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1.
Anticancer Res ; 44(6): 2453-2458, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38821602

ABSTRACT

BACKGROUND/AIM: Synovial sarcoma (SS) is a rare malignant tumor with a poor survival rate. We previously reported that a combination of auranofin (AUR), a thioredoxin reductase inhibitor, and celecoxib (CE), an anti-inflammatory drug, significantly impedes the local progression of osteosarcoma (OS). However, the role of redox regulation in SS remains to be elucidated. This study aimed to investigate the efficacy of combined treatment of AUR and CE on the local progression of SS in vivo. MATERIALS AND METHODS: Nu/nu mice were implanted with the human SS cell line, Aska-SS, and treated with vehicle control, AUR, or a combination of AUR and CE (AUR-CE). Primary tumor size and weight were evaluated for the study duration and upon resection, respectively. Hematoxylin and eosin (H&E) and Ki-67 staining were performed to assess the local progression of SS. RESULTS: A statistically significant reduction in tumor size and weight was observed in the AUR- and AUR-CE-treated groups upon excision compared to that in the vehicle-treated group. The AUR-CE-treated group showed synergistic inhibition of local tumor growth. H&E staining of local SS tumors revealed decreased cell density and nuclear deformation in the AUR- and AUR-CE-treated groups compared to those in the vehicle-treated group. Immunohistochemical staining revealed a statistically significant decrease in Ki-67-positive cells in the AUR-CE-treated group compared to the vehicle-treated group. CONCLUSION: The combination of AUR and CE showed significant potential for delaying the local progression of SS. These findings support the repurposing of AUR and CE as early treatment options for SS.


Subject(s)
Auranofin , Celecoxib , Disease Progression , Sarcoma, Synovial , Xenograft Model Antitumor Assays , Celecoxib/pharmacology , Celecoxib/administration & dosage , Animals , Sarcoma, Synovial/drug therapy , Sarcoma, Synovial/pathology , Sarcoma, Synovial/metabolism , Auranofin/pharmacology , Auranofin/therapeutic use , Humans , Mice , Cell Line, Tumor , Mice, Nude , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cell Proliferation/drug effects
2.
Genes Chromosomes Cancer ; 63(5): e23246, 2024 05.
Article in English | MEDLINE | ID: mdl-38747331

ABSTRACT

Dermatofibroma (DF) is a benign tumor that forms pedunculated lesions ranging in size from a few millimeters to 2 cm, usually affecting the extremities and trunks of young adults. Histopathologically, DF is characterized by the storiform proliferation of monomorphic fibroblast-like spindle cells. In addition to neoplastic cells, secondary elements such as foamy histiocytes, Touton-type giant cells, lymphoplasmacytes, and epidermal hyperplasia are characteristic histological features. Several histological variants, including atypical, cellular, aneurysmal, and lipidized variants, have been reported; cases with variant histologies are sometimes misdiagnosed as sarcomas. We present a case of metastasizing aneurysmal DF that was initially diagnosed as an angiosarcoma on biopsy. A 26-year-old woman was referred to our hospital with a gradually enlarging subcutaneous mass in her lower left leg. Positron emission tomography-computed tomography revealed high fluorodeoxyglucose uptake not only in the tumor but also in the left inguinal region. On biopsy, ERG and CD31-positive atypical spindle cells proliferated in slit-like spaces with extravasation, leading to the diagnosis of angiosarcoma. Histology of the wide-resection specimen was consistent with DF, and lymph node metastasis was also observed. Nanopore DNA sequencing detected CD63::PRKCD fusion and copy number gain, although CD63 was not included in the target region of adaptive sampling. This report highlights the importance of recognizing the unusual clinical, radiological, and pathological features of DF to avoid misdiagnosis, and the potential diagnostic utility of nanopore sequencer.


