Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 239
Filter
1.
JCO Precis Oncol ; 8: e2300647, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38635933

ABSTRACT

PURPOSE: To understand the mutational landscape of circulating tumor DNA (ctDNA) and tumor tissue of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (MBC) treated with abemaciclib + endocrine therapy (ET). METHODS: Blood samples for ctDNA and/or tissue samples were collected from abemaciclib-treated patients with HR+/HER2- MBC enrolled in the SCRUM-Japan MONSTAR-SCREEN project. Blood samples were collected before abemaciclib initiation (baseline) and at disease progression/abemaciclib discontinuation (post abemaciclib treatment). Clinical and genomic characteristics including neoplastic burden (measured by shedding rate and maximum variant allele frequency [VAF]) were assessed at baseline. Genomic alterations in ctDNA were compared in paired baseline and post abemaciclib treatment samples. RESULTS: All patients (N = 97) were female (median age, 57 years [IQR, 50-67]). In baseline ctDNA (n = 77), PIK3CA (37%), TP53 (28%), ESR1 (16%), and GATA3 (11%) were the most frequently mutated genes. Baseline tissue samples (n = 79) showed similar alteration frequencies. Among patients with baseline ctDNA data, 30% had received previous ET. ESR1 alteration frequency (35% v 8%; P < .01), median shedding rate (3 v 2), and maximum somatic VAF (4 v 0.8; both P < .05) were significantly higher in ctDNA from patients with previous ET than those without previous ET. In paired ctDNA samples (n = 33), PIK3CA and ESR1 alteration frequencies were higher after abemaciclib treatment than at baseline, though not statistically significant. Among the post-treatment alterations, those newly acquired were detected most frequently in FGF3/4/19 (18%); PIK3CA, TP53, CCND1, and RB1 (all 15%); and ESR1 (12%). CONCLUSION: We summarized the ctDNA and cancer tissue mutational landscape, including overall neoplastic burden and PIK3CA and ESR1 hotspot mutations in abemaciclib-treated patients with HR+/HER2- MBC. The data provide insights that could help optimize treatment strategies in this population.


Subject(s)
Aminopyridines , Benzimidazoles , Breast Neoplasms , Circulating Tumor DNA , Female , Humans , Male , Middle Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Circulating Tumor DNA/genetics , Class I Phosphatidylinositol 3-Kinases/genetics , Early Detection of Cancer , ErbB Receptors , Genomics , Japan , Aged
2.
Rapid Commun Mass Spectrom ; 38(5): e9695, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38355879

ABSTRACT

RATIONALE: Osilodrostat is an inhibitor of 11-beta-hydroxylase (CYP11B) and is used for the treatment of Cushing's disease but also categorized as an anabolic agent. The use of osilodrostat is prohibited in horseracing and equestrian sports. To the best of our knowledge, this is the first metabolic study of osilodrostat in equine plasma. METHODS: Potential metabolites of osilodrostat were identified by differential analysis using data acquired from pre- and post-administration plasma samples after protein precipitation with liquid chromatography electrospray ionization high-resolution mass spectrometry (LC/ESI-HRMS). [Correction added on 27 January 2023, after first online publication: In the preceding sentence, "C-HRMS" was changed to "LC/ESI-HRMS" in this version.] For quantification of osilodrostat, a strong cation exchange solid-phase extraction was employed, and the extracts were analyzed using LC/ESI-triple quadrupole tandem mass spectrometry (LC/ESI-QqQ-MS/MS) to establish its elimination profile. Such extracts were further analyzed using LC/ESI-HRMS to investigate the detectability of osilodrostat and its identified mono-hydroxylated metabolite over a 2-week sampling period. RESULTS: Mono-hydroxylated osilodrostat was identified based on the differential analysis and mass spectrometric interpretations, and it was found to be the most abundant metabolite in plasma. Elimination profile of osilodrostat in plasma was successfully established over the 24-h post-administration period. Both osilodrostat and its mono-hydroxylated metabolite were detected up to the last sampling point at 2 weeks using HRMS, and osilodrostat could be confirmed up to 8-day post-administration with its reference material using HRMS as well. CONCLUSIONS: For doping control, screening of both the parent drug osilodrostat and its mono-hydroxylated metabolite in equine plasma would be recommended due to their extended detection windows of up to 2 weeks. Given the availability of reference material for potential confirmation in forensic samples, osilodrostat is considered the most appropriate monitoring target.


