Prevalence, characteristics, evaluation, and management of carotid body tumors: Systematic analysis based on available evidence.

BACKGROUND: Although carotid body tumors (CBTs) are rare, they attract particular attention because of their propensity for malignant transformation and the high surgical risk. Because data are scarce and as it is difficult to achieve a large sample size, no study has yet comprehensively analyzed the characteristics, management, or operative complications of CBTs. Therefore, we collected and analyzed all currently available information on CBTs and used the pooled data to derive quantitative information on disease characteristics and management. METHODS: We systematically searched PubMed, Embase, the Cochrane Library, and the Web of Science up to 1 December 2022 for studies that investigated the characteristics and management of CBTs. The primary objective was to identify the prevalence of the various characteristics and the incidence of complications. The secondary objective was to compare patients who underwent preoperative embolization (PE) and those who did not (non-PE), as well as to compare patients with different Shamblin grades and those with and without succinate dehydrogenase (SDH) mutations in terms of CBT characteristics and complications. Two reviewers selected studies for inclusion and independently extracted data. All statistical analyses were performed using the standard statistical procedures of Review Manager 5.2 and Stata 12.0. RESULTS: A total of 155 studies with 9,291 patients and 9,862 tumors were identified. The pooled results indicated that the median age of CBT patients was 45.72 years and 65% were female. The proportion of patients with bilateral lesions was 13%. In addition, 16% of patients had relevant family histories, and the proportion of those with SDH gene mutations was 36%. 16% patients experienced multiple paragangliomas and 12% CBTs had catecholamine function. The incidence of cranial nerve injury (CNI) was 27%, and 14% of patients suffered from permanent CNI. The incidence rates of operative mortality and stroke were both 1%, and 4% of patients developed transient ischemic attacks. Of all CBTs, 6% were malignant or associated with metastases or recurrences. The most common metastatic locations were the lymph nodes (3%) and bone (3%), followed by the lungs (2%). Compared to non-PE, PE reduced the estimated blood loss (EBL) (standardized mean difference [SMD] -0.95; 95% confidence interval [CI] -1.70, -0.20) and the operation time (SMD -0.56; 95% CI -1.03, -0.09), but it increased the incidence of stroke (odds ratio 2.44; 95% CI 1.04‒ 5.73). Higher Shamblin grade tumors were associated with more operative complications. SDH gene mutation-positive patients were more likely to have a relevant family history and had more symptoms. CONCLUSIONS: CBT was most common in middle-aged females, and early surgical resection was feasible; there was a low incidence of serious operative complications. Routine PE is not recommended because this may increase the incidence of stroke, although PE somewhat reduced the EBL and operation time. Higher Shamblin grade tumors increased the incidence of operative complications. SDH gene mutation-positive patients had the most relevant family histories and symptoms.

Over-expression of gastrin inhibits apoptosis of gastric cancer cells via reactive oxygen species and annexin A2-mediated mitochondrial dysfunction / La sobreexpresión de gastrina inhibe la apoptosis de las células de cáncer gástrico a través de especies reactivas de oxígeno y disfunción mitocondrial mediada por anexina A2

SUMMARY: Gastrin plays a vital role in the development and progression of gastric cancer (GC). Its expression is up-regulated in GC tissues and several GC cell lines. Yet, the underlying mechanism remains to be investigated. Here, we aim to investigate the role and mechanism of gastrin in GC proliferation. Gastrin-overexpressing GC cell model was constructed using SGC7901 cells. Then the differentially expressed proteins were identified by iTRAQ analysis. Next, we use flow cytometry and immunofluorescence to study the effect of gastrin on the mitochondrial potential and mitochondria-derived ROS production. Finally, we studied the underlying mechanism of gastrin regulating mitochondrial function using Co-IP, mass spectrometry and immunofluorescence. Overexpression of gastrin promoted GC cell proliferation in vitro and in vivo. A total of 173 proteins were expressed differently between the controls and gastrin- overexpression cells and most of these proteins were involved in tumorigenesis and cell proliferation. Among them, Cox17, Cox5B and ATP5J that were all localized to the mitochondrial respiratory chain were down-regulated in gastrin-overexpression cells. Furthermore, gastrin overexpression led to mitochondrial potential decrease and mitochondria-derived ROS increase. Additionally, gastrin-induced ROS generation resulted in the inhibition of cell apoptosis via activating NF-kB, inhibiting Bax expression and promoting Bcl-2 expression. Finally, we found gastrin interacted with mitochondrial membrane protein Annexin A2 using Co-IP and mass spectrometry. Overexpr ession of gastrin inhibits GC cell apoptosis by inducing mitochondrial dysfunction through interacting with mitochondrial protein Annexin A2, then up-regulating ROS production to activate NF-kB and further leading to Bax/Bcl-2 ratio decrease.

