[Oral cancer screening: what can the healthcare system do to reduce the burden of disease?] / Szájüregi daganatszurés: mit tehet az egészségügyi ellátórendszer a betegségteher mérsékléséért?

Due to its high incidence and mortality, oral cancer makes a group of diseases of public health importance. Oral screening is a simple three-step procedure: the first step is questioning the patient about his/her smoking/drinking habits, secondly, visual inspection of the oral cavity, and finally, palpation of regional lymph nodes. If precancerous conditions or any form of oral cancer are suspected, the task is to send the examined person to oral clinical care. The examination can routinly be performed by dentists, but also by general practitioners and occupational health personnel. The difficulty of oral screening arises from the fact that most of the patients are of low socio-economic status. The organization of oral screening is the responsibility of the healthcare system personnel: their task is to identify the high-risk persons and to direct them to the scene of the screening. Orv Hetil. 2023; 164(38): 1497-1505.

Ancient schwannoma of the cauda equina. / A cauda equina "ancient" típusú schwannomája.

Összefoglaló. A cauda equina daganatai a leggyakrabban lumbagós panaszokkal jelentkeznek. Általában késoi stádiumban ismerik fel oket, mivel lassan növekednek, az anatómiai környezet tágas, a megjeleno tünetek nem specifikusak, valamint az érintett betegek többsége fiatal és egyébként egészséges. Jelen közleményünkben egy ritka variáns, a cauda equinát érinto "ancient" típusú schwannoma esetének kórtörténetét és kezelését mutatjuk be. Mutéti ellátás során a daganat totális eltávolítása történt, ezt követoen a beteg panaszai megszuntek. Ezen daganat klinikai kimutatását preoperatív T1-, T2-súlyozott MRI tette lehetové, a pontos diagnózist azonban az eltávolított daganat patológiai szövettani feldolgozása biztosította. Irodalmi áttekintésünk alapján a cauda equinában ez a szövettani altípusú schwannoma kifejezetten ritka: nemzetközi szinten 3 ilyen publikált eset jelent meg, magyar nyelvu közlést a témában azonban nem találtunk. Orv Hetil. 2022; 163(5): 195-200. Summary. Tumors of the cauda equina generally present with lower back pain. They are usually recognized at a late stage as they grow slowly, the surrounding anatomical environment is spacious, the symptoms that appear are not specific, and the majority of the affected patients are young and otherwise healthy. In this paper, we present the diagnosis and treatment of a young male patient who has undergone the surgical removal of an ancient schwannoma of the cauda equina. During the operation, the tumor was completely resected, and following that the patient's complaints disappeared. The key point to an accurate diagnosis of this kind of tumor before the operation was the appropriate radiological study, i.e., T1-, T2-weighted MRI, and postoperatively the histological processing of the removed neoplasm. Reviewing the literature, this pathological type of schwannoma appeared to be extremely rare in the cauda equina: so far, only three cases have been published internationally, however, we could not find a single paper in the Hungarian medical literature on this topic. Orv Hetil. 2022; 163(5): 195-200.

[Anticancer drug research in Hungary, 1950-2000]. / Daganat-kemoterápiás kutatások Magyarországon az 1950−2000 közötti években.

The present review about the history of anticancer drug research in Hungary intends to call attention to the importance of studies on their mode of action. Several lines of evidence suggest that clinically usable oncopharmacological properties could be revealed by this way. Among the numerous compounds certain alkylating sugar alcohols and 2'-deoxyuridine derivatives were submitted to detailed investigations concerning their mode of action. Myelobromol with selective action on the myeloid elements of bone marrow has been justified for its application in chronic myeloid leukemia therapy and also in bone marrow ablation before transplantation. Mitolactol is able to cross bloodbrain barrier, consequently could control certain brain tumors. 5-etil-2'-deoxyuridine by reducing dihydropyrimidine dehydrogenase activity is able to increase 5-fluorouracil concentration in the blood, resulting in improved antitumor effect. In contrast, 5-hexil-2'-deoxyuridine, as an inhibitor of glycoconjugate pathway by reducing heparan sulfate production, has the ability to prevent metastasis. Noteworthy, the remarkable effects of vinca alkaloids, antiestrogens, and GNRH analogues were also presented in this review.

