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1.
Turk J Med Sci ; 52(3): 691-698, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36326339

RESUMO

BACKGROUND: We aimed to elucidate the causes of the increased melanisation in basal cell carcinoma (BCC) and seborrheic keratosis (SK), and the role of melanocytes in this process. METHODS: This study was a retrospective-cohort study conducted in the pathology department of a university hospital between January 2019 and October 2020. Forty-nine SK and 30 pigmented BCC were included in our study. SRY-box transcription factor 10 (SOX10), CD68, and Masson-Fontana staining was used for analysis in all samples. A representative section of each specimen was photographed under ×400 magnification to facilitate the assessments of the morphology of the melanocytes and their following morphometric parameters: density, nuclear diameter, and distribution. The density of pigmented keratinocytes in the lesional epidermis was scored. The nuclear diameters of melanocytes located in the nonlesional epidermis, the density of the melanophages, and the presence or absence of ulceration and solar elastosis were also recorded. RESULTS: The morphometric findings confirmed a statistically significant increase in melanocyte density in the BCC group compared with that in the SK group (p < 0.001). Moreover, the nuclear minor diameters in the melanocytes of the BCC sections were significantly higher than those in the SK specimens (p < 0.001). The epidermal melanocytes were distributed diffusely in almost all BCC specimens (96.7%), whereas they were mainly limited to the basal layer in the majority of the SK sections (59.2%). The number of epidermal melanised keratinocytes with a score of 3 was significantly higher in the SK group (n = 31; 63.2%) than in the BCC group (n = 6; 20%) (p = 0.001), and they were the main cells representing the pigmented appearance of the tumours. No significant difference was found between both tumour groups in terms of their melanophage density scores (p = 0.206). DISCUSSION: This study is the first step towards an objective quantification of the melanocytes in pigmented epithelial tumours and may provide a morphological background for future studies on these skin lesions.


Assuntos
Carcinoma Basocelular , Ceratose Seborreica , Neoplasias Epiteliais e Glandulares , Dermatopatias , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Estudos Retrospectivos , Estudos de Coortes , Carcinoma Basocelular/patologia , Melanócitos/patologia , Ceratose Seborreica/patologia , Neoplasias Epiteliais e Glandulares/patologia
2.
BMC Cancer ; 22(1): 1183, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397047

RESUMO

BACKGROUND: The C-reactive protein to albumin ratio (CAR) is associated with poor prognosis in various cancers. However, its value in thymic epithelial tumors remains to be elucidated, we aimed to evaluate the prognostic significance of preoperative CAR in patients with surgically resected thymic epithelial tumors (TETs). METHODS: We retrospectively collected data from 125 patients with TETs who underwent thymoma resection at our center. The best cutoff values ​​for the continuous variable, CAR, were obtained using X-tile software. Univariate and multivariate Cox regression analyses were used to evaluate CAR as an independent predictor of overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier analysis and log-rank tests were used to present risk stratification of patients based on CAR and the Glasgow-prognostic-score (GPS). The prognostic effect of CAR was assessed using a receiver operating characteristic curve. RESULTS: Patients were categorized into high (≥ 0.17) and low (< 0.17) CAR groups according to the optimal cutoff value of 0.17. Univariate and multivariate analyses showed that CAR was an independent predictor of prognosis. World health organization stage, CAR level, GPS score, and drinking history were important independent prognostic factors for OS (p < 0.05). T stage, CAR level, and drinking history were important independent prognostic factors for RFS (p < 0.05). The area under the curve value of CAR to predict prognosis was 0.734 for OS and 0.680 for RFS. CONCLUSIONS: Elevated preoperative CAR was independently associated with poor OS and RFS after thymectomy. Therefore, CAR may be a valuable biomarker for the postoperative prognosis of TETs.


