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1.
Clin Cancer Res ; 30(18): 4082-4099, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39018564

RESUMO

PURPOSE: Pseudomyxoma peritonei (PMP) is a rare and poorly understood malignant condition characterized by the accumulation of intra-abdominal mucin produced from peritoneal metastases. Currently, cytoreductive surgery remains the mainstay of treatment but disease recurrence and death after relapse frequently occur in patients with PMP. New therapeutic strategies are therefore urgently needed for these patients. EXPERIMENTAL DESIGN: A total of 120 PMP samples from 50 patients were processed to generate a collection of 50 patient-derived organoid (PDO) and xenograft (PDX) models. Whole exome sequencing, immunohistochemistry analyses, and in vitro and in vivo drug efficacy studies were performed. RESULTS: In this study, we have generated a collection of PMP preclinical models and identified druggable targets, including BRAFV600E, KRASG12C, and KRASG12D, that could also be detected in intra-abdominal mucin biopsies of patients with PMP using droplet digital PCR. Preclinical models preserved the histopathological markers from the original patient sample. The BRAFV600E inhibitor encorafenib reduced cell viability of BRAFV600E PMP-PDO models. Proof-of-concept in vivo experiments showed that a systemic treatment with encorafenib significantly reduced tumor growth and prolonged survival in subcutaneous and orthotopic BRAFV600E-PMP-PDX mouse models. CONCLUSIONS: Our study demonstrates for the first time that systemic targeted therapies can effectively control PMP tumors. BRAF signaling pathway inhibition represents a new therapeutic opportunity for patients with BRAFV600E PMP who have a poor prognosis. Importantly, our present data and collection of preclinical models pave the way for evaluating the efficacy of other systemic targeted therapies toward extending the promise of precision oncology to patients with PMP.


Assuntos
Terapia de Alvo Molecular , Neoplasias Peritoneais , Medicina de Precisão , Pseudomixoma Peritoneal , Ensaios Antitumorais Modelo de Xenoenxerto , Pseudomixoma Peritoneal/patologia , Pseudomixoma Peritoneal/tratamento farmacológico , Pseudomixoma Peritoneal/genética , Humanos , Animais , Camundongos , Medicina de Precisão/métodos , Terapia de Alvo Molecular/métodos , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Feminino , Masculino , Proteínas Proto-Oncogênicas p21(ras)/genética , Sequenciamento do Exoma , Mutação , Linhagem Celular Tumoral , Organoides/efeitos dos fármacos , Organoides/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo
2.
Dig Liver Dis ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38811247

RESUMO

BACKGROUND: The Baveno VII guidelines were proposed to identify which patients could safely avoid screening esophagogastroduodenoscopy (EGD) for gastroesophageal varices. We aimed to evaluate the frequency of gastric neoplasia in compensated advanced chronic liver disease (cACLD) patients who underwent EGD for screening of gastroesophageal varices (GOEV) compared to a healthy population. METHODS: Retrospective study that enrolled all cACLD patients who underwent EGD for GOEV screening (January 2008-June 2018) in a tertiary reference center. cACLD patients were compared with asymptomatic healthy individuals who underwent EGD in a private hospital setting (April 2017-March 2018). RESULTS: We evaluated 1845 patients (481 cACLD patients, 1364 healthy individuals). A significantly higher frequency of gastric neoplasia was observed in patients with cACLD compared to healthy individuals (4.0% vs. 1.0 %; p < 0.001). Rare histopathological subtypes (WHO Classification) accounted for 28.7 % of gastric carcinoma cases in the cACLD cohort. Seven cases of gastric neoplasia (36.8 % of gastric neoplasia cases in the cACLD patients) were diagnosed in patients who, according to the Baveno VII criteria, would have not been submitted to EGD. CONCLUSION: We found an increased frequency of gastric neoplasia in patients with cACLD in comparison with healthy individuals. In countries with intermediate-high risk for GC, continuing to perform EGD could be beneficial.

