In Patients with Acute Ischemic Stroke and Cancer: The Shorter Interval, the Higher D-Dimer.

OBJECTIVES: Acute ischemic stroke in cancer patients is uncommon. The study was aimed to identify the relationship of patients' characteristics and the interval time between the diagnosis of stroke and cancer. METHODS: The clinical features of acute ischemic stroke patients with cancer were retrospectively analyzed from May, 2016 to April, 2021. Categorical data was compared between groups using chi-square test. Hematological biomarkers were compared using Mann-Whitney U test. RESULTS: A total of 70 acute ischemic stroke patients with cancer were identified. The median interval time between the diagnosis of acute ischemic stroke and cancer was 53.0 months. Patients with interval < 53.0 months and > 53.0 months were regarded the short interval group and the long interval group, respectively. Between the short and long interval groups, there was no significant differences in respect to sex, age, chemotherapy, hypertension, diabetes, smoking, atrial fibrillation and dyslipidemia. The medians of homocysteine, high-sensitivity C-reactive protein and fibrinogen were also not significantly different between the two different interval groups. D-dimer in the short interval group was higher than that in the long interval group (216 vs. 142 ng/mL, p = 0.037). The long interval group had more surgery for cancer than the short interval group (94.3% vs. 57.1%, p = 0.000). CONCLUSION: In conclusion, in patients with ischemic stroke and cancer, patients with short interval time between the diagnosis of ischemic stroke and cancer had higher D-dimer than patients with long interval time.

LncRNA TUG1 promotes bladder cancer malignant behaviors by regulating the miR-320a/FOXQ1 axis.

BACKGROUND: Growing evidence has showed long noncoding RNAs (lncRNAs) play critical roles in bladder cancer (BC) progression. LncRNA taurine upregulated gene 1 (TUG1) was involved in the development of human malignancies. However, the intrinsic and concrete molecular mechanisms of TUG1 in BC remain largely unknown. METHODS: Expression patterns of TUG1, miR-320a and FOXQ1 in BC tissues and cell lines were measured using qRT-PCR and western blot, respectively. Cell proliferation was detected by CCK-8 and colony formation assays. The capacity of cell migration and invasion was evaluated using wound healing and transwell assay. Tumor xenograft assay was performed to further validate the role of TUG1 in BC progression. Dual luciferase reporter assay and FISH analysis were employed to verify the TUG1/miR-320a/FOXQ1 regulatory network. RESULTS: TUG1 was significantly higher expression in BC specimens and cell lines. TUG1 knockdown suppressed BC cells malignant behaviors in vitro and inhibited tumor growth and metastasis in vivo, while TUG1 overexpression promoted BC cells malignant behaviors in vitro. However, the function of miR-320a was opposite to that of TUG1, and miR-320a inhibitor partially eliminated the inhibitory effect of TUG1 knockdown on the malignant behavior of BC cells. As a microRNA sponge, TUG1 actively elevated FOXQ1 expression to sponge miR-320a and subsequently promoted BC cells malignant phenotypes. CONCLUSION: TUG1 may have great potential as therapeutic target for BC, since TUG1 silencing inhibited cell proliferation, migration and invasion in BC, while promoted cell apoptosis, by regulating the miR-320a/FOXQ1 axis.

Clinical features and survival of patients with multiple primary malignancies.

BACKGROUND: Multiple primary malignancies (MPM) are characterized by two or more primary malignancies in the same patient, excluding relapse or metastasis of prior cancer. We aimed to elucidate the clinical features and survival of MPM patients. AIM: To elucidate the clinical features and survival of MPM patients. METHODS: A retrospective study of MPM patients was conducted in our hospital between June 2016 and June 2019. Overall survival (OS) was calculated using the Kaplan-Meier method. The log-rank test was used to compare the survival of different groups. RESULTS: A total of 243 MPM patients were enrolled, including 222 patients with two malignancies and 21 patients with three malignancies. Of patients with two malignancies, 51 (23.0%) had synchronous MPM, and 171 (77.7%) had metachronous MPM. The most common first cancers were breast cancer (33, 14.9%) and colorectal cancer (31, 14.0%). The most common second cancers were non-small cell lung cancer (NSCLC) (66, 29.7%) and gastric cancer (24, 10.8%). There was no survival difference between synchronous and metachronous MPM patients (36.4 vs 35.3 mo, P = 0.809). Patients aged > 65 years at diagnosis of the second cancer had a shorter survival than patients ≤ 65 years (28.4 vs 36.4 mo, P = 0.038). Patients with distant metastasis had worse survival than patients without metastasis (20.4 vs 86.9 mo, P = 0.000). Following multivariate analyses, age > 65 years and distant metastasis were independent adverse prognostic factors for OS. CONCLUSION: During follow-up of a first cancer, the occurrence of a second or more cancers should receive greater attention, especially for common concomitant MPM, to ensure early detection and treatment of the subsequent cancer.

