On the way to the azygos vein: a road of return rather than ruined.

BACKGROUND: The malposition of central venous catheters (CVCs) may lead to vascular damage, perforation, and even mediastinal injury. The malposition of CVC from the right subclavian vein into the azygos vein is extremely rare. Here, we report a patient with CVC malposition into the azygos vein via the right subclavian vein. We conduct a comprehensive review of the anatomical structure of the azygos vein and the manifestations associated with azygos vein malposition. Additionally, we explore the resolution of repositioning the catheter into the superior vena cava by carefully withdrawing a specific length of the catheter. CASE PRESENTATION: A 79-year-old female presented to our department with symptoms of complete intestinal obstruction. A double-lumen CVC was inserted via the right subclavian vein to facilitate total parenteral nutrition. Due to the slow onset of sedative medications during surgery, the anesthetist erroneously believed that the CVC had penetrated the superior vena cava, leading to the premature removal of the CVC. Postoperative contrast-enhanced computed tomography of the chest confirmed that the central venous catheter had not penetrated the superior vena cava but malpositioned into the azygos vein. The patient was discharged 15 days after surgery without any complications. CONCLUSIONS: CVC malposition into the azygos vein is extremely rare. Clinical practitioners should be vigilant regarding this form of catheter misplacement. Ensuring the accurate positioning of the CVC before each infusion is crucial. Utilizing chest X-rays in both frontal and lateral views, as well as chest computed tomography, can aid in confirming the presence of catheter misplacement.

E2F7 serves as a potential prognostic biomarker for lung adenocarcinoma.

E2F transcription factors (E2Fs) are a family of transcription factors critical regulators of the cell cycle, apoptosis, and differentiation, thus influencing tumorigenesis. However, the specific roles of E2Fs in lung adenocarcinoma (LUAD) remain unclear. Data from The Cancer Genome Atlas (TCGA) were used. R version. 4.0.3 and multiple databases (TIMER, cBioportal, gene expression profile interaction analysis [GEPIA], LinkedOmics, and CancerSEA) were utilized to investigate mRNA expression, mutational analysis, prognosis, clinical correlations, co-expressed gene, pathway and network, and single-cell analyses. Immunohistochemistry (IHC) confirmed that E2F transcription factor 7 (E2F7) correlated with LUAD. Among the E2Fs, E2F7 was identified by constructing a prognostic model most significantly associated with overall survival (OS) in LUAD patients. The univariate and multivariate Cox regression analyses showed that E2F7, p-T stage, and p-TNM stage were closely related to OS and progression-free survival (PFS) (P < .05) in LUAD. E2F 7/8 were also identified as significantly associated with tumor stage in the GEPIA database. Compared with paracancerous tissues, E2F7 was up-regulated in LUAD by IHC, and E2F7 might be positively correlated with larger tumors and higher TNM stages. E2F7 may primarily regulate DNA repair, damage, and cell cycle processes and thus affect LUAD tumorigenesis, invasion, and metastasis by LinkedOmics and CancerSEA. E2F7 serves as a potential prognostic biomarker for LUAD.

Discrimination between human epidermal growth factor receptor 2 (HER2)-low-expressing and HER2-overexpressing breast cancers: a comparative study of four MRI diffusion models.

