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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 20, 2019

[P53 – the suppressor]

KOPPER László

[Our basic nature requere cells quantity and quality to perform differenciate activity. p53 has the responsibility for quick out those cells who carries molecular failures in DNA avoiding transfer mutations into doughter cells. If the DNA-repair insuffi cient p53s with on apoptosis. Whe p53 is mutated the phenotypes are different in a wide range due to the heterogenity of the DNA damages, and also the expression pattern of a suppressor protein. With the increasing amout the damaged DNA the genomic instability elevates D the risk to development of tumors. It is linict mutated gene could be a promosing tr, 10t for therapy. So far the attempts have little value for the clinic.]

Clinical Oncology

MAY 10, 2017

[Why don’t immune checkpoint inhibitors work in colorectal cancer?]

SHI Yuequan, ZOU Zifang, KERR David

[In recent years, immune checkpoint inhibitors have been shown to be effective in treating manifold types of cancer but less robust in colorectal cancer (CRC). While, the subgroup of CRC with microsatellite instability (MSI; also termed as mismatch repair defi cient) showed a moderate response to Pembrolizumab in a single arm phase II clinical trial, microsatellite stable (MSS) cancers were unresponsive. Possible mechanisms that affect immune response in colorectal cancer will be reviewed in this article. We will also propose that histone deacetylase (HDAC) inhibition may reverse the immune editing commonly seen in advanced CRC and render them sensitive to immune checkpoint blockade.]

Clinical Oncology

MAY 10, 2017

[Signaling pathways in cancer stem cells (Notch, Hedgehog, Wnt)]

KOPPER László, NAGY Noémi, SEBESTYÉN Anna

[OThe key regulators in the embryonic life, and later in the differentiation of tissues and organs are the evolutionary reserved signalling pathways, as Notch, Hedgehog and Wnt. Mutations of these pathways have been identifi ed in many tumor types, increasing the risk to the appearance of cancer stem cells (CSC), with very similar geno- and phenotype as normal stem cells have. Such CSCs with stemness functions can be developed not only from normal stem cells, but also from progenitor and differentiated cells. The main characteristics of CSC are the self maintenance, slow growth rate, very effective DNA-repair system, etc. All of these can contribute to the resistance. Further problems are the low number of CSC in the whole tumor mass, which makes rather diffi cult to achieve the effective drug concentration in CSC. The mentioned ancient pathways interact with many other pathways to form a network, which can infl uence the strategy of therapy. No doubt, that these pathways are promising targets, however, till now the clinical effectiveness is very low due to some reasons mentioned above. Nevertheless, some drugs are already in clinical use, either as monotherapy or part of the combinations. Little is known about the relationship between the pathways and the microenvironment, which has an outstanding role in the cellular activities, sometimes resulting opposite output. It is a great challenge to design effective drugs against CSC, similarly to fi nd reliable predictive biomarkers, which unfortunately still missing, since a reasonable drug-marker interactions would speed up the personalized treatment.]

Clinical Oncology

DECEMBER 10, 2016

[Defi ciency of DNA-repair]

KOPPER László

[The cell uses the DNA to keep those information, which are vital to function properly. It is essential to maintain the integrity of the DNA, the stability of the genome. Since DNA damages, caused by external or internal factors, are continuously produced, DNA-repair mechanisms should be ready to identify and eliminate the damages. Either the repair system is successful and the cell can continue its duty, or, if the damages are unrepaired, the programed cell death (apoptosis) is activated according to the rule, that it is prohibited to transfer genomic/epigenomic damages into the daughter cells. It is true that the severness of the damages are not the same. The most important is the identifi cation and repair of those damages which can make genomic instability increasing the risk of cancer development. This may happen when the repair system is insuffi cient, sometimes due to inherited mutations (e.g. BRCA1 mutations can increase the risk of breast cancer, ovarian cancer etc.). Among the damages the DNA double strand breaks are rather common, and also, that the breaks are intended to be repaired in most cases. However, if such repair fails, the cell, here the cancer cell, due to the overhelming damages will dye. This phenomenon is the synthetic lethality. An example: „cooperation” of inherited BRCA1 mutation and PARP-inhibition, can lead to clinical response using PARP inhibitors, as oliparib. New agents and clinical trials intend to take advantage from synthetic lethality.]