PDB-1 from Potentilla discolor Bunge induces apoptosis and autophagy by downregulating the PI3K/Akt/mTOR signaling pathway in A549 cells.

PDB-1 is a new C-27-carboxylated-lupane-triterpenoid derivative isolated from Potentilla discolor Bunge. In our previous research, PDB-1 was suggested to have an obvious selectivity for tumor cells. This study focused on clarifying PDB-1's anticancer mechanism in the inhibition of proliferation and in the induction of apoptosis and autophagy in A549 cells. In general, A549 cells were treated with PDB-1 for different times, and cell survival was assessed by a CCK8 assay. The assessment of intracellular reactive oxygen species, a mitochondrial membrane potential assay, a cell cycle assay, an annexin V-FITC/PI assay, and MDC staining were performed in A549 cells treated with PDB-1. Moreover, the mRNA and protein expression of cell cycle-, apoptosis- and autophagy-related factors were detected by RT-qPCR and western blotting. The results showed that PDB-1 inhibited A549 cell proliferation and colony formation in a dose- and time-dependent manner. The decrease in the viability of A549 cells was due to a G2/M cell cycle arrest. Moreover, PDB-1 induced cell apoptosis, accompanied by an increase in the Bax/Bcl-2 ratio and an increase in the expression levels of cleaved caspase-3/caspase-9. We also found that PDB-1 induced autophagy by increasing the conversion of LC3-I to LC3-II and elevating Beclin-1. In addition, further studies indicated that pretreatment with a specific PI3K inhibitor (LY294002) enhanced the effects of PDB-1 on the expression of proteins associated with apoptosis and autophagy, demonstrating that the PI3K/Akt/mTOR pathway was related to PDB-1-induced apoptosis and autophagy. These results indicated that PDB-1 may be considered a potential candidate for the future treatment of lung adenocarcinoma. These findings should benefit the development of the C14-COOH type of pentacyclic triterpenoids.

Microenvironment-related prognostic genes in esophageal cancer.

BACKGROUND: Esophageal cancer is one of the most common malignant tumors. The role of tumor microenvironment in esophageal cancer is unclear. METHODS: The gene expression profiles and clinical data of 158 patients with esophageal cancer were extracted from The Cancer Genome Atlas database. Immune scores and stromal scores were calculated based on ESTIMATE algorithm. According to different immune/stromal scores, differentially expressed genes (DEGs) were identified. The function enrichment, protein interactions of shared DEGs and their associations with overall survival were analyzed. RESULTS: In regard to the association of the immune/stromal scores and disease stage, pathological type and overall survival, only the stromal scores among the different stages were significantly different (P=0.015). In the high immune and stromal score groups, 603 shared up-regulated genes were found. The related function and pathways included regulation of lymphocyte activation, cytokine binding and chemokine signaling pathway. Protein-protein interaction analysis showed that ITGAM had the most connections, followed by CXCL10 and CCR2. High expression of 11 genes, including MS4A7, TMIGD3, MS4A4A, EVI2A, MS4A6A, FCER1G, AIF1, GNGT2, LCP2, DNAJC5B and RNASE6, were found to be associated with shorter overall survival. CONCLUSIONS: Microenvironment-associated functions and pathways were analyzed in esophageal cancer, and 11 microenvironment-associated genes were correlated to poor prognoses. Further studies on these genes may be helpful to understand the tumor microenvironment and provide new therapies for esophageal cancer.

Supercritical CO2 fluid extraction of croton crassifolius Geisel root: Chemical composition and anti-proliferative, autophagic, apoptosis-inducing, and related molecular effects on A549 tumour cells.

