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1.
Hum Cell ; 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39174825

ABSTRACT

Synovial sarcoma (SS) is identified as a sarcoma with monomorphic blue spindle cells that display variable epithelial differentiation and is characterized by the SS18::SSX fusion gene. SS accounts for approximately 5-10% of all soft tissue sarcomas, making it a relatively common type within this group of tumors. Since SS is generally sensitive to chemotherapy, the standard treatment for SS includes extensive surgical resection, complemented by neoadjuvant chemotherapy with several approved anticancer drugs. However, in advanced and metastatic cases, the efficacy of these drugs is limited, resulting in poor prognoses. This underscores the need for innovative therapeutic strategies. Patient-derived cancer cell lines are essential tools for basic and preclinical research, yet only four SS cell lines are publicly available. To facilitate the studies of SS, we have developed a novel SS cell line, named NCC-SS6-C1, derived from surgically excised tumor tissue of an SS patient. NCC-SS6-C1 cells preserve the SS18::SSX1 fusion gene, consistent with the genetic characteristics of the original tumor. The cells exhibit continuous proliferation, invasiveness, and the ability to form spheroids. Additionally, we confirmed that this cell line was useful for evaluating the efficacy of anticancer drugs. Our results suggest that NCC-SS6-C1 is a useful tool for basic and pre-clinical studies of SS.

2.
Hum Cell ; 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39214957

ABSTRACT

Myxofibrosarcoma (MFS), an aggressive soft tissue sarcoma, presents a significant challenge because of its high recurrence rate, distal metastasis, and complex genetic background. Although surgical resection is the standard treatment for MFS, the outcomes are unsatisfactory and effective non-surgical treatment strategies, including drug therapy, are urgently warranted. MFS is a rare tumor that requires comprehensive preclinical research to develop promising drug therapies; however, only two MFS cell lines are publicly available worldwide. The present study reports two novel patient-derived MFS cell lines, NCC-MFS7-C1 and NCC-MFS8-C1. These cell lines have been extensively characterized for their genetic profile, proliferation, spheroid-forming capacity, and invasive behavior, confirming that they retain MFS hallmarks. Furthermore, we conducted comprehensive drug screening against these cell lines and six others previously established in our laboratory to identify potential therapeutic candidates for MFS. Among the screened agents, actinomycin D, bortezomib, and romidepsin demonstrated considerable antiproliferative effects that were superior to those of doxorubicin, a standard drug, highlighting their potential as novel drugs. In conclusion, NCC-MFS7-C1 and NCC-MFS8-C1 are valuable research resources that contribute to the understanding of the pathogenesis and development of novel therapies for MFS.

3.
Nihon Ronen Igakkai Zasshi ; 61(1): 80-83, 2024.
Article in Japanese | MEDLINE | ID: mdl-38583974

ABSTRACT

A 75-year-old man with type 2 diabetes and a history of previous empyema surgery was admitted to our hospital due to difficulty moving caused by chronic obstructive pulmonary disease and dehydration. During the first two days of hospitalization, intestinal myiasis was diagnosed after maggots were found in his diapers. After the maggots disappeared, he developed a fever, prompting antibiotic therapy for a suspected secondary infection, resulting in clinical improvement. Despite thorough home cleaning, no flies or maggots were found, and the source of infection and the fly species remained unknown. Recent reports suggest a higher prevalence of myiasis among the elderly, even with overall improvement in hygiene. While myiasis is typically mild, it is a condition that requires consideration in an aging society. Myiasis is a disease that should be considered in the differential diagnosis of the elderly, especially in people who are bedridden or frail.


Subject(s)
Diabetes Mellitus, Type 2 , Myiasis , Male , Animals , Humans , Aged , Anti-Bacterial Agents/therapeutic use , Myiasis/diagnosis , Myiasis/drug therapy , Diagnosis, Differential , Larva
4.
J Appl Clin Med Phys ; 25(6): e14330, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38478368

