Actions of Thyroid Hormones on Thyroid Cancers

L-Thyroxine (T4) is the principal ligand of the thyroid hormone analogue receptor on the extracellular domain of integrin αvβ3. The integrin is overexpressed and activated in cancer cells, rapidly dividing endothelial cells, and platelets. The biologic result is that T4 at physiological concentration and without conversion to 3,3’,5-triiodo-L-thyronine (T3) may stimulate cancer cell proliferation and cancer-relevant angiogenesis and platelet coagulation. Pro-thrombotic activity of T4 on platelets is postulated to support cancer-linked blood clotting and to contribute to tumor cell metastasis. We examine some of these findings as they may relate to cancers of the thyroid. Differentiated thyroid cancer cells respond to physiological levels of T4 with increased proliferation. Thus, the possibility exists that in patients with differentiated thyroid carcinomas in whom T4 administration and consequent endogenous thyrotropin suppression have failed to arrest the disease, T4 treatment may be stimulating tumor cell proliferation. In vitro studies have shown that tetraiodothyroacetic acid (tetrac), a derivative of T4, acts via the integrin to block T4 support of thyroid cancer and other solid tumor cells. Actions of T4 and tetrac or chemically modified tetrac modulate gene expression in thyroid cancer cells. T4 induces radioresistance via induction of a conformational change in the integrin in various cancer cells, although not yet established in thyroid cancer cells. The thyroid hormone receptor on integrin αvβ3 mediates a number of actions of T4 on differentiated thyroid cancer cells that support the biology of the cancer. Additional studies are required to determine whether T4 acts on thyroid cancer cells

Order-Preserving Abstractive Summarization for Spoken Content Based on Connectionist Temporal Classification

Connectionist temporal classification (CTC) is a powerful approach for sequence-to-sequence learning, and has been popularly used in speech recognition. The central ideas of CTC include adding a label "blank" during training. With this mechanism, CTC eliminates the need of segment alignment, and hence has been applied to various sequence-to-sequence learning problems. In this work, we applied CTC to abstractive summarization for spoken content. The "blank" in this case implies the corresponding input data are less important or noisy; thus it can be ignored. This approach was shown to outperform the existing methods in term of ROUGE scores over Chinese Gigaword and MATBN corpora. This approach also has the nice property that the ordering of words or characters in the input documents can be better preserved in the generated summaries.Comment: Accepted by Interspeech 201

Constrained K-means and Genetic Algorithm-based Approaches for Optimal Placement of Wireless Structural Health Monitoring Sensors

Optimal placement of wireless structural health monitoring (SHM) sensors has to consider modal identification accuracy and power efficiency. In this study, two-tier wireless sensor network (WSN)-based SHM systems with clusters of sensors are investigated to overcome this difficulty. Each cluster contains a number of sensor nodes and a cluster head (CH). The lower tier is composed of sensors communicating with their associated CHs, and the upper tier is composed of the network of CHs. The first step is the optimal placement of sensors in the lower tier via the effective independence method by considering the modal identification accuracy. The second step is the optimal placement of CHs in the upper tier by considering power efficiency. The sensors in the lower tier are partitioned into clusters before determining the optimal locations of CHs in the upper tier. Two approaches, a constrained K-means clustering approach and a genetic algorithm (GA)-based clustering approach, are proposed in this study to cluster sensors in the lower tier by considering two constraints: (1) the maximum data transmission distance of each sensor; (2) the maximum number of sensors in each cluster. Given that each CH can only manage a limited number of sensors, these constraints should be considered in practice to avoid overload of CHs. The CHs in the upper tier are located at the centers of the clusters determined after clustering sensors in the lower tier. The two proposed approaches aim to construct a balanced size of clusters by minimizing the number of clusters (or CHs) and the total sum of the squared distance between each sensor and its associated CH under the two constraints. Accordingly, the energy consumption in each cluster is decreased and balanced, and the network lifetime is extended. A numerical example is studied to demonstrate the feasibility of using the two proposed clustering approaches for sensor clustering in WSN-based SHM systems. In this example, the performances of the two proposed clustering approaches and the K-means clustering method are also compared. The two proposed clustering approaches outperform the K-means clustering method in terms of constructing balanced size of clusters for a small number of clusters. Doi: 10.28991/CEJ-2022-08-12-01 Full Text: PD

AKT/mTOR as Novel Targets of Polyphenol Piceatannol Possibly Contributing to Inhibition of Proliferation of Cultured Prostate Cancer Cells

The polyphenol piceatannol has shown inhibition against tyrosine and serine/threonine kinases. Whether piceatannol also exerts activity on the mammalian target of rapamycin (mTOR), a kinase involved in growth control of eukaryotic cells, is not known. In this study, we tested the effects of piceatannol on proliferation of androgen-dependent (AD) LNCaP and androgen-independent (AI) DU145 and PC-3 prostate cancer (CaP) cells. Suppression of AD and AI CaP cell growth by piceatannol was accompanied by cell cycle blockade in G1/S and S phases for LNCaP and PC-3 and induction of apoptosis in DU145 cells. Induction of apoptosis by piceatannol in DU145 cells was evident by reduced expression of poly(ADP-ribose) polymerase (PARP), cleavage of caspase 3 and apoptosis inducing factor AIF, and an increase in cytochrome c. The apoptotic changes occurred in concordance with DNA damage, supported by increased phosphorylated histone H2AX. Immunoblot analyses showed that exposure of different-stage CaP cells to piceatannol also resulted in cell-type-specific downregulation of mTOR and its upstream and downstream effector proteins, AKT and eIF-4E-BP1. We propose that the observed AKT and mTOR changes are new targets of piceatannol possibly contributing to its inhibitory activities on proliferation of CaP cells

High expression FUT1 and B3GALT5 is an independent predictor of postoperative recurrence and survival in hepatocellular carcinoma.

