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Clinical Oncology

FEBRUARY 28, 2020

[Role of infl ammation in the carcinogenesis]

KOPPER László, TÍMÁR József

[Chronic infl ammation is an important promoter of the carcinogenesis of several cancer types and also an important contributor to mutagenicity beside the known carcinogens. Beside the continous regeneration of the affected epithelia chronic infl ammation provide a special microenvironment intra and extracellular environment which support malignant transformation and block emerging immune reactions. On the other hand, cancer is generating chronic infl ammation itself independent from its role in the carcinogenic process. It is due to cancer necrosis as well as to the production of infl ammatory cytokines. Cancer-induced infl ammatory reactions block antitumoral immune responses and continous monitoring of this process provide valuable clinical parameter of cancer progression.]

Clinical Oncology

DECEMBER 30, 2019

[Chemicals and tumors]

MARCSEK Zoltán

[Tumorigenesis is driven usually by non-lethal genetic alterations such as malfunctioning regulatory systems; mainly by inactivating suppressor genes or activating proto-oncogenes or malfunctioning of apoptatic system or decresed activity of the DNA repair system. Several chemicals induces mutations in the regulatory genes forces the cell for continous divisions increasing the chance of accumulation of further mutations. Chemicals, inducing mutations (mutagens) increase the rate of tumor occurrence, are carcinogens.]

Clinical Oncology

FEBRUARY 20, 2019

[Molecular subtypes and the evolution of treatment decisions in metastatic colorectal cancer]

RODRIGO Dienstmann, RAMON Salazar, JOSEP Tabernero

[Colorectal cancer (CRC) has clinically-relevant molecular heterogeneity at multiple levels: genomics, epigenomics, transcriptomics and microenvironment features. Genomic events acquired during carcinogenesis remain drivers of cancer progression in the metastatic setting. For example, KRAS and NRAS mutations defi ne a population refractory to EGFR monoclonal antibodies, BRAFV600E mutations associate with poor outcome under standard therapies and response to targeted inhibitors in combinations, while HER2 amplifi cations confer unique sensitivity to double HER2 blockade. Multiple rare gene alterations driving resistance to EGFR monoclonal antibodies have been described with signifi cant overlap in primary and acquired mechanisms, in line with a clonal selection process. In this context, sequential analysis of circulating tumor DNA has the potential to guide drug development in a treatment refractory setting. Rare kinase fusion events and complex alterations in genes involved in DNA damage repair have been described, with emerging evidence for targetability. On the other hand, transcriptomic subtypes and pathway activation signatures have also shown prognostic and potential predictive value in metastatic CRC. These markers refl ect stromal and immune microenvironment interactions with cancer cells. For example, the microsatellite instable (MSI) or POLE ultramutant CRC population is particularly sensitive to immune checkpoint inhibitors, while tumors with a mesenchymal phenotype are characterized by activation of immunosuppressive molecules that mandate stratifi ed development of novel immunotherapy combinations. In this manuscript we review the expanding landscape of targetable oncogenic alterations and signatures in metastatic CRC and discuss the clinical implementation of novel molecular diagnostic tests.]

Clinical Oncology

FEBRUARY 15, 2016

[Prevention and therapy of cervical cancer ]

RÉVÉSZ János, BÍRÓ Mátyás

[The global incidence of cervical cancer is ~530000, the death rate is ~270000 per year. These data shows, that cervical cancer is the fourth common malignancy in woman worldwide and the leading cancer related death in developing countries. HPV infection is the most important factor of carcinogenesis. Immunisation against HPV can prevent infection, and decrease the cancer incidence. In case of invasive cancer the therapeutic principles are surgery and radiotherapy. In case of high risk patients and/or locally advanced disease the adjuvant and neoadjuvant cytostatic treatment has limited evidences. The traditional cytotoxic therapy and the recent antiangiogenic therapy recommended for patients who have extrapelvic metastasis, residual tumor after primary radiotherapy or recidiv non curable tumor by radiotherapy or radical surgery.]