Assuntos
Proteína C-Reativa , Neoplasias Epiteliais e Glandulares , Humanos , Proteína C-Reativa/análise , Prognóstico , Estudos Retrospectivos , Albumina Sérica/análise , Neutrófilos/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Epiteliais e Glandulares/patologia
4.
Cancer Control ; 29: 10732748221129108, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36373938

RESUMO

INTRODUCTION: Thymic epithelial tumors are the most common mediastinal tumors. Despite the high survival rate after surgery, some patients still require postoperative adjuvant therapy and closer follow-up. Hematological indicators such as biochemical routines and coagulation indicators have been reported to be independently associated with the prognosis of various malignancies. Therefore, we included hematological indicators in the analysis. METHODS: The data of 105 patients with thymic epithelial tumors were retrospectively collected from Sun Yat-sen University Cancer Center, and the patients with missing preoperative hematological indicators were excluded. X-tile software was used to obtain the best cutoff value of each preoperative hematological indicator, and COX regression analysis and Kaplan-Meier survival curves were used to demonstrate statistically significant results. RESULTS: COX univariate regression analysis of all patients showed that Masaoka stage, T stage, WHO histologic types, D-dimer, albumin-fibrinogen ratio (AFR), Fibrinogen (Fbg) were associated with postoperative overall survival (P < .05). T stage, WHO histologic types, D-dimer, and AFR were associated with postoperative recurrence-free survival (P < .05). Finally, multivariate regression analysis showed that T stage, D-dimer levels were independently associated with postoperative overall survival (OS) and recurrence-free survival (RFS) in patients with thymic epithelial tumors. CONCLUSIONS: For thymic epithelial tumors, higher preoperative D-dimer levels predict poorer survival and shorter recurrence-free survival. This may help guide postoperative adjuvant therapy and follow-up patterns in patients with thymic epithelial tumors.


Assuntos
Neoplasias Epiteliais e Glandulares , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias Epiteliais e Glandulares/cirurgia , Fibrinogênio , Estadiamento de Neoplasias
6.
Medicine (Baltimore) ; 101(46): e31741, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401408

RESUMO

BACKGROUND: Whether the size of thymic epithelial tumors (TETs) has an impact on prognosis has long been a controversial issue. Our study was designed to investigate the value of tumor size in the prognosis (overall survival (OS) and relapse-free survival) of patients with TETs. METHODS: We searched the databases such as PubMed, EMBASE, Web of Science, and clinical trials registration system for articles illustrating the impact of tumor size on survival data in TETs patients. We did a meta-analysis for OS and relapse-free survival. RESULTS: We recruited 9 studies in our meta-analysis. Our study illustrates that TETs patients with small tumor size had better relapse-free survival (hazard ratio = 1.66, 95% confidence interval 1.18-2.35, P = .004) and OS (hazard ratio = 1.93, 95% confidence interval 1.30-2.80, P = .001) in comparison to patients with large tumor size. CONCLUSIONS: In conclusion, the results of our meta-analysis showed that TET size was significantly associated with overall and relapse-free survival of patients, with relatively small tumors tending to have a better prognosis.


Assuntos
Neoplasias Epiteliais e Glandulares , Neoplasias do Timo , Humanos , Prognóstico , Modelos de Riscos Proporcionais
7.
Technol Cancer Res Treat ; 21: 15330338221119340, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36217838

RESUMO

Introduction: Tumor markers have been shown to be closely related to the long-term survival of patients with cancer and the recurrence of various malignant tumors. However, their role in thymic epithelial tumors (TETs) remains to be elucidated. We aimed to investigate whether the preoperative tumor biomarkers carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) could serve as independent predictors of postoperative prognosis in patients with TETs. Materials and Methods: We retrospectively included a total of 111 patients with TETs who underwent thymectomy at our hospital. Cox regression analysis was used to evaluate the statistical significance of CEA and NSE as independent predictors of overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier curves were used to present the results of our survival analyses. Results: Cox regression analysis showed that T stage, World Health Organization (WHO) histologic type, tumor size, and CEA levels served as independent prognostic factors for OS (P < .05). Whereas for RFS, multivariate analysis showed that only T stage, WHO histologic type, and drinking history were independently associated with it (P < .05). Conclusion: Our study found that preoperative serum CEA levels and tumor size may be strong predictors of postoperative OS in patients with TETs.


