Mechanical regulation of cancer cell apoptosis and autophagy: Roles of bone morphogenetic protein receptor, Smad1/5, and p38 MAPK

AbstractMechanical forces induced by interstitial fluid flow in and surrounding tissues and by blood/lymphatic flow in vessels may modulate cancer cell invasion and metastasis and anticancer drug delivery. Our previous study demonstrated that laminar flow-induced shear stress induces G2/M arrest in tumor cells. However, whether shear stress modulates final cell fate remains unclear. In this study, we investigated the role of flow-induced shear stress in modulating the survival of four human tumor cell lines, i.e., Hep3B hepatocarcinoma cells, MG63 osteosarcoma cells, SCC25 oral squamous carcinoma cells, and A549 carcinomic alveolar basal epithelial cells. Laminar shear stress (LSS) ranging from 0.5 to 12dyn/cm2 induced death of these four tumor cell lines. In contrast to LSS at 0.5dyn/cm2, oscillatory shear stress (OSS) at 0.5±4dyn/cm2 cannot induce cancer cell death. Both LSS and OSS had no effect on human normal hepatocyte, lung epithelial, and endothelial cells. Application of LSS to these four cell lines increased the percentage of cells stained positively for annexin V–FITC, with up-regulations of cleaved caspase-8, -9, and -3, and PARP. In addition, LSS also induced Hep3B cell autophagy, as detected by acidic vesicular organelle formation, LC3B transformation, and p62/SQSTM1 degradation. By transfecting with small interfering RNA, we found that the shear-induced apoptosis and autophagy are mediated by bone morphogenetic protein receptor type (BMPR)-IB, BMPR-specific Smad1 and Smad5, and p38 mitogen-activated protein kinase in Hep3B cells. Our findings provide insights into the molecular mechanisms by which shear stress induces apoptosis and autophagy in tumor cells

Concurrent Papillary Thyroid Cancer with Pituitary ACTH-secreting Tumor

Concomitant thyroid cancer with pituitary tumor is uncommon. This study reports a case of advanced papillary thyroid carcinoma with pituitary adrenocorticotropic hormone (ACTH)-secreting tumor. A 58-year-old male patient had thyroid cancer in 1991 and presented with headache caused by pituitary tumor with apoplexy in 1993. Due to hypopituitarism, the patient underwent radioactive iodide (131I) for detection and treatment of metastatic thyroid cancer after the use of recombinant human thyroid-stimulating hormone (rhTSH) in 2000. During follow-up for thyroid cancer 201thallium scan proved to be an effective tool for detecting metastatic thyroid cancer in the patient without pituitary TSH reserve. Pituitary ACTH-secreting tumor was confirmed in 2001 based on the high serum ACTH level and positive immunohistochemical stain for ACTH. The patient had no Cushingoid features. Moreover, serum ACTH levels were 337 and 232 pg/mL with normal serum cortisol and urine-free cortisol. Although the patient underwent three operations and a total of 370 mCi 131I therapy for recurrent thyroid cancer, the cancer continued to progress. Finally, the patient died of pneumonia with septic shock 12 years after the diagnosis of thyroid cancer. [J Formos Med Assoc 2007;106(4):330-335

Fabrication and Characterization of High-Sensitivity Underwater Acoustic Multimedia Communication Devices with Thick Composite PZT Films

This paper presents a high-sensitivity hydrophone fabricated with a Microelectromechanical Systems (MEMS) process using epitaxial thin films grown on silicon wafers. The evaluated resonant frequency was calculated through finite-element analysis (FEA). The hydrophone was designed, fabricated, and characterized by different measurements performed in a water tank, by using a pulsed sound technique with a sensitivity of −190 dB ± 2 dB for frequencies in the range 50-500 Hz. These results indicate the high-performance miniaturized acoustic devices, which can impact a variety of technological applications

Therapeutic Lung Lavage with Diluted Surfactant in Neonates with Severe Meconium Aspiration Syndrome