Subject(s)
Hemangiosarcoma , Histiocytoma, Benign Fibrous , Nanopore Sequencing , Oncogene Proteins, Fusion , Adult , Female , Humans , Hemangiosarcoma/genetics , Hemangiosarcoma/diagnosis , Hemangiosarcoma/pathology , Histiocytoma, Benign Fibrous/genetics , Histiocytoma, Benign Fibrous/diagnosis , Histiocytoma, Benign Fibrous/pathology , Nanopore Sequencing/methods , Oncogene Proteins, Fusion/analysis , Oncogene Proteins, Fusion/genetics , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Skin Neoplasms/diagnosis , Tetraspanin 30/genetics , Tetraspanin 30/metabolism
3.
Virchows Arch ; 484(3): 533-538, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38483612

ABSTRACT

EWSR1::NFATC2 sarcoma, a rare round cell sarcoma constituting the majority of EWSR1::non-ETS sarcomas, has recently been defined in the latest WHO classification. To date, the cytological findings of EWSR1::NFATC2 sarcoma remain undocumented. We present the case of a 25-year-old man with a history of polyostotic fibrous dysplasia in the right leg, referred to our hospital with left thigh pain. Cytological findings included metachromasia, minimally pleomorphic round cells, and eosinophilic infiltration. There was no precursor fibrous dysplasia and the initial diagnosis was undifferentiated pleomorphic sarcoma. Following histologic review, we successfully performed immunocytochemistry and fluorescence in situ hybridization (FISH) on archival cytology specimens. The tumor cells were positive for NKX2-2, NKX3-1, and PAX7 and showed amplified 5' single signals of EWSR1 gene. Reverse transcriptase-polymerase chain reaction revealed an in-frame fusion of EWSR1 and NFATC2. This report describes the cytological features of EWSR1::NFATC2 sarcoma and highlights the diagnostic utility of archival cytology specimens.


Subject(s)
Cytology , Oncogene Proteins, Fusion , Sarcoma , Adult , Humans , Male , Diagnosis, Differential , In Situ Hybridization, Fluorescence , NFATC Transcription Factors/genetics , Oncogene Proteins, Fusion/genetics , RNA-Binding Protein EWS/genetics , Sarcoma/diagnosis , Sarcoma/genetics , Transcription Factors/genetics
4.
Anticancer Res ; 44(3): 1045-1049, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38423669

ABSTRACT

BACKGROUND/AIM: Osteosarcoma (OS) is a rare malignant tumor with a poor survival rate. Our previous study reported that auranofin (AUR), a thioredoxin reductase inhibitor, suppresses OS pulmonary metastases; however, the local progression of OS is not affected, in vivo. Nonetheless, the development of augmentation therapy with AUR to inhibit OS local progression remains challenging. Celecoxib (CE), an anti-inflammatory drug, potently enhances the therapeutic activity of AUR against colon cancer. Consequently, this study investigated the combined effects of AUR and CE on OS local progression and pulmonary metastases, in vivo. MATERIALS AND METHODS: C3H/HeSlc mice were implanted with the murine OS cell line, LM8. The mice were treated either with a vehicle control, AUR, or combination of AUR and CE (AUR-CE). The primary tumor size and weight were evaluated for the study duration and at resection, respectively. Hematoxylin and eosin and Ki-67 staining were performed to evaluate OS local progression and pulmonary metastases. RESULTS: Mice in the AUR-CE group showed statistically significantly suppressed tumor sizes and weights at the time of excision compared with those in the vehicle. The mice in the AUR group did not show a statistically significant effect. Histopathological analysis of the primary tumor revealed a statistically significant decrease of the Ki-67-positive cells in the AUR-CE group compared with the vehicle group. Histopathological and quantitative analyses demonstrated that the AUR and AUR-CE groups had statistically significant reductions in the development of OS pulmonary metastases compared with the vehicle group. CONCLUSION: The combination of AUR and CE significantly inhibited OS local progression and pulmonary metastases.


