Constitutive type-1 interferons signaling activity in malignant gliomas.

PURPOSE: Recent studies revealed a pro-tumor effect of constitutive Type-1 interferons (IFN-I) production and the downstream signaling activity in several malignancies. In contrast, heterogeneity and clinical significance of the signaling activity in gliomas remain unknown. Thus, we aimed to depict the heterogeneity and clinical significance of constitutive Type-1 interferon (IFN-I) production and the downstream signaling activity in gliomas. METHODS: We utilized multiplex immunofluorescence (mIF) on a 364 gliomas tissue microarray from our cohort. Moreover, we conducted bioinformatic analyses on the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases to investigate the heterogeneity and clinical significance of constitutive IFN-I signaling activity in gliomas. RESULTS: We observed high heterogeneity of the constitutive IFN-I signaling activity among glioma subtypes. Signaling increased with the WHO malignancy grade while decreasing in the gliomas with IDH mutations. Additionally, high IFN-I activity served as an independent predictor of unfavorable outcomes, and global DNA hypermethylation in IDH-mutant gliomas was associated with decreased IFN-I signaling activity. Positive correlations were observed between the IFN-I activity and glioma-associated inflammation, encompassing both anti-tumor and pro-tumor immune responses. Furthermore, the IFN-I activity varied significantly among tumor and immune cells in the glioma microenvironment (GME). Notably, a distinct pattern of IFN-I signaling activity distribution in GME cells was observed among glioma subtypes, and the pattern was independently associated with patient overall survival. CONCLUSIONS: Constitutive IFN-I signaling activity varies significantly among glioma subtypes and represents a potential indicator for increased glioma inflammation and unfavorable clinical outcomes.

Clinicopathologic characteristics of low-grade thyroid-like nasopharyngeal papillary adenocarcinoma: a case report.

Low-grade thyroid-like nasopharyngeal papillary adenocarcinoma is a rare malignant tumor characterized by morphologic analogy to papillary thyroid carcinoma and aberrant thyroid transcription factor-1 (TTF-1) expression. To date, a limited number of cases have been reported in the literature. We report a case of a 20-year-old Chinese male patient with complaints of headaches and nosebleeds for 5 months. The histopathologic examination showed thyroid-like low-grade nasopharyngeal papillary adenocarcinoma that was confirmed by immunohistochemical staining. The patient was treated with macroscopic complete resection without adjuvant therapy. The epidemiologic characteristics and clinical and pathologic features of the disease are summarized. In addition, we summarize the treatments used previously. In general, TL-LGNPPA is a very rare low-grade adenocarcinoma with aberrant expression of TTF-1, and its diagnosis depends on morphology and immunophenotype. The prognosis is good.

gp96 Expression in Gliomas and Its Association with Tumor Malignancy and T Cell Infiltrating Level.

Heat shock protein glycoprotein 96 kDa (gp96) implicates in glioma invasiveness and engages antitumor immune response, representing a potential target for glioma treatment. However, its expression in different types of gliomas, its association with glioma-infiltrating T cells (GITs), and their clinical significance remain unknown. Herein, we utilized multiplex immunofluorescence staining (MIS) to detect gp96 expression and GIT levels on a tissue microarray (TMA), that comprises 234 glioma cases. We then validated the TMA results and explored possible mechanisms by investigating the RNA-seq data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). We observed that gp96 was ubiquitously expressed in all types of gliomas whereas overexpressed in grade IV gliomas. Also, high gp96 expression predicted unfavorable outcomes independent of the malignancy grade. Meanwhile, gp96 expression positively correlated CD8+, CD4+, and PD-1+ cell densities, and especially associated with increased infiltration of CD4+ PD-1+ GITs. Clinically, the gp96-immune cell score (GI score), by summing the values measuring gp96 expression and immune cell densities, is capable of stratifying patients into four outcome-distinct groups (hazard ratio, 1.945; 95% CI, 1.521-2.486; P < 0.0001). Mechanistically, the interferon-γ/α response pathways were revealed to engage in the association between gp96 and GITs. Taken together, gp96 was ubiquitously expressed in gliomas, overexpressed in grade IV gliomas, and increased with GIT infiltrative levels. The GI score, that integrates levels of gp96 expression and GIT infiltration, is a potential prognostic classification system for gliomas.

Anatomical Study of Arachnoid Granulation in Superior Sagittal Sinus Correlated to Growth Patterns of Meningiomas.

