Identification of Aging and Young Subtypes for Predicting Colorectal Cancer Prognosis and Immunotherapy Responses.

Colorectal cancer (CRC) is critically related to aging and severely threatens human lives. To better explore the effects of aging on CRC progression and therapy outcome, a reliable aging subtypes identification of CRC is urgently desired. Here, 28 aging-related genes associated with the CRC prognosis were selected by univariate Cox analyses. Based on these 28 genes, CRC patients were divided into the aging subtype and young subtype by non-negative matrix factorization clustering. Aging subtype and young subtype of CRC were identified with distinct molecular features and clinical prognosis. The aging subtype was characterized by upregulation of senescence-associated secretory phenotype, higher frequencies of TP53 and immune checkpoint molecules, and high sensitivity to protein kinase and angiogenesis inhibitors. Furthermore, 14 genes were selected by LASSO penalized Cox regression analyses for aging-related risk signature construction. The constructed aging risk signature exhibited good prediction and the nomogram showed robust discrimination power over the traditional CRC staging system. In conclusion, this study successfully established aging subtype and young subtype of CRC, which is helpful to identify patients with aging characteristics to evaluate prognosis and treatment outcomes. Introducing aging-based subtypes into clinical concern and patient prognostication provides new opportunities for personalized CRC treatment.

Optical properties and application potential of a hybrid cavity compound grating structure.

In this paper, we propose a new type of metal-insulator-metal (MIM) hybrid cavity compound grating micro-structure array, which can achieve dual narrowband super-absorption in the near-infrared window. The thin plasmonic microstructure effectively modulates coupling and hybridization effects between surface plasmon polaritons of different transmission resonance cavities to form designable dual narrowband resonance states to achieve near-infrared operation proving manipulation of the optical characteristics in the near-infrared light field. Furthermore, we conduct an in-depth theoretical exploration of the structure's unique properties, such as its high-quality factor, low noise, super-absorption, precise control, and the physical mechanism of its excellent performance in ambient refractive index sensing and detection. This study provides developmental insights for the miniaturization, easy modulation, and multi-function development of surface plasmon superabsorbers while broadening their application in near-infrared environment refractive index detection. The proposed microstructure is also suitable for integration with optical elements.

MYBL2 regulates de novo purine synthesis by transcriptionally activating IMPDH1 in hepatocellular carcinoma cells.

BACKGROUND: Metabolic reprogramming is a hallmark of cancer, alteration of nucleotide metabolism of hepatocellular carcinoma (HCC) is not well-understood. MYBL2 regulates cell cycle progression and hepatocarcinogenesis, its role in metabolic regulation remains elusive. PATIENTS AND METHODS: Copy number, mRNA and protein level of MYBL2 and IMPDH1 were analyzed in HCC, and correlated with patient survival. Chromatin Immunoprecipitation sequencing (Chip-seq) and Chromatin Immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR) were used to explore the relationship between MYBL2 and IMPDH1. Metabolomics were used to analyze how MYBL2 affected purine metabolism. The regulating effect of MYBL2 in HCC was further validated in vivo using xenograft models. RESULTS: The Results showed that copy-number alterations of MYBL2 occur in about 10% of human HCC. Expression of MYBL2, IMPDH1, or combination of both were significantly upregulated and associated with poor prognosis in HCC. Correlation, ChIP-seq and ChIP-qPCR analysis revealed that MYBL2 activates transcription of IMPDH1, while knock-out of MYBL2 retarded IMPDH1 expression and inhibited proliferation of HCC cells. Metabolomic analysis post knocking-out of MYBL2 demonstrated that it was essential in de novo purine synthesis, especially guanine nucleotides. In vivo analysis using xenograft tumors also revealed MYBL2 regulated purine synthesis by regulating IMPDH1, and thus, influencing tumor progression. CONCLUSION: MYBL2 is a key regulator of purine synthesis and promotes HCC progression by transcriptionally activating IMPDH1, it could be a potential candidate for targeted therapy for HCC.

Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 cooperates with enhancer of zeste homolog 2 to promote hepatocellular carcinoma development by modulating the microRNA-22/Snail family transcriptional repressor 1 axis.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an oncogenic long noncoding RNA that has been found to promote carcinogenesis and metastasis in many tumors. However, the underlying role of MALAT1 in the progression and metastasis of hepatocellular carcinoma (HCC) remains unclear. In this study, aberrantly elevated levels of MALAT1 were detected in both HCC specimens and cell lines. We found that knockdown of MALAT1 caused retardation in proliferation, migration, and invasion both in vivo and in vitro. Mechanistic investigations showed that Snail family transcriptional repressor 1 (SNAI1) is a direct target of microRNA (miR)-22 and that MALAT1 modulates SNAI1 expression by acting as a competing endogenous RNA for miR-22. Inhibition of miR-22 restored SNAI1 expression suppressed by MALAT1 knockdown. Furthermore, MALAT1 facilitated the enrichment of enhancer of zeste homolog 2 (EZH2) at the promoter region of miR-22 and E-cadherin, which was repressed by MALAT1 knockdown. Cooperating with EZH2, MALAT1 positively regulated SNAI1 by repressing miR-22 and inhibiting E-cadherin expression, playing a vital role in epithelial to mesenchymal transition. In conclusion, our results reveal a mechanism by which MALAT1 promotes HCC progression and provides a potential target for HCC therapy.

Linewidth reduction effect of a cavity-coupled dual-passband plasmonic filter.

We propose a novel cavity-coupled MIM nano-hole array structure that exhibits a tunable dual passband in the near-infrared regime. When compared with the traditional single metal film, the designed structure provides a coupling effect between Gspp and SPP to significantly reduce the linewidths of the two transmission peaks. We also reveal the physical origin of the positive and negative influence of the cavity effect on the transmission of high-frequency and low-frequency peaks. This work supplies a new modulation theory for plasmonic devices based on the EOT phenomenon and has a wide application prospect in the fields of infrared sensor, plasmonic filter, and hyperspectral imaging.

Primary Gastrointestinal Stromal Tumor Mimicking as Gynecologic Mass: Characteristics, Management, and Prognosis.

BACKGROUND: Primary gastrointestinal stromal tumor (GIST)-mimicking gynecologic masses are easily misdiagnosed. This study aimed to investigate the clinicopathological features, management, and prognosis of primary GIST mimicking as gynecologic mass. METHODS: Clinicopathological and survival data of GIST mimicking as gynecologic mass admitted to our center from January 2005 to December 2017 were retrospectively analyzed. RESULTS: Thirty-eight patients were included. The most common primary tumor site was the jejunoileum (n = 33, 86.9%), and 33 patients (86.9%) were classified as high recurrence risk. The short-term outcomes of operative incision length (P = 0.004), time to gas passage (P = 0.002), and hospital stay (P = 0.012) with laparoscopy-assisted resection were significantly shorter than those with open resection, showing no significant differences of long-term outcomes. With a median follow-up of 56 mo for 31 patients (81.6%), 18 (58.1%) received adjuvant therapy with imatinib. The 5-year disease-free survival and disease-specific survival of pelvic high-risk GIST was 37.0% and 48.3%, respectively; both were significantly lower than those of the other female high-risk group (both P < 0.05). CONCLUSIONS: GIST mimicking as gynecologic mass is not uncommon, most originate from the jejunoileum and have a high risk of recurrence. Laparoscopy-assisted resection may be preferable for more favorable short-term outcomes. Compared with the other female high-risk GIST, pelvic high-risk GIST has a significantly worse prognosis; a longer duration of adjuvant therapy with imatinib than recommended may be beneficial.

The aggressive surgical treatment and outcome of a colon cancer patient with COVID-19 in Wuhan, China.

BACKGROUND: Cancer patients are at increased risk of novel coronavirus disease 2019 (COVID-19). Currently, surgeries for cancer patients with COVID-19 are generally suggested to be properly delayed. CASE PRESENTATION: We presented a 69-year-old Chinese female colon cancer patient with COVID-19, the first case accepted the surgical treatment during the pandemic in China. The patient developed a fever on January 28, 2020. After treatments with Ceftriaxone and Abidol, her fever was not moderated yet. A repeat chest computed tomography (CT) scan showed significantly exacerbated infectious lesions with a positive result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid. An abdomen CT scan indicated the tumor of ascending colon with local wrapped changes. She was diagnosed with 'Severe novel coronavirus pneumonia' and 'Incomplete bowel obstruction: Colon cancer?'. After actively anti-inflammatory and anti-viral therapies, a right colectomy with lymph node dissection was performed on March 11, followed by a pathological examination. The patient successfully recovered from COVID-19 pneumonia and incomplete bowel obstruction after surgery without any postoperative related complications and was discharged on the 9th day after operation. Significant degeneration, necrosis and slough of focal intestinal and colonic mucosal epithelial cells were observed under microscope. No surgeons, nurses or anesthetists in our team were infected with SARS-CoV-2. CONCLUSIONS: It is meaningful and imperative to share our experience of protecting health care personnels from SARS-CoV-2 infection and providing references for optimizing treatment of cancer patients, at least for the operative intervention with absolute necessity or surgical emergency, during the outbreak of COVID-19.

