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1.
Clin. transl. oncol. (Print) ; 26(2): 363-374, feb. 2024.
Artigo em Inglês | IBECS | ID: ibc-230182

RESUMO

Introduction The critical role of microRNA-128 (miR-128) in gastrointestinal-related diseases has been documented. In the current study, we tried to clarify the specific role miR-128 in gastrointestinal stromal tumor (GIST) and the underlying mechanism. Methods Differentially expressed genes in GIST were identified following bioinformatics analysis. Then, expression patterns of miR-128 and B-lymphoma Mo-MLV insertion region 1 (BMI-1) in clinical tissue samples and cell lines were characterized, followed by validation of their correlation. GIST-T1 cells were selected and transfected with different mimic, inhibitor, or siRNA plasmids, after which the biological functions were assayed. Results We identified low miR-128 and high BMI-1 expression in GIST tissues of 78 patients and 4 GIST cell lines. Ectopic expression of miR-128 or silencing of BMI-1 suppressed the malignant potentials of GIST-T1 cells. As a target of miR-128, BMI-1 re-expression could partly counteract the suppressive effect of miR-128 on the malignancy of GIST-T1 cells. Conclusion Our study provided evidence that miR-128-mediated silencing of BMI-1 could prevent malignant progression of GIST, highlighting a promising anti-tumor target for combating GIST (AU)


Assuntos
Humanos , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Linfoma , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , RNA Interferente Pequeno/farmacologia
2.
Nat Commun ; 15(1): 63, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167404

RESUMO

Avapritinib is the only potent and selective inhibitor approved for the treatment of D842V-mutant gastrointestinal stromal tumors (GIST), the most common primary mutation of the platelet-derived growth factor receptor α (PDGFRA). The approval was based on the NAVIGATOR trial, which revealed overall response rates of more than 90%. Despite this transformational activity, patients eventually progress, mostly due to acquired resistance mutations or following discontinuation due to neuro-cognitive side effects. These patients have no therapeutic alternative and face a dismal prognosis. Notable, little is known about this drug's binding mode and its medicinal chemistry development, which is instrumental for the development of the next generation of drugs. Against this background, we solve the crystal structures of avapritinib in complex with wild-type and mutant PDGFRA and stem cell factor receptor (KIT), which provide evidence and understanding of inhibitor binding and lead to the identification of a sub-pocket (Gα-pocket). We utilize this information to design, synthesize and characterize avapritinib derivatives for the determination of key pharmacophoric features to overcome drug resistance and limit potential blood-brain barrier penetration.


Assuntos
Antineoplásicos , Tumores do Estroma Gastrointestinal , Humanos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Pirazóis/uso terapêutico , Pirróis/farmacologia , Pirróis/uso terapêutico , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Antineoplásicos/farmacologia
3.
Int J Hyperthermia ; 41(1): 2292950, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38159558

RESUMO

OBJECTIVES: This study aimed to analyze the survival outcomes and prognostic factors of radiofrequency ablation (RFA) for liver metastases from gastrointestinal stromal tumors (GISTs). METHODS: Between March 2011 and November 2022, 34 patients (16 males; age range, 25-72 [median age, 52.5] years) who underwent RFA for liver metastasis from GISTs were included. The mean maximum diameter of metastatic lesions was 2.4 ± 1.0 (range, 1.1-5.2) cm. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analyses were performed using a Cox proportional hazards model. RESULTS: For 79 lesions among 34 patients, all targeted lesions were completely ablated. The mean hepatic progression-free survival (HPFS) period was 28.4 ± 3.8 (range, 1.0-45.7) months. The 1-, 3-, and 5-year HPFS rates were 67.2%, 60.5%, and 20.2%, respectively. Based on the univariate analysis, the number of metastatic tumors and tyrosine kinase inhibitors(TKI) therapy before RFA were prognostic factors for HPFS. Multivariate analysis showed that pre-RFA TKI therapy was associated with a better HPFS(p = 0.030). The mean overall survival (OS) period was 100.5 ± 14.1 (range, 3.8-159.5) months and the 1-, 3-, and 5-year survival rates were 96.9%, 77.1%, and 58.7%, respectively. Both univariate and multivariate analysis indicated that extrahepatic metastasis before RFA (p = 0.044) was a significant prognostic factor for OS. CONCLUSIONS: Liver metastases from GIST exhibit relatively mild biological behavior. RFA is safe and effective, particularly in patients without pre-RFA extrahepatic metastases. Patients received targeted therapy before RFA can obtain an extended HPFS.