OBJECTIVES: To determine the value of conventional DWI, continuous-time random walk (CTRW), fractional order calculus (FROC), and stretched exponential model (SEM) in discriminating human epidermal growth factor receptor 2 (HER2) status of breast cancer (BC). METHODS: This prospective study included 158 women who underwent DWI, CTRW, FROC, and SEM and were pathologically categorized into the HER2-zero-expressing group (n = 10), HER2-low-expressing group (n = 86), and HER2-overexpressing group (n = 62). Nine diffusion parameters, namely ADC, αCTRW, ßCTRW, DCTRW, ßFROC, DFROC, µFROC, αSEM, and DDCSEM of the primary tumor, were derived from four diffusion models. These diffusion metrics and clinicopathologic features were compared between groups. Logistic regression was used to determine the optimal diffusion metrics and clinicopathologic variables for classifying the HER2-expressing statuses. Receiver operating characteristic (ROC) curves were used to evaluate their discriminative ability. RESULTS: The estrogen receptor (ER) status, progesterone receptor (PR) status, and tumor size differed between HER2-low-expressing and HER2-overexpressing groups (p < 0.001 to p = 0.009). The αCTRW, DCTRW, ßFROC, DFROC, µFROC, αSEM, and DDCSEM were significantly lower in HER2-low-expressing BCs than those in HER2-overexpressing BCs (p < 0.001 to p = 0.01). Further multivariable logistic regression analysis showed that the αCTRW was the single best discriminative metric, with an area under the curve (AUC) being higher than that of ADC (0.802 vs. 0.610, p < 0.05); the addition of ER status, PR status, and tumor size to the αCTRW improved the AUC to 0.877. CONCLUSIONS: The αCTRW could help discriminate the HER2-low-expressing and HER2-overexpressing BCs. CLINICAL RELEVANCE STATEMENT: Human epidermal growth factor receptor 2 (HER2)-low-expressing breast cancer (BC) might also benefit from the HER2-targeted therapy. Prediction of HER2-low-expressing BC or HER2-overexpressing BC is crucial for appropriate management. Advanced continuous-time random walk diffusion MRI offers a solution to this clinical issue. KEY POINTS: • Human epidermal receptor 2 (HER2)-low-expressing BC had lower αCTRW, DCTRW, ßFROC, DFROC, µFROC, αSEM, and DDCSEM values compared with HER2-overexpressing breast cancer. • The αCTRW was the single best diffusion metric (AUC = 0.802) for discrimination between the HER2-low-expressing and HER2-overexpressing breast cancers. • The addition of αCTRW to the clinicopathologic features (estrogen receptor status, progesterone receptor status, and tumor size) further improved the discriminative ability.

A HER2-targeted Antibody-Drug Conjugate, RC48-ADC, Exerted Promising Antitumor Efficacy and Safety with Intravesical Instillation in Preclinical Models of Bladder Cancer.

More than half of non-muscle-invasive bladder cancer (NMIBC) patients eventually relapse even if treated with surgery and BCG without optional bladder-preserving therapy. This study aims to investigate the antitumor activity and safety of a HER2-targeted antibody-drug conjugate, RC48-ADC, intravesical instillation for NMIBC treatment. In this preclinical study, it is revealed that human epidermal growth factor receptor 2 (HER2) expression scores of 1+, 2+, and 3+ are recorded for 16.7%, 56.2%, and 14.6% of NMIBC cases. The antitumor effect of RC48-ADC is positively correlated with HER2 expression in bladder cancer (BCa) cell lines and organoid models. Furthermore, RC48-ADC is revealed to exert its antitumor effect by inducing G2/M arrest and caspase-dependent apoptosis. In an orthotopic BCa model, tumor growth is significantly inhibited by intravesical instillation of RC48-ADC versus disitamab, monomethyl auristatin E, epirubicin, or phosphate-buffered saline control. The potential toxicity of intravesical RC48-ADC is also assessed by dose escalation in normal nude mice and revealed that administration of RC48-ADC by intravesical instillation is safe within the range of effective therapeutic doses. Taken together, RC48-ADC demonstrates promising antitumor effects and safety with intravesical administration in multiple preclinical models. These findings provide a rational for clinical trials of intravesical RC48-ADC in NMIBC patients.

TFE3 gene rearrangement and protein expression contribute to a poor prognosis of renal cell carcinoma.