Subject(s)
Doping in Sports , Imidazoles , Pyridines , Animals , Horses , Doping in Sports/prevention & control , Tandem Mass Spectrometry/methods , Spectrometry, Mass, Electrospray Ionization/methods , Chromatography, Liquid/methods
3.
Br J Cancer ; 130(6): 1023-1035, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38238427

ABSTRACT

BACKGROUND: Triple-negative breast cancer (TNBC) is the most heterogeneous breast cancer subtype. Partly due to its heterogeneity, it is currently challenging to stratify TNBC patients and predict treatment outcomes. METHODS: In this study, we examined blood cytokine profiles of TNBC patients throughout treatments (pre-treatment, during chemotherapy, pre-surgery, and 1 year after the surgery in a total of 294 samples). We analyzed the obtained cytokine datasets using weighted correlation network analyses, protein-protein interaction analyses, and logistic regression analyses. RESULTS: We identified five cytokines that correlate with good clinical outcomes: interleukin (IL)-1α, TNF-related apoptosis-inducing ligand (TRAIL), Stem Cell Factor (SCF), Chemokine ligand 5 (CCL5 also known as RANTES), and IL-16. The expression of these cytokines was decreased during chemotherapy and then restored after the treatment. Importantly, patients with good clinical outcomes had constitutively high expression of these cytokines during treatments. Protein-protein interaction analyses implicated that these five cytokines promote an immune response. Logistic regression analyses revealed that IL-1α and TRAIL expression levels at pre-treatment could predict treatment outcomes in our cohort. CONCLUSION: We concluded that time-series cytokine profiles in breast cancer patients may be useful for understanding immune cell activity during treatment and for predicting treatment outcomes, supporting precision medicine. TRIAL REGISTRATION: The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index-j.htm ) with the unique trial number UMIN000023162. The association Japan Breast Cancer Research Group trial number is JBCRG-22. The clinical outcome of the JBCRG-22 study was published in Breast Cancer Research and Treatment on 25 March 2021. https://doi.org/10.1007/s10549-021-06184-w .


Subject(s)
Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/metabolism , Cytokines/metabolism , Chemokines , Treatment Outcome , Japan
4.
J Biochem ; 175(4): 439-446, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38153270

ABSTRACT

Aspartate/alanine exchange transporter (AspT) is a secondary transporter isolated from the lactic acid bacterium Tetragenococcus halophilus D10 strain. This transporter cooperates with aspartate decarboxylase to produce proton-motive force through decarboxylative phosphorylation. A method that successfully analyzes the AspT mechanism could serve as a prototype for elucidating the substrate transport mechanism of other exchange transporters; therefore, the purpose of this study was to search for conditions that improve the thermal stability of AspT for 3D structure analysis. We used the fluorescence size-exclusion chromatography-based thermostability assay to evaluate conditions that contribute to AspT stability. We found that the AspT thermostability was enhanced at pH 5.0 to 6.0 and in the presence of Na+ and Li+. Pyridoxal phosphate, a coenzyme of aspartate decarboxylase, also had a thermostabilizing effect on AspT. Under the conditions obtained from these results, it was possible to increase the temperature at which 50% of dimer AspT remained by 14°C. We expect these conditions to provide useful information for future structural analysis of AspT.


