Risk of thoracic soft tissue sarcoma after breast cancer radiotherapy: a population-based cohort study in Osaka, Japan.

Postoperative radiotherapy for breast cancer reportedly increases the risk of thoracic soft tissue sarcomas, particularly angiosarcomas; however, the risk in the Japanese population remains unknown. Therefore, this study aimed to investigate the incidence of thoracic soft tissue sarcoma among patients with breast cancer in Japan and determine its association with radiotherapy. This retrospective cohort study used data from the population-based cancer registry of the Osaka Prefecture. The inclusion criteria were female sex, age 20-84 years, diagnosis of breast cancer between 1990 and 2010, no supraclavicular lymph node or distant metastasis, underwent surgery and survived for at least 1 year. The primary outcome was the occurrence of thoracic soft tissue sarcomas 1 year or later after breast cancer diagnosis. Among the 13 762 patients who received radiotherapy, 15 developed thoracic soft tissue sarcomas (nine angiosarcomas and six other sarcomas), with a median time of 7.7 years (interquartile range, 4.0-8.6 years) after breast cancer diagnosis. Among the 27 658 patients who did not receive radiotherapy, four developed thoracic soft tissue sarcomas (three angiosarcomas and one other sarcoma), with a median time of 11.6 years after diagnosis. The 10-year cumulative incidence was higher in the radiotherapy cohort than in the non-radiotherapy cohort (0.087 vs. 0.0036%, P < 0.001). Poisson regression analysis revealed that radiotherapy increased the risk of thoracic soft tissue sarcoma (relative risk, 6.8; 95% confidence interval, 2.4-24.4). Thus, although rare, breast cancer radiotherapy is associated with an increased risk of thoracic soft tissue sarcoma in the Japanese population.

Acquisition of drug resistance in endothelial cells by tumor-derived extracellular vesicles and cancer progression.

Angiogenesis by endothelial cells (ECs) is essential for tumor growth. Angiogenesis inhibitors are used in combination with anticancer drugs in many tumor types, but tumors eventually become resistant. Previously, the underlying mechanism for developing drug resistance was considered to be a change in the characteristics of tumor cells whereas ECs were thought to be genetically stable and do not contribute to drug resistance. However, tumor endothelial cells (TECs) have been shown to differ from normal endothelial cells (NECs) in that they exhibit chromosomal abnormalities, angiogenic potential, and drug resistance. Extracellular vesicles (EVs) secreted by tumor cells have recently attracted attention as a factor involved in the acquisition of such abnormalities. Various cells communicate with each other through EVs, and it has been reported that tumor-derived EVs act on other tumor cells or stromal cells to develop drug resistance. Drug-resistant tumor cells confer drug resistance to recipient cells by transporting mRNAs encoding ATP-binding cassette subfamily B member 1 (ABCB1) and ATP-binding cassette subfamily C member 1 (ABCC1) as well as miRNAs involved in signaling such as Akt, drug efflux transporters, and P-glycoprotein modulators via EVs. However, there are limited reports on the acquisition of drug resistance in ECs by tumor-derived EVs. Since drug resistance of ECs may induce tumor metastasis and support tumor cell proliferation, the mechanism underlying the development of resistance should be elucidated to find therapeutic application. This review provides insight into the acquisition of drug resistance in ECs via tumor EVs in the tumor microenvironment.

Combination treatment with paclitaxel, carboplatin and cetuximab in maxillary sinus cancer: A case report.

The standard treatment for maxillary sinus cancer is surgery; however, surgery for advanced cases often leads to significant aesthetic and functional disability. Combination treatment (induction chemotherapy) with paclitaxel, carboplatin and cetuximab (PCE) can be effective in head and neck cancer. The present study describes the case of a patient with advanced maxillary sinus cancer that was successfully treated using the PCE regimen. A 69-year-old man presented to the Department of Dentistry and Oral Surgery, Hokuto Hospital (Obihiro, Japan) with left buccal swelling and an irregular mass on the left maxillary gingiva. The lesion filled the ethmoid and maxillary sinus, and destroyed the pterygoid process. Numerous lymph node metastases were suspected in the bilateral cervical region. The patient was diagnosed with left maxillary sinus cancer T4aN2cM0 and treated with PCE. The size of the tumor was markedly reduced after the initial treatment. After six cycles of PCE, bioradiotherapy (BRT; 66 Gy/33 Fr) was performed for the remaining lesion, and a complete response was achieved. Ten months after BRT, the tumor recurred in the anterior wall of the left maxillary sinus, which was treated by partial maxillary resection and split-thickness skin grafting. No local or cervical recurrence was observed 2 years after the surgery. These findings suggested that PCE could be considered as the first step for the treatment of highly advanced malignant tumors in the head and neck.