Meningiomas in the parasagittal region were formed by arachnoidal cells disseminated among arachnoid granulations. The purpose of this study was to characterize the morphology of chordae willisii, and AGs found in the superior sagittal sinus. This study used 20 anatomical specimens. Rigid endoscopes were introduced via torcula herophili into the sinus lumen. The morphological features of arachnoid granulation and chordae willisii were analyzed, and then arachnoid granulations and chordae willisii were assessed by elastic fiber stains, Masson's stains, and imaging analysis. Three types of arachnoid granulations were present in the examined sinuses. There were 365 counts of arachnoid granulations in examined sinuses by imaging analysis, averaging 1.36 ± 2.58 per sinus. Types I, II, and III made up 20.27, 45.20, and 34.52% of 268 patients, respectively. Microscopy of chordae willisii transverse sections indicated the existence of a single layer and a multiple-layered dura sinus wall. The dural sinus wall was the thickest one in the superior sagittal sinus. The thickness of longitudinal lamellae was significantly greater than trabeculae. This study reveals the anatomical differences between arachnoid granulations in the superior sagittal sinus. The arachnoid granulations classification enables surgeons to predict preoperatively growth patterns, followed by safely achieving the optimal range of parasagittal meningioma resection.

Case Report: Anlotinib Reverses Nivolumab Resistance in Advanced Primary Pulmonary Lymphoepithelioma-Like Carcinoma With FGFR3 Gene Amplification.

BACKGROUND: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer (NSCLC). Currently, anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) has become an important treatment for NSCLC. Anti-human PD-1 monoclonal antibodies, such as nivolumab, significantly prolong the survival time of patients with advanced lung adenocarcinoma and lung squamous cell carcinoma. However, there are few reports on the therapeutic effect, drug resistance mechanism, and strategies to overcome resistance to anti-PD-1/PD-L1 treatment in advanced pulmonary LELC. We report the case of a patient with advanced pulmonary LELC harboring fibroblast growth factor receptor (FGFR)3 gene amplification that showed resistance to nivolumab. After treatment with anlotinib, a multi-targeted small-molecule tyrosine kinase inhibitor, the patient's resistance to nivolumab was reversed. She achieved long-term disease remission with a combination of anlotinib and nivolumab treatment. CASE PRESENTATION: A 68-year-old woman was diagnosed with stage IVA pulmonary LELC. After multiple-line chemotherapy, her disease progressed. Since the PD-L1 expression rate of the patient was 90%, nivolumab was administered. However, the therapeutic effect of nivolumab was not ideal; the disease continued to progress, and a new cervical lymph node metastasis appeared. FGFR3 gene amplification was detected in lymph node metastasis. Based on this gene abnormality, we added anlotinib to the treatment. After two cycles of anlotinib and nivolumab, the metastatic focus of the patient was significantly reduced. The patient continued to receive this combined treatment and achieved remission for more than 15 months. CONCLUSION: Pulmonary LELC with FGFR3 gene amplification may not respond well to nivolumab monotherapy. The combination of anlotinib and nivolumab can reverse the resistance to nivolumab in pulmonary LELC with FGFR3 gene amplification.

Preparation and evaluation of an injectable curcumin loaded chitosan/hydroxyapatite cement.

Curcumin (Cur) is an active ingredient of Curcuma longa. Cur has many pharmacological effects, such as anti-inflammation, anti-oxidation, anticoagulation, hypolipidemic, anti-angiogenesis and anti-cancer. An injectable curcumin loaded chitosan/hydroxyapatite bone cement (Cur-CS/HA) was prepared as a bone scaffold and drug delivery. Tween 20, a nonionic surfactant, was incorporated into the cement to improve the solubility of curcumin. Four types of Cur-CS/HA (Group0, Group1, Group5 and Group10) were prepared with different Tween 20 ratios (0, 1, 5 and 10%, respectively). The samples were characterized by infrared spectroscopy (IR), X-ray diffraction (XRD) and scanning electron microscope (SEM). Compression tests were carried out to evaluate the strength of the scaffolds. In addition, the inhibition assay was carried out on MG63 cells with the extracts of drug loaded materials. The results showed that Cur had an effect on the setting time (p < 0.05). Cur reduced the compressive strength of the CS/HA cement (p < 0.05). The release studies showed that Tween 20 could effectively improve the solubility of curcumin. When the Tween 20 content in cement increased from 0 to 10%, the cumulative release (30 d) of Cur increased from 5.5 to 10.6%. Moreover, the cement had good injectability, good anti-collapsibility and good biocompatibility to meet the clinical requirements. The result of inhibition assay showed that Cur-CS/HA could inhibit the proliferation of MG63 cells. Tween 20 incorporated Cur-CS/HA had great potential to use as a drug-loaded artificial bone material.