Subject(s)
Alanine , Aspartic Acid , Alanine/chemistry , Membrane Transport Proteins , Enterococcaceae
5.
Breast Cancer ; 30(6): 872-884, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37804479

ABSTRACT

The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer were updated to the 2022 edition through a process started in 2018. The updated guidelines consist of 12 background questions (BQs), 33 clinical questions (CQs), and 20 future research questions (FRQs). Multiple outcomes including efficacy and safety were selected in each CQ, and then quantitative and qualitative systematic reviews were conducted to determine the strength of evidence and strength of recommendation, which was finally determined through a voting process among designated committee members. Here, we describe eight selected CQs as important updates from the previous guidelines, including novel practice-changing updates, and recommendations based on evidence that has emerged specifically from Japanese clinical trials.


Subject(s)
Breast Neoplasms , Female , Humans , Breast Neoplasms/drug therapy , East Asian People , Japan
6.
J Equine Sci ; 34(3): 93-99, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37781566

ABSTRACT

Equine piroplasmosis is an infectious disease caused by Babesia caballi and Theileria equi. A competition horse that had been imported to the Equestrian Park for the Tokyo 2020 Olympic Games and had a fever over 40°C and severe anemia was diagnosed with equine piroplasmosis by blood smear and direct polymerase chain reaction (PCR) tests for Theileria equi. Treatment with protozoan anthelmintics and whole blood transfusion diminished the fever, improved the anemia, and allowed the horse to return home safely. Preparation for routine cases of this infection should include the development of a system that allows accurate and prompt international dissemination of information and implementation of quarantine measures.

7.
J Equine Vet Sci ; 131: 104956, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37879453

ABSTRACT

Equine influenza virus (EIV) infection is one of the most important respiratory diseases in the equine industry around the world. Rapid diagnosis, facilitated by point-of-care testing, is essential to implement movement restrictions and control disease outbreaks. This study evaluated a microfluidic immunofluorescence assay kit, which detects influenza virus and SARS-CoV-2 antigens in human specimens with a 12 min turnaround time, for its potential use in detecting EIV. The microfluidic immunofluorescence assay kit succeeded in detecting 11 EIV strains. Using the real-time reverse transcription polymerase chain reaction as a reference assay, the microfluidic immunofluorescence assay kit showed a sensitivity of 60.7% when evaluating nasopharyngeal swab samples of three horses experimentally infected with EIV. Comparing with the other two rapid antigen detection kits based on immunochromatography and silver amplification immunochromatography, the microfluidic immunofluorescence assay kit exhibited higher sensitivity than the former assay (53.6%) and the same sensitivity as the latter (60.7%). The microfluidic immunofluorescence assay kit did not detect nine non-EIV viruses including one equine coronavirus strain and seven bacteria, suggesting a high specificity for EIV antigens. Similar to other rapid antigen detection kits, the microfluidic immunofluorescence assay kit could be an effective diagnostic tool to detect EIV in the field.


Subject(s)
Horse Diseases , Influenza A Virus, H3N8 Subtype , Orthomyxoviridae Infections , Humans , Animals , Horses , Orthomyxoviridae Infections/diagnosis , Orthomyxoviridae Infections/veterinary , Microfluidics , Horse Diseases/diagnosis , Fluorescent Antibody Technique/veterinary
8.
NPJ Breast Cancer ; 9(1): 82, 2023 Oct 11.
Article in English | MEDLINE | ID: mdl-37821514

ABSTRACT

Therapeutic options for breast cancer patients with brain metastases (BM)/leptomeningeal carcinomatosis (LMC) are limited. Here, we report on the effectiveness and safety of trastuzumab deruxtecan (T-DXd) in human epidermal growth factor receptor 2-positive breast cancer patients with BM. Data were analyzed for 104 patients administered T-DXd. Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), intracranial (IC)-ORR, and IC-PFS were evaluated. ORR by investigator assessment was 55.7% (total population). Median PFS was 16.1 months; 12-month OS rate was 74.9% (total population). Median time-to-treatment failure was 9.7 months. In 51 patients with BM imaging, IC-ORR and median IC-PFS by independent central review were 62.7% and 16.1 months, respectively. In 19 LMC patients, 12-month PFS and OS rates were 60.7% and 87.1%, respectively. T-DXd showed effectiveness regarding IC-ORR, IC-PFS, PFS, and OS in breast cancer patients with BM/active BM, and sustained systemic and central nervous system disease control in LMC patients.Trial Registration: UMIN000044995.

