enhancement factor
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The tumor microenvironment (TME) is a complex, highly structured, and dynamic ecosystem that plays a pivotal role in the progression of both primary and metastatic tumors. Precise assessment of the dynamic spatiotemporal features of the TME is crucial for understanding cancer evolution and designing effective therapeutic strategies. Cancer is increasingly recognized as a systemic disease, influenced not only by the TME, but also by a multitude of systemic factors, including whole-body metabolism, gut microbiome, endocrine signaling, and circadian rhythm. In this review, we summarize the intrinsic, extrinsic, and systemic factors contributing to the formation of 'cold' tumors within the framework of the cancer-immunity cycle. Correspondingly, we discuss potential strategies for converting 'cold' tumors into 'hot' ones to enhance therapeutic efficacy.
- MeSH
- cirkadiánní rytmus MeSH
- lidé MeSH
- nádorové mikroprostředí * imunologie MeSH
- nádory * patologie terapie MeSH
- střevní mikroflóra MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
MicroRNAs (miRNAs) have emerged as important regulators of gene expression in various biological processes, including cancer. miR-182-5p has gained attention for its potential implications in gynecologic cancers, including breast, ovarian, endometrial, and cervical cancers. miR-182-5p dysregulation has been associated with multiple facets of tumor biology in gynecologic cancers, including tumor initiation, progression, metastasis, and therapeutic response. Studies have highlighted its involvement in key signaling pathways and cellular processes that contribute to cancer development and progression. In addition, miR-182-5p has shown potential as a diagnostic and prognostic biomarker, with studies demonstrating its correlation with clinicopathological features and patient outcomes. Furthermore, the therapeutic potential of miR-182-5p is being explored in gynecologic cancers. Strategies such as miRNA mimics or inhibitors targeting miR-182-5p have shown promise in preclinical and early clinical studies. These approaches aim to modulate miR-182-5p expression, restoring normal cellular functions and potentially enhancing treatment responses. Understanding the biologic and clinical implications of miR-182-5p in gynecologic cancers is crucial for the development of targeted therapeutic strategies and personalized medicine approaches. Further investigations are needed to unravel the specific target genes and pathways regulated by miR-182-5p. It is important to consider the emerging biologic and clinical implications of miR-182-5p in gynecologic cancers.
Microbial transglutaminase (MTG) is an enzyme widely used in the food industry because it creates cross-links between proteins, enhancing the texture and stability of food products. Its unique properties make it a valuable tool for modifying the functional characteristics of proteins, significantly impacting the quality and innovation of food products. In this study, response surface methodology was employed to optimize the fermentation conditions for microbial transglutaminase production by the strain Streptoverticillium cinnamoneum KKP 1658. The effects of nitrogen dose, cultivation time, and initial pH on the activity of the produced transglutaminase were investigated. The significance of the examined factors was determined as follows: cultivation time > nitrogen dose > pH. The interaction between nitrogen dose and cultivation time was found to be crucial, having the second most significant impact on transglutaminase activity. Optimal conditions were identified as 48 h of cultivation with a 2% nitrogen source dose and an initial medium pH of approximately 6.0. Under these conditions, transglutaminase activity ranged from 4.5 to 5.5 U/mL. The results of this study demonstrated that response surface methodology is a promising approach for optimizing microbial transglutaminase production. Future applications of transglutaminase include the development of modern food products with improved texture and nutritional value, as well as its potential use in regenerative medicine for creating biomaterials and tissue scaffolds. This topic is particularly important and timely as it addresses the growing demand for innovative and sustainable solutions in the food and biomedical industries, contributing to an improved quality of life.