Assuntos
Ablação por Cateter , Tumores do Estroma Gastrointestinal , Neoplasias Hepáticas , Ablação por Radiofrequência , Masculino , Humanos , Pessoa de Meia-Idade , Adulto , Idoso , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/cirurgia , Tumores do Estroma Gastrointestinal/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Ablação por Radiofrequência/métodos , Intervalo Livre de Progressão , Ultrassonografia de Intervenção , Estudos Retrospectivos , Resultado do Tratamento , Taxa de Sobrevida
4.
Drugs Aging ; 41(2): 165-176, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38123766

RESUMO

BACKGROUND: While the effectiveness of tyrosine kinase inhibitors (TKIs) seems similar in older patients with gastrointestinal stromal tumors (GIST) compared with younger patients, toxicities in older patients treated with TKIs more often lead to discontinuation of treatment. OBJECTIVE: To better understand the age-related pharmacology and pharmacodynamic differences in patients with GIST treated with TKIs, the primary aim of this study was to evaluate TKI dosing patterns in older patients with GIST, while the secondary aims were to evaluate differences in imatinib trough plasma concentrations between age groups and to compare the overall survival (OS) in patients with and without dose reductions in all treatment lines in a palliative setting. METHODS: Patients (18 years of age or older) with histologically proven GIST diagnosed between January 2009 and June 2021 and treated with one or more lines of TKIs were selected from the Dutch GIST Registry (DGR) database. Age groups were divided into younger patients (age <70 years) and older patients (age ≥70 years). All imatinib trough plasma concentrations of blood withdrawals taken from initiation of imatinib until a maximum of 1 year of treatment with imatinib were collected. Reasons for first adjustment of treatment were classified as adverse event, dose modification, progressive disease and other reasons. The next treatment steps after first adjustment of treatment were defined as dose escalation, dose reduction, dose interruption, or end of treatment. The association of dose reduction and OS was analyzed using the landmark approach. RESULTS: Overall, 871 patients were included in this study, including 577 younger patients and 294 older patients. Older patients more often had an adverse event as the reason for first adjustment of treatment with both imatinib (45.6%; p < 0.001) and sunitinib (58.6%; p = 0.224) compared with younger patients (19.5% and 42.7%, respectively). Adjustment of imatinib and sunitinib after starting on a standard dose because of an adverse event most often resulted in dose reduction in both age groups. Median trough plasma concentrations of all samples taken within the first year after initiation of imatinib were higher in older patients (1228 ng/mL, interquartile range [IQR] 959-1687) compared with younger patients (1035 ng/mL [IQR 773-1377]; p < 0.001). No significant differences were seen between OS in patients with or without dose reduction in all treatment lines (imatinib: p = 0.270; sunitinib: p = 0.547; and regorafenib: p = 0.784). CONCLUSION: Older patients showed higher imatinib trough plasma concentrations compared with younger patients and also had earlier and more often adverse events as the reason for first adjustment of treatment with imatinib followed by dose reduction. However, in a landmark analysis, patients with imatinib dose reductions had no poorer outcomes compared with patients not requiring a dose reduction.


Assuntos
Antineoplásicos , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Humanos , Adolescente , Adulto , Idoso , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Mesilato de Imatinib/efeitos adversos , Sunitinibe/uso terapêutico , Estudos de Coortes , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologia , Inibidores de Proteínas Quinases/efeitos adversos , Sistema de Registros , Antineoplásicos/efeitos adversos
5.
Surg Endosc ; 38(2): 1106-1112, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38110795

