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1.
BMC Cancer ; 23(1): 384, 2023 Apr 27.
Article in English | MEDLINE | ID: mdl-37106324

ABSTRACT

BACKGROUND: There is pressing needs to find the biomarker in the selection of neoadjuvant therapy in postmenopausal luminal breast cancer patients. We examined the hypothesis that PIK3CA mutations and low phosphatase and tensin homolog (PTEN) expression affect the response to neoadjuvant therapy and prognosis in postmenopausal luminal breast cancer patients. METHODS: Postmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, up to stage II, who underwent neoadjuvant chemotherapy (NAC; n = 60) or neoadjuvant endocrine therapy (NAE; n = 55) were selected. PIK3CA exon 9 and exon 20 mutations were screened by high resolution melting analysis and confirmed by Sanger sequence. PTEN expression was evaluated by immunohistochemistry. The relationships among PIK3CA mutations, PTEN expression, clinicopathological features, the pathological effect of neoadjuvant therapy, recurrence-free survival (RFS) and overall survival were analyzed. RESULTS: Among 115 patients, PIK3CA mutations and low PTEN expression before treatment were detected in 35 patients (30.4%) and in 28 patients (24.3%), respectively. In the NAC group, tumor with PIK3CA mutations showed significantly poorer response than tumor with PIK3CA wild-type (p = 0.03). On the other hand, in the NAE group, there was no significant difference in pathological therapeutic effect between tumor with PIK3CA mutations and tumor with PIK3CA wild-type (p = 0.54). In the NAC group, the log-rank test showed no difference in RFS between patients with PIK3CA mutations and PIK3CA wild-type (p = 0.43), but patients with low PTEN expression showed significantly worse RFS compared to patients with high PTEN expression (5 year RFS 0.64 vs. 0.87, p = 0.01). In the Cox proportional hazards model for RFS, PTEN expression, progesterone receptor, and pathological therapeutic effect were predictive factors for time to recurrence (All p < 0.05). CONCLUSIONS: PIK3CA mutations are associated with resistance to NAC but do not affect the response to NAE. Low PTEN expression does not affect response to either NAC or NAE but correlates with shorter RFS in patients who received NAC. These biomarkers will be further evaluated for clinical use to treat postmenopausal luminal breast cancer patients.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Neoadjuvant Therapy , Postmenopause , Receptor, ErbB-2/metabolism , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Class I Phosphatidylinositol 3-Kinases/genetics , Mutation , Biomarkers, Tumor/genetics
2.
Cancer Sci ; 112(1): 331-338, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33075165

ABSTRACT

Non-Hodgkin lymphoma (NHL) treated with chemoimmunotherapy has limited efficacy in some patients, resulting in relapsed or refractory disease. Avadomide (CC-122) is a novel cereblon-binding agent that exhibits antilymphoma and immune-modulation activities with a biological profile distinct from similar agents, such as lenalidomide. This phase I multicenter study evaluated avadomide in Japanese patients with advanced solid tumors or NHL. Fourteen patients with NHL and one with a solid tumor (esophageal carcinoma), were enrolled in four dose-escalation cohorts using a 3 + 3 design. Primary endpoints included safety, dose-limiting toxicities (DLT), maximum-tolerated dose and/or recommended phase II dose (RP2D), and pharmacokinetics. Secondary endpoints included overall response rate (ORR) and duration of response. One patient with NHL experienced DLT, which included face edema, pharyngeal edema, and tumor flare (all grade 1) that led to a dose reduction. Eleven patients had grade ≥3 treatment-emergent adverse events, most frequently decreased neutrophil count (33%) and decreased lymphocyte count (20%). The ORR in patients with NHL (n = 13) was 54%, including four complete and three partial responses. The best response for the solid tumor patient was progressive disease. Avadomide dose intensity was consistent across cohorts, and the 3-mg dose given five consecutive days/week was established as the RP2D. This phase I study identified a tolerable dose of avadomide, with an acceptable toxicity profile and clinically meaningful efficacy in Japanese patients with previously treated NHL.