Lege Artis Medicinae

SEPTEMBER 20, 2011

[The development of insulin treatment from discovery of insulin to analogue preparations]

KÁPLÁR Miklós, PARAGH György

[The discovery of insulin was a milestone in the treatment of diabetes mellitus. Animalderived (porcine and cattle) insulins available at the beginning were later replaced by human insulins. Recently, analogue insulins are the most widespreadly used. Besides the increase in the quantity and improvement in the quality of the insulin products, the growth of the treatment regimes is apparent, as well. That varies from the once-given daily basal insulin treatment added to oral antidiabetic drugs to intensified insulin therapy, administering insulin 4-5 times daily. Considering the benefits proved by previous basic and clinical studies, the authors summarize the most important properties of the commonly used insulin treatment regimes in this review. They also briefly outline the important aspects of the patient-centered personalized therapy and the connection between insulin therapy and carcinogenesis.]

Hypertension and nephrology

FEBRUARY 28, 2011

[The importance of epithelial-mesenchymal transition in kidney fibrosis]

NAGY SZAKÁL Dorottya, SZEBENI Beáta, SZIKSZ Erna, HIMER Leonóra, REUSZ György, VÁSÁRHELYI Barna, TULASSAY Tivadar, VANNAY Ádám

[Epithelial-mesenchymal transition (EMT) plays a central role in physiological and pathological processes of embryogenesis, carcinogenesis and tissue fibrosis. During EMT epithelial cells may transform to myofibroblasts, which are the effector cells of fibrosis. In our summary the process of EMT and its medical importance will be reviewed in relation to renal fibrosis. Regardless of the initiating cause the final common mechanism of organ fibrosis is similar in the different chronic renal diseases. It always involves major inflammatory responses, however the molecular mechanisms involved are still elusive. The EMT now takes centre stage as the point of convergence between inflammation and the progression of degenerative fibrotic diseases. Understanding the pathomechanism of EMT and the significance of signalling pathways involved in this process may lead to a new therapeutic approach in the treatment of chronic renal diseases.]

Lege Artis Medicinae

JANUARY 22, 2008

[TISSUE HORMONAL SHOCK: INTRACRINOLOGY - THE IMPORTANCE OF LOCALLY PRODUCED HORMONES IN THE PATHOGENESIS OF VARIOUS DISEASES]

SPEER Gábor, LAKATOS Péter

[This review describes the function and tissuespecific expression of the 11- and 17-beta-hydroxysteroid- dehydrogenase enzyme families as well as the aromatase and 1-alpha-hydroxylase enzymes. Recently, in situ formation of active steroids by these enzymes at the sites of their actions from biologically inactive precursors in the circulation have been demonstrated to play an important role in sex steroid-dependent neoplasms (such as breast and prostate cancer), and in some metabolic diseases (such as obesity, osteoporosis and insulin resistance). Tissuespecific Cushing syndrome (local hypercortisolism) may contribute to the pathogenesis of the latter group of diseases, suggesting that obesity may be considered the Cushing-syndrome of the omentum and that osteoporosis is the obesity of bone. Intracrinology is the science of alterations in tissue hormone synthesis catalysed by enzymes such as those mentioned above, which cannot be detected by measuring circulating hormone levels. The effects of local hormone production differ from those of the well-described autocrine, paracrine and endocrine actions. Based on the hormonal changes within various tissues, the pathogenesis of a number of diseases may be interpreted in a novel way.]

Lege Artis Medicinae

OCTOBER 18, 2006

[CHEMOPREVENTION OF COLORECTAL CANCER]

LAKATOS Péter László

[Colorectal cancer is the second leading cause of cancer mortality in developed countries; in Hungary, the mortality has almost tripled in the past four decades. A decrease in mortality can only be expected from a consistently applied diagnostic and management strategy, including preventive measures. Primary prevention is defined as dietary, medicinal and lifestyle actions that can reduce the risk of developing cancer in people with average risk. Secondary prevention is the prophylactic treatment of high-risk patients or praecancerous lesions; tertiary prevention is the prevention of recurrence in patients cured of colorectal cancer. Drugs or dietary supplements used for chemoprevention block, delay or reverse the process of carcinogenesis. The most important drugs used for chemoprevention are aspirin and nonsteroidal anti-inflammatory drugs. Long-term administration of these drugs reduces the risk of developing colorectal cancer or adenoma both in the high-risk and in the average-risk population. The risk-lowering effect seems to be in positive correlation with the dose and the duration of use. Other chemoprophylactic drugs such as calcium, folate, oestrogen and antioxidants, as well as 5-aminosalicylates in patients with ulcerative colitis are also discussed in this review. Based on the current knowledge, chemoprophylaxis of colorectal cancer is recommended as secondary prevention in patients at high risk (e.g., familial adenomatous polyposis, extensive ulcerative colitis). In contrast, based on adverse event profile and cost-effectiveness analysis, primary prevention with chemopreventive drugs is currently not recommended in the averagerisk population.]

