BACKGROUND: Diffuse midline glioma, H3 K27-altered (DMG) is a fatal tumour that arises in the midline structures of the brain. When located in the pons, it is more commonly referred to as diffuse intrinsic pontine glioma (DIPG). DMG/DIPG is usually diagnosed when children are < 10 years, and it has a median overall survival of < 12 months after diagnosis. Radiological imaging is still the gold standard for DIPG diagnosis while the use of biopsy procedures led to our knowledge on its biology, such as with the identification of the canonical histone H3K27M mutation. However, the need to improve survival encourages the development of non-invasive, fast and inexpensive assays on biofluids for optimizing molecular diagnoses in DMG/DIPG. Here, we propose a rapid, new, imaging and epigenetics-based approach to diagnose DMG/DIPG in the plasma of paediatric patients. METHODS: A total of 20 healthy children (mean age: 10.5 years) and 24 children diagnosed with DMG/DIPG (mean age: 8.5 years) were recruited. Individual histones (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2), histone dimers and nucleosomes were assayed in biofluids by means of a new advanced flow cytometry ImageStream(X)-adapted method. RESULTS: We report a significant increase in circulating histone dimers and tetramers (macroH2A1.1/H2B versus control: p value < 0.0001; macroH2A1.2/H2B versus control: p value < 0.0001; H2A/H2B versus control: p value < 0.0001; H3/H4 versus control: p value = 0.008; H2A/H2B/H3/H4 versus control: p value < 0.0001) and a significant downregulation of individual histones (H2B versus control: p value < 0.0001; H3 versus control: p value < 0.0001; H4 versus control: p value < 0.0001). Moreover, histones were also detectable in the cerebrospinal fluid (CSF) of patients with DMG/DIPG and in the supernatant of SF8628, OPBG-DIPG002 and OPBG-DIPG004 DMG/DIPG cell lines, with patterns mostly similar to each other, but distinct compared to blood plasma. CONCLUSIONS: In summary, we identified circulating histone signatures able to detect the presence of DMG/DIPG in biofluids of children, using a rapid and non-invasive ImageStream(X)-based imaging technology, which may improve diagnosis and benefit the patients.

• MeSH
• Diffuse Intrinsic Pontine Glioma genetics   diagnosis   blood   MeSH
• Child MeSH
• Epigenesis, Genetic MeSH
• Glioma genetics   diagnosis   blood   pathology   diagnostic imaging   MeSH
• Histones * genetics   metabolism   blood   MeSH
• Humans MeSH
• Adolescent MeSH
• Mutation MeSH
• Biomarkers, Tumor blood   MeSH
• Brain Stem Neoplasms genetics   diagnosis   blood   diagnostic imaging   pathology   metabolism   MeSH
• Child, Preschool MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't 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

BACKGROUND: Emerging evidence suggests that tumour morphological heterogeneity may influence mutational profiles relevant to therapy response. In this pilot study, we aimed to assess whether mutations identified within specific morphological patterns or at the invasion front correlate with shorter time to progression after anti-EGFR therapy, as compared to whole-tissue analysis. METHODS: We investigated genetic mutations in 142 samples from primary tumours of 39 KRAS wild-type metastatic colorectal cancer (CRC) patients receiving anti-EGFR therapy. Deep next-generation sequencing was performed on whole-tumour sections and six morphology-defined tumour regions. RESULTS: Mutations in genes linked to anti-EGFR therapy response (KRAS, BRAF, NRAS, PTEN and PI3KCA) were found uniquely in the non-responder group, with substantial variability across morphological sub-regions. BRAF mutations were aligned with serrated and mucinous morphologies, while KRAS mutations (p.Lys147Glu and p.Ala146Thr) were associated with mucinous and desmoplastic morphologies. In all cases, the cumulative mutational profile from sub-regions provided more details than that of the whole-tumour profile. CONCLUSION: Our findings highlight that comprehensive analysis, considering morphological heterogeneity, is crucial for personalised CRC treatment strategies.