Subject(s)
Antineoplastic Agents/administration & dosage , Esophageal Neoplasms/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , Piperidones/administration & dosage , Quinazolinones/administration & dosage , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacokinetics , Dose-Response Relationship, Drug , Female , Humans , Japan , Male , Maximum Tolerated Dose , Middle Aged , Piperidones/adverse effects , Piperidones/pharmacokinetics , Quinazolinones/adverse effects , Quinazolinones/pharmacokinetics
3.
Sensors (Basel) ; 21(7)2021 Apr 02.
Article in English | MEDLINE | ID: mdl-33918315

ABSTRACT

Visually impaired licensed therapists must have the ability to perceive stiffness through their fingertips in the school for the blind. The teachers strive to provide careful introductory education based on a quantitative assessment of new students' basic stiffness perception. However, assessment materials to help teachers understand new students' stiffness perception are lacking. This study aimed to develop suitable fundamental assessment materials that visually impaired licensed teachers could use to quantitatively assess the difference in the stiffness perception ability of beginning learners in the early stages of learning. They were asked to discriminate the presented materials one at a time, which consisted of thermoplastic elastomers with different degrees of stiffness. We used these materials to compare the beginning learners' ability to perceive stiffness with that of teachers and found that teachers answered correctly at an overall significantly higher rate. Specifically, the teachers' correct response rate (78.8%) for the stiffness perception of all presented stimuli was approximately 15% higher than the beginning learners' correct response rate (64.2%). These results revealed areas of stiffness that are difficult for beginning learners to identify.


Subject(s)
Acupressure , Humans , Learning , Massage , Perception , Pilot Projects
4.
Breast Cancer Res Treat ; 179(2): 435-443, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31620935

ABSTRACT

PURPOSE: Recent studies suggest that the quality and quantity of visceral adipose tissue (VAT) play significant roles in adipocyte function, and are related to insulin resistance. We tested the hypothesis that high amounts of upper VAT (aVAT) and low-quality VAT worsen treatment outcomes via altered insulin metabolism. METHODS: Cohort 1 included 106 women with breast cancer who were undergoing surgery. Homeostasis model assessment of insulin resistance (HOMA-R), insulin-like growth factor (IGF)-1, and IGF-binding protein 3 (IGFBP3) were measured before the initiation of treatment. aVAT was measured via computed tomography (CT). VAT quality was assessed using CT-determined Hounsfield units (VAT-HU). Associations between the variables investigated and VAT quality and quantity were analyzed. Cohort 2 included 271 patients who underwent chemotherapy. Associations between the variables investigated and survival outcomes after chemotherapy were analyzed via retrospective chart review. RESULTS: In cohort 1, aVAT was significantly correlated with insulin and HOMA-R levels. As body mass index (BMI) class increased, mean IGF-1 increased and mean IGFBP3 decreased, but these trends were not statistically significant. In cohort 2, aVAT was significantly positively correlated with BMI. The patients in the third aVAT tertiles had significantly shorter distant disease-free survival (dDFS) after neoadjuvant chemotherapy setting. In multivariate analysis, aVAT and VAT-HU were significantly associated with shorter dDFS. CONCLUSIONS: High aVAT and low-quality VAT were associated with poor survival outcome, increased insulin levels, and insulin resistance. The present study suggests the importance of evaluating the quality and quantity of VAT when estimating insulin resistance and treatment outcomes.


Subject(s)
Breast Neoplasms/epidemiology , Insulin Resistance , Intra-Abdominal Fat , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers , Body Mass Index , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Female , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Proportional Hazards Models , Tomography, X-Ray Computed , Treatment Outcome
5.
Breast Cancer Res Treat ; 180(3): 625-634, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32124135

ABSTRACT

PURPOSE: Although recent advances in molecular target therapy have improved the survival of breast cancer patients, high cost and frequent hospital visits result in both societal and individual burden. To reduce these problems, it has been proposed to produce antibodies in vivo. Here, we constructed gene-transduced human ceiling culture-derived proliferative adipocytes secreting anti-HER2 antibody (HER2-ccdPAs) and evaluated their ability to secrete antibody and mediate an anti-tumor effect. METHODS: Plasmid lentivirus was used as a recipient for anti-HER2 antibody cDNA and transduced into human proliferative adipocyte. Secretory antibody expression was evaluated by ELISA and western blot. Specific binding of secretory antibody to HER2 was examined by immunofluorescence analysis. Direct and indirect anti-tumor effects of supernatants from HER2-ccdPAs were evaluated using BT474 (HER2+) and MDA-MB-231 (HER2-) breast cancer cell lines. Additionally, whether adipocyte differentiation affects antibody secretion was investigated using supernatant collected from different cell maturation states. RESULTS: Anti-HER2 antibody was identified in the supernatant from HER2-ccdPAs and its production increased with the differentiation into mature adipocyte. Antibodies in supernatants from HER2-ccdPAs bound to HER2-positive breast cancer cells similar to trastuzumab. Supernatant from HER2-ccdPAs inhibited the proliferation of BT474 but not MDA-MB-231 cells, and downregulated AKT phosphorylation in BT474 cells compared with controls. Supernatants from HER2-ccdPAs also had an indirect anti-tumor effect on BT474 cells through ADCC. Additionally, Single inoculation of HER2-ccdPAs showed an anti-tumor effect in BT474 xenograft model. CONCLUSIONS: HER2-ccdPAs might be useful for cell-based gene therapy. This system could be a platform for various antibody therapies.


