Influencing factors of futile recanalization after endovascular therapy for cerebral infarction with posterior circulation occlusion of large vessels: a retrospective study.

BACKGROUND: The optimal treatment for cerebral infarction caused by posterior circulation occlusion of large vessels has not yet been determined. Intravascular interventional therapy is an important treatment for cerebral infarction with posterior circulation occlusion of large vessels. However, endovascular therapy (EVT) of some posterior circulation cerebrovascular is ineffective and eventually become futile recanalization. Therefore, we performed a retrospective study to explore the factors influencing futile recanalization after EVT in patients with posterior circulation large-vessel occlusion. METHODS: Eighty-six patients with acute cerebral infarction and posterior circulation large vessel occlusion after intravascular intervention were divided into two groups according to their modified Rankin scale (mRS) scores after 3 months: group 1, mRS scores less than or equal to 3 (the effective recanalization group); group 2, mRS scores greater than 3 (the ineffective recanalization group). The basic clinical data, imaging index scores, time from onset to recanalization, and operation time between the two groups were compared and analyzed. Logistic regression was used to analyze the factors influencing indicators of good prognosis, and the ROC curve and Youden index were used to determine the best cutoff value. RESULTS: Between the two groups, there were significant differences in the posterior circulation CT angiography (pc-CTA) scores, GCS scores, pontine midbrain index scores, time from discovery to recanalization, operation time, NIHSS score and incidence of gastrointestinal bleeding. The logistic regression revealed that the NIHSS score and time from discovery to recanalization were associated with good prognoses. CONCLUSION: NIHSS score and recanalization time were independent influencing factors of ineffective recanalization of cerebral infarctions caused by posterior circulation occlusion. EVT is relatively effective for cerebral infarction caused by posterior circulation occlusion when the NIHSS score is less than or equal to 16 and the time from onset to recanalization is less than or equal to 570 min.

Astrocytoma with myelin oligodendrocyte glycoprotein antibody associated encephalomyelitis: A case report.

BACKGROUND: Demyelination is similar with malignancy in clinical symptoms. Magnetic resonance imaging (MRI) is an important auxiliary examination in the diagnosis of demyelinating diseases and malignancy. Since MRI and symptoms can be difficult to distinguish demyelination from malignancy, other auxiliary examinations, such as demyelinating disease-specific antibodies, play an important role in distinguishing them. Previous studies have reported demyelinating disease-specific antibodies in patients with malignancy. What's more, it is more difficult to confirm the diagnosis when the malignant tumor co-occurs with demyelinating diseases, which has never been reported in previous studies. We report the diagnosis of myelin oligodendrocyte glycoprotein antibody associated encephalomyelitis (MOG-EM) in a patient who had astrocytoma for several years. CASE PRESENTATION: Patient's concerns and diagnoses: our case report records a 49-year-old woman with astrocytoma for more than 4 years, who recently developed the symptoms of MOG-EM, including dizziness, vomiting, and vision loss. This astrocytoma patient was diagnosed with MOG-EM according to comprehensive evidence, including MRI, visual evoked potential (VEP), serum myelin oligodendrocyte glycoprotein antibody (MOG-IgG), and therapeutic effect. Interventions and outcomes: this patient was diagnosed with astrocytoma by surgical biopsy 4 years earlier. This patient has been treated with tumor resection, postoperative radiation treatment and chemotherapy. After treatment, the patient was left with right limb weakness while other symptoms were improved. Recently, the intravenous steroid agent was used to treat this patient after being diagnosed with MOG-EM. Dizziness, vomiting, and vision loss have gone into remission. This patient did not relapse in 7 months after discharge. This patient is still being followed up at the outpatient clinic. And the patient will next be treated with azathioprine. CONCLUSIONS: In previous studies, polyclonal antibody has been found in cancer patients, such as aquaporin-4 and MOG-IgG in astrocytoma patients. But the case of our study finds that astrocytoma can coexist with MOG-EM. Therefore, MOG-EM should not be excluded easily in astrocytoma patients when the relative antibody of encephalomyelitis is positive. What's more, it reminds us that the pathogenesis of MOG-EM might be related to astrocytoma.

Identification and validation of prognostic autophagy-related genes associated with immune microenvironment in human gastric cancer.