ABSTRACT

BACKGROUND: This study aimed to evaluate the clinical acceptability of rotational gantry-based single-position carbon-ion radiotherapy (CIRT) to reduce the gastrointestinal (GI) dose in pancreatic cancer. We also evaluated the usefulness of the deformable image registration (DIR)-based dosimetry method for CIRT. MATERIAL AND METHODS: Fifteen patients with pancreatic cancer were analyzed. The treatment plans were developed for four beam angles in the supine (SP plan) and prone (PR plan) positions. In the case of using multiple positions, the treatment plan was created with two angles for each of the supine and prone position (SP + PR plan). Dose evaluation for multiple positions was performed in two ways: by directly adding the values of the DVH parameters for each position treatment plan (DVH sum), and by calculating the DVH parameters from the accumulative dose distribution created using DIR (DIR sum). The D2cc and D6cc of the stomach and duodenum were recorded for each treatment plan and dosimetry method and compared. RESULTS: There were no significant differences among any of the treatment planning and dosimetry methods (p > 0.05). The DVH parameters for the stomach and duodenum were higher in the PR plan and SP plan, respectively, and DVH sum tended to be between the SP and PR plans. DVH sum and DIR sum, DVH sum tended to be higher for D2cc and DIR sum tended to be higher for D6cc. CONCLUSION: There were no significant differences in the GI dose, which suggests that treatment with a simple workflow performed in one position should be clinically acceptable. In CIRT, DIR-based dosimetry should be carefully considered because of the potential for increased uncertainty due to the steep dose distributions.


Subject(s)
Heavy Ion Radiotherapy , Organs at Risk , Pancreatic Neoplasms , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Intensity-Modulated , Humans , Pancreatic Neoplasms/radiotherapy , Pancreatic Neoplasms/diagnostic imaging , Radiotherapy Planning, Computer-Assisted/methods , Heavy Ion Radiotherapy/methods , Organs at Risk/radiation effects , Radiotherapy, Intensity-Modulated/methods , Patient Positioning , Male , Female , Image Processing, Computer-Assisted/methods , Aged , Middle Aged , Prognosis
5.
Hum Cell ; 37(3): 874-885, 2024 May.
Article in English | MEDLINE | ID: mdl-38466561

ABSTRACT

Giant cell tumor of bone (GCTB) is a rare osteolytic bone tumor consisting of mononuclear stromal cells, macrophages, and osteoclast-like giant cells. Although GCTB predominantly exhibits benign behavior, the tumor carries a significant risk of high local recurrence. Furthermore, GCTB can occasionally undergo malignant transformation and distal metastasis, making it potentially fatal. The standard treatment is complete surgical resection; nonetheless, an optimal treatment strategy for advanced GCTB remains unestablished, necessitating expanded preclinical research to identify appropriate therapeutic options. However, only one GCTB cell line is publicly available from a cell bank for research use worldwide. The present study reports the establishment of two novel cell lines, NCC-GCTB8-C1 and NCC-GCTB9-C1, derived from the primary tumor tissues of two patients with GCTB. Both cell lines maintained the hallmark mutation in the H3-3A gene, which is associated with tumor formation and development in GCTB. Characterization of these cell lines revealed their steady growth, spheroid-formation capability, and invasive traits. Potential therapeutic agents were identified via extensive drug screening of the two cell lines and seven previously established GCTB cell lines. Among the 214 antitumor agents tested, romidepsin, a histone deacetylase inhibitor, and mitoxantrone, a topoisomerase inhibitor, were identified as potential therapeutic agents against GCTB. Conclusively, the establishment of NCC-GCTB8-C1 and NCC-GCTB9-C1 provides novel and crucial resources that are expected to advance GCTB research and potentially revolutionize treatment strategies.


Subject(s)
Antineoplastic Agents , Bone Neoplasms , Giant Cell Tumor of Bone , Humans , Giant Cell Tumor of Bone/genetics , Giant Cell Tumor of Bone/pathology , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Bone Neoplasms/genetics , Bone Neoplasms/pathology
6.
Hum Cell ; 37(3): 865-873, 2024 May.
Article in English | MEDLINE | ID: mdl-38478355

ABSTRACT

Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor characterized by rearrangement of the ASPSCR1 and TFE3 genes and a histologically distinctive pseudoalveolar pattern. ASPS progresses slowly, but is prone to late metastasis. As ASPS is refractory to conventional chemotherapy, the only curative treatment is complete surgical resection. The prognosis of advanced and metastatic cases is poor, highlighting the need for preclinical research to develop appropriate treatment options. However, ASPS is extremely rare, accounting for < 1% of all soft tissue sarcomas, and only one patient-derived ASPS cell line is available from public cell banks worldwide for research. This study reports the establishment of a novel ASPS cell line derived from the primary tumor tissue of an ASPS patient, named NCC-ASPS2-C1. This cell line retains the ASPSCR1-TFE3 fusion gene, which is characteristic of ASPS. The characterization of this cell line revealed stable growth, spheroid formation, and invasive properties. By screening a drug library using NCC-ASPS2-C1, we identified several drugs that inhibited the proliferation of ASPS cells. In conclusion, the establishment of NCC-ASPS2-C1 provides a valuable resource for advancing ASPS research and developing novel treatments for this challenging disease.