[Barrier- and autophagic functions of the intestinal epithelia: role of disturbances in the pathogenesis of Crohn's disease]. / A bélnyálkahártyahám barrier- és autophagiás funkciózavarainak szerepe a Crohn-betegség patogenezisében.

Crohn's disease is a widely known debilitating chronic inflammatory disease, mostly affecting terminal ileum and/or colon. Epidemiological, familial and twin studies suggest that genetic factors play an important role in susceptibility to the disease. Clinical observations suggest that ill-defined environmental factors also play a part. Advances in molecular genotyping technology, statistical methodologies, bioinformatics and the combined use of them in genome wide scanning and association studies resulted in the identification of more than 30 susceptibility genes and loci associated with Crohn's disease and revealed and highlighted a number of new previously unsuspected pathways playing a role in the pathogenesis of Crohn's disease. Close association of the disease with polymorphisms in the genes encoding the pattern recognition receptors particularly the NOD2 protein, the Wnt pathway transcription factor Tcf4 (also known as TCFL2) and the autophagic regulator ATG16L1 have been found. The polymorphisms involved are associated with decreased defensin production (defensin deficiency) which can lead to changes in the composition of the commensal microbial flora, defects in the intestinal barrier functions and bacterial invasion of the mucosa. Other recently recognized consequences of the polymorphisms involving the genes encoding NOD2 and ATG16L1 proteins are that the truncated NOD2 protein is unable to induce autophagy and this protein, just like the ATG16L1 T300A mutant protein, leads to failure adequately to destroy phagocytosed bacteria. The consequence is persisting low level infection, chronic intestinal inflammation, tissue injury and the clinical symptoms of the disease. Thus, Crohn's disease can be seen to be caused by defects in the innate immune defense, in particular defects in bacterial processing and clearance. The accumulated evidence suggests that Crohn's disease is associated with an exaggerated adaptive immune response to the persisting intestinal microbes in genetically susceptible hosts. Intervention in these circumstances should probably be geared to strengthening of the innate immune responses rather than simple attempts to suppress adaptive immunity.

[Host defense peptides and peptidomimetics as new weapons for cancer treatment]. / Gazdavédo peptidek és peptidomimetikumok, mint a rákterápia potenciális új eszközei.

Host defence peptides (HDP) produced by almost all species of living organisms and widely recognized as antimicrobial antibiotics have also proved to be capable of killing a wide variety of cancer cells. In this respect they have many advantages over conventional cytotoxic chemotherapeutic agents. They seem to kill cancer cells by effects on plasma membranes and/or the membranes of mitochondria. They are often effective against multidrug-resistant cells. They have a broad spectrum of activity in that their killing effects are not restricted to particular kinds of cancer. Above all they commonly have few side effects in that they do not have the same detrimental effects on normal cells as they do on cancer cells. It has been demonstrated that HDP can be used as effective adjuvants to conventional chemotherapeutic agents. In addition they have effects on neo-angiogenesis which is important in relation to tumour growth. HDP have been shown to be powerful immunomodulators in a number of circumstances and in this respect they are believed to be instrumental in strengthening immunological host defence against cancer cells. Importantly it has also been shown that certain HDP have the capability to alter the capacity of cells to import Ca ions by affecting the location and thus function of calreticulin. Such changes it has been argued are significant in facilitating the killing of tumour cells by immunogical means. HDP constitute a novel class of anticancer agents for which, as we develop better knowledge of their pharmacokinetic profiles and learn better how to tailor their administration, hold high promise to augment or even replace the currently available cytotoxic anticancer chemotherapeutic agents most of which owe their efficacy to their capacity to bind to and damage target cell DNA.

