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Tumor-associated macrophages (TAMs), are crucial for the survival and development of tumor cells. Heat shock factor 1 (HSF1) is a potent, complex carcinogenesis modulator, and esophageal cancer (EC) patients have a bad prognosis when HSF1 is highly expressed. HSF1's clinical importance and biological role in TAMs are still unknown.The HSF1 expression profile and patient survival information were analyzed from the TCGA database. The infiltration of different types of immune cells in EC was evaluated based on HSF1 gene expression by Sangerbox 3.0. Immunochemistry was employed to assess HSF1 protein expression in 134 individuals with esophageal squamous cell carcinoma (ESCC), proceeded by association with clinicopathological variables. The role of macrophage-driven HSF1 were observed using HSF1-knockdown THP1 cells.High level of HSF1 have a poorer prognosis in individuals with EC. The expressing level of HSF1 was positively related to infiltration of M2 macrophages (P 0.05). The expression of HSF1 in macrophages was an independent factor for DFS (P = 0.002) and OS (P = 0.002) in ESCC cases. HSF1 was up-regulated in IL-4 stimulation THP1 cells in a time-dependent manner. Under the heat stimulation condition, THP1-derived macrophages were more sensitive than tumor cells. Compared to IL-4 induced-THP1 cells control, the HSF1 knockdown in THP1 cell inhibited the growth and proliferation of ESCC cells.The up-regulation of HSF1 was more rapid and could affect the proliferation of tumor cells in IL4-induced macrophages. The expression of HSF1 in TAMs can also serve as a marker for ESCC prognosis.

Dissolving microneedle (DMN) patches are emerging as a minimally invasive and efficient transdermal drug delivery platform. Generally, noncrystalline, water-soluble, and high-molecular-weight polymers are employed in DMNs because their sufficient intermolecular interactions can endow the DMNs with necessary mechanical strength and toughness. However, high viscosity and heavy chain entanglement of polymer solutions greatly hinder processing and dissolution of polymeric DMNs. Here, a strong and tough supramolecular DMN patch made of highly water-soluble cyclodextrin (CD) derivatives is described. Due to the synergy of multiple supramolecular interactions, the CD DMN patch exhibits robust mechanical strength outperforming the state-of-the-art polymeric DMNs. The CD DMN displays ultrafast dissolution (30 s) in skin models by virtue of the dynamic and weak noncovalent bonds, which also enables the CD DMN and its payloads to diffuse rapidly into the deep skin layer. Moreover, the unique supramolecular structure of CD allows the CD DMNs to load not only hydrophilic drugs (e.g., rhodamine B as a model) but also hydrophobic model drugs (e.g., ibuprofen). As a proof-of-concept, CD DMNs loading ibuprofen show a rapid onset of therapeutic action in a xylene-induced acute inflammation model in mice. This work opens a new avenue for the development of mechanically robust supramolecular DMNs and broadens the applications of supramolecular materials.

Background: The genomic spectrum of biliary tract carcinoma (BTC) has been characterized and is associated with distinct anatomic and etiologic subtypes, yet limited studies have linked genomic alterations with personalized therapies in BTC patients. Methods: This study analyzed 803 patients with BTC:164 with gallbladder cancer, 475 with intrahepatic cholangiocarcinoma (ICC) and 164 with extrahepatic cholangiocarcinoma. We determined genomic alterations, mutational signatures related to etiology and histopathology and prognostic biomarkers. Personalized targeted therapies for patients harboring potentially actionable targets (PATs) were investigated. Results: The median tumor mutation burden (TMB) was 1.23 Mut/Mb, with 4.1% of patients having hypermutated BTCs. Unlike the results obtained from the Western population, the most frequently altered cancer-related genes in our cohort included TP53 (53%), KRAS (26%), ARID1A (18%), LRP1B (14%) and CDKN2A (14%). Germline mutations occurred mostly in DNA damage repair genes. Notably, 35.8% of the ICCs harbored aristolochic acid related signatures and an elevated TMB. TP53 and KRAS mutations and amplified 7q31.2 were demonstrated to negatively affect patient prognosis. Moreover, 19 genes were proposed to be PATs in BTCs, with 25.4% of patients harboring these PATs. Forty-six patients received PAT-matched targeted therapies, achieving a 26.1% objective response rate; the median progression-free survival (PFS) was 5.0 months, with 56.8% of patients obtaining PFS benefits. Conclusions: Extensive genomic diversity and heterogeneity were observed among BTC patients, with contributions according to potential etiology exposures, anatomical subtypes and clinicopathological characteristics. We also demonstrated that patients with refractory BTCs who have PATs can derive considerable benefit from receiving a matched therapy, initiating further prospective clinical trials guided by molecular profiling among this aggressive cancer.