Cavity-driven hybrid plasmonic ultra-narrow bandpass filter.

We propose a novel compound grating structure that exhibits a tunable ultra-narrowband transmission in the near infrared regime. The thin microstructure can realize a steep wave form through a Fano-like resonance by coupling different propagation-type SPP modes and with a narrow line width formed by the energy band gap. Additionally, the out-of-band suppression is remarkably enhanced. It effectively solves the constraint relationship between high transmittance, narrow line width, and weak side peak of the plasmonic filter, and the structure is suitable for integration with detectors in the near infrared regime.

Oncological consequence of emergent resection of perforated colon cancer with complete obstruction after stent insertion as a bridge to surgery.

PURPOSE: Colonic perforation is a life-threatening complication after colonic stent insertion as a bridge to surgery for acute obstruction caused by colorectal cancer. The oncological consequence of colonic perforation after emergent surgical intervention was unknown. The aim of this short communication was to investigate whether or not the perforation and emergent surgery had obviously impact on the peritoneal recurrence and long-term survival of patients. METHODS: Data of the patients who underwent colorectal stenting as a bridge to surgery in 5 years from 2012 to 2017 was collected by the Endoscopical Surgery Group of Hubei. The perforated cases treated by emergent operation were retrospectively analyzed. RESULTS: During 5 years from 2012 to 2017, 116 cases of colorectal stenting as a bridge to surgery had been performed, and 7 patients had perforation after stent placement and treated by emergent surgery, including 1 case of synchronic liver metastasis treated by one-stage metastasectomy. One of the 7 patients died of septic shock after operation, and the remaining patients were followed up for 6-60 months. There was no evidence of abdominal implantation or extra-abdominal metastasis. CONCLUSION: This small case series implicated that colonic perforation after stent insertion for malignant colorectal obstruction treated by emergent surgery might not obviously increase the peritoneal implantation and metastasis.

Secreted AGR2 promotes invasion of colorectal cancer cells via Wnt11-mediated non-canonical Wnt signaling.

Human anterior gradient-2 (AGR2), a member of protein disulfide isomerase (PDI) family, is present in both intracellular and extracellular compartments. Although AGR2 is overexpressed in various human cancers and reported to promote aggressive tumor features, little is known regarding AGR2's extracellular functions during tumorigenesis. Here, we demonstrate that secreted AGR2 promotes cell migration and metastasis of colorectal cancer (CRC) in vitro and in vivo. Mechanistically, secreted AGR2 elevated Wnt11 expression, triggering non-canonical Wnt signaling: the Ca2+/Calmodulin-dependent protein kinase II (CaMKII) and c-jun amino-terminal kinase (JNK) pathways. Knockdown of Wnt11 or pretreatment with CaMKII and JNK inhibitors reversed the secreted AGR2's migration-promoting effect. Further studies revealed that AGR2 antagonized canonical Wnt/ß-catenin signaling via activating CaMKII. Collectively, our study uncovers a critical role of Wnt11-mediated non-canonical Wnt signaling (CaMKII and JNK pathways) in secreted AGR2's promoted migration of CRC cells. These results raise the possibility that secreted AGR2 may be a potential therapeutic target towards inhibiting CRC metastasis.

Comparative efficacy and tolerability of antiemetic prophylaxis for adult highly emetogenic chemotherapy: A network meta-analysis of 143 randomized controlled trials.