Meconium aspiration syndrome (MAS) may result in considerable morbidity and mortality in newborn infants. The current standard treatment is still in need of improvement for the most severe patients. We report 3 cases with devastating MAS that was successfully treated with therapeutic lung lavage. These cases were all delivered in local obstetrics clinics or hospitals with meconium-stained amniotic fluid and non-vigorous appearance at birth. However, no endotracheal suction was performed when they were born. All of them suffered from severe hypoxia and unstable vital signs despite there being high ventilatory settings when they were transferred to the tertiary medical center. Therapeutic lung lavage with diluted surfactant (Survanta, 5 mg/mL, 30 mL/kg in 2 aliquots) was performed within 24 hours of age. Bloody fluid (about 40–50% of total lavage amount) was recovered in all 3 cases. Although brief desaturation and bradycardia were observed during the procedures, 2 of them tolerated the procedures well and improved soon after lavage. The other patient received lung lavage in a relatively unstable condition and needed chest tapping to relieve bilateral pleural effusion. Their respiratory condition improved after the procedures, and they were all discharged within 1 month without major respiratory complications. These successful experiences are compatible with previous animal studies and other case reports with different lavage protocols. We conclude that therapeutic lung lavage may improve the outcome in newborn infants with severe MAS, and there were no significant adverse side effects observed. Before performing lung lavage, stabilization and optimal support may prevent unexpected results during and after lavage

Fabrication and Characterization of High-Sensitivity Underwater Acoustic Multimedia Communication Devices with Thick Composite PZT Films

This paper presents a high-sensitivity hydrophone fabricated with a Microelectromechanical Systems (MEMS) process using epitaxial thin films grown on silicon wafers. The evaluated resonant frequency was calculated through finite-element analysis (FEA). The hydrophone was designed, fabricated, and characterized by different measurements performed in a water tank, by using a pulsed sound technique with a sensitivity of −190 dB ± 2 dB for frequencies in the range 50–500 Hz. These results indicate the high-performance miniaturized acoustic devices, which can impact a variety of technological applications

Effects of Acupuncture at Neiguan (PC 6) on Electroencephalogram

Abstract The aim of this study was to investigate if there were any effects on the electroencephalogram (EEG) of human brain by the manual stimulation of Neiguan (PC 6) acupuncture site. In this paper, two groups of six healthy male volunteers of ages 27.6 ± 14.2 (mean ± SD) and 28.5 ± 13.0 (mean ± SD) and no neurological disease participated in this study. A digital storage of 12-channel EEG recorder was used and spectral analyses of the data set of 18 trials were obtained before, during, and after sham/ manual acupuncture. To minimize artefacts, all data were collected with the subjects alert but eyes closed. No significant changes (P > 0.05) were obtained for the sham acupuncture group. As for the manual acupuncture group, the needle was inserted perpendicularly into the PC 6 acupuncture site and manually stimulated about 15 to 30 seconds to achieve De Qi sensation. Needles were left in place for 30 min and then removed. Analysis of the EEG data due to acupuncture was compared to the baseline data and changes were obtained. First, all trials had an increase in the amplitude and power of the alpha band during manual acupuncture (P < 0.05) when compared with the baseline data. Secondly, in the mean time, the frequency peaks in alpha band of 12-channels were all synchronized with much smaller standard deviation (P < 0.01). Thirdly, the manual acupuncture effects of higher power and synchronized frequencies persisted for at least 10 minutes after the experiment (P < 0.05) and did not disappear immediately for all 18 experiments. Finally, we hypothesized that the higher power and synchronized rhythms in brain oscillations may have to do with autonomic nervous system

Impact Analysis of Earthquake-Induced Cracks in Deep Geological Repositories for Nuclear Waste Fuel

Based on the concept of deep geologic repositories, high-level radioactive waste will be stored in deep deposition holes away from the ground surface. The heat generated by the waste will induce both significant stress increments and ground water seepage in a multiple geologic barrier system. The long-term ability of a barrier system is significantly impacted by coupling between the thermal, hydrological, and mechanical processes. The stability of a system may also depend particularly upon unanticipated factors such as the development of post-earthquake macrocracks. Therefore, this study investigates the three-dimensional transient and long term thermo-hydro-mechanical behavior of a barrier system. The results can be used for future reference in practical engineering design.高放射性用過核燃料所產生之長期衰變熱會對生物圈造成極大衝擊，目前國際上多傾向以深層地質處置作為最終處置之方式。處置過程中，極可能因為地震或地層變動等不可預期之因素，在天然障壁中產生大形裂縫，由此伴隨的災損效應將會加速障壁之劣化。本研究依據我國深層地質處置的初步設計概念，針對天然障壁系統長期之熱-水力-力學耦合效應，利用依序耦合分析方法，考慮不同的裂縫尺寸，針對其可能引致之熱應力與地下水影響進行評估