Angiogenesis plays an important role in the occurrence and development of skin tumors and vascular anomalies (VAs). Many drugs have been adopted for the inhibition of angiogenesis, among which rapamycin (RAPA) possesses good application prospects. However, the clinical potential of RAPA for VAs is limited by its poor solubility, low bioavailability, and high cytotoxicity. To extend its application prospect for VAs treatment, in this study, we develop RAPA-loaded dissolving polymeric microneedles (RAPA DMNs) made of polyvinylpyrrolidone (PVP) due to its excellent solubilizing ability. RAPA DMNs are shown to have sufficient mechanical strength to overcome the skin barrier of the stratum corneum and could deliver RAPA to a depth of 200 μm. The microneedle shafts completely dissolve and 80% of the drug could be released within 10 min after insertion ex vivo. The DMNs-penetrated mice skin could repair itself within 4 h after the application of RAPA DMNs. RAPA DMNs also show good anti-angiogenic effect by inhibiting the growth of human umbilical vein endothelial cells (HUVECs) and decreasing the secretion of vascular endothelial growth factor (VEGF). Therefore, RAPA DMNs promisingly provide a safe and efficient approach for VAs treatment.

BackgroundThe gut microbiome is associated with the response to immunotherapy for different cancers. However, the impact of the gut microbiome on hepatobiliary cancers receiving immunotherapy remains unknown. This study aims to investigate the relationship between the gut microbiome and the clinical response to anti-programmed cell death protein 1 (PD-1) immunotherapy in patients with advanced hepatobiliary cancers.MethodsPatients with unresectable hepatocellular carcinoma or advanced biliary tract cancers who have progressed from first-line chemotherapy (gemcitabine plus cisplatin) were enrolled. Fresh stool samples were collected before and during anti-PD-1 treatment and analyzed with metagenomic sequencing. Significantly differentially enriched taxa and prognosis associated taxa were identified. The Kyoto Encyclopedia of Genes and Genomes database and MetaCyc database were further applied to annotate the differentially enriched taxa to explore the potential mechanism of the gut microbiome influencing cancer immunotherapy.ResultsIn total, 65 patients with advanced hepatobiliary cancers receiving anti-PD-1 treatment were included in this study. Seventy-four taxa were significantly enriched in the clinical benefit response (CBR) group and 40 taxa were significantly enriched in the non-clinical benefit (NCB) group. Among these taxa, patients with higher abundance of Lachnospiraceae bacterium-GAM79 and Alistipes sp Marseille-P5997, which were significantly enriched in the CBR group, achieved longer progression-free survival (PFS) and overall survival (OS) than patients with lower abundance. Higher abundance of Ruminococcus calidus and Erysipelotichaceae bacterium-GAM147 enriched in the CBR group was also observed in patients with better PFS. In contrast, worse PFS and OS were found in patients with higher abundance of Veillonellaceae, which was significantly enriched in the NCB group. Functional annotation indicated that the taxa enriched in the CBR group were associated with energy metabolism while the taxa enriched in the NCB group were associated with amino acid metabolism, which may modulate the clinical response to immunotherapy in hepatobiliary cancers. In addition, immunotherapy-related adverse events were affected by the gut microbiome diversity and relative abundance.ConclusionsWe demonstrate that the gut microbiome is associated with the clinical response to anti-PD-1 immunotherapy in patients with hepatobiliary cancers. Taxonomic signatures enriched in responders are effective biomarkers to predict the clinical response and survival benefit of immunotherapy, which might provide a new therapeutic target to modulate the response to cancer immunotherapy.

