Efficacy of first-line immunization combined with antiangiogenesis treatment and chemotherapy for the treatment of tongue cancer: A case report.

BACKGROUND: There is currently no uniform and effective treatment for patients with locally advanced oral cancer who cannot tolerate surgery or radiotherapy. The prognosis of oral cancer patients with lymph node metastasis is very poor, but the clinical treatment of such patients faces certain challenges. PATIENTS AND METHODS: Case 1 was a 59-year-old patient with tongue cancer (cT 3 N x M 0 G 2) who refused radiotherapy because of a history of leukoderma. After evaluation of disease condition, a 4-drug combination therapy of toripalimab + anlotinib + nabpaclitaxel + carboplatin was administered. Case 2 was a 55-year-old patient with tongue cancer (cT 3 N 2 M 0 G 1) who could not receive radiotherapy because of a medical history of cervicofacial burns. After disease evaluation, toripalimab + anlotinib + docetaxel + carboplatin combination therapy was administered. CASE SUMMARY: Both patients did not experience any adverse reactions during treatment and achieved a complete response after 2 cycles of treatment. Their progression-free survival is currently 6 and 8 months, respectively, and they are in sustained remission. CONCLUSION: Currently, the efficacy of immune checkpoint inhibitors targeting programmed death-1 as a first-line treatment of inoperable and non-radiatable locally advanced oral cancer is unknown. Here, we describe 2 cases of locally advanced oral cancer treated with first-line immune checkpoint inhibitors in combination with targeted therapy and chemotherapy. This approach was successful in these patients, but a larger sample size is required to verify our findings.

CCT3 as a Diagnostic and Prognostic Biomarker in Cervical Cancer.

The chaperonin-containing TCP1 complex subunit 3 (CCT3) has been reported to be involved in the development and prognosis of many tumors, including cervical cancer (CC). This study aimed to analyze the expression and prognostic value of CCT3 in CC by bioinformatics and retrospective study. CCT3 gene expression profiles and clinical information in CC were downloaded from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases. CCT3 expression was verified by quantitative real-time polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry (IHC). Logistic regression and chi-square testing were used to analyze the relationship between CCT3 expression and the clinical characteristics of CC. Kaplan-Meier and Cox analyses were used to evaluate whether CCT3 affects the prognosis of CC. Nomogram and calibration curves were used to test the predictive value of CCT3. The expression of CCT3 in CC tissues was significantly upregulated compared with that in adjacent benign tissues, and was related to HPV16/18 infection, grade, and positive lymph nodes. High expression of CCT3 is associated with poor prognosis of CC and can be used as an independent risk factor for CC. The prognostic model based on CCT3 and CC clinical features has good predictive ability. CCT3 is overexpressed in CC, which is related to poor prognosis and expected to become a biomarker for CC.

Molecular and Supramolecular Approach to Highly Photocytotoxic Phthalocyanines with Dual Cell Uptake Pathways and Albumin-Enhanced Tumor Targeting.

Phototherapy for non-invasive cancer treatment has been extensively studied. An urgent challenge in phototherapy application is to fabricate appropriate targeted agents to achieve efficient therapeutic effect. Herein, a molecular and supramolecular approach for targeting phototherapy was reasonably designed and realized through the axial sulfonate modification of silicon(IV) phthalocyanines (Pcs), followed by supramolecular interaction with albumin. This approach can not only improve the photoactivities (e.g., fluorescence emission and reactive oxygen species production) of the Pcs but also enhance their tumor targeting. Most importantly, one of the deigned Pcs (4) can target HepG2 cells through dual cell pathways, leading to an extremely high phototoxicity with an EC50 (i.e., concentration of Pcs to kill 50% of cells under light irradiation) value of 2.0 nM. This finding presents a feasible strategy to realize efficient targeting phototherapy.

A pH-sensitive nanoagent self-assembled from a highly negatively-charged phthalocyanine with excellent biosafety for photothermal therapy.