Background: TFE3-rearranged renal cell carcinoma (TFE3-rearranged RCC) is a type of kidney cancer with a low incidence, with no consensus about whether it has a worse prognosis than clear cell renal cell carcinoma (ccRCC). This study attempted to elucidate the impact of TFE3-rearranged RCC by analyzing its clinical features and prognosis. Methods: Patients treated in Sun Yat-sen Memorial Hospital (SYSMH) who were suspected to be diagnosed with TFE3-rearranged RCC were divided into two groups, TFE3-rearranged RCC and ccRCC with positive TFE3 protein expression on immunohistochemistry [TFE3(+) ccRCC], by dual-color, break-apart fluorescence in situ hybridization (FISH). After balancing the baseline characteristics with TFE3(+) ccRCC using the propensity score matching (PSM) method in a ratio of 2, we selected patients diagnosed with ccRCC with negative TFE3 protein expression on immunohistochemistry [TFE3(-) ccRCC]. The impact of TFE3 gene rearrangement and protein expression on renal cell carcinoma was determined by feature comparison with a nonparametric test and survival analysis with the Kaplan‒Meier method. Results: Among 37 patients suspected of having TFE3-rearranged RCC, 13 patients were diagnosed with TFE3-rearranged RCC, and 24 patients had TFE3(+) ccRCC. The recurrence and new metastasis of TFE3-rearranged RCC was relatively common, even if the tumor stage was early at the first diagnosis. Through feature comparison and survival analysis, we found that TFE3-rearranged RCC was quite similar to TFE3(+) ccRCC. Compared with TFE3(-) ccRCC, TFE3(+) ccRCC tended to have a larger tumor diameter (P = 0.011), higher neutrophil/lymphocyte ratio (NLR) (P = 0.017) and metastatic potential (P = 0.022), and worse overall survival (OS) (P = 0.043) and PFS (P = 0.016). The survival analysis showed that TFE3-rearranged RCC had a worse PFS than ccRCC (P = 0.002), and TFE3(+) RCC had a worse PFS than TFE3(-) RCC (P = 0.001). According to the stratification system based on the combination of TFE3 and lymphovascular invasion (LVI), we further found that the prognosis from good to poor was TFE3(-) LVI(-), TFE3(+) LVI(-), TFE3(+) LVI(+) and TFE3(-) LVI(+), with statistically significant differences in both OS (P = 0.001) and PFS (P < 0.001). In addition, we also reported two cases with poor prognosis, of which one was TFE3-rearranged RCC and the other was TFE3(+) ccRCC. Conclusions: This is a novel finding that both FISH confirmed TFE3 gene rearrangement-mediated TFE3-rearranged RCC and IHC confirmed positive TFE3 protein expression [TFE3(+)] contribute to a poor prognosis in RCC, suggesting more active treatment and careful follow-up for TFE3(+) RCC patients. The combination of TFE3 and LVI may be a new risk stratification system for RCC.

PIN1 and CDK1 cooperatively govern pVHL stability and suppressive functions.

The VHL protein (pVHL) functions as a tumor suppressor by regulating the degradation or activation of protein substrates such as HIF1α and Akt. In human cancers harboring wild-type VHL, the aberrant downregulation of pVHL is frequently detected and critically contributes to tumor progression. However, the underlying mechanism by which the stability of pVHL is deregulated in these cancers remains elusive. Here, we identify cyclin-dependent kinase 1 (CDK1) and peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) as two previously uncharacterized regulators of pVHL in multiple types of human cancers harboring wild-type VHL including triple-negative breast cancer (TNBC). PIN1 and CDK1 cooperatively modulate the protein turnover of pVHL, thereby conferring tumor growth, chemotherapeutic resistance and metastasis both in vitro and in vivo. Mechanistically, CDK1 directly phosphorylates pVHL at Ser80, which primes the recognition of pVHL by PIN1. PIN1 then binds to phosphorylated pVHL and facilitates the recruitment of the E3 ligase WSB1, therefore targeting pVHL for ubiquitination and degradation. Furthermore, the genetic ablation or pharmacological inhibition of CDK1 by RO-3306 and PIN1 by all-trans retinoic acid (ATRA), the standard care for Acute Promyelocytic Leukemia could markedly suppress tumor growth, metastasis and sensitize cancer cells to chemotherapeutic drugs in a pVHL dependent manner. The histological analyses show that PIN1 and CDK1 are highly expressed in TNBC samples, which negatively correlate with the expression of pVHL. Taken together, our findings reveal the previous unrecognized tumor-promoting function of CDK1/PIN1 axis through destabilizing pVHL and provide the preclinical evidence that targeting CDK1/PIN1 is an appealing strategy in the treatment of multiple cancers with wild-type VHL.

Autoencoder in Autoencoder Networks.

Modeling complex correlations on multiview data is still challenging, especially for high-dimensional features with possible noise. To address this issue, we propose a novel unsupervised multiview representation learning (UMRL) algorithm, termed autoencoder in autoencoder networks (AE 2 -Nets). The proposed framework effectively encodes information from high-dimensional heterogeneous data into a compact and informative representation with the proposed bidirectional encoding strategy. Specifically, the proposed AE 2 -Nets conduct encoding in two directions: the inner-AE-networks extract view-specific intrinsic information (forward encoding), while the outer-AE-networks integrate this view-specific intrinsic information from different views into a latent representation (backward encoding). For the nested architecture, we further provide a probabilistic explanation and extension from hierarchical variational autoencoder. The forward-backward strategy flexibly addresses high-dimensional (noisy) features within each view and encodes complementarity across multiple views in a unified framework. Extensive results on benchmark datasets validate the advantages compared to the state-of-the-art algorithms.