3.
Sci Data ; 11(1): 512, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760418

RESUMO

Given the high prevalence of lung cancer, an accurate diagnosis is crucial. In the diagnosis process, radiologists play an important role by examining numerous radiology exams to identify different types of nodules. To aid the clinicians' analytical efforts, computer-aided diagnosis can streamline the process of identifying pulmonary nodules. For this purpose, medical reports can serve as valuable sources for automatically retrieving image annotations. Our study focused on converting medical reports into nodule annotations, matching textual information with manually annotated data from the Lung Nodule Database (LNDb)-a comprehensive repository of lung scans and nodule annotations. As a result of this study, we have released a tabular data file containing information from 292 medical reports in the LNDb, along with files detailing nodule characteristics and corresponding matches to the manually annotated data. The objective is to enable further research studies in lung cancer by bridging the gap between existing reports and additional manual annotations that may be collected, thereby fostering discussions about the advantages and disadvantages between these two data types.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Bases de Dados Factuais , Nódulo Pulmonar Solitário/diagnóstico por imagem , Diagnóstico por Computador
4.
Eur J Radiol ; 173: 111377, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382425

RESUMO

PURPOSE: To establish Portuguese Diagnostic Reference Levels (DRLs), for six body fluoroscopy guided interventional procedures (FGIP). METHOD: A retrospective study was conducted in five interventional departments most representative of Interventional Radiology (IR) practice. Dose values, in terms of air kerma area product (PKA in Gy.cm2), air kerma at the patient entrance reference point (Ka,r in mGy), and exposure parameters (fluoroscopy time (FT) and number of cine runs) were collected. Examinations were selected per procedure (at least 20), according to the antero-posterior and lateral diameter mean value (±5 cm), measured on previous Computed Tomography (CT) examinations. RESULTS: Data of 489 body FGIP show a large variation on dose values per procedure and per department. National DRLs in terms of PKA were 20.2 Gy.cm2 for Percutaneous transhepatic biliary drainage (PTBD), 98.2 Gy.cm2 for Bronchial artery embolisation (BAE), 247.7 Gy.cm2 for Transarterial chemoembolisation (TACE), 331.6 Gy.cm2 for Inferior epigastric arteries embolisation (IEAE), 312.0 Gy.cm2 for Transjugular intrahepatic portosystemic shunt (TIPS) and 19.3 Gy.cm2 for Endovascular treatment of femoral popliteal arteries (ETFPA). CONCLUSIONS: This is the first study reporting Interventional Radiology DRLs in Portugal and we propose preliminary national estimates for the six more common body FGIP. The results of this study will be presented and discussed with all Portuguese IR departments, to promote procedures optimisation.


Assuntos
Quimioembolização Terapêutica , Níveis de Referência de Diagnóstico , Humanos , Doses de Radiação , Portugal/epidemiologia , Radiologia Intervencionista/métodos , Estudos Retrospectivos , Fluoroscopia/métodos , Radiografia Intervencionista , Valores de Referência
6.
Skeletal Radiol ; 53(2): 253-261, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37400605

RESUMO

OBJECTIVE: To compare the clinical efficacy of capsule-rupturing versus capsule-preserving ultrasound-guided hydrodilatation in patients with shoulder adhesive capsulitis (AC). To determine potential factors affecting the outcome over a 6-month follow-up. MATERIALS AND METHODS: Within a 2-year period, 149 consecutive patients with AC were prospectively enrolled and allocated into (i) group-CR, including 39 patients receiving hydrodilatation of the glenohumeral joint (GHJ) with capsular rupture and (ii) group-CP, including 110 patients treated with GHJ hydrodilatation with capsular preservation. Demographics, affected shoulder, and AC grade were recorded. Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and visual analog scale (VAS) were used for clinical assessment at baseline/1/3/6 months. Comparisons were performed with Mann-Whitney U test and Kolmogorov-Smirnov test. Linear regression was used to identify predictors of outcome. P value < 0.05 defined significance. RESULTS: DASH and VAS scores in both groups improved significantly compared to baseline (P < 0.001) and were significantly lower in the CP compared to CR group at all time-points following intervention (P < 0.001). Capsule rupture was a significant predictor of DASH score at all time-points (P < 0.001). DASH scores correlated to initial DASH score at all time-points (P < 0.001). DASH/VAS scores at 1 month were correlated to the AC grade (P = 0.025/0.02). CONCLUSION: GHJ hydrodilatation results in pain elimination and functional improvement till the mid-term in patients with AC, with improved outcome when adopting the capsule-preserving compared to the capsule-rupturing technique. Higher initial DASH score is predictive of impaired functionality in the mid-term.