BACKGROUND: Robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly adopted in centers worldwide, with ongoing refinements to enhance results. This study aims to assess the current state of RAMIE worldwide and to identify potential areas for improvement. METHODS: This descriptive study analyzed prospective data from esophageal cancer patients who underwent transthoracic RAMIE in Upper GI International Robotic Association (UGIRA) centers. Main endpoints included textbook outcome rate, surgical techniques, and perioperative outcomes. Analyses were performed separately for intrathoracic (Ivor-Lewis) and cervical anastomosis (McKeown), divided into three time cohorts (2016-2018, 2019-2020, 2021-2023). A sensitivity analysis was conducted with cases after the learning curve (> 70 cases). RESULTS: Across 28 UGIRA centers, 2012 Ivor-Lewis and 1180 McKeown procedures were performed. Over the time cohorts, textbook outcome rates were 39%, 48%, and 49% for Ivor-Lewis, and 49%, 63%, and 61% for McKeown procedures, respectively. Fully robotic procedures accounted for 66%, 51%, and 60% of Ivor-Lewis procedures, and 53%, 81%, and 66% of McKeown procedures. Lymph node yield showed 27, 30, and 30 nodes in Ivor-Lewis procedures, and 26, 26, and 34 nodes in McKeown procedures. Furthermore, high mediastinal lymphadenectomy was performed in 65%, 43%, and 37%, and 70%, 48%, and 64% of Ivor-Lewis and McKeown procedures, respectively. Anastomotic leakage rates were 22%, 22%, and 16% in Ivor-Lewis cases, and 14%, 12%, and 11% in McKeown cases. Hospital stay was 13, 14, and 13 days for Ivor-Lewis procedures, and 12, 9, and 11 days for McKeown procedures. In Ivor-Lewis and McKeown, respectively, the sensitivity analysis revealed textbook outcome rates of 43%, 54%, and 51%, and 47%, 64%, and 64%; anastomotic leakage rates of 28%, 18%, and 15%, and 13%, 11%, and 10%; and hospital stay of 11, 12, and 12 days, and 10, 9, and 9 days. CONCLUSIONS: This study demonstrates favorable outcomes over time in achieving textbook outcome after RAMIE. Areas for improvement include a reduction of anastomotic leakage and shortening of hospital stay.
- MeSH
- ezofagektomie * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- miniinvazivní chirurgické výkony metody MeSH
- nádory jícnu * chirurgie patologie MeSH
- následné studie MeSH
- pooperační komplikace epidemiologie MeSH
- prognóza MeSH
- prospektivní studie MeSH
- registrace * MeSH
- roboticky asistované výkony * metody MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are crucial diagnostic modalities that require patients to remain immobile for extended periods, with anesthesia sometimes used for comfort and image quality enhancement. The study compares dexmedetomidine and propofol in reducing recovery time and sedation onset in pediatric and elderly patients undergoing CT and MRI procedures. A meta-analysis of fifteen studies assessing recovery time, sedation onset, and failed sedation between dexmedetomidine and propofol in pediatric and elderly patients during CT and MRI was conducted. The study indicated that the administration of anaesthesia markedly improved patient compliance and reduced motion artefacts in both CT and MRI (P<0.00001, I2=94%). The meta-analysis indicated that the mean difference (MD) in the onset of sedation was significantly faster in the control group (P<0.00001, I2=96%). The study reveals that dexmedetomidine and propofol anesthesia can improve patient image quality during CT and MRI procedures by reducing motion artefacts. Dexmedetomidine sedated people more quickly than propofol, but no significant differences in sedation duration were observed.