[Role of antimicrobial peptides (AMP) and pattern recognition receptors (PRR) in the intestinal mucosa homeostasis]. / Az antimikrobiális peptidek és a mintázatfelismero receptorok szerepe a bélrendszer homeosztázisának fenntartásában.

Homeostasis and integrity of bowel mucosa is assured by well controlled mechanical, biochemical and immunological mechanisms. First line of defense is presented by the antimicrobial peptides (AMP), which form a continuous layer on the bowel surface, produced by intestinal specific (Paneth) and non-specific epithelial cells. AMPs have a significant antimicrobial, antifungal and antiviral, as well as immunomodulatory effects. Next line of defense is the pattern recognition receptors (PRR), which allows identifying conservative molecular patterns of different pathogens, and starts antimicrobial and inflammatory mechanisms through gene-expression induction. We review the most recent knowledge and studies concerning these mechanisms.

[Characteristics of the main groups of human host-defensive peptides]. / Egyes humán gazdavédo peptidek jellegzetességei.

In humans the three main groups of antimicrobial peptides are the defensins, the cathelicidins and the histatins. They differ widely in their biochemical properties and in the spectrum of their antimicrobial activities. For quite a while they were regarded only as new-type antimicrobial agents. Recent studies revealed, however, that functions of these peptides extend far beyond their antimicrobial activities. They were shown to be implicated in a remarkably broad range of other - likewise host defence related - biological processes. They proved to be important components of the innate immune system. Furthermore it was also shown that they interact with various receptors on the immature dendritic cells and lymphocytes resulting in the activation of adaptive immune responses, in which they were shown to play further immunomodulatory roles, too. Pertaining LL-37 it has even been proposed that it has more potent immunomodulatory activities than antimicrobial function. Human alpha-defensins were shown to be active across species in mice and to have immunoadjuvant effects. Recently numerous papers have been reported on studies providing abundant evidences that several diseases in humans are characterized by impairment in the function of these small host defensive peptides. The recognition of the multifunctional role of these peptides further raised the interest of the pharmaceutical industry toward them.

[Physiologic and pathophysiologic significance of antimicrobial (host defensive) small peptides]. / Az antimikrobiális (gazdavédô) kis peptidek élettani és kórtani jelentôsége.

Antimicrobial peptides are typically small cationic and amphiphilic molecules, which exhibit a wide spectrum of antimicrobial activity. These peptides are seen as an important and ancient mechanism of defence for most living organisms. Some of these peptides are produced constitutively whereas others are induced by exogenous microbial products or by proinflammatory cytokines. The antimicrobial peptides differ widely in their biochemical properties, but typically they act directly against microbes through a mechanism involving membrane disruption and pore formation leading to leakage of cell content and cell death. In human beings the defensins, cathelicidins and histatins are the principal antimicrobial peptides. They are found in neutrophils, in some other white blood cells and in the epithelium of every major organ system examined. Recent studies revealed that, beyond antimicrobial activity, the antimicrobial peptides are involved in a remarkably broad range of host defence related functions including neutralisation of some bacterial toxins and augmentation of both innate and adaptive immune mechanisms. Since several of them have proved to be effective against antibiotic resistant bacteria, these peptides are being widely used as blueprints for the design of new antimicrobial agents.

Fermented wheat germ extract (avemar) inhibits adjuvant arthritis.