Subject(s)
Antineoplastic Agents , Sarcoma, Alveolar Soft Part , Soft Tissue Neoplasms , Humans , Sarcoma, Alveolar Soft Part/genetics , Sarcoma, Alveolar Soft Part/pathology , Cell Line, Tumor , Soft Tissue Neoplasms/pathology , Transcription Factors , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Antineoplastic Agents/pharmacology
7.
Hum Cell ; 37(3): 854-864, 2024 May.
Article in English | MEDLINE | ID: mdl-38372888

ABSTRACT

Dermatofibrosarcoma protuberans (DFSP) is the most prevalent dermal sarcoma, characterized by the presence of the fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor beta chain (PDGFB) gene. Although PDGF receptor inhibitor imatinib mesylate was approved for the treating patients with unresectable or metastatic DFSP, disease progression was shown in 9.2% of the patients. Therefore, developing novel therapeutic strategies is crucial for improving the prognosis of DFSP. Patient-derived cell lines play a vital role in preclinical studies; however, only a limited number of DFSP cell lines are currently available in public cell banks. Here, we successfully established a novel DFSP cell line (NCC-DFSP5-C1) using surgically resected tumor tissue from a patient with DFSP. NCC-DFSP5-C1 cells were confirmed to carry the COL1A1-PDGFB translocation and maintain the same mutation as the original tumor tissue. They exhibited consistent growth, formed spheroids, and were invasive. By screening a drug library using NCC-DFSP5-C1 and four previously established DFSP cell lines, we identified anti-cancer drugs that inhibit DFSP cell proliferation. Our observations suggest that the NCC-DFSP5-C1 cell line holds promise as a valuable tool for conducting fundamental and preclinical studies for DFSP.


Subject(s)
Antineoplastic Agents , Dermatofibrosarcoma , Skin Neoplasms , Humans , Dermatofibrosarcoma/genetics , Dermatofibrosarcoma/pathology , Proto-Oncogene Proteins c-sis/genetics , Imatinib Mesylate/pharmacology , Imatinib Mesylate/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Skin Neoplasms/genetics , Cell Line
8.
Hum Cell ; 37(1): 337-344, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37907774

ABSTRACT

Leiomyosarcoma (LMS) is an aggressive mesenchymal malignancy, which originates from the smooth muscle cells or from the precursor mesenchymal stem cells that potentially differentiate into smooth muscle cells. LMS is one of the most common sarcomas. LMS has genomic instability, reflecting complex and unbalanced karyotypes, and the cytogenetic and molecular changes in LMS are not consistent. The standard treatment of the primary LMS is complete resection, and the metastasis is often observed even after curative surgery. Patient-derived cancer models are a key bioresource to develop a novel therapy, and we aimed to establish and characterize a novel cell line for LMS. We established a cell line from tumor tissues of the patient with LMS and named it NCC-LMS3-C1. We maintained NCC-LMS3-C1 cells for 12 months and passed them more than 30 times. Genome-wide copy number analysis demonstrated that NCC-LMS3-C1 cells harbored genetic abnormalities. NCC-LMS3-C1 cells exhibited aggressive phenotypes such as continuous growth, spheroid formation, and invasion in the tissue culture condition, which may reflect the clinical behaviors of LMS. We performed a drug screening using NCC-LMS3-C1 cells and found that four anti-cancer agents, such as bortezomib, dasatinib, mitoxantrone, and romidepsin, had remarkable anti-proliferative effects on NCC-LMS3-C1 cells. We conclude that NCC-LMS3-C1 cells will be a useful resource for the study of LMS.