Subject(s)
Adipocytes/metabolism , Antibodies, Monoclonal/administration & dosage , Breast Neoplasms/drug therapy , Receptor, ErbB-2/antagonists & inhibitors , Adipocytes/cytology , Animals , Antibodies, Monoclonal/metabolism , Apoptosis , Breast Neoplasms/immunology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Differentiation , Cell Movement , Cell Proliferation , Female , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Phosphorylation , Receptor, ErbB-2/immunology , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
6.
J Surg Oncol ; 121(2): 216-223, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31840262

ABSTRACT

BACKGROUND AND OBJECTIVES: We investigated the effects of oncoplastic breast-conserving surgery (BCS) using chest wall perforator flaps (CWPFs) on the subsequent expected deformity and evaluated the longevity of flap volume. METHODS: We retrospectively reviewed oncological and cosmetic outcomes of 33 women who had undergone the above procedure. We calculated the percentage of breast volume excised (PBVE) from computed tomography volumetry and compared it between a historical BCS alone and the study (flap) group. We also sequentially evaluated flap volumes by magnetic resonance imaging volumetry. RESULTS: Oncoplastic BCS using 25 lateral flaps and eight inferior flaps, depending on the site of the defect, was performed; mean PBVEs were 31.1% and 19.0%, respectively. No local and two distant recurrences occurred in a median follow-up of 61 months. PBVE was 2.6 times larger in the flap than in the BCS alone group. Over half the patients in the BCS alone group had poor cosmetic results when PBVE exceeded 15%, whereas patients in the flap group achieved good cosmetic results with PBVE >25%. In most patients, 80% of flap volume was maintained 5 years after surgery. CONCLUSIONS: CWPF improves cosmetic outcomes in patients with predicted deformity after BCS alone and maintains its volume for at least 5 years.

7.
Aging Ment Health ; 23(5): 595-601, 2019 05.
Article in English | MEDLINE | ID: mdl-29528693

ABSTRACT

OBJECTIVE: To investigate the effects of interactions between memory impairment, depressive symptoms, and anosognosia. METHODS: Anosognosia for memory impairment was assessed in 118 patients with Alzheimer's disease (AD), 47 patients with mild cognitive impairment (MCI), and 17 non-diagnosed controls (NC) using a questionnaire and evaluation of the anosognosia score as the discrepancy between ratings of the patient and a relative. Demographic characteristics, such as the relationship of the patient with the relative and the activities of daily living (ADL) were evaluated. Memory impairment was evaluated with the Rivermead Behavioral Memory Test (RBMT), depressive symptoms were evaluated using the Geriatric Depression Scale (GDS) 15 items version. RESULTS: In the MCI group, a stepwise multiple regression analysis showed an interaction between RBMT and GDS scores, and simple slope analysis indicated that scores for RBMT at low GDS (-1 standard deviation) were positively correlated with self-rated memory impairment. In the AD group, the relationship of the patient with the relative, ADL, and GDS and RBMT scores were associated with the anosognosia score. CONCLUSION: Patients with MCI who have no depressive symptoms may be able to more accurately evaluate their memory impairment than those who have depressive symptoms and patients with AD. The evaluation by relatives, depressive symptoms or ADL of patients may distort evaluation of anosognosia for memory impairment in patients with AD or MCI. It seems necessary to include not only depression scale scores but also results of objective memory tests in the patients' medical information for the correct assessment of anosognosia.