BackgroundHepatocellular carcinoma (HCC) has a high risk of recurrence after surgical resection, particularly among patients with multifocal HCC. Genomic heterogeneity contributes to the early recurrence. Few studies focus on targeted next-generation sequencing (tNGS) to depict mutational footprints of heterogeneous multifocal HCC.MethodsWe conducted tNGS with an ultra-deep depth on 31 spatially distinct regions from 11 resected multifocal HCC samples. Matched preoperative peripheral circulating-free DNA (cfDNA) were simultaneously collected. Genomic alterations were identified and compared to depict the heterogeneity of multifocal HCC.ResultsWidespread intertumoral heterogeneity of driver mutations was observed in different subfoci of multifocal HCC. The identified somatic mutations were defined as truncal drivers or branchy drivers according to the phylogenetic reconstruction. TP53 and TERT were the most commonly altered truncal drivers in multifocal HCC, while the most frequently mutated branchy driver was TSC2. HCC patients with a higher level of intertumoral heterogeneity, defined by the ratio of truncal drivers less than 50%, had a shorter RFS after surgical resection (HR=0.17, p=0.028). Genome profiling of cfDNA could effectively capture tumor-derived driver mutations, suggesting cfDNA was a non-invasive strategy to gain insights of genomic alterations in patients with resected multifocal HCC.ConclusionsTruncal mutations and the level of genomic heterogeneity could be identified by tNGS panel in patients with resected multifocal HCC. cfDNA could serve as a non-invasive and real-time auxiliary method to decipher the intertumoral heterogeneity and identify oncodrivers of multifocal HCC.

BackgroundThis study was designed to screen potential biomarkers in plasma cell-free DNA (cfDNA) for predicting the clinical outcome of immune checkpoint inhibitor (ICI)-based therapy in advanced hepatobiliary cancers.MethodsThree cohorts including 187 patients with hepatobiliary cancers were recruited from clinical trials at the Peking Union Medical College Hospital. Forty-three patients received combination therapy of programmed cell death protein 1 (PD-1) inhibitor with lenvatinib (ICI cohort 1), 108 patients received ICI-based therapy (ICI cohort 2) and 36 patients received non-ICI therapy (non-ICI cohort). The plasma cfDNA and blood cell DNA mutation profiles were assessed to identify efficacy biomarkers by a cancer gene-targeted next-generation sequencing panel.ResultsBased on the copy number variations (CNVs) in plasma cfDNA, the CNV risk score model was constructed to predict survival by using the least absolute shrinkage and selection operator Cox regression methods. The results of the two independent ICI-based therapy cohorts showed that patients with lower CNV risk scores had longer overall survival (OS) and progression-free survival (PFS) than those with high CNV risk scores (log-rank pConclusionsThe CNVs in plasma cfDNA could predict the clinical outcome of the combination therapy of PD-1 inhibitor with lenvatinib and other ICI-based therapies in hepatobiliary cancers.

BackgroundPD-1/L1 inhibitor-based immunotherapy is currently under investigation in biliary tract cancer (BTC). Apatinib combined with camrelizumab has achieved promising results in various tumor types. The aim of this study was to assess the safety and efficacy of apatinib plus camrelizumab for advanced biliary tract cancer patients who have received previously treatments.MethodsThis prospective, non-randomized, open-label trial was conducted at Peking Union Medical College Hospital (PUMCH). All included patients received apatinib orally at 250 mg per a day and camrelizumab intravenously at 200 mg every three weeks until disease progression or intolerable toxicity occurred. Efficacy was evaluated based on the Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1). Adverse events (AEs) were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0).ResultsA total of 22 patients were consecutively enrolled from 1st December, 2018 until 1st August, 2020. Among 21 patients for whom we could conduct efficacy evaluations, no patients achieved a complete response (CR), 4 patients (19%) achieved partial response (PR), and 11 patients had stable disease with a disease control rate of 71.4%. The median overall survival was 13.1 months (95% CI, 8.1-18.2), and the median progression-free survival was 4.4 months (95% CI, 2.4-6.3). All patients experienced treatment related AEs, and grade 3 or 4 AEs occurred in 14 (63.6%) of 22 patients. No treatment related deaths were observed.ConclusionsThis is the first report focusing on the efficacy and safety of camrelizumab plus apatinib in pretreated biliary tract cancer patients. The finding suggests this regimen has favorable therapeutic effects with relatively manageable toxicity. Further trials with a control arm are required to investigate.Clinical Trial Registrationidentifier NCT04642664.