• MeSH
• Drug Resistance, Neoplasm * genetics   MeSH
• Adult MeSH
• ErbB Receptors antagonists & inhibitors   MeSH
• PTEN Phosphohydrolase genetics   MeSH
• GTP Phosphohydrolases genetics   MeSH
• Protein Kinase Inhibitors * therapeutic use   MeSH
• Colorectal Neoplasms * genetics   drug therapy   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation * MeSH
• DNA Mutational Analysis MeSH
• Pilot Projects MeSH
• Antineoplastic Agents * therapeutic use   MeSH
• Proto-Oncogene Proteins B-raf genetics   MeSH
• Proto-Oncogene Proteins p21(ras) genetics   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• High-Throughput Nucleotide Sequencing 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

Zoonózy se každoročně v České republice významně podílejí na počtu hlášených infekčních onemocnění. Stoupající tendence výskytu zoonotických virů, jako je virus zika virus, virus horečky dengue, virus chikungunyi a virus západonilské horečky, přenášených invazivními tropickými druhy komárů, je v první řadě důsledkem dlouhodobého, postupného a prakticky nezastavitelného šíření tohoto hmyzu po evropském kontinentu, včetně severských států. Evropa nyní již pravidelně zažívá opakované každoroční vlny veder, stejně jako časté záplavy. Navyšuje se nejen počet letních dnů s tropickými teplotami, ale období léta jako takového se významně prodlužuje. Stírají se jarní a podzimní období, rychlost nástupu letních teplot po období zim je často až drastická. Tento proces navozuje příznivé životní podmínky pro etablování tropických druhů komárů na našem území. Například ještě v roce 2013 se invazivní druh komára Aedes albopictus, původem z Asie, vyskytoval „pouze" v osmi evropských zemích a zasaženo bylo 114 regionů. O pouhých deset let později byl jeho výskyt potvrzen již ve třinácti zemích a 337 oblastech, včetně České republiky. Tento trend bude pokračovat, je proto nutné očekávat nárůsty autochtonních infekcí, včetně komplikovaných průběhů infekcí a úmrtí, obzvláště v rizikových skupinách rychle stárnoucí evropské populace. Kromě nutnosti hledat nové způsoby kontroly populací komárů, vývoje nových desinsekčních a larvicidních chemikálií je třeba zásadně posilovat programy surveillance napříč spolupracující Evropou, prosazovat používání osobních ochranných pomůcek a jednoznačně posílit výzkum a vývoj specifických antivirotik a nových očkovacích látek.

Zoonoses contribute significantly to the number of reported infectious diseases in the Czech Republic each year. The rising trend in zoonotic viruses such as Zika virus, dengue virus, Chikungunya virus, West Nile virus, transmitted by invasive tropical mosquito species, is primarily due to the long-term, gradual and virtually unstoppable spread of these insects across the European continent, including the Nordic countries. Europe now regularly experiences recurrent annual heat waves as well as frequent flooding. Not only are the number of summer days with tropical temperatures increasing, but the summer period itself is being significantly extended. The spring and autumn seasons are becoming shorter, and the speed of the onset of summer temperatures after winter is often drastic. This process creates favorable living conditions for the establishment of tropical mosquito species in our territory. For example, as recently as 2013, the invasive mosquito species Aedes albopictus, native to Asia, was present in "only" eight European countries and 114 regions were affected. In 2023, its presence has already been confirmed in thirteen countries and 337 regions, including the Czech Republic. This trend is set to continue, so increases in autochthonous infections, including complicated infection patterns and deaths, are to be expected, especially in at-risk groups of the rapidly ageing European population. In addition to the need to find new ways of controlling mosquito populations, the development of new disinsecticidal and larvicidal chemicals, surveillance programs across a cooperating Europe need to be substantially strengthened, the use of personal protective equipment needs to be promoted, and research and development of specific antivirals and new vaccines needs to be clearly stepped up.

