Semiquantitative Analysis by Scanning Electron Microscopy of Cochlear Hair Cell Damage by Ototoxic Drugs

The ototoxicity of cisplatin and carboplatin in the organ of Corti of the guinea pig was evaluated semiquantitatively. Damage of the stereocilia of outer hair cells (OHCs) observed by scanning electron microscopy (SEM) was classified into normal, grade 1 (10-50% loss of stereocilia), grade 2 (less than 50% remaining stereocilia), or grade 3 (missing stereocilia). The OHCs observed by light microscopy (LM) were classified as remaining or missing cells. Fifty OHCs of each row in the middle part of each turn of the cochlea were counted (a total of 150 cells per turn). Guinea pigs were administered 5 mg/kg of cisplatin or 50 mg/kg of carboplatin intraperitoneally for three consecutive days. In groups 1 and 2, in which both cochleae were fixed in 2.5% glutaraldehyde and 1% osmium tetroxide (OsO4) and observed by SEM, the percentages of damage of the OHC stereocilia were similar in each cochlear turn bilaterally. In group 3, the right cochleae were fixed in OsO4 and observed by phase contrast microscopy as surface preparations. Left cochleae were submitted for SEM observation. Missing and grade 3 cells were observed at similar percentages in each row of each turn. In group 4, succinate dehydrogenase staining was performed in the right cochleae and observed by LM. The degree of damage in the right cochleae was compared with that of the left cochleae which was observed by SEM. On average, the mean numbers of missing cells and cells showing grade 3 damage were similar in each row of each turn. From these similarities of evaluation of ototoxicity at LM and SEM levels, it was concluded that semiquantitative analysis by SEM only is appropriate for the assessment of ototoxicity

Interleukin-1α enhances the aggressive behavior of pancreatic cancer cells by regulating the α(6)β(1)-integrin and urokinase plasminogen activator receptor expression

BACKGROUND: In human pancreatic cancer progression, the α(6)β(1)-integrin is expressed on cancer cell surface during invasion and metastasis formation. In this study, we investigated whether interleukin (IL)-1α induces the alterations of integrin subunits and urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) expression in pancreatic cancer cells. We hypothesize that the alterations of integrin subunits and uPA/uPAR expression make an important role in signaling pathways responsible for biological behavior of pancreatic cancer cells. RESULTS: IL-1α upregulated the expression of α(6 )and β(1 )integrins without any alterations of α(5 )and α(v )integrins expression. IL-1α also induced enhancement in the expression of uPA/uPAR in pancreatic cancer cells. IL-1α enhanced the proliferation, adhesion, and migration in pancreatic cancer cells, and IL-1α-induced alterations of uPA/uPAR expression correlated with the increased the migration of pancreatic cancer cells. Upregulation of α(6 )integrin subunit and uPA/uPAR correlated with the activation of Ras and downstream extracellular signal-regulated kinase (ERK) pathways. IL-1α-induced activation of Ras and downstream ERK can be inhibited by using inhibitory antibodies against α(6 )and β(1 )integrin and uPAR, consistent with the inhibition of proliferation, adhesion and migration of pancreatic cancer cells. Immunohistochemical analysis demonstrated a significant association between strong expressions of α(6 )integrin with uPAR in pancreatic cancer specimens. Furthermore, the strong expression of α(6 )integrin and uPAR was found to be independent prognosticator in pancreatic cancer patients. CONCLUSION: Based on these findings, we conclude that IL-1α can induce selective upregulation of α(6)β(1)-integrin and uPA/uPAR in pancreatic cancer cells and these changes may modulate the aggressive functions of pancreatic cancer

The Effects of Malonic Acid Derivatives and Acetic Acid Derivatives as Coadsorbents on the Photovoltaic Performance of Dye-Sensitized Solar Cells

The effects of malonic acid derivatives and acetic acid derivatives as coadsorbents on the photovoltaic performance of D908 dye-sensitized nanocrystalline TiO 2 solar cells were investigated. Each of phenylmalonic acid (PMA) and cyclopentylacetic acid (CPEAA) coadsorptions was revealed to improve both the photocurrent and the photovoltage of the solar cells. The improved photocurrent was probably due to the suppression of self-quenching of the excited electrons in the dyes by coadsorption of PMA or CPEAA on the TiO 2 that increased in the electron-injection yields from the dye to the TiO 2 . The improved photovoltage was probably due to suppression of recombination between the injected electrons and I 3 − ions on the TiO 2 surface. ATR-FTIR spectroscopy indicated that PMA or CPEAA coadsorption increased the content of bound dye on the TiO 2 surface. This result suggests that PMA or CPEAA coadsorption improved the photocurrent of the solar cells. Electrochemical impedance spectroscopy indicated that PMA or CPEAA coadsorption on the TiO 2 surface increased the charge recombination resistance (R2) and decreased the diffusion resistance in the electrolyte (R3). These results suggest that the coadsorption of PMA or CPEAA on the TiO 2 may improve its photovoltage and photocurrent

The stem cell factor/c-kit receptor pathway enhances proliferation and invasion of pancreatic cancer cells