Hypertrophic scarring is a widespread skin disorder that affects a patient's confidence and quality of life. Intralesional injection of bleomycin is one of the most commonly employed treatments for hypertrophic scars, which, however, always brings pain and requires long-term treatment. To overcome these limitations, new methods for bleomycin delivery enabling painlessness, self-administration, the fast onset of action, and good bioavailability are urgently needed. In this study, we developed bleomycin-loaded dissolving microneedles (BMN) made up of hyaluronic acid (HA) with excellent aqueous solubility and enhanced efficacy for inhibiting hypertrophic scars. The as-obtained BMN possesses sufficient mechanical strength to pierce porcine skin ex vivo with an insertion depth of over 300 μm. Moreover, BMN can dissolve rapidly and release 20% of loaded bleomycin within 1 min and 52% within 10 min, and the BMN-treated skin could recover to its original status within 3 h, demonstrating good biocompatibility. Besides, the HA matrix also maintains the stability and activity of bleomycin. Furthermore, we show that BMN consisting of HA and bleomycin can inhibit the proliferation of human hypertrophic scar fibroblasts (hHSFs) and the secretion of transforming growth factor-β (TGF-β1) in vitro. Therefore, bleomycin-loaded dissolving HA microneedles provide a potential route to treat hypertrophic scars in a convenient, efficient, and minimally invasive manner.

Cholangiocarcinoma (CCA) is a type of cancer with limited treatment options and a poor prognosis. Although some important genes and pathways associated with CCA have been identified, the relationship between coexpression and phenotype in CCA at the systems level remains unclear. In this study, the relationships underlying the molecular and clinical characteristics of CCA were investigated by employing weighted gene coexpression network analysis (WGCNA). The gene expression profiles and clinical features of 36 patients with CCA were analyzed to identify differentially expressed genes (DEGs). Subsequently, the coexpression of DEGs was determined by using the WGCNA method to investigate the correlations between pairs of genes. Network modules that were significantly correlated with clinical traits were identified. In total, 1478 mRNAs were found to be aberrantly expressed in CCA. Seven coexpression modules that significantly correlated with clinical characteristics were identified and assigned representative colors. Among the 7 modules, the green and blue modules were significantly related to tumor differentiation. Seventy-eight hub genes that were correlated with tumor differentiation were found in the green and blue modules. Survival analysis showed that 17 hub genes were prognostic biomarkers for CCA patients. In addition, we found five new targets (ISM1, SULT1B1, KIFC1, AURKB and CCNB1) that have not been studied in the context of CCA and verified their differential expression in CCA through experiments. Our results not only promote our understanding of the relationship between the transcriptome and clinical data in CCA but will also guide the development of targeted molecular therapy for CCA.

Purpose: There is limited standard treatment for patients with advanced cholangiocarcinoma after refractory of chemotherapy. Apatinib is a tyrosine kinase inhibitor targeting VEGFR-2, which exhibited broad-spectrum antitumor activities in previous studies. We aim to evaluate the efficacy and safety of apatinib as non-first-line treatment in patients with advanced cholangiocarcinoma. Methods: This was a prospective open-label phase II trial (NCT03251443). Patients with pathology-confirmed cholangiocarcinoma after prior systemic therapy were enrolled. Participants were treated with apatinib 500 mg orally once daily. The primary end point was overall response rate (ORR). Results: Between August 8, 2017 and November 13, 2018, 30 patients participated in this study, and 26 patients received apatinib treatment except 4 patients withdrew consent before the first dosage. For full analysis set, the ORR was 11.5% and the disease control rate was 50.0%. 3 patients (11.5%) achieved partial response and no patients achieved complete response. The median progression free time was 2.0 (95% CI: 0.7-3.3) months and median overall survival was 9. 0 (95% CI: 4.6-13.4) months. The most common adverse events of any grade were fatigue (80.8%), hypertension (73.1%) and decreased appetite (38.5%). Grade 3 adverse events occurred in 23.1% patients and no grade 4 adverse events occurred. The most common grade 3 adverse events were hypertension (23.1%) and elevated transaminase (11.5%). Conclusion: Apatinib as non-first-line monotherapy has potential therapeutic efficacy in patients with advanced cholangiocarcinoma.