Lege Artis Medicinae

MAY 20, 2010

[Successful chest-wall reconstruction after the resection of a chondrosarcoma using muscle-flap and polytetrafluorethylene mesh repair]

AGÓCS László, KOCSIS Ákos, TAMÁS Róbert, LÉVAY Bernadett, CSEKEŐ Attila

[INTRODUCTION - Approximately 30% of malignant, primary bone tumours are chondrosarcomas, which most frequently develop on the anterior chest wall. Patients who are treated with adequate surgical intervention recover, 10-year survival rate is 97%. Besides the aesthetic outcome, preservation of breathing functions is crucial. CASE REPORT - The 36-years-old patient presented with a large chondrosarcoma, which infiltrated the left chest wall (4-6th ribs, the parietal pleura and the underlying muscles). Surgical resection was performed by opening the left thoracic cavity, sparing the skin and the subcutaneous layer. Reconstruction of the chest wall’s stability was carried out with a 20×25cm, polytetrafluoroethylene alloplastic Dualmesh, and an extensive myocutaneous dorsal flap (including the latissimus dorsi and serratus anterior muscles) that was pedicled on the left thoracodorsal vessels. After a normal postoperative period, the patient was released with sufficiently expanded lungs. No tumour remission was detected on the follow-up CT examination at 6 months after surgery. CONCLUSION - This case demonstrates that radical resection of chest-wall tumours and the above described reconstruction method allows the avoidance of paradoxial respiratory movements and provides excellent functional and aesthetic outcomes.]

Hungarian Radiology

DECEMBER 20, 2006

[Aquired non-inflammatory and non-traumatic hypoplasia-dysplasia of the femoral neck Report of two cases]

NICOL Richard, MARZENA Wisniewska, KAZIMIERZ Kozlowski

[Recently DiFazio et al reported four children with remarkable femoral neck deformity who had extracorporeal membrane oxygenation (ECMO) therapy. We report two patients with similar femoral neck changes who did not have ECMO treatment but have had complicated, strenuous first few weeks after birth. The first patient had been operated on twice for diaphragm repair at the age of 18 hours and 1 month. The second patient had cardiac surgery at the age of two months, with one hour of extracorporeal cardiorespiratory bypass. We agree with DiFazio et al and believe that four of their patients and both of ours have femoral neck growth cartilage injury secondary to hypoxia, vascular disturbance and coagulopathy.]

Hungarian Immunology

JANUARY 20, 2003

[Undifferentiated connective tissue disease]

BODOLAY Edit, SZEGEDI Gyula

[Undifferentiated connective tissue disease (UCTD) is a term used by many authors to define a group a diffuse connective tissue disorders that lack definitive characteristics of any particular well-defined disorder. UCTD was diagnosed if the patients had at least two clinical symptoms and their sera contained one type of the anti nuclear antibody. Six hundred and sixty five patients with UCTD were followed between 1994 and 1999. The presence of the fever and anti-DNS antibodies correlated with SLE, arthritis/arthralgia and anti-RNP antibodies with MCTD, Raynaud phenomenon and ANA positivity with scleroderma, xerostomia/xerophtalmia and anti-SSA/SSB antibodies with Sjögren' syndromes, rheumatoid factor positivity and polyarthritis with rheumatoid arthritis. In conclusion, the UCTD represents a dynamic phase, one part of the patients show progression to definite connective tissue diseases, one part show regression, and on part of the patients stay in UCTD phase.]

Lege Artis Medicinae

MAY 20, 2002

[Changing tendencies in retinal surgery]

MILIBÁK Tibor

[Retinal detachment, a disease caused by pathologic alteration of the vitreoretinal relationship, may decrease vision to blindness without treatment. Although some of the patients with retinal detachment become blind for the time being, last two decades produced significant improvement both in diagnosis and treatment. As a result of new surgical techniques we can perform successful surgery even in cases that were earlier inoperable. Recent methods are significantly less traumatic to the eye than they were 20 years ago. Dramatically reduced bedrest before and after surgery, regional or even topical anaesthesia instead of general anaesthesia, short term hospitalisation or one day surgery, short term restriction of physical activity after surgery are the most important consequences of the new wave of retinal detachment repair. According to recent recommendations of the prophylactic treatment of peripheral retinal lesions we treat only horse tears with sudden retinal complaints.]