9.
J Gen Intern Med ; 38(16): 3517-3525, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37620717

ABSTRACT

BACKGROUND: With rising worldwide population aging, the number of homebound individuals with multimorbidity is increasing. Improvement in the quality of home medical care (HMC), including medications, contributes to meeting older adults' preference for "aging in place" and securing healthcare resources. OBJECTIVE: To evaluate the changes in drug prescriptions, particularly potentially inappropriate medications (PIMs), among older adults receiving HMC in recent years, during which measures addressing inappropriate polypharmacy were implemented, including the introduction of clinical practice guidelines and medical fees for deprescribing. DESIGN: A cross-sectional study. PARTICIPANTS: Using data from the national claims database in Japan, this study included older adults aged ≥ 75 years who received HMC in October 2015 (N = 499,850) and October 2019 (N = 657,051). MAIN MEASURES: Number of drugs, prevalence of polypharmacy (≥ 5 regular drugs), major drug categories/classes, and PIMs according to Japanese guidelines were analyzed. Random effects logistic regression models were used to evaluate the differences in medications between 2015 and 2019, considering the correlation within individuals who contributed to the analysis in both years. KEY RESULTS: The number of drugs remained unchanged from 2015 to 2019 (median: 6; interquartile range: 4, 9). The prevalence of polypharmacy also remained unchanged at 70.0% in both years (P = 0.93). However, the prescription of some drugs (e.g., direct oral anticoagulants, new types of hypnotics, acetaminophen, proton pump inhibitors, and ß-blockers) increased, whereas others (e.g., warfarin, vasodilators, H2 blockers, acetylcholinesterase inhibitors, and benzodiazepines) decreased. Among the frequently prescribed PIMs, benzodiazepines/Z-drugs (25.6% in 2015 to 21.1% in 2019; adjusted odds ratio: 0.52) and H2 blockers (11.2 to 7.3%; 0.45) decreased, whereas diuretics (23.8 to 23.6%; 0.90) and antipsychotics (9.7 to 10.5%; 1.11) remained unchanged. CONCLUSIONS: We observed some favorable changes but identified some continuous and new challenges. This study suggests that continued attention to medication optimization is required to achieve safe and effective HMC.


Subject(s)
Inappropriate Prescribing , Potentially Inappropriate Medication List , Humans , Aged , Inappropriate Prescribing/prevention & control , Japan/epidemiology , Polypharmacy , Cross-Sectional Studies , Acetylcholinesterase , Drug Prescriptions , Benzodiazepines
10.
Breast Cancer Res Treat ; 202(3): 563-573, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37650999

ABSTRACT

PURPOSE: Low-grade adenosquamous carcinoma (LGASC) is a rare type of metaplastic carcinoma of the breast (MBC) with an indolent clinical course. A few LGASC cases with high-grade transformation have been reported; however, the genetics underlying malignant progression of LGASC remain unclear. METHODS: We performed whole-genome sequencing analysis on five MBCs from four patients, including one case with matching primary LGASC and a lymph node metastatic tumor consisting of high-grade MBC with a predominant metaplastic squamous cell carcinoma component (MSC) that progressed from LGASC and three cases of independent de novo MSC. RESULTS: Unlike de novo MSC, LGASC and its associated MSC showed no TP53 mutation and tended to contain fewer structural variants than de novo MSC. Both LGASC and its associated MSC harbored the common GNAS c.C2530T:p.Arg844Cys mutation, which was more frequently detected in the cancer cell fraction of MSC. MSC associated with LGASC showed additional pathogenic deletions of multiple tumor-suppressor genes, such as KMT2D and BTG1. Copy number analysis revealed potential 18q loss of heterozygosity in both LGASC and associated MSC. The frequency of SMAD4::DCC fusion due to deletions increased with progression to MSC; however, chimeric proteins were not detected. SMAD4 protein expression was already decreased at the LGASC stage due to unknown mechanisms. CONCLUSION: Not only LGASC but also its associated high-grade MBC may be genetically different from de novo high-grade MBC. Progression from LGASC to high-grade MBC may involve the concentration of driver mutations caused by clonal selection and inactivation of tumor-suppressor genes.