Prednisolone improves hippocampal regeneration after trimethyltin-induced neurodegeneration in association with prevention of T lymphocyte infiltration.

The endogenous regenerative capacity of the brain is quite weak; however, a regenerative reaction, the production of new neurons (neurogenesis), has been reported to occur in brain lesions. In addition, leukocytes are well known to infiltrate brain lesions. Therefore, leukocytes would also have a link with regenerative neurogenesis; however, their role has not been fully elucidated. In this study, we investigated leukocyte infiltration and its influence on brain tissue regeneration in a trimethyltin (TMT)-injected mouse model of hippocampal regeneration. Immunohistochemically, CD3-positive T lymphocytes were found in the hippocampal lesion of TMT-injected mice. Prednisolone (PSL) treatment inhibited T lymphocyte infiltration and increased neuronal nuclei (NeuN)-positive mature neurons and doublecortin (DCX)-positive immature neurons in the hippocampus. Investigation of bromodeoxyuridine (BrdU)-labeled newborn cells revealed the percentage of BrdU/NeuN- and BrdU/DCX-positive cells increased by PSL treatment. These results indicate that infiltrated T lymphocytes prevent brain tissue regeneration by inhibiting hippocampal neurogenesis.

Outcomes in patients with high- and very high-risk localized prostate cancer treated with definitive IMRT and long-term hormone therapy.

BACKGROUND: The aim of this study was to evaluate the effectiveness of intensity-modulated radiation therapy in combination with long-term androgen deprivation therapy for high-risk and very high-risk localized prostate cancer while also investigating factors associated with the therapeutic effect. METHODS: Men who fulfilled criteria for the National Comprehensive Cancer Network high-risk or very high-risk localized prostate cancer and were treated with definitive intensity-modulated radiation therapy (74-78 Gy) of the prostate and the seminal vesicle combined with androgen deprivation therapy in our institution from 2007 to 2016 were identified (n = 197). In principle, patients received androgen deprivation therapy for 3-6 months before radiation, concurrently, and for 2 years after completion of intensity-modulated radiation therapy. RESULTS: The median follow-up period was 96 months. The 5-year and 10-year overall survival rates in the overall population were 96.9% and 89.3%, respectively. The 5-year and 10-year cumulative incidence rates of biochemical failure were 2.5% and 16.3% in the high-risk group, and 8.6% and 32.0% in the very high-risk group, respectively, indicating a significant difference between the two groups (P = 0.023). Grade Group 5 and younger age (cutoff: 70 years old) were independent predictors of recurrence (P = 0.016 and 0.017, respectively). Patients exhibiting biochemical failure within <18 months after completion of androgen deprivation therapy displayed an increased risk of cancer-specific mortality (P = 0.039) when contrasted with those who had a longer interval to biochemical failure. CONCLUSIONS: Patients with the National Comprehensive Cancer Network very high-risk prostate cancer, particularly those with Grade Group 5 and younger age, showed worse outcomes following intensity-modulated radiation therapy and long-term androgen deprivation therapy.

mHealth Intervention to Promote Physical Activity Among Employees Using a Deep Learning Model for Passive Monitoring of Depression and Anxiety: Single-Arm Feasibility Trial.