Photothermal therapy (PTT) is a promising strategy for cancer treatment. However, the development of highly efficient photothermal agents with excellent biosafety, particularly with low liver retention, is very meaningful for clinical applications, but it is also challenging. We herein prepared a pH-sensitive nanoagent (NanoPc3) by the self-assembly of a zinc(ii) phthalocyanine substituted with hexadeca-sulphonates linked by hydrazone bonds for photoacoustic imaging and PTT. Due to the highly negative surface potential (-30.80 mV in water), NanoPc3 could effectively escape the phagocytosis of the reticuloendothelial system and be rapidly cleared from normal tissues, leading to little accumulation in the liver and excellent biosafety. The highly negatively-charged NanoPc3 changed into nearly neutral nanoparticles (NanoPc3H) under slightly acidic conditions, resulting in enhanced cellular uptake and retention time in tumor tissues. Moreover, the tumor of H22 tumor-bearing mice treated with NanoPc3 almost disappeared, suggesting an outstanding photothermal antitumor effect. NanoPc3 also hardly showed skin phototoxicity under irradiation. Its excellent antitumor effect and biosafety make NanoPc3 highly promising in clinical applications. This work will provide a new strategy for the design of tumor-targeted photothermal nanoagents with high biosafety.

Recent progresses in the pharmacological activities of caffeic acid phenethyl ester.

The past decades have seen a growing interest in natural products. Caffeic acid phenethyl ester (CAPE), a flavonoid isolated from honeybee propolis, has shown multiple pharmacological potentials, including anti-cancer, anti-inflammatory, antioxidant, antibacterial, antifungal, and protective effects on nervous systems and multiple organs, since it was found as a potent nuclear factor κB (NF-κB) inhibitor. This review summarizes the advances in these beneficial effects of CAPE, as well as the underlying mechanisms, and proposes that CAPE offers an opportunity for developing therapeutics in multiple diseases. However, clinical trials on CAPE are necessary and encouraged to obtain certain clinically relevant conclusions.

Acute myeloid leukemia with inv(16)(p13.1q22) and deletion of the 5'MYH11/3'CBFB gene fusion: a report of two cases and literature review.

BACKGROUND: Abnormalities of chromosome 16 are found in about 5-8% of acute myeloid leukemia (AML). The AML with inv(16)(p13.1q22) or t (16;16)(p13.1;q22) is associated with a high rate of complete remission (CR) and favorable overall survival (OS) when treated with high-dose Cytarabine. At the inversion breakpoints, deletion of 3'CBFB has been reported, but most of them were studied by chromosome and fluorescence in situ hybridization (FISH) analyses. The genomic characteristics of such deletions remain largely undefined, hindering further understanding of the clinical significance of the deletions. CASE PRESENTATION: We report here two AML cases with inv(16) and deletion of the 5'MYH11/3'CBFB gene fusion, which were characterized by chromosome, FISH, and single nucleotide polymorphism (SNP) microarray analyses. Both cases have achieved CR for more than three years. CONCLUSIONS: Deletion of 3'CBFB in AML with inv(16) is also accompanied with deletion of 5'MYH11 in all the cases studied by SNP microarray, suggesting that 3'CBFB and 5'MYH11 were most likely deleted together as a fusion product of inv(16) instead of occurring separately. In concert with the findings of other published studies of similar patients, our study suggests that deletion of 5'MYH11/3'CBFB in AML with inv(16) may not have negative impact on the prognosis of the disease.

Apatinib, combined with chemotherapy or alone is effective in treating angiosarcoma: a case report.

Angiosarcomas are rare but aggressive tumors with poor prognosis. The treatment of angiosarcomas with vascular endothelial growth factor receptor inhibitors is still in the stage of clinical exploration. Herein we reported a patient of skin angiosarcoma with multiple organ metastasis. She was resistance to multiline chemotherapy and pazopanib but achieved remarkable shrinkage of the lesion after apatinib treatment combined with chemotherapy or alone. The progression-free survival of the primary lesion with KRAS V14I and RBM10 E119D mutations (10 months) was shorter than that of the brain without the mutation ( ≥ 12 months). Although it is not clear whether the KRAS V14I and RBM10 E119D mutations are the main factors that impact the effect of apatinib treatment or not, the results of this study will provide valuable clues for relevant follow-up basic and clinical studies.

microRNA-944 inhibits the malignancy of hepatocellular carcinoma by directly targeting IGF-1R and deactivating the PI3K/Akt signaling pathway.