RESUMO

BACKGROUND: Intragastric wedge resection is an effective method for treating endophytic gastric subepithelial tumors (SETs). However, retracting the stomach wall to the umbilicus is difficult in certain patients. In response, we developed a novel surgical technique for single-port intragastric wedge resection, which we termed the "tunnel method." METHODS: A transumbilical incision is made, and a wound retractor is applied. After diagnostic laparoscopy, a gastrostomy is made on the greater curvature, lower body. Another small wound retractor is inserted into the gastrostomy, and extracted through the transumbilical incision, creating a tunnel from the gastrostomy site to the umbilicus. Articulating laparoscopic instruments are inserted via the tunnel, and intragastric wedge resection is performed. We collected and analyzed the clinicopathologic and operative data of patients who underwent intragastric wedge resection via the tunnel method. RESULTS: Twenty-seven patients who underwent single-port intragastric wedge resection via the tunnel method in a single tertiary referral hospital were included in this study. The mean age of the patients was 54.6 ± 11.4 years, body mass index was 26.5 ± 3.4 kg/m2. Twenty-four (88.9%) patients had tumors located in the upper third of the stomach. The average operative time was 65.0 ± 24.2 min. None of the patients experienced Clavien-Dindo grade IIIa or higher postoperative complications. The average postoperative hospital stay length was 2.5 ± 0.8 days. Thirteen gastrointestinal stromal tumors, nine leiomyomas, and one neuroendocrine carcinoma, schwannoma, lipoma, spindle cell proliferative lesion, and fibrotic lesion were pathologically diagnosed. The average tumor size was 2.6 ± 1.3 cm. All cases had negative resection margins. CONCLUSIONS: Single-port intragastric wedge resection by the tunnel method is a feasible and safe approach for treating endophytic gastric SETs.


Assuntos
Tumores do Estroma Gastrointestinal , Laparoscopia , Neoplasias Gástricas , Ferida Cirúrgica , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Gastrectomia/métodos , Laparoscopia/métodos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Tumores do Estroma Gastrointestinal/patologia
6.
Clin Transl Oncol ; 26(2): 363-374, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38103120

RESUMO

INTRODUCTION: The critical role of microRNA-128 (miR-128) in gastrointestinal-related diseases has been documented. In the current study, we tried to clarify the specific role miR-128 in gastrointestinal stromal tumor (GIST) and the underlying mechanism. METHODS: Differentially expressed genes in GIST were identified following bioinformatics analysis. Then, expression patterns of miR-128 and B-lymphoma Mo-MLV insertion region 1 (BMI-1) in clinical tissue samples and cell lines were characterized, followed by validation of their correlation. GIST-T1 cells were selected and transfected with different mimic, inhibitor, or siRNA plasmids, after which the biological functions were assayed. RESULTS: We identified low miR-128 and high BMI-1 expression in GIST tissues of 78 patients and 4 GIST cell lines. Ectopic expression of miR-128 or silencing of BMI-1 suppressed the malignant potentials of GIST-T1 cells. As a target of miR-128, BMI-1 re-expression could partly counteract the suppressive effect of miR-128 on the malignancy of GIST-T1 cells. CONCLUSION: Our study provided evidence that miR-128-mediated silencing of BMI-1 could prevent malignant progression of GIST, highlighting a promising anti-tumor target for combating GIST.


Assuntos
Tumores do Estroma Gastrointestinal , Linfoma , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Proliferação de Células , RNA Interferente Pequeno/farmacologia , Linhagem Celular Tumoral , Apoptose
8.
J Med Case Rep ; 17(1): 546, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38098096

RESUMO

BACKGROUND: Gastrointestinal stromal tumor is considered the most common mesenchymal neoplasm of the gastrointestinal tract. The majority of gastrointestinal stromal tumor cases are located in the stomach and usually affects older adults. Most of gastrointestinal stromal tumor cases are sporadic; however, few have a syndromic association, including Carney triad, Carney-Stratakis syndrome, familial gastrointestinal stromal tumor syndrome, and neurofibromatosis type 1. CASE PRESENTATION: Herein, we report a rare case of a 54-year-old Middle-Eastern female with multifocal gastrointestinal stromal tumor mixed type (epithelioid and spindle cell type) with osseous metaplasia. Fluoresce in situ hybridization analysis of platelet-derived growth factor receptor alpha revealed deletion in 42% of the tumor cells studied. Interestingly, next generation sequencing revealed platelet-derived growth factor receptor alpha exon 12 mutation (p.Y555C) and exon 14 mutation (p.N659Y). CONCLUSIONS: In conclusion, osseous metaplasia in GIST is a very rare event and only few cases are reported in the literature. The number of reported cases is inadequate to confirm the pathogenesis and the prognosis.