BACKGROUND: Physical activity effectively prevents depression and anxiety. Although mobile health (mHealth) technologies offer promising results in promoting physical activity and improving mental health, conflicting evidence exists on their effectiveness, and employees face barriers to using mHealth services. To address these problems, we recently developed a smartphone app named ASHARE to prevent depression and anxiety in the working population; it uses a deep learning model for passive monitoring of depression and anxiety from information about physical activity. OBJECTIVE: This study aimed to preliminarily investigate (1) the effectiveness of the developed app in improving physical activity and reducing depression and anxiety and (2) the app's implementation outcomes (ie, its acceptability, appropriateness, feasibility, satisfaction, and potential harm). METHODS: We conducted a single-arm interventional study. From March to April 2023, employees aged ≥18 years who were not absent were recruited. The participants were asked to install and use the app for 1 month. The ideal usage of the app was for the participants to take about 5 minutes every day to open the app, check the physical activity patterns and results of an estimated score of psychological distress, and increase their physical activity. Self-reported physical activity (using the Global Physical Activity Questionnaire, version 2) and psychological distress (using the 6-item Kessler Psychological Distress Scale) were measured at baseline and after 1 month. The duration of physical activity was also recorded digitally. Paired t tests (two-tailed) and chi-square tests were performed to evaluate changes in these variables. Implementation Outcome Scales for Digital Mental Health were also measured for acceptability, appropriateness, feasibility, satisfaction, and harm. These average scores were assessed by comparing them with those reported in previous studies. RESULTS: This study included 24 employees. On average, the app was used for 12.54 days (44.8% of this study's period). After using the app, no significant change was observed in physical activity (-12.59 metabolic equivalent hours per week, P=.31) or psychological distress (-0.43 metabolic equivalent hours per week, P=.93). However, the number of participants with severe psychological distress decreased significantly (P=.01). The digitally recorded duration of physical activity increased during the intervention period (+0.60 minutes per day, P=.08). The scores for acceptability, appropriateness, and satisfaction were lower than those in previous mHealth studies, whereas those for feasibility and harm were better. CONCLUSIONS: The ASHARE app was insufficient in promoting physical activity or improving psychological distress. At this stage, the app has many issues that are to be addressed in terms of both implementation and effectiveness. The main reason for this low effectiveness might be the poor evaluation of the implementation outcomes by app users. Improving acceptability, appropriateness, and satisfaction are identified as key issues to be addressed in future implementation. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN000050430; https://tinyurl.com/mrx5ntcmrecptno=R000057438.

Blue organic light-emitting diode with a turn-on voltage of 1.47 V.

Among the three primary colors, blue emission in organic light-emitting diodes (OLEDs) are highly important but very difficult to develop. OLEDs have already been commercialized; however, blue OLEDs have the problem of requiring a high applied voltage due to the high-energy of blue emission. Herein, an ultralow voltage turn-on at 1.47 V for blue emission with a peak wavelength at 462 nm (2.68 eV) is demonstrated in an OLED device with a typical blue-fluorescent emitter that is widely utilized in a commercial display. This OLED reaches 100 cd/m2, which is equivalent to the luminance of a typical commercial display, at 1.97 V. Blue emission from the OLED is achieved by the selective excitation of the low-energy triplet states at a low applied voltage by using the charge transfer (CT) state as a precursor and triplet-triplet annihilation, which forms one emissive singlet from two triplet excitons.

Linear accelerator-based stereotactic radiotherapy for brain metastases, including multiple and large lesions, carries a low incidence of acute toxicities: a retrospective analysis.

BACKGROUND: Data on acute toxicities after stereotactic radiotherapy (SRT) for brain metastases, including multiple and large lesions, are lacking. We aimed to evaluate the incidence and nature of toxicities immediately after SRT using a linear accelerator. METHODS: This retrospective study reviewed the medical records of 315 patients with brain metastases treated with SRT at our institution between May 2019 and February 2022. In total, 439 SRT sessions were performed for 2161 brain metastases. The outcome of interest was immediate side effects (ISEs), defined as new or worsening symptoms occurring during SRT or within 14 days after the end of SRT. RESULTS: Grade ≥ 2 and ≥ 3 ISEs occurred in 16 (3.6%) and 7 (1.6%) cases, respectively. Among 63 treatments for 10 or more lesions (range: 10-40), 1 (1.6%) ISE occurred. Among 22 treatments for lesions with a maximum tumor volume of > 10 cc, 2 (9.1%) ISEs occurred. Grade ≥ 3 ISEs included 1, 4, 1, and 1 cases of grade 3 nausea, grade 3 new-onset partial and generalized seizures, grade 3 obstructive hydrocephalus, and grade 5 intracranial hemorrhage, respectively. ISEs were more common in patients with a larger maximum tumor volume, primary sites other than lung and breast cancer, and pre-treatment neurological symptoms. CONCLUSION: SRT using a linear accelerator for brain metastases, including multiple and large lesions, is safe, with a low incidence of ISEs. Serious complications immediately after SRT are rare but possible; therefore, careful follow-up is necessary after treatment initiation.

miR-1246 in tumor extracellular vesicles promotes metastasis via increased tumor cell adhesion and endothelial cell barrier destruction.

