PURPOSE: To evaluate treatment outcomes and toxicity in patients with stage T1-3N0M0 oral cancer treated with surgery followed by high-dose-rate brachytherapy (HDR-BT). METHODS AND MATERIALS: Retrospective study of 50 patients with stage T1-T3N0 tongue and floor-of-mouth cancer who underwent tumour excision (+ elective neck dissection) followed by postoperative HDR-BT due to the presence of negative prognostic factors (close or positive resection margins, lymphovascular and/or perineural invasion, deep invasion). The plastic tube technique (dose: 18 x 3 Gy b.i.d.) was used. Survival outcomes, toxicity, and prognostic factors were evaluated. RESULTS: At a median follow-up of 81 months (range, 4-121), actuarial 5-year local control (LC), nodal control (NC) and progression-free survival (PFS) rates were 79%, 69%, and 64%. After salvage treatment (surgery + external beam radiotherapy), LC, NC, and PFS increased to 87%, 77%, and 72.3%, respectively. Five-year overall survival and cancer-specific survival (CSS) rates were 73% and 77%. Treatmentrelated toxicity included two cases of mandibular osteoradionecrosis and five cases of small soft tissue necrosis. T stage was significantly correlated with nodal control (p=0.02) and CSS (p=0.04). Tumour grade correlated with DFS (p=0.01). CONCLUSION: Postoperative HDR-BT 18 x 3 Gy b.i.d. seems to be an effective method in patients with T1-3N0M0 oral cancer with negative prognostic factors after tumour resection.
- MeSH
- Brachytherapy * methods MeSH
- Radiotherapy Dosage * MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Survival Rate MeSH
- Mouth Neoplasms * radiotherapy pathology surgery MeSH
- Prognosis MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Neoplasm Staging * MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Cancer is a heterogeneous disease, which contributes to its rapid progression and therapeutic failure. Besides interpatient tumor heterogeneity, tumors within a single patient can present with a heterogeneous mix of genetically and phenotypically distinct subclones. These unique subclones can significantly impact the traits of cancer. With the plasticity that intratumoral heterogeneity provides, cancers can easily adapt to changes in their microenvironment and therapeutic exposure. Indeed, tumor cells dynamically shift between a more differentiated, rapidly proliferating state with limited tumorigenic potential and a cancer stem cell (CSC)-like state that resembles undifferentiated cellular precursors and is associated with high tumorigenicity. In this context, CSCs are functionally located at the apex of the tumor hierarchy, contributing to the initiation, maintenance, and progression of tumors, as they also represent the subpopulation of tumor cells most resistant to conventional anti-cancer therapies. Although the CSC model is well established, it is constantly evolving and being reshaped by advancing knowledge on the roles of CSCs in different cancer types. Here, we review the current evidence of how CSCs play a pivotal role in providing the many traits of aggressive tumors while simultaneously evading immunosurveillance and anti-cancer therapy in several cancer types. We discuss the key traits and characteristics of CSCs to provide updated insights into CSC biology and highlight its implications for therapeutic development and improved treatment of aggressive cancers.
- MeSH
- Humans MeSH
- Neoplastic Stem Cells * pathology metabolism MeSH
- Tumor Microenvironment * MeSH
- Neoplasms * pathology genetics metabolism therapy MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND AND OBJECTIVES: En bloc sacrectomy is associated with sacral root transection causing loss of urinary bladder, rectum, and sexual function. The aim of the study was to determine the position of the pudendal branches (sensorimotor) and pelvic splanchnic nerves (parasympathetic) on the sacral roots relative to the sacrum, and the minimal and maximal defects in the sacral roots that can be reconstructed by grafting after various types of sacrectomy. METHODS: Five cadaveric pelves were dissected bilaterally. The lengths and widths of the S1-S4 roots and their branches were measured. Then, the minimal and maximal defects between the proximal and distal stumps of the sacrificed roots were measured following 3 models of sacrectomy (below S2, below S1, and total sacrectomy). RESULTS: The mean distance of the splanchnic nerves from the S2 and S3 anterior sacral foramina was 17.7 ± 7.3 and 23.6 ± 11.1 mm, respectively, and the mean distance of the pudendal S2 and S3 branches was 36.8 ± 13.7 and 30.2 ± 10.8 mm, respectively. The mean widths of the S2 and S3 roots were 9.3 ± 1.9 and 5.4 ± 1.2 mm, respectively. The mean maximal defects in S2 and S3 roots after various types of sacrectomies were between 61.8 ± 16.3 and 100.7 ± 14.3 mm and between 62.7 ± 20.2 and 84.7 ± 25.1 mm, respectively. There were no statistically significant differences between sides or sexes for all obtained measurements. CONCLUSION: The reconstruction of the S2-S3 roots is anatomically feasible after partial or total sacrectomies in which the resection of the soft tissue does not extend further than approximately 1.5 to 2 cm ventrally from the sacrum.