Binary Binder for Cf/C-SiC Composites with Enhanced Mechanical Property.

Cf/C-SiC composites have become the preferred material for high-temperature load-bearing applications because of their low density, high strength, and excellent thermal-physical properties. Due to the composite's poor sintering performance, the sintering temperature and pressure required for the preparation of Cf/C-SiC by traditional methods are also relatively high, which limits its engineering application. Herein, based on the precursor-derived ceramic route and C/C composites material preparation process, a binary binder (coal pitch and polysilylacetylene) is developed, which combines a carbon source, SiC precursor, and semi-ceramic SiC filler organically. Then, the SiC phase was successfully introduced into C/C composites by the slurry impregnation-hot pressing sintering method. The prepared Cf/C-SiC composites showed good mechanical properties, with a density of 1.53 g/cm3 and a bending strength of 339 ± 21 MPa. Moreover, the effects of the binary binder on the microstructure, density, and mechanical properties of Cf/C-SiC composites were investigated. This work provides a novel and effective approach to fabricating Cf/C-SiC composites with low density and high strength.

Electrochemical C-N bond activation for deaminative reductive coupling of Katritzky salts.

Electrosynthesis has received great attention among researchers in both academia and industry as an ideal technique to promote single electron reduction without the use of expensive catalysts. In this work, we report the electrochemical reduction of Katritzky salts to alkyl radicals by sacrificing the easily accessible metal anode. This catalyst and electrolyte free platform has broad applicability to single electron transfer chemistry, including fluoroalkenylation, alkynylation and thiolation. The deaminative functionalization is facilitated by the rapid molecular diffusion across microfluidic channels, demonstrating the practicality that outpaces the conventional electrochemistry setups.

STEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling in hepatocellular carcinoma.

STEAP3 (Six-transmembrane epithelial antigen of the prostate 3, TSAP6, dudulin-2) has been reported to be involved in tumor progression in human malignancies. Nevertheless, how it participates in the progression of human cancers, especially HCC, is still unknown. In the present study, we found that STEAP3 was aberrantly overexpressed in the nuclei of HCC cells. In a large cohort of clinical HCC tissues, high expression level of nuclear STEAP3 was positively associated with tumor differentiation and poor prognosis (p < 0.001), and it was an independent prognostic factor for HCC patients. In HCC cell lines, nuclear expression of STEAP3 significantly promoted HCC cells proliferation by promoting stemness phenotype and cell cycle progression via RAC1-ERK-STAT3 and RAC1-JNK-STAT6 signaling axes. Through upregulating the expression and nuclear trafficking of EGFR, STEAP3 participated in regulating EGFR-mediated STAT3 transactivity in a manner of positive feedback. In summary, our findings support that nuclear expression of STEAP3 plays a critical oncogenic role in the progression of HCC via modulation on EGFR and intracellular signaling, and it could be a candidate for prognostic marker and therapeutic target in HCC.

Engineering the Direct Repeat Sequence of crRNA for Optimization of FnCpf1-Mediated Genome Editing in Human Cells.

FnCpf1-mediated genome-editing technologies have enabled a broad range of research and medical applications. Recently, we reported that FnCpf1 possesses activity in human cells and recognizes a more compatible PAM (protospacer adjacent motif, 5'-KYTV-3'), compared with the other two commonly used Cpf1 enzymes (AsCpf1 and LbCpf1), which requires a 5'-TTTN-3' PAM. However, due to the efficiency and fidelity, FnCpf1-based clinical and basic applications remain a challenge. The direct repeat (DR) sequence is one of the key elements for FnCpf1-mediated genome editing. In principle, its engineering should influence the corresponding genome-editing activity and fidelity. Here we showed that the DR mutants [G(-9)A and U(-7)A] could modulate FnCpf1 performance in human cells, enabling enhancement of both genome-editing efficiency and fidelity. These newly identified features will facilitate the design and optimization of CRISPR-Cpf1-based genome-editing strategies.