Assuntos
Bursite , Articulação do Ombro , Humanos , Ombro , Ultrassonografia , Articulação do Ombro/diagnóstico por imagem , Resultado do Tratamento , Bursite/diagnóstico por imagem , Bursite/terapia , Amplitude de Movimento Articular , Ultrassonografia de Intervenção
7.
Minerva Anestesiol ; 89(12): 1092-1098, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38019173

RESUMO

BACKGROUND: Laparotomy is assumed to decrease cough strength due to three factors: abdominal muscle trauma, postoperative pain, and diaphragmatic dysfunction. However, the effect of trauma from laparotomy itself on strength (net of the other two factors) has not been measured to our knowledge. The aim of this study was to measure the effect of laparotomy on cough strength after first measuring the effect of epidural analgesia. METHODS: In 11 patients scheduled for open midline laparotomy, cough pressure (PCOUGH), a proxy for strength, was measured with a rectal balloon at three moments: before the procedure, at baseline; before surgery, under epidural bupivacaine to T6; and postoperatively, under epidural bupivacaine to the same analgesic level (T6). Continuous variables were compared using the Wilcoxon signed-rank test. The repeatability of PCOUGH measurements was confirmed with the intraclass correlation coefficient (ICC). Pain on coughing, hand grip strength, and the Ramsay and modified Bromage scores were also recorded. RESULTS: Median (interquartile range) PCOUGH decreased from a baseline of 103 (89-137) to 71 (56-116) cmH2O under presurgical epidural bupivacaine (P=0.003). Postoperative PCOUGH remained unchanged at 76 (46-85) cmH2O under epidural analgesia (P=0.131). The ICCs indicated excellent repeatability of the PCOUGH measurements (P<0.001). Pain on coughing was 0 to 1 in all subjects. Hand grip strength and the Ramsay and Bromage scores were unchanged. CONCLUSIONS: Although thoracic epidural bupivacaine reduces cough strength as measured by PCOUGH, midline laparotomy does not further reduce strength in the presence of adequate epidural analgesia.


Assuntos
Tosse , Força da Mão , Humanos , Tosse/etiologia , Laparotomia , Estudos Prospectivos , Bupivacaína , Dor Pós-Operatória
8.
Int J Parasitol Parasites Wildl ; 22: 108-112, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37799291

RESUMO

The current study describes a new species of nematode, Orientatractis matosi n. sp. (Atractidae), from the stomach and large intestine of Podocnemis unifilis Troschel, 1848 (Testudinidae), collected in the Tocantins and Xingu rivers in the Brazilian state of Pará. The new species was described using light and scanning electron microscopy and differs from its congeners mainly in the number and distribution of the male caudal papillae and by having a shorter right spicule. Orientatracits matosi n. sp. is the eleventh species of the genus Orientatractis Petter, 1966, the third reported from the Amazon, and the second described from P. unifilis.