Subject(s)
Activities of Daily Living , Agnosia/diagnosis , Agnosia/physiopathology , Alzheimer Disease/physiopathology , Cognitive Dysfunction/physiopathology , Depression/physiopathology , Diagnostic Self Evaluation , Memory Disorders/physiopathology , Aged , Aged, 80 and over , Family , Female , Humans , Male , Middle Aged
8.
Radiology ; 286(1): 239-248, 2018 01.
Article in English | MEDLINE | ID: mdl-28745939

ABSTRACT

Purpose To evaluate pineal volume in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and healthy control subjects and to correlate the findings with results of cognitive testing and brain parenchymal volumes. Materials and Methods The ethics committee approved this retrospective study. The participants included 63 patients with AD, 33 patients with MCI, and 24 healthy control subjects. There were 36 men and 84 women, with a mean age (±standard deviation) of 76.7 years ± 7.6. The pineal gland volume and pineal parenchymal volume were measured by using three-dimensional volumetric magnetic resonance imaging (T1-weighted magnetization-prepared rapid gradient-echo sequence; spatial resolution, 0.9 × 0.98 × 0.98 mm). With age and total intracranial volume as covariates, analysis of covariance with the Bonferroni post hoc test was performed to compare the pineal volume among the AD, MCI, and control groups. Multiple regression analyses were used to identify predictor variables associated with pineal volume. Results The mean pineal gland volume in patients with AD (72.3 mm3 ± 5.4; 95% confidence interval [CI]: 61.5 mm3, 83.1 mm3) was significantly smaller than that in control subjects (102.1 mm3 ± 9.0; 95% CI: 84.4 mm3, 119.9 mm3) (P = .019). The mean pineal parenchymal volume in patients with AD (63.8 mm3 ± 4.2; 95% CI: 55.4 mm3, 72.1 mm3) was significantly smaller than that in patients with MCI (81.7 mm3 ± 5.8; 95% CI: 70.3 mm3, 93.1 mm3; P = .044) and control subjects (89.1 mm3 ± 6.9; 95% CI: 75.4 mm3, 102.9 mm3; P = .009). Multiple regression analyses demonstrated that the Mini-Mental State Examination score and total intracranial volume were significant independent predictors of both pineal gland volume and pineal parenchymal volume (P < .001). Conclusion Pineal volume reduction showed correlation with cognitive decline and thus might be useful to predict cognitive decline in patients with AD. © RSNA, 2017.


Subject(s)
Alzheimer Disease/diagnostic imaging , Alzheimer Disease/epidemiology , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Pineal Gland/diagnostic imaging , Aged , Aged, 80 and over , Alzheimer Disease/pathology , Female , Humans , Male , Pineal Gland/pathology , Reproducibility of Results , Retrospective Studies
9.
Appl Opt ; 57(33): 9845-9854, 2018 Nov 20.
Article in English | MEDLINE | ID: mdl-30462020

ABSTRACT

A quantitative study of image matching techniques applied to fiber specklegram sensor analysis is presented. The fiber status is modulated by a microbending transducer, so the output speckle field can be correlated to the input displacements. Once acquired and preprocessed, the specklegrams' variations were evaluated according to seven approaches. Although the average intensity did not provide reliable information per se, the correlation and sum of differences methods yielded ∼11 mm-1 and ∼14 mm-1 sensitivities, respectively, within a ∼0.06 mm range and low linearity and hysteresis errors, with enhancement possibility by intensity level cancellation. Moreover, the phase-only correlation and the mutual information metrics provided very high sensitivities (22 mm-1 and 120 mm-1, respectively) for a <0.02 mm range, making these techniques suitable for detecting subtle variations in the fiber status due to physical or chemical stimuli.

10.
Aesthetic Plast Surg ; 42(2): 442-446, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29101435

ABSTRACT

We describe a new wound management technique using a soft dressing material to stabilize the areola skin graft and protect the nipple after nipple-areola reconstruction at the final stage of breast reconstruction. We introduced a center-fenestrated multilayered hydrocellular polyurethane foam dressing material that provides adequate pressure and retains a moist environment for a smooth skin graft "take." Moreover, the reconstructed nipple can be monitored at any time through the fenestrated window for adequate blood circulation. Altogether, this simple and inexpensive wound dressing technique improves the clinical outcome. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Subject(s)
Bandages , Mammaplasty/methods , Nipples/surgery , Polyurethanes , Surgical Flaps/transplantation , Wound Healing/physiology , Adult , Breast Neoplasms/surgery , Cohort Studies , Esthetics , Female , Humans , Japan , Mastectomy/methods , Middle Aged , Postoperative Care/methods , Retrospective Studies
11.
Psychogeriatrics ; 18(1): 42-48, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29372597

