Specialities

Immune Oncology

Clinical Neuroscience

SEPTEMBER 30, 2020

TLR4 (Toll-like receptor-4) expression and frontal-cingulate volumes in schizophrenia

LI Hua, KÉRI Szabolcs

Evidence suggests that pathogen-associated pattern recognition receptors (Toll-like receptors, TLRs) are implicated in the pathophysiology of schizophrenia. TLRs are important in both peripheral immune responses and neuronal plasticity. However, the relationship between peripheral TLR expression and regional brain volumes is unknown in schizophrenia. We therefore assessed 30 drug-naïve, first-episode patients with schizophrenia. TLR4+/TLR1+ monocytes were measured using flow-cytometry. High resolution magnetic resonance images (T1 MRI) were obtained and analyzed with FreeSurfer. Results revealed significant negative correlations between the percentage of TLR4+ monocytes, mean fluorescent intensities, and brain volumes in frontal and anterior cingulate regions. The measures of TLR1+ monocytes did not show significant relationships with regional brain volumes. These results raise the possibility that abnormal TLR-activation is associated with decreased brain volumes in schizophrenia.

Clinical Neuroscience

SEPTEMBER 30, 2020

[Prognostic significance of invasion in glioblastoma]

SZIVÓS László, VIRGA József, HORTOBÁGYI Tibor, ZAHUCZKY Gábor, URAY Iván, JENEI Adrienn, BOGNÁR László, ÁRKOSY Péter, KLEKNER Álmos

[Glioblastoma is the most common malignant CNS tumor, its surgical removal is hindered by the tumors invasive nature, while current anti-tumor therapies show limited effectiveness – mean overall survival is 16-24 months. Some patients show minimal response towards standard oncotherapy, however there are no routinely available prognostic and predictive markers in clinical practice to identify the background of mentioned differences in prognosis. This research aims to identify the prognostic significance of invasion-related extracellular (ECM) components. Patient groups with different prognoses were created (OS: group A <16 months, group B > 16 months), and internationally recognized prognostic markers (IDH1 mutation and MGMT promoter hyper-methylation) were tested in the flash-frozen tumor samples. Furthermore, the mRNA levels of 46 invasion-related ECM molecules were measured. Clinical data of the patients who have been operated on at the University of Debrecen Clinical Center Department of Neurosurgery and treated at the Department of Clinical Oncology showed no significant differences except for survival data (OS and PFS), and reoperation rate. All samples were IDH wild type. MGMT promoter hypermethylation rate showed significant differences (28.6% vs 68.8%). The expressional pattern of the invasion-related ECM molecules, i.e. the invasion spectrum also showed major differences, integrin β2, cadherin-12, FLT4/VEGFR-3 and versican molecules having signficantly different mRNA levels. The accuracy of the inivasion spectrum was tested by statistical classifier, 83.3% of the samples was sorted correctly, PPV was 0.93. The difference found in the reoperation rate when comparing different prognostic groups aligns with literature data. MGMG promoter region methylation data in Hungarian samples has not been published yet, and further confirming current knowledge urges the implementation of MGMT promoter analysis in clinical practice. Studying the invasion spectrum provides extra information on tumors, as a prognostic marker it helps recognizing more aggressive tumors, and calls attention to the necessity of using anti-invasive agents in GBM therapies in the future.]

Clinical Neuroscience

SEPTEMBER 30, 2020

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Lege Artis Medicinae

SEPTEMBER 30, 2020

[The pain-trigger role of cytokines in the nervous system – the direct analgesic effect of anti-cytokine therapy ]

