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3.
Endocrine ; 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38353885

RESUMEN

Cowden syndrome (CS) is a rare genetic condition due to the various germline mutations in the phosphatase and tensin homologue on chromosome ten (PTEN) tumour suppressor gene. As a result, CS is characterised by an increased risk of developing various benign and malignant tumours, such as thyroid, breast, endometrial and urogenital neoplasms, as well as gastrointestinal tract tumours. However, the neuroendocrine tumour association with CS is not elucidated yet. We present a case of a 46-year-old male patient diagnosed with testicular seminoma and follicular thyroid cancer in his medical history. Our patient met the clinical diagnostic criteria of Cowden syndrome. Genetic analysis established the clinical diagnosis; a known heterozygous PTEN mutation was detected [PTEN (LRG_311t1)c.388 C > T (p.Arg130Ter)]. Incidentally, he was also seen with multiple pulmonary lesions during his oncological follow-up. A video-assisted thoracoscopic left lingula wedge resection and later resections from the right lung were performed. Histological findings revealed typical pulmonary carcinoid tumours and smaller tumorlets. Somatostatin receptor SPECT-CT, 18F-FDG-PET-CT and 18F-FDOPA-PET-CT scans and endoscopy procedures could not identify any primary tumours in other locations. Our patient is the first published case of Cowden syndrome, associated with multifocal pulmonary carcinoids. Besides multiple endocrine neoplasia type 1, we propose Cowden syndrome as another hereditary condition predisposing to multiple pulmonary tumorlets and carcinoid tumours.

4.
Water Res ; 252: 121244, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38340455

RESUMEN

The global spread of antimicrobial resistance (AMR) in the environment is a growing health threat. Large rivers are of particular concern as they are highly impacted by wastewater discharge while being vital lifelines serving various human needs. A comprehensive understanding of occurrence, spread and key drivers of AMR along whole river courses is largely lacking. We provide a holistic approach by studying spatiotemporal patterns and hotspots of antibiotic resistance genes (ARGs) along 2311 km of the navigable Danube River, combining a longitudinal and temporal monitoring campaign. The integration of advanced faecal pollution diagnostics and environmental and chemical key parameters allowed linking ARG concentrations to the major pollution sources and explaining the observed patterns. Nine AMR markers, including genes conferring resistance to five different antibiotic classes of clinical and environmental relevance, and one integrase gene were determined by probe-based qPCR. All AMR targets could be quantified in Danube River water, with intI1 and sul1 being ubiquitously abundant, qnrS, tetM, blaTEM with intermediate abundance and blaOXA-48like, blaCTX-M-1 group, blaCTX-M-9 group and blaKPC genes with rare occurrence. Human faecal pollution from municipal wastewater discharges was the dominant factor shaping ARG patterns along the Danube River. Other significant correlations of specific ARGs were observed with discharge, certain metals and pesticides. In contrast, intI1 was not associated with wastewater but was already established in the water microbiome. Animal contamination was detected only sporadically and was correlated with ARGs only in the temporal sampling set. During temporal monitoring, an extraordinary hotspot was identified emphasizing the variability within natural waters. This study provides the first comprehensive baseline concentrations of ARGs in the Danube River and lays the foundation for monitoring future trends and evaluating potential reduction measures. The applided holistic approach proved to be a valuable methodological contribution towards a better understanding of the environmental occurrence of AMR.


Asunto(s)
Genes Bacterianos , Ríos , Animales , Humanos , Antibacterianos/farmacología , Antibacterianos/análisis , Aguas Residuales , Farmacorresistencia Microbiana/genética , Agua/análisis
5.
Pathology ; 56(3): 343-356, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38184384

RESUMEN

Accurate characterisation of gastrointestinal stromal tumours (GIST) is important for prognosis and the choice of targeted therapies. Histologically the diagnosis relies on positive immunostaining of tumours for KIT (CD117) and DOG1. Here we report that GISTs also abundantly express the type 3 Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA3). SERCA enzymes transport calcium ions from the cytosol into the endoplasmic reticulum and play an important role in regulating the intensity and the periodicity of calcium-induced cell activation. GISTs from various localisations, histological and molecular subtypes or risk categories were intensely immunopositive for SERCA3 with the exception of PDGFRA-mutated cases where expression was high or moderate. Strong SERCA3 expression was observed also in normal and hyperplastic interstitial cells of Cajal. Decreased SERCA3 expression in GIST was exceptionally observed in a zonal pattern, where CD117 staining was similarly decreased, reflecting clonal heterogeneity. In contrast to GIST, SERCA3 immunostaining of spindle cell tumours and other gastrointestinal tumours resembling GIST was negative or weak. In conclusion, SERCA3 immunohistochemistry may be useful for the diagnosis of GIST with high confidence, when used as a third marker in parallel with KIT and DOG1. Moreover, SERCA3 immunopositivity may be particularly helpful in cases with negative or weak KIT or DOG1 staining, a situation that may be encountered de novo, or during the spontaneous or therapy-induced clonal evolution of GIST.


Asunto(s)
Tumores del Estroma Gastrointestinal , Humanos , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/genética , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/genética , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Calcio , Retículo Endoplásmico/metabolismo , Inmunohistoquímica , Proteínas Proto-Oncogénicas c-kit/metabolismo
6.
Artículo en Inglés | MEDLINE | ID: mdl-38175383

RESUMEN

INTRODUCTION: POLE mutant phenotype in colon adenocarcinomas represents a rare molecular subtype. These tumours are generally responsive to immune-checkpoint inhibition therapy and, therefore, are currently considered as a subtype with good prognosis. We hereby present the first detailed case presentation of a POLE mutant colon adenocarcinoma with useful microscopic features. CASE REPORT: A 53-year-old male patient's colon adenocarcinoma histologically showed wide variety of growth patterns and massive intra- and peritumoural lymphocytic infiltrate. The majority of the tumour consisted of a high-grade component resembling medullary carcinoma of the colon, while approximately one-third of the tumour was composed of conventional areas exhibiting a tubular pattern. A minority of the tumour was constituted by poorly cohesive rhabdoid cells. Immunohistochemistry was performed, and colorectal origin was proven with CDX-2 and SATB2. Furthermore, proficiency in mismatch repair proteins and SMARCB1 deficiency was observed. The unusually high-grade colon adenocarcinoma, with areas mimicking medullary carcinoma, and generally aggressive morphology raised suspicion of microsatellite instability. The diverse morphology and the SMARCB1 deficiency also raised suspicion of ultramutation caused by POLE alteration. Next-generation sequencing panel confirmed a pathogenetic mutation in POLE exon 9: p.Pro286Arg, c.857C > G. DISCUSSION: The diverse, high-grade morphology and increased intratumoural lymphoid infiltration should raise suspicion for POLE-mutated adenocarcinoma during everyday histopathological practice. Mismatch repair proficiency results on immunohistochemistry should not determine the final diagnosis, as only a minor percentage of these tumours are MSI. In every case suspicious for POLE-mutated adenocarcinoma, a 500-cancer gene panel should be carried out.

7.
Artículo en Inglés | MEDLINE | ID: mdl-38180316

RESUMEN

A Gram-stain-negative strain, designated as D2M1T was isolated from xylene-degrading enrichment culture and characterized using a polyphasic approach to determine its taxonomic position. The 16S rRNA gene sequence analysis revealed that strain D2M1T belongs to the genus Acidovorax, with the highest 16S rRNA gene similarity to Acidovorax delafieldii DSM 64T (99.93 %), followed by Acidovorax radicis DSM 23535T (98.77 %) and Acidovorax kalamii MTCC 12652T (98.76 %). The draft genome sequence of strain D2M1T is 5.49 Mb long, and the G+C content of the genome is 64.2 mol%. Orthologous average nucleotide identity and digital DNA-DNA hybridization relatedness values between strain D2M1T and its closest relatives were below the threshold values for species demarcation confirming that strain D2M1T is distinctly separated from its closest relatives. The whole genome analysis of the strain revealed a phenol degradation gene cluster, encoding a multicomponent phenol hydroxylase (mPH) together with a complete meta-cleavage pathway including an I.2.C-type catechol 2,3-dioxygenase (C23O) gene. The strain was able to degrade benzene and ethylbenzene as sole sources of carbon and energy under aerobic and microaerobic conditions. Cells were facultatively aerobic rods and motile with a single polar flagellum. The predominant fatty acids (>10 % of the total) of strain D2M1T were summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c), C16 : 0 and summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c). The major ubiquinone of strain D2M1T was Q8, while the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Based on polyphasic data, it is concluded that strain D2M1T represents a novel species of the genus Acidovorax, for which the name of Acidovorax benzenivorans sp. nov. is proposed. The type strain of the species is strain D2M1T (=DSM 115238T=NCAIM B.02679T).


Asunto(s)
Hidrocarburos Aromáticos , Xilenos , ARN Ribosómico 16S/genética , Composición de Base , Ácidos Grasos/química , Filogenia , Análisis de Secuencia de ADN , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana , Bacterias
9.
J Clin Oncol ; 42(4): 452-466, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38055913

RESUMEN

PURPOSE: Primary mediastinal large B-cell lymphoma (PMBCL) is a rare aggressive lymphoma predominantly affecting young female patients. Large-scale genomic investigations and genetic markers for risk stratification are lacking. PATIENTS AND METHODS: To elucidate the full spectrum of genomic alterations, samples from 340 patients with previously untreated PMBCL were investigated by whole-genome (n = 20), whole-exome (n = 78), and targeted (n = 308) sequencing. Statistically significant prognostic variables were identified using a multivariable Cox regression model and confirmed by L1/L2 regularized regressions. RESULTS: Whole-genome sequencing revealed a commonly disrupted p53 pathway with nonredundant somatic structural variations (SVs) in TP53-related genes (TP63, TP73, and WWOX) and identified novel SVs facilitating immune evasion (DOCK8 and CD83). Integration of mutation and copy-number data expanded the repertoire of known PMBCL alterations (eg, ARID1A, P2RY8, and PLXNC1) with a previously unrecognized role for epigenetic/chromatin modifiers. Multivariable analysis identified six genetic lesions with significant prognostic impact. CD58 mutations (31%) showed the strongest association with worse PFS (hazard ratio [HR], 2.52 [95% CI, 1.50 to 4.21]; P < .001) and overall survival (HR, 2.33 [95% CI, 1.14 to 4.76]; P = .02). IPI high-risk patients with mutated CD58 demonstrated a particularly poor prognosis, with 5-year PFS and OS rates of 41% and 58%, respectively. The adverse prognostic significance of the CD58 mutation status was predominantly observed in patients treated with nonintensified regimens, indicating that dose intensification may, to some extent, mitigate the impact of this high-risk marker. By contrast, DUSP2-mutated patients (24%) displayed durable responses (PFS: HR, 0.2 [95% CI, 0.07 to 0.55]; P = .002) and prolonged OS (HR, 0.11 [95% CI, 0.01 to 0.78]; P = .028). Upon CHOP-like treatment, these patients had very favorable outcome, with 5-year PFS and OS rates of 93% and 98%, respectively. CONCLUSION: This large-scale genomic characterization of PMBCL identified novel treatment targets and genetic lesions for refined risk stratification. DUSP2 and CD58 mutation analyses may guide treatment decisions between rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab.


Asunto(s)
Linfoma de Células B Grandes Difuso , Humanos , Femenino , Rituximab/uso terapéutico , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Prednisona/uso terapéutico , Vincristina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Resultado del Tratamiento , Factores de Intercambio de Guanina Nucleótido/uso terapéutico
10.
Virchows Arch ; 484(3): 527-531, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38151535

RESUMEN

NTRK-rearranged uterine sarcoma is a recently described entity that represents a subset of uterine sarcomas with distinct clinicopathological features. From a molecular point of view, this tumour is defined by NTRK gene rearrangement, resulting in overexpression or constitutive activation of Trk receptors. The presence of NTRK fusion is indicative of treatment response with a selective small-molecule inhibitor of the Trk kinases. Here, we report a case of an NTRK-rearranged sarcoma of the uterine cervix in a 43-year-old patient, measuring 80 mm in its largest dimension, with a novel NUMA1-NTRK1 fusion, not previously reported in NTRK-rearranged uterine sarcomas or other NTRK-rearranged tumours. The fusion, involving NUMA1 exon 14 (NM_006185.4) and NTRK1 exon 11 (NM_002529.4), was identified by next-generation sequencing (NGS) studies (FusionPlex Pan Solid Tumor v2 panel). Although the presence of NTRK fusion has been reported in a variety of neoplasms, a fusion involving NUMA1 (nuclear mitotic apparatus protein 1) and a tyrosine kinase partner has previously been reported in human neoplasms only in a handful of cases. The resulting fusion protein comprises the oligomerization domain of NUMA1, which is predicted to cause constant activation of the tyrosine kinase domain of NTRK1. The recognition and accurate diagnosis of these tumours are important due to the availability of potential targeted therapeutic options.


Asunto(s)
Sarcoma , Neoplasias del Cuello Uterino , Neoplasias Uterinas , Femenino , Humanos , Adulto , Receptor trkA/genética , Neoplasias del Cuello Uterino/genética , Sarcoma/genética , Sarcoma/patología , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Proteínas de Fusión Oncogénica/genética , Fusión Génica , Proteínas de Ciclo Celular/genética
11.
Int J Syst Evol Microbiol ; 73(12)2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38108591

RESUMEN

In this study, a Gram-stain-positive, non-motile, oxidase- and catalase-negative, rod-shaped, bacterial strain (SG_E_30_P1T) that formed light yellow colonies was isolated from a groundwater sample of Sztaravoda spring, Hungary. Based on 16S rRNA phylogenetic and phylogenomic analyses, the strain was found to form a distinct linage within the family Microbacteriaceae. Its closest relatives in terms of near full-length 16S rRNA gene sequences are Salinibacterium hongtaonis MH299814 (97.72 % sequence similarity) and Leifsonia psychrotolerans GQ406810 (97.57 %). The novel strain grows optimally at 20-28 °C, at neutral pH and in the presence of NaCl (1-2 w/v%). Strain SG_E_30_P1T contains MK-7 and B-type peptidoglycan with diaminobutyrate as the diagnostic amino acid. The major cellular fatty acids are anteiso-C15 : 0, iso-C16 : 0 and iso-C14 : 0, and the polar lipid profile is composed of diphosphatidylglycerol and phosphatidylglycerol, as well as an unidentified aminoglycolipid, aminophospholipid and some unidentified phospholipids. The assembled draft genome is a contig with a total length of 2 897 968 bp and a DNA G+C content of 65.5 mol%. Amino acid identity values with it closest relatives with sequenced genomes of <62.54 %, as well as other genome distance results, indicate that this bacterium represents a novel genus within the family Microbacteriaceae. We suggest that SG_E_30_P1T (=DSM 111415T=NCAIM B.02656T) represents the type strain of a novel genus and species for which the name Antiquaquibacter oligotrophicus gen. nov., sp. nov. is proposed.


Asunto(s)
Actinomycetales , Agua Subterránea , Filogenia , ARN Ribosómico 16S/genética , Composición de Base , Ácidos Grasos/química , Análisis de Secuencia de ADN , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana , Bacterias , Aminoácidos
12.
Case Rep Oncol ; 16(1): 1598-1605, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38116298

RESUMEN

Most of the neck node metastases from cancer of unknown primary (CUP) are squamous cell carcinomas (SCCs). The majority of which are human papillomavirus (HPV)-related, frequently show cystic morphology referring to Waldeyer's ring origin. Here, we report four cases of neck node SCCs metastases from CUP. In our institute, 432 patients with head and neck (HN) SCC underwent pretreatment mutagen sensitivity (MS) assay between 1996 and 2006. Among them, 4 patients ≤50 years of age had metastatic cervical nodes from CUP. The primary treatment was cervical node dissection ± radiotherapy. All patients had elevated (>1.0 chromatid break/cell) MS. One male patient died of progressive neck metastasis within 3 years and the 3 female patients are still alive more than 15 years after initial treatment of HPV+ (two) or cystic (one) SCC. Two female patients developed second and third distant site metachronous primary cancers. HPV+ or cystic HNSCC from CUP with elevated MS indicates good outcome. Distant site metachronous cancers of different histologic origins cannot be explained by field cancerization. The clinical significance of elevated MS in neck node SCC metastasis from CUP requires further investigation.

13.
Sci Rep ; 13(1): 18638, 2023 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-37903868

RESUMEN

The purpose of the analysis was to identify the risk and protective factors for health behaviour in European adolescents from population health status and expenditure, mental health status, sexual life, social life and education indices and the existence of national strategies, programmes. National and international databases providing information on the presumed health behaviour predictors were used in the analysis. The existence of national health strategies, the level of health expenditure, the socioeconomic conditions, the level of education and literacy had significant influence on the health-risk behaviour of adolescents in the European societies. Six clusters of European countries were extracted by considering the health behaviour risks and health protection strategies. National health strategies combined with governmental support for health prevention and action plans have the most effective impact on the health-risk behaviour of adolescents.


Asunto(s)
Conductas Relacionadas con la Salud , Estado de Salud , Humanos , Adolescente , Factores Protectores , Europa (Continente) , Escolaridad , Factores de Riesgo
14.
Orv Hetil ; 164(39): 1556-1559, 2023 Oct 01.
Artículo en Húngaro | MEDLINE | ID: mdl-37778012

RESUMEN

Primary squamous cell carcinoma (SCC) of the thyroid gland is now considered as a member of the anaplastic thyroid carcinoma group based on the latest version of the WHO tumor classification. It is a very rare entity, the prognosis is adverse with a short survival time. The aim of this article is to emphasize the therapeutic complexity of this disease. A 68-year-old woman presented with rapidly growing right-sided neck mass with hoarseness and compressive symptoms. Physical examination revealed a hard fixed tumor with right-sided vocal cord palsy. Fine-needle aspiration cytology revealed a case of SCC in the location of the thyroid gland, imaging studies excluded the possibility of other primary malignancies. Surgical intervention was performed aiming the total removal of the tumor. Histopathological result confirmed the diagnosis of SCC of the thyroid. Finally the patient died during the palliative radiation therapy. SCC of the thyroid gland is a great challenge for both the surgeon and the multidisciplinary team to come up with the best treatment option which is suitable for the patient due to its unfavorable prognosis. Because of the poor response to the radiation and chemotherapy, complete surgical removal and the identification of any possible targetable molecular pathological change play a unique role in the therapy. Orv Hetil. 2023; 164(39): 1556-1559.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de la Tiroides , Femenino , Humanos , Anciano , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/cirugía , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/cirugía , Pronóstico , Tomografía Computarizada por Rayos X
15.
Magy Seb ; 76(3): 96-98, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37747834

RESUMEN

Case-report: Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy is a rare, benign non-Langerhans cell histiocytosis, that typically involves the lymph nodes, but may also involve extranodal sites. We present a 58- years- old female patient who complained of a palpable mass in her left breast surrounded by 15-20 livid cutaneous lesions, resembling malignant breast cancer with cutaneous metastasis. Despite of core biopsy of the tumor and excisional biopsy one of the lesions, correct diagnosis of RDD was achieved only by complete pathological examination of the whole lesion after surgical excision. Conclusion: Rosai-Dorfman disease confined to the breast is extremely rare, that clinically may mimic breast cancer.


Asunto(s)
Neoplasias de la Mama , Histiocitosis Sinusal , Humanos , Femenino , Persona de Mediana Edad , Histiocitosis Sinusal/diagnóstico , Histiocitosis Sinusal/cirugía , Neoplasias de la Mama/cirugía , Biopsia , Biopsia con Aguja Gruesa , Mama
16.
Sci Total Environ ; 897: 166094, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37582445

RESUMEN

Increasing metal(loid) contamination in urban soils and its impact on soil microbial community have attracted considerable attention. In the present study, the physicochemical parameters and the effects of twelve metal(loid) pollution on soil microbial diversity, their ecotoxic effects, and human health risk assessment in urban soils with different industrial background were studied in comparison with an unpolluted forest soil sample. Results showed that urban soils were highly contaminated, and metal(loid) contamination significantly influenced structure of the soil microbial communities. In all samples the bacterial community was dominated by Proteobacteria, and on the level of phyla characteristic differences were not possible to observe between polluted and control sampling sites. However, clear differences emerged at class and genus level, where several rare taxa disappeared from contaminated urban soils. Simper test results showed that there is 71.6 % bacterial OTU and 9.5 % bacterial diversity dissimilarity between polluted and control samples. Ratio of Patescibacteria, Armatimonadetes, Chlamydiae, Fibrobacteres, and Gemmatimonadetes indicated a significant (p < 0.05) positive correlation with soil Zn, Cr, Pb, Sn, Cu, Mn content, suggest that metal(loid)s strongly influence the structure of microbial community. In contrast, the presence of metal(loid) contamination in urban soils has been found to significantly reduce the population of Archaeal communities. This can be attributed to the depletion of organic matter caused by contamination that reached a minimum of 0.5 m/m% for nitrate and 0.9 m/m% for total organic carbon. The values of urban soil pH were close to neutral, ranging from 5.9 to 8.3. The findings of ecotoxicology test are alarming, as all the studied urban soil sites were cytotoxic to soil microorganisms, and in one site metal(loid) contamination reached genotoxic level. Moreover, all the metal(loid) contaminated sites pose severe and persistent health risk to children, highlighting the urgent need for effective measures to mitigate metal(loid) pollution in urban areas.


Asunto(s)
Metales Pesados , Microbiota , Contaminantes del Suelo , Niño , Humanos , Suelo/química , Contaminantes del Suelo/análisis , Metales/análisis , Contaminación Ambiental , Bacterias , Metales Pesados/análisis , Monitoreo del Ambiente
17.
Orv Hetil ; 164(34): 1350-1357, 2023 Aug 27.
Artículo en Húngaro | MEDLINE | ID: mdl-37634158

RESUMEN

Histiocytic sarcoma is an uncommon hematological malignancy. Its occurrence in the lung is very rare. Due to the small number of cases and the clinical and pathological features of the disease, the diagnosis can be challenging. Its optimal treatment is not yet known, in locally confined cases - depending on the location and size - surgical removal is part of complex oncotherapy. We report the case of a 52-year-old man with a tumor of central localization in the left lung. Pulmonectomy was performed. Histology verified histiocytic sarcoma of the lung. An overview of clinical features of the entity is presented in connection with our case report. Orv Heti. 2023; 164(34): 1350-1357.


Asunto(s)
Neoplasias Hematológicas , Sarcoma Histiocítico , Neoplasias Pulmonares , Masculino , Humanos , Persona de Mediana Edad , Sarcoma Histiocítico/diagnóstico , Sarcoma Histiocítico/cirugía , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirugía , Pulmón
18.
J Clin Med ; 12(13)2023 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-37445290

RESUMEN

BACKGROUND: Oral or laryngeal leukoplakia has an increased risk for malignant transformation but the risk of the two anatomical sites has not been compared to each other yet. MATERIALS AND METHODS: Clinical data of 253 patients with leukoplakia (oral = 221 or laryngeal = 32) enrolled from January 1996 to January 2022 were analyzed. One hundred and seventy underwent biopsy and 83 did not. The mean follow-up time was 148.8 months. Risk factors for the malignant transformation of leukoplakia were identified using Cox proportional hazard models. RESULTS: In the oral or laryngeal group, the rate of cancer was 21.7% and 50% (p = 0.002), respectively. The 10-year estimated malignant transformation was 15.1% and 42% (p < 0.0001), respectively. The laryngeal group had an increased risk of malignant transformation (p < 0.0001). The 5-year estimated survival with leukoplakia-associated cancer for the oral or laryngeal group was 40.9% and 61.1% (p = 0.337), respectively. Independent predictors of malignant transformation in the oral group were dysplasia and the grade of dysplasia of the leukoplakia, and in the laryngeal group, dysplasia had a significant impact. The malignant transformation rate was low for oral patients without biopsy or with no dysplasia, 3.9% and 5.1%, respectively. The malignant transformation occurred over 10 years. CONCLUSIONS: Patients with dysplastic leukoplakia have an increased risk of malignant transformation, but the risk is higher with laryngeal than with oral leukoplakia. There is no significant difference between the groups regarding survival with leukoplakia-associated cancer. Oral patients with no dysplastic lesions have a low risk of malignant transformation. A complete excision and long-term follow up are suggested for high-risk patients to diagnose cancer in an early stage and to control late (over 10 years) malignant events.

19.
J Intern Med ; 294(3): 295-313, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37259686

RESUMEN

BACKGROUND: Recent genomic studies revealed enhancer of zeste homolog 2 (EZH2) gain-of-function mutations, representing novel therapeutic targets in follicular lymphoma (FL) in around one quarter of patients. However, these analyses relied on single-site tissue biopsies and did not investigate the spatial heterogeneity and temporal dynamics of these alterations. OBJECTIVES: We aimed to perform a systematic analysis of EZH2 mutations using paired tissue (tumor biopsies [TB]) and liquid biopsies (LB) collected prior to treatment within the framework of a nationwide multicentric study. METHODS: Pretreatment LB and TB samples were collected from 123 patients. Among these, 114 had paired TB and LB, with 39 patients characterized with paired diagnostic and relapse samples available. The EZH2 mutation status and allele burden were assessed using an in-house-designed, highly sensitive multiplex droplet digital PCR assay. RESULTS: EZH2 mutation frequency was found to be 41.5% in the entire cohort. In patients with paired TB and LB samples, EZH2 mutations were identified in 37.8% of the patients with mutations exclusively found in 5.3% and 7.9% of TB and LB samples, respectively. EZH2 mutation status switch was documented in 35.9% of the patients with paired diagnostic and relapse samples. We also found that EZH2 wild-type clones may infiltrate the bone marrow more frequently compared to the EZH2 mutant ones. CONCLUSION: The in-depth spatio-temporal analysis identified EZH2 mutations in a considerably higher proportion of patients than previously reported. This expands the subset of FL patients who most likely would benefit from EZH2 inhibitor therapy.


Asunto(s)
Linfoma Folicular , Humanos , Linfoma Folicular/diagnóstico , Linfoma Folicular/genética , Linfoma Folicular/tratamiento farmacológico , Proteína Potenciadora del Homólogo Zeste 2/genética , Recurrencia Local de Neoplasia , Mutación , Biopsia , Biopsia Líquida , Recurrencia
20.
Microorganisms ; 11(6)2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37374949

RESUMEN

Non-steroidal anti-inflammatory drugs (NSAIDs) are increasingly recognized as potential environmental contaminants that may induce toxicity in aquatic ecosystems. This 3-week microcosm experiment explores the acute impacts of NSAIDs, including diclofenac (DCF), ibuprofen (IBU), and acetylsalicylic acid (ASA), on bacterial communities using a wide range of these substances (200-6000 ppm). The results showed that the NSAID-treated microcosms had higher cell count values than control samples, though the diversity of microbial communities decreased. The isolated heterotrophic bacteria mostly belonged to Proteobacteria, particularly Klebsiella. Next-generation sequencing (NGS) revealed that NSAIDs altered the structure of the bacterial community composition, with the proportion of Proteobacteria aligning with the selective cultivation results. Bacteria had higher resistance to IBU/ASA than to DCF. In DCF-treated microcosms, there has been a high reduction of the number of Bacteroidetes, whereas in the microcosms treated with IBU/ASA, they have remained abundant. The numbers of Patescibacteria and Actinobacteria have decreased across all NSAID-treated microcosms. Verrucomicrobia and Planctomycetes have tolerated all NSAIDs, even DCF. Cyanobacteria have also demonstrated tolerance to IBU/ASA treatment in the microcosms. The archaeal community structure was also impacted by the NSAID treatments, with Thaumarchaeota abundant in all microcosms, especially DCF-treated microcosms, while Nanoarchaeota is more typical of IBU/ASA-treated microcosms with lower NSAID concentrations. These results indicate that the presence of NSAIDs in aquatic environments could lead to changes in the composition of microbial communities.

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