ABSTRACT

BACKGROUND: The Executive Interview (EXIT25), the executive clock-drawing task (CLOX1), and the Frontal Assessment Battery (FAB) are used to assess executive function at the bedside. These tests assess distinct psychometric properties. The aim of this study was to examine differences in the neural correlates of the EXIT25, CLOX1, and FAB based on magnetic resonance imaging. METHODS: Fifty-eight subjects (30 with Alzheimer's disease, 10 with mild cognitive impairment, and 18 healthy controls) participated in this study. Multiple regression analyses were performed to examine the brain regions correlated with the EXIT25, CLOX1, and FAB scores. Age, gender, and years of education were included as covariates. Statistical thresholds were set to uncorrected P-values of 0.001 at the voxel level and 0.05 at the cluster level. RESULTS: The EXIT25 score correlated inversely with the regional grey matter volume in the left lateral frontal lobe (Brodmann areas 6, 9, 44, and 45). The CLOX1 score correlated positively with the regional grey matter volume in the right orbitofrontal cortex (Brodmann area 11) and the left supramarginal gyrus (Brodmann area 40). The FAB score correlated positively with the regional grey matter volume in the right precentral gyrus (Brodmann area 6). The left lateral frontal lobe (Brodmann area 9) and the right lateral frontal lobe (Brodmann area 46) were identified as common brain regions that showed association with EXIT25, CLOX1, and FAB based only a voxel-level threshold. CONCLUSIONS: The results of this study suggest that the EXIT25, CLOX1, and FAB may be associated with the distinct neural correlates of the frontal cortex.


Subject(s)
Alzheimer Disease/physiopathology , Brain/diagnostic imaging , Executive Function/physiology , Frontal Lobe/diagnostic imaging , Magnetic Resonance Imaging/methods , Neuropsychological Tests , Adult , Aged , Aged, 80 and over , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/psychology , Brain/physiopathology , Female , Geriatric Assessment/methods , Humans , Interview, Psychological/methods , Male , Mental Status Schedule , Middle Aged , Psychomotor Performance
12.
Breast Cancer Res Treat ; 150(2): 255-63, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25721605

ABSTRACT

The objective of this study is to investigate interactions between adipocytes and breast cancer cells, and identify the responsible factors for the observed effects. In 27 breast cancer patients undergoing mastectomy, mammary adipose tissue was obtained from the breast quadrant bearing the tumor and corresponding non-tumoral quadrant. Isolated normal breast adipocytes (NBAs) and cancer-associated adipocytes (CAAs) were cultured in collagen gels to mimic the in vivo environment. Immunohistochemistry, qRT-PCR, and cell proliferation assays were performed to analyze adipocyte phenotypes. MCF7 and MDA-MB-231 breast cancer cell lines were co-cultured with adipocytes to detect phenotypic changes. Migration of MCF7 and MDA-MB-231 cells was assessed in NBA- and CAA-conditioned media. Cytokine levels in conditioned media were measured by cytokine array. Migration assays were repeated using conditioned media containing neutralizing antibodies. NBAs and CAAs lost their morphological phenotype in culture, acquiring a spindle-like shape, and CAAs showed higher cell proliferation, suggesting reversion to an immature phenotype. In co-cultures with MCF7 or MDA-MB-231 cells, NBAs exhibited increased cell proliferation, indicating acquisition of the immature phenotype of CAAs. MCF7 and MDA-MB-231 showed higher migration in a CAA-conditioned medium than in an NBA-conditioned medium. Cytokine array analysis of conditioned media revealed higher levels of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) in the CAA-conditioned medium. Neutralization experiments using antibodies against IL-6 or MCP-1 showed abrogation of migration-enhancing effects of the CAA-conditioned medium. Adipocytes revert to an immature and proliferative phenotype in the presence of breast cancer cells, and promote cancer cell migration via adipokines including IL-6 and MCP-1.