- MeSH
- Sacrum * surgery anatomy & histology innervation MeSH
- Middle Aged MeSH
- Humans MeSH
- Spinal Nerve Roots * anatomy & histology surgery MeSH
- Cadaver * MeSH
- Aged MeSH
- Splanchnic Nerves anatomy & histology surgery MeSH
- Plastic Surgery Procedures methods MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Glioblastomas are aggressive brain tumors for which effective therapy is still lacking, resulting in dismal survival rates. These tumors display significant phenotypic plasticity, harboring diverse cell populations ranging from tumor core cells to dispersed, highly invasive cells. Neuron navigator 3 (NAV3), a microtubule-associated protein affecting microtubule growth and dynamics, is downregulated in various cancers, including glioblastoma, and has thus been considered a tumor suppressor. In this study, we challenge this designation and unveil distinct expression patterns of NAV3 across different invasion phenotypes. Using glioblastoma cell lines and patient-derived glioma stem-like cell cultures, we disclose an upregulation of NAV3 in invading glioblastoma cells, contrasting with its lower expression in cells residing in tumor spheroid cores. Furthermore, we establish an association between low and high NAV3 expression and the amoeboid and mesenchymal invasive phenotype, respectively, and demonstrate that overexpression of NAV3 directly stimulates glioblastoma invasive behavior in both 2D and 3D environments. Consistently, we observed increased NAV3 expression in cells migrating along blood vessels in mouse xenografts. Overall, our results shed light on the role of NAV3 in glioblastoma invasion, providing insights into this lethal aspect of glioblastoma behavior.
- MeSH
- Phenotype * MeSH
- Glioblastoma * pathology genetics metabolism MeSH
- Neoplasm Invasiveness * genetics MeSH
- Humans MeSH
- Membrane Proteins MeSH
- Microtubules metabolism MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Brain Neoplasms * pathology genetics metabolism MeSH
- Cell Movement genetics physiology MeSH
- Nerve Tissue Proteins metabolism genetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Talk
331 stran, 16 nečíslovaných stran obrazové přílohy : ilustrace ; 21 cm
Publikace obsahuje rozhovor s českým plastickým chirurgem Ondřejem Měšťákem o jeho profesním i osobním životě.; Lze krásu vyjádřit matematickým vzorcem? Dají se prsa zvětšit vlastním tukem? S čím nejčastěji chodí na plastiky muži? Na tyto a mnoho dalších otázek odpovídá renomovaný plastický chirurg Ondřej Měšťák, mimo jiné specialista na rekonstrukce prsů a operace nosů, vědec a v neposlední řadě syn legendárního plastického chirurga Jana Měšťáka. V knižním rozhovoru se čtenář dozví, jak těžké je stát se plastickým chirurgem, jak si správně plastického chirurga vybrat a které úkony hradí zdravotní pojišťovna. Projdeme různé druhy plastických operací na jednotlivých částech těla. Zabrousíme i do vážnějších témat, jako jsou mikrochirurgické operace onkologických pacientek nebo operace rozestupu břišních svalů po těhotenství. Prostor ale dostanou i odlehčenější dotazy, jako například zda Ondřej dostává nevyžádané zprávy od žen, zda si bere svou práci domů nebo odkud čerpá energii. Společně s autorem knihy Pavlem Hénikem si také zafilozofují o kráse.
- MeSH
- Surgeons MeSH
- History, 20th Century MeSH
- History, 21st Century MeSH
- Surgery, Plastic MeSH
- Check Tag
- History, 20th Century MeSH
- History, 21st Century MeSH
- Publication type
- Interview MeSH
- Geographicals
- Czech Republic MeSH
- Conspectus
- Ortopedie. Chirurgie. Oftalmologie
- Biografie
- NML Fields
- plastická chirurgie
- About
- Měšťák, Ondřej Authority
V současnosti jsou estetické zákroky pomocí výplňových materiálů (VM) zejména na bázi hyaluronové kyseliny (HA) celosvětově hojně rozšířeny. Tento fenomén však s sebou nese i problémy, jako jsou nekontrolovaná produkce a variabilita kvality výplní, stejně jako neodborné aplikace. Roste proto výskyt nežádoucích reakcí a komplikací, z nichž zejména vaskulární mohou být velmi vážné až fatální. V důsledku rychlé globalizace a rozmachu sociálních médií dochází k posunu vnímání krásy napříč různými generacemi. V tomto kontextu je nezbytné, aby lékař uměl identifikovat motivaci pacienta. Rozlišil mezi tím, co si pacient přeje, a tím, co skutečně potřebuje, a přetvořil často přehnaná očekávání na realistické cíle (1). Komplikace spojené s aplikací dermálních výplní jsou tradičně rozděleny do čtyř základních kategorií: hypersenzitivní reakce, cévní příhody, infekce a opožděné zánětlivé změny. Jiné dělení zohleduje časový průběh komplikací na akutní (vaskulární okluze, zánětlivé reakce, reakce související s injekční aplikací, šíření materiálu) a opožděné (záněty, nodulární léze, dyspigmentace, dislokace výplně). Článek se zabývá pouze nevaskulárními komplikacemi a pro přehlednost je dělí na hypersenzititvní reakce (alergie), infekce, noduly, otoky, změny zabarvení kůže a ostatní. Pro optimální zvládání nežádoucích účinků je zásadní mít k dispozici praktický a přehledný protokol s rozhodovacím algoritmem. Součástí bezpečné praxe by měla být také interdisciplinární spolupráce.