Background A therapeutic strategy involving combined treatment with lenvatinib plus pembrolizumab (LEP) has demonstrated a relatively high antitumor response in several solid tumors; however, the efficacy and safety of LEP in patients with refractory bile tract carcinoma (BTC) remains unknown. Methods This is a single-arm study for a preliminary assessment of the efficacy and tolerability of LEP in patients who experienced progression from prior systemic treatments. Pre-treatment tumor tissues were collected to retrospectively evaluate the expression status of PDL1. Results Thirty-two patients received second-line and above treatment with LEP. Overall, the objective response rate (ORR) was 25%, the disease control rate (DCR) was 78.1%, and the clinical benefit rate (CBR) was 40.5%. The median progression-free survival (PFS) was 4.9 months (95% CI: 4.7-5.2 months), and the median overall survival (OS) was 11.0 months (95% CI: 9.6-12.3 months). For tolerability, no grade 5 serious adverse events (AEs) were reported. All patients had any-grade AEs, and 59.3% of the patients experienced grade 3 AEs, while only 1 patient experienced a grade 4 AE of stomach bleeding. Fatigue was the most common AE, followed by hypertension and elevated aminotransferase levels. Retrospective analysis for PDL1 expression revealed that PDL1 positive tumor cells were associated with improved clinical benefits and survival outcomes. Conclusions LEP is a promising alternative as a non-first-line therapeutic regimen for patients with refractory BTC. Furthermore, well-designed prospective clinical trials with a control arm are still needed to obtain more evidences to confirm the efficacy and safety of this particular regimen as well as the role of PDL1 expression.

BACKGROUND: Lung cancer is the most malignant tumor with the highest morbidity and mortality. This study aimed to investigate the role of the expression and the significance of the p42.3 gene in non-small cell lung cancer (NSCLC). METHODS: Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were analyzed based on the biological information data of The Cancer Genome Atlas (TCGA). Furthermore, 142 postoperative tumor tissue and normal tissue samples (70 cases of LUAD and 72 cases of LUSC) from NSCLC patients admitted to our hospital from 2005 to 2009 were retrospectively collected. Paraffin-embedded tissues were used to make the tissue microarrays (TMA), and the expression of the p42.3 protein was detected by immunohistochemical staining. RESULTS: The expression of p42.3 in both LUAD and LUSC was significantly upregulated (P

Tumour mutation burden (TMB) and the immune microenvironment (IME) are reportedly associated with immunotherapy responses, but this relationship remains unclear in hepatocellular carcinoma (HCC). We classified HCC patients in the liver hepatocellular carcinoma cohort from The Cancer Genome Atlas into low- and high-TMB groups and evaluated differences in immune infiltrates. Additionally, differentially expressed genes in the low- and high-TMB groups were identified, and functional analyses were conducted. A risk score model was constructed based on three differentially expressed immune genes (DEIGs). The Tumor Immune Estimation Resource database was utilized to analyse how the IME was affected by the three hub DEIGs. Finally, a prognostic nomogram combining risk scores and stages was established and externally validated with the International Cancer Genome Consortium and GSE14520 cohorts. High-TMB (top 20%) patients exhibited a worse prognosis (P = 0.017). Follicular helper cells (P = 0.001) and activated natural killer cells (P = 0.003) were enriched in high-TMB patients, while resting dendritic cells (P = 0.002) were enriched in low-TMB samples. A risk score model was generated with three hub DEIGs (CCR7, STC2 and S100A9) to predict overall survival in HCC cohorts. Moreover, copy number variations mainly reduced infiltration levels. The nomogram performed better than the risk score model in the training and validation datasets. Higher TMB was associated with IME diversification and worse prognosis in HCC. Mutations in three hub TMB-associated DEIGs correlated with lower immune cell infiltration.