Cancer may arise from dedifferentiation of mature cells or maturation-arrested stem cells. Previously we reported that definitive endoderm from which liver was derived, expressed Globo H, SSEA-3 and SSEA-4. In this study, we examined the expression of their biosynthetic enzymes, FUT1, FUT2, B3GALT5 and ST3GAL2, in 135 hepatocellular carcinoma (HCC) tissues by qRT-PCR. High expression of either FUT1 or B3GALT5 was significantly associated with advanced stages and poor outcome. Kaplan Meier survival analysis showed significantly shorter relapse-free survival (RFS) for those with high expression of either FUT1 or B3GALT5 (P = 0.024 and 0.001, respectively) and shorter overall survival (OS) for those with high expression of B3GALT5 (P = 0.017). Combination of FUT1 and B3GALT5 revealed that high expression of both genes had poorer RFS and OS than the others (P < 0.001). Moreover, multivariable Cox regression analysis identified the combination of B3GALT5 and FUT1 as an independent predictor for RFS (HR: 2.370, 95% CI: 1.505-3.731, P < 0.001) and OS (HR: 2.153, 95% CI: 1.188-3.902, P = 0.012) in HCC. In addition, the presence of Globo H, SSEA-3 and SSEA-4 in some HCC tissues and their absence in normal liver was established by immunohistochemistry staining and mass spectrometric analysis

Critical Success Factors of Alignment between Websites and OCAs in the Manufacturing Industry

In this study, a list containing twelve organizational critical activities (OCAs) of manufacturing industry is found out by the interviews with executives and revision of two experts. The analysis on secondary data and the deeper interviews are carried out to obtain the critical success factors of the alignment between websites and OCAs in the manufacturing industry. Six common critical success factors of the three companies are: Support of Executives, Excellent and Professional Team, Full Communication, Harmonic Website Build Process, Technical Support, and Complete Information System Architecture. Finally, this study hopes that companies in the manufacturing industry can improve the competitiveness according to the result of this study

Thyroid Hormone Replacement Therapy in Patients with Various Types of Cancer

Primary hypothyroidism is a common endocrine disorder that is effectively treated with l-thyroxine (T4) replacement. Preclinical and limited clinical evidence, however, indicates that T4 is a growth factor for a variety of cancers, acting at the thyroid hormone receptor on plasma membrane integrin αvβ3. T4 is the primary ligand for this receptor, whereas 3,5,3′-triiodo-l-thyronine (T3) is the principal intracellular thyroid hormone analogue. The evidence is reviewed here that T4 is a proliferative for breast, lung, kidney and prostate cancers and for glioblastoma, regulates cancer cell respiration and is a pro-angiogenic factor in established tumors. The recommendation is made that T3 be considered alternative replacement treatment for patients with primary hypothyroidism who also have cancer

S-Petasin, the Main Sesquiterpene of Petasites formosanus, Inhibits Phosphodiesterase Activity and Suppresses Ovalbumin-Induced Airway Hyperresponsiveness

S-Petasin is the main sesquiterpene of Petasites formosanus, a traditional folk medicine used to treat hypertension, tumors and asthma in Taiwan. The aim of the present study was to investigate its inhibitory effects on phosphodiesterase (PDE) 1–5, and on ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) in a murine model of allergic asthma. S-Petasin concentration-dependently inhibited PDE3 and PDE4 activities with 50% inhibitory concentrations (IC50) of 25.5, and 17.5 μM, respectively. According to the Lineweaver-Burk analysis, S-petasin competitively inhibited PDE3 and PDE4 activities with respective dissociation constants for inhibitor binding (Ki) of 25.3 and 18.1 μM, respectively. Both IC50 and Ki values for PDE3 were significantly greater than those for PDE4. S-Petasin (10–30 μmol/kg, administered subcutaneously (s.c.)) dose-dependently and significantly attenuated the enhanced pause (Penh) value induced by methacholine (MCh) in sensitized and challenged mice. It also significantly suppressed the increases in total inflammatory cells, lymphocytes, neutrophils, eosinophils and levels of cytokines, including interleukin (IL)-2, IL-4 and IL-5, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in bronchoalveolar lavage fluid (BALF) of these mice. In addition, S-petasin (10–30 μmol/kg, s.c.) dose-dependently and significantly attenuated total and OVA-specific immunoglobulin E (IgE) levels in the serum and BALF, and enhanced the IgG2a level in serum of these mice. The PDE4H value of S-petasin was >300 μM; therefore, its PDE4H/PDE4L value was calculated to be >17. In conclusion, the present results for S-petasin at least partially explain why Petasites formosanus is used as a folk medicine to treat asthma in Taiwan