• Keywords
• tropičtí komáři,
• MeSH
• Culicidae MeSH
• Zika Virus Infection epidemiology   transmission   therapy   MeSH
• Mosquito Vectors * MeSH
• Humans MeSH
• Zika Virus * isolation & purification   drug effects   MeSH
• Zoonoses * epidemiology   transmission   therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH

At a population level, the European Society of Gastrointestinal Endoscopy (ESGE), the European Helicobacter and Microbiota Study Group (EHMSG), and the European Society of Pathology (ESP) suggest endoscopic screening for gastric cancer (and precancerous conditions) in high-risk regions (age-standardized rate [ASR] > 20 per 100 000 person-years) every 2 to 3 years or, if cost-effectiveness has been proven, in intermediate risk regions (ASR 10-20 per 100 000 person-years) every 5 years, but not in low-risk regions (ASR < 10).ESGE/EHMSG/ESP recommend that irrespective of country of origin, individual gastric risk assessment and stratification of precancerous conditions is recommended for first-time gastroscopy. ESGE/EHMSG/ESP suggest that gastric cancer screening or surveillance in asymptomatic individuals over 80 should be discontinued or not started, and that patients' comorbidities should be considered when treatment of superficial lesions is planned.ESGE/EHMSG/ESP recommend that a high quality endoscopy including the use of virtual chromoendoscopy (VCE), after proper training, is performed for screening, diagnosis, and staging of precancerous conditions (atrophy and intestinal metaplasia) and lesions (dysplasia or cancer), as well as after endoscopic therapy. VCE should be used to guide the sampling site for biopsies in the case of suspected neoplastic lesions as well as to guide biopsies for diagnosis and staging of gastric precancerous conditions, with random biopsies to be taken in the absence of endoscopically suspected changes. When there is a suspected early gastric neoplastic lesion, it should be properly described (location, size, Paris classification, vascular and mucosal pattern), photodocumented, and two targeted biopsies taken.ESGE/EHMSG/ESP do not recommend routine performance of endoscopic ultrasonography (EUS), computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)-CT prior to endoscopic resection unless there are signs of deep submucosal invasion or if the lesion is not considered suitable for endoscopic resection.ESGE/EHMSG/ESP recommend endoscopic submucosal dissection (ESD) for differentiated gastric lesions clinically staged as dysplastic (low grade and high grade) or as intramucosal carcinoma (of any size if not ulcerated or ≤ 30 mm if ulcerated), with EMR being an alternative for Paris 0-IIa lesions of size ≤ 10 mm with low likelihood of malignancy.ESGE/EHMSG/ESP suggest that a decision about ESD can be considered for malignant lesions clinically staged as having minimal submucosal invasion if differentiated and ≤ 30 mm; or for malignant lesions clinically staged as intramucosal, undifferentiated and ≤ 20 mm; and in both cases with no ulcerative findings.ESGE/EHMSG/ESP recommends patient management based on the following histological risk after endoscopic resection: Curative/very low-risk resection (lymph node metastasis [LNM] risk < 0.5 %-1 %): en bloc R0 resection; dysplastic/pT1a, differentiated lesion, no lymphovascular invasion, independent of size if no ulceration and ≤ 30 mm if ulcerated. No further staging procedure or treatment is recommended.Curative/low-risk resection (LNM risk < 3 %): en bloc R0 resection; lesion with no lymphovascular invasion and: a) pT1b, invasion ≤ 500 μm, differentiated, size ≤ 30 mm; or b) pT1a, undifferentiated, size ≤ 20 mm and no ulceration. Staging should be completed, and further treatment is generally not necessary, but a multidisciplinary discussion is required. Local-risk resection (very low risk of LNM but increased risk of local persistence/recurrence): Piecemeal resection or tumor-positive horizontal margin of a lesion otherwise meeting curative/very low-risk criteria (or meeting low-risk criteria provided that there is no submucosal invasive tumor at the resection margin in the case of piecemeal resection or tumor-positive horizontal margin for pT1b lesions [invasion ≤ 500 μm; well-differentiated; size ≤ 30 mm, and VM0]). Endoscopic surveillance/re-treatment is recommended rather than other additional treatment. High-risk resection (noncurative): Any lesion with any of the following: (a) a positive vertical margin (if carcinoma) or lymphovascular invasion or deep submucosal invasion (> 500 μm from the muscularis mucosae); (b) poorly differentiated lesions if ulceration or size > 20 mm; (c) pT1b differentiated lesions with submucosal invasion ≤ 500 μm with size > 30 mm; or (d) intramucosal ulcerative lesion with size > 30 mm. Complete staging and strong consideration for additional treatments (surgery) in multidisciplinary discussion.ESGE/EHMSG/ESP suggest the use of validated endoscopic classifications of atrophy (e. g. Kimura-Takemoto) or intestinal metaplasia (e. g. endoscopic grading of gastric intestinal metaplasia [EGGIM]) to endoscopically stage precancerous conditions and stratify the risk for gastric cancer.ESGE/EHMSG/ESP recommend that biopsies should be taken from at least two topographic sites (2 biopsies from the antrum/incisura and 2 from the corpus, guided by VCE) in two separate, clearly labeled vials. Additional biopsy from the incisura is optional.ESGE/EHMSG/ESP recommend that patients with extensive endoscopic changes (Kimura C3 + or EGGIM 5 +) or advanced histological stages of atrophic gastritis (severe atrophic changes or intestinal metaplasia, or changes in both antrum and corpus, operative link on gastritis assessment/operative link on gastric intestinal metaplasia [OLGA/OLGIM] III/IV) should be followed up with high quality endoscopy every 3 years, irrespective of the individual's country of origin.ESGE/EHMSG/ESP recommend that no surveillance is proposed for patients with mild to moderate atrophy or intestinal metaplasia restricted to the antrum, in the absence of endoscopic signs of extensive lesions or other risk factors (family history, incomplete intestinal metaplasia, persistent H. pylori infection). This group constitutes most individuals found in clinical practice.ESGE/EHMSG/ESP recommend H. pylori eradication for patients with precancerous conditions and after endoscopic or surgical therapy.ESGE/EHMSG/ESP recommend that patients should be advised to stop smoking and low-dose daily aspirin use may be considered for the prevention of gastric cancer in selected individuals with high risk for cardiovascular events.