Background: Tumor blood vessels play a key role in tumor metastasis. We have previously reported that tumor endothelial cells (TECs) exhibit abnormalities compared to normal endothelial cells. However, it is unclear how TECs acquire these abnormalities. Tumor cells secrete extracellular vesicles (EVs) to create a suitable environment for themselves. We have previously identified miR-1246 to be more abundant in high metastatic melanoma EVs than in low metastatic melanoma EVs. In the current study, we focused on miR-1246 as primarily responsible for acquiring abnormalities in TECs and examined whether the alteration of endothelial cell (EC) character by miR-1246 promotes cancer metastasis. Methods: We analyzed the effect of miR-1246 in metastatic melanoma, A375SM-EVs, in vivo metastasis. The role of tumor EV-miR-1246 in the adhesion between ECs and tumor cells and the EC barrier was addressed. Changes in the expression of adhesion molecule and endothelial permeability were examined. Results: Intravenous administration of A375SM-EVs induced tumor cell colonization in the lung resulting in lung metastasis. In contrast, miR-1246 knockdown in A375SM decreased lung metastasis in vivo. miR-1246 transfection in ECs increased the expression of adhesion molecule ICAM-1 via activation of STAT3, followed by increased tumor cell adhesion to ECs. Furthermore, the expression of VE-Cadherin was downregulated in miR-1246 overexpressed EC. A375SM-EV treatment enhanced endothelial permeability. VE-Cadherin was validated as the potential target gene of miR-1246 via the target gene prediction database and 3' UTR assay. Conclusion: miR-1246 in high metastatic tumor EVs promotes lung metastasis by inducing the adhesion of tumor cells to ECs and destroying the EC barrier.

Histiocytic sarcoma with spinal necrosis in a dog with progressing non-ambulatory tetraparesis.

Background: Histiocytic sarcoma (HS) is an aggressive malignant neoplasm, and widespread metastasis occurs with a fatal outcome. HS involving the central nervous system is relatively uncommon. Spinal cord necrosis, a very rare condition, could be induced by ischemia or infarction. Here, we report a dog progressing non-ambulatory tetraparesis with spinal cord necrosis caused by HS. Case Description: A 9-year-old male Labrador Retriever was presented with a progressing non-ambulatory tetraparesis. CT imaging revealed lysis of the spinous process of T7 and a ring-shaped lesion surrounding the soft tissue of lung fields. T2-weighted MRI showed the spinous processes of T6 to T8 as hyperintense, and the lesion infiltrated into the T7 vertebra and the spinal cord. After euthanasia, the final diagnosis upon necropsy was HS, which was observed in the lung, spinous process, thoracic cord, and the pulmonary hilar lymph node. Moreover, necrotic spots were spread widely through the thoracic spinal cord. Conclusion: This report outlines a case of canine HS in the lung, spinous process, thoracic cord, and pulmonary hilar lymph node. Ischemic deficit and necrosis of the thoracic spinal cord resulted from the compression of perivascular tumor cells, which rapidly led to progressive tetraparesis. Although the diagnosis was difficult, MRI and CT images helped determine the prognosis. To our knowledge, this is the first case report of canine HS with direct spinal cord involvement associated with spinal necrosis.

Quadrant laser photocoagulation trial to ameliorate choroidal congestion in central serous chorioretinopathy.

PURPOSE: To investigate the efficacy and safety of quadrant laser photocoagulation to ameliorate the choroidal congestion in central serous choroidopathy (CSC). STUDY DESIGN: Historically controlled study. METHODS: We prospectively studied 20 eyes with acute CSC in the quadrant laser group, in which laser photocoagulation was applied to the macular leakage point(s) as well as the quadrant of the fundus showing vortex vein dilatation. Central choroidal thickness (CCT), vertical diameter of dilated vortex vein, resolution rate of serous retinal detachment (SRD), and visual field were evaluated post-treatment. We also compared the results with those of 18 retrospectively analyzed eyes with acute CSC in an external control group, in which laser photocoagulation had been applied only to the macular leakage point(s). RESULTS: In the quadrant laser group, 2 eyes were excluded from data analysis due to choroidal neovascularization (CNV). CCT was significantly reduced in both groups, but more significantly in the quadrant laser group. The vertical diameter of the dilated vortex vein was significantly decreased only in the quadrant laser group. The resolution rate of SRD was similar in the two groups. In the quadrant laser group, 8 eyes (44.4%) showed mild deterioration of the visual field, consistent with the area subjected to quadrant laser photocoagulation. CONCLUSION: Quadrant laser photocoagulation can have limited efficacy for ameliorating vortex vein congestion in CSC. When laser photocoagulation to the macular area is combined with quadrant laser photocoagulation, attention must be paid to the possible development of CNV and visual field deterioration.