BACKGROUND: The use of plant essential oils as pharmaceuticals is a fast-growing market especially in China. Throughout the 20th century, a rapid increase took place in the use of many essential oil-derived products in the medicinal industry as nutraceuticals, medicinal supplements, and pharmaceuticals. PURPOSE: The objective of this study was to explore the chemical composition of Croton crassifolius essential oil as well as its potential anti-tumour properties and related anti-proliferative, autophagic, and apoptosis-inducing effects. METHODS: Supercritical CO2 fluid extraction technology was used to extract CCEO and the chemical constituents of the essential oil were identified by comparing the retention indices and mass spectra data taken from the NIST library with those calculated based on the C7-C40 n-alkanes standard. The cytotoxic activity and anti-proliferative effects of CCEO were evaluated against five cancer cell lines and one normal human cell line via CCK-8 assays. In addition, flow cytometry was used to detect cell cycle arrest. The efficacy of CCEO treatments in controlling cancer cell proliferation was assessed by cell cycle analysis, clonal formation assays, RT-qPCR, and western blot analysis. Autophagic and apoptosis-inducing effects of oils and the associated molecular mechanisms were assessed by flow cytometry, cell staining, reactive oxygen species assays, RT-qPCR, and western blot analysis. CONCLUSION: Forty compounds representing 92.90% of the total oil were identified in CCEO. The results showed that CCEO exerted a measurable selectivity for cancer cell lines, especially for A549 with the lowest IC50 value of 25.00 ± 1.62 µg/mL. Assessment of the anti-proliferative effects of CCEO on A549 cells showed that the oil inhibited cell proliferation and colony formation in a dose- and time-dependent manner. Investigation of the molecular mechanisms of cell cycle regulation confirmed that the oil arrested A549 cells in G2/M phase by decreasing the expression of cyclin B1-CDK1 and cyclin A-CDK1 and increasing the expression of cyclin-dependent kinase inhibitor (CKI) P21 at both the transcriptional and translational levels. Autophagy staining assays and western blot analysis revealed that CCEO promoted the formation of autophagic vacuoles in A549 cells and increased the expression of autophagy-related proteins beclin-1 and LC3-II in a dose-dependent manner. A series of apoptosis analyses indicated that CCEO induces apoptosis through a mitochondria-mediated intrinsic pathway. This study revealed that CCEO is a promising candidate for development into an anti-tumour drug of the future.

[Value of Magnetic Resonance Imaging Findings in Differential Diagnosis between the Adult Reversible Splenial Lesion Syndrome and Ischemic Infarction of the Splenium of the Corpus Callosum].

Objective To evaluate the magnetic resonance imaging (MRI) findings in differential diagnosis between the adult reversible splenial lesion syndrome (RESLES) and ischemic infarction of the splenium of the corpus callosum (SCC). Methods The MRI findings and clinical data of 7 RESLES patients and 13 patients with ischemic infarction of SCC who were clinically diagnosed and treated in our center from May 2015 to June 2017 were analyzed retrospectively. The main MRI findings included location,morphology,signal intensity,maximum cross-sectional area,diffusion weighted imaging (DWI),and apparent diffusion coefficient (ADC) value. Results On the MRI findings of 7 RESLES patients (5 males and 2 females),the centers of all lesions of the SCC were located in the midline of SCC,the lesion shapes were round,ellipse,or spindle,and the distribution of the lesions was bilateral and symmetric as the center of the midline of SCC. The lesions were hyperintense on DWI,and the mean maximum cross-sectional area of lesions was (56.9±32.6) mm2 and the mean ADC value was (0.3963±0.0715) ×10-3 mm2/s. On the review MRI,all the lesions disappeared (mean interval:10 days). On the MRI findings of 13 patients with ischemic infarction of SCC (10 males and 3 females),the lesions were irregular or patchy in shape and were almost laterally and asymmetrically distributed. The lesions were hyperintense on DWI,and the mean maximum cross-sectional area was (55.1±43.9) mm2 and the mean ADC value was (0.4978±0.0123) ×10-3 mm2/s. The mean maximum cross-sectional area (t=0.096,P=0.925) and the ADC value (t=-1.988,P=0.062) were not significantly different between RESLES group and ischemic infarction of SCC group. Conclusions The location,morphology,and distribution of the SCC lesions and the co-existence of other lesions in the brain are helpful for the differential diagnosis between RESLES and ischemic infarction of SCC. However,the mean maximum cross-sectional area and the ADC value show no obvious difference between these two diseases.

[Correlations between apparent diffusion coefficient in diffusion?weighted magnetic resonance imaging and molecular subtypes of invasive breast cancer masses].