Subject(s)
Breast Neoplasms , Carcinoma, Adenosquamous , Carcinoma , Humans , Female , Carcinoma, Adenosquamous/genetics , Carcinoma, Adenosquamous/chemistry , Carcinoma, Adenosquamous/pathology , Breast Neoplasms/pathology , Breast/pathology
11.
Geriatr Gerontol Int ; 23(8): 589-594, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37385723

ABSTRACT

AIM: In 2022, the Japanese Orthopaedic Association developed "Locomo Age," which can be used to measure mobility. The potential effects of measuring Locomo Age on motivation to exercise are yet to be explored. This study aimed to determine whether the measurement of Locomo Age improved motivation for exercise. METHODS: In total, 90 fitness club users (17 men and 73 women) were enrolled in the study. The participants performed the locomotive syndrome risk test. These results were entered on a smartphone website, and their Locomo Age was automatically calculated. Questionnaires about impressions of Locomo Age and changes in motivation for exercise after measuring Locomo Age were surveyed. RESULTS: The mean Locomo Age of the participants was 84.4 ± 8.5 years, which was significantly higher than their actual age (75.9 ± 7.2 years, P < 0.001). Questionnaires showed that 55 participants (61.1%) felt that their Locomo Age was higher than expected; 42 participants (46.7%) had increased motivation for exercise, and only two participants (2.2%) had decreased motivation. The rate of improvement in motivation for exercise was higher in the group of participants who reported having an older Locomo Age than they expected compared with that of the group with a Locomo Age that was the same as they expected (P < 0.05). CONCLUSIONS: The measurement of Locomo Age improved the motivation for exercise. This result remained true even when the Locomo Age was higher than expected, as it did not decrease the participants' motivation. Locomo Age allows for the comprehension of participants' mobility without medical knowledge. Geriatr Gerontol Int 2023; 23: 589-594.


Subject(s)
Exercise , Motivation , Male , Humans , Female , Aged , Aged, 80 and over , Syndrome , Surveys and Questionnaires
12.
J Vet Med Sci ; 85(7): 751-754, 2023 Jul 17.
Article in English | MEDLINE | ID: mdl-37258221

ABSTRACT

A two-dose revaccination against tetanus is recommended for horses over 2 years old in Japan with no history of vaccination in the previous year. Here, the need for two-dose revaccination was evaluated in terms of antibody titers for each vaccine type, namely monovalent or multivalent. There was no difference in antibody titers between one- and two-dose regimens for up to 1 year, except at 8 weeks with the multivalent vaccine, and all horses had sufficient antibody titers for 1 year of tetanus prophylaxis. These results suggest that one-dose revaccination, regardless of the vaccine type, is as effective as two-dose in preventing tetanus for at least 1 year in horses not vaccinated in the previous year.


Subject(s)
Horse Diseases , Tetanus , Horses , Animals , Tetanus/prevention & control , Tetanus/veterinary , Immunization, Secondary/veterinary , Tetanus Toxoid , Vaccination/veterinary , Japan , Antibodies, Bacterial , Horse Diseases/prevention & control
13.
J Vet Diagn Invest ; 35(4): 430-432, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37129383

ABSTRACT

Using 85 sera collected from horses that had been experimentally infected with equine infectious anemia virus (EIAV) and 200 field sera collected from racehorses in Japan, we compared 4 agar gel immunodiffusion (AGID) kits for serologic detection of EIAV antibodies from Idexx, VMRD, IDvet, and the National Engineering Research Center of Veterinary Biologics, China (NECVB). The positive control lines were sufficiently clear in all kits for evaluation to be made, with slight differences in sharpness: NECVB was the sharpest, followed by VMRD, IDvet, and Idexx. The test results for all 285 samples agreed among the 4 kits, with 62 positives and 223 negatives. The sensitivities and specificities of VMRD, IDvet, and NECVB compared with the Idexx kit were 100%, and the kappa coefficient values between the kits were 1.0 for all combinations. We concluded that the testing capacity of these 4 kits was virtually identical.


