The Significance of the Redox Gene in the Prognosis and Therapeutic Response of Glioma.

OBJECTIVE: Glioblastoma (GBM) is a fatal adult central nervous system tumor. Due to its high heterogeneity, the survival rate and prognosis of patients are poor. Thousands of people die of this disease every year all over the world. At present, the treatment of GBM is mainly through surgical resection and the combination of later drugs, radiotherapy, and chemotherapy. An abnormal redox system is involved in the malignant progression and treatment tolerance of glioma, which is the main reason for poor survival and prognosis. The construction of a GBM redox-related prognostic model may be helpful in improving the redox immunotherapy and prognosis of GBM. METHODS: Based on glioma transcriptome data and clinical data from The Cancer Genome Atlas, databases, a risk model of redox genes was constructed by univariate and multivariate Cox analysis. The good prediction performance of the model was verified by the internal validation set of The Cancer Genome Atlas, and the external data of Chinese Glioma Genome Atlas. RESULTS: The results confirmed that the higher the risk score, the worse the survival of patients. Age and isocitrate dehydrogenase status were significantly correlated with risk scores. The analysis of immune infiltration and immunotherapy found that there were significant differences in the immune score, matrix score, and ESTIMATE score between high and low-risk groups. reverse transcription polymerase chain reaction and immunohistochemical staining of glioma samples confirmed the expression of the hub gene. CONCLUSION: Our study suggests that the 5 oxidative-related genes nitricoxidesynthase3, NCF2, VASN, FKBP1B, and TXNDC2 are hub genes, which may provide a reliable prognostic tool for glioma clinical treatment.

The impact of time to evacuation on outcomes in endoscopic surgery for supratentorial spontaneous intracerebral hemorrhage: a single-center retrospective study.

Supratentorial spontaneous intracerebral hemorrhage (SICH) can be treated with endoscopic surgery, but the optimal timing remains uncertain. We retrospectively analyzed data from 46 patients who underwent endoscopic surgery for supratentorial SICH. We examined the relationship between time to evacuation and functional outcome at 3 months, adjusting for prognostic factors. Surgical outcomes and complications were compared between patients with early (≤ 12 h) or late (> 12 h) evacuation. Median time to evacuation was 12 h, and the rate of unfavorable outcome (modified Rankin Scale > 3 at 3 months) was 32.6%. Longer time to evacuation was independently associated with unfavorable outcome (odds ratio per hour delay: 1.26). Late evacuation carried a 7.25-fold higher risk of unfavorable outcome compared to early evacuation. This association held across subgroups based on hematoma volume, location, and intraventricular extension (P for interaction > 0.05). Patients with late evacuation had fewer spot signs (24% vs. 4.8%, P = 0.035) and markers of hemorrhagic expansion (36% vs. 9.5%, P = 0.018), longer neurosurgical intensive care unit (NSICU) stay (3.2 vs. 1.9 days, P = 0.011) and hospital stay (15.7 vs. 11.9 days, P = 0.014), and higher 30-day mortality (28.6 vs. 4%, P = 0.036) and complication rates (57.1% vs. 28.0%, P = 0.023). This study suggests a potential association between early endoscopic evacuation of supratentorial SICH and improved functional outcomes, lower 30-day mortality and reduced complications. The need for timely intervention in managing supratentorial SICH is highlighted, yet further validation through multi-center prospective studies is essential to substantiate these findings and provide a higher level of evidence.

Endoport Assisted Endoscopic Surgery for Hypertensive Basal Ganglia Hemorrhage by Transsylvian Approach: Technical Nuances and Preliminary Clinical Results.