Assuntos
Antígeno Carcinoembrionário , Neoplasias Epiteliais e Glandulares , Biomarcadores Tumorais , Humanos , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/cirurgia , Fosfopiruvato Hidratase , Prognóstico , Estudos Retrospectivos , Neoplasias do Timo
8.
Cancer Imaging ; 22(1): 56, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36199129

RESUMO

PURPOSES: This study aimed to evaluate the diagnostic capacity of apparent diffusion coefficient (ADC) in predicting pathological Masaoka and T stages in patients with thymic epithelial tumors (TETs). METHODS: Medical records of 62 patients who were diagnosed with TET and underwent diffusion-weighted imaging (DWI) prior to surgery between August 2017 and July 2021 were retrospectively analyzed. ADC values were calculated from DWI images using b values of 0, 400, and 800 s/mm2. Pathological stages were determined by histological examination of surgical specimens. Cut-off points of ADC values were calculated via receiver operating characteristic (ROC) analysis. RESULTS: Patients had a mean age of 56.3 years. Mean ADC values were negatively correlated with pathological Masaoka and T stages. Higher values of the area under the ROC curve suggested that mean ADC values more accurately predicated pathological T stages than pathological Masaoka stages. The optimal cut-off points of mean ADC were 1.62, 1.31, and 1.48 × 10-3 mm2/sec for distinguishing pathological T2-T4 from pathological T1, pathological T4 from pathological T1-T3, and pathological T3-T4 from pathological T2, respectively. CONCLUSION: ADC seems to more precisely predict pathological T stages, compared to pathological Masaoka stage. The cut-off values of ADC identified may be used to preoperatively predict pathological T stages of TETs.


Assuntos
Neoplasias Epiteliais e Glandulares , Neoplasias do Timo , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/diagnóstico por imagem , Curva ROC , Estudos Retrospectivos , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/patologia
9.
Tumour Biol ; 44(1): 205-213, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189508

RESUMO

BACKGROUND: CA125 is the gold standard serum biomarker for monitoring patients with epithelial ovarian cancer (EOC). Human epididymal protein 4 (HE4) is a novel serum biomarker for EOC patients. OBJECTIVE: The objective of this trial was to examine the utility of measuring serum HE4 levels for monitoring EOC patients and to compare HE4 performance parameters to serum CA125. METHODS: A retrospective trial using residual longitudinal serum samples drawn during treatment and monitoring from EOC patients. Serum CA125 and HE4 levels were analyzed at each time point, and a velocity of change was calculated and correlated with clinical status. The null hypothesis was that HE4 is inferior to CA125, and this was tested using concordance and two-sided Fisher's exact testing. McNemar's test was used to assess the overall agreement of the two assays with the clinical status. RESULTS: A total of 129 patients with 272 separate clinical periods and 1739 events (serum samples) were evaluated. Using a 25% change in serum biomarker levels to indicate change in disease status, the accuracy and NPV determined for HE4 versus CA125 were 81.8% versus 82.6% (p = 0.846) and 87.4% versus 89.7% (p = 0.082), respectively. Concordance comparison of HE4 accuracy / CA125 accuracy was 0.990, indicating HE4 was not inferior to CA125 (McNemar's test p-value = 0.522). Performing a velocity of change analysis, the accuracy and NPV determined for HE4 versus CA125 were 78.3% versus 78.6% (p = 0.995) and 74.9% versus 76.3% (p = 0.815), respectively. Concordance comparison of HE4 velocity accuracy / CA125 velocity accuracy was 0.996, again indicating HE4 was not inferior to CA125 (McNemar's test p-value = 0.884). The combination of HE4 and CA125 velocity changes showed a similar accuracy of 81.3% (p = 0.797 compared to HE4 and CA125 alone) and NPV of 81.1% (p≥0.172 compared to HE4 and CA125 alone), and an increased sensitivity of 70.5% (p≤0.070 compared to HE4 and CA125 alone). CONCLUSION: HE4 is equivalent to CA125 for monitoring of EOC patients. The combination of CA125 and HE4 velocities is superior to either marker alone.