Subject(s)
Equine Infectious Anemia , Horse Diseases , Infectious Anemia Virus, Equine , Animals , Horses , Equine Infectious Anemia/diagnosis , Agar , Immunodiffusion/veterinary , Immunodiffusion/methods , Antibodies, Viral , Enzyme-Linked Immunosorbent Assay/veterinary
14.
J Rural Med ; 18(2): 154-158, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37032982

ABSTRACT

Objective: This quick literature review aimed to organize information on the detailed components of total pain in older people with advanced dementia in a holistic manner. Materials and Methods: The authors analyzed qualitative data from relevant clinical guidelines or textbooks, focusing on certain types of pain and distress in older people with advanced dementia, followed by an expert panel review by research team members. In the search, the authors defined a person with advanced dementia as having a functional assessment staging tool scale score greater than or equal to six. Results: The model covered a wide variety of pain, from physical pain to dementia-related psychological and spiritual aspects of total pain, including living environment change, stigma, discrimination, lack of communication and understanding, loss of sense of control and dignity, and cultural distress. It also identified physical appearance as an important factor in dying with dignity, as established by existing research on individuals with incurable cancers. Conclusion: The conceptual model of total pain in people with advanced dementia is expected to help turn healthcare professionals' attention to physical, psychological, social, and spiritual contributors to total pain in advanced dementia.

15.
Anticancer Res ; 43(5): 2145-2154, 2023 May.
Article in English | MEDLINE | ID: mdl-37097684

ABSTRACT

BACKGROUND/AIM: This study aimed to examine the clinical significance of the protein expression of the cancer stem cell (CSC) markers ALDH1A1, CD133, CD44, and MSI-1 in primary and metastatic tissues of patients with breast cancer (BC). PATIENTS AND METHODS: ALDH1A1, CD133, CD44, and MSI-1 protein expression in pairs of primary and metastatic tissues of 55 patients with BC with metastases treated at Kanagawa Cancer Center between January 1970 and December 2016 were evaluated using immunohistochemical assay and their association with clinicopathological factors and survival was examined. RESULTS: There were no significant differences in CSC marker expression rates between primary and metastatic tissues for any CSC markers. Regarding the relationship between CSC marker expression in primary tissues and survival, patients with high CD133 expression had significantly lower recurrence-free survival (DFS) and overall survival. On multivariate analysis, they were also a poor independent predictor of DFS (hazard ratio=4.993, 95%CI=2.189-11.394, p=0.0001). In contrast, there was no significant association between the expression of any CSC marker in metastatic tissues and survival. CONCLUSION: CD133 expression in the primary BC tissue may be a useful risk factor for recurrence in patients with BC.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Neoplastic Stem Cells , Neoplastic Stem Cells/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Neoplasm Metastasis , Biomarkers, Tumor/metabolism , Aldehyde Dehydrogenase 1 Family/metabolism , Retinal Dehydrogenase/metabolism , AC133 Antigen/metabolism , Hyaluronan Receptors/metabolism , Nerve Tissue Proteins/metabolism , RNA-Binding Proteins/metabolism , Humans , Female , Middle Aged , Disease-Free Survival , Japan
16.
Cancer Sci ; 114(6): 2674-2688, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36916999