Chemotherapy-induced nausea and vomiting (CINV) is one of the commonest side-effects among cancer patients. However, there is lacking of hierarchical evidences comparing different antiemetics against highly emetogenic chemotherapy. Therefore, we conducted a network meta-analysis to investigate their comparative efficacy and tolerability. Randomized controlled trials that compared different antiemetic categories for adult highly emetogenic chemotherapy were included after searching PubMed, Web of Science, Embase and Cochrane Central. Acute-phase no emesis and no nausea were identified as primary endpoints. We made pairwise and hierarchical calculations by random-effects model. Effect sizes were presented by odds ratio and 95% confidential interval. Subgroup analysis was additionally performed. 143 randomized trials were included into pooled analysis, containing 22,776 patients and 18 antiemetic categories. 5-HT3 RA plus corticosteroid plus NK-1 RA plus other (5CNO) displayed best protection against both acute emesis (SUCRA: 99.7%) and nausea (95.6%). 5CNO (99.7%) and 5-HT3 RA plus corticosteroid plus other (5CO, 85.3%) topped subgroup hierarchies for no-naivety and anthracycline plus cyclophosphamide (AC)-based studies. On the other hand, 5-HT3 RA plus dopamine RA plus other (5DO) may be best fit for delayed emesis (92.0%) and nausea (92.7%). Subgroups featuring no-naivety and AC-based trials preferred 5DO (91.9%) and 5CN (88.6%), respectively. In addition, dopamine RA plus other (DO) had the lowest incidence of TRAE in most circumstances, except for AC-based subgroup where corticosteroid plus dopamine RA plus other (CDO) preponderated (69.2%). 5CNO and 5DO should be considered as first-line regimens against highly emetogenic chemotherapy induced acute and delayed CINV, respectively.

One-Pot Multicomponent Synthesis of Glycopolymers through a Combination of Host-Guest Interaction, Thiol-ene, and Copper-Catalyzed Click Reaction in Water.

There is a common phenomenon that the heterogeneity of natural oligosaccharides contains various sugar units, which can be used to enhance affinity and selectivity toward a specific receptor, so the synthesis of heterogeneous glycopolymers is always an important issue in the glycopolymer field. Herein, this study conducts a one-pot method to prepare polyrotaxane-based heteroglycopolymers anchored with different sugar units and fluorescent moieties via the combination of host-guest interaction, thiol-ene, and copper-catalyzed click chemistry in water. Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, gel permeation chromatography, X-ray diffraction, and Ellman's assay test are used in the paper to characterize the compounds. Quartz crystal microbalance-dissipation (QCD-D) experiments and bacterial adhesion assay are utilized to study the interactions of polyrotaxane-based heteroglycopolymers with Con A and Escherichia coli. The results reveal that polyrotaxanes (PRs) with mannose and glucose present better specificity toward Con A and E. coli than PRs with glucose due to synergistic effects.

Technical Standardization of Laparoscopic Left Hemicolectomy - Video Vignette.

Large multicentre trials have shown good safety profiles and low complication rates for laparoscopic management of left-sided colon cancer [1-3]. However, there are a wide range of options and variations in technique, which extend the learning curve of trainee surgeons. Here we provide a video to demonstrate a standardized operative technique simplified into 'one plane, two points and three lines' when applied to laparoscopic left hemicolectomy. This article is protected by copyright. All rights reserved.

Comparison of infrared canopy temperature in a rubber plantation and tropical rain forest.

Canopy temperature is a result of the canopy energy balance and is driven by climate conditions, plant architecture, and plant-controlled transpiration. Here, we evaluated canopy temperature in a rubber plantation (RP) and tropical rainforest (TR) in Xishuangbanna, southwestern China. An infrared temperature sensor was installed at each site to measure canopy temperature. In the dry season, the maximum differences (Tc - Ta) between canopy temperature (Tc) and air temperature (Ta) in the RP and TR were 2.6 and 0.1 K, respectively. In the rainy season, the maximum (Tc - Ta) values in the RP and TR were 1.0 and -1.1 K, respectively. There were consistent differences between the two forests, with the RP having higher (Tc - Ta) than the TR throughout the entire year. Infrared measurements of Tc can be used to calculate canopy stomatal conductance in both forests. The difference in (Tc - Ta) at three gc levels with increasing direct radiation in the RP was larger than in the TR, indicating that change in (Tc - Ta) in the RP was relatively sensitive to the degree of stomatal closure.

Clinicopathologic features and prognosis of primary gastrointestinal stromal tumor patients under 35 years of age: A 10-year retrospective study.

