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Clinical Neuroscience

JULY 30, 2020

[Recurrent inhibition during Jendrassik maneuver]

LUKÁCS Miklós

[Objective – Conflicting theoretical models exist regarding the mechanism related to the ability of the Jendrassik maneuver to reinforce reflex parameters. Our objective was to investigate if vigorous handgrip would induce changes in recurrent inhibition of soleus motoneurons. Method – Soleus H reflex was evoked by stimulating the tibial nerve at rest and during bilateral vigorous handgrip, alternating single (H1) and paired stimulation (H2). At paired stimulation we used interstimulus intervals of 10, 15, 20 and 25 ms and supramaximal test stimulus. H1- and H2-wave amplitudes were expressed as percentage of maximal M-wave amplitude. Conditioned H2 wave maximal (H2max) and minimal (H2) amplitudes evoked at rest and expressed as a percentage of the unconditioned H1max amplitude were compared with the corresponding values obtained during handgrip by means of paired Student test and Bonferroni correction. Subjects – At the study participated 28 healthy volunteers. Results – The H1max/Mmax × 100 values obtained during handgrip (37.5±10.1) were significantly higher than those obtained at rest (27.1±7.4). The H2max/H1max × 100-va­lues obtained at paired stimulation were significantly higher during handgrip than at rest, while no significant diffe­rence was found between the H2/H1max × 100-values obtained during handgrip and at rest respectively. Discussion – The H2max/H1max is determined by both the excitability of the motoneurons and the recurrent inhibition elicited by the conditioning stimulus, while H2/H1max indicates only the level of recurrent inhibition. According to our results the Renshaw cells retain their inhibitory effect on the soleus alpha motoneurons during remote muscle contraction. Conclusion – Soleus H reflex enhancement during Jendrassik maneuver is not due to decrease of recurrent inhibition. ]

Clinical Oncology

APRIL 10, 2019

[New perspectives in the treatment of lung cancer]

SZONDY Klára, BOGOS Krisztina

[In recent years, huge research is going on in the fi eld of oncology and as a result, we can see a signifi cantly longer survival in this area of medicine. Lung cancer, which has been taken places in the back for decades, it has not become a curable disease, but begins to belong to the chronic diseases. As a result of brilliant surgical technics and stereotactic radiotherapy, or as a result of changes in drug treatment, 5-year survival is not uncommon in metastatic lung cancer patients, next to relatively long progression free survive. After the third-generation cytotoxic combinations the added growth inhibition (VEGF inhibitor) maintenance therapy or continuous pemetrexed cytotoxic chemotherapy were resulted in high survival benefi ts. The fi rst real breakthrough, long progression-free survival was achieved by targeted treatment, which proved to be effective with known driver mutations. The other great result, especially in squamous cell carcinoma, was the immunotherapy, the inhibition of immune checkpoints, which effi cacy was confi rmed in adenocarcinoma also. Several studies are going on with adjuvant or neoadjuvant immunotherapy, and combined use of immunotherapy (either in combination with radiotherapy or cytotoxic chemotherapy).]

Lege Artis Medicinae

MAY 20, 2019

[Immuno-oncology therapy in patients with non-small cell lung cancer]

CSÁNKY Eszter

[Despite decades of smoking cessation programs, and lung cancer screening programs, mortality due to bronchial cancer leads the mortality statistics among cancer deaths worldwide. Platinum-based chemotherapy has not fundamentally altered the effectiveness of treating non-small cell lung cancer (NSCLC). One of the newest approaches to the use of immunotherapeutic treatments in recent years is the so-called. use of immune checkpoint blocking agents. PD-1 and PD-L1 blockers of this type have been subjected to a large number of clinical trials in lung cancer and were reported by the tumor III.b / IV. stage. Last year, in 2018, we again came up with a milestone in the treatment of lung cancer immuno-oncology, as compared to the previous stage, III.a / III.b Durvalumab con­solidation therapy for non-small cell lung cancer after inoperative, non-chemo-radiotherapy phase I, is based on the results of the PACIFIC clinical trial. PACIFIC was a triple-phase, randomized, double-blind, placebo-controlled, multicentre study to evaluate the efficacy and safety of durvalumab consolidation therapy, irresistible, III. patients with non-small cell lung carcinoma who have not progressed after platinum-based chemo-radiotherapy. The PD-L1 expression level of the tumor was not an admission criterion. In the study, 713 patients were randomized to durvalumab and placebo for 2:1, progression-free survival (PFS) and over­all survival (OS) as their primary endpoint. Summarizing the results of the study, durvalumab provided significant benefit to patients at both endpoints. PFS and OS values were also significantly longer for durvalumab than placebo, and the safety profile of durvalumab was consistent with previous PD-1, PD-L1 inhibition tests.]