Autophagy-related genes (ATGs) play critical roles in tumorigenesis and progression in gastric cancer (GC). The present study aimed to identify immune-based prognostic ATGs and verify their functions in tumor immune microenvironment (TIME) in GC. Macrophage infiltration was found to negatively correlate with prognosis in GC patients. After stratifying by infiltration levels of macrophages, we screened The Cancer Genome Atlas and Human Autophagy Database to identify the differentially expressed ATGs (DE-ATGs). Of 1,433 differentially expressed genes between the two groups, seven genes qualified as DE-ATGs. Of these, CXCR4, DLC1, and MAP1LC3C, exhibited strong prognostic prediction ability in Kaplan-Meier survival-log-rank test. High expression of these genes correlated with increased occurrence of advanced grade 3 tumors and poor prognoses. Furthermore, GSEA indicated that they were significantly associated with oncogenic and immune-related pathways. The comprehensive evaluation of TIME via GEPIA, ESTIMATE, CIBERSORT, and TIMER suggested that the three DE-ATGs were closely associated with immune condition, both in terms of immune cells and immune scores. Thus, the outcome of this study may aid in better understanding of the ATGs and their interaction with the immune microenvironment, which would allow the development of novel inhibitors, personalized treatment, and immunotherapy in gastric cancer.

Acute pontine infarction in a patient with 8-shaped basilar artery fenestration malformation: A case report.

INTRODUCTION: Cerebrovascular fenestration malformation is a relatively rare vascular dysplasia, and an 8-shaped basilar artery fenestration malformation is even rarer. The characteristics of transcranial Doppler cerebral blood flow in cerebrovascular fenestration malformations have rarely been studied or reported. PATIENT CONCERNS: A 58-year-old woman presented with hypertension, diabetes, with no history of smoking or drinking. The patient had no relevant family history. The patient experienced left limb weakness for 2 days, which gradually worsened. DIAGNOSIS: Head and neck computed tomography angiography revealed an 8-shaped fenestration deformity of the lower segment of the basilar artery with multiple stenoses of the local vessels. Transcranial Doppler cerebral blood flow examination at a depth of 85 cm revealed an eddy current in the lower segment of the basilar artery. INTERVENTIONS: Tirofiban was administered intravenously for 3 days and subsequently changed to oral clopidogrel antiplatelet treatment. OUTCOMES: The modified Rankin Scale score at 3 months after disease onset was 0, indicating that the patient recovered well after treatment. CONCLUSION: A basilar artery 8-shaped fenestration is extremely rare and has seldom been reported. Cerebral vascular fenestration can lead to an acute cerebral infarction and its pathogenesis may include local hemodynamic abnormalities and thrombosis. Eddy currents can be detected by transcranial Doppler cerebral blood flow examination.

Clinical significance of circulating tumour cells and tumour marker detection in the chemotherapeutic evaluation of advanced colorectal cancer.

AIM: Systemic chemotherapy combining biological targeted therapies is the standard therapy for patients with metastatic colorectal cancer (mCRC), but effective markers are needed to identify clinical responders. Circulating tumour cells (CTCs) have been associated with prognosis in patients with mCRC. This study aimed to explore the relationship between CTC number and the clinical response of patients with advanced CRC. METHOD: Epithelial cell adhesion molecule-independent enrichment and CD45- fluorescence in situ hybridization immunofluorescence were used to detect peripheral blood CTCs in 79 patients with advanced CRC. Fisher's exact test and Spearman's rank correlation coefficient were used to analyse the correlation between CTC number and efficacy of chemotherapy. Kaplan-Meier and Cox regression analyses were used to evaluate progression-free survival (PFS). RESULTS: Among the evaluable patients, CTCs were significantly correlated with clinical response (r =4.891, p = 0.031). High CTC numbers were associated with a poor treatment response (r = -0.250, p = 0.027). Dynamic decrease in CTC number was associated with clinical response (p = 0.046). High baseline CTC number and carcinoembryonic antigen levels were prognostic factors for unfavourable PFS in multivariable analysis [hazard ratio (HR) = 3.30, p = 0.011 and HR = 2.04, p = 0.044, respectively]. Compared with the CTC-positive group, the CTC-negative group showed superior PFS (median PFS 15.53 vs. 9.43 months, p = 0.041) among CRC patients receiving first-line treatment. CONCLUSION: CTC number is a feasible biomarker for predicting outcomes in mCRC patients receiving systemic chemotherapy.

TINAGL1 promotes hepatocellular carcinogenesis through the activation of TGF-ß signaling-medicated VEGF expression.