9.
J Pers Med ; 13(10)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37888093

RESUMO

Respiratory infections are frequent and life-threatening complications of surgery. This study aimed to evaluate the clinical, microbiological and treatment characteristics of severe postoperative pneumonia (POP) and tracheobronchitis (POT) in a large series of patients. This single-center, prospective observational cohort study included patients with POP or POT requiring intensive care unit admission in the past 10 years. We recorded demographic, clinical, microbiological and therapeutic data. A total of 207 patients were included, and 152 (73%) were men. The mean (SD) age was 70 (13) years and the mean (SD) ARISCAT score was 46 (19). Ventilator-associated pneumonia was reported in 21 patients (10%), hospital-acquired pneumonia was reported in 132 (64%) and tracheobronchitis was reported in 54 (26%). The mean (SD) number of days from surgery to POP/POT diagnosis was 6 (4). The mean (SD) SOFA score was 5 (3). Respiratory microbiological sampling was performed in 201 patients (97%). A total of 177 organisms were cultured in 130 (63%) patients, with a high proportion of Gram-negative and multi-drug resistant (MDR) bacteria (20%). The most common empirical antibiotic therapy was a triple-drug regimen covering MDR Gram-negative bacteria and MRSA. In conclusion, surgical patients are a high-risk population with a high proportion of early onset severe POP/POT and nosocomial bacteria isolation.

10.
Gut ; 73(1): 105-117, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-37666656

RESUMO

OBJECTIVE: To evaluate the risk factors for lymph node metastasis (LNM) after a non-curative (NC) gastric endoscopic submucosal dissection (ESD) and to validate and eventually refine the eCura scoring system in the Western setting. Also, to assess the rate and risk factors for parietal residual disease. DESIGN: Retrospective multicentre multinational study of prospectively collected registries from 19 Western centres. Patients who had been submitted to surgery or had at least one follow-up endoscopy were included. The eCura system was applied to assess its accuracy in the Western setting, and a modified version was created according to the results (W-eCura score). The discriminative capacities of the eCura and W-eCura scores to predict LNM were assessed and compared. RESULTS: A total of 314 NC gastric ESDs were analysed (72% high-risk resection (HRR); 28% local-risk resection). Among HRR patients submitted to surgery, 25% had parietal disease and 15% had LNM in the surgical specimen. The risk of LNM was significantly different across the eCura groups (areas under the receiver operating characteristic curve (AUC-ROC) of 0.900 (95% CI 0.852 to 0.949)). The AUC-ROC of the W-eCura for LNM (0.916, 95% CI 0.870 to 0.961; p=0.012) was significantly higher compared with the original eCura. Positive vertical margin, lymphatic invasion and younger age were associated with a higher risk of parietal residual lesion in the surgical specimen. CONCLUSION: The eCura scoring system may be applied in Western countries to stratify the risk of LNM after a gastric HRR. A new score is proposed that may further decrease the number of unnecessary surgeries.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Estudos Retrospectivos , Fatores de Risco , Gastrectomia/métodos , Endoscopia Gastrointestinal , Mucosa Gástrica/cirurgia , Mucosa Gástrica/patologia
11.
Cureus ; 15(7): e42075, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37602015

RESUMO

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has notably impacted healthcare systems and everyday life worldwide. Regulatory authorities have approved the emergency use of SARS-CoV-2 vaccines due to the rapid spread of the virus. However, during vaccination testing, pregnant and breastfeeding women were initially excluded, leading to a lack of evidence-based recommendations. When taking the COVID-19 pandemic into account, breastfeeding has emerged as a potential defense mechanism against this infection due to its numerous benefits for newborns. Human breast milk contains immunoglobulins (IgA, IgG, and IgM), lactoferrin, and various cells that play an inevitable role in the newborn's protection against respiratory infections and immune system development. Various studies have highlighted that the onset and severity of respiratory infections in infants can be reduced through breastfeeding, and the effects are noticeable during the first six months of life and that breast milk also has the potential to enhance mucosal immunity and promote a diverse microbiome, reducing the risk of asthma, allergies, and enteric diseases through the provision of specific antibodies and immunological factors. Researchers have indicated that breastfeeding mothers who contracted and recovered from COVID-19 or received vaccination passed protective antibodies to their infants through breast milk. Although rare cases of detection of SARS-CoV-2 RNA in breast milk have been reported, the virus has not been cultured from these samples, suggesting a low risk of transmission to the breastfed baby. However, further research is essential to understand the extent of protection provided by breast milk against COVID-19 and the potential effect of distinct phases of lactation. Nonetheless, the current evidence supports the benefits and safety of breastfeeding during the pandemic. With appropriate safety measures, promoting breastfeeding can contribute to the overall health and well-being of infants during the phase of COVID-19.