Purpose: Recent studies have identified microRNA-944 (miR-944) as a cancer-related miRNA, but its expression and precise functions in hepatocellular carcinoma (HCC) remain unknown. Patients and methods: miR-944 expression in HCC tissues and cell lines were detected by RT-qPCR. A series of functional assays were utilized to examine the influence of miR-944 on the malignant phenotypes of HCC cells in vitro and in vivo. More importantly, the associated mechanisms underlying the activity of miR-944 in HCC cells were investigated using bioinformatics, luciferase reporter assays, RT-qPCR, and western blot analysis. Results: In this study, we report for the first time, a significant downregulation of miR-944 in HCC tissues and cell lines and the correlation between its downregulation and malignant clinical parameters, including Edmondson-Steiner grade, TNM stage, and venous infiltration. Low miR-944 expression predicted poorer overall survival rate and disease-free survival rate in patients with HCC. Functionally, exogenous miR-944 expression attenuated cell proliferation, clone formation, metastasis, and epithelial-mesenchymal transition and increased apoptosis in HCC, whereas miR-944 knockdown produced the opposite results. In addition, ectopic miR-944 expression hindered HCC tumor growth in vivo. Mechanistically, insulin-like growth factor 1 receptor (IGF-1R) was demonstrated to be the direct target gene of miR-944 in HCC cells. Furthermore, the expression level of miR-944 was inversely correlated with IGF-1R expression in HCC tissues. Rescue experiments showed that IGF-1R was at least partially responsible for the effects of miR-944 on the malignant phenotypes of HCC cells. In addition, the PI3K/Akt pathway was notably deactivated, both in vitro and in vivo, upon miR-944 upregulation. Conclusion: This study provides the first evidence that miR-944 directly targets IGF-1R and inhibits the aggressiveness of HCC, in vitro and in vivo, by decreasing PI3K/Akt signaling. Hence, targeting miR-944 may open a new avenue for the treatment of patients with HCC.

A complex translocation (1;17;15) with spliced short-type PML-RARA fusion transcripts in acute promyelocytic leukemia: A case report.

The promyelocytic leukemia (PML)-retinoic acid receptor α (RARA) fusion is hypothesized to serve a vital role in the pathogenesis of acute promyelocytic leukemia (APL), which results from a reciprocal translocation between chromosomes 15 and 17, t(15;17)(q24;q21). A minority of APL cases lack the classical t(15;17) and have been identified to have cryptic or masked t(15;17) or complex translocations. The present study reports on a case of a 37-year-old male with APL harboring a complex three-way translocation t(1;17;15)(q21;q21;q24). This karyotypic interpretation was further confirmed by fluorescence in situ hybridization, and 98% of the bone marrow cells analyzed were positive for the PML-RARA fusion gene. After combined treatment with all-trans retinoic acid and arsenic trioxide, the patient achieved complete remission with no recurrence for 3 years to date. To the best of our knowledge, the present study is the first to report on the novel variant of t(15;17) involving the breakpoint 1q21.

Studies on the Exergy Transfer Law for the Irreversible Process in the Waxy Crude Oil Pipeline Transportation.

With the increasing demand of oil products in China, the energy consumption of pipeline operation will continue to rise greatly, as well as the cost of oil transportation. In the field of practical engineering, saving energy, reducing energy consumption and adapting to the international oil situation are the development trends and represent difficult problems. Based on the basic principle of non-equilibrium thermodynamics, this paper derives the field equilibrium equations of non-equilibrium thermodynamic process for pipeline transportation. To seek the bilinear form of "force" and "flow" in the non-equilibrium thermodynamics of entropy generation rate, the oil pipeline exergy balance equation and the exergy transfer pipeline dynamic equation of the irreversibility were established. The exergy balance equation was applied to energy balance evaluation system, which makes the system more perfect. The exergy flow transfer law of the waxy oil pipeline were explored deeply from the directions of dynamic exergy, pressure exergy, thermal exergy and diffusion exergy. Taking an oil pipeline as an example, the influence factors of exergy transfer coefficient and exergy flow density were analyzed separately.

MicroRNA-296 Targets Specificity Protein 1 to Suppress Cell Proliferation and Invasion in Cervical Cancer.

Cervical cancer is the third most commonly diagnosed malignancy and the fourth leading cause of cancer-related deaths in women worldwide. MicroRNA-296 (miR-296) is aberrantly expressed in a variety of human cancer types. However, the expression levels, biological roles, and underlying molecular mechanisms of miR-296 in cervical cancer remain unclear. This study aimed to detect miR-296 expression in cervical cancer and evaluate its roles and underlying mechanisms in cervical cancer. This study demonstrated that miR-296 was significantly downregulated in cervical cancer tissues and cell lines. Restoring the expression of miR-296 inhibited the proliferation and invasion of cervical cancer cells. Moreover, miR-296 directly targeted the 3'-untranslated regions of specificity protein 1 (SP1) and decreased its endogenous expression at both the mRNA and protein levels. Similar to induced miR-296 expression, SP1 knockdown suppressed the proliferation and invasion of cervical cancer cells. Besides, resumption expression of SP1 rescued the tumor-suppressing roles of miR-296 in cervical cancer. These results indicated that miR-296 may act as a tumor suppressor in cervical cancer by directly targeting SP1. Therefore, SP1 may be developed as a therapeutic target for the treatment of patients with this malignancy.