Assuntos
Tumores do Estroma Gastrointestinal , Neoplasias Gástricas , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Tumores do Estroma Gastrointestinal/patologia , Neoplasias Gástricas/patologia , Metaplasia , Receptores do Fator de Crescimento Derivado de Plaquetas/genética , Mutação
10.
BMC Res Notes ; 16(1): 318, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932827

RESUMO

BACKGROUND: Gastrointestinal Stromal Tumour is a rare but potentially curable tumour of the gastrointestinal tract accounting for up to 1% of all gastrointestinal tumours. The discovery of Imatinib mesylate, a novel tyrosine kinase inhibitor has improved the chances even for unresectable, recurrent, or metastatic diseases. METHODS: This study sought to document the clinical and pathological characteristics of GISTs from two tertiary hospitals in Ghana that have undergone immunohistochemistry confirmation between 2014 and 2021. RESULTS: The median age of the subjects was 50 years with most of them (28.0%) being above 61 years. There were more females than males (64.0% vs. 36.0%). Abdominal mass and abdominal pain made up the majority of the clinical presentations. The majority of the subjects had partial gastrectomy (32.0%) which was followed by wedge resection (28.0%). Appendectomy and sleeve gastrectomy were the least performed procedures (8% each). Four of the 25 patients (16.0%) had resections of involved contiguous organs done with splenectomy being the most common procedure. The majority of GISTs were found in the stomach (68.0%) followed by the appendix (12.0%) and small bowel (12.0%). Gastrointestinal bleeding (55.8%) and abdominal pain (38.5%) were the most reported symptoms. Free resection margins were observed in 84.0% of the subjects and only 3/25 (12.0%) experienced tumour recurrence. CONCLUSION: GIST is a potentially curable tumour that once was obscure but currently gaining popularity. Surgical resection offers the hope of a cure for localized disease while targeted therapies is a viable option for recurrent, metastatic, or unresectable tumours.


Assuntos
Antineoplásicos , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Tumores do Estroma Gastrointestinal/patologia , Antineoplásicos/uso terapêutico , Gana , Recidiva Local de Neoplasia , Neoplasias Gastrointestinais/terapia , Dor Abdominal
11.
BMJ Case Rep ; 16(11)2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37967927

RESUMO

Hypercalcaemia is recognised as the most common oncological metabolic emergency, with several proposed underlying mechanisms. Nevertheless, hypercalcaemia has been rarely reported as a complication in patients with gastrointestinal stromal tumours (GISTs). GISTs are uncommon mesenchymal tumours of the gastrointestinal tract. There are only nine previous cases of hypercalcaemia occurring in patients with GIST reported in the literature. We report a case of a man in his 70s with a background of metastatic GIST on fourth-line treatment. The patient presented with new hypercalcaemia and acute kidney injury. Despite medical management, his calcium remained elevated and he deteriorated secondary to significant disease progression.


Assuntos
Tumores do Estroma Gastrointestinal , Hipercalcemia , Masculino , Humanos , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/patologia , Hipercalcemia/complicações , Progressão da Doença
12.
West Afr J Med ; 40(11 Suppl 1): S25, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37978874

RESUMO

Introduction: Gastrointestinal stromal tumours (GISTs) are neoplastic lesions that primarily affect the digestive tract and develop from interstitial cells of Cajal. Due to their malignant potential and personalized treatment, these lesions require histopathologic and immunohistochemical characterization. In this investigation, the sex, age, lesional sites of origin, histopathologic types, the prevalence of HER-2 expression, prognostic indices (based on tumour size and mitotic figures), expression of CD117 and DOG1, and characteristics of patients with GIST were all characterized. Methodology: This is a retrospective cross-sectional analysis of GIST cases seen at four tertiary healthcare centers in Nigeria over ten years (2008 to 2017) and investigated utilizing histopathological and immunohistochemical (CD117, DOG1, and HER-2) methods. Result: In this study, there were twenty GIST cases. Notably, the majority (40%) of the cases had tumours with sizes between 7.0 and 8.0, the stomach was the most frequent site (70%) and the spindle cell type of GIST was the most prevalent (80%) histopathological type. Additionally, the stomach was significantly associated with GIST as an origin site (with a P value of 0.001), and 100% and 50% of these tumours were immunoreactive with CD117 and DOG1 respectively. Finally, HER-2 immunoreactivity was negatively stained with GIST tumour. Conclusion: In our study, GISTs most frequently develop in the stomach, and CD117& DOG1 are essential for correctly diagnosing these tumours. However, HER-2 immunoreactivity is a predictive marker of survival for personalized care.