- MeSH
- časové faktory MeSH
- dexmedetomidin * aplikace a dávkování MeSH
- dítě MeSH
- hypnotika a sedativa * aplikace a dávkování MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- počítačová rentgenová tomografie * metody MeSH
- předškolní dítě MeSH
- probouzení z anestezie * MeSH
- propofol * aplikace a dávkování MeSH
- senioři MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- předškolní dítě MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
The FGFR3::TACC3 fusion has been reported in subsets of diverse cancers including urothelial and squamous cell carcinomas (SCC). However, the morphology of FGFR3::TACC3-positive head and neck carcinomas has not been well studied and it is unclear if this fusion represents a random event, or if it might characterize a morphologically distinct tumor type. We describe nine FGFR3::TACC3 fusion-positive head and neck carcinomas affecting six males and three females aged 38 to 89 years (median, 59). The tumors originated in the sinonasal tract (n = 4), parotid gland (n = 2), and one case each in the oropharynx, submandibular gland, and larynx. At last follow-up (9-21 months; median, 11), four patients developed local recurrence and/or distant metastases, two died of disease at 11 and 12 months, one died of other cause, one was alive with disease, and two were disease-free. Three of six tumors harbored high risk oncogenic HPV infection (HPV33, HPV18, one unspecified). Histologically, three tumors revealed non-keratinizing transitional cell-like or non-descript morphology with variable mixed inflammatory infiltrate reminiscent of mucoepidermoid or DEK::AFF2 carcinoma (all were HPV-negative), and three were HPV-associated (all sinonasal) with multiphenotypic (1) and non-intestinal adenocarcinoma (2) pattern, respectively. One salivary gland tumor showed poorly cohesive large epithelioid cells with prominent background inflammation and expressed AR and GATA3, in line with a possible salivary duct carcinoma variant. Two tumors were conventional SCC. Targeted RNA sequencing revealed an in-frame FGFR3::TACC3 fusion in all cases. This series highlights heterogeneity of head and neck carcinomas harboring FGFR3::TACC3 fusions, which segregates into three categories: (1) unclassified HPV-negative category, morphologically distinct from SCC and other entities; (2) heterogeneous group of HPV-associated carcinomas; and (3) conventional SCC. A driver role of the FGFR3::TACC3 fusion in the first category (as a potential distinct entity) remains to be further studied. In the light of available FGFR-targeting therapies, delineation of these tumors and enhanced recognition is recommended.
- MeSH
- dlaždicobuněčné karcinomy hlavy a krku virologie patologie genetika MeSH
- dospělí MeSH
- fenotyp MeSH
- fúzní onkogenní proteiny genetika MeSH
- infekce papilomavirem * patologie komplikace genetika virologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery genetika MeSH
- nádory hlavy a krku * patologie virologie genetika MeSH
- proteiny asociované s mikrotubuly genetika MeSH
- receptor fibroblastových růstových faktorů, typ 3 * genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinocelulární karcinom patologie genetika virologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Apple replant disease (ARD) is a significant factor restricting the healthy development of the apple industry. Biological control is an important and sustainable method for mitigating ARD. In this study, a strain of Paenibacillus polymyxa GRY-11 was isolated and screened from the rhizosphere soil of healthy apple trees in old apple orchards in Shandong Province, China, and the effects of strain GRY-11 on soil microbial community and ARD were studied. The result showed that P. polymyxa GRY-11 could effectively inhibit the growth of the main pathogenic fungi that caused ARD, and the inhibition rates of the strain against Fusarium moniliforme, Fusarium proliferatum, Fusarium solani, and Fusarium oxysporum were 80.00%, 71.60%, 75.00%, and 70.00%, respectively. In addition, the fermentation supernatant played an active role in suppressing the growth of pathogenic fungi. The results of the pot experiment showed that the bacterial fertilizer of the GRY-11 promoted the growth of Malus hupehensis seedlings, improved the activity of protective enzymes in plant roots, enhanced the soil enzyme content, and optimized the soil microbial environment. In general, the GRY-11 can be used as an effective microbial preparation to alleviate ARD. Our study offers novel perspectives for the prevention of ARD.