12.
J Clin Med ; 12(16)2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37629398

RESUMO

Endoscopic submucosal dissection (ESD) in colorectal lesions is demanding, and a significant rate of non-curative procedures is expected. We aimed to assess the rate of residual lesion after a piecemeal ESD resection, or after an en bloc resection but with positive horizontal margins (local-risk resection-LocRR), for colorectal benign neoplasia. A retrospective multicenter analysis of consecutive colorectal ESDs was performed. Patients with LocRR ESDs for the treatment of benign colorectal lesions with at least one follow-up endoscopy were included. A cohort of en bloc resected lesions, with negative margins, was used as the control. A total of 2255 colorectal ESDs were reviewed; 352 of the ESDs were "non-curative". Among them, 209 were LocRR: 133 high-grade dysplasia and 76 low-grade dysplasia. Ten cases were excluded due to missing data. A total of 146 consecutive curative resections were retrieved for comparison. Compared to the "curative group", LocRRs were observed in lengthier procedures, with larger lesions, and in non-granular LSTs. Recurrence was higher in the LocRR group (16/199, 8% vs. 1/146, 0.7%; p = 0.002). However, statistical significance was lost when considering only en bloc resections with positive horizontal margins (p = 0.068). In conclusion, a higher rate of residual lesion was found after a piecemeal ESD resection, but not after an en bloc resection with positive horizontal margins.

14.
Dalton Trans ; 52(21): 7196-7207, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37162287

RESUMO

Metal-organic frameworks (MOFs) are attractive candidates to meet the requirement of next-generation batteries, as functional materials with a high surface area, well-defined metal centers, and organic linkers through coordination bonds. Due to their great tunability, MOFs have been investigated as electrodes or electrolytes in lithium batteries and more recently as protective layers in anode-less batteries. Here, we synthesize a Ni3(HHTP)2 MOF directly at the air-liquid interface of a Langmuir trough and grow the electrode on a conductive substrate by the transference process. The characterization during Langmuir film formation shows that the addition of crystallization time during the compression process enhances the formation of 2D crystalline domains, as observed by in situ grazing-incidence X-ray diffraction. Next, the transferred Ni3(HHTP)2 ultrathin films were studied as working electrodes in Li batteries in a half-cell configuration and compared with bare copper. The results show that the Ni3(HHTP)2 film protects the Cu collector from oxidation, and the negative charge accumulates in the organic ligand during the lithiation process while NiII oxidizes to NiIII, unlike other triphenylene-based MOFs with CuII or CoII metal nodes. The galvanostatic plating-stripping cycles of the batteries show that the inclusion of the crystallization time improves the coulombic efficiency, especially significantly in the first cycles when the SEI is formed. This work shows the Langmuir technique as a useful tool to test MOF based materials for batteries with the advantages of using a low amount of raw materials and without the need to introduce additives (binder and electron conductor) in the electrodes. The electrochemical study of this type of electrode allows a first screening to synthesize electrodes based on MOFs and can be a tool for the preparation of protective coatings under optimized conditions.