Comparison of the 2-Year Results of Photodynamic Therapy with Aflibercept and Aflibercept Monotherapy for Polypoidal Choroidal Vasculopathy.

Purpose: To compare the efficacies of photodynamic therapy (PDT) combined with intravitreal aflibercept (IVA) injections and IVA monotherapy using a treat-and-extend regimen (TAE) for treatment-naïve polypoidal choroidal vasculopathy (PCV). Patients and Methods: One hundred and nine eyes treated with PDT combined with IVA (PDT+IVA group: 51 eyes) or IVA monotherapy (IVA group: 58 eyes) were assessed for 2 years. The main outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), number of IVA injections, and macular atrophy (MA). Polypoidal lesions before and after the loading phase were assessed using indocyanine green angiography. Results: In both groups, BCVA significantly improved after the loading phase and was maintained for 2 years. CMT and CCT were significantly reduced in both groups, without significant differences after 2 years between the groups (P=0.2708). The mean number of IVA injections in the IVA and PDT+IVA groups during the 2 years were 13.2±3.3 and 12.7±1.8, respectively, without a significant difference (P=0.06). The frequencies of MA expansion in the IVA and PDT+IVA groups during the 2 years were 25.9% and 33.4%, respectively, with no significant difference in the incidence (odds ratio: 1.40, P=0.4253). The ratios of polyp regression after the loading phase in the IVA and PDT+IVA groups were 55.2% and 94.1%, respectively, with a significant difference (P<0.0001). Conclusion: PDT combined with IVA injections using a TAE regimen is effective for anatomical and visual function improvement, without a significant difference as compared to IVA monotherapy. It can facilitate complete regression of polyps with higher odds.

Disseminated histiocytic sarcoma in a squirrel monkey (Saimiri sciureus).

A 14-years-old squirrel monkey was euthanized due to weakness. Histopathological examination revealed multifocal growth of oval cells with severe atypia in the liver, spleen, and bone marrow. The neoplastic cells were positive for histiocytic markers (Iba1, HLA-DR, CD204). This is the fourth case of histiocytic sarcoma in non-human primates.

Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is a fatal viral disease characterized by high fever, thrombocytopenia, leukopenia, and multi-organ haemorrhage. Disruption of the humoral immune response and decreased lymphocyte numbers are thought to contribute to the disease severity. These findings have been obtained through the analysis of peripheral blood leukocytes in human patients, whereas analysis of lymph nodes has been limited. Thus, in this study, we characterized the germinal centre response and apoptosis in the lymph nodes of cats with fatal SFTS, because SFTS in cats well mimics the pathology of human SFTS. Methods: Lymph node tissue sections collected during necropsy from seven fatal SFTS patients and five non-SFTS cases were used for histopathological analysis. Additionally, lymph node tissue sections collected from cats with experimental infection of SFTS virus (SFTSV) were also analysed. Results: In the lymphoid follicles of cats with SFTS, a drastic decrease in Bcl6- and Ki67-positive germinal centre B cells was observed. Together, the number of T cells in the follicles was also decreased in SFTS cases. In the paracortex, a marked increase in cleaved-caspase3 positivity was observed in T cells. These changes were independent of the number of local SFTS virus-positive cell. Furthermore, the analysis of cats with experimental SFTSV infection revealed that the intrafollicular Bcl6- and CD3-positive cell numbers in cats with low anti-SFTSV antibody production were significantly lower than those in cats with high anti-SFTSV antibody production. Discussion: These results suggest that dysfunction of the humoral response in severe SFTS was caused by the loss of germinal centre formation and massive apoptosis of T cells in the lymph nodes due to systemically circulating viruses.