Insight into the proteomic profiling of exosomes secreted by human OM-MSCs reveals a new potential therapy.

Mesenchymal stromal cells (MSCs) have been used for the treatment of neuronal injury and neurodegenerative diseases. Their underlying mechanism may involve increased secretion of paracrine factors, which promotes tissue repair. Presently, exosomes have been regarded as important components of paracrine secretion and paracrine factors. MSC exosomes represent a promising opportunity to develop novel cell-free therapy approaches. In this study, exosomes from nasal olfactory mucosa MSCs (OM-MSCs) were extracted and purified using ultracentrifugation, resulting in exosome diameters of 40-130 nm. Similar to other exosomes, OM-MSC exosomes were CD63- and CD81-positive and calnexin-negative. Functionally, OM-MSC exosomes promoted human brain microvascular endothelial cell (HBMEC) proliferation and migration. The present study analyzed the OM-MSC exosome paracrine proteome. A total of 304 exosome-associated proteins were identified by LC-MS/MS, including plasminogen activator inhibitor 1 (SERPINE 1), insulin-like growth factor binding protein family members (IGFBP 4 and 5), epidermal growth factor receptor (EGFR), neurogenic locus notch homolog protein 2 (NOTCH 2), apolipoprotein E (APOE), and heat shock protein HSP90-beta (HSP90AB1). These molecules are known to be important in neurotrophic, angiogenesis, cell growth, differentiation, apoptosis, and inflammation and are highly correlated with the mechanism of tissue repair and neural restoration. These observations may provide a basis for further evaluation of OM-MSC exosome potential as a novel therapeutic modality.

Insights on CXC chemokine receptor 2 in breast cancer: An emerging target for oncotherapy.

Breast cancer is the most common malignant neoplasm in women worldwide, and the treatment regimens currently available are far from optimal. Targeted therapy, based on molecular typing of breast cancer, is the most precise form of treatment, and CXC chemokine receptor 2 (CXCR2) is one of the molecular markers used in targeted therapies. As a member of the seven transmembrane G-protein-coupled receptor family, CXCR2 and its associated ligands have been increasingly implicated in tumor-associated processes. These processes include proliferation, angiogenesis, invasion, metastasis, chemoresistance, and stemness and phenotypic maintenance of cancer stem cells. Thus, the inhibition of CXCR2 or its downstream signaling pathways could significantly attenuate tumor progression. Therefore, studies on the biological functions of CXCR2 and its association with neoplasia may help improve the prognosis of breast cancer. Furthermore, the targeting of CXCR2 could supplement the present clinical approaches of breast cancer treatment strategies. The present review discusses the structures and mechanisms of CXCR2 and its ligands. Additionally, the contribution of CXCR2 to the development of breast cancer and its potential therapeutic benefits are also discussed.

Solitary renal metastasis from squamous cell carcinoma of the lung: A case report.

RATIONALE: Non-small cell cancer with isolated unilateral renal metastasis is rare, and the role of radical nephrectomy has not been determined. In the present study, a case of a patient with solitary kidney metastasis from squamous cell lung cancer who underwent radical nephrectomy is reported. PATIENT CONCERNS: A 74-year-old patient diagnosed with pulmonary squamous cell lung cancer who had undergone radical pulmonary lobectomy and mediastinal lymph node dissection revealed a solitary mass in the right kidney during the follow-up. DIAGNOSES: Unilateral isolated kidney metastasis originated from squamous cell lung cancer. INTERVENTIONS: The patient underwent radical right nephrectomy and squamous cell cancer metastasis was confirmed by the postoperative pathology results. OUTCOME: Lung cancer relapse was diagnosed and the patient died of cancer progression 10 months after the right nephrectomy. LESSONS: Solitary renal metastasis is rare and squamous cell lung cancer might be the primary disease. Abdominal computed tomography (CT) is important in detecting solitary kidney metastasis during the follow up of patients with squamous cell lung cancer. Due to the rareness of isolated renal metastasis, the role of radical nephrectomy needs to be further investigated.