• MeSH
• Biopsy MeSH
• Early Detection of Cancer * methods   standards   MeSH
• Gastroscopy * standards   MeSH
• Risk Assessment MeSH
• Helicobacter Infections complications   MeSH
• Humans MeSH
• Stomach Neoplasms * pathology   diagnosis   therapy   MeSH
• Precancerous Conditions * pathology   diagnosis   therapy   MeSH
• Societies, Medical MeSH
• Gastric Mucosa pathology   diagnostic imaging   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Practice Guideline MeSH
• Geographicals
• Europe MeSH

BACKGROUND: Detrimental effects of misinformation were observed during the COVID-19 pandemic. Presently, amid Russia's military aggression in Ukraine, another wave of misinformation is spreading on the web and impacting our daily lives, with many citizens and politicians embracing Russian propaganda narratives. Despite the lack of an objective connection between these 2 societal issues, anecdotal observations suggest that supporters of misinformation regarding COVID-19 (BM-C) have also adopted misinformation about the war in Ukraine (BM-U) while sharing similar media use patterns and political attitudes. OBJECTIVE: The aim of this study was to determine whether there is a link between respondents' endorsement of the 2 sets of misinformation narratives, and whether some of the selected factors (media use, political trust, vaccine hesitancy, and belief rigidity) are associated with both BM-C and BM-U. METHODS: We conducted a survey on a nationally representative sample of 1623 individuals in the Czech Republic. Spearman correlation analysis was performed to identify the relationship between BM-C and BM-U. In addition, multiple linear regression was used to determine associations between the examined factors and both sets of misinformation. RESULTS: We discovered that BM-C and BM-U were moderately correlated (Spearman ρ=0.57; P<.001). Furthermore, increased trust in Russia and decreased trust in the local government, public media, and Western allies of the Czech Republic predicted both BM-C and BM-U. Media use indicating frustration with and avoidance of public or mainstream media, consumption of alternative information sources, and participation in web-based discussions indicative of epistemic bubbles predicted beliefs in misinformation narratives. COVID-19 vaccine refusal predicted only BM-C but not BM-U. However, vaccine refusers were overrepresented in the BM-U supporters (64/161, 39.8%) and undecided (128/505, 25.3%) individuals. Both beliefs were associated with belief rigidity. CONCLUSIONS: Our study provides empirical evidence that supporters of COVID-19 misinformation were susceptible to ideological misinformation aligning with Russian propaganda. Supporters of both sets of misinformation narratives were primarily linked by their shared trust or distrust in the same geopolitical actors and their distrust in the local government.