OBJECTIVES: To investigate gastrointestinal stromal tumor (GIST) clinicopathologic characteristics in young adults. METHODS: Clinicopathologic data from GIST patients under 35 years diagnosed at our hospital from January 2005 to December 2014 were retrospectively collected. RESULTS: Thirty-one (5.3%, 31/585) patients were included; 17 (54.8%) were female. The most common presentation and primary tumor site were gastrointestinal bleeding (n = 18, 58.1%) and the small intestine (n = 13, 41.9%), respectively. Fifteen (48.4%) GISTs were classified as having a high relapse risk; two (6.4%), intermediate; nine (29.0%), low; and five (16.1%), very low. All patients underwent tumor resection. With a median follow-up of 51 months for 20 (64.5%) patients, 12 (60%) were given imatinib methylate as adjuvant therapy. One (5%) patient died of peritoneal GIST dissemination, four (20%) developed abdominal recurrences, two (10%) had hepatic metastasis, and thirteen (65%) were disease free. The 5-year disease-free survival rate was 51.2%. CONCLUSIONS: GISTs rarely occur in young adults. The most common location is the small intestine. A slight female predominance was observed in the current study. Adjuvant therapy longer than the recommended duration may be beneficial for GISTs with a high relapse risk. Combined targeted therapy and surgery is appropriate for recurrent and metastatic GISTs in select patients. J. Surg. Oncol. 2016;114:977-981. © 2016 Wiley Periodicals, Inc.

Sodium phosphate versus polyethylene glycol for colonoscopy bowel preparation: an updated meta-analysis of randomized controlled trials.

BACKGROUND: Adequate bowel cleansing is of great importance for a high-quality colonoscopy examination. Nevertheless, whether sodium phosphate or polyethylene glycol is a gold standard agent for bowel preparation is still under debate. In consideration of the clinical needs, we thus performed an updated meta-analysis of randomized controlled trials concerning the comparison between both regimens. The efficacy, safety and acceptability of each regimen are major indicators to measure and appraise. METHODS: By searching PubMed, EMBASE, Web of Science and Cochrane Library databases, 15 original trials published from 2000 to 2014 were included as eligible studies. We carried out data extraction and subsequent pooling analysis for each indicator in a standard manner. Sensitivity analysis was performed by elimination of low-quality trials, while a funnel plot and Egger's test were employed to analyze the publication bias across studies. RESULTS: Our pooling analysis revealed that patients undergoing sodium phosphate as a cleansing agent displayed better acceptability, compliance, cleansing scores, preparation taste, polyp detection rate and less adverse effects including nausea, vomiting and abdominal pain (P < 0.05). In terms of procedure time, adequate preparation rate and electrolyte concentration, there was no significant difference between both regimens (P > 0.05). The pooling analysis offered stable conclusions which were verified by our sensitivity analysis. There was no publication bias across studies as a symmetric funnel plot was demonstrated and the result of Egger's test was P = 0.56. CONCLUSIONS: Regarding preparation efficacy, safety and acceptability, sodium phosphate was a better agent than polyethylene glycol for colonoscopy bowel cleansing, with its advantages of higher efficacy, better tolerability and acceptability as well as comparable safety.

Syntheses and characterization of non-bisphosphonate quinoline derivatives as new FPPS inhibitors.

BACKGROUND: Farnesyl pyrophosphate synthase (FPPS) is a key regulatory enzyme in the biosynthesis of cholesterol and in the post-translational modification of signaling proteins. It has been reported that non-bisphosphonate FPPS inhibitors targeting its allosteric binding pocket are potentially important for the development of promising anti-cancer drugs. METHODS: The following methods were used: organic syntheses of non-bisphosphonate quinoline derivatives, enzyme inhibition studies, fluorescence titration assays, synergistic effect studies of quinoline derivatives with zoledronate, ITC studies for the binding of FPPS with quinoline derivatives, NMR-based HAP binding assays, molecular modeling studies, fluorescence imaging assay and MTT assays. RESULTS: We report our syntheses of a series of quinoline derivatives as new FPPS inhibitors possibly targeting the allosteric site of the enzyme. Compound 6b showed potent inhibition to FPPS without significant hydroxyapatite binding affinity. The compound showed synergistic inhibitory effect with active-site inhibitor zoledronate. ITC experiment confirmed the good binding effect of compound 6b to FPPS, and further indicated the binding ratio of 1:1. Molecular modeling studies showed that 6b could possibly bind to the allosteric binding pocket of the enzyme. The fluorescence microscopy indicated that these compounds could get into cancer cells. CONCLUSIONS: Our results showed that quinoline derivative 6b could become a new lead compound for further optimization for cancer treatment. GENERAL SIGNIFICANCE: The traditional FPPS active-site inhibitors bisphosphonates show poor membrane permeability to tumor cells, due to their strong polarity. The development of new non-bisphosphonate FPPS inhibitors with good cell membrane permeability is potentially important.