Clinical Oncology

DECEMBER 05, 2017

[Complex therapy of bladder cancer]

LANDHERR László

[Bladder cancer is the most common malignancy involving the urinary system. Urothelial (formerly called transitional cell) carcinoma is the predominant histologic type in the developed countries, where it accounts for approximately 90 percent of all bladder cancers. The optimal management of nonmuscle invasive urothelial cancer is highly important. For patients with muscle invasive cancer the gold standard treatment is the cystectomy. If the patient unable or unwilling to undergo radical cystectomy with urinary diversion, complete TURBT combined with radiation therapy plus chemotherapy may offer an alternative bladder-sparing approach. Patients with muscle invasive disease and regional lymph node metastasis limited to the pelvis (N1-N3), but without more distant lymph node or visceral metastasis may be treated with six cycles of cisplatin-based chemotherapy followed by cystectomy or a combined-modality approach. In metastatic cases the combination chemotherapy may prolong survival and often provides palliation of symptomatic disease. Checkpoint inhibition immunotherapy has substantial clinical activity in post-chemotherapy patients and is the preferred therapy for patients who have progressed after platinumbased therapy or is not suitable for them.]

Clinical Oncology

DECEMBER 05, 2017

[Inhibition of proteasome in cancer therapy]

KOPPER László

[The ubiquitin-proteasome pathway is the most important element in the regulation of intracellular protein metabolism. Its main function is the degradation of the unnecessary proteins either as part of normal metabolic balance or in case of misfolding or part of the deregulation as in cancer cells using proteolytic enzymes. The importance of this pathway has been acknowledge by Nobel prize. In certain diseases as in several malignancies, where the ubiquitin-proteasome pathway is not able to remove the proteins due to dysfunction or accumulation in a high quantity. The unregulated accumulation of proteins could lead to cell death. This phenomenon was proven by the appearance of proteasome-inhibitors targeting mainly myeloma. It should be mentioned that clinical aspects myeloma has been discussed in an excellent review by Mikala and his colleagues in Klinikai Onkológia.]

Clinical Oncology

SEPTEMBER 10, 2017

[Targeted therapy of the clear cell renal cancer ]

TORDAY László

[The renal cell cancer is among the ten most frequent cancers in developed countries. Its inci dence rate continuously increased until recently. On the other hand, survival parameters of renal cell cancer patients considerably improved in the last decade due to early diagnosis and developments in the treatment of irresectable disease. Huge progress had been made in understanding of the biological background of this chemo- and radiotherapy resistant disease, leading to the introduction of drugs in fi rst and further line treatment acting on VEGF and mTOR signal transduction pathways. Simultaneously, the era of widespread cytokine treatments had been ended. Recent studies had ensured the introduction of several drugs with new mechanism of action (MET, AXL; FGFR, PD-1 inhibition) into the therapy; these new advances completely changed the treatment landscape of RCC further improving progression free and overall survival. In this publication a review of data regarding the targeted treatment of clear cell renal cancer will be provided and as of our recent knowledge therapeutic positions of different drugs used will be discussed.]

Clinical Oncology

SEPTEMBER 10, 2017

[MEK and ERK - against RAS and RAF ]

KOPPER László

[In most cases, the targeted therapy is able to produce clinical response, but after a certain interval it turns to be ineffective due to secondary resistance against the therapy. One of the most demanding challenge in treatment of cancer is to prevent or inhibit such resistance, which could have several forms, e.g. appearance of new driver activating mutations in the treated tumor, clon(s) existed in minority with different mutations (targets) can grow and replace the temporarely sensitive tumor cells (on the basis of tumor heterogeneity); another pathway takes over the role in cancer progression, etc. Such problems are very common in the RAS-RAF-MEK-ERK pathway. These are very important proteins to collect extracellular signals in order to regular different cell functions, especially proliferation. With activating mutations make the RAS-pathway independent from the normal .regulation. To inhibit the consequence of the mutations is largely still an unsolved problem, with few exceptions (e.g. inhibition of BRAF mutations). Theoretically, the inhibition of the next steps of the pathway, MEK and ERK, may stop the pathologically activated signals, partly due to their inhibition, and party to effi ciently decrease the feedback inside the pathway. This review discusses aspects of this possibilities, especially to overcome resistance and prolong the effectiveness of therapy.]

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

FEBRUARY 10, 2017

[Cell cycle as therapeutic target – CDK4/6 inhibition]

KOPPER László

[One of the most important decision of a cell: to live or die. If survival is the choice, there are three options: proliferate, to stay in sleeping state for a while, or differentiate in order to perform its specifi c function. These decisions are under a very strict molecular regulation infl uenced by internal and external factors. Tumor cells more and more disregard the regulations, and move into independency for a continuous proliferation, which has a very similar program in normal and tumor cells. The main route towards mitosis is the cell cycle, under the supervision of positive and negative regulators, forming checkpoints, telling to the cell - under the infl uence of mitogenic signals - to go or to stop. The most critical checkpoint is at the border of G1 and S phases where the main players are cyclinD, CDK4/6 and RB1. It turned out that the best targets to inhibit cell proliferation are the CDKs, but this approach, when used unselected targets, was unsuccessful due to the toxicity. To improve the clinical results, the selection of CDK4/6 as a therapeutic target seems to fulfi l most of the hopes. Today three drugs are the most promising: palbociclib (with an acceptance by FDA and EMA to treat breast cancer patients), abemaciclib and ribociclib (underclinical trials). Now, most of the data concern breast cancer, especially the combinations of CDK4/6 inhibitors and endocrine therapy, but many other malignancies are studied (e.g. liposarcoma, mantel cell lymphoma, melanoma, renal cancer, lung cancer, pancreatic cancer, ovarian cancer, teratomas etc.). The key points are the side-effects, the most frequently observed is neutropenia, but so far it is managed without serious toxicity.]