BACKGROUND: There is no clear evidence on the indication and surgical approaches on evacuating basal ganglia hemorrhage caused by hypertensive bleeding. Some studies have shown that minimally invasive approaches have therapeutic potentials, but its benefits remain inconclusive. We describe an endoport assisted endoscopic transsylvian approach for basal ganglia hemorrhage evacuation. We evaluate the safety and efficacy of this approach in a cohort study. METHODS: We included 19 patients (mean age 57 years) who underwent the surgery at a single county-level hospital in Yunan Province, China. The majority had a Glasgow coma scale between 9 and 12 on admission. The midline shift ranged from 16-29 mm (mean 19 mm). Hematoma volume ranged from 46 to 106 ml (mean 67 ml). Six patients (31.6%) presented with intraventricular hemorrhage. RESULTS: All patients achieved greater than 90% decrease in hematoma volume at postoperative computed tomography scan. The average operative time was 115 minutes and average blood loss of 44 ml. The most common postoperative complication was pulmonary infection (63.2%). No rebleeding, seizure, infectious meningitis, or postoperative mortality was observed. A total of 17 patients (89.5%) achieved good functional recovery at follow up within 90 days after surgery (Glasgow outcome scale 4-5) and 2 patients had severe disability (Glasgow outcome scale 3). CONCLUSIONS: Endoport assisted endoscopic surgery through transsylvian approach is safe and effective treatment for hypertensive basal ganglia hemorrhage. The majority of patients have good functional recovery and the rate of severe complications is low.

Chimeric Antigen Receptor (CAR)-T Cell Immunotherapy Against Thoracic Malignancies: Challenges and Opportunities.

Different from surgery, chemical therapy, radio-therapy and target therapy, Chimeric antigen receptor-modified T (CAR-T) cells, a novel adoptive immunotherapy strategy, have been used successfully against both hematological tumors and solid tumors. Although several problems have reduced engineered CAR-T cell therapeutic outcomes in clinical trials for the treatment of thoracic malignancies, including the lack of specific antigens, an immunosuppressive tumor microenvironment, a low level of CAR-T cell infiltration into tumor tissues, off-target toxicity, and other safety issues, CAR-T cell treatment is still full of bright future. In this review, we outline the basic structure and characteristics of CAR-T cells among different period, summarize the common tumor-associated antigens in clinical trials of CAR-T cell therapy for thoracic malignancies, and point out the current challenges and new strategies, aiming to provide new ideas and approaches for preclinical experiments and clinical trials of CAR-T cell therapy for thoracic malignancies.

5­Aza­dC suppresses melanoma progression by inhibiting GAS5 hypermethylation.

The in­depth study of melanoma pathogenesis has revealed that epigenetic modifications, particularly DNA methylation, is a universal inherent feature of the development and progression of melanoma. In the present study, the analysis of the tumor suppressor gene growth arrest­specific transcript 5 (GAS5) demonstrated that its expression was downregulated in melanoma, and its expression level had a certain negative association with its methylation modification level. The promoter of GAS5 presented with detectable CpG islands, and methylation­specific polymerase chain reaction analysis demonstrated that GAS5 was actually modified by methylation in melanoma tissues and cells; however, no methylation modification of GAS5 was detected in normal tissues. Following the treatment of melanoma cells with 5­Aza­2'­deoxycytidine (5­Aza­dC), GAS5 methylation was significantly reversed. The analysis of melanoma cell proliferation revealed that 5­Aza­dC inhibited A375 and SK­MEL­110 cell proliferation in a time­dependent manner. Further analysis of apoptosis demonstrated that 5­Aza­dC significantly increased the apoptosis level of the two cell lines. Moreover, migration analysis of melanoma cells revealed that 5­Aza­dC significantly reduced cell migration. Furthermore, 5­Aza­dC significantly decreased the invasive ability of the two cell lines. However, when the expression of GAS5 was silenced, the effects of 5­Aza­dC on cell proliferation, apoptosis, invasion and migration were not significant. Furthermore, the subcutaneous injection of A375 cells in nude mice successfully resulted in xenograft tumor formation. However, following an intraperitoneal injection of 5­Aza­dC, the volume and weight of xenograft tumors and Ki­67 expression were significantly reduced, and caspase­3 activity and GAS5 expression were enhanced; following the silencing of GAS5, the antitumor effect of 5­Aza­dC was significantly blocked. On the whole, the present study demonstrates that 5­Aza­dC inhibits the growth of melanoma, and its function may be related to the methylation modification of GAS5.