ABSTRACT

Bone metastasis occurs frequently in cancer patients. Conventional therapies have limited therapeutic outcomes, and thus, exploring the mechanisms of cancer progression in bone metastasis is important to develop new effective therapies. In the bone microenvironment, adipocytes are the major stromal cells that interact with cancer cells during bone metastasis. However, the comprehensive functions of bone marrow adipocytes in cancer progression are not yet fully understood. To address this, we investigated the role of bone marrow adipocytes on cancer cells, by focusing on an invasive front that reflects the direct effects of stromal cells on cancer. In comprehensive histopathological and genetic analysis using bone metastasis specimens, we examined invasive fronts in bone metastasis and compared invasive fronts with adipocyte-rich bone marrow (adipo-BM) to those with hematopoietic cell-rich bone marrow (hemato-BM) as a normal counterpart of adipocytes. We found morphological complexity of the invasive front with adipo-BM was significantly higher than that with hemato-BM. Based on immunohistochemistry, the invasive front with adipo-BM comparatively had a significantly increased cancer-associated fibroblast (CAF) marker-positive area and lower density of CD8+ lymphocytes compared to that with hemato-BM. RNA sequencing analysis of primary and bone metastasis cancer revealed that bone metastasized cancer cells acquired drug resistance-related gene expression phenotypes. Clearly, these findings indicate that bone marrow adipocytes provide a favorable tumor microenvironment for cancer invasion and therapeutic resistance of bone metastasized cancers through CAF induction and immune evasion, providing a potential target for the treatment of bone metastasis.


Subject(s)
Bone Neoplasms , Cancer-Associated Fibroblasts , Humans , Bone Marrow/metabolism , Immune Evasion , Stromal Cells , Bone Marrow Cells/metabolism , Bone Neoplasms/pathology , Adipocytes/pathology , Tumor Microenvironment
17.
Arch Virol ; 168(3): 94, 2023 Feb 19.
Article in English | MEDLINE | ID: mdl-36806782

ABSTRACT

Equine influenza virus strains of Florida sublineage clade 1 (Fc1) have been circulating in North America. In this study, virus neutralization assays were performed to evaluate antigenic differences between Fc1 vaccine strains and North American Fc1 strains isolated in 2021-2022, using equine antisera against A/equine/South Africa/4/2003 (a vaccine strain recommended by the World Organisation for Animal Health) and A/equine/Ibaraki/1/2007 (a Japanese vaccine strain). Antibody titers against four North American Fc1 strains isolated in 2021-2022 were comparable to those against the homologous vaccine strains. These results suggest that current Fc1 vaccine strains are effective against North American strains from 2021-2022.


Subject(s)
Horse Diseases , Influenza A Virus, H3N8 Subtype , Influenza Vaccines , Orthomyxoviridae Infections , Vaccines , Animals , Horses , Florida , North America
18.
J Vasc Interv Radiol ; 34(1): 31-37.e1, 2023 01.
Article in English | MEDLINE | ID: mdl-36209996

ABSTRACT

PURPOSE: To explore what extent of ablative margin depicted by computed tomography (CT) immediately after radiofrequency (RF) ablation is required to reduce local tumor progression (LTP) for colorectal cancer (CRC) lung metastases. MATERIALS AND METHODS: This retrospective study was undertaken as a supplementary analysis of a previous prospective trial. Seventy patients (49 men and 21 women; mean age ± standard deviation, 64.9 years ± 10.6 years) underwent RF ablation for CRC lung metastases, and 95 tumors that were treated in the trial and followed up with CT at least 12 months after RF ablation were evaluated. The mean tumor size was 1.0 cm ± 0.5 cm. The ablative margin was estimated as the shortest distance between the outer edge of the tumor and the surrounding ground-glass opacity on CT obtained immediately after RF ablation. The impact of the ablative margin on LTP was evaluated using logistic regression analysis. Multivariate logistic regression analysis was also performed to identify the risk factors for LTP. The result was validated with multivariate logistic regression applying a bootstrap method (1,000 times resampling). RESULTS: The mean ablative margin was 2.7 mm ± 1.3 (range, 0.4-7.3 mm). LTP developed in 6 tumors (6%, 6/95) 6-19 months after RF ablation. The LTP rate was significantly higher when the margin was less than 2 mm (P = .023). A margin of <2 mm was also found to be a significant factor for LTP (P = .048) on multivariate analysis and validated using the bootstrap method (P = .025). CONCLUSIONS: An ablative margin of at least 2 mm is important to reduce LTP after RF ablation for CRC lung metastases.