Methods and results of surgical treatment for aortic root pathology due to Stanford A aortic dissection / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effectiveness of surgical approaches, outcomes and prognosis of aortic root pathology due to Stanford A aortic dissection.</p><p><b>METHODS</b>Retrospective analysis the clinical data of 161 patients (122 male and 39 female, mean age of (44 ± 21) years) underwent surgical treatment for Stanford A aortic dissection between January 2001 and June 2011. There were 146 patients of acute aortic dissection and 15 patients of chronic aortic dissection. All the patients had aortic root pathologies that included commissural prolapsed in 140 cases, more than moderate aortic insufficiency in 75 cases, aortic sinus intima rupture in 15 cases, right and/or left coronary artery tearing in 8 cases, right and/or left coronary artery dissection in 16 cases, aortic root aneurysm in 31 cases.</p><p><b>RESULTS</b>Aortic root replacement (Bentall procedures) were used in 72 cases, aortic root remodeling (including aortic valve replacement) in 80 cases, aortic root reimplantation (David procedure) in 9 cases. The cardiopulmonary bypass time was shorter in aortic root remodeling group ((193 ± 42) minutes) than the other two groups ((210 ± 61) minutes, (197 ± 34) minutes, F = 3.22, P = 0.04). The in-hospital mortality was 8.1% (13 cases), 5 cases (6.9%) in aortic root replacement group, 7 cases (8.8%) in aortic root remodeling group, 1 case in aortic root reimplantation. The cause of death included respiratory failure (4 cases), permanent neurological deficits (3 cases), multiple organ failure (4 cases), acute renal failure (2 cases). The survivors were followed up for 6 months to 6 years. There was no patient required reoperation for aortic root pathologies. There was no statistically significant difference between aortic root remodeling group and reimplantation group (P > 0.05).</p><p><b>CONCLUSIONS</b>The surgical treatment for aortic root pathology due to Stanford A aortic dissection is challenging. Appropriate procedures according to the specialty of aortic root pathology can be performed with favorable functional results.</p>

Congenital quadricuspid aortic valve: analysis of 11 surgical cases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Congenital quadricuspid aortic valve is rarely seen during aortic valve replacement (AVR). The diagnosis and treatment of the disease were reported in 11 cases.</p><p><b>METHODS</b>Eleven patients (nine men and two women, mean age 33.4 years) with quadricuspid aortic valve were retrospectively evaluated. Medical records, echocardiograms and surgical treatment were reviewed.</p><p><b>RESULTS</b>In accordance with the Hurwitz and Roberts classification, the patients were classified as type A (n = 2), type B (n = 7), type F (n = 1) and type G (n = 1). Three patients were associated with other heart diseases, including infective endocarditis and mitral prolaps, left superior vena cava, aortic aneurysm. All had aortic regurgitation (AR) except two with aortic stenosis (AS), detected by color-flow Doppler echocardiography. The congenital quadricuspid aortic valve deformity in seven patients was diagnosed by echocardiography. All patients underwent successful aortic valve replacement.</p><p><b>CONCLUSION</b>Quadricuspid aortic valve is a rare cause of aortic insufficiency, while echocardiography plays an important role in diagnosing the disease. Aortic valve replacement is the major therapy for the disease.</p>

Reoperative valve replacement in patients undergoing cardiac reoperation: a report of 104 cases / 中华外科杂志

<p><b>OBJECTIVE</b>To review the experience of reoperative valve replacement for 104 patients.</p><p><b>METHODS</b>From January 2002 to December 2009, 104 patients underwent heart valve replacement in reoperations, accounting for 2.92% of the total patient population (3557 cases) who had valve replacement during this period. In this group, 53 male and 51 female patients were included with a median age of 46 years (ranged from 13 to 72 years). The reasons of reoperation included 28 cases suffered from another valve lesion after valve replacement, 10 cases suffered from valve lesion after mitral valvuloplasty, 19 cases suffered from perivalvular leakage after valve replacement, 18 cases suffered from valve lesion after previous correction of congenital heart defect, 7 cases suffered from bioprosthetic valve decline, 10 cases suffered from prosthetic valve endocarditis, 9 cases suffered from dysfunction of machine valve, and 3 cases suffered from other causes. The re-operations were mitral and aortic valve replacement in 2 cases, mitral valve replacement in 59 cases, aortic valve replacement in 24 cases, tricuspid valve replacement in 16 cases, and Bentall's operation in 3 cases. The interval from first operation to next operation was 1 month-19 years.</p><p><b>RESULTS</b>There were 8 early deaths from heart failure, renal failure and multiple organ failure (early mortality 7.69%). Major complications were intraoperative hemorrhage in 2 cases, re-exploration for mediastinal bleeding in 2 cases and sternotomy surgical site infection in 1 case. Complete follow-up (3 months-7 years and 2 months) was available for all patients. Two patients died, one patient died of intracranial hemorrhage, and another cause was unknown.</p><p><b>CONCLUSION</b>Satisfactory short-term and long-term results can be obtained in reoperative valve replacement with appropriate timing of operation control, satisfactory myocardial protection, accurate surgical procedure and suitable perioperative treatment.</p>