Aesthetic interventions using hyaluronic acid-based filler materials are now widespread worldwide. However, this phenomenon also brings with it problems. Uncontrolled production and variation in the quality of fillers. Application of fillers by non-experts. Increasing incidence of adverse reactions and complications. Vascular complications can be very serious or even fatal. Due to rapid globalization and the rise of social media, there is a shift in the perception of beauty across generations. Therefore, it is essential for the physician to be able to identify the patient's motivation and differentiate between what the patient wants and what he or she actually needs and transform exaggerated expectations into realistic goals (1). Complications associated with the application of dermal fillers are commonly divided into four basic categories: hypersensitivity reactions, vascular events, infections, and delayed inflammatory changes. Another division considers the time course into acute (vascular occlusion, inflammatory reactions, injection-related reactions, spread of material) and delayed (inflammation, nodular lesions, dyspigmentation, dislocation of the filler). The article deals only with non-vascular complications and for clarity divides them into hypersensitivity reactions (allergy), infections, nodules, edema, skin discoloration and others. For optimal management of adverse effects, it is essential to have a practical and clear protocol with a decision-making algorithm. Interdisciplinary collaboration should also be part of safe practice.
- Keywords
- výplň rtu,
- MeSH
- Hypersensitivity etiology complications MeSH
- Edema etiology MeSH
- Hematoma etiology MeSH
- Skin Diseases, Infectious etiology MeSH
- Hyaluronic Acid * administration & dosage adverse effects MeSH
- Humans MeSH
- Plastic Surgery Procedures * methods adverse effects MeSH
- Check Tag
- Humans MeSH
The serotonergic psychedelics psilocybin, LSD and DMT hold great promise for the development of new treatments for psychiatric conditions such as major depressive disorder, addiction and end-of-life anxiety. Previous studies in both animals and humans have confirmed the effects of these drugs on neuronal activity and plasticity. However, the understanding of the mechanisms of action of these substances is limited. Here we show rapid effects of psychedelics on presynaptic properties, using live cell imaging at the level of single synapses in primary rat cortical neurons. Using the genetically encoded reporter of synaptic vesicle fusion synaptopHluorin, we detected a reduced fraction of synaptic vesicles that fused in response to mild or strong electrical stimulation 3-30 min after application of serotonergic psychedelics. These effects were transient and no longer present 24 h after treatment. While DMT only reduced the total recycling pool, LSD and psilocin also reduced the size of the readily releasable vesicle pool. Imaging with the sensors for glutamate, iGluSnFR, and presynaptic calcium, synGCaMP6, showed that while psilocin and DMT increased evoked glutamate release, LSD and psilocin reduced evoked presynaptic calcium levels. Interestingly, psilocin also affected short-term plasticity leading to a depression of responses to paired stimuli. The rapid and drug-specific modulation of glutamatergic neurotransmission described in this study may contribute to distinct anxiolytic and antidepressant properties of serotonergic psychedelics.