15.
Clin Transl Oncol ; 25(12): 3378-3394, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37140736

RESUMO

Peritoneal metastases (PM) occur when cancer cells spread inside the abdominal cavity and entail an advanced stage of colorectal cancer (CRC). Prognosis, which is poor, correlates highly with tumour burden, as measured by the peritoneal cancer index (PCI). Cytoreductive surgery (CRS) in specialized centres should be offered especially to patients with a low to moderate PCI when complete resection is expected. The presence of resectable metastatic disease in other organs is not a contraindication in well-selected patients. Although several retrospective and small prospective studies have suggested a survival benefit of adding hyperthermic intraperitoneal chemotherapy (HIPEC) to CRS, the recently published phase III studies PRODIGE-7 in CRC patients with PM, and COLOPEC and PROPHYLOCHIP in resected CRC with high-risk of PM, failed to show any survival advantage of this strategy using oxaliplatin in a 30-min perfusion. Final results from ongoing randomized phase III trials testing CRS plus HIPEC based on mitomycin C (MMC) are awaited with interest. In this article, a group of experts selected by the Spanish Group for the Treatment of Digestive Tumours (TTD) and the Spanish Group of Peritoneal Oncologic Surgery (GECOP), which is part of the Spanish Society of Surgical Oncology (SEOQ), reviewed the role of HIPEC plus CRS in CRC patients with PM. As a result, a series of recommendations to optimize the management of these patients is proposed.


Assuntos
Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Humanos , Neoplasias Colorretais/patologia , Neoplasias Peritoneais/secundário , Estudos Retrospectivos , Estudos Prospectivos , Terapia Combinada , Hipertermia Induzida/métodos , Taxa de Sobrevida
16.
Proc Natl Acad Sci U S A ; 120(20): e2214853120, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37155874

RESUMO

Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane proteoglycan, is highly expressed in intestinal subtype gastric tumors and that this signature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.


Assuntos
Neoplasias Gástricas , Sindecana-4 , Humanos , Heparitina Sulfato/metabolismo , Invasividade Neoplásica , Neoplasias Gástricas/genética , Sindecana-4/genética , Sindecana-4/metabolismo
17.
Small ; 19(28): e2301244, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37010019

RESUMO

A Cu2 O-TiO2 photoelectrode is pr+oposed for simultaneous solar light energy harvesting and storing of electrochemical energy in an adapted lithium coin cell. The p-type Cu2 O semiconductor layer is the light harvester component of the photoelectrode and the TiO2 film performs as the capacitive layer. The rationale of the energy scheme shows that the photocharges generated in the Cu2 O semiconductor induce lithiation/delithiation processes in the TiO2 film as a function of the applied bias voltage and light power. A photorechargeable lithium button cell drilled on one side recharges with visible white light in ≈9 h in open circuit. It provides an energy density of ≈150 mAh g-1 at 0.1 C discharge current in dark, and the overall efficiency is 0.29%. This work draws a new approach for the photoelectrode role to advance in monolithic rechargeable batteries.

18.
Glycoconj J ; 40(4): 421-433, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37074623

RESUMO

Expression of sialyl Lewis X (SLeX) is a well-documented event during malignant transformation of cancer cells, and largely associates with their invasive and metastatic properties. Glycoproteins and glycolipids are the main carriers of SLeX, whose biosynthesis is known to be performed by different glycosyltransferases, namely by the family of ß-galactoside-α2,3-sialyltransferases (ST3Gals). In this study, we sought to elucidate the role of ST3GalIV in the biosynthesis of SLeX and in malignant properties of gastrointestinal (GI) cancer cells. By immunofluorescent screening, we selected SLeX-positive GI cancer cell lines and silenced ST3GalIV expression via CRISPR/Cas9. Flow cytometry, immunofluorescence and western blot analysis showed that ST3GalIV KO efficiently impaired SLeX expression in most cancer cell lines, with the exception of the colon cancer cell line LS174T. The impact of ST3GalIV KO in the biosynthesis of SLeX isomer SLeA and non sialylated Lewis X and A were also evaluated and overall, ST3GalIV KO led to a decreased expression of SLeA and an increased expression in both LeX and LeA. In addition, the abrogation of SLeX on GI cancer cells led to a reduction in cell motility. Furthermore, ST3GalVI KO was performed in LS174T ST3GalIV KO cells, resulting in the complete abolishment of SLeX expression and consequent reduced motility capacity of those cells. Overall, these findings portray ST3GalIV as the main, but not the only, enzyme driving the biosynthesis of SLeX in GI cancer cells, with a functional impact on cancer cell motility.


