Postoperative Intensity-Modulated Radiation Therapy for Myoepithelial Carcinoma in the Parotid Gland.

Myoepithelial carcinoma (MC) is an extremely rare form of tumor, with no standard treatment established to date. Although several reports have discussed postoperative radiation therapy (PORT), few have applied intensity-modulated radiation therapy (IMRT), and none has described the dose and radiation field in detail. In this report, we describe a case of MC of the parotid gland that was treated with high-dose IMRT (70 Gy) after partial resection. The patient, a 61-year-old female, underwent excisional surgery and was diagnosed with MC arising from a pleomorphic adenoma (PA). Postoperative irradiation was administered as 70 Gy in 35 fractions of local radiation. The patient had cancer recurrence in the irradiated field. However, no serious adverse events associated with the radiation therapy have been confirmed, implying that postoperative high-dose radiation therapy may be safely administered via IMRT.

Automatic detection of acute ischemic stroke using non-contrast computed tomography and two-stage deep learning model.

BACKGROUND AND OBJECTIVE: Currently, it is challenging to detect acute ischemic stroke (AIS)-related changes on computed tomography (CT) images. Therefore, we aimed to develop and evaluate an automatic AIS detection system involving a two-stage deep learning model. METHODS: We included 238 cases from two different institutions. AIS-related findings were annotated on each of the 238 sets of head CT images by referring to head magnetic resonance imaging (MRI) images in which an MRI examination was performed within 24 h following the CT scan. These 238 annotated cases were divided into a training set including 189 cases and test set including 49 cases. Subsequently, a two-stage deep learning detection model was constructed from the training set using the You Only Look Once v3 model and Visual Geometry Group 16 classification model. Then, the two-stage model performed the AIS detection process in the test set. To assess the detection model's results, a board-certified radiologist also evaluated the test set head CT images with and without the aid of the detection model. The sensitivity of AIS detection and number of false positives were calculated for the evaluation of the test set detection results. The sensitivity of the radiologist with and without the software detection results was compared using the McNemar test. A p-value of less than 0.05 was considered statistically significant. RESULTS: For the two-stage model and radiologist without and with the use of the software results, the sensitivity was 37.3%, 33.3%, and 41.3%, respectively, and the number of false positives per one case was 1.265, 0.327, and 0.388, respectively. On using the two-stage detection model's results, the board-certified radiologist's detection sensitivity significantly improved (p-value = 0.0313). CONCLUSIONS: Our detection system involving the two-stage deep learning model significantly improved the radiologist's sensitivity in AIS detection.

TERT enhances the survival rate of human fibroblasts under endoplasmic reticulum, Golgi apparatus, and lysosomal stresses.

OBJECTIVE: The exposure of organelles, such as the endoplasmic reticulum (ER), Golgi apparatus (GA), and lysosomes, to stress activates death mechanisms. Recently, telomerase reverse transcriptase (TERT) has been shown to be involved in cell survival. However, the relationship between TERT and the stress responses is still unclear. Here, we aimed to clarify the possible mechanisms of action through which TERT promotes cell survival by studying its effect on the stresses faced by multiple organelles in human fibroblasts. RESULTS: We found that TERT enhanced the survival rate of cells under ER stress, regardless of ER stress inducers such as tunicamycin (protein glycosylation inhibitor), thapsigargin (Ca2+-ATPase inhibitor), brefeldin A (protein transport inhibitor), or dithiothreitol (disulfide bond formation inhibitor). We also found that TERT enhanced the survival rate of cells under GA and lysosomal stresses. CONCLUSION: Collectively, these results suggest that TERT suppresses cell stress and promotes cell survival via different mechanisms. These findings may offer new insights into the implications of TERT in the treatment of stress-induced conditions such as aging, obesity, and neurodegenerative diseases.

Inhibition of telomerase causes vulnerability to endoplasmic reticulum stress-induced neuronal cell death.

Endoplasmic reticulum (ER) stress is implicated in several diseases, such as cancer and neurodegenerative diseases. In the present study, we investigated the possible involvement of telomerase in ER stress-induced cell death. ER stress-induced cell death was ameliorated in telomerase reverse transcriptase (TERT) over-expressing MCF7 cells (MCF7-TERT cell). Telomerase specific inhibitor, BIBR1532, reversed the inhibitory effect of TERT on ER stress-induced cell death in MCF7-TERT cells. These findings suggest that BIBR1532 may specifically inhibit telomerase activity, thereby inducing cell death in ER stress-exposed cells. TERT was expressed in the SH-SY5Y neuroblastoma cell line. To analyze the possible involvement of telomerase in ER stress-induced neuronal cell death, we treated SH-SY5Y neuroblastoma cells with BIBR1532 and analyzed ER stress-induced cell death. We found that BIBR1532 significantly enhanced the ER stress-induced neuronal cell death. These findings suggest that inhibition of telomerase activity may enhance vulnerability to neuronal cell death caused by ER stress.

Synthesis of a peptide that can translocate to the endoplasmic reticulum.

The accumulation of unfolded proteins in the endoplasmic reticulum (ER) leads to ER stress, which has been implicated in the development of diseases. In the present study, we synthesized a peptide that entered cells and translocated to the ER. This peptide possessed fluorescein isothiocyanate (FITC), HIV-TAT, mini-αA-crystallin, and KDEL sequences. We demonstrated that this peptide entered cells and translocated to the ER. Time course experiments revealed that this peptide existed in the ER of cos-7 cells for 16 h. Furthermore, we detected the full-length peptide in cells by fluorescent immunostaining followed by SDS-PAGE. The peptide also entered glial and neuronal cells. These results suggest that this peptide has the ability to enter cells and exert chaperone activity at the ER, and provide an insight into the development of new drugs.

TERT attenuated ER stress-induced cell death.

Tumor cells are frequently encountered in nutrient-deprived areas, though the mechanisms underlying their survival are unclear. In the present study, we found that depriving cells of glucose caused endoplasmic reticulum stress (ER stress) in a breast cancer cells line, MCF-7, and that specific activation of ER stress increased telomerase reverse transcriptase (TERT) expression. TERT expression would function in counteracting against the stress because over-expression of TERT diminished ER stress-induced cell death. Therefore, the results provide evidence for the underlying mechanisms of tumor progression in stressed conditions, highlighting that ER stress induces TERT expression to withstand environmental stress, a mechanism which we termed the "ER stress-TERT axis".

Caffeine attenuated ER stress-induced leptin resistance in neurons.

Exposing the endoplasmic reticulum (ER) to stress causes the accumulation of unfolded proteins, and subsequently results in ER stress. ER stress may be involved in various disorders such as obesity, diabetes, and neurodegenerative diseases. Leptin is an important circulating hormone, that inhibits food intake and accelerates energy consumption, which suppresses body weight gain. Recent studies demonstrated that leptin resistance is one of the main factors involved in the development of obesity. We and other groups recently reported the role of ER stress in the development of leptin resistance. Therefore, identifying drugs that target ER stress may be a promising fundamental strategy for the treatment of obesity. In the present study, we investigated whether caffeine could affect ER stress and the subsequent development of leptin resistance. We showed that caffeine exhibited chaperone activity, which attenuated protein aggregation. Caffeine also inhibited the ER stress-induced activation of IRE1 and PERK, which suggested the attenuation of ER stress. Moreover, caffeine markedly improved ER stress-induced impairments in the leptin-induced phosphorylation of STAT3. Therefore, these results suggest caffeine may have pharmacological properties that ameliorate leptin resistance by reducing ER stress.