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This case report describes a diagnosis of streaky multifocal choroiditis in a boy who presented with distorted vision in his left eye for 3 years.
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Corioidite , Angiofluoresceinografia , Coroidite Multifocal , Humanos , Masculino , Criança , Corioidite/diagnóstico , Corioidite/tratamento farmacológico , Angiofluoresceinografia/métodos , Tomografia de Coerência Óptica/métodos , Acuidade VisualRESUMO
AIM: To investigate the association between central serous chorioretinopathy (CSC) and Helicobacter pylori (Hp) by summarizing all available evidence. METHODS: The Scopus, Embase, EBSCO, PubMed, Web of Science, and Cochrane Library databases for all relevant studies published from inception to October 2022 were searched, and manually searched for relevant reference lists as a supplement. Studies investigating the association between CSC and Hp infection were included. Finally, 8 case-control studies were included in the Meta-analysis after study selection. RESULTS: The results showed no significant correlation between Hp infection and CSC [odds ratio (OR) 1.89, 95% confidential interval (CI) 0.58-6.15, I 2=96%, P=0.29]. After subgroup analysis based on the degree of development of the study (developing/developed countries), it was found that the results of the two subgroups were the same as the whole, and no significant difference between the two subgroups existed. Meta-regression showed that the effect of sample size on heterogeneity among studies was more prominent (P<0.01, adjusted R 2=89.72%), which can explain 89.72% of the sources of heterogeneity. CONCLUSION: This Meta-analysis reveals no significant correlation between Hp infection and CSC, which still warrants further well-designed extensive sample studies to reach a more reliable conclusion and promote a better understanding of the treatment of CSC.
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AIM: To summarize the application of deep learning in detecting ophthalmic disease with ultrawide-field fundus images and analyze the advantages, limitations, and possible solutions common to all tasks. METHODS: We searched three academic databases, including PubMed, Web of Science, and Ovid, with the date of August 2022. We matched and screened according to the target keywords and publication year and retrieved a total of 4358 research papers according to the keywords, of which 23 studies were retrieved on applying deep learning in diagnosing ophthalmic disease with ultrawide-field images. RESULTS: Deep learning in ultrawide-field images can detect various ophthalmic diseases and achieve great performance, including diabetic retinopathy, glaucoma, age-related macular degeneration, retinal vein occlusions, retinal detachment, and other peripheral retinal diseases. Compared to fundus images, the ultrawide-field fundus scanning laser ophthalmoscopy enables the capture of the ocular fundus up to 200° in a single exposure, which can observe more areas of the retina. CONCLUSION: The combination of ultrawide-field fundus images and artificial intelligence will achieve great performance in diagnosing multiple ophthalmic diseases in the future.
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Objective: To report a case of macular injury caused by short-term exposure to a handheld high-intensity light emitting diode (LED) light. Design: Interventional case report. Participant: A patient with macular injury caused by short-term exposure to the light of a handheld high-intensity LED device. Intervention: The patient was examined and followed for 3 months after exposure with ophthalmologic examinations (including funduscopy, optical coherence tomography [OCT], fluorescein angiography [FA], and multifocal electroretinography [mfERG]). The injured eye was treated with one retrobulbar injection of 20 mg triamcinolone acetonide at 5 days after exposure. Main outcome measures: Visual acuity, ophthalmoscopic, and OCT findings. Results: 3 days after exposure, the best corrected visual acuity (BCVA) of the right eye was 6/20. OCT revealed the acute stage of the injury with eminence of the retinal pigment epithelium (RPE). BCVA was improved to 16/20 and 20/20 at 19 and 33 days after exposure, respectively. OCT results of follow-ups at five days, 19 days, 33 days and 3 months after exposure have demonstrated the restoration process of the injury. Conclusions: Short-term exposure to high-intensity LED light may cause damage to the retina. As the expansion of LED use in modern life, education and supervision are of urgent need for public health.
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Choroidal osteoma is a benign ossifying tumor within the choroid. Complications associated with choroidal osteoma, including disruption of retinal pigment epithelium, atrophy of photoreceptors, subretinal fluid, and choroidal neovascularization, present challenges for clinicians, and management remain controversial. We performed a comprehensive search in the PubMed, EMBASE, and Ovid databases for published studies and case reports relating to the management of choroidal osteoma. Since it was first described in 1978, various case reports of ocular complications associated with choroidal osteoma have been documented, and various therapies have yielded different outcomes. We systematically evaluate the literature published on this rare entity.