A Single Multiplex crRNA Array for FnCpf1-Mediated Human Genome Editing.

Cpf1 has been harnessed as a tool for genome manipulation in various species because of its simplicity and high efficiency. Our recent study demonstrated that FnCpf1 could be utilized for human genome editing with notable advantages for target sequence selection due to the flexibility of the protospacer adjacent motif (PAM) sequence. Multiplex genome editing provides a powerful tool for targeting members of multigene families, dissecting gene networks, modeling multigenic disorders in vivo, and applying gene therapy. However, there are no reports at present that show FnCpf1-mediated multiplex genome editing via a single customized CRISPR RNA (crRNA) array. In the present study, we utilize a single customized crRNA array to simultaneously target multiple genes in human cells. In addition, we also demonstrate that a single customized crRNA array to target multiple sites in one gene could be achieved. Collectively, FnCpf1, a powerful genome-editing tool for multiple genomic targets, can be harnessed for effective manipulation of the human genome.

Selective killing of Helicobacter pylori with pH-responsive helix-coil conformation transitionable antimicrobial polypeptides.

Current clinical treatment of Helicobacter pylori infection, the main etiological factor in the development of gastritis, gastric ulcers, and gastric carcinoma, requires a combination of at least two antibiotics and one proton pump inhibitor. However, such triple therapy suffers from progressively decreased therapeutic efficacy due to the drug resistance and undesired killing of the commensal bacteria due to poor selectivity. Here, we report the development of antimicrobial polypeptide-based monotherapy, which can specifically kill H. pylori under acidic pH in the stomach while inducing minimal toxicity to commensal bacteria under physiological pH. Specifically, we designed a class of pH-sensitive, helix-coil conformation transitionable antimicrobial polypeptides (HCT-AMPs) (PGA)m-r-(PHLG-MHH)n, bearing randomly distributed negatively charged glutamic acid and positively charged poly(γ-6-N-(methyldihexylammonium)hexyl-l-glutamate) (PHLG-MHH) residues. The HCT-AMPs showed unappreciable toxicity at physiological pH when they adopted random coiled conformation. Under acidic condition in the stomach, they transformed to the helical structure and exhibited potent antibacterial activity against H. pylori, including clinically isolated drug-resistant strains. After oral gavage, the HCT-AMPs afforded comparable H. pylori killing efficacy to the triple-therapy approach while inducing minimal toxicity against normal tissues and commensal bacteria, in comparison with the remarkable killing of commensal bacteria by 65% and 86% in the ileal contents and feces, respectively, following triple therapy. This strategy renders an effective approach to specifically target and kill H. pylori in the stomach while not harming the commensal bacteria/normal tissues.

Hepatic perivascular epithelioid cell neoplasm: A clinical and pathological experience in diagnosis and treatment.

Hepatic perivascular epithelioid cell neoplasm (PEComa) is a rare type of neoplasm derived from mesenchymal tumors that is often misdiagnosed as hepatocellular carcinoma (HCC), hepatic hemangioma or other liver malignancies. The clinical and histological characteristics of PEComa have yet to be fully documented. To optimize the diagnosis and treatment of the disease, a retrospective analysis was performed to investigate the clinicopathological characteristics of 7 patients diagnosed with hepatic PEComa in the Sun Yat-Sen Memorial Hospital between January 2004 and December 2015. Briefly, all the patients lacked specific symptoms, and a serological examination provided no further useful information. Additionally, non-specific imaging manifestations were observed. Microscopically, detection of epithelioid or spindle-shaped cells with adipocytes was suggestive of the disease, and an analysis of biomarkers, including the monoclonal antibody HMB-45, the melanocytic differentiation marker, Melan-A, and smooth muscle α-actin (SMA), helped to confirm the diagnosis. Regarding the treatment, 6 patients (85.7%) received surgical resection procedures, and 1 patient (14.3%) was admitted for tumor arterial embolization and percutaneous microwave coagulation therapy. After a follow-up period of 12-20 months, no recurrence was observed. Taken together, hepatic PEComa should be suspended in patients with a liver tumor with asymptomatic manifestation and normal serological test results. In imaging studies, hepatic PEComa was able to mimic HCC, hepatic hemangioma and metastatic tumor, although the mass did not invade the adjacent organs and vessel. The definitive diagnosis was made on the basis of the typical morphological features and notable markers of the tumor tissue. It is recommended that patients with PEComa in a benign pattern deserve serial imaging follow-up, but surgery is indicated in patients suffering from large tumors (>5 cm), or progressive enlargement or malignant tendency.