Subject(s)
Colorectal Neoplasms , Lung Neoplasms , Radiofrequency Ablation , Female , Humans , Male , Colorectal Neoplasms/pathology , Disease Progression , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/secondary , Lung Neoplasms/surgery , Radiofrequency Ablation/adverse effects , Retrospective Studies , Treatment Outcome , Middle Aged , Aged
19.
Interv Radiol (Higashimatsuyama) ; 7(3): 85-92, 2022 Nov 04.
Article in English | MEDLINE | ID: mdl-36483663

ABSTRACT

Purpose: To retrospectively evaluate the treatment outcomes of thermal ablation for renal metastatic tumors. Materials and Methods: Thirteen consecutive patients with small renal metastatic tumors (≤3 cm), who underwent thermal ablation between 2009 and 2020, were included in this study. Eight patients had extra-renal tumors during renal ablation. The primary tumors were adenoid cystic carcinoma in four patients, lung cancer in three, hemangiopericytoma in three, leiomyosarcoma in two, and thyroid cancer in one. The therapeutic effects, safety, survival rate, prognostic factor, and renal function were evaluated. Results: We performed 18 ablation sessions (cryoablation, n = 13; radiofrequency ablation, n = 5) on 19 renal metastases with a mean diameter of 1.7 cm, which resulted in a primary technique efficacy rate of 100% without procedure-related deaths or major complications. Renal function significantly declined 6 months after ablation (P = 0.0039). During the mean follow-up period of 31.2 ± 22.4 months (range, 2.7-71.4 months), one patient had local tumor progression at 11.9 months following radiofrequency ablation. The overall survival rates at 1 and 3 years after ablation were 76.9% (95% confidence interval [CI], 54.0%-99.8%) and 59.3% (95% CI, 31.3%-87.3%), respectively. Tumor size ≥ 2 cm (P = 0.02) and metastasis from non-small cell lung cancer (P = 0.001) were significant worse prognostic factors in univariate analysis, and metastasis from non-small cell lung cancer (P = 0.01) was significant in multivariate analysis. Conclusions: Percutaneous thermal ablation for small renal metastases is safe and feasible and can control local tumors.

20.
Geriatr Gerontol Int ; 22(11): 943-949, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36190740

ABSTRACT

AIM: Older adults at the end-of-life stage receiving home visits from physicians often experience symptoms such as dyspnea, pain and fatigue, among others. This study aimed to investigate the practices and opinions of physicians providing home visits regarding palliative care for older adults with respiratory symptoms due to non-malignant diseases in Japan. METHODS: A nationwide questionnaire survey on home palliative care for non-cancer chronic respiratory diseases was sent to 2988 home-care physicians in 2020 through postal mail and/or email. The questions focused on their background, their use of rating scales to evaluate the intensity of dyspnea, and their practices and opinions regarding home palliative care for respiratory diseases or symptoms. RESULTS: Valid responses were collected from 592 physicians (19.8%). A total of 251 participants (43.1%) used a rating scale to evaluate the intensity of dyspnea. While 87.8%, 86.6%, 67.3%, and 60.0% of physicians considered pulmonary rehabilitation, morphine, sedative medications, and non-invasive positive pressure ventilation (NPPV), respectively, as effective in relieving respiratory distress, 73.0%, 66.9%, 57.3%, and 55.2% of those physicians, respectively, used each modality to relieve respiratory distress. Frequently involved physicians in the aforementioned care prescribed morphine or sedative medications and used NPPV more frequently. CONCLUSIONS: This study found a discrepancy between the proportion of physicians who considered palliative care as effective and those who prescribed it. Geriatr Gerontol Int 2022; 22: 943-949.


Subject(s)
Home Care Services , Neoplasms , Physicians , Respiratory Distress Syndrome , Humans , Aged , Palliative Care , Japan , Dyspnea , Surveys and Questionnaires , Hypnotics and Sedatives/therapeutic use , Morphine Derivatives/therapeutic use
SELECTION OF CITATIONS
SEARCH DETAIL
...