• MeSH
• COVID-19 * prevention & control   epidemiology   psychology   MeSH
• Adult MeSH
• Trust MeSH
• Communication * MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Vaccination Hesitancy psychology   MeSH
• Pandemics MeSH
• Politics MeSH
• Surveys and Questionnaires MeSH
• SARS-CoV-2 MeSH
• Aged MeSH
• COVID-19 Vaccines administration & dosage   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Russia MeSH
• Ukraine MeSH

PURPOSE: This study aimed to assess the impact of positional changes on upper airway obstruction patterns during drug-induced sleep endoscopy (DISE) in patients with obstructive sleep apnea (OSA) and identify the airway regions most responsive to this change. Special focus was placed on the tongue base, a critical area in OSA pathophysiology. METHODS: This prospective study was conducted from June 2021 to June 2024. DISE was performed in patients with obstructive sleep apnea (OSA) in supine and lateral positions to simulate the effect of positional therapy. Findings were evaluated using the VOTE classification. RESULTS: The examination was performed on 186 patients, with a median Apnea-Hypopnea Index (AHI) of 19.3. In the supine position, complete obstructions were noted at the soft palate (88.2%), oropharynx (33.3%), tongue base (53.2%), and epiglottis (15.6%). Lateral positioning significantly reduced obstructions, particularly at the tongue base, where obstruction resolved in 94/99 of cases (94.9%). This improvement was significantly more pronounced at the tongue base than at other sites (p < 0.001). CONCLUSION: These results suggest that DISE can identify airway regions responsive to positional changes, potentially guiding clinical decisions on positional therapy. The findings show a significant reduction in tongue base obstruction during lateral positioning in DISE. Since tongue base obstruction is a key contributor to airway collapse in OSA, this improvement suggests a practical, non-invasive treatment approach. While these findings highlight an acute association between lateral positioning and reduced obstruction, further studies are needed to evaluate its long-term clinical efficacy.

• MeSH
• Adult MeSH
• Endoscopy * methods   MeSH
• Tongue physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Airway Obstruction therapy   MeSH
• Sleep Apnea, Obstructive * therapy   physiopathology   MeSH
• Oropharynx physiopathology   MeSH
• Palate, Soft physiopathology   MeSH
• Patient Positioning * methods   MeSH
• Polysomnography MeSH
• Prospective Studies MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Canalicular tumors of the salivary glands have recently emerged as an entity characterized by distinct morphology and recurrent HMGA2 gene rearrangement. In this study, we analyzed 40 cases intending to elucidate their features further. The monophasic or biphasic tumors exhibited a growth pattern of interconnected anastomosing trabeculae and canaliculi, accompanied by a classical pleomorphic adenoma in one-third of the cases. Invasive growth into surrounding adipose tissue was revealed in one case which was, therefore, diagnosed as epithelial-myoepithelial carcinoma. Although the tumor cells uniformly expressed HMGA2 protein in all cases, cytokeratin 7, S100 protein, and SOX10 displayed either diffuse positivity or highlighted the luminal and abluminal cell populations, respectively. Areas with morphological oncocytoid change and AR-immunopositivity of luminal cells were seen in 13/14 (93%) of tested biphasic cases. HMGA2 rearrangement was detected by RNA-sequencing in 30 cases. The most common alteration was an HMGA1::WIF1 fusion, but several novel or rare fusion partners were identified, including ARID2 , FHIT , MSRB3 and its antisense variant MSRB3-AS1 , IFNG-AS1 , and the long intergenic region LINC02389 . In addition, FISH revealed HGMA2 break-apart in the remaining 10 cases where targeted sequencing failed to detect any alteration or where RNA sequencing could not be performed. Notably, the loss of the 3'-untranslated region of HMGA2 emerges as the common denominator for the described rearrangements, possibly disrupting its negative regulation by small regulatory RNAs. Awareness of this lesion ensures appropriate diagnosis and clinical management, especially with regard to the possibility of malignant transformation described in this and previous studies.