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Neoplasias da Coroide , Neovascularização de Coroide , Osteoma , Humanos , Neoplasias da Coroide/diagnóstico , Neoplasias da Coroide/terapia , Neoplasias da Coroide/complicações , Corioide/patologia , Osteoma/diagnóstico , Osteoma/terapia , Osteoma/complicações , Neovascularização de Coroide/tratamento farmacológico , Epitélio Pigmentado da Retina/patologia , Angiofluoresceinografia , Tomografia de Coerência ÓpticaRESUMO
Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.
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Inibidores da Angiogênese , Vasculopatia Polipoidal da Coroide , Humanos , Inibidores da Angiogênese/uso terapêutico , Terapia Combinada , Fator A de Crescimento do Endotélio Vascular , Hemorragia Retiniana/tratamento farmacológico , Tomografia de Coerência Óptica/métodos , Angiofluoresceinografia/métodos , Estudos RetrospectivosRESUMO
Anti-MDA5 antibody dermatomyositis (DM) is a special type of myositis, which can potentially cause rapidly progressive interstitial lung disease (RP-ILD). Mixed connective tissue disease (MCTD) is a complex disease with different characteristics of autoimmune connective tissue disease, associated with ILD. Both are rare diseases, and few patients with both diseases have been reported. A 71-year-old woman complained of palpitations, with a 2 months history of rash around her hands, extensor surface of right elbow, and the nape of her neck. Subsequently, the patient had acute exacerbation of dyspnea and tachypnea. Anti-Ro52, U1 RNP and MDA5 antibodies were positive; the presenting evidence was suggestive of anti-MDA5+ DM-RP-ILD complicated with MCTD. Our patient deteriorated rapidly and had a fatal outcome, despite "triple therapy" for RP-ILD. This case illustrates that patients with coexisting anti-MDA5+ DM and MCTD have the former's typical clinical manifestations, and may develop ILD quickly rather than slowly as in MCTD, especially with the coexistence of anti-Ro52 antibodies.
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Doenças Autoimunes , Dermatomiosite , Doenças Pulmonares Intersticiais , Doença Mista do Tecido Conjuntivo , Humanos , Feminino , Idoso , Doença Mista do Tecido Conjuntivo/complicações , Autoanticorpos , Doenças Autoimunes/complicações , Estudos RetrospectivosRESUMO
BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a treatable but frequently misdiagnosed autoimmune disease. Speech dysfunction, as one of the common manifestations of anti-NMDAR encephalitis, is usually reported as a symptom secondary to psychiatric symptoms or seizures rather than the initial symptom in a paroxysmal form. We report a case of anti-NMDAR encephalitis with paroxysmal speech disorder as a rare initial manifestation, and hope that it will contribute to the literature. CASE SUMMARY: A 39-year-old man with anti-NMDAR encephalitis initially presented with paroxysmal nonfluent aphasia and was misdiagnosed with a transient ischemic attack and cerebral infarction successively. The patient subsequently presented with seizures, but no abnormalities were found on brain magnetic resonance imaging or electroencephalogram. Cerebrospinal fluid (CSF) analysis revealed mild pleocytosis and increased protein levels. Anti-NMDAR antibodies in serum and CSF were detected for a conclusive diagnosis. After immunotherapy, the patient made a full recovery. CONCLUSION: This case suggests that paroxysmal speech disorder may be the presenting symptom of anti-NMDAR encephalitis in a young patient.