Assuntos
Tumores do Estroma Gastrointestinal , Humanos , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/metabolismo , Tumores do Estroma Gastrointestinal/patologia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/metabolismo , Estudos Retrospectivos , Nigéria/epidemiologia , Estudos Transversais
13.
Int J Colorectal Dis ; 38(1): 253, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37855869

RESUMO

PURPOSE: Survival after local resection (LR) versus radical resection (RR) has been revealed comparable for patients with rectal and duodenal gastrointestinal stromal tumors (GISTs), but is unknown for jejunoileal (JI) GISTs. This study aimed to compare the long-term survival between patients with JI GISTs who underwent LR and RR, and to find out the prognostic factors for JI GISTs. METHODS: Patients diagnosed with JI GISTs in 1975-2019 were identified from Surveillance, Epidemiology, and End Results (SEER) database and grouped according to surgical modality. Propensity score matching (PSM) was performed to balance the LR and RR groups. Overall survival (OS) and disease-specific survival (DSS) were compared in the full and matched cohorts using Kaplan-Meier (KM) analysis. Subgroup sensitivity analyses were also performed. Risk factors associated with DSS were analyzed in multivariate Cox analysis following model selection. RESULTS: 1107 patients diagnosed with JI GISTs were included in the study cohort. After PSM, OS and DSS were comparable in LR and RR groups. Consistently, the two groups had similar DSS in all subgroup analyses. Moreover, multivariate Cox analysis identified lymphadenectomy, older age, larger tumor size, distant metastasis, high and unknown mitotic rate, but not LR, as independent prognostic risk factors for JI GISTs. CONCLUSIONS: We conducted the first population-based comparison between the effect of different surgical modes on survival for patients with JI GISTs. LR can be carried out safely without compromising oncological outcome, and should be considered as a treatment option in selected patients with JI GISTs.


Assuntos
Neoplasias Duodenais , Tumores do Estroma Gastrointestinal , Humanos , Tumores do Estroma Gastrointestinal/cirurgia , Tumores do Estroma Gastrointestinal/patologia , Neoplasias Duodenais/patologia , Neoplasias Duodenais/cirurgia , Pontuação de Propensão , Pancreaticoduodenectomia/efeitos adversos , Estudos Retrospectivos , Prognóstico
14.
Zhonghua Wei Chang Wai Ke Za Zhi ; 26(10): 997-1000, 2023 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-37849273

RESUMO

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor among gastrointestinal tumors, with an inherent potential for malignancy. The primary approach to addressing GIST remains surgical intervention. Laparoscopic and endoscopic cooperative surgery (LECS) has emerged as an innovative treatment approach for GIST. LECS includes various techniques, such as classic LECS, inverted LECS, and laparoscopic-assisted endoscopic full-thickness resection, all of which aim to combine the advantages of laparoscopy and endoscopy. This treatment offers benefits such as accurate localization, complete lesion removal, and a good prognosis. Generally, LECS can be used for GIST with a tumor diameter less than 50 mm, which cannot be completely removed through traditional endoscopic surgery. The clinical application of LECS deserves further exploration and expansion in the future, ultimately benefiting patients.