Subject(s)
Antineoplastic Agents , Leiomyosarcoma , Sarcoma , Humans , Leiomyosarcoma/genetics , Leiomyosarcoma/pathology , Cell Line, Tumor , Sarcoma/genetics , Antineoplastic Agents/pharmacology , Mitoxantrone
9.
J Appl Clin Med Phys ; 25(1): e14217, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38018758

ABSTRACT

PURPOSE: Chest wall postmastectomy radiation therapy (PMRT) should consider the effects of chest wall respiratory motion. The purpose of this study is to evaluate the effectiveness of robustness planning intensity modulated radiation therapy (IMRT) for respiratory movement, considering respiratory motion as a setup error. MATERIAL AND METHODS: This study analyzed 20 patients who underwent PMRT (10 left and 10 right chest walls). The following three treatment plans were created for each case and compared. The treatment plans are a planning target volume (PTV) plan (PP) that covers the PTV within the body contour with the prescribed dose, a virtual bolus plan (VP) that sets a virtual bolus in contact with the body surface and prescribing the dose that includes the PTV outside the body contour, and a robust plan (RP) that considers respiratory movement as a setup uncertainty and performs robust optimization. The isocenter was shifted to reproduce the chest wall motion pattern and the doses were recalculated for comparison for each treatment plan. RESULT: No significant difference was found between the PP and the RP in terms of the tumor dose in the treatment plan. In contrast, VP had 3.5% higher PTV Dmax and 5.5% lower PTV V95% than RP (p < 0.001). The RP demonstrated significantly higher lung V20Gy and Dmean by 1.4% and 0.4 Gy, respectively, than the PP. The RP showed smaller changes in dose distribution affected by chest wall motion and significantly higher tumor dose coverage than the PP and VP. CONCLUSION: We revealed that the RP demonstrated comparable tumor doses to the PP in treatment planning and was robust for respiratory motion compared to both the PP and the VP. However, the organ at risk dose in the RP was slightly higher; therefore, its clinical use should be carefully considered.


Subject(s)
Breast Neoplasms , Radiotherapy, Intensity-Modulated , Thoracic Wall , Humans , Female , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Radiotherapy Planning, Computer-Assisted , Radiotherapy Dosage , Mastectomy
10.
Hum Cell ; 37(2): 511-522, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38143259

ABSTRACT

Pseudomyxoma peritonei (PMP) is a rare phenomenon, characterized by accumulation of mucus in the abdominal cavity due to a mucinous neoplasm. Histologically, PMP is divided into three prognostic classes, namely low-grade mucinous carcinoma peritonei (LGMCP), high-grade mucinous carcinoma peritonei (HGMCP), and high-grade mucinous carcinoma peritonei with signet ring cells (HGMCP-S); HGMCP-S exhibits the worst prognosis. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have been established as the standard therapy for PMP. However, 50% of patients with PMP experience a recurrence, and 30-40% are unable to receive the standard treatment due to invasive diseases. Therefore, novel therapies are required for their treatment. Although patient-derived cell lines are important tools for basic and pre-clinical research, PMP cell lines derived from patients with HGMCP-S have never been reported. Thus, we established a novel PMP cell line NCC-PMP2-C1, using surgically resected tumor tissue from a patient with HGMCP-S. NCC-PMP2-C1 cells were maintained for more than five months and passaged 30 times under culture conditions. NCC-PMP2-C1 cells exhibited multiple deletions and somatic mutations, slow growth, histological features, and dissemination of tumor cells in nude mice. Screening for the anti-proliferative effects of anti-cancer drugs on cells revealed that bortezomib, mubritinib, and romidepsin had a significant response against NCC-PMP2-C1 cells. Thus, the NCC-PMP2-C1 cell line is the first PMP cell line harboring signet ring cells and will be a valuable resource for basic and preclinical studies of HGMCP-S.


Subject(s)
Adenocarcinoma, Mucinous , Carcinoma, Signet Ring Cell , Peritoneal Neoplasms , Pseudomyxoma Peritonei , Animals , Mice , Humans , Pseudomyxoma Peritonei/therapy , Pseudomyxoma Peritonei/metabolism , Pseudomyxoma Peritonei/pathology , Mice, Nude , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/therapy , Adenocarcinoma, Mucinous/pathology , Carcinoma, Signet Ring Cell/therapy , Carcinoma, Signet Ring Cell/pathology , Myelin P2 Protein
12.
Hum Cell ; 36(6): 2187-2194, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37490236