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OBJECTIVE: Abdominal aortic aneurysm (AAA) is a significant medical problem with a high mortality rate. Nevertheless, the underlying mechanism for the progression and regression of AAA is unknown. METHODS: Experimental model of AAA was first created by porcine pancreatic elastase incubation around the infrarenal aorta of C57BL/6 mice. Then, AAA progression and regression were evaluated based on the diameter and volume of AAA. The aortas were harvested for hematoxylin-eosin staining (HE), orcein staining, sirius red staining, immunofluorescence analysis and perls' prussian blue staining at the indicated time point. Finally, ß-aminopropionitrile monofumarate (BAPN) was used to explore the underlying mechanism of the regression of AAA. RESULTS: When we extended the observation period to 100 days, we not only observed an increase in the AAA diameter and volume in the early stage, but also a decrease in the late stage. Consistent with AAA diameter and volume, the aortic thickness showed the same tendency based on HE staining. The elastin and collagen content first degraded and then regenerated, which corresponds to the early deterioration and late regression of AAA. Then, endogenous up-regulation of lysyl oxidase (LOX) was detected, accompanying the regression of AAA, as detected by an immunofluorescent assay. BAPN and LOX inhibitor considerably inhibited the regression of AAA, paralleling the degradation of elastin lamella and collagen. CONCLUSION: Taken together, we tentatively conclude that endogenous re-generation of LOX played an influential role in the regression of AAA. Therefore, regulatory factors on the generation of LOX exhibit promising therapeutic potential against AAA.
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Aminopropionitrilo/análogos & derivados , Aneurisma da Aorta Abdominal/patologia , Proteínas da Matriz Extracelular/metabolismo , Elastase Pancreática/efeitos adversos , Proteína-Lisina 6-Oxidase/metabolismo , Aminopropionitrilo/administração & dosagem , Aminopropionitrilo/farmacologia , Animais , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/tratamento farmacológico , Aneurisma da Aorta Abdominal/metabolismo , Colágeno/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Elastina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Regulação para CimaRESUMO
Intrahepatic cholangiocarcinoma (ICC) is a highly fatal malignancy characterized by a vast amount of intra-tumoral fibroblasts. These fibroblasts are potentially implicated in maintaining the high aggressiveness of ICC, whereas its pro-cancer mechanisms remain scarcely reported. Here, by establishing co-culture models of ICC cells and hepatic stellate cells (HSCs), we identified that HSCs triggered the expression of nuclear receptor family 4 subgroup A member 2 (NR4A2), a transcription factor previously reported as a molecular switch between inflammation and cancer, in ICC cells. Functionally, NR4A2 promotes tumor proliferation, metastatic potentiality and represents an independent prognostic indicator for overall survival in ICC patients. Mechanistically, NR4A2 upregulates osteopontin (OPN) expression through transcriptional activation and thereby augments the activity of Wnt/ß-catenin signaling. Intriguingly, in the context of co-culture, vascular endothelial growth factor (VEGF), a previously proved NR4A2 stimulus, not only enhances NR4A2 expression, but also can be blunted by the interference of the NR4A2-OPN axis. Altogether, this study suggests the NR4A2/OPN/Wnt signaling axis to be a pivotal executor of HSC-instigated cancer-promoting roles in ICC, and the NR4A2/OPN/VEGF positive feedback loop may help to reinforce the effect.
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Colangiocarcinoma/genética , Células Estreladas do Fígado/metabolismo , Osteopontina/metabolismo , Via de Sinalização Wnt/genética , Colangiocarcinoma/patologia , Progressão da Doença , Humanos , TransfecçãoRESUMO
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly mortal malignancy with limited therapeutic options. Immunotherapies targeting PD-1/PD-L1 pathway represent a promising treatment for ICC. However, PD-L1 expression and microsatellite instability are not common in ICC. This study aimed to investigate whether HHLA2, a newly identified B7 family immune checkpoint for T cells, could be a therapeutic target next to PD-L1 in ICC. METHODS: Expression levels of PD-L1 and HHLA2 as well as infiltrations of CD3+, CD8+, CD4 + Foxp3+, CD68+, CD163+ and CD20+ cells were evaluated by immunohistochemistry in 153 resected ICC samples. Comprehensive comparisons were made between PD-L1 and HHLA2 in terms of the expression rates, clinicopathological features and infiltrations of different immune cells. The expression level and prognostic significance of HHLA2 were further validated in an independent cohort. RESULTS: Expression of HHLA2 is more frequent than PD-L1 in ICC (49.0% vs 28.1%). Co-expression of both immune checkpoints was infrequent (13.1%) and 50% PD-L1 negative cases were with elevated HHLA2. HHLA2 overexpression was associated with sparser CD3+ tumor infiltrating lymphocytes (TILs), CD8+ TILs and a higher CD4 + Foxp3+/CD8+ TIL ratio, whereas PD-L1 expression was associated with prominent T cells and CD163+ tumor associated macrophages infiltrations. PD-L1 failed to stratify overall survival (OS) but HHLA2 was identified as an independent prognostic indicator for OS in two independent cohorts. CONCLUSIONS: Compared with PD-L1, HHLA2 is more prevalent and possesses more explicit prognostic significance, which confer the rationale for HHLA2 as a potential immunotherapeutic target next to PD-L1 for ICC patients.