Assuntos
Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Laparoscopia , Neoplasias Gástricas , Humanos , Tumores do Estroma Gastrointestinal/cirurgia , Tumores do Estroma Gastrointestinal/patologia , Neoplasias Gástricas/cirurgia , Laparoscopia/métodos , Neoplasias Gastrointestinais/cirurgia , Endoscopia Gastrointestinal
16.
Curr Med Sci ; 43(5): 935-946, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37828372

RESUMO

OBJECTIVE: Gastrointestinal stromal tumors (GISTs) can rapidly proliferate through angiogenesis. Previous studies indicated the potential influence of microRNA on the progression of tumor immature angiogenesis. This study aimed to explore the specific mechanism by which microRNA-409-5p (miR-409-5p) contributes to GIST. METHODS: To identify genes potentially involved in the development and progression of GIST, the differences of miR-409-5p between tumors and adjacent tissues were first analyzed. Following this analysis, target genes were predicted. To further investigate the function of miRNA in GIST cells, two GIST cell lines (GIST-T1 and GIST882) were transfected with lentiviruses that stably expressed miR-409-5p and scrambled miRNA (negative control). Later, the cells were subjected to Western blotting and ELSA to determine any differences in angiogenesis-related genes. RESULTS: In GISTs, there was a decrease in the expression levels of miR-409-5p compared to the adjacent tissues. It was observed that the upregulation of miR-409-5p in GIST cell lines effectively inhibited the proteins hypoxia-inducible transcription factor 1ß (HIF1ß) and vascular endothelial growth factor A (VEGF-A). Further investigations revealed that miR-409-5p acted as an inhibitor of angiogenesis by binding to the 3'-UTR of Lysine-specific demethylase 4D (KDM4D) mRNA. Moreover, the combination of miR-409-5p with imatinib enhanced its inhibitory effect on angiogenesis. CONCLUSION: This study demonstrated that the miRNA-409-5p/KDM4D/HIF1ß/VEGF-A signaling pathway could serve as a novel target for the development of therapeutic strategies for the treatment of imatinib-resistance in GIST patients.


Assuntos
Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , MicroRNAs , Humanos , Carcinogênese/genética , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Mesilato de Imatinib/farmacologia , Histona Desmetilases com o Domínio Jumonji , MicroRNAs/genética , MicroRNAs/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Resistencia a Medicamentos Antineoplásicos/genética
17.
Sci Rep ; 13(1): 17568, 2023 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-37845257

RESUMO

To investigate clinical data and computed tomographic (CT) imaging features in differentiating gastric schwannomas (GSs) from gastric stromal tumours (GISTs) in matched patients, 31 patients with GSs were matched with 62 patients with GISTs (1:2) in sex, age, and tumour site. The clinical and imaging data were analysed. A significant (P < 0.05) difference was found in the tumour margin, enhancement pattern, growth pattern, and LD values between the 31 patients with GSs and 62 matched patients with GISTs. The GS lesions were mostly (93.5%) well defined while only 61.3% GIST lesions were well defined.The GS lesions were significantly (P = 0.036) smaller than the GIST lesions, with the LD ranging 1.5-7.4 (mean 3.67 cm) cm for the GSs and 1.0-15.30 (mean 5.09) cm for GIST lesions. The GS lesions were more significantly (P = 0.001) homogeneously enhanced (83.9% vs. 41.9%) than the GIST lesions. The GS lesions were mainly of the mixed growth pattern both within and outside the gastric wall (74.2% vs. 22.6%, P < 0.05) compared with that of GISTs. No metastasis or invasion of adjacent organs was present in any of the GS lesions, however, 1.6% of GISTs experienced metastasis and 3.2% of GISTs presented with invasion of adjacent organs. Heterogeneous enhancement and mixed growth pattern were two significant (P < 0.05) independent factors for distinguishing GS from GIST lesions. In conclusion: GS and GIST lesions may have significantly different features for differentiation in lesion margin, heterogeneous enhancement, mixed growth pattern, and longest lesion diameter, especially heterogeneous enhancement and mixed growth pattern.


Assuntos
Tumores do Estroma Gastrointestinal , Neurilemoma , Neoplasias Gástricas , Humanos , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/patologia , Estudos de Casos e Controles , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios X/métodos , Neurilemoma/diagnóstico por imagem , Neurilemoma/patologia
18.
Ann Surg Oncol ; 30(13): 8660-8668, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37814179