Assuntos
Neoplasias do Colo , Humanos , Movimento Celular , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Glicolipídeos , Oligossacarídeos/metabolismo , Antígeno Sialil Lewis X
19.
Endoscopy ; 55(3): 235-244, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35863354

RESUMO

BACKGROUND : Endoscopic submucosal dissection (ESD) in colorectal lesions is technically demanding and a significant rate of noncurative procedures is expected. We aimed to assess the rate of residual lesions after a noncurative ESD for colorectal cancer (CRC) and to establish predictive scores to be applied in the clinical setting. METHODS : Retrospective multicenter analysis of consecutive colorectal ESDs. Patients with noncurative ESDs performed for the treatment of CRC lesions submitted to complementary surgery or with at least one follow-up endoscopy were included. RESULTS : From 2255 colorectal ESDs, 381 (17 %) were noncurative, and 135 of these were performed in CRC lesions. A residual lesion was observed in 24 patients (18 %). Surgery was performed in 96 patients and 76 (79 %) had no residual lesion in the colorectal wall or in the lymph nodes. The residual lesion rate for sm1 cancers was 0 %, and for > sm1 cancers was also 0 % if no other risk factors were present. Independent risk factors for lymph node metastasis were poor differentiation and lymphatic permeation (NC-Lymph score). Risk factors for the presence of a residual lesion in the wall were piecemeal resection, poor differentiation, and positive/indeterminate vertical margin (NC-Wall score). CONCLUSIONS : Lymphatic permeation or poor differentiation warrant surgery owing to their high risk of lymph node metastasis, mainly in > sm1 cancers. In the remaining cases, en bloc and R0 resections resulted in a low risk of residual lesions in the wall. Our scores can be a useful tool for the management of patients who undergo noncurative colorectal ESDs.


Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Humanos , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Metástase Linfática , Endoscopia , Estudos Retrospectivos , Neoplasia Residual , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Resultado do Tratamento
20.
J Ultrasound Med ; 42(3): 665-674, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35869694

RESUMO

OBJECTIVES: To compare the additive value of immediate post-procedural manipulation versus physiotherapy, following ultrasound (US)-guided hydrodistention of the glenohumeral joint (GHJ) in patients with adhesive capsulitis (AC) and define predictors of outcome. METHODS: Within a 19-month period, 161 consecutive patients with AC were prospectively enrolled and allocated to two groups according to treatment, based on patients' individual preferences: 1) group-I, US-guided hydrodistension plus immediate post-procedural manipulations and 2) group-II, US-guided hydrodistension plus supervised physiotherapy program. The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and a visual analog scale (VAS) were used for clinical assessment at baseline (immediately after treatment), 1, 3, and 6 months. Comparisons were performed with Mann-Whitney U test and Kolmogorov-Smirnov test. Linear regression was used to identify predictors of outcome. P value <.05 defined significance. RESULTS: GHJ hydrodistension with manipulation or physiotherapy was linked to clinical improvement at all follow-up time-points. DASH scores of group-I remained constantly lower than DASH scores of group-II at all time-points (P < .001). VAS scores were lower in group-I than group-II at 1 and 3 months (P < .001 and P = .0019, respectively). Both groups had improved to a similar degree with respect to pain at 6 months (P = .29). The performance of post-interventional manipulations was predictive of improved shoulder functionality (as assessed with DASH scores) at all time-points, while low-grade disease and milder symptoms at presentation were associated with improved short-term pain. CONCLUSIONS: Immediate post-procedural manipulations appeared to be superior to physiotherapy following GHJ hydrodistension for AC in terms of shoulder functionality during a 6-month follow-up period. Post-interventional manipulations, the stage of AC and lower DASH and VAS scores at presentations were predictive of improved outcome.


Assuntos
Bursite , Articulação do Ombro , Humanos , Modalidades de Fisioterapia , Ultrassonografia , Bursite/diagnóstico por imagem , Bursite/terapia , Ultrassonografia de Intervenção , Dor , Resultado do Tratamento , Amplitude de Movimento Articular
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