ABSTRACT

Dermatofibrosarcoma protuberans (DFSP) is a superficial low-grade sarcoma, genetically characterized by a fusion gene in collagen type I α (COL1A1) gene and platelet-derived growth factor subunit ß (PDGFB). DFSP is locally aggressive and does not typically metastasize. However, DFSP with fibrosarcomatous transformation, which occurs in 7-16% of DFSP cases, demonstrates a poor prognosis than classic DFSP with a higher local recurrence rate and metastatic potential. Although imatinib, a PDGF receptor inhibitor, is a potent therapeutic agent for classic DFSP, it is less effective for DFSP with fibrosarcomatous transformation. The development of definitive chemotherapies for DFSP with fibrosarcomatous transformation is required. Patient-derived tumor cell lines are indispensable tools for preclinical research to discover novel therapeutic agents. However, only seven cell lines were derived from DFSP, out of which only two were established from DFSP with fibrosarcomatous transformation. Hence, in the present study, we established a novel DFSP cell line, NCC-DFSP4-C1, from a surgically resected DFSP tumor specimen with fibrosarcomatous transformation. NCC-DFSP4-C1 harbored an identical COL1A1-PDGFB fusion gene as its donor tumor. NCC-DFSP4-C1 cells retained the morphology of their donor tumor and demonstrated constant proliferation, spheroid formation, and invasion capability in vitro. By screening a drug library, we found that bortezomib and romidepsin demonstrated the strongest suppressive effects on the proliferation of NCC-DFSP4-C1 cells. In conclusion, we report a novel cell line of DFSP with fibrosarcomatous transformation, and demonstrate its utility in the development of novel therapeutic agents for DFSP.

13.
Hum Cell ; 36(5): 1804-1812, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37328637

ABSTRACT

Giant cell tumor of bone (GCTB) is a rare bone tumor with osteolytic features, composed of stromal cells with a monotonous appearance, macrophages, and osteoclast-like giant cells. GCTB is commonly associated with a pathogenic mutation in the H3-3A gene. While complete surgical resection is the standard cure for GCTB, it often results in local recurrence and, rarely, metastasis. Thus, an effective multidisciplinary treatment approach is necessary. Although patient-derived cell lines is an essential tool for investigating novel treatment strategies, there are only four GCTB cell lines available in public cell banks. Therefore, this study aimed to establish novel GCTB cell lines and successfully created NCC-GCTB6-C1 and NCC-GCTB7-C1 cell lines from two patients' surgically removed tumor tissues. These cell lines exhibited H3-3A gene mutations, consistent proliferation, and invasive properties. After characterizing their behaviors, we performed high-throughput screening of 214 anti-cancer drugs for NCC-GCTB6-C1 and NCC-GCTB7-C1 and integrated their screening data with those of NCC-GCTB1-C1, NCC-GCTB2-C1, NCC-GCTB3-C1, NCC-GCTB4-C1, and NCC-GCTB5-C1 that we previously established. We identified histone deacetylase inhibitor romidepsin as a possible treatment for GCTB. These findings suggest that NCC-GCTB6-C1 and NCC-GCTB7-C1 could be valuable tools for preclinical and basic research on GCTB.


Subject(s)
Antineoplastic Agents , Bone Neoplasms , Giant Cell Tumor of Bone , Humans , Giant Cell Tumor of Bone/genetics , Cell Line, Tumor , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Antineoplastic Agents/pharmacology , Cell Proliferation/genetics
14.
Expert Rev Proteomics ; 20(4-6): 109-119, 2023.
Article in English | MEDLINE | ID: mdl-37229542

ABSTRACT

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma with a poor prognosis that requires novel therapeutic agents. Proteome information is useful for identifying new therapeutic candidates because it directly reflects the biological phenotype. Additionally, in vitro drug screening is an effective tool to identify candidate drugs for common cancers. Hence, we attempted to identify novel therapeutic candidates for MPNST by integrating proteomic analysis and drug screening. METHODS: We performed comprehensive proteomic analysis on 23 MPNST tumor samples using liquid chromatography - tandem mass spectrometry to identify therapeutic targets. We also conducted drug screening of six MPNST cell lines using 214 drugs. RESULTS: Proteomic analysis revealed that the MET and IGF pathways were significantly enriched in the local recurrence/distant metastasis group of MPNST, whereas drug screening revealed that 24 drugs showed remarkable antitumor effects on the MPNST cell lines. By integrating the results of these two approaches, MET inhibitors, crizotinib and foretinib, were identified as novel therapeutic candidates for the treatment of MPNST. CONCLUSIONS: We successfully identified novel therapeutic candidates for the treatment of MPNST, namely crizotinib and foretinib, which target the MET pathway. We hope that these candidate drugs will contribute to the treatment of MPNST.