Subject(s)
Breast Neoplasms/pathology , Cell Movement , Chemokine CCL2/physiology , Interleukin-6/physiology , Adipocytes/physiology , Cell Proliferation , Cell Shape , Coculture Techniques , Epithelial-Mesenchymal Transition , Female , Humans , MCF-7 Cells
13.
Int Psychogeriatr ; 26(8): 1387-97, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24832196

ABSTRACT

BACKGROUND: The aim of the study was to develop the Japanese versions of Executive Interview (J-EXIT25) and Executive Clock Drawing Task (J-CLOX) and to evaluate the aspects of executive function that these two tests will be examining. METHODS: The concurrent validity and reliability of J-EXIT25 and J-CLOX were first examined in all participants (n = 201). Next, the relationship between the two tests was examined using receiver operating characteristic (ROC), correlation, and regression analyses in healthy participants (n = 45) and participants with mild cognitive impairment (n = 36) and dementia (n = 95). RESULTS: Satisfactory concurrent validity and reliability of J-EXIT25 and J-CLOX were shown. ROC analysis indicated that J-EXIT25 and J-CLOX1 were superior to the Frontal Assessment Battery, but inferior to the Mini-Mental State Examination (MMSE), in discriminating between non-dementia and dementia. J-EXIT25, J-CLOX1, and J-CLOX2 scores were significantly correlated with age, scores on the MMSE, Instrumental Activities of Daily Living (IADL) and Physical Self-Maintenance Scale (PSMS), and care level. In stepwise regression analyses of IADL scores, MMSE and J-EXIT25 were significantly independent predictors in men, and MMSE, age, and J-CLOX1 were significantly independent predictors in women. J-EXIT25, MMSE, and J-CLOX1 were significantly independent predictors in stepwise regression analysis of PSMS scores, and J-EXIT25 was the only significantly independent predictor in stepwise regression analysis of care level. CONCLUSIONS: J-EXIT25 and J-CLOX are valid and reliable instruments for assessment of executive function in older people. The present results suggest that these tests have common and distinct psychometric properties in the assessment of executive function.


Subject(s)
Activities of Daily Living/psychology , Cognition Disorders , Executive Function , Interview, Psychological , Psychometrics , Self Care/psychology , Age Factors , Aged , Aged, 80 and over , Asian People , Cognition Disorders/diagnosis , Cognition Disorders/psychology , Dementia , Female , Geriatric Assessment/methods , Humans , Intelligence Tests/standards , Interview, Psychological/methods , Interview, Psychological/standards , Male , Psychometrics/methods , Psychometrics/standards , ROC Curve , Regression Analysis , Reproducibility of Results , Sex Factors , Statistics as Topic , Translating
14.
Article in English | MEDLINE | ID: mdl-38955134

ABSTRACT

Invasive ductal carcinoma (IDC) in breast specimens has been detected in the quadrant breast area: (I) upper outer, (II) upper inner, (III) lower inner, and (IV) lower outer areas by electrical impedance tomography implemented with Gaussian relaxation time distribution (EIT-GRTD). The EIT-GRTD consists of two steps which are 1) the optimum frequencyfoptselection and 2) the time constant enhancement of breast imaging reconstruction.foptis characterized by a peak in the majority measurement pair of the relaxation time distribution function γ, which indicates the presence of IDC. γ represents the inverse of conductivity and indicates the response of breast tissues to electrical currents across varying frequencies based on the Voigt circuit model. The EIT-GRTD is quantitatively evaluated by multi-physics simulations using a hemisphere container of mimic breast, consisting of IDC and adipose tissues as normal breast tissue under one condition with known IDC in quadrant breast area II. The simulation results show that EIT-GRTD is able to detect the IDC in four layers atfopt=30,170 Hz. EIT-GRTD is applied in the real breast by employed six mastectomy specimens from IDC patients. The placement of the mastectomy specimens in a hemisphere container is an important factor in the success of quadrant breast area reconstruction. In order to perform the evaluation, EIT-GRTD reconstruction images are compared to the CT scan images. The experimental results demonstrate that EIS-GRTD exhibits proficiency in the detection of the IDC in quadrant breast areas while compared qualitatively to CT scan images.

15.
Sci Rep ; 14(1): 14146, 2024 06 19.
Article in English | MEDLINE | ID: mdl-38898119

ABSTRACT

Eribulin (ERI), clinically utilized for locally advanced or metastatic breast tumors, has shown potential links to the immune system. Notably, the cGAS-STING pathway, a key component of innate immunity, has gained prominence. Yet, limited reports explore ERI's effects on the cGAS-STING pathway. Additionally, the nuclear presence of cGAS remains poorly understood. This study uniquely delves into ERI's impact on both the cytosolic cGAS-STING pathway and nuclear cGAS. ERI enhances nuclear localization of cGAS, resulting in hyper-activation of the cGAS-STING pathway in triple-negative breast cancer cells. Reduction of cGAS heightened both cell proliferation and ERI sensitivity. In clinical data using ERI in a neo-adjuvant setting, patients with low cGAS cases exhibited reduced likelihood of achieving pathological complete response after ERI treatment. These findings illuminate the potential of cGAS and IFNß as predictive biomarkers for ERI sensitivity, providing valuable insights for personalized breast cancer treatment strategies.