• MeSH
• Adult MeSH
• Phenotype MeSH
• Genetic Predisposition to Disease MeSH
• Gene Rearrangement * MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Biomarkers, Tumor * genetics   analysis   MeSH
• Salivary Gland Neoplasms * genetics   pathology   chemistry   MeSH
• Adenoma, Pleomorphic * genetics   pathology   chemistry   MeSH
• HMGA2 Protein * genetics   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

The development of metastasis is a leading cause of cancer-related death that involves specific changes in the plasma membrane (PM) and nucleus of cancer cells. Elevated levels of membrane lipids, including sphingomyelin, cholesterol, and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), in the PM, contribute to changes in membrane rigidity, lipid raft formation, and actin polymerisation dynamics, processes that drive cell invasion. This review discusses the relationship between well-studied cytoplasmic phosphoinositides and their lesser-known nuclear counterparts, highlighting their functional role in metastatic progression. Nuclear phosphoinositides, particularly PI(4,5)P2, are essential for regulating transcription factors and chromatin organisation, thereby shaping gene expression patterns. We also explore the role of PI(4,5)P2 and its metabolism in cancer cell invasiveness and metastasis, proposing a model in which the dysregulation of cytosolic and/or nuclear PI(4,5)P2 pool triggers malignant transformation. Understanding the PI(4,5)P2-related mechanisms underlying metastasis may provide insights into potential therapeutic targets, paving the way for more effective therapies and improved patient outcomes.

• MeSH
• Cell Membrane * metabolism   MeSH
• Cell Nucleus * metabolism   MeSH
• Phosphatidylinositol 4,5-Diphosphate * metabolism   MeSH
• Humans MeSH
• Membrane Microdomains metabolism   MeSH
• Neoplasm Metastasis MeSH
• Neoplasms * metabolism   pathology   genetics   MeSH
• Signal Transduction * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Despite currently used intravesical therapies in non-muscle-invasive bladder cancer (NMIBC), the rate of intravesical recurrence remains very high. We aimed to evaluate the effectiveness of adding nonintravesical interventions to standard intravesical therapies to prevent intravesical recurrence. In April 2024, 3 databases were queried for prospective studies evaluating nonintravesical interventions in addition to standard intravesical therapies for NMIBC (CRD42024490988). The primary outcome was intravesical recurrence-free survival (iRFS). Standard pairwise meta-analyses were performed using hazard ratios (HR) and 95% confidence intervals (95% CI) with a random-effects model. We identified 18 eligible studies (14 RCTs and 4 prospective trials) comprising 4,593 NMIBC patients, which investigated pharmacological interventions (eg, selenium, vitamins, Lactobacillus casei, celecoxib, metformin, mistletoe lectin) and lifestyle modifications (diet). The addition of Lactobacillus casei significantly improved iRFS (HR: 0.50; 95% CI: 0.34-0.73; P < .001). A high western diet pattern significantly worsened iRFS (HR:1.48, 95%CI:1.06-2.06, P = .03). The other nonintravesical interventions were not associated with iRFS. Our comprehensive review of the published literature highlights the need for further research into the efficacy of nonvesical interventions for NMIBC. While Lactobacillus was shown to improve iRFS in 2 RCTs, additional high-quality randomized studies are required to evaluate the effectiveness of other interventions.

• MeSH
• Administration, Intravesical MeSH
• Celecoxib administration & dosage   therapeutic use   MeSH
• Lacticaseibacillus casei MeSH
• Humans MeSH
• Neoplasm Recurrence, Local * prevention & control   MeSH
• Metformin therapeutic use   administration & dosage   MeSH
• Urinary Bladder Neoplasms * pathology   drug therapy   MeSH
• Probiotics administration & dosage   therapeutic use   MeSH
• Randomized Controlled Trials as Topic MeSH
• Selenium administration & dosage   therapeutic use   MeSH
• Vitamins administration & dosage   therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Review MeSH
• Systematic Review MeSH