LncRNA TUG1 contributes to the tumorigenesis of lung adenocarcinoma by regulating miR-138-5p-HIF1A axis.

INTRODUCTION: Increasing evidence indicates that lncRNA TUG1 represents an oncogenic factor in cancer. But, the mechanisms by which lncRNA TUG1 contributes to lung adenocarcinoma (LAC) remain undocumented. METHODS: The relationship between lncRNA TUG1/miR-138-5p expression and clinical outcomes in patients with LAC was indicated by qPCR, FISH, and TCGA cohort. Gain- or loss-of-function experiments and in vivo tumorigenesis were used to assess the role of lncRNA TUG1 in LAC. The interplay between TUG1 and miR-138-5p was validated by luciferase gene report and RIP assays. qPCR and Western blot analyses were used to investigate the effects of TUG1 on miR-138-5p/HIF1A axis in LAC cells. RESULTS: We found that upregulation of TUG1 or downregulation of miR-138-5p was associated with lymph node or distant metastasis and indicated a poor survival in LAC. Reduced expression of TUG1 restrained the growth of LAC cells, while restored expression of TUG1 had the opposite effects. TUG1 was identified to negatively regulate miR-138-5p expression, and miR-138-5p reversed TUG1-induced cell proliferation by targeting HIF1A. Elevated expression of HIF1A predicted a poor survival in LAC. CONCLUSION: Our findings demonstrate that lncRNA TUG1 promotes the growth of LAC by regulating miR-138-5p-HIF1A axis.

WITHDRAWN: Resveratrol partially prevents learning and memory deficits in rats exposed to gaseous formaldehyde.

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MUC16 in non-small cell lung cancer patients affected by familial lung cancer and indoor air pollution: clinical characteristics and cell behaviors.

BACKGROUND: Inherited susceptibility and environmental carcinogens are crucial players in lung cancer etiology, and both exhibit population heterogeneity. MUC16 is overexpressed in various cancers and often associated with poor prognosis. Present work was to investigate the clinical significance of MUC16 in non-small cell lung cancer patients affected by familial lung cancer (FLC) and indoor air pollution caused by coal use. METHODS: Clinicopathologic characteristics and MUC16 expression were analyzed and evaluated in our subject population. Vectors were constructed for MUC16 gene knockout and overexpression, then we examined how MUC16 affected lung cancer cell behaviors, including proliferation, migration, invasion and chemoresistance. RESULTS: FLC showed significant association with early-onset (P<0.01) and later stage (P<0.01). Indoor air pollution was associated with younger age (P<0.01), later stage (P<0.05) and AD histology type (P<0.05). Interestingly, two age peaks were observed in our FLC and sporadic group respectively, possibly suggesting multiple major contributors to lung cancer in our subject population. MUC16 overexpression was significantly associated with FLC (P<0.05), indoor air pollution (P<0.01) and later stage (P<0.01), additionally more metastasis cases were observed in patients with up-regulated MUC16 (18.1% vs. 10.3%). Taken together, elevated MUC16 may potentially be one molecular character of FLC in local residents. Intriguingly, patients with more MUC16 up-regulation seemed to have a lower number of white blood cells, especially neutrophils, this reflected MUC16's role in immune regulation. In cell behavior experiments, high MUC16 level could contribute to lung cancer cell proliferation, migration, invasion and chemoresistance, but there were variations among cell lines. CONCLUSIONS: MUC16 plays crucial roles in lung cancer pathogenesis, progression and chemoresistance. Interestingly, its association with FLC and indoor air pollution highlights the complexity of lung cancer etiology. Our findings provide useful information to study the intricate interaction between environmental carcinogens and population genetic background.