Porous polymer microneedles (MNs) have great potential in transdermal medical applications due to their three-dimensional (3D) porous structures and high porosity. However, existing approaches for the fabrication of such porous polymer MNs are complicated and only applicable to limited types of polymers. Here, we describe a facile yet effective phase inversion route to prepare polymer MNs with highly porous and interconnected pore structures. The fabrication process is simple and mild without involving high temperatures or irradiation, and can be applied to a broad spectrum of commonly used polymers (e.g., cellulose acetate (CA), polysulfone (PSF), polyethersulfone (PES), polylactic acid (PLA), etc.). Thanks to the capillary effect and large cavity given by highly porous and interconnected structures, the resulting porous polymer MNs show the capability of rapidly extracting dermal interstitial fluid (ISF) and efficiently loading/releasing drug compounds. As a proof of concept, we demonstrate the use of these porous CA MNs in the highly efficient extraction of ISF for glucose level detection and administration of insulin for hyperglycemia. Given the recent trend of painless techniques in diagnosis and treatment, the current study provides a new opportunity for the fabrication of MN-based devices for transdermal ISF extraction and drug delivery.

Background: This study aimed to investigate the clinical characteristics and treatment methods for intra-abdominal aggressive fibromatosis. Methods: We reviewed the clinical data from 16 patients who were diagnosed with intra-abdominal aggressive fibromatosis and were admitted to Peking Union Medical College Hospital between March 1983 and September 2018. Results: Among the 16 patients, 11 patients presented with a hard smooth abdominal mass with clear borders and a diameter of 4.3-25.0 cm. Six patients had a history of abdominal surgery and 3 patients had a history of familial adenomatous polyposis. Computed tomography imaging revealed a slightly dense mass with mild-to-moderate enhancement. Of all the 16 patients, 11 patients underwent surgical treatment and no recurrence occurred in 10 case after complete resection while recurrence occurred in 1 case after partial resection. Two patients underwent surveillance and 3 patients received cytotoxic drugs treatment, and no disease progression was observed via imaging during their follow-up. Conclusions: Intra-abdominal aggressive fibromatosis is histologically benign tumor with high local recurrence rate. Surgery is an effective treatment and complete resection is essential in reducing the local recurrence rate.

Background/Aims: As a type of malignant tumor commonly found in the bile duct, cholangiocarcinoma (CCA) has a poor prognosis. Long non-coding RNA (lncRNA) has recently drawn increasing attention because it functions as a competing endogenous RNA (ceRNA) to hinder miRNA functions that participate in posttranscriptional regulatory networks in tumors. Therefore, to investigate the mechanisms of CCA carcinogenesis and to enhance treatment efficiency, the expression profiles, including lncRNA, miRNA, and mRNA data, were comprehensively integrated and analyzed in this study. Methods: A comprehensive comparison was performed on the RNA-sequencing and miRNA profiles data of 36 CCA samples and 9 normal samples from The Cancer Genome Atlas (TCGA) database. Then, a dysregulated lncRNA-related ceRNA network was established by using four public databases. Results: In summary, 1,410 lncRNAs, 64 miRNAs, and 3,494 mRNAs appeared as genes that were aberrantly expressed in CCA. Then, a dysregulated ceRNA network related to the lncRNAs was constructed. The network included 116 lncRNAs, 13 miRNAs and 60 mRNAs specific to CCA. The survival analysis showed that, among them, 26 lncRNAs, 3 miRNAs, and 13 mRNAs were prognostic biomarkers for patients with CCA. Finally, three mRNAs were selected for validation of their expression levels in the Gene Expression Omnibus (GEO) database. The results indicated that the expression of those genes was highly consistent between the TCGA and GEO databases. Conclusions: The findings in this study provide a better understanding of the ceRNA network involved in CCA biology and lay a solid foundation for improving CCA diagnosis and prognosis.