Anti-inflammatory efficacy of the fermented wheat germ extract (FWGE, Avemar) in the rat adjuvant arthritis (AA) model was examined. To Wistar rats with AA, different doses of FWGE and anti-inflammatory drugs (indomethacin, dexamethasone) as monotherapies were administered and FWGE and either diclofenac or dexamethasone were also given in combination. Besides plethysmographies of the paws, histological investigations of synovial tissues were also performed along with detection of CD4+ and CD8+ T lymphocytes. Gene expressions of COX-1 and 2 were determined by real-time polymerase chain reaction (PCR). FWGE monotherapy significantly inhibited the development of the secondary (immune-mediated) response in AA, and dexamethasone and indomethacin exerted inhibitory effects in a degree comparable to that of FWGE. Histological analysis of the affected joints confirmed the results. FWGE inhibited COX-1 and -2, while indomethacin enhanced COX-2 gene expressions. FWGE had an additive interaction with diclofenac. It is concluded that FWGE has significant anti-inflammatory efficacy confirmed by plethysmography, histology, and real-time PCR.

A path or a new road in laboratory diagnostics? Biological mass spectrometry: facts and perspectives.

Proteins in tissues and biofluids and their many attributes define the proteome. Proteome can be directly correlated to known diseases and histological regions allowing the diagnosis and monitoring of disease progression as well predicting the patient's response to specific treatments. Proteomics performs large-scale, high-throughput characterization of the human proteome, among others by biological mass spectrometry. Proteinchip technology coupled with bioinformatics is able to screen any protein source for putative disease biomarkers from a small sample volume (microliter range) by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). This article discusses on a basic level both the technology and reliability of these methods.

Platelet-mimicry of cancer cells: epiphenomenon with clinical significance.

Stem cell mimicry of cancer cells has been known for a long time and is considered to be responsible for ectopic gene expressions. The stem cell characteristics of tumor cells are shown to be involved in epithelial-mesenchymal transition and in the phenomenon of vascular mimicry. Certain cancer types acquire a geno-phenotype closely resembling the platelets and express several megakaryocytic genes (adhesion receptors alpha IIb beta 3, thrombin receptor and PECAM/CD 31 and/or platelet-type 12-LOX) able to activate the coagulation cascade or the platelets themselves. Here we define these potentials as platelet mimicry of cancer cells typical of pancreatic, breast, prostate, colorectal and urogenital cancers and melanoma. Data all support that platelet mimicry of certain cancer types is an important factor in their hematogenous dissemination and provides an attractive therapeutic target. Besides the long-available preclinical data, clinical trials have only recently provided evidence that targeting platelet mimicry of cancers is an efficient way to prevent tumor progression. The systematic discovery of the markers of platelet mimicry in various cancer types and their molecular targeting may provide new supportive therapeutic modalities for the management of the progressing disease.

Proteoglycans and tumor progression: Janus-faced molecules with contradictory functions in cancer.

Understanding the details of the molecular mechanism of tumor dissemination revealed that several proteoglycan species are involved in the process but their role can be described as Janus-faced. One level of proteoglycan alterations is at the expression of their genes coding for the core protein. Characteristically, in progressing tumors two patterns emerged: loss or neoexpression of surface proteoglycans (PG) depending on the initial expression pattern of the cell type of origin. The situation is similarly complex concerning the changes of glycosaminoglycan (GAG) of the PG during tumor progression. This is due to the fact that the majority of PGs involved is hybrid molecule meaning that their core protein can be glycanated both with chondroitin and heparan sulfate. However, such an alteration in glycanation of PG may fundamentally change the function of the molecule, especially the one operating at the cell surface. Among the extracellular PGs, decorin emerged as inhibitor of progression while perlecan as a promoter of the process. Analysis of the available data indicate that during metastatization tumor cells must express at least one cell surface HSPG species from the syndecan-glypican-CD44v3 group. Furthermore, the HS-chain of these proteoglycan(s) carry important molecular signatures (suphution or epimerization patterns). Experimental data suggest that tumor cell surface heparan sulfate (PG) may provide a target for specific anti-metastatic interventions.

Role of elastin-matrix interactions in tumor progression.