Multi-Component Intervention to Promote Physical Activity in Japanese Office Workers: A Single-Arm Feasibility Study.

This study investigated the feasibility of a multi-component intervention to promote physical activity (PA) among Japanese office workers. It was an 8-week single-arm trial conducted in Japan in 2021, in which 76 employees aged 20 or older, from an insurance company, participated. They received a multi-component PA intervention that comprised individual (lecture, print material, goal setting, and feedback), socio-cultural (team building and supportive atmosphere), physical (poster), and organizational (encouraging message from an executive) strategies. The primary outcome was change in objectively measured moderate-to-vigorous PA (MVPA). A paired t-test was used to compare the changes between weeks 0 and 8. We also conducted a subdomain analysis of PA divided into four domains (working, non-working, commuting working, and remote working). Excluding 26 participants who could not complete valid assessments, the MVPA among participants (n = 50, age 49.6 ± 9.7) significantly increased by +7.3 min/day [95% confidence interval (CI) 0.8 to 13.8]. We also identified significant changes in MVPA by +10.0 min/day [95% CI, 3.7 to 16.3] in working days (n = 40), and by +7.1 min/day [95% CI, 0.4 to 13.7] in remote working days (n = 34). We demonstrated that multi-component PA interventions might improve MVPA among Japanese office workers.

The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study.

Purpose: Intensity-modulated radiotherapy (IMRT) is currently used more commonly than 3-dimensional conformal radiation for definitive thoracic radiation. We examined the efficacy profiles of concurrent chemoradiotherapy (CCRT) with IMRT after durvalumab became clinically available. Methods: We reviewed the clinical records of patients with stage III non-small cell lung cancer (NSCLC) treated with CCRT and IMRT at seven centers in Japan and investigated relapse and survival from May 2018 to December 2019. The primary endpoint of this report was progression-free survival (PFS). Results: Among 107 patients enrolled in the study, 87 were sequentially administered durvalumab. From CCRT commencement, patients were followed up for a median period of 29.7 months. The median PFS at the end of the CCRT was 20.7 months. Among the 87 patients, 58 experienced disease relapses, of whom 36 (62.1 %) had distant metastases. Multivariate Cox regression analysis revealed that a favorable response to CCRT, a radiation dose ≥ 62 Gy, and stage IIIA NSCLC were associated with prolonged PFS (all P = 0.04). Multivariate logistic regression by landmark analysis revealed that mortality risk factors were durvalumab treatment duration ≤ 11.7 months, a lower maximum grade of immune-related adverse events, FEV1 < 2805 mL, and radiation dose < 62 Gy (P = 0.01, 0.01, 0.03, and 0.04, respectively). Conclusions: In patients with NSCLC receiving CCRT using IMRT, long PFS was associated with a better response to CCRT, stage IIIA NSCLC, and an increased radiation dose. The duration of durvalumab consolidation also played an essential role in the survival of patients receiving CCRT with IMRT. (250 words).

Volumetric reduction of brain metastases after stereotactic radiotherapy: Prognostic factors and effect on local control.

BACKGROUND AND PURPOSE: Few reports include volumetric measurements as endpoints after stereotactic radiotherapy (SRT) despite the importance of such measurements. This study aimed to (1) investigate the impact of the volumetric response (specifically, an over 65% and over 90% volume reduction in brain metastases) at 6 months post-SRT on local control and (2) identify the predictive factors for a volumetric response of over 65% and over 90%. MATERIALS AND METHODS: This study included 250 unresected brain metastases (>0.3 cc) treated with SRT. Doses were stratified according to the biological effective dose (BED). The BED was calculated using four models: linear-quadratic (LQ): α/ß = 10; LQ: α/ß = 20; LQ cubic: α/ß = 12; and LQ linear: α/ß = 10. The median prescription dose was 30 Gy/3 fractions (BED20, 45). The median follow-up time after SRT was 18.6 months (range, 6.4-81.8 months). RESULTS: In the multivariate analysis, over 65% volume reduction and over 90% volume reduction were prognostic factors for local control (hazard ratio: 2.370, p = 0.011 and hazard ratio: 3.161, p = 0.014, respectively). A dose of 80% of the gross tumor volume (GTV) D80 > BED20 58 was a predictive factor for over 65% and over 90% volume reductions (odds ratio: 1.975, p = 0.023; odds ratio: 3.204, p < 0.001, respectively). CONCLUSION: Robust volume reduction of brain metastases at 6 months post-SRT can predict local control. GTV D80 in the LQ model: α/ß = 20 may be warranted for good volume reduction.