Gli1, a potential cancer stem cell marker, is strongly associated with prognosis in prostate cancer.

BACKGROUND: Although glioma-associated oncogene homolog 1 (Gli1) is a key mediator of the Hedgehog pathway, Gli1 involvement in the maintenance of cancer stem-like cells (CSCs) in prostate cancer (PCa) is unclear. METHODS: Herein, we assessed the expression of Gli1 and its relationship with cancer stemness genes, cell cycle markers, epithelial-mesenchymal transition (EMT), and signaling pathway genes in 145 paraffin-embedded PCa tissue samples using immunohistochemistry. In addition, we further confirmed the correlation between Gli1 and CSC marker in PC3 cells using immunofluorescence imaging. RESULTS: High Gli1 expression was significantly associated with advanced primary tumor stage, positive lymph node metastasis, advanced clinical stage, and HIF-1α expression. The microvessel density was significantly higher in the Gli1 positive-cases than in the negative-cases. Furthermore, Gli1 expression was positively correlated with stemness markers CD44. Survival analysis demonstrated that Gli1 and CD44 were strongly associated with the worse clinical outcome and an independent poor prognostic factor for overall survival. The enrichment analysis revealed that Gli1 was not correlated with E-cadherin, while positively correlated with Snail and vimentin. Notably, Gli1 expression was positively associated with the expression of cell cycle regulating genes such as cyclin D1, p21 and CDK4. Additionally, Gli1 expression was positively correlated with pPI3K p85, pAkt-Ser473 and NF-κB p65 expression. CONCLUSIONS: Our results indicate that Gli1 is a potential diagnostic marker of CSCs and that Gli1 expression is strongly associated with epithelial-mesenchymal transition in PCa via PI3K/Akt/NF-κB signaling.

SPA70 is a potent antagonist of human pregnane X receptor.

Many drugs bind to and activate human pregnane X receptor (hPXR) to upregulate drug-metabolizing enzymes, resulting in decreased drug efficacy and increased resistance. This suggests that hPXR antagonists have therapeutic value. Here we report that SPA70 is a potent and selective hPXR antagonist. SPA70 inhibits hPXR in human hepatocytes and humanized mouse models and enhances the chemosensitivity of cancer cells, consistent with the role of hPXR in drug resistance. Unexpectedly, SJB7, a close analog of SPA70, is an hPXR agonist. X-ray crystallography reveals that SJB7 resides in the ligand-binding domain (LBD) of hPXR, interacting with the AF-2 helix to stabilize the LBD for coactivator binding. Differential hydrogen/deuterium exchange analysis demonstrates that SPA70 and SJB7 interact with the hPXR LBD. Docking studies suggest that the lack of the para-methoxy group in SPA70 compromises its interaction with the AF-2, thus explaining its antagonism. SPA70 is an hPXR antagonist and promising therapeutic tool.The xenobiotic-activated human pregnane X receptor (hPXR) regulates drug metabolism. Here the authors develop hPXR modulators, which are of potential therapeutic interest and functionally and structurally characterize the antagonist SPA70 and the structurally related agonist SJB7.

The inhibiting effect of intravenous anesthesia on adrenal gland functions under the sepsis condition.

This study aims to explore the effect of intravenous anesthesia on the adrenal gland functions of rats with sepsis as well as on their lungs and adrenal gland tissues in order to provide a theoretical reference for the cure of sepsis. Female Sprague Dawley (SD) rats were taken as the research objects in this study. Venous channels of rats were constructed by catheterization through the external jugular vein, and the cecal ligation and puncture technique was adopted to duplicate the sepsis rat models. The level of tumor necrosis factor-α (TNF-α) in serum was detected using enzyme-linked immunosorbent assay (ELISA), and necrocytosis was observed by the fluorescent staining method. The results showed that the survival rates of groups A, B, C, and D were 100%, 60%, 60%, and 50%, respectively, while their concentrations of TNF-α in serum were101.26 ± 43.38, 1398.68 ± 178.56, 451.16 ± 78.68, and 649.83 ± 98.56 pg/mL, respectively. Results of fluorescent staining showed that the number of living cells per unit view in group A was 1428 ± 166 and those of groups B, C and D were 175 ± 56, 618 ± 76, and 468 ± 55, respectively. Besides, it was found that changes of inflammatory pathology of lung tissues of each group were significant. In conclusion, etomidate does not affect the survival of sepsis rats and does not exacerbate lung tissue inflammation in sepsis rats. Instead, it can inhibit TNF-α in serum of sepsis rats, as well as the apoptosis of adrenal cells in sepsis rats.