Data from the literature now indicate that cancer cells can specifically interact with the unique extracellular matrix protein, elastin. The interaction is mediated by two elastin-binding proteins (EBP), S-gal/EBP (organized into the elasin receptor/elastonectin complex) and galectin-3, components of two laminin receptors. Studies revealed that the expression of both EBPs is closely associated to the invasive/metastatic potential of various cancer types. This is due to the fact that elastin-ligation of S-gal/EBP induces motogenic, as well as mitogenic signals and releases various elastases from cancer cells and the induction depends on the metastatic potential. Studies also demonstrated that certain cancer cells can synthesize elastin and express lysyl oxydase, providing explanation for frequent appearance of elastic tissue in tumors such as breast or gastric cancers. Clinico-pathological data suggest some correlation with tumor progression of the presence of the elastic tumor stroma. Since elastic tissue may be a significant reservoir of angiostatic molecule(s) this extracellular matrix protein can also have a role in tumor-induced angiogenesis. Soluble elastin as well as elastin peptides are potent inhibitors of the metastatic process in experimental tumor models. On the other hand, elastin peptides can also be used to design targeted therapies exploiting the unique physicochemical nature of this matrix protein. Altogether, these data suggest a significant role for tumor cell-elastin interactions in tumor progression.

Marker Enzymes of Rat Chemical Hepatocarcinogenesis in Human Liver Tumors.

Reduced glucose-6-phosphatase, increased GGT activity and reduction of cytochrome P-450 content are considered to be markers of chemical hepatocarcinogenesis in rats. The significance of these changes were studied in certain human liver lesions; adenoma, focal nodular hyperplasia and hepatocellular carcinoma all developed in non-cirrhotic livers. Enzymes showed normal values in 4 out of 5 adenomas, in 2/13 FNH and in 4/18 HCC samples. The decreased cP-450 content in HCC proved to be the most consistent alteration (12/18). Only 3 HCC samples possessed changes off all enzymes. These data suggest that at least those enzymes which are used as markers in rat chemical hepatocarcinogenesis have little or no biological significance in human liver tumors, primarily due to the intertumoral heterogeneity of enzyme activity. Such heterogeneity was observed in the peritumoral "normal" liver tissue, too.

Modification of Acute and Chronic Liver Damage by Thiazolidine Compounds.

As high sulfhydril levels were shown to reduce the action of agents causing tissueinjury, increasing glutathion concentrations may have cytoprotective potential. In this study the hepatoprotective effects of several derivatives of 4carboxy5,5dimethyl thiazolidine, a modulator of glutathion metabolism were studied in rat liver damaged with CCl4. It was found that 4(S) carboxy 5,5dimethyl2 (5'nitro2furyl) thiazolidine (dimethylthiazolidinenitrofuran: DTNF) had the most significant hepatoprotective action; therefore it was subjected to detailed investigation in various models for acute and chronic liver injury. This compound was shown to ameliorate allylalcohol induced liver injury in rats, galactosamine induced hepatitis of mice and CCl4 induced chronic liver damage in rats. Our study on protein synthesis in primary hepatocyte suspension culture showed that cell injury induced by CCl4 could be reduced in the presence of this thiazolidine compound.

Ameloblastoma de células granulosas. Contribución al estudio de su ultraestructura / Granule-cells ameloblastome. A contribution to the study of its ultrastructure

Se presenta el estudio de un caso de ameloblastoma de células granulosas. La lesión objeto del estudio fue obtenida de un hombre blanco de 53 años de edad, a quien se le realizó estudio por microscopia óptica y electrónica. Para el estudio con el microscopio óptico el espécimen fue fijado en formalina neutra al 10 porciento, procesado por la técnica de inclusión en parafina y coloreado con hematoxilina y eosina, mucicarmín, ácido peryódico de Schiff y plata de Gomory. Para el estudio por microscopia electrónica, el tejido fue fijado en glutaraldehído al 2,5 porciento a pH 7,4 y posfijado en tetróxido de osmio al 2 porciento, fue coloreado con uranil acetato, y observado con un microscopio electrónico JEM 100B(AU)