1,25-Dihydroxyvitamin D3 alleviates salivary adenoid cystic carcinoma progression by suppressing GPX1 expression through the NF-κB pathway.

1,25-Dihydroxyvitamin D3 (1,25D3) is the active form of vitamin D with antineoplastic effects. The glutathione peroxidase-1 (GPX1) gene is associated with tumour progression. The present study aimed to explore the role of GPX1 in 1,25D3-mediated progression of salivary adenoid cystic carcinoma (SACC). Downregulating GPX1 expression inhibited SACC cell proliferation, chemoresistance, motility, and uPA secretion, but promoted apoptosis via the NF-κB pathway. Pre-processing 1,25D3 inhibited expression of NF-κB/GPX1/uPA, which subsequently suppressed cell motility and cisplatin-resistance in ACC-2 cells. In conclusion, 1,25D3 works as a modifier of NF-κB/GPX1/uPA expression, inhibiting cisplatin-resistance and cell invasive ability of SACC cells. The present study comprehensively elucidated the potential mechanism underlying the effects of vitamin D on chemoresistance and invasive potential in SACC.

Methylation of neurofilament light polypeptide promoter is associated with cell invasion and metastasis in NSCLC.

The role of NEFL in NSCLC remains largely unknown. Immunohistochemistry was performed to investigate the expression of NEFL in 108 lung cancer specimens. NEFL expression was associated with decreased lymph node metastases and favorable prognosis. Furthermore, real-time PCR and Western blot were used to investigate the expression of the NEFL gene in NSCLC cell lines. Subsequently, lentivirus-mediated RNA interference and overexpression were used to demonstrate that knocked-down of NEFL enhanced the invasion and migration of A549 and H460 NSCLC cells, whereas NEFL overexpression resulted in a suppression of the invasion and migration of GLC-82 and L78 cells in vitro. In addition, bisulfite sequence PCR assay demonstrated that NEFL downregulation was associated with promoter methylation, and NEFL expression was restored after treatment with 5-Aza-dC. Finally, we demonstrated that NEFL inhibited the NF-κB pathway, thereby suppressing the expression of uPA and decreasing NSCLC invasiveness and migration. Our studies suggest that NEFL methylation is a novel mechanism for NSCLC invasion and metastasis and that NEFL may represent a candidate biomarker for recurrence and survival in patients with NSCLC.

CPEB4 interacts with Vimentin and involves in progressive features and poor prognosis of patients with astrocytic tumors.

Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a regulator of gene transcription and has been reported to be associated with biological malignancy in cancers. However, it is unclear whether CPEB4 has any clinical significance in patients with astrocytic tumors, and mechanisms that CPEB4 contribute to progression of astrocytic tumors remain largely unknown. Here, correlation between CPEB4 expression and prognosis of patients with astrocytic tumors were explored by using qPCR, WB and IHC, and X-tile, SPSS software. Cell lines U251 MG and A172 were used to study CPEB4's function and mechanisms. Co-immunoprecipitation, mass spectrometry, immunofluorescent assay, and western blot were performed to observe the interaction between CPEB4 and Vimentin. CPEB4 mRNA and protein levels were markedly elevated in 12/12 astrocytic tumors in comparison to paratumor. High expression of CPEB4 was significantly correlated with clinical progressive futures and work as an independent adverse prognostic factor for overall survival of patients with astrocytic tumors (relative risk 4.5, 95 % CI 2.1-11.2, p = 0.001). Moreover, knockdown of CPEB4 in astrocytic tumor cells inhibited their proliferation ability , clonogenicity, and invasiveness. Five candidate proteins, GRP78, Mortalin, Keratin, Vimentin, and ß-actin, were identified, and the interaction between CPEB4 and Vimentin was finally confirmed. Downregulation of CPEB4 could reduce the protein expression of Vimentin. Our studies first validated that CPEB4 interacts with Vimentin and indicated that high CPEB4 expression in astrocytic tumors correlates closely with a clinically aggressive future, and that CPEB4 might represent a valuable prognostic marker for patients with astrocytic tumors.