La gastrina juega un papel vital en el desarrollo y progresión del cáncer gástrico (CG). Su expresión está regulada al alza en tejidos de CG y en varias líneas celulares de CG. Sin embargo, el mecanismo subyacente aun no se ha investigado. El objetivo de este estudio fue investigar el papel y el mecanismo de la gastrina en la proliferación de CG. El modelo de células CG que sobre expresan gastrina se construyó usando células SGC7901. Luego, las proteínas expresadas diferencialmente se identificaron mediante análisis iTRAQ. A continuación, utilizamos la citometría de flujo y la inmunofluorescencia para estudiar el efecto de la gastrina en el potencial mitocondrial y la producción de ROS derivada de las mitocondrias. Finalmente, estudiamos el mecanismo subyacente de la gastrina que regula la función mitocondrial utilizando Co-IP, espectrometría de masas e inmunofluorescencia. La sobreexpresión de gastrina promovió la proliferación de células CG in vitro e in vivo. Un total de 173 proteínas se expresaron de manera diferente entre los controles y las células con sobreexpresión de gastrina y la mayoría de estas proteínas estaban implicadas en la tumorigenesis y la proliferación celular. Entre estas, Cox17, Cox5B y ATP5J, todas localizadas en la cadena respiratoria mitocondrial, estaban reguladas a la baja en las células con sobreexpresión de gastrina. Además, la sobreexpresión de gastrina provocó una disminución del potencial mitocondrial y un aumento de las ROS derivadas de las mitocondrias. Por otra parte, la generación de ROS inducida por gastrina resultó en la inhibición de la apoptosis celular mediante la activación de NF-kB, inhibiendo la expresión de Bax y promoviendo la expresión de Bcl-2. Finalmente, encontramos que la gastrina interactuaba con la proteína de membrana mitocondrial Anexina A2 usando Co-IP y espectrometría de masas. La sobreexpresión de gastrina inhibe la apoptosis de las células CG al inducir la disfunción mitocondrial a través de la interacción con la proteína mitocondrial Anexina A2, luego regula el aumento de la producción de ROS para activar NF-kB y conduce aún más a la disminución de la relación Bax/Bcl-2.

Novel albendazole-glucan particles for enhancing intestinal absorption and improving hepatic targeting.

Background: Glucan particles (GPs) are derived from the Saccharomyces cerevisiae cell wall. The hollow particles composed of ß-1,3-D-glucan have been extensively studied in terms of immune regulation and macrophage-targeted drug delivery. Albendazole (ABZ) is a benzimidazole drug with good anti-parasitic activity and is the drug recommended by the World Health Organization for the first-line treatment of hydatid disease. Methods: A dynamic light scatterometer, scanning electron microscope, and transmission electron microscope were used to characterize the ABZ-GPs. High-performance liquid chromatography (HPLC), laser scanning confocal microscope (LSCM) and an in vivo small animal imaging system were used to evaluate theability of ABZ-GPs to be recognized by macrophages, whether ABZ-GPs are more readily absorbed and eliminated in the blood than the original ABZ drug in rats, and the ability of ABZ-GPs to target the mouse liver. Results: The ABZ-GPs were successfully constructed to achieve fluorescence, magnetic resonance imagining, and laser confocal microscopy imaging. The glucan shell effectively protects ABZ from enzymatic degradation and from being pumped out in the gastrointestinal tract. The analysis of ABZ and its major metabolite albendazole sulfoxide in the rat plasma and mouse liver showed that compared to the ABZ suspension group, the degradation of ABZ-GPSs in the blood was low, and the targeting of ABZ-GPSs in the liver was significantly enhanced. Conclusions: In the oral treatment of hepatic hydatid disease, GPs can be used as carriers to achieve the targeted transport of ABZ, which in turn can be used for the targeted therapy of liver echinococcosis. Thus, ABZ-GPs may be a promising form of targeted therapy.

The characteristics of carotid body tumors in high-altitude region: Analysis from a single center.