Subject(s)
Nerve Sheath Neoplasms , Neurofibrosarcoma , Humans , Nerve Sheath Neoplasms/drug therapy , Nerve Sheath Neoplasms/diagnosis , Nerve Sheath Neoplasms/genetics , Proteome , Drug Evaluation, Preclinical , Crizotinib/pharmacology , Crizotinib/therapeutic use , Proteomics , Cell Line, Tumor
15.
BMC Pulm Med ; 23(1): 146, 2023 Apr 26.
Article in English | MEDLINE | ID: mdl-37101265

ABSTRACT

BACKGROUND: Although cases of respiratory bacterial infections associated with coronavirus disease 2019 (COVID-19) have often been reported, their impact on the clinical course remains unclear. Herein, we evaluated and analyzed the complication rates of bacterial infections, causative organisms, patient backgrounds, and clinical outcome in Japanese patients with COVID-19. METHODS: We performed a retrospective cohort study that included inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021) and obtained demographic, epidemiological, and microbiological results and the clinical course and analyzed the cases of COVID-19 complicated by respiratory bacterial infections. RESULTS: Of the 1,863 patients with COVID-19 included in the analysis, 140 (7.5%) had respiratory bacterial infections. Community-acquired co-infection at COVID-19 diagnosis was uncommon (55/1,863, 3.0%) and was mainly caused by Staphylococcus aureus, Klebsiella pneumoniae and Streptococcus pneumoniae. Hospital-acquired bacterial secondary infections, mostly caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were diagnosed in 86 patients (4.6%). Severity-associated comorbidities were frequently observed in hospital-acquired secondary infection cases, including hypertension, diabetes, and chronic kidney disease. The study results suggest that the neutrophil-lymphocyte ratio (> 5.28) may be useful in diagnosing complications of respiratory bacterial infections. COVID-19 patients with community-acquired or hospital-acquired secondary infections had significantly increased mortality. CONCLUSIONS: Respiratory bacterial co-infections and secondary infections are uncommon in patients with COVID-19 but may worsen outcomes. Assessment of bacterial complications is important in hospitalized patients with COVID-19, and the study findings are meaningful for the appropriate use of antimicrobial agents and management strategies.


Subject(s)
Bacterial Infections , COVID-19 , Coinfection , Community-Acquired Infections , Cross Infection , Respiratory Tract Infections , Staphylococcal Infections , Humans , COVID-19/complications , COVID-19/epidemiology , SARS-CoV-2 , Retrospective Studies , Coinfection/epidemiology , COVID-19 Testing , East Asian People , Bacterial Infections/epidemiology , Bacterial Infections/microbiology , Respiratory Tract Infections/epidemiology , Community-Acquired Infections/epidemiology , Disease Progression
16.
J Appl Clin Med Phys ; 24(5): e13987, 2023 May.
Article in English | MEDLINE | ID: mdl-37018016

ABSTRACT

The errors on the stopping power ratio (SPR) of mouthpiece samples from ERKODENT were evaluated. Erkoflex and Erkoloc-pro from ERKODENT and samples that combined Erkoflex and Erkoloc-pro were computed tomography (CT)-scanned using head and neck (HN) protocol at the East Japan Heavy Ion Center (EJHIC), and the values were averaged to obtain the CT number. The integral depth dose of the Bragg curve with and without these samples was measured for 292.1, 180.9, and 118.8 MeV/u of the carbon-ion pencil beam using an ionization chamber with concentric electrodes at the horizontal port of the EJHIC. The average value of the water equivalent length (WEL) of each sample was obtained from the difference between the range of the Bragg curve and the thickness of the sample. To calculate the difference between the theoretical and measured values, the theoretical CT number and SPR value of the sample were calculated using the stoichiometric calibration method. Compared with the Hounsfield unit (HU)-SPR calibration curve used at the EJHIC, the SPR error on each measured and theoretical value was calculated. The WEL value of the mouthpiece sample had an error of approximately 3.5% in the HU-SPR calibration curve. From this error, it was evaluated that for a mouthpiece with a thickness of 10 mm, a beam range error of approximately 0.4 mm can occur, and for a mouthpiece with a thickness of 30 mm, a beam range error of approximately 1 mm can occur. For a beam passing through the mouthpiece in HN treatment, it would be practical to consider a mouthpiece margin of 1 mm to avoid beam range errors if ions pass through the mouthpiece.