Lung cancer family history and exposure to occupational/domestic coal combustion contribute to variations in clinicopathologic features and gene fusion patterns in non-small cell lung cancer.

BACKGROUND: Both genetic and environmental factors contribute to the development of cancer and its mutant spectrum. Lung cancer has familial aggregation. Lung cancer caused by non-tobacco factors has unique pathological and molecular characteristics. The interaction between genetic lung cancer susceptibility and carcinogens from coal burning remains complex and understudied. METHODS: We selected 410 non-small cell lung cancer (NSCLC) patients with a family history of lung cancer (FLC) and exposure to coal combustion between 2014 and 2017. Clinicopathologic parameters were analyzed. Reverse transcription-PCR was performed to detect ALK, ROS1, RET, and NTRK1 rearrangement. RESULTS: Among the 410 NSCLC patients, 192 had FLC and 204 (49.8%) were exposed to occupational or domestic coal combustion. FLC patients had the same characteristics regardless of gender and coal exposure: younger age, high female ratio, adenocarcinoma, increased metastasis, later stage at diagnosis, and higher frequency of gene fusion. Sixty-seven patients (16.3%) had gene rearrangement: 51 (12.4%) harbored EML4-ALK fusions and 16 ROS1 fusions (3.9%). The highest gene fusion rate (35.1%, 33/94) occurred in patients with both FLC and high tobacco and coal exposure. ALK fusions and total gene rearrangement were closely associated with women, never smokers, younger age, FLC, and coal exposure. CONCLUSION: FLC and exposure to coal combustion have an important impact on the clinicopathological characteristics and gene fusion mode of NSCLC, particularly in cases of higher levels of carcinogens, and genetic susceptibility has a greater impact. Our findings may help evaluate the effect of FLC and coal exposure on the pathogenesis of lung cancer.

Characteristics of Familial Lung Cancer in Yunnan-Guizhou Plateau of China.

Background: Lung cancer has inherited susceptibility and show familial aggregation, the characteristics of familial lung cancer exhibit population heterogeneity. Despite previous studies, familial lung cancer in China's Yunnan-Guizhou plateau remains understudied. Methods: Between 2015 and 2017, 1,023 lung cancer patients (residents of Yunnan-Guizhou plateau) were enrolled with no limitation on other parameters, 152 subjects had familial lung cancer. Clinicopathologic parameters were analyzed and compared, 4,754 lung cancer patients from NCI-GDC were used to represent a general population. Results: Familial lung cancer (FLC) subjects showed unique characters: early-onset; increased rate of female, adenocarcinoma, stage IV and other cancer history; unbalance in anatomic sites; all ruling out significant difference in smoking status. Unbalanced distribution of co-existing diseases or symptoms was also discovered. FLC patients were more likely to develop benign lesions (polyps, nodules, cysts) early in life, especially early-growth of multiple pulmonary nodules at higher frequency. Typical diseases with family history like diabetes and hypertension were also increased in FLC population. Compared to GDC data, our subject population was younger: the age peak of our FLC group was in 50-59; our sporadic group had an age peak around 60; while GDC patients' age peak was in 60-69. Importantly, the biggest difference happened in age 40-49: our FLC group and sporadic group had 3 times and 2 times higher ratio than GDC population, respectively. Moreover, the age peaks of our FLC males and FLC females were both in 50-59; while our sporadic females had the age peak in 50-59, much earlier than sporadic males (around 60-69); reflecting gender-specific or age-specific characters in our subject population. Conclusions: Familial lung cancer in China's Yunnan-Guizhou plateau showed unique clinicopathologic characters, differences were found in gender, age, histologic type, TNM stage and co-existing diseases or symptoms. Identification of hereditary factors which lead to increased lung cancer risk will be a challenge of both scientific and clinical significance.