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Antígeno B7-H1/metabolismo , Neoplasias dos Ductos Biliares/imunologia , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/imunologia , Imunoglobulinas/metabolismo , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Prognóstico , Análise de Sobrevida , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/imunologia , Regulação para CimaRESUMO
Oct4 and Nanog are reported to promote tumor progression in several cancers, but the effect on intrahepatic cholangiocarcinoma (ICC) is unknown. The aim of our present study was to explore the prognostic role of Oct4 and Nanog on patients with ICC. Immunohistochemistry was used to detect the expression of Oct4 and Nanog in a random cohort of 116 ICC patients, and validated in another independent cohort of 103 patients. Prognostic nomograms were formulated for OS and RFS prediction of ICC patients. Our results showed Oct4 and Nanog highly expressed in ICC tumor tissues and were identified as independent prognostic factors for patients' OS and RFS. Significant positive correlation was found between Oct4 and Nanog expression. Co-expression of Oct4 and Nanog implied the poorest OS and RFS in ICC patients. Our nomograms comprising Oct4 and Nanog achieved better predictive accuracy in training and validation cohorts compared with AJCC 7th edition and LCSGJ stage for OS and RFS prediction. Our study support the high expression of Oct4 and Nanog in ICC implies aggressive tumor behaviors and suggest a poor clinical prognosis, which emerges as valuable biomarkers for identifying patients at high risk after curative resection.
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S100A11 is reported to associate with progression and poor prognosis in several tumors. We previously reported that S100A11 was highly expressed in intrahepatic cholangiocarcinoma (ICC) cells and promoted TGF-ß1-induced EMT through SMAD2/3 signaling pathway. Here, we explored the prognostic role of S100A11 on ICC patients and preliminary molecular mechanisms how S100A11 regulated ICC cell proliferation. Our results showed that S100A11 was obviously increased in ICC tumor tissues. High expression of S100A11 was closely correlated with lymph node metastasis (LNM) and TNM stage and was an independent risk factor for patients' overall survival (OS) and recurrence-free survival (RFS). The nomograms comprising LNM and S100A11 achieved better predictive accuracy compared with TNM staging system for OS and RFS prediction. Silencing S100A11 significantly suppressed RBE cells and HCCC9810 cells proliferation, colony formation, and activation of P38/mitogen-activated protein kinase (MAPK) signaling pathway in vitro and inhibited tumor growth in vivo. In contrast, the overexpression of S100A11 in RBE cells and HCCC9810 cells achieved the opposite results. S100A11-induced proliferation was abolished after treatment with P38 inhibitor. Our findings suggest S100A11/P38/MAPK signaling pathway may be a potential therapeutic target for ICC patients.
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Neoplasias dos Ductos Biliares/secundário , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Colangiocarcinoma/patologia , Recidiva Local de Neoplasia/patologia , Proteínas S100/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Apoptose , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/metabolismo , Biomarcadores Tumorais/genética , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Proteínas S100/genética , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
Tyrosine kinase inhibitors (TKIs) have improved the overall survival of patients with gastrointestinal stromal tumors (GISTs), but their side effects can impact dose intensity and, consequently, the clinical benefit. To date, no guideline or consensus has been published on the TKI-associated adverse reactions. Therefore, the Chinese Society of Surgeons for Gastrointestinal Stromal Tumor of the Chinese Medical Doctor Association organized an expert panel discussion involving representatives from gastrointestinal surgery, medical oncology, cardiology, dermatology, nephrology, endocrinology, and ophthalmology to consider the systemic clinical symptoms, molecular and cellular mechanisms, and treatment recommendations of GISTs. Here, we present the resultant evidence- and experience-based consensus to guide the management of TKI-associated side events in clinical practice.