Assuntos
Neoplasias Epiteliais e Glandulares , Neoplasias Ovarianas , Biomarcadores Tumorais , Antígeno Ca-125 , Carcinoma Epitelial do Ovário , Feminino , Humanos , Proteínas de Membrana , Estudos Retrospectivos
10.
Medicine (Baltimore) ; 101(39): e30867, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36181069

RESUMO

BACKGROUND: Thymic epithelial tumors (TETs) originate in the thymic epithelial cell, including thymoma and thymic carcinoma. Surgical resection is the first choice for most patients. However, some studies have shown that the factors affecting the prognosis of these patients are not consistent. To evaluate prognostic factors in patients with surgically resected thymic epithelial tumors, we performed a meta-analysis. METHODS: We searched the Chinese biomedical literature database, Pubmed, Embase, Cochrane Library and other electronic databases. Studies including postoperative overall survival (OS) and predictors of TETs were included. We made a comprehensive analysis the hazard ratios (HRs) through a single proportional combination. HRs were combined using single proportion combinations. RESULTS: The meta-analysis included 11,695 patients from 26 studies. The pooled OS was 84% at 5 years and 73% at 10 years after TETs operation. The age as continuous-year (HR 1.04, 95% confidence interval (CI) 1.02-1.04), incomplete resection (HR 4.41, 95% CI 3.32-5.85), WHO histologic classification (B2/B3 vs A/AB/B1 HR 2.76, 95% CI 1.25-6.21), Masaoka Stage (stage III/IV vs I/II HR 2.74, 95% CI 2.12-3.55,) were the poor prognostic factors. CONCLUSIONS: For patients with TETs after surgical resection, advanced age, incomplete resection, WHO classification B2/B3, and higher Masaoka stage are risk factors for poor prognosis.


Assuntos
Neoplasias Epiteliais e Glandulares , Timoma , Neoplasias do Timo , Humanos , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Prognóstico , Estudos Retrospectivos , Timoma/patologia , Neoplasias do Timo/patologia
11.
Int J Med Sci ; 19(11): 1638-1647, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36237993

RESUMO

Background: Thymic epithelial tumors (TETs) are clinically the most frequently encountered neoplasm of the prevascular mediastinum in adults. The role of chest magnetic resonance (MR) imaging has been increasingly stressed thanks to its excellent contrast resolution, freedom from ionizing radiation, and capability to provide additional information regarding tumors' cellular structure and vascularity. Methods: This study aimed to establish the relationship between the MR findings and pathological classification of TETs, focusing on diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) imaging. This retrospective cross-sectional study included 44 TET patients who underwent chest MR scanning. The tumors were classified into three groups according to the WHO classification: low-risk thymoma (LRT), high-risk thymoma (HRT), and non-thymoma (NT). Along with morphological characteristics, the apparent diffusion coefficient (ADC) value, time-intensity curve (TIC) pattern, and time to peak enhancement (TTP) of the tumors were recorded and compared between the three groups. Results: A smooth contour and complete or almost complete capsule were suggestive of LRTs. The median ADC value of the 44 tumors was 0.95 × 10-3 mm2/sec. Among the three groups, LRTs had the highest ADC values, while NTs had the lowest. The differences between the ADC values of the three groups were statistically significant (p = 0.006). Using an ADC cutoff of 0.82 × 10-3 mm2/sec to differentiate between LRTs and tumors of the two remaining groups, the area under the curve was 0.775, sensitivity was 100%, specificity was 50%, and accuracy was 65.91%. The washout (type 3) TIC pattern was the most prevalent, accounting for 45.45% of the population; this pattern was also predominantly observed in LRTs (71.43%). Although the median TTP of LRTs was lower than that of HRTs or NTs, no statistically significant differences were found between the TTPs of the three groups (p = 0.170). Conclusions: MR is a good imaging modality to preoperatively assess TETs. Morphological features, ADC value, TIC pattern, and TTP are helpful in preoperatively predicting TET pathology.