Subject(s)
Cell Nucleus , Furans , Ketones , Nucleotidyltransferases , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/genetics , Nucleotidyltransferases/metabolism , Female , Ketones/pharmacology , Cell Nucleus/metabolism , Cell Nucleus/drug effects , Cell Line, Tumor , Furans/pharmacology , Cell Proliferation/drug effects , Membrane Proteins/metabolism , Membrane Proteins/genetics , Signal Transduction/drug effects , Polyether Polyketides
16.
J Org Chem ; 78(7): 3095-103, 2013 Apr 05.
Article in English | MEDLINE | ID: mdl-23373629

ABSTRACT

The catalytic activity of Lewis acid activated oxazaborolidines in the Diels-Alder reaction between cyclopentadiene and methacrolein is investigated by using the DFT method. Oxazaborolidine is not able to coordinate to methacrolein in the absence of AlBr3 because the bonding stabilization is too small to cover the destabilization arising from the deformation of the two species. Accordingly, oxazaborolidine hardly catalyzes the cycloaddition by itself. The calculations show that the attachment of AlBr3 to the nitrogen atom of oxazaborolidine enhances the Lewis acidity of its boron center and enables it to coordinate to methacrolein. When the AlBr3-assisted oxazaborolidine is once coordinated, the catalytic activity originates mainly from the oxazaborolidine framework, and to a smaller extent from the attached AlBr3 part. The Lewis acid AlBr3 plays an additional role to facilitate the reaction by reducing the overlap repulsion between the diene and the dienophile. The attachment of AlBr3 to the oxygen atom, another Lewis basic site in oxazaborolidine, also gives a stable AlBr3-oxazaborolidine complex, but the reaction catalyzed by this complex is not preferred to that catalyzed by the complex in which AlBr3 is attached to the nitrogen atom. The electrophilicity of boron center in oxazaborolidine and those in the AlBr3-oxazaborolidine complexes are compared in terms of localized reactive orbitals.


Subject(s)
Aldehydes/chemical synthesis , Boron Compounds/chemistry , Lewis Acids/chemistry , Quantum Theory , Aldehydes/chemistry , Catalysis , Molecular Structure
17.
J Org Chem ; 78(24): 12505-12, 2013 Dec 20.
Article in English | MEDLINE | ID: mdl-24168454

ABSTRACT

The hydrosilylation reaction of a carbonyl group catalyzed by tris(pentafluorophenyl)borane, B(C6F5)3, is investigated by using the DFT method. M06-2X level calculations suggest the presence of a stable complex between trimethylsilane and B(C6F5)3. The attack of the carbonyl group in acetone from the back side of the Si-H bond prompts the abstraction of the hydride ion by B(C6F5)3. This reaction path is lower in free energy than the conventional carbonyl-activation path via a four-membered cyclic transition state. The silane-activation mechanism is supported in this case, in agreement with experimental results reported by Piers and by Oestreich. The calculations show, on the other hand, that the silane-activation mechanism does not apply to the reaction catalyzed by BF3. This difference in mechanisms arises from a stronger electrophilicity of the boron center in B(C6F5)3 than in BF3 toward a hydride ion, as demonstrated by an analysis of reactive orbitals. Attractions between the silane part and the fluorine atoms at the ortho positions of C6F5 groups in the Lewis acid assist the path by making up for the destabilization of the reacting system that is caused by the distortion of the B(C6F5)3 framework in forming a bond with the hydrogen of silane.


Subject(s)
Boranes/chemistry , Hydrocarbons, Fluorinated/chemistry , Quantum Theory , Silanes/chemical synthesis , Catalysis , Molecular Structure , Silanes/chemistry
18.
J Med Ultrason (2001) ; 50(3): 367-373, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37231224