The expression of MACC1 and its role in the proliferation and apoptosis of salivary adenoid cystic carcinoma.

BACKGROUND: The objective of this study was to investigate the relationship between metastasis-associated in colon cancer-1 and patient clinical characteristics. We also examined the role of metastasis-associated in colon cancer-1 in the proliferation and apoptosis in adenoid cystic carcinoma. MATERIAL AND METHODS: Metastasis-associated in colon cancer-1 expression was analysed in 65 paraffin-embedded tissue specimens of salivary adenoid cystic carcinoma and 25 adjacent non-cancerous tissues by immunohistochemistry (IHC). We used RNA interference technology to silence metastasis-associated in colon cancer-1 expression in ACCM cells. Cell Counting Kit-8 tests, transwell experiments and flow cytometry were used to test the proliferation, cisplatin resistance, migration, invasion and apoptosis of ACCM cells. RESULTS: Metastasis-associated in colon cancer-1 nuclear and cytoplasmic expression in salivary adenoid cystic carcinoma tissue was higher than in the adjacent normal salivary tissue. The expression level was closely associated with tumour histological grading, perineural invasion and surrounding tumour invasion. The downregulation of metastasis-associated in colon cancer-1 expression inhibited proliferation and induced apoptosis in ACCM cells. The knock-down of metastasis-associated in colon cancer-1 expression had no effect on migration, invasion and chemoresistance. CONCLUSIONS: Metastasis-associated in colon cancer-1 may have an important role in tumour development in adenoid cystic carcinoma. Metastasis-associated in colon cancer-1 is a potential biomarker for adenoid cystic carcinoma.

Downregulation of MACC1 inhibits invasion, migration and proliferation, attenuates cisplatin resistance and induces apoptosis in tongue squamous cell carcinoma.

The aim of the present study was to investigate the expression and function of metastasis-associated in colon cancer 1 (MACC1) in tongue squamous cell carcinoma (TSCC) and its relationship with the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) (CD147). Levels of MACC1 and EMMPRIN expression were analyzed in 65 paraffin­embedded tissue specimens of TSCC and in the adjacent non-cancerous tissues using immunohistochemistry (IHC). MACC1 expression was highly associated with lymphatic metastasis and EMMPRIN expression. Overexpression of MACC1 was significantly correlated with poor overall patient survival. A small interfering RNA (siRNA) was delivered into TSCCA cells to downregulate MACC1 expression. The CCK-8 assay showed that TSCCA cell proliferation was markedly reduced and that cisplatin resistance was attenuated. The suppression of MACC1 promoted the apoptosis of the TSCCA cell line. A Transwell experiment demonstrated that the migration and invasion abilities of the TSCCA cells were extremely downregulated. An ELISA experiment and western blotting revealed that the secretion of urokinase-type plasminogen activator system (uPA) in the supernatant of the culture medium and uPA expression were significantly reduced. Experiments revealed that the secretion of metalloproteinase 2 (MMP2) in the supernatant of the culture medium and MMP2 expression were not affected. MACC1 may serve as a novel biomarker and therapeutic target for TSCC.

Expression of beclin 1 in non-small cell lung cancer: an immunohistochemical study.

BACKGROUND: Cigarette smoking causes a variety of adverse human health effects, including lung cancer. The molecular events associated with smoke-induced carcinogenesis are thought to be related in part to autophagy. Beclin 1 is an important autophagy-related protein involved in cell death and cell survival. AIM: The purpose of this investigation was to determine the beclin 1 protein and its association with cigarette smoke and the mutation of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC). MATERIAL AND METHODOLOGY: Our study included 108 cases of non-small cell lung cancer who were admitted in our hospital. The beclin 1 protein was detected by immunohistochemistry and EGFR mutation by direct sequencing. RESULTS: Beclin 1 expression could be detected in 15 (13.9%) of 108 specimens. These studies investigated that beclin 1 expression was associated with heavy smoking, the gender and the histological type of NSCLC (P = 0.023, 0.035 and 0.039). No association of beclin 1 with EGFR mutation was found (P > 0.05). CONCLUSION: The results from these experiments indicate that heavy smoking may induce the beclin 1 protein in NSCLC.