Expression of protein kinase C-delta (PKC delta) is up-regulated by apoptosis-inducing stimuli. However, very little is known about the signaling pathways that control PKC delta gene transcription. In the present study, we demonstrate that JNK stimulates PKC delta gene expression via c-Jun and ATF2 in response to the anticancer agent doxorubicin (DXR) in mouse lymphocytic leukemia L1210 cells. Luciferase reporter assays showed that DXR-induced activation of the PKC delta promoter was enhanced by ectopic expression of JNK1, c-Jun, or ATF2, whereas it was strongly reduced by expression of dominant negative JNK1 or by treatment with the JNK inhibitor SP600125. Furthermore, point mutations in the core sequence of the c-Jun/ATF2 binding site suppressed DXR-induced activation of the PKC delta promoter. Our results suggest an additional role for a JNK signaling cascade in DXR-induced PKC delta gene expression.
Activating Transcription Factor 2/*physiology ; Animals ; Anthracenes/pharmacology ; Antibiotics, Antineoplastic/*pharmacology ; Apoptosis ; Cell Line, Tumor ; Doxorubicin/*pharmacology ; Mice ; Mitogen-Activated Protein Kinase 8/*physiology ; Mutation ; Promoter Regions, Genetic ; Protein Kinase C-delta/genetics/*metabolism ; Proto-Oncogene Proteins c-jun/antagonists & inhibitors/*physiology ; Signal Transduction/physiology ; Transcription, Genetic

9-cis-retinoic acid (9CRA) plays an important role in the immune response; this includes cytokine production and cell migration. We have previously demonstrated that 9CRA increases expression of chemokine receptors CCR1 and CCR2 in human monocytes. To better understand how 9CRA induces CCR1 and CCR2 expression, we examined the contribution of signaling proteins in human monocytic THP-1 cells. The mRNA and surface protein up-regulation of CCR1 and CCR2 in 9CRA-stimulated cells were weakly blocked by the pretreatment of SB202190, a p38 MAPK inhibitor, and PD98059, an upstream ERK inhibitor. Activation of p38 MAPK and ERK1/2 was induced in both a time and dose-dependent manner after 9CRA stimulation. Both p38 MAPK and ERK1/2 phosphorylation peaked at 2 h after a 100 nM 9CRA treatment. 9CRA increased calcium influx and chemotactic activity in response to CCR1-dependent chemokines, Lkn-1/CCL15, MIP-1alpha/CCL3, and RANTES/CCL5, and the CCR2-specific chemokine, MCP-1/CCL2. Both SB202190 and PD98059 pretreatment diminished the increased calcium mobilization and chemotactic ability due to 9CRA. SB202190 inhibited the expression and functional activities of CCR1 and CCR2 more effectively than did PD98059. Therefore, our results demonstrate that 9CRA transduces the signal through p38 MAPK and ERK1/2 for CCR1 and CCR2 up-regulation, and may regulate the pro-inflammatory process through the p38 MAPK and ERK-dependent signaling pathways.
Calcium Signaling/drug effects ; Cell Line ; Chemokines/pharmacology ; Chemotaxis, Leukocyte/drug effects ; Enzyme Activation/drug effects ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; Flavonoids/pharmacology ; Gene Expression Regulation/*drug effects ; Humans ; Imidazoles/pharmacology ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Monocytes/drug effects/*enzymology ; Pyridines/pharmacology ; RNA, Messenger/genetics/metabolism ; Receptors, CCR1 ; Receptors, CCR2 ; Receptors, Chemokine/*genetics/metabolism ; Tretinoin/*pharmacology ; p38 Mitogen-Activated Protein Kinases/*metabolism

PURPOSE: To see the gross tumor volume (GTV) dependency according to the phase selection and reconstruction methods, we measured and analyzed the changes of tumor volume and motion at each phase in 20 cases with lung cancer patients who underwent image-guided radiotherapy. MATERIALS AND METHODS: We retrospectively analyzed four-dimensional computed tomography (4D-CT) images in 20 cases of 19 patients who underwent image-guided radiotherapy. The 4D-CT images were reconstructed by the maximum intensity projection (MIP) and the minimum intensity projection (Min-IP) method after sorting phase as 40%–60%, 30%–70%, and 0%–90%. We analyzed the relationship between the range of motion and the change of GTV according to the reconstruction method. RESULTS: The motion ranges of GTVs are statistically significant only for the tumor motion in craniocaudal direction. The discrepancies of GTV volume and motion between MIP and Min-IP increased rapidly as the wider ranges of duty cycles are selected. CONCLUSION: As narrow as possible duty cycle such as 40%–60% and MIP reconstruction was suitable for lung cancer if the respiration was stable. Selecting the reconstruction methods and duty cycle is important for small size and for large motion range tumors.
Four-Dimensional Computed Tomography* ; Humans ; Lung Neoplasms* ; Lung* ; Methods* ; Radiotherapy, Image-Guided ; Range of Motion, Articular ; Respiration ; Retrospective Studies ; Tumor Burden*