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Antineoplásicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Tirosina Quinases/antagonistas & inibidores , China , Consenso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Humanos , Médicos/normas , Sociedades Médicas/normasRESUMO
BACKGROUND: Radical resection is the treatment of choice for hepatocellular carcinoma (HCC). However, even with this treatment, HCC prognosis and the efficacy of current predictive models for such patients remain unsatisfactory. Here, we describe an accurate and easy-to-use prognostic index for patients with HCC who have undergone curative resection. METHODS: The study population comprised of 1,041 patients with HCC who underwent curative resection at Zhongshan Hospital. This population was reduced to 768 patients who were treated in 2012 analyzed as the training cohort and 273 patients treated in 2007 who were used as a validation cohort. RESULTS: The lactic dehydrogenase to albumin ratio (LAR) was identified as a significant prognostic index for both overall survival and recurrence-free survival in two independent cohorts. The optimal cutoff value for LAR was determined to be 5.5. The C-index of LAR was superior to other inflammatory scores and serum parameters. This biomarker was also shown to be a stable predictive index in the validation cohort. The new nomogram combining LAR with the Barcelona Clinic Liver Cancer staging system had an improved ability to discriminate overall survival and recurrence-free survival. Nomogram predictions were consistent with observations based on calibration and decisive curve analysis in both independent cohorts. CONCLUSION: LAR is a novel, convenient, reliable, and accurate prognostic predictor in patients with HCC undergoing curative resection. Our results suggest the recommendation of LAR to be used in routine clinical practice.
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BACKGROUND: Fibrotic tumor stroma (FTS) has been implicated in cancer promotion in several neoplasms. The histological features of FTS are convenient and easily accessible in clinical routine in intrahepatic cholangiocarcinoma (ICC) specimens. The goal of this study was to explore prognostic impacts of the quantity and maturity of FTS on surgical ICC patients. Moreover, we aimed to propose an efficient prognostic nomogram for postoperative ICC patients. MATERIALS AND METHODS: The clinical profiles of 154 consecutive postoperative ICC patients were retrospectively analyzed. Tumor-stroma ratio and morphological maturity of FTS were evaluated on hematoxylin and eosin-stained tumor sections. CD3, CD8, and α-smooth muscle actin (α-SMA) staining were performed on corresponding tissue microarrays. The nomogram was established on variables selected by multivariate analyses and was validated in 10-fold cross-validation. RESULTS: Rich tumor stroma and strong α-SMA expression were associated with poor overall survival (OS). However, in multivariate analyses, these two biomarkers failed to stratify both OS and recurrence-free survival (RFS). Immature FTS was correlated with tumor multiplicity, advanced clinical stage, and sparser CD3 and CD8 positive tumor-infiltrating lymphocytes (TILs) and was identified as an independent prognostic indicator for both OS and RFS. The nomogram comprising FTS maturity, tumor number, microvascular invasion, and lymph node metastasis possessed higher predictive power relative to conventional staging systems. CONCLUSION: Immature FTS was an independent risk factor for survival and was associated with sparser CD3 and CD8 positive TILs in ICC. The prognostic nomogram integrating the maturity of FTS offers a more accurate risk stratification for postoperative ICC patients. IMPLICATIONS FOR PRACTICE: Accumulating evidence has suggested that fibrotic components in tumor microenvironment (TME) play a complicated and vital role in TME reprogramming and cancer progression. However, in clinical practice, the evaluation of fibrotic tumor stroma (FTS) is still neglected to some extent. This study's findings indicated that, in intrahepatic cholangiocarcinoma (ICC), the histological maturity of FTS is a robust prognostic indicator for patients who underwent curative resection. Moreover, prognostic nomogram constructed on the maturity of FTS possessed higher predictive power relative to the conventional tumor-node-metastasis staging systems. Taken together, the evaluation of FTS should be emphasized in clinical routine for more accurate prognostic prediction in postoperative ICC patients.