- MeSH
- antibióza MeSH
- biologická kontrola škůdců * MeSH
- biologická ochrana * MeSH
- Fusarium růst a vývoj MeSH
- houby růst a vývoj MeSH
- kořeny rostlin mikrobiologie MeSH
- Malus * mikrobiologie růst a vývoj MeSH
- nemoci rostlin * mikrobiologie prevence a kontrola MeSH
- Paenibacillus polymyxa * izolace a purifikace fyziologie genetika klasifikace MeSH
- půdní mikrobiologie MeSH
- rhizosféra MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Čína MeSH
Immunotherapy represents a revolutionary advancement in cancer treatment, which has traditionally focused on T cells; however, the role of B cells in cancer immunotherapy has gained interest because of their role in antigen presentation, antibody production, and cytokine release. In this study, we examined the role of B cells in previously developed intratumoral MBTA therapy (mannan-BAM, TLR ligands, and anti-CD40 antibody) in murine models of MTT pheochromocytoma. The results indicated that B cells significantly enhance the success of MBTA therapy, with wild-type mice exhibiting a lower tumor incidence and smaller tumors compared with B cell-deficient mice. Increased IL-6 and TNF-alpha levels indicated severe inflammation and a potential cytokine storm in B cell-deficient mice. Neutralization of TNF-alpha ameliorated these complications but resulted in increased tumor recurrence. The results highlight the important role of B cells in enhancing the immune response and maintaining immune homeostasis during MBTA therapy. Our findings offer new insights into improving therapeutic outcomes.
- MeSH
- B-lymfocyty * imunologie MeSH
- feochromocytom * imunologie terapie MeSH
- imunoterapie * metody MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádory nadledvin * imunologie terapie MeSH
- TNF-alfa MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Intramural MeSH
OBJECTIVES: This study quantified blood bicarbonate (HCO3-) kinetics and gastrointestinal upset to determine the gender-related ergogenic potential of sodium bicarbonate (0.15-, 0.25- and 0.35 gSB·kgFat-free mass (FFM)-1) in high intensity functional training. DESIGN: Double-blind randomized placebo-controlled crossover. METHODS: Thirty female and male athletes performed two bouts of the Wingate Anaerobic Test (WAnTPRE-HIFT and WAnTPOST-HIFT) interspaced with two 3-min bouts of Wall Balls and Burpees 120 min after ingestion of three sodium bicarbonate doses. Blood HCO3- was determined pre-ingestion, after supplementation and before/post exercise. Gastrointestinal upset was evaluated 120 min post-ingestion. Control (CTRL) measurements were performed. RESULTS: There were significant gender × treatment interactions for: changes in blood HCO3- at 60 min post-ingestion (p = 0.014; η2p = 0.104; at 0.15 gSB·kgFFM-1 males experienced higher increase than females); peak power (p = 0.015; η2p = 0.103) and average power (p = 0.005; η2p = 0.124) during WAnTPOST-HIFT, and changes in peak power between the Wingate Anaerobic Test bouts (p = 0.049; η2p = 0.081). Sodium bicarbonate compared to PLA had no significant impact on Wall Balls and Burpees performance. The dose of 0.35 gSB·kgFFM-1 resulted in higher less severe gastrointestinal symptoms compared to CTRL and 0.15 gSB·kgFFM-1 (p = 0.001; W = 0.178); and higher total gastrointestinal upset compared to CTRL, PLA and 0.15 gSB·kgFFM-1 (p < 0.001; W = 0.323). CONCLUSIONS: There were dose- and gender-related differences in extracellular buffering capacity and ergogenic potential of sodium bicarbonate. The study suggested a detrimental impact of gastrointestinal upset on performance.
- MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- hydrogenuhličitan sodný * aplikace a dávkování farmakologie krev MeSH
- klinické křížové studie * MeSH
- látky zvyšující výkon aplikace a dávkování farmakologie MeSH
- lidé MeSH
- mladý dospělý MeSH
- sexuální faktory MeSH
- zátěžový test MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
Cieľ: Cieľom tejto štúdie bolo analyzovať rizikové faktory, ktoré sa odlišujú u novorodencov s nízkou pôrodnou hmotnosťou vzhľadom na gestačný vek (SGA – small for gestational age) a novorodencov s primeranou pôrodnou hmotnosťou vzhľadom na gestačný vek (AGA – appropriate for gestational age). Materiály a metódy: Retrospektívno-prospektívna kohortová štúdia bola realizovaná v rokoch 2019–2024 na II. gynekologicko-pôrodníckej klinike Univerzitnej nemocnice Bratislava. Do štúdie bolo zahrnutých 174 donosených novorodencov z jednoplodových tehotenstiev, z toho 125 novorodencov s nízkou pôrodnou hmotnosťou (SGA) a 49 novorodencov s primeranou pôrodnou hmotnosťou (AGA). Analyzované boli rôzne materské, fetálne a placentárne rizikové faktory, s osobitným zameraním na kongenitálnu cytomegalovírusovú infekciu (cCMV). Výsledky: Pôrodná hmotnosť novorodencov sa pohybovala v rozmedzí od 1 480 do 4 470 gramov. Z hodnotených rizikových faktorov bola významne asociovaná s AGA materská infekcia covidom-19 počas tehotenstva (p = 0,009). Nebola zistená štatisticky významná súvislosť medzi bežnými rizikovými faktormi (napr. hypertenzia, diabetes mellitus) a rastovou reštrikciou plodu. Kongenitálna CMV infekcia nebola významne spojená s SGA. Analýza pomocou logistickej regresie potvrdila asociáciu infekcie covidom-19 s pôrodnou hmotnosťou, zatiaľ čo pri CMV nebol pozorovaný žiadny významný vplyv. Záver: Materská infekcia covidom-19 bola asociovaná s primeranou pôrodnou hmotnosťou vzhľadom na gestačný vek, pravdepodobne v dôsledku zvýšeného lekárskeho dohľadu a imunitnej odpovede. Interpretácia týchto výsledkov je však obmedzená malou veľkosťou súboru, a preto je potrebný ďalší výskum na pochopenie vplyvu covidu-19 na tehotenstvo. V tejto kohorte nebola zistená významná súvislosť medzi kongenitálnou CMV infekciou a rastovou reštrikciou plodu, pravdepodobne v dôsledku nízkej prevalencie cCMV. Dokumentované rizikové faktory intrauterinná rastove reštrikcie, vrátane hypertenzie a diabetes mellitus, neboli v študovanej populácii štatisticky významné.
Objective: This study aimed to analyse the risk factors differentiating small for gestational age (SGA) and appropriate for gestational age (AGA) neonates. Materials and methods: A retrospective-prospective cohort study was conducted from 2019 to 2024 at the 2nd Department of Obstetrics and Gynaecology, University Hospital Bratislava. The study involved 174 term neonates from singleton pregnancies, including 125 SGA and 49 AGA infants. Various maternal, foetal, and placental risk factors were analysed, with a particular focus on congenital cytomegalovirus infection (cCMV). Results: Neonates’ birth weights ranged from 1,480 to 4,470 grams. Of the risk factors assessed, only maternal COVID-19 infection during pregnancy was significantly associated with AGA outcomes (P = 0.009). No significant associations were found between common risk factors (e. g. hypertension, diabetes mellitus) and foetal growth restriction. Congenital CMV infection was not significantly associated with SGA. Logistic regression analysis confirmed the association of COVID-19 infection with foetal weight, while no significant effect was observed for CMV. Conclusion: Maternal COVID-19 infection was associated with AGA outcomes, potentially due to enhanced medical surveillance and immune responses. However, the study’s small sample size limits the interpretation of these findings, and further research is required to fully understand the impacts of COVID-19 on pregnancy. No significant association between congenital CMV infection and foetal growth restriction was found in this cohort, which was most likely due to the low prevalence of cCMV. Moreover, documented risk factors for foetal growth restriction, including hypertension and diabetes mellitus, were not statistically significant in our study population.