Subject(s)
Heavy Ion Radiotherapy , Proton Therapy , Humans , Phantoms, Imaging , Polyethylenes , Polyvinyls , Water , Radiotherapy Planning, Computer-Assisted/methods
17.
Hum Cell ; 36(2): 847-853, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36629983

ABSTRACT

Desmoid fibromatosis (DSM) is a rare, locally aggressive mesenchymal tumor genetically characterized by mutations in the CTNNB1 gene. A local control rate of up to 65‒80% for DSM is achieved with multiple modality treatments, including watchful monitoring, radiation therapy, chemotherapy, and surgery. However, several variables, such as age < 30 years, extremity tumor location, and tumor size of > 10 cm in diameter, are associated with poor local control rates in patients with DSM. The definitive treatments for DSM have not been established. Therefore, it is necessary to develop novel treatments for DSM. Moreover, although patient-derived tumor cell lines are potent tools for preclinical research, no DSM cell lines have been reported. Therefore, this study aimed to establish and characterize a novel DSM cell line for preclinical studies on DSM. Herein, we established the first cell line derived from a patient with DSM exhibiting poor prognostic factors (27-year-old male patient with a DSM tumor of > 10 cm in diameter located at the lower extremity) and named it NCC-DSM1-C1. NCC-DSM1-C1 cells had a T41A mutation in CTNNB1 and exhibited constant proliferation, spheroid formation, and invasion capability in vitro. Screening of antitumor agents in NCC-DSM1-C1 cells showed that bortezomib and romidepsin are effective against DSM. In conclusion, we report the first officially characterized DSM cell line derived from a patient with DSM exhibiting factors associated with poor prognosis. We believe that NCC-DSM1-C1 cell line is a useful tool for developing novel treatments for DSM.


Subject(s)
Antineoplastic Agents , Fibromatosis, Aggressive , Male , Humans , Adult , Cell Line, Tumor , Mutation , Bortezomib
18.
J Infect Chemother ; 29(4): 422-426, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36682606

ABSTRACT

OBJECTIVES: We investigated the occurrence of non-respiratory bacterial and fungal secondary infections, causative organisms, impact on clinical outcomes, and association between the secondary pathogens and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: This was a retrospective cohort study that included data from inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021). We obtained demographic, epidemiological, and microbiological data throughout the course of hospitalization and analyzed the cases of COVID-19 complicated by non-respiratory bacterial infections. RESULTS: Of the 1914 patients included, non-respiratory bacterial infections with COVID-19 were diagnosed in 81 patients (4.2%). Of these, 59 (3.1%) were secondary infections. Bacteremia was the most frequent bacterial infection, occurring in 33 cases (55.9%), followed by urinary tract infections in 16 cases (27.1%). Staphylococcus epidermidis was the most common causative organism of bacteremia. Patients with COVID-19 with non-respiratory secondary bacterial infections had significantly higher mortality, and a multivariate logistic regression analysis demonstrated that those with bacteremia (aOdds Ratio = 15.3 [5.97-39.1]) were at higher risk of death. Multivariate logistic regression analysis showed that age, male sex, use of steroids to treat COVID-19, and intensive care unit admission increased the risk for nosocomial bacteremia. CONCLUSIONS: Secondary bacteremia is an important complication that may lead to poor prognosis in cases with COVID-19. An appropriate medical management strategy must be established, especially for patients with concomitant predisposing factors.


Subject(s)
Bacteremia , Bacterial Infections , COVID-19 , Coinfection , Mycoses , Humans , Male , COVID-19/complications , COVID-19/epidemiology , Retrospective Studies , Coinfection/epidemiology , Bacteremia/drug therapy , Bacteremia/epidemiology , Bacteremia/microbiology , Bacterial Infections/microbiology , Mycoses/microbiology , COVID-19 Testing
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