Synthesis and characterization of 1H-phenanthro[9,10-d]imidazole derivatives as multifunctional agents for treatment of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder that is characterized by dementia, cognitive impairment, and memory loss. Diverse factors are related to the development of AD, such as increased level of ß-amyloid (Aß), acetylcholine, metal ion deregulation, hyperphosphorylated tau protein, and oxidative stress. METHODS: The following methods were used: organic syntheses of 1H-phenanthro[9,10-d]imidazole derivatives, inhibition of self-mediated and metal-induced Aß1-42 aggregation, inhibition studies for acetylcholinesterase and butyrylcholinesterase, anti-oxidation activity studies, CD, MTT assay, transmission electron microscopy, dot plot assay, gel electrophoresis, Western blot, and molecular docking studies. RESULTS: We synthesized and characterized a new type of 1H-phenanthro[9,10-d]imidazole derivatives as multifunctional agents for AD treatment. Our results showed that most of these derivatives exhibited strong Aß aggregation inhibitory activity. Compound 9g had 74% Aß1-42 aggregation inhibitory effect at 10µM concentration with its IC50 value of 6.5µM for self-induced Aß1-42 aggregation. This compound also showed good inhibition of metal-mediated (Cu(2+) and Fe(2+)) and acetylcholinesterase-induced Aß1-42 aggregation, as indicated by using thioflavin T assay, transmission electron microscopy, gel electrophoresis, and Western blot. Besides, compound 9g exhibited cholinesterase inhibitory activity, with its IC50 values of 0.86µM and 0.51µM for acetylcholinesterase and butyrylcholinesterase, respectively. In addition, compound 9g showed good anti-oxidation effect with oxygen radical absorbance capacity (ORAC) value of 2.29. CONCLUSIONS: Compound 9g was found to be a potent multi-target-directed agent for Alzheimer's disease. GENERAL SIGNIFICANCE: Compound 9g could become a lead compound for further development as a multi-target-directed agent for AD treatment.

Multi-target-directed design, syntheses, and characterization of fluorescent bisphosphonate derivatives as multifunctional enzyme inhibitors in mevalonate pathway.

BACKGROUND: Mevalonate pathway is an important cellular metabolic pathway present in all higher eukaryotes and many bacteria. Four enzymes in mevalonate pathway, including MVK, PMK, MDD, and FPPS, play important regulatory roles in cholesterol biosynthesis and cell proliferation. METHODS: The following methods were used: cloning, expression and purification of enzymes in mevalonate pathway, organic syntheses of multifunctional enzyme inhibitors, measurement of their IC50 values for above four enzymes, kinetic studies of enzyme inhibitions, molecular modeling studies, cell viability tests, and fluorescence microscopy. RESULTS AND CONCLUSIONS: We report our multi-target-directed design, syntheses, and characterization of two blue fluorescent bisphosphonate derivatives compounds 15 and 16 as multifunctional enzyme inhibitors in mevalonate pathway. These two compounds had good inhibition to all these four enzymes with their IC50 values at nanomolar to micromolar range. Kinetic and molecular modeling studies showed that these two compounds could bind to the active sites of all these four enzymes. The fluorescence microscopy indicated that these two compounds could easily get into cancer cells. GENERAL SIGNIFICANCE: Multifunctional enzyme inhibitors are generally more effective than single enzyme inhibitors, with fewer side effects. Our results showed that these multifunctional inhibitors could become lead compounds for further development for the treatment of soft-tissue tumors and hypercholesteremia.

Targeting eIF5A2 reduces invasion and reverses chemoresistance in SCC-9 cells in vitro.

BACKGROUND AND AIMS: Eukaryotic translation initiation factor 5A2 (EIF5A2) has been reported to be involved in metastasis and chemotherapy resistance in many human cancers. However, the effect and mechanism of EIF5A2 in oral cancer cells are unknown. Here, we investigated the effects of targeting EIF5A2 on chemotherapy resistance in oral cancer cells in vitro. METHODS: By using a lentiviral system, we investigated the effects of targeting EIF5A2 on the invasion, migration, growth, and chemosensitivity of SCC-9 cells to CDDP in vitro. Through the method of gene intervention, we explore the role of pro-apoptotic Bim and epithelial and mesenchymal marker E-cadherin protein in this process and the regulation of EIF5A2 on Bim and E-cadherin. RESULTS: Targeting EIF5A2 reduces invasion and migration in SCC-9 cells partly through upregulation of E-cadherin expression; Targeting EIF5A2 promotes cell apoptosis and inhibits cell survival as well as increasing chemosensitivity in SCC-9 cells through upregulation of Bim expression. CONCLUSION: EIF5A2 may be a novel potential therapeutic target for oral cancer by upregulation of Bim and E-cadherin.