BACKGROUND AND PURPOSE: Tubulointerstitial nephritis antigen-like 1 (TINAGL1) is an extracellular matrix protein that plays an important role in cell adhesion and therefore modulates cell proliferation, migration, and differentiation. In addition, it is frequently upregulated in highly metastatic tumors. The aim of our study was to determine the role of TINAGL1 in the progression and metastasis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: TINAGL1 mRNA levels were analyzed in HCC and adjacent non-tumorous samples by reverse transcription polymerase chain reaction (RT-PCR). Human HCC cell lines were transfected with lentiviral plasmids expressing either si-TINAGL1 or TINAGL1 and subjected to CCK-8, colony forming, transwell migration, Annexin V/propidium iodide, and 5-ethynyl-2'-deoxyuridine uptake assays. Suitably transfected HCC cells were injected into athymic nude mice to establish xenograft tumors that were imaged and measured on a weekly basis. Mediators of the TGF-ß signaling pathway were analyzed by Western blot. RESULTS: TINAGL1 was upregulated in human HCC tissues and associated with poor prognosis. TINAGL1 knockdown suppressed HCC cell growth, proliferation, and migration and induced apoptosis in HCC cells, whereas TINAGL1 overexpression had opposite effects. In addition, inhibition of TINAGL1 retarded xenograft tumor growth in a nude mouse model. Mechanistically, TINAGL1 activated the TGF-ß signaling pathway and increased VEGF secretion. CONCLUSION: TINAGL1 promotes hepatocellular carcinogenesis and metastasis via the TGF-ß/Smad3/VEGF axis and is a potential new biomarker of HCC.

Overexpression of Pyruvate Dehydrogenase E1α Subunit Inhibits Warburg Effect and Induces Cell Apoptosis Through Mitochondria-Mediated Pathway in Hepatocellular Carcinoma.

Most cancers rely disproportionately on glycolysis for energy even in the presence of an adequate oxygen supply, a condition known as "aerobic glycolysis," or the "Warburg effect." Pyruvate dehydrogenase E1α subunit (PDHA1) is one of the main factors for the metabolic switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis and has been suggested to be closely associated with tumorigenesis. Here we observed that the PDHA1 protein was reduced in hepatocellular carcinoma (HCC) specimens by immunohistochemistry and Western blot, which was significantly associated with poor overall survival. To further analyze the function of PDHA1 in cancer cells, PDHA1 was upregulated in the HCC cell lines SMMC-7721 and HepG2. The results demonstrated that overexpression of the PDHA1 gene inhibited aerobic glycolysis with lower lactate via increased PDH activity; meanwhile, mitochondrial OXPHOS was enhanced accompanied with higher ATP and lower glucose consumption. We also found that apoptosis was promoted and intrinsic pathway proteins were increased in PDHA1-overexpressing cells. Collectively, our data indicate that reduced PDHA1 protein expression is associated with the poor clinical outcome of HCC. Upregulated PDHA1 gene expression can inhibit the Warburg effect and enhance the mitochondria-mediated apoptosis pathway.

Upregulation of phosphatase and tensin homolog is essential for the effect of 4-aminopyridine on A549/CDDP cells.

4-aminopyridine (4-AP), a voltage-gated potassium channel blocker, was revealed to possess pro­apoptotic properties in various types of cancer cells. The present study aimed to explore the effect of 4­AP on a cisplatin (DDP) resistant lung cancer cell line A549/CDDP and the underlying mechanism by which it had an effect. In the present study, an MTT assay and cell cycle analysis were used to determine that 4­AP inhibited cell growth in vitro and a tumorigenesis assay in nude mice determined that 4­AP also inhibited cell growth in vivo. 4­AP induced cell apoptosis of A549/CDDP cells observed by electron microscopy and Annexin V­APC/7­ADD analysis. In addition, 4­AP enhanced the sensitivity of A549/CDDP cells to DDP as revealed by an MTT assay. Mechanistically, 4­AP upregulated the phosphatase and tensin homolog (PTEN) and modulated the phosphoinositide 3­kinase/protein kinase B signaling pathway and its downstream cell cycle factors, including cyclin D1, cyclin­dependent kinase 4 and p21, as well as apoptosis­associated proteins B­cell lymphoma 2, pro­caspase 9, pro­caspase 3, cleaved caspase 9 and cleaved caspase 3. The effects of 4­AP on cell growth and apoptosis were reversed by PTEN silencing. In conclusion, the results indicated that 4­AP inhibited cell growth, induced apoptosis and sensitized A549/CDDP cells to DDP via the upregulation of PTEN. 4­AP may be a potential therapeutic agent for patients with DDP resistance.

Reduced PDCD4 Expression Promotes Cell Growth Through PI3K/Akt Signaling in Non-Small Cell Lung Cancer.