FKBP52 and FKBP51 differentially regulate the stability of estrogen receptor in breast cancer.

Estrogen receptor α (ERα) is a transcription factor that induces cell proliferation and exhibits increased expression in a large subset of breast cancers. The molecular mechanisms underlying the up-regulation of ERα activity, however, remain poorly understood. We identified FK506-binding protein 52 (FKBP52) as a factor associated with poor prognosis of individuals with ERα-positive breast cancer. We found that FKBP52 interacts with breast cancer susceptibility gene 1 and stabilizes ERα, and is essential for breast cancer cell proliferation. FKBP52 depletion resulted in decreased ERα expression and proliferation in breast cancer cell lines, including MCF7-derived fulvestrant resistance (MFR) cells, suggesting that inhibiting FKBP52 may provide a therapeutic effect for endocrine therapy­resistant breast cancer. In contrast, FKBP51, a closely related molecule to FKBP52, reduced the stability of ERα. Consistent with these findings, FKBP51 was more abundantly expressed in normal tissues than in cancer cells, suggesting that these FKBPs may function in the opposite direction. Collectively, our study shows that FKBP52 and FKBP51 regulate ERα stability in a reciprocal manner and reveals a regulatory mechanism by which the expression of ERα is controlled.

Rapidly Growing Superficial Angiomyxoma in Mandibular Gingiva: A Case Report and Literature Review.

Superficial angiomyxoma (SA) is a benign tumor characterized by extensive myxoid stroma, numerous small blood vessels, sparse spindle-shaped fibroblastic cells, and inflammatory cell infiltrate. Oral cavity SA is extremely rare and typically presents as a painless, slow growth. We experienced SA in the mandibular gingiva that is rapidly growing. The patient was a 15-year-old female whose chief complaint was a painless mass in the lingual gingiva of the mandible that increased in size over 1 month. An excisional biopsy was performed under local anesthesia. According to histopathological examination, the mass was diagnosed as SA. The patient experienced recurrence twice because of positive margins. The second recurrent lesion, including periosteum, was resected, and no recurrence has been observed for 1 year. The cause of rapid growth was attributed to edematous changes due to tongue habit or traumatic stimuli. As this case exhibited repeated local recurrence, careful follow-up is required.

Novel antiangiogenic therapy targeting biglycan using tumor endothelial cell-specific liposomal siRNA delivery system.

Tumor blood vessels play important roles in tumor progression and metastasis. Targeting tumor endothelial cells (TECs) is one of the strategies for cancer therapy. We previously reported that biglycan, a small leucine-rich proteoglycan, is highly expressed in TECs. TECs utilize biglycan in an autocrine manner for migration and angiogenesis. Furthermore, TEC-derived biglycan stimulates tumor cell migration in a paracrine manner leading to tumor cell intravasation and metastasis. In this study, we explored the therapeutic effect of biglycan inhibition in the TECs of renal cell carcinoma using an in vivo siRNA delivery system known as a multifunctional envelope-type nanodevice (MEND), which contains a unique pH-sensitive cationic lipid. To specifically deliver MEND into TECs, we incorporated cyclo(Arg-Gly-Asp-D-Phe-Lys) (cRGD) into MEND because αV ß3 integrin, a receptor for cRGD, is selective and highly expressed in TECs. We developed RGD-MEND-encapsulating siRNA against biglycan. First, we confirmed that MEND was delivered into OS-RC-2 tumor-derived TECs and induced in vitro RNAi-mediated gene silencing. MEND was then injected intravenously into OS-RC-2 tumor-bearing mice. Flow cytometry analysis demonstrated that MEND was specifically delivered into TECs. Quantitative RT-PCR indicated that biglycan was knocked down by biglycan siRNA-containing MEND. Finally, we analyzed the therapeutic effect of biglycan silencing by MEND in TECs. Tumor growth was inhibited by biglycan siRNA-containing MEND. Tumor microenvironmental factors such as fibrosis were also normalized using biglycan inhibition in TECs. Biglycan in TECs can be a novel target for cancer treatment.