The aim of this study was to investigate the expression level of Ras homolog gene family, member A (RhoA) in patients with hepatocellular carcinoma (HCC) and to investigate the prognostic and diagnostic value of RhoA. Data mining from various data bases and wet experiments on samples from Peking Union Medical College Hospital showed that RhoA mRNA and protein expression were significantly higher in the HCC tissues than in the normal tissues. Higher expression at both the mRNA and protein levels was associated with a poorer prognosis. High sensitivity (92.5%) and specificity (90.0%) were observed in the diagnostic model based on protein level rather than mRNA level. RhoA expression was modulated by genetic amplification. The lysosome, pathogenic Escherichia coli infection, purine metabolism and pyrimidine metabolism pathways were mainly enriched in the high RhoA level group, while the hedgehog signaling, linoleic acid metabolism, olfactory transduction and taste transduction pathways were enriched in the low RhoA level group. RhoA is commonly upregulated in HCC tissues, and its expression at both the mRNA and protein levels is associated with poor prognosis. Notably, RhoA protein levels serve as a diagnostic biomarker for HCC.

Background Lung cancer is the most malignant tumor with the highest morbidity and mortality. This study aimed to investigate the role of the expression and the significance of the p42.3 gene in non-small cell lung cancer (NSCLC). Methods Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were analyzed based on the biological information data of The Cancer Genome Atlas (TCGA). Furthermore, 142 postoperative tumor tissue and normal tissue samples (70 cases of LUAD and 72 cases of LUSC) from NSCLC patients admitted to our hospital from 2005 to 2009 were retrospectively collected. Paraffin-embedded tissues were used to make the tissue microarrays (TMA), and the expression of the p42.3 protein was detected by immunohistochemical staining. Results The expression of p42.3 in both LUAD and LUSC was significantly upregulated (P

5-Aminolevulinic acid (5-ALA) is one of the most widely used prodrug in clinical photodynamic therapy of dermatological diseases and cancers; yet, its clinical application is still limited by the shallow skin penetration and unsatisfied stability in any existed formulations. Here, 5-ALA-loaded hyaluronic acid dissolving microneedles (5-ALA@HAMNs) are prepared for photodynamic therapy of superficial tumors. The HAMNs can not only assist the loaded 5-ALA to effectively penetrate the stratum corneum but also provide 5-ALA with an acidic and oxygen-free environment to reduce the dimerization of 5-ALA molecules via Schiff-base bonds and formation of inactive pyrazine derivatives, thus maintaining its chemical structure and biological activity. The chemical stability of 5-ALA in HAMNs is confirmed by UV-vis spectra and mass spectra measurements. The 5-ALA@HAMNs display remarkable tumor elimination both in vitro and in vivo, even after storage at room temperature for nine months, making it a highly potential device for effective delivery of 5-ALA in cancer photodynamic therapy.

BACKGROUND: The objective was to study soil water conservation and physiological growth of corn (Zea mays L.) using water-saving super-absorbent polymer (SAP) at 30 kg ha−1. The effectiveness of SAP was studied under three irrigation levels (adequate, moderate and deficit) using a new type of negative hydraulic pressure controlled auto-irrigator in the years 2009 and 2010 in a greenhouse at Beijing, P.R. China. RESULTS: Eight weeks after sowing, plant height and leaf area increased significantly by 41.6 and 79.6% under deficit irrigation for SAP treatment. The SAP had little effect on shoot dry mass under adequate and moderate irrigation but increased it significantly by 133.5% under deficit irrigation. Similarly, the efficiency of water use also increased by 97.1%. Leaf water potential under adequate and moderate irrigation differs slightly for SAP application, whereas under deficit irrigation the values were exceeded significantly by 27.8%. The superior growth and water use efficiency of corn treated with SAP under deficit irrigation was ascribed to maintenance of higher relative water contents in leaves as well as intercellular carbon dioxide concentration, net photosynthesis and transpiration rate. CONCLUSIONS: Our results suggested that plant growth and different physiological activities are restricted by drought stress and the application of super-absorbent polymer could conserve soil water, making same available to plants for increased growth and biomass accumulation especially under severe water stress. Thus, application of SAP is a suitable soil management practice for the locations characterised by severe water stress. Copyright © 2011 Society of Chemical Industry