- MeSH
- Hallucinogens * pharmacology MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Glutamic Acid * metabolism MeSH
- Lysergic Acid Diethylamide pharmacology MeSH
- Cerebral Cortex * drug effects metabolism cytology MeSH
- Neurons * drug effects metabolism MeSH
- Rats, Sprague-Dawley MeSH
- Psilocybin pharmacology MeSH
- Serotonin Agents pharmacology MeSH
- Synaptic Vesicles drug effects metabolism MeSH
- Tryptamines pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The disease currently known as frontotemporal dementia (FTD) has undergone a complex evolution from its first description by Arnold Pick and later by Alois Alzheimer, through the first clinicopathological criteria introduced by David Neary and David Mann, to its current nomenclatural perception as a complex clinicopathological entity. Currently, Frontotemporal lobar degeneration is viewed as a heterogeneous syndrome caused by progressive degeneration of the frontal and temporal lobes of the brain. Clinically, it can manifest as three syndromes of frontotemporal dementia (behavioral variant of FTD, progressive non-fluent aphasia and semantic dementia) but also as so-called "overlap" syndromes involving corticobasal degeneration and progressive supranuclear palsy. Its prevalence is about 10 % among all dementias and 40 % among dementias with onset between 45 and 65 years of age. The clinical manifestation of the different subtypes varies, the common denominator being behavioral disturbances and impairment of fatic, gnostic and executive functions. Mnestic and visuo-spatial functions, although preserved for a relatively long time, are superimposed by personality disintegration, fatic, gnostic and executive dysfunction. Compared with Alzheimer's disease, it generally has an earlier age of onset, a more rapid course and more devastating impairment of individual cognitive domains. FTD has a heritability of more than 30 % according to current knowledge. The main genes involved are MAPT, C9orf72 and GRN. More rarely affected genes are VCP, TDP-43, FUS and CHMP2B. In our article, we focus on the genetics of FTD and the clinic-genetic-pathological correlations. We also aim to provide a plastic picture of how individual mutations affect the molecular mechanisms of neurodegeneration.
Brachyterapie je pokročilá metoda radioterapie používaná při léčbě onkologických onemocnění. Umožňuje nám zavedení radioaktivního zdroje přímo do nádoru nebo do jeho těsné blízkosti. Tato metoda umožňuje aplikovat záření s minimálním dopadem na okolní zdravé tkáně a používá se při léčbě u specifických typů nádorů. Avšak i při této metodě mohou vznikat nežádoucí vedlejší účinky, proto je důležitá spolupráce pacienta se zdravotnickým personálem. Je kladen důraz na správnou edukaci pacienta o péči ozařované oblasti a plastových katétrů. Tento článek se zaměřuje na roli všeobecné sestry při ošetřování pacientů podstupujících intersticiální brachyterapii karcinomu penisu, karcinomu prsu a nádorů ORL oblasti.
Brachytherapy is an advanced method of radiotherapy used in the treatment of cancer. It allows us to introduce a radioactive source directly into the tumour or in close proximity to it. This method allows radiation to be applied with minimal impact on surrounding healthy tissue and is used in the treatment of specific types of tumours. However, this method can also cause unwanted side effects, so it is important that the patient cooperates with the medical staff. Emphasis is placed on proper patient education about the care of the irradiated area and the plastic catheters. This article focuses on the role of the nurse in the care of patients undergoing interstitial brachytherapy for penile cancer, breast cancer and ENT region tumors.
Extracellular matrix (ECM) is a network of macromolecules which has two forms-perineuronal nets (PNNs) and a diffuse ECM (dECM)-both influence brain development, synapse formation, neuroplasticity, CNS injury and progression of neurodegenerative diseases. ECM remodeling can influence extrasynaptic transmission, mediated by diffusion of neuroactive substances in the extracellular space (ECS). In this study we analyzed how disrupted PNNs and dECM influence brain diffusibility. Two months after oral treatment of rats with 4-methylumbelliferone (4-MU), an inhibitor of hyaluronan (HA) synthesis, we found downregulated staining for PNNs, HA, chondroitin sulfate proteoglycans, and glial fibrillary acidic protein. These changes were enhanced after 4 and 6 months and were reversible after a normal diet. Morphometric analysis further indicated atrophy of astrocytes. Using real-time iontophoretic method dysregulation of ECM resulted in increased ECS volume fraction α in the somatosensory cortex by 35%, from α = 0.20 in control rats to α = 0.27 after the 4-MU diet. Diffusion-weighted magnetic resonance imaging revealed a decrease of mean diffusivity and fractional anisotropy (FA) in the cortex, hippocampus, thalamus, pallidum, and spinal cord. This study shows the increase in ECS volume, a loss of FA, and changes in astrocytes due to modulation of PNNs and dECM that could affect extrasynaptic transmission, cell-to-cell communication, and neural plasticity.
- MeSH
- Astrocytes metabolism MeSH
- Chondroitin Sulfate Proteoglycans metabolism MeSH
- Extracellular Matrix * metabolism MeSH
- Extracellular Space * metabolism MeSH
- Glial Fibrillary Acidic Protein metabolism MeSH
- Hymecromone pharmacology MeSH
- Rats MeSH
- Hyaluronic Acid MeSH
- Brain metabolism MeSH
- Nerve Net drug effects diagnostic imaging MeSH
- Rats, Sprague-Dawley MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH