian genes and development of carcinomas. More data suggest a relationship between tumor metabolism and CLOCK genes and their regulations. Based on all these data, the circadian rhythm, so the time of day, may need to be taken into account during cancer therapy.]

Clinical Oncology

APRIL 30, 2020

[Coronavirus pandemic – new challenges in oncotherapy]

MINÁROVITS János

[This review outlines some of the basic observations related to coronaviruses infecting animals and describes – in a nutshell – the characteristics of human coronaviruses causing mild or severe respiratory diseases in infected individuals. A special attention is given to SARS-CoV-2, the causative agent of the current coronavirus disease (Covid-19) pandemic, and to the pathomechanism of severe acute respiratory syndrome (SARS) which is also accompanied with multiorgan failure in a subset of infected patients. Recently discovered unique molecular features of SARS-CoV-2 are described as well. These molecular cues may affect human to human virus transmission whereas they are absent, remarkably, from the other lung-targeting highly pathogenic human coronaviruses (SARS-CoV-1 and MERS-CoV) which did not spread all over the world. The possibilities of active immunization to prevent SARS-CoV-2 infection and the development of selective small molecule inhibitors curbing the replication of the virus are also touched upon. The review closes with a few remarks regarding the Hungarian and international recommendations concerning the treatment of SARSCoV- 2 infected cancer patients.]

Clinical Oncology

APRIL 30, 2020

[Immunotherapy of hepatocellular carcinoma]

DEMETER Gyula

[The systemic treatment of HCC was based exclusively on sorafenib near 10 years. In the past 2-3 years some new molecules demostrated their effectivites in phase III clinical trials. So the immuncheckpoint-inhibitors (ICI) demands their place in systemic treatment of HCC. Nivolumab and pembrolizumab are recommended already in second line in NCCN and ESMO clinical guidelines. Nivolumab demostrated his effectivity against the standard treatment sorafenib in a phase III clinical trial, although the results were not signifi cant. However, the combination treatment of atezolizumab and bevacizumab seems better than sorafenib in a phase III clinical trial, so the combination is recommended already in fi rst line in the NCCN guideline. There are more clinical trials with ICIs in progress as in monotherapy as in combination therapy with other modalities.]

Clinical Oncology

APRIL 30, 2020

[Hormone replacement therapy in cancer survivors – Review of the literature]

DELI Tamás, OROSZ Mónika, JAKAB Attila

[Rapid advance in oncology leads to increasing survival of oncologic patients. More and more of them live long enough to reach either the natural age of menopause or, as a side effect of their oncotherapy, experience the cessation of gonadal function, leading to premature ovarian insuffi ciency, with disturbing vasomotor symtoms and long-term negative cardiovascular and skeletal effects. Thus, an ever increasing number of cancer survivors search endocrinologic help in the form of hormone replacement therapy (HRT). The misinterpretation of the WHI (Women’s Health Initiative) Study has lead to an irrational fear of female hormone replacement, both by the general population and medical professionals. It has seemed the logical and safe conclusion to many physicians to avoid HRT, supposing that this attitude defi nitely causes no harm, whereas the decision of prescribing estrogen alone or with progestins might bear oncologic and thromboembolic risks and may even lead to litigation in case of a potentially related complication. However, it was known even before the WHI results that premature menopause and hypogonadism decreases the life expectancy of women by years through its skeletal and cardiovascular effects, and this negative effect correlates with the length of the hypoestrogenaemic period. Yet, the oncologic risk of HRT is extremely diffi cult to assess. In this work we review the latest evidence from in vitro experiments to clinical studies. We group tumours regarding the oncologic risk of properly chosen female hormone replacement therapy in cancer survivors as follows: ’HRT is advanageous’ (e.g. endometrial cancer type I, cervical adenocarcinoma, haematologic malignancies, local cutaneous malignant melanoma, colorectal cancer, hepatocellular cancer); ’HRT is neutral’ (e.g. BRCA 1/2 mutation carriers without cancer, endometrial cancer type II, uterinal carcinosarcoma and adenosarcoma, certain types of ovarian cancer, cervical, vaginal and vulvar squamous cell carcinoma, prolactinoma, kidney cancer, pancreatic cancer, thyroid cancer); ’HRT is relatively contraindicated’ for various reasons (e.g. leiomyosarcoma, certain types of ovarian tumours, brain tumours, advanced metastatic malignant melanoma, lung cancer, gastric cancer, bladder cancer); ’HRT is diasadvantageous and thus contraindicated’ (e.g. breast cancer, endometrial stroma sarcoma, meningioma, glioma, hormone receptor positive gastric and bladder cancer).]