Assuntos
Neoplasias Epiteliais e Glandulares , Adulto , Meios de Contraste , Estudos Transversais , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias Epiteliais e Glandulares/diagnóstico por imagem , Estudos Retrospectivos , Tiamina , Neoplasias do Timo
12.
Cancer Genomics Proteomics ; 19(6): 692-702, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36316042

RESUMO

BACKGROUND: Transmembrane emp24 domain-containing protein 9 (TMED9) belongs to the TMED/p24 family that transports, modifies, and packs proteins and lipids into vesicles for delivery to specific locations and is important in innate immune signaling via the endoplasmic reticulum-Golgi cargo pathway. TMED9 has been implicated in various cancer types; however, its role in epithelial ovarian cancer (EOC) is unclear. In this study, we aimed to elucidate the role and clinical significance of TMED9 in EOC. MATERIALS AND METHODS: mRNA and protein levels of TMED9 and their associations with clinicopathological features in EOCs were evaluated using RNA-sequencing and immunohistochemistry data. Functional studies assessing the tumorigenic role of TMED9 in EOC cell lines were also performed. RESULTS: The mRNA expression of TMED9 was up-regulated in EOC compared to that in normal ovarian epithelium. TMED9 protein expression increased in progression from normal ovarian epithelium to EOC (p<0.001). Moreover, high expression of TMED9 was associated with advanced stage, serous cell type and poor histological grade in EOC and demonstrated independent prognostic significance for both disease-free and overall survival. Further functional studies showed that TMED9 knockdown reduced migration, invasion, cell proliferation, and colony formation of EOC cells. CONCLUSION: Overall, our results support the use of TMED9 as a valuable prognostic biomarker and provide evidence for targeting of TMED9 as a novel strategy for EOC treatment.


Assuntos
Neoplasias Epiteliais e Glandulares , Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/patologia , Prognóstico , Proliferação de Células/genética , Biomarcadores Tumorais/metabolismo , RNA Mensageiro/genética , Neoplasias Epiteliais e Glandulares/genética
13.
J Gastroenterol ; 57(12): 927-941, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36260172

RESUMO

Duodenal cancer is considered to be a small intestinal carcinoma in terms of clinicopathology. In Japan, there are no established treatment guidelines based on sufficient scientific evidence; therefore, in daily clinical practice, treatment is based on the experience of individual physicians. However, with advances in diagnostic modalities, it is anticipated that opportunities for its detection will increase in future. We developed guidelines for duodenal cancer because this disease is considered to have a high medical need from both healthcare providers and patients for appropriate management. These guidelines were developed for use in actual clinical practice for patients suspected of having non-ampullary duodenal epithelial malignancy and for patients diagnosed with non-ampullary duodenal epithelial malignancy. In this study, a practice algorithm was developed in accordance with the Minds Practice Guideline Development Manual 2017, and Clinical Questions were set for each area of epidemiology and diagnosis, endoscopic treatment, surgical treatment, and chemotherapy. A draft recommendation was developed through a literature search and systematic review, followed by a vote on the recommendations. We made decisions based on actual clinical practice such that the level of evidence would not be the sole determinant of the recommendation. This guideline is the most standard guideline as of the time of preparation. It is important to decide how to handle each case in consultation with patients and their family, the treating physician, and other medical personnel, considering the actual situation at the facility (and the characteristics of the patient).