Saikosaponins induced hepatotoxicity in mice via lipid metabolism dysregulation and oxidative stress: a proteomic study.

BACKGROUND: Radix Bupleuri (RB) has been popularly used for treating many liver diseases such as chronic hepatic inflammation and viral Hepatitis in China. Increasing clinical and experimental evidence indicates the potential hepatotoxicity of RB or prescriptions containing RB. Recently, Saikosaponins (SS) have been identified as major bioactive compounds isolated from RB, which may be also responsible for RB-induced liver injury. METHODS: Serum AST, ALT and LDH levels were determined to evaluate SS-induced liver injury in mice. Serum and liver total triglyceride and cholesterol were used to indicate lipid metabolism homeostasis. Liver ROS, GSH, MDA and iNOS were used to examine the oxidative stress level after SS administration. Western blot was used to detect CYP2E1 expression. A 8-Plex iTRAQ Labeling Coupled with 2D LC - MS/MS technique was applied to analyze the protein expression profiles in livers of mice administered with different doses of SS for different time periods. Gene ontology analysis, cluster and enrichment analysis were employed to elucidate potential mechanism involved. HepG2 cells were used to identify our findings in vitro. RESULTS: SS dose- and time-dependently induced liver injury in mice, indicated by increased serum AST, ALT and LDH levels. According to proteomic analysis, 487 differentially expressed proteins were identified in mice administrated with different dose of SS for different time periods. Altered proteins were enriched in pathways such as lipid metabolism, protein metabolism, macro molecular transportation, cytoskeleton structure and response to stress. SS enhanced CYP2E1 expression in a time and dose dependent manner, and induced oxidative stress both in vivo and in vitro. CONCLUSION: Our results identified hepatotoxicity and established dose-time course-liver toxicity relationship in mice model of SS administration and suggested potential mechanisms, including impaired lipid and protein metabolism and oxidative stress. The current study provides experimental evidence for clinical safe use of RB, and also new insights into understanding the mechanism by which SS and RB induced liver injury.

Okadaic acid inhibits cell multiplication and induces apoptosis in a549 cells, a human lung adenocarcinoma cell line.

This essay aims to research the effect of okadaic acid (OA) on A549 cell multiplication, and cell apoptosis induced by OA was observed by cell morphology. MTT assay, trypan blue exclusion test (TBET), Giemsa staining method and acridine orange (AO) fluorescence staining assay were applied. The results of cell survival evaluated by TBET and colorimetric assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) showed: The number of A549 cells was decreased in a dose-dependent manner. Cytomorphology observation of okadaic acid-treated cells showed that cells became shrinkage and turned round, some cells floated in the nutrient medium with nucleus agglutination broken, resulting in apoptotic bodies. Above-mentioned results indicated that OA exerted significantly inhibitory effect on A549 cell multiplication due to the apoptosis induced by OA.

High-performance liquid chromatographic determination of hexanal and heptanal in human blood by ultrasound-assisted headspace liquid-phase microextraction with in-drop derivatization.

In this paper, an ultrasound-assisted headspace liquid-phase microextraction with in-drop derivatization was developed for the extraction and determination of hexanal and heptanal as the biomarkers in human blood. In the method, a polychloroprene rubber (PCR) tube was utilized as container to load extraction solvent (methyl cyanide) and derivatization reagent (2,4-dinitrophenylhydrazine, 2,4-DNPH). Volatile aldehydes were headspace extracted and simultaneously derivatized in the droplet, followed by LC-UV detection of the formed hydrazones. The stability of organic solvent and the sensitivity of the method enhanced greatly. Under the optimal conditions, good linearity was obtained in the concentration range of 0.01-10mumolL(-1) (r>0.997) and the limits of detection (LOD) for hexanal and heptanal were 0.79 and 0.80nmolL(-1), respectively. The recoveries in blood sample ranged from 75.2% to 101.1% with the inter- and intra-day precisions less than 9.8%. The method possesses the advantages such as simplicity, sensitivity, efficiency, low consumption of solvent, and little interference from sample matrix. It provides great potential for the investigation of volatile disease biomarkers (aldehydes) in complex biological samples.