OBJECTIVES: Though carotid body tumors are rare, increasing attentions have been given because of malignant transformation and high surgical risk. However, at present, the characteristics and etiology still remain unclear. Our study was designed to describe the clinical features of carotid body tumors in our institution and to compare the results with previous reports. METHODS: We retrospectively reviewed carotid body tumor patients diagnosed in our institution from January 2015 to May 2020. The demographics, comorbidities, lesion location, anatomic characteristics, complications, and postoperative outcomes were evaluated. Carotid body tumor measurements were determined from computed tomography, magnetic resonance imaging, and carotid arteriography examination. We described and compared the clinical features of carotid body tumors in our institution and other reports. RESULTS: We totally identified 122 carotid body tumor cases for the present analysis. The mean age was 50.26 years, with the majority being female (82%). The commonest presentation was a painless neck mass (68%). For the distribution of nationality, most patients were the Han nationality (69.7%). The mean altitude of habitat of patients was 2689.4 km; 19.7% patients suffered bilateral lesions. The main blood supply of carotid body tumors was from external carotid artery (54.1%). For patients who received operation, 11 (11.2%) patients experienced cranial nerve injury. The maximal diameter of tumors was 3.99 ± 1.98 cm in male and 3.38 ± 1.36 cm in female. The volume of tumors was 31.49 ± 29.76 cm3 in male and 15.27 ± 13.06 cm3 in female. The distance to base of skull of tumors was 3.39 ± 1.07 cm (3.99 ± 1.98 cm in male vs 3.38 ± 1.36 cm, P < 0.05). Two patients (2.04%) were identified as having malignant carotid body tumor. CONCLUSIONS: Though carotid body tumor had a low morbidity and multitudinous clinicopathologic features, it was apt to middle-aged women and the main blood supply was from external carotid artery. The painless neck mass was the commonest presentation of carotid body tumors. There were significant difference between male and female patients regarding platelet, hemoglobin, distance to base of skull, tumor volume, altitude of habitat, carotid body tumor location, and hypertension.

The noninferiority of transcatheter aortic valve implantation compared to surgical aortic valve replacement for severe aortic disease: Evidence based on 16 randomized controlled trials.

BACKGROUND: Currently, transcatheter aortic valve implantation (TAVI) as an effective and convenient intervention has been adopted extensively for patients with severe aortic disease. However, the efficacy and safety of TAVI have not yet been well evaluated and its noninferiority compared with traditional surgical aortic valve replacement (sAVR) still lack sufficient evidence. This meta-analysis was designed to comprehensively compare the noninferiority of TAVI with sAVR for patients with severe aortic disease. METHODS: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science up to October 1, 2020 was conducted for relevant studies that comparing TAVI and sAVR in the treatment of severe aortic disease. The primary outcomes were early, midterm and long term mortality. The secondary outcomes included early complications and other late outcomes. Two reviewers assessed trial quality and extracted the data independently. All statistical analyzes were performed using the standard statistical procedures provided in Review Manager 5.2. RESULTS: A total of 16 studies including 14394 patients were identified. There was no difference in 30-day, 1-year, 2-year, and 5-year all-cause or cardiovascular mortality as well as stroke between TAVI and sAVR. Regarding to the 30-day outcomes, compared with sAVR, TAVI experienced a significantly lower incidence of myocardial infarction (risk ratio [RR] 0.62; 95% confidence interval [CI] 0.40-0.97; 5441 pts), cardiogenic shock (RR 0.34; 95% CI 0.19-0.59; 1936 pts), acute kidney injury (AKI) > stage 2 (RR 0.37; 95% CI 0.25-0.54; 5371 pts), and new-onset atrial fibrillation (NOAF) (RR 0.29; 95% CI 0.24-0.35; 5371 pts) respectively, but higher incidence of permanent pacemaker implantation (RR 3.16; 95% CI 1.61-6.21; 5441 pts) and major vascular complications (RR 2.22; 95% CI 1.14-4.32; 5371 pts). Regarding to the 1- and 2-year outcomes, compared with sAVR, TAVI experienced a significantly lower incidence of NOAF, but higher incidence of neurological events, transient ischemic attacks (TIA), permanent pacemaker and major vascular complications respectively. Regarding to the 5-year outcomes, compared with sAVR, TAVI experienced a significantly lower incidence of NOAF, but higher incidence of TIA and reintervention respectively. CONCLUSIONS: Our analysis shows that TAVI was equal to sAVR in early, midterm and long term mortality for patients with severe aortic disease. In addition, TAVI may be favorable in reducing the incidence of both early, midterm and long term NOAF. However, pooled results showed superiority of sAVR in reducing permanent pacemaker implantation, neurological events, TIA, major vascular complications and reintervention.

Knockdown of Gastrin Promotes Apoptosis of Gastric Cancer Cells by Decreasing ROS Generation.