OBJECTIVE: To study the correlation of apparent diffusion coefficient (ADC) measured by diffusion-weighted magnetic resonance imaging (MRI) with the molecular subtypes and biological prognostic factors of invasive breast cancer masses. METHODS: Breast MRI data (including dynamic enhanced and diffusion-weighted imaging) were collected from 64 patients with pathologically confirmed invasive breast cancer masses (a total of 69 lesions). The mean ADC values of the lesions were calculated and their correlations were analyzed with the 5 molecular subtypes of invasive breast cancer and the biological prognostic factors including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67 index. RESULTS: The ADC values did not differ significantly among the 5 molecular subtypes of invasive breast cancer masses (P>0.05) or among lesions with different ER, PR, or HER2 status (P>0.05). The mean ADC values were significantly higher in Ki-67-positive lesions than in the negative lesions (P=0.023 and negatively correlated with the expressions of Ki-67 (r=-0.249). CONCLUSION: ADC value can not be used to identify the molecular subtypes of invasive breast cancer masses or to evaluate the biological prognosis of the lesions, but its correlation with Ki-67 expression may help in prognostic evaluation and guiding clinical therapy of the tumors.

[Magnetic resonance imaging findings of Chromophobe renal cell carcinoma].

OBJECTIVE: To document the MRI features of Chromophobe cell carcinoma and to explore whether MR features vary with the tumor size. METHODS: MRI features of 34 patients (16 male, 18 female, age range from 24 - 61, average age is 49 years old), totally 35 focuses with histologically proved chromophobe cell carcinoma were studied retrospectively. All the patients underwent MR plain and dynamic contrast-enhanced scan before their surgery. Variation of signal intensity (3D LAVA) and ADC values of the lesions, and the analysis of images of T1WI, T2WI and chemical shift were all evaluated on the GE Advantage 4.4 work station. All lesions were categorized into 2 groups (tumor diameter ≤ 4 cm, or > 4 cm). The difference of imaging characteristics between these two groups was analyzed using Fisher exact test. Signal intensity variation and ADC values were analyzed by using one-way ANOVA method. RESULTS: None of the 35 cases contained fat or lipid. On T2WI 27 cases showed slightly low signal intensity (77.1%). In all cases, 4 appeared local cystic change (11.4%); 4 spotty hemorrhage (11.4%); 5 necrosis (covering less than 20% of whole tumor) (14.2%); 30 clear pseudo capsule (85.7%); 29 round-like lesions (the difference among the length, width and height was within 0.5 cm) (82.8%); and no cases showed signs of invasiveness or metastasis. The average changes of signal intensity of all the 35 cases were 119.8% on cortex period, 176.4% on medulla period and 154.5% on delayed phase. The mean ADC value of tumor was 1.08 ± 0.28×10(-3)mm(2)/s. 35 lesions were divided into two groups , 21 in group 1(diameter ≤ 4 cm) and 14 in group 2 (diameter > 4 cm). Cystic degeneration was seen in 0/21 in group 1 versus 4/14 in group 2 respectively, and hemorrhage 0/21 versus 4/14, necrosis 0/21 versus 5/14 , central scar 2/21 versus 8/14. The difference of these findings between two groups demonstrated statistical significance (P < 0.05). Variation of signal intensity and ADC values in two groups has no statistical significance. CONCLUSION: The MR features of Chromophobe renal cell carcinoma were hypointensity on T2WI, clear pseudocapsule, However, cystic degeneration, hemorrhage, necrosis and central scar are more common in larger tumors.

[Magnetic resonance imaging features of pancreatic neuroendocrine carcinoma: a literature review].

OBJECTIVE: To explore the magnetic resonance imaging (MRI) manifestations of pancreatic neuroendocrine carcinoma (PNC). METHODS: The clinical data of 7 PNC patients as confirmed by pathological examination were analyzed retrospectively and the relevant literatures discussed. RESULTS: Among them, 2 patients were misdiagnosed for benign tumor lesion, one for SPT and another for pancreatic cancer with liver metastasis. And 3 were diagnosed correctly. The lesions showed irregular or lobulated shapes: 5 in body and tail of pancreas and 2 in head of pancreas. All lesions were hypointense on T(1)WI. They were iso- to slightly hyperintense (n = 5) and heterogeneously hyperintense (n = 2) on T(2)WI. Dynamic contrast-enhanced MRI was performed in all. There were slight enhancement (n = 2) and moderate enhancement (n = 5) during arterial phase. During interstitial and delayed phases, there were gradual enhancement (n = 2) and less enhancement (n = 5) than pancreatic parenchyma. There were metastasis of lymph nodes (n = 1), splenic metastasis (n = 2), liver metastasis (n = 1) and invasion of pancreatic capsule (n = 3). CONCLUSION: Due to the lack of MRI specificities, a definite diagnosis of pancreatic neuroendocrine carcinoma must be made by pathological examination and immunohistochemistry.