ABSTRACT

The ultrasound fusion imaging system is a diagnostic device developed in Japan that utilizes ultrasound and magnetic positioning/navigation. A position sensor with a probe reads spatial location information from a magnetic field generator and by synchronously displaying ultrasound images and magnetic resonance (MR)/computed tomography (CT) images in real time. Lesions that are difficult to observe via ultrasonography alone, such as non-mass enhancement, can be identified. Furthermore, lesions that are difficult to identify with ultrasound alone indicated for MRI-guided biopsy under the National Health Insurance Scheme can be identified using ultrasound fusion technology, thereby enabling tissue biopsy to be performed under ultrasound guidance. Using this ultrasound fusion technology, not only non-mass enhancement but also small lesions that are difficult to identify using ultrasound alone can be detected, thus ensuring that a more accurate preoperative imaging diagnosis is established, and leading to safer, more reassuring examinations and surgical procedures. In this paper, we outline the use of this ultrasound fusion technology and fusion techniques in the treatment of breast cancer.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/therapy , Ultrasonography/methods , Tomography, X-Ray Computed/methods , Magnetic Resonance Imaging/methods , Image-Guided Biopsy/methods
19.
Cancer Med ; 12(12): 13193-13203, 2023 06.
Article in English | MEDLINE | ID: mdl-37162105

ABSTRACT

BACKGROUND: In monarchE and Postoperative Therapy with Endocrine and TS-1 (POTENT) trials, abemaciclib and S-1 have, respectively, shown to be effective as adjuvant therapies for luminal breast cancer (BC), although whether patients who meet the criteria are at high risk of recurrence compared to non-eligible patients is still unknown. Here, we investigated recurrence risk according to the criteria of each trial in Japanese patients. METHODS: We reviewed the records of 992 patients who received surgery at Chiba University Hospital for stage I-III BC from January 2017 to May 2022 and selected 553 analytic cohort patients and retrospectively analyzed the relapse-free survival of the patients as the primary endpoint. High-recurrence risk was defined according to monarchE trial and POTENT trial. RESULTS: The 5-year RFS for monarchE cohort 1 and cohort 2 eligible patients were 77.78% and 89.33%, respectively, which were significantly lower than monarchE non-eligible patients (98.31%; p < 0.0001). However, the 5-year RFS rate for POTENT eligible patients (90.51%) was lower than for POTENT non-eligible patients (98.75%; p = 0.0001); excluding those who met the monarchE criteria, the prognosis of POTENT eligible patients had no significant differences from the prognosis of patients with POTENT non-eligible BC (p = 0.3100). CONCLUSION: MonarchE criteria accurately identify patients who are prone to relapse. Moreover, although POTENT criteria also suggested a reasonable capacity for recurrence prediction, there was no significant difference in recurrence between POTENT non-eligible patients and the patients who were POTENT but not monarchE eligible. This might offer justification for reconsidering the use of S-1 in monarchE non-eligible patients.


Subject(s)
Breast Neoplasms , Neoplasm Recurrence, Local , Humans , Female , Retrospective Studies , Neoplasm Recurrence, Local/drug therapy , Prognosis , Combined Modality Therapy , Chemotherapy, Adjuvant
20.
Nutrients ; 15(20)2023 Oct 13.
Article in English | MEDLINE | ID: mdl-37892436

ABSTRACT

Although elevated serum levels of soluble CD40 ligand (sCD40L) were reported in patients with cancer, the importance of high sCD40L levels in clinical oncology remains unknown. We conducted a post hoc analysis of the AMATERASU randomized clinical trial of vitamin D3 supplementation (2000 IU/day) in patients with digestive tract cancer to assess its significance. Serum sCD40L levels were measured by ELISA in 294 residual samples, and were divided into tertiles. In patients with colorectal cancer (CRC), 5-year relapse-free survival (RFS) rates in the middle and highest tertiles were 61.6% and 61.2%, respectively, which was significantly lower than 83.8% in the lowest tertile. A Cox proportional hazard analysis showed that the lowest tertile had a significantly lower risk of relapse or death than the highest tertile even with multivariate adjustment (hazard ratio (HR), 0.30; 95% confidence interval (CI), 0.11-0.80; p = 0.016). In the subgroup of CRC patients with the highest tertile of sCD40L, the 5-year RFS rate in the vitamin D group was 77.9%, which was significantly higher than 33.2% in the placebo group (HR, 0.30; 95% CI, 0.11-0.81; p = 0.018 [Pinteraction = 0.04]). In conclusion, elevated sCD40L might be a biomarker of poor prognosis in patients with CRC, but vitamin D supplementation might improve RFS in patients with high sCD40L.


Subject(s)
CD40 Ligand , Colorectal Neoplasms , Humans , Neoplasm Recurrence, Local , Cholecalciferol/therapeutic use , Dietary Supplements , Colorectal Neoplasms/drug therapy
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