Clinical Oncology

APRIL 30, 2020

[Development and 10-year history of a biosimilar: the example of Binocrit®]

AAPRO Matti, KRENDYUKOV Andriy, HÖBEL Nadja, SEIDL Andreas, GASCÓN Pere

[Patent expirations for several biological products have prompted the development of alternative versions, termed ‘biosimilars’, which have comparable quality, safety and effi cacy to a licensed biological medicine (also referred to as the ‘reference’ medicine). The fi rst biosimilars developed in oncology were the supportive-care agents fi lgrastim and epoetin. Binocrit® (HX575) is a biosimilar version of epoetin alfa, indicated in the oncology setting for the treatment of chemotherapy-induced anemia (CIA). The process for development and approval of Binocrit® as a biosimilar included extensive analytical characterization and comparison with the reference epoetin alfa. This was followed by a clinical development program comprising phase I pharmacokinetic/pharmacodynamic studies to show bioequivalence to the reference medicine and a confi rmatory phase III study to confi rm therapeutic effectiveness in CIA. Since its approval, Binocrit® has been extensively used and studied in real-world clinical practice. The accumulated data confi rm that Binocrit® is an effective and well-tolerated option for the treatment of CIA in patients with cancer.]

Clinical Oncology

APRIL 30, 2020

[Molecular residual tumor monitoring in solid cancers]

SZÁSZ A. Marcell, TOBIÁS Bálint, KÓSA János, LAKATOS Péter

[Blood-based diagnostics has long been used in the oncological practice of solid tumors, but its full potential is just unfolding recently. Quantitative measurement of tumor markers, circulating tumor cells, and some of their products or components have now become available and are part of a multimodal system that provides additive parameters in clinical decision making. The most challenging oncological questions can be answered by the detection, characterization and measurement of circulating free DNA (cfDNA), which, due to its growing importance, bears the potential of incorporation into routine practice. In this overview, we review the „blood impressions” of solid tumors and present the most promising results in different patient groups, especially in lung, breast, colon, and bladder tumors, which are also valid for other solid tumors.]

Clinical Oncology

APRIL 30, 2020

[Tumor induction by chemotherapy]

[Without chemotherapy, the fi ve-year survival rate of detected cancers would be between 0 and 15%, depending on the tumor, and between 17 and 85% with current therapy. Several warnings call attention to the dangers of chemotherapy-induced side effects, most notably the potential for tumor-inducing ability, which can affect 5-10% of patients who have recovered beyond fi ve years. Some systematically applied drugs used in chemotherapy (alkylating agents, etoposide, arsenic trioxide) are able to cause mutations in healthy cells of the patients, increasing the likelihood that the mutated cells will start a later (secondary) tumor formation. In addition to mutagenic effects, some chemotherapeutic agents exert their effects on normal myeloid and epithelial cells of the body, which, by altering the tissue microenvironment, create the potential for malignant transformation. Tumor-associated macrophages (TAMs), which can alter gene expression patterns by tumor cell secreted factors and promote the survival and invasiveness of tumor cells by pro-carcinogenic signals, are very important in this process. It is of utmost importance that doctors, pharmacists, technicians and nurses working with cancer-causing materials do not come into direct contact with dangerous substances and wear appropriate protective equipment.]

Lege Artis Medicinae

NOVEMBER 30, 2020

[A short chronicle of three decades ]

KAPRONCZAY Katalin

[Hungarian professional periodicals started quite late in European context. Their publish­ing, editing and editorial philosophy were equally influenced by specific historical and political situations. Certain breaking points of history resulted in termina­tion of professional journals (War of In­de­pendence 1848-1849, First and Se­cond World Wars), however there were pe­riods, which instigated the progress of sciences and founding of new scientific journals. Both trends were apparent in years after the fall of former Hungarian regime in 1990. The structure of book and journal publishing has changed substantially, some publishers fell “victim” others started successfully as well. The latters include the then-established publishing house Literatura Medica and its own scientific journal, Lege Artis Me­di­cinae (according to its subtitle: New Hun­garian Medical Herald) issued first in 1990. Its appearance enhanced significantly the medical press market. Its scientific publications compete with articles of the well-established domestic medical journals however its philosophy set brand-new trends on the market. Concerning the medical community, it takes on its problems and provides a forum for them. These problems are emerging questions in health care, economy and prevention, in close interrelation with system of public health institutions, infrastructure and situation of those providing individual health services. In all of them, Lege Artis Medicinae follows consequently the ideas of traditional social medicine.]