Assuntos
Neoplasias Duodenais , Neoplasias Epiteliais e Glandulares , Humanos , Neoplasias Duodenais/diagnóstico , Neoplasias Duodenais/epidemiologia , Neoplasias Duodenais/terapia , Endoscopia , Japão/epidemiologia
14.
Turk J Pediatr ; 64(5): 964-969, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36305451

RESUMO

BACKGROUND: Placental transmogrification of the lung (PTL) is a clinical spectrum varying from asymptomatic to severe pulmonary impairment; such as recurrent pneumothorax, bronchopneumonia, respiratory distress syndrome and chronic obstructive airway disease. PTL usually presents as a bullous lesion, and rarely can appear in nodule or cyst formation on chest imaging. PTL with giant bullous emphysema has a male preference, is more commonly unilateral and mostly affects one lobe, but can rarely involve more than one lobe. CASE: Here we report a 13-year-old boy presenting with bullous emphysema and coexisting with a borderline testicular tumor. He had no complaints of cough, sputum, or shortness of breath. He had a past medical history of pneumonia five years ago. In order to elucidate the underlying lung pathology, a wedge lung biopsy was performed and the patient was diagnosed with PTL. Scrotum ultrasonography was performed because of hydrocele in both testes, and bilateral epididymal cysts with papillary solid projections were reported. Pathological examination of the epididymal tumor revealed a `Mullerian type borderline epithelial neoplasm` which is an analogue of the ovarian serous borderline tumor. CONCLUSIONS: In conclusion, we reported the youngest PTL case in the literature, a rare disease with unknown pathophysiology, presenting as bullous emphysema and coincidental Mullerian type borderline epithelial neoplasm. It is important to diagnose placental transmogrification of the lung in a child with bullous emphysema because compared to other cystic lung diseases it is a benign disease and if no additional malignity exists, lobectomy or pneumonectomy is the cure for the disease.


Assuntos
Enfisema , Neoplasias Epiteliais e Glandulares , Enfisema Pulmonar , Criança , Masculino , Feminino , Humanos , Gravidez , Adolescente , Placenta/patologia , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/diagnóstico por imagem , Pulmão/patologia , Enfisema/patologia , Neoplasias Epiteliais e Glandulares/patologia
15.
Expert Opin Biol Ther ; 22(11): 1379-1391, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36302510

RESUMO

INTRODUCTION: High-grade serous ovarian carcinoma (HGSC) is an aggressive subtype of epithelial ovarian carcinoma (EOC) and remains the most lethal gynecologic cancer. A lack of effective and tolerable therapeutic options and nonspecific symptoms at presentation with advanced stage of disease are among the challenges in the management of the disease. AREAS COVERED: An overview of ovarian cancer, followed by a discussion of the current therapeutic regimes and challenges that arise during and after the treatment of EOC. We discuss different formats of antibody therapeutics and their usage in targeting validated targets implicated in ovarian cancer, as well as three emerging novel proteins as examples recently implicated in their contribution to adaptive resistance in ovarian cancer. EXPERT OPINION: Antibody therapeutics allow for a unique and effective way to target proteins implicated in cancer and other diseases, and have the potential to radically change the outcomes of patients suffering from ovarian cancer. The vast array of targets that have been implicated in ovarian cancer and yet the lack of effective therapeutic options for patients further stresses the importance of discovering novel proteins that can be targeted, as well as predictive biomarkers that can inform the stratification of patients into treatment-specific populations.


Assuntos
Neoplasias Epiteliais e Glandulares , Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico
16.
BMC Genomics ; 23(1): 656, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114454

RESUMO

BACKGROUND: General transcription factor IIi (GTF2I) mutations are very common in thymic epithelial tumors (TETs) and are related to a more favorable prognosis in TET patients. However, limited research has been conducted on the role of GTF2I in the tumor immune microenvironment (TIME). Further, long non-coding RNAs (lncRNAs) have been associated with the survival of patients with TETs. Therefore, this study aimed to explore the relationship between GTF2I mutations and TIME and build a new potential signature for predicting tumor recurrence in the TETs. Research data was downloaded from The Cancer Genome Atlas database and the CIBERSORT algorithm was used to evaluate TIME differences between GTF2I mutant and wild-type TETs. Relevant differentially expressed lncRNAs based on differentially expressed immune-related genes were identified to establish lncRNA pairs. We constructed a signature using univariate and multivariate Cox regression analyses. RESULTS: GTF2I is the most commonly mutated gene in TETs, and is associated with an increased number of early-stage pathological types, as well as no history of myasthenia gravis or radiotherapy treatment. In the GTF2I wild-type group, immune score and immune cell infiltrations with M2 macrophages, activated mast cells, neutrophils, plasma, T helper follicular cells, and activated memory CD4 T cells were higher than the GTF2I mutant group. A risk model was built using five lncRNA pairs, and the 1-, 3-, and 5-year area under the curves were 0.782, 0.873, and 0.895, respectively. A higher risk score was related to more advanced histologic type. CONCLUSION: We can define the GTF2I mutant-type TET as an immune stable type and the GTF2I wild-type as an immune stressed type. A signature based on lncRNA pairs was also constructed to effectively predict tumor recurrence.