RESUMO

BACKGROUND: Neoadjuvant imatinib is considered for gastrointestinal stromal tumors (GISTs) when decreased tumor size provides less extensive surgery and higher R0 resection rates. This study evaluates the effectivity and safety of neoadjuvant imatinib for large or locally advanced GIST. PATIENTS AND METHODS: From the prospective database of the Dutch GIST Consortium, all patients who underwent surgery after neoadjuvant imatinib at our center between 2009 and 2022 were selected. Independent and blinded assessment of surgical strategy was performed by two surgeons, based on anonymized computed tomography (CT) scans before and after neoadjuvant imatinib. RESULTS: Of 113 patients that received neoadjuvant imatinib, 108 (95%) [mean age 61.6, standard deviation (SD) 11.5, 54% male] underwent a GIST resection. Of all GISTs, 67% was localized in the stomach and 25% in the duodenum or small intestine. In 74% of the patients with GIST, a KIT exon 11 mutation was found. Decreased tumor size was seen in 95 (88%) patients. Having a KIT exon 11 mutation [odds ratio (OR) 5.64, 95% confidence interval (CI) 1.67-19.1, p < 0.01] or not having a mutation (OR 0.19, 95% CI 0.04-0.89, p = 0.04) were positive and negative predictive values for partial response, respectively. In 55 (51%) patients, there was deescalation of surgical strategy after neoadjuvant imatinib. Surgical complications were documented in 16 (15%) patients (n = 8, grade II; n = 5, grade IIIa; n = 3, grade IIIb) and R0 resection was accomplished in 95 (89%) patients. The 5-year disease-free and overall survival were 80% and 91%, respectively. CONCLUSION: This study shows that neoadjuvant imatinib is effective and safe for patients with large or locally advanced GIST.


Assuntos
Antineoplásicos , Tumores do Estroma Gastrointestinal , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Mesilato de Imatinib/uso terapêutico , Tumores do Estroma Gastrointestinal/patologia , Terapia Neoadjuvante/métodos , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Benzamidas/uso terapêutico , Antineoplásicos/uso terapêutico
20.
Diagn Pathol ; 18(1): 110, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37789344

RESUMO

BACKGROUND: Neurofibromatosis type 1 (NF1) is known to be associated with the frequent occurrence of unique gastrointestinal stromal tumors (GISTs), preferably occurring in the small intestine, with no mutations in the c-kit proto-oncogene or platelet-derived growth factor receptor-alpha (PDGFRA), with a high tendency for multifocal development, indolent nature, with low proliferation activity and favorable prognosis. CASE PRESENTATION: A woman in her forties visited her local doctor complaining of menstrual pain; a large mass was detected in her lower abdomen, and she was referred to our hospital. The patient had hundreds of skin warts and café au lait spots. The patient's mother had been diagnosed with type 1 neurofibromatosis. The patient met the diagnostic criteria for NF1 and was diagnosed with NF1. Ultrasonography showed a large heterogeneous cystic mass with various echo patterns, solid compartments and multiple septations. Magnetic resonance imaging showed a multilocular cystic mass with liquid content exhibiting various intensities, including that of blood. A small round solid mass was also observed close to the cystic tumor. Contrast-enhanced computed tomography showed that the round solid mass showed strong enhancement in the early phase, unlike the cystic tumor component. Open laparotomy revealed a multicystic exophytic tumor measuring 11.5 cm originating from the jejunal wall, 20 cm distal to the duodenojejunal flexure. A solid tumor measuring 2.1 cm was also found on the anal side of the large tumor. We resected the short segment of the jejunum, including the two lesions. Microscopic findings revealed that the cystic and solid tumors consisted of spindle-shaped tumor cells showing little atypia with a fascicular or bundle arrangement. Nuclear mitosis was scarce. Immunostaining of the tumor cells showed positive staining for KIT and DOG1 and negative staining for S100 and desmin. The NF1 patient was diagnosed with multiple GISTs accompanied by intratumoral hemorrhagic denaturation arising from the jejunum. The TNM staging was pT4N0M0, stage IIIA. CONCLUSION: We report a case of GISTs associated with NF1 that showed a jejunal origin, multifocal development and few mitotic figures. The recurrence risk, survival prognosis and need for adjuvant chemotherapy, particularly in cases where the initial GIST exhibits a very indolent pathology in NF1-related GISTs, remain to be elucidated.


Assuntos
Tumores do Estroma Gastrointestinal , Neurofibromatose 1 , Feminino , Humanos , Tumores do Estroma Gastrointestinal/patologia , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/genética , Jejuno/patologia , Intestino Delgado/patologia , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética
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