PURPOSE: To see the gross tumor volume (GTV) dependency according to the phase selection and reconstruction methods, we measured and analyzed the changes of tumor volume and motion at each phase in 20 cases with lung cancer patients who underwent image-guided radiotherapy. MATERIALS AND METHODS: We retrospectively analyzed four-dimensional computed tomography (4D-CT) images in 20 cases of 19 patients who underwent image-guided radiotherapy. The 4D-CT images were reconstructed by the maximum intensity projection (MIP) and the minimum intensity projection (Min-IP) method after sorting phase as 40%–60%, 30%–70%, and 0%–90%. We analyzed the relationship between the range of motion and the change of GTV according to the reconstruction method. RESULTS: The motion ranges of GTVs are statistically significant only for the tumor motion in craniocaudal direction. The discrepancies of GTV volume and motion between MIP and Min-IP increased rapidly as the wider ranges of duty cycles are selected. CONCLUSION: As narrow as possible duty cycle such as 40%–60% and MIP reconstruction was suitable for lung cancer if the respiration was stable. Selecting the reconstruction methods and duty cycle is important for small size and for large motion range tumors.
Four-Dimensional Computed Tomography* ; Humans ; Lung Neoplasms* ; Lung* ; Methods* ; Radiotherapy, Image-Guided ; Range of Motion, Articular ; Respiration ; Retrospective Studies ; Tumor Burden*

OBJECTIVE: To evaluate the care status of the amyotrophic lateral sclerosis (ALS) patients with long-term use of tracheostomy tube by caregivers of ALS patients. METHODS: A survey was conducted in the form of questionnaires to ALS patients and their caregivers. All measurements were performed by two visiting nurses. For statistical analysis, SPSS ver. 22.0 and Mann-Whitney U test on non-normal distribution were used. RESULTS: In total, 19 patients (15 males and 4 females) and their caregivers participated in the survey. In the case of patients, the average duration of care was 5.9+/-3.7 years, and the mean periods of illness and tracheostomy were 5.3+/-3.2 years and 3.0+/-2.6 years, respectively. Replacement intervals were 14 days in 11 patients, 7 days in 4 patients, 28 days in 2 patients, and 21 days in 1 patient. One patient was unable to provide an accurate replacement interval. Eighteen (99%) caregivers had experience of adding volume to a cuff without pressure measure in the following instances: due to patients' needs in 7 cases, air leakage in 7 cases, and no reason in 4 cases. Mean pressure of tracheostomy cuff was 40+/-9.4 cmH2O, and air volume of tracheostomy cuff was 6.7+/-3.2 mL, but real mean volume was 7.0+/-2.9 mL. The number of suctioning for airway clearance was a mean 27.5+/-18.2 times a day. CONCLUSION: According to this survey, we notice that almost all the patients and caregivers had an erroneous idea about cuff volume and pressure. Moreover, education and long-term professional care of tracheostomy cannot be overemphasized in this manner.
Amyotrophic Lateral Sclerosis ; Caregivers ; Education ; Humans ; Long-Term Care ; Male ; Nurses, Community Health ; Suction ; Tracheostomy*

Purpose: This study aimed to evaluate the long-term effect of esophagectomy in patients with esophageal squamous cell carcinoma (ESCC) by comparing the chemoradiotherapy (CRT)-only group and the trimodality treatment (TMT) group who received concurrent CRT followed by surgery. Materials and Methods: We included 412 operable ESCC patients treated with TMT or CRT between January 2005 and December 2015. The oncological outcomes of the two groups were compared using a weighted Cox proportional-hazards model with inverse probability of treatment weighting (IPTW). Results: The median survival time was 64 and 32 months in the TMT (n=270) and CRT (n=142) groups, respectively (p < 0.001). After IPTW, the median overall survival (OS) remained significantly higher in the TMT group than in the CRT group (61 months vs. 32 months, p=0.016). Moreover, the TMT group showed a better local recurrence-free rate (LRFR, p < 0.001) and distant metastasis-free rate (p=0.007). In the subgroup of patients with clinical complete response (cCR), the OS was not significantly different between the two groups, both before and after IPTW adjustment (p=0.35 and p=0.93). However, among non-cCR patients, the OS was significantly higher in the TMT group (64% vs. 45%, p < 0.001). Conclusion In patients with locally advanced ESCC, TMT was superior to CRT in terms of OS and LRFR. Such difference was more prominent in the non-cCR subgroup. In patients who achieved cCR, esophagectomy was effective in improving LRFR but not OS, suggesting that esophagectomy may be omitted in complete responders.