Lege Artis Medicinae

NOVEMBER 30, 2004

[NOVEL ASPECTS OF COX-2 SELECTIVE NON-STEROIDAL ANTI-INFLAMMATORY DRUG THERAPY]

MŰZES Györgyi

[The cyclooxygenase (COX) metabolic pathway and prostaglandin production appear to play a causal role in the promotion and progression of human cancers. Recently COX-2 has received a great deal of interest since it is frequently overexpressed in a wide spectrum of cancers and precancerous lesions. Furthermore, elevated production of prostanoids (particularly PGE2) via COX-2 is associated with several pro-carcinogenic effects including increased proliferation, apoptosis resistance, tumor neoangiogenesis and invasiveness, host immunosuppression, and altered xenobiotic metabolism. Inhibitors of COX-1 and COX-2 (aspirin and most other nonsteroidal anti-inflammatory drugs) and of COX-2 alone (e.g. coxibs) have shown cancer preventive efficacy in epidemiological studies, experimental studies and in human clinical trials. Due to their improved side effect profile, COX-2 selective inhibitors appear to hold substantial promise for long-term administration in the setting of cancer prevention. Emerging data suggest that these agents may have potential in cancer treatment as well. In addition recent results indicate that COX-2 enzyme is also overexpressed in inflammatory processes of the central nervous system, e.g. in Alzheimer’s disease, so its suppression could offer a possible new therapeutic strategy even in the prevention and treatment of Alzheimer’s disease.]

Lege Artis Medicinae

DECEMBER 19, 2008

[SECONDARY MALIGNANCIES IN RHEUMATOID ARTHRITIS]

SZEKANECZ Éva, SZŰCS Gabriella, KISS Emese, SZABÓ Zoltán, SZÁNTÓ Sándor, TARR Tünde, SZÁNTÓ János, SZEKANECZ Zoltán

[INTRODUCTION - Survival data for rheumatoid arthritis (RA) have improved during the past years. Due to longer life expectancy, more attention has to be paid to prevention and treatment of long-term sequelae, including secondary malignancies. Incidence of malignant lymphoproliferative diseases and bronchial cancer is higher in a number of rheumatic diseases including RA. Some drugs nowadays very rarely used in RA - primarily cyclophosphamide and azathioprine - may further increase cancer risk. According to several large meta-analyses, biological therapy may also increase the risk of lymphomas, however, as these agents are used for the treatment of active, refractory arthritis, benefit may override such risks. PATIENTS AND METHODS - Altogether 516 RA patients managed at our department were assessed for the incidence and type of secondary malignancies. Although the absolute number of RA patients with a tumor was relatively small, we compared our cohort to the Health for All database and calculated standard incidence ratios (SIR). RESULTS - We identified 13 cases of malignancy (11 females and 2 males) in 516 RA patients (2.5%). In two patients, cancer developed before the onset of RA. RA patients with malignancy had an even higher female predominance (5.5 to 1) than usual. Mean age at onset of RA was 51.4 years, while age at the diagnosis of malignancy was 61.8 years. Mean duration of RA at the time of cancer diagnosis was 11.2 years. Five patients died, 4 due to the underlying malignancy. In the fifth patient, the tumor was considered cured but the patient died of amyloidosis. Among the 8 surviving patients, mean survival is 7.3 years until now, while overall survival of all 13 cancer patients is 4.7 years. Regarding types of malignancies, there were 6 cases of bronchial cancer, 2 cases of follicular thyroid cancer, and one cutaneous B cell lymphoma, one breast cancer, one gall bladder cancer, one colorectal cancer, and one pancreatic cancer. In comparison to the Health for All database, the overall SIR of all malignancies in RA was 1.12 (CI 0,91-1,33), varying between 2.2 and 70.7 among different tumor types. Only one cancer patient received cyclophosphamide therapy and some received methotrexate or anti-TNF agents. CONCLUSION - We identified 13 cases of malignancy among our RA patients. In RA, secondary tumors including bronchial cancer and lymphomas are more common than in the general population. Adequate treatment and monitoring of these patients may help us to lower the risk of malignancies secondary to RA]