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Colangiocarcinoma/complicações , Fibrose/patologia , Neoplasias/patologia , Nomogramas , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Feminino , Humanos , Masculino , Metástase Neoplásica , PrognósticoRESUMO
BACKGROUND: There is currently no established model for predicting the recurrence of hepatocellular carcinoma (HCC) in patients with negative alpha-fetoprotein (AFP) after curative resection. Therefore, the objective of this study was to establish a nomogram to identify the risk of recurrence in AFP-negative (Assuntos
Biomarcadores Tumorais/sangue
, Carcinoma Hepatocelular/patologia
, Hepatectomia
, Neoplasias Hepáticas/patologia
, Recidiva Local de Neoplasia/patologia
, Nomogramas
, Cuidados Pré-Operatórios
, alfa-Fetoproteínas/análise
, Adulto
, Idoso
, Carcinoma Hepatocelular/sangue
, Carcinoma Hepatocelular/cirurgia
, Feminino
, Seguimentos
, Humanos
, Neoplasias Hepáticas/sangue
, Neoplasias Hepáticas/cirurgia
, Masculino
, Pessoa de Meia-Idade
, Recidiva Local de Neoplasia/sangue
, Recidiva Local de Neoplasia/cirurgia
, Prognóstico
, Estudos Retrospectivos
, Fatores de Risco
, Taxa de Sobrevida
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Interleukin-35 (IL-35) is implicated in tumorigenesis, but its exact impact on intrahepatic cholangiocarcinoma (ICC) is not clear. The aim of the present study was to explore the specific effect of IL-35 on patient prognosis. Additionally, we formulated an effective prognostic nomogram for ICC patients after curative resection. Immunohistochemistry was applied to explore IL-35 expression as well as IL-35 receptor (IL-35R) in 102 ICC patients. Results showed that IL-35 was highly expressed in ICC tumor tissues and was positively associated with lymph node metastasis (LNM), TNM stage and vascular invasion and was an independent prognostic factor for patients' overall survival (OS) and recurrence-free survival (RFS). High expression of IL-35R (gp130 and IL-12Rß2) was also observed in ICC cancer tissues, but only gp130 was an independent prognostic factor for OS and RFS and was indispensable in IL-35-mediated ICC clinical prognosis. The nomogram comprising carcinoembryonic antigen, LNM, IL-35 and gp130 expression achieved better predictive accuracy compared with TNM stage for OS. Our data support that high IL-35 expression correlates with ICC aggressiveness and emerges as a valuable biomarker for evaluating ICC progression and prognosis in clinical work.
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Neoplasias dos Ductos Biliares/metabolismo , Ductos Biliares Intra-Hepáticos/metabolismo , Colangiocarcinoma/metabolismo , Interleucinas/metabolismo , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Linhagem Celular Tumoral , Colangiocarcinoma/patologia , Receptor gp130 de Citocina/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Interleucina-1/metabolismo , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias/métodos , Prognóstico , Receptores de Interleucina-12/metabolismo , Estudos RetrospectivosRESUMO
The aim of this study was to investigate the role of G-protein signaling modulator 2 in the carcinogenesis and progression of hepatocellular carcinoma. We previously showed that G-protein signaling modulator 2 was upregulated in hepatitis B virus-related hepatocellular carcinoma tissues through a hierarchical clustering analysis. With this study, we first assessed the expression pattern of G-protein signaling modulator 2 in hepatocellular carcinoma specimens and adjacent noncancerous tissues; clinical data were analyzed, along survival times, utilizing the Kaplan-Meier method. Moreover, the functions of G-protein signaling modulator 2 were examined using small-interfering RNAs in vitro. The results showed that G-protein signaling modulator 2 was clearly overexpressed in hepatocellular carcinoma tissues and cell lines and that the G-protein signaling modulator 2 expression level was related to tumor size and hepatitis B virus infection. Furthermore, G-protein signaling modulator 2 knockdown studies suggested that G-protein signaling modulator 2 accelerates cell growth, cell cycle, migration, and invasion and inhibits apoptosis, acting as an oncogene in hepatocellular carcinoma. Western blotting indicated that silencing of G-protein signaling modulator 2 in HepG2 and SMMC-7721 cells increased the expression levels of Bax, caspase-3, and E-cadherin, while notably suppressing the cyclin-dependent kinase 4, cyclin-dependent kinase 6, CyclinD1, Snail1, Vimentin, and matrix metallopeptidase 9 expression levels, compared with that in the control groups. In addition, we found that G-protein signaling modulator 2 can affect the expression of key proteins involved in protein kinase B activation. In conclusion, high expression of G-protein signaling modulator 2 was involved in the pathological processes of hepatocellular carcinoma through activation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, which may provide an attractive potential diagnostic biomarker and therapeutic target for treatment of hepatocellular carcinoma.