HODINKA László, VERECKEI Edit

[Nociceptive, neuropathic and central me­chanisms are involved in the perception, transmission and processing of chronic pain and shaping of cerebral pain image. Alar­mins – molecules alarming defence and signing the presence of pathogens and tissue damage - trigger a series of pathogenic events resulting in inflammatory pain stimuli. Proinflammatory cytokines play a determining role in the pain perception at the level of the nervous system. Continuous inflammatory stimuli while sensitizing the periferic and central neurons activate the pain-related cerebral areas and develop the complex pain image, the pain matrix. Ce­reb­ral functional connections are operating in networks and can be visualized by functional MRI. Cytokines activate the neurons directly or indirectly by other neuromediators. Cytokine receptors are expressed on no­ciceptors and even on higher-level neurons and on various non-neural cells, such as microglia and astrocytes. The most ubiquitous cytokines are the Tumour Necrosis Factor and Interleukin 6 in the nervous sys­tem. The signaling pathways are the Nuclear Factor κB and the Janus-kinase enzyme system. The proinflammatory cytokines and the Janus-kinase are therefore primary therapeutic targets. Anti-cytokine biologicals and small molecular kinase inhibitors decrease the pain and improve functional activity in rheumatoid arthritis. Decrease of pain was more pronounced than expected only from the decrease of the clinical biomarkers of inflammation. The early and ra­pid painkiller effect of targeted biological and chemical-biological response modifiers is attributed to their direct analgesic effect on the brain.]

Lege Artis Medicinae

SEPTEMBER 30, 2020

[Frequency and risk factors of “de novo” tumors after kidney transplantation ]

BORDA Bernadett, HÓDI Zoltán, SZEDERKÉNYI Edit, OTTLAKÁN Aurél, SEREGÉLY Edit, LÁZÁR György, KERESZTES Csilla, VIRÁG Katalin

[After kidney transplantation, the administration of immunosuppressive therapy not only renders the patient susceptible to infections, but it may also damage the function of tumor cell recognition and elimination. Our study was performed at the Department of Surgery, University of Szeged. After establishing the inclusion criteria, 570 patients were involved in the study. We examined the age, sex, immunosuppressive therapy of the patients, and searched for the rela­tionship between the different immunosuppressive agents and the type of the tumor. In 81 cases, de novo cancer was diagnosed. Among patients treated with cyclosporin and tacrolimus there was no significant difference in the mean age (p = 0.734) and body mass index (p = 0.543). There was no significant difference in graft function between the two groups of patients (Tac vs Cyc; 44 vs 20). Related to the time passed since the trans­plantation to diagnosing the tumors the earliest were prostate and cervix cancers however without significant difference. Skin cancers are the most frequent followed by post-transplant lym­pho­prolife­ra­tive diseases. The increasing risk of developing tumors is mainly due to immunosuppressive therapy. ]

Lege Artis Medicinae

JULY 01, 2020

[Sarcopenia – muscle loss – pathomechanism, clinical presentation and metabolic comorbidities]

VERECKEI Edit, HODINKA László

[Sarcopenia, or the age-related involution of muscle strength and muscle mass, is a serious public health concern, due to the growing number of elderly population caused by nowadays demographic changes i.e. prolonged life expectancy. By ageing, the muscle tissue is shrinking gradually, leading to the loss of muscle strength and masses. This condition is called sarcopenia. Sar­co­penia is the simultaneous decrease of muscle mass, muscle strength and functional independence. In parallel the physical performance deteriorates (weakness, slowness and poor physical balancing). Fatigue, el­derly behaviour and weight loss are the consequences of these accumulating deficits, which associate with cognitive decline and result in increasing social isolation. The primary form of sarcopenia is the decrease of the energy production of muscle cells and then the death of muscle cells. Se­con­dary, endocrine dysfunctions, diseases of the nervous system, decreased physical activity, malnutrition or malabsorption, chronic infection accelerate the process and aggravate the patient’s condition. Complex genetic, biochemical and endocrine mechanisms take part in the development of sarcopenia. This involution is due to the impaired balance of restoring and depleting processes of muscles. A questionnaire and algorithm have been developed to recognize, screen and diagnose the risks of sarcopenic condition; these separate the sarcopenic and non-sarcopenic patients with specific cut-off values. Sar­co­penia can be diagnosed based on walking speed, decreased handgrip strength and measured or calculated muscle mass in persons over 65. Sarcopenia can be considered as a phenomenon of “physiological” aging, however, it becomes a disease when diagnostic cut-offs are exceeded and the patient experiences functional disability and declining quality of life. Prevention and treatment of sarcopenia and reducing the risk of falling are based on regular active resistance and coordination exercises. Options for pharmaceutical treatments are limited since despite of identified molecular targets there are no convincingly effective innovative therapy on the horizon. Nevertheless, there are some weak evidence for efficacy of the application of amino acids stimulating muscle cell differentiation, such as leucine or the analogue of beta-hydoxy-methylbutyrate beside exercise therapy.]