Assuntos
Neoplasias Epiteliais e Glandulares , RNA Longo não Codificante , Fatores Genéricos de Transcrição , Fatores de Transcrição TFIII , Fatores de Transcrição TFII , Regulação Neoplásica da Expressão Gênica , Humanos , Mutação , Recidiva Local de Neoplasia/genética , Neoplasias Epiteliais e Glandulares/genética , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias do Timo , Fatores Genéricos de Transcrição/genética , Fatores Genéricos de Transcrição/metabolismo , Fatores de Transcrição TFII/genética , Fatores de Transcrição TFII/metabolismo , Fatores de Transcrição TFIII/genética , Fatores de Transcrição TFIII/metabolismo , Microambiente Tumoral
17.
Front Immunol ; 13: 908453, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059463

RESUMO

Background: Thymic epithelial tumors (TETs) are frequently accompanied by Good Syndrome (GS), a rare immunodeficiency, characterized by hypogammaglobulinemia and peripheral B cell lymphopenia. TETs can be also associated to other immunological disorders, both immunodeficiency and autoimmunity. Methods: In this study, we enrolled TET patients with GS to address differences between patients with or without associated autoimmune diseases (AD). We analyzed the immunophenotype from peripheral blood of these patients focusing on selected immune cell subsets (CD4+T cells, CD8+T cells, T regulatory cells, NK cells, B-cells, monocytes, eosinophils, basophils, neutrophils) and serum levels of cytokines, chemokines and growth factors. Results: We observed higher number of leucocytes, in particular lymphocytes, B lymphopenia and lower number of T regulatory cells in TET patients with associated AD compared to TET patients without AD. In the group of TET patients with AD, we also observed increased serum levels of IL-15, VEGF, IP-10, GM-CSF, IL-6, and MIP-1α. Thus, we identified considerable differences in the lymphocyte profiles of TET patients with and without ADs, in particular a reduction in the numbers of B lymphocytes and T-regulatory cells in the former, as well as differences in the serum levels of various immune modulators. Conclusions: Although the pathogenic mechanisms are still unclear, our results add new knowledge to better understand the disease, suggesting the need of surveilling the immunophenotype of TET patients to ameliorate their clinical management.


Assuntos
Doenças Autoimunes , Linfopenia , Neoplasias Epiteliais e Glandulares , Doenças da Imunodeficiência Primária , Neoplasias do Timo , Doenças Autoimunes/patologia , Linfócitos T CD4-Positivos , Humanos , Linfopenia/patologia , Neoplasias Epiteliais e Glandulares/complicações , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias do Timo/complicações
18.
Int J Oncol ; 61(4)2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36082820