BACKGROUND: The transmembrane protein c-kit is a receptor tyrosine kinase (KIT) and KIT is expressed in solid tumors and hematological malignancies such as gastrointestinal stromal tumor (GIST), small-cell lung cancer and chronic myelogenous leukemia (CML). KIT plays a critical role in cell proliferation and differentiation and represents a logical therapeutic target in GIST and CML. In pancreatic cancer, c-kit expression has been observed by immunohistochemical techniques. In this study, we examined the influence of c-kit expression on proliferation and invasion using five pancreatic cancer cell lines. In addition, the inhibitory effect of imatinib mesylate on stem cell factor (SCF)-induced proliferation and invasion was evaluated. Finally, we also analyzed KIT and SCF expression in pancreatic cancer tissues using immunohistochemistry and correlated the results with clinical features. RESULTS: RT-PCR revealed that two pancreatic cancer cell lines, PANC-1 and SW1990, expressed c-kit mRNA. By Western blot analysis, c-kit protein was also present in those lines. In KIT-positive pancreatic cancer cell lines, proliferation and invasion were significantly enhanced by addition of SCF. In contrast, SCF did not enhance proliferation and invasion in the three KIT-negative lines (BxPC-3, Capan-2 and MIA PaCa-2). 5 μM imatinib mesylate significantly inhibited SCF-enhanced proliferation to the same extent compared with the control. Similarly, SCF-enhanced invasive ability was significantly inhibited by 5 μM imatinib mesylate. KIT was expressed in 16 of 42 clinical specimens by immunohistochemistry, and KIT expression was significantly related to venous system invasion. Furthermore, patients expressing both KIT and SCF had a somewhat lower survival. CONCLUSION: Our results demonstrated that the SCF-KIT pathway enhanced the proliferation and invasiveness in KIT-positive pancreatic cancer cell lines and that the enhanced proliferation and invasion were inhibited by imatinib mesylate. We propose that inhibitors of c-kit tyrosine kinase receptor have the potential to slow the progression of KIT-positive pancreatic cancers

Successful paclitaxel-based chemotherapy for an alpha-fetoprotein-producing gastric cancer patient with multiple liver metastases

<p>Abstract</p> <p>Background</p> <p>Alpha-fetoprotein (AFP)-producing gastric cancer is known to frequently cause multiple liver metastases and to have an extremely poor prognosis.</p> <p>Case presentation</p> <p>A 64-year-old Japanese man admitted to our hospital was diagnosed with gastric cancer with liver metastases. He underwent a total gastrectomy with splenectomy, and pathological stage IV disease according to the classification proposed by the Japanese Gastric Cancer Association was assigned. The histological diagnosis was poorly differentiated adenocarcinoma, and tumor production of AFP was confirmed by immunohistochemical staining. Following surgery, the patient received combination chemotherapy consisting of TS-1 and paclitaxel. Initially, AFP levels decreased dramatically and computed tomography (CT) revealed regression of liver metastases. However, multiple new liver metastases appeared and serum AFP levels increased after 5 months. A regimen of 5-FU plus paclitaxel followed by paclitaxel monotherapy was used next. Serum AFP levels once again decreased and CT showed regression or disappearance of liver metastases. The patient currently has a very good quality of life, and is receiving weekly paclitaxel monotherapy as an outpatient. No progression of liver metastases has been observed to date.</p> <p>Conclusion</p> <p>We consider this rare case to have significant value with respect to treatment of AFP-producing gastric cancer with multiple liver metastases, and propose that combining surgery with chemotherapeutic agents such as paclitaxel may lead to a better prognosis in such cases.</p

Effect of Patient Clinical Variables in Osteoporosis Classification Using Hip X-rays in Deep Learning Analysis

Background and Objectives: A few deep learning studies have reported that combining image features with patient variables enhanced identification accuracy compared with image-only models. However, previous studies have not statistically reported the additional effect of patient variables on the image-only models. This study aimed to statistically evaluate the osteoporosis identification ability of deep learning by combining hip radiographs with patient variables. Materials andMethods: We collected a dataset containing 1699 images from patients who underwent skeletal-bone-mineral density measurements and hip radiography at a general hospital from 2014 to 2021. Osteoporosis was assessed from hip radiographs using convolutional neural network (CNN) models (ResNet18, 34, 50, 101, and 152). We also investigated ensemble models with patient clinical variables added to each CNN. Accuracy, precision, recall, specificity, F1 score, and area under the curve (AUC) were calculated as performance metrics. Furthermore, we statistically compared the accuracy of the image-only model with that of an ensemble model that included images plus patient factors, including effect size for each performance metric. Results: All metrics were improved in the ResNet34 ensemble model compared with the image-only model. The AUC score in the ensemble model was significantly improved compared with the image-only model (difference 0.004; 95% CI 0.002-0.0007; p = 0.0004, effect size: 0.871). Conclusions: This study revealed the additional effect of patient variables in identification of osteoporosis using deep CNNs with hip radiographs. Our results provided evidence that the patient variables had additive synergistic effects on the image in osteoporosis identification

Two Ck1δ transcripts regulated by m6A methylation code for two antagonistic kinases in the control of the circadian clock.

Fustin, J.-M., Kojima, R., Itoh, K., Chang, H.-Y., Shiqi, Y., Zhuang, B., . . . Okamura, H. (2018). Two Ck1δ transcripts regulated by m6A methylation code for two antagonistic kinases in the control of the circadian clock. Proceedings of the National Academy of Sciences of the United States of America, 115(23), 5980-5985. doi:10.1073/pnas.172137111