Overexpressed gastrin is reported to promote oncogenesis and development of gastric cancer by inhibiting apoptosis of cancer cells; however, the underlying mechanism remains unclear. Our study is aimed at revealing the mechanism underlying the effect of gastrin on apoptosis of gastric cancer cells. Gastrin-interfering cell line was constructed by stably transfecting gastrin-specific pshRNA plasmid to gastric cancer cell line BGC-823. Then, differentially expressed proteins between untreated BGC-823 and gastrin-interfering BGC-823 cell lines were detected by the iTRAQ technique. GO and KEGG analysis was used to analyze the differentially expressed genes that code these differentially expressed proteins. The Annexin V-FITC staining assay was used to detect gastric cancer cell apoptosis. The DCFH-DA fluorescent probe staining assay was used to measure intracellular ROS. Mitochondrial membrane potential was detected by flow cytometry. Western blot was used to analyze the mitochondria respiratory chain proteins and apoptosis-related proteins. A total of 107 differentially expressed proteins were identified by iTRAQ. GO and KEGG analysis showed that proteins coded by the corresponding differentially expressed genes were mainly enriched in the mitochondrial oxidative respiratory chain, and the expression of three proteins (COX17, COX5B, ATP5J) was upregulated. The three proteins with higher scores were verified by Western blot. The apoptosis rate of the gastrin knockdown cancer cell was significantly increased; meanwhile, gastrin knockdown leads to increase of membrane potential and decrease of intracellular ROS production. Additionally, Bax was significantly increased, whereas NF-κB-p65 and Bcl-2 were downregulated after knockdown of gastrin. Concomitantly, pretreatment with NAC reversed the effect of gastrin on the Bax and Bcl-2 expression. Gastrin promotes the production of ROS from mitochondria, activates NF-κB, and inhibits apoptosis via modulating the expression level of Bcl-2 and Bax.

Dysregulation of MiR-30a-3p/Gastrin Enhances Tumor Growth and Invasion throughSTAT3/MMP11 Pathway in Gastric Cancer.

BACKGROUND: Gastrin (GAST) is a well-known hormone regulating gastric biofunctions in the secretion of acid and maintaining its structural integrity. Furthermore, the dysregulation of GAST is also involved in the development of various forms of cancer. However, there are some limitations for illustrating the cellular regulation of GAST and its regulatory mechanisms in gastric malignant transformation and the potential epigenetic regulators systematically. METHODS: We explored the role of GAST expression in gastric cancer (GC) and normal tissues with the clinical features and investigated the potential relationship between GAST and STAT3/MMP11 pathway by gain or loss of function analyses. Besides, based on our microRNA/mRNA expression profiles, miR-30a-3p was the potential epigenetic regulator and additional experiments were performed to identify the hypothesis. RESULTS: Elevated GAST expression was frequently detected in GC and was associated with worse outcomes (p<0.001). And we firstly demonstrated that GAST was negatively regulated by miR-30a-3p. Moreover, GAST induced GC cell proliferation, migration and invasion mediating STAT3/MMP11 pathway in this study. CONCLUSION: MiR-30a-3p was the promising suppressor gene through negatively regulating the expression of GAST, and dysregulation of GAST was a prognostic signature associated cell proliferation and metastasis through STAT3/MMP11 pathway in GC.

[Expressions of gastrin and apoptosis-associated proteins involved in mitochondrial pathway in gastric cancer tissues and the clinical significance].

Objective To investigate the expressions and correlations of gastrin and apoptosis-associated proteins involved in mitochondrial apoptotic pathway in gastric cancer tissues, and explore their clinicopathological characteristics. Methods The tissue chip technology and immunohistochemistry (IHC) were used to detect the expressions of gastrin and apoptosis-associated proteins (Bcl2, caspase-9 and caspase-3) in human gastric cancer tissues and their paracancerous tissues. The correlations of these markers and their clinicopathological characteristics were analyzed using Spearman rank correlation analysis and Chi-square test. Results The expressions of gastrin and Bcl2 in gastric cancer tissues were significantly higher than those in the corresponding paracancerous tissues, whereas the expressions of caspase-9 and caspase-3 in gastric cancer tissues was significantly lower than those in the corresponding tissues. There was a significant positive correlation between the expressions of gastrin and Bcl2 in gastric cancer tissues (r=0.237). The expression of gastrin was associated with tumor position, and the expression of Bcl2 was associated with tumor size, TNM stage and lymph node metastasis. Conclusion Gastrin and Bcl2 are highly expressed in gastric cancer tissues, and they are correlated with the clinicopathologic features.