RESUMO

Epithelial ovarian cancer (EOC) is divided into type I and type II based on histopathological features. Type I is clinically more indolent, but also less sensitive to chemotherapy, compared with type II. The basis for this difference is not fully clarified. The present study investigated the pattern of drug activity in type I and type II EOC for standard cytotoxic drugs and recently introduced tyrosine kinase inhibitors (TKIs), and assessed the association with treatment history and clinical outcome. Isolated EOC tumor cells obtained at surgery were investigated for their sensitivity to seven standard cytotoxic drugs and nine TKIs using a short­term fluorescent microculture cytotoxicity assay (FMCA). Drug activity was compared with respect to EOC subtype, preoperative chemotherapy, cross­resistance and association with progression­free survival (PFS). Out of 128 EOC samples, 120 samples, including 21 type I and 99 type II, were successfully analyzed using FMCA. Patients with EOC type I had a significantly longer PFS time than patients with EOC type II (P=0.01). In line with clinical experience, EOC type I samples were generally more resistant than type II samples to both standard cytotoxic drugs and the TKIs, reaching statistical significance for cisplatin (P=0.03) and dasatinib (P=0.002). A similar pattern was noted in samples from patients treated with chemotherapy prior to surgery compared with treatment­naive samples, reaching statistical significance for fluorouracil, irinotecan, dasatinib and nintedanib (all P<0.05). PFS time gradually shortened with increasing degree of drug resistance. Cross­resistance between drugs was in most cases statistically significant yet moderate in degree (r<0.5). The clinically observed relative drug resistance of EOC type I, as well as in patients previously treated, is at least partly due to mechanisms in the tumor cells. These mechanisms seemingly also encompass kinase inhibitors. Ex vivo assessment of drug activity is suggested to have a role in the optimization of drug therapy in EOC.


Assuntos
Antineoplásicos , Neoplasias Epiteliais e Glandulares , Neoplasias Ovarianas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Dasatinibe/farmacologia , Dasatinibe/uso terapêutico , Resistência a Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/patologia
19.
World J Gastroenterol ; 28(34): 5047-5057, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36160642

RESUMO

BACKGROUND: Solid pseudopapillary tumor (SPT) is a rare pancreatic tumor. Considering its malignant behaviors, SPT has been classified as a low-grade malignant tumor. Indeed, only 9.2% of all SPT patients are initially diagnosed as malignant with invasion or metastasis. Thus, one of the challenges in managing SPT patients is predicting malignant behavior. AIM: To investigate the malignant behavior and tumor-associated macrophage (TAM) infiltration between different histopathologic features of SPT patients. METHODS: Twenty-five formalin-fixed paraffin-embedded tissue samples from 22 patients pathologically diagnosed with an SPT between 2009 and 2019 at West China Hospital were included in this retrospective study. Integrity of the capsule and growth pattern of the tumor cells was assessed microscopically in hematoxylin-eosin (HE)-stained sections. Based on the histopathological features, the SPT patients were divided into two groups: capsule or invasion. Clinical features, malignant behavior, and TAM infiltration were compared between the two groups. RESULTS: Among the 22 SPT patients, 11 were identified for each group, having either a capsule or invasion histopathologic feature. Malignant behavior was more frequent in the invasion group, including 2 patients who had peripheral organ invasion, 3 with liver metastasis, and 1 with both lymph node and spleen metastases (P= 0.045). Ki-67 index of more than 3% was also more frequent in the invasion group (P = 0.045). Immunohistochemical analysis showed that the invasion group had a significant increase of CD68-positive TAMs in intratumor and peritumor sites in comparison with the capsule group (all P < 0.0001). Similarly, CD163-positive M2-like macrophages were also markedly increased in the intratumor and peritumor sites in the invasion group (all P < 0.0001). At the liver metastasis site, both intratumor and peritumor tissues showed relatively high-level CD68-positive TAMs and CD163-positive M2-like macrophages infiltration. However, the differences between the intratumor, peritumor and normal hepatic tissues did not reach statistical significance (all P > 0.05). CONCLUSION: SPT patients with invasion evident under microscope were more likely to exhibit malignant behavior and TAM infiltration, especially M2-like macrophages. This finding can help in future investigations of the underlying mechanism of TAM-mediated SPT malignant behavior.


Assuntos
Neoplasias Hepáticas , Neoplasias Epiteliais e Glandulares , Humanos , Antígeno Ki-67/análise , Neoplasias Hepáticas/secundário , Pâncreas , Estudos Retrospectivos , Macrófagos Associados a Tumor
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