It is largely recognized that PDCD4 is frequently lost in tumors of various origins, including lung cancer, and its loss contributes to tumor progression. However, its role and molecular mechanism remain largely unexplored in non-small cell lung cancer (NSCLC). In this study, downregulated PDCD4 mRNA expression was found in NSCLC tissues compared to their corresponding paracarcinoma tissues and distal paracarcinoma tissues. Induced expression of PDCD4 inhibited cell growth and proliferation and cell cycle transition in vitro. Conversely, knocking down PDCD4 expression promoted cell growth and proliferation. Mechanistically, PDCD4 inactivated PI3K/Akt signaling and its downstream cell cycle factors CCND1 and CDK4 to regulate cell growth in NSCLC. Additionally, PI3K-specific inhibitor Ly294002 suppressed the expression of pPI3K (Tyr458), pAkt (Ser473), CCND1, and CDK4 in PC9-shPDCD4 and A549-shPDCD4 cells. Furthermore, Akt-specific inhibitor MK2206 inhibited the expression of pAkt (Ser473), CCND1, and CDK4 in PC9-shPDCD4 and A549-shPDCD4 cells. Taken together, our study provides evidence that PDCD4 inhibits cell growth through PI3K/Akt signaling in NSCLC and may be a potential therapeutic target for NSCLC.

Low EphA7 Expression Correlated with Lymph Node Metastasis and Poor Prognosis of Patients with Esophageal Squamous Cell Carcinoma.

As a member of the Eph family of receptor tyrosine kinases, EphA7 plays an important role in cancer. However, the expression and significance of Eph receptors in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we detected the expression of EphA7 by immunohistochemistry in a sample of 352 patients with ESCC, and aimed to investigate the expression status of EphA7 in ESCC and its impact on prognosis. The results showed that low EphA7 expression significantly correlated with lymph node metastases (N0: 29%; N1: 64%. p<0.001), poor degree of tumor differentiation (G1: 31%; G2: 49%; G3: 58%. p=0.009) and pTNM staging (I+II: 33%; III+IV: 58%. p<0.001). Furthermore, in a combined analysis, patients with low EphA7-expressing tumors showed a shorter overall survival than those with high expression, resulting in a five-year overall survival rate of 47.4% vs. 52.6%, respectively (p=0.016). Consequently, patients with a low EphA7 expression have poorer prognosis in ESCC compared with those manifesting high expression.

[Role of pharmacokinetic monitoring of serum fluorouracil concentration in patients with local advanced and metastatic colorectal cancer and further improving efficacy of fluorouracil-based chemotherapy].

OBJECTIVE: To investigate the relationship between serum concentration of fluorouracil and therapeutic efficacy as well as adverse reactions in patients with unresectable locally advanced or measurable metastatic colorectal cancer, and to analyze its role in further improving therapeutic efficacy and reducing adverse reactions of fluorouracil-based chemotherapy. METHODS: Eighty-six patients were randomly assigned into three groups according to the average plasma concentration of fluorouracil after three cycles of chemotherapy with the initial regimen of two weeks FOLFOX-4 (oxaliplatin + leucovorin + fluorouracil) or FOLFIRI (irinotecan + leucovorin + fluorouracil): group 1 (plasma concentration of fluorouracil < 25 ng/ml), group 2 (25 - 35 ng/ml) and group 3 (> 35 ng/ml). The blood samples were taken at 12 h after continuous infusion of fluorouracil in each cycle and the plasma concentration of fluorouracil was detected by high performance liquid chromatography (HPLC) (about 5 am ± 1 h). The relationship between the drug plasma concentration, therapeutic efficacy and adverse reactions in different fluorouracil plasma concentration arms was analyzed retrospectively. RESULTS: The average plasma concentrations of fluorouracil of the three groups were (23.48 ± 1.95) ng/ml, (31.47 ± 2.33) ng/ml and (39.89 ± 3.87) ng/ml, respectively (P < 0.01). As for therapeutic efficacy, the median OS of the groups 2 and 3 were 18.0 and 17.5 months, significantly higher than that in the group 1 (13.0 months, P < 0.01). The PFS were 4.5, 7.5 and 8.0 months, respectively (P < 0.01). In terms of adverse reactions, the incidences of bone marrow suppression, mucositis and diarrhea in the group 3 were significantly higher than that in the first two groups (P = 0.02, P = 0.04 and P = 0.02). CONCLUSIONS: The patients with local advanced and metastatic colorectal cancer, receiving fluorouracil-based chemotherapy, and with an average plasma concentration of fluorouracil between 25 - 35 mg/L have a better prognosis, and lower incidence of adverse reactions such as bone marrow suppression, mucositis and diarrhea.