Subject(s)
Bone Neoplasms , Lung Neoplasms , Osteosarcoma , Animals , Mice , Auranofin/pharmacology , Celecoxib/pharmacology , Celecoxib/therapeutic use , Ki-67 Antigen , Mice, Inbred C3H , Osteosarcoma/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Cell Line, Tumor , Bone Neoplasms/pathology
5.
Cancer Genomics Proteomics ; 21(2): 178-185, 2024.
Article in English | MEDLINE | ID: mdl-38423598

ABSTRACT

BACKGROUND/AIM: Chemoresistance in rhabdomyosarcoma (RMS) is associated with poor survival, necessitating the development of novel anticancer drugs. Auranofin (AUR), an anti-rheumatic drug, is a thioredoxin reductase (TXNRD) inhibitor with anticancer properties. Although patient-derived xenograft (PDX) models are essential for studying cancer biology, reports on sarcomas using the PDX model are scarce because of their rarity. This study aimed to investigate the effectiveness of AUR treatment in RMS using a PDX model to evaluate its impact on local progression. MATERIALS AND METHODS: A 20-year-old woman who was diagnosed with alveolar RMS was used to generate the PDX model. RMS PDX tumors were implanted in nude mice and divided into non-treated (vehicle) and treated (AUR) groups. Tumor volume and weight were evaluated, and immunohistochemical staining was performed to evaluate local progression of the sarcoma. The relationship between the TXNRD-1 expression and survival probability of patients with RMS was evaluated using publicly available expression cohorts. RESULTS: AUR significantly suppressed RMS tumor progression over time. It also significantly suppressed the tumor size and weight at the time of excision. Histological evaluation showed that AUR induced oxidative stress in the PDX mouse models and inhibited the local progression of RMS by inducing apoptosis. High TXNRD-1 expression was found to be a negative prognostic factor for overall survival in patients with RMS. CONCLUSION: AUR-induced inhibition of TXNRDs can significantly impede the local progression of RMS through the oxidative stress-apoptosis pathway as demonstrated in PDX models. Thus, targeting TXNRD inhibition may be a promising therapeutic strategy for the treatment of RMS.


Subject(s)
Rhabdomyosarcoma , Sarcoma , Female , Humans , Animals , Mice , Young Adult , Adult , Thioredoxin-Disulfide Reductase , Mice, Nude , Rhabdomyosarcoma/drug therapy , Auranofin , Disease Models, Animal , Xenograft Model Antitumor Assays , Cell Line, Tumor
6.
Jpn J Clin Oncol ; 53(10): 950-956, 2023 Oct 04.
Article in English | MEDLINE | ID: mdl-37461196

ABSTRACT

OBJECTIVE: The present study investigated the relationships between the preoperative and operative findings of solitary fibrous tumour (SFT) and between preoperative findings and prognosis. METHODS: We reviewed 50 SFT patients treated at our musculoskeletal oncology hospital group. We analyzed preoperative clinical findings, particularly MRI imaging findings, and intraoperative information as well as the relationship between preoperative findings and outcomes. RESULTS: Mean age was 48.9 years and the mean follow-up was 51.8 months. Prior to surgery, needle biopsy was performed on 27 patients and open biopsy on 14. T2-weighted images showed a high signal intensity in 24 patients and heterogeneous signal intensity in 20. Tumours had polylobular contours in 17 patients and smooth and round contours in 27. Collateral feeding vessels were detected in 22 patients. Gd-enhanced MRI was performed on 23 patients, and showed 15 with homogeneous enhancement and 8 with heterogeneous enhancement. Surgical times were significantly longer in patients with a retroperitoneal origin, a tumour of 10 cm or more, and polylobular-type tumours. Intraoperative blood loss was significantly greater in patients with a retroperitoneal origin and heterogeneous Gd-MRI-enhanced tumours. In histopathological evaluations, surgical margins were positive in 12 patients. Local recurrence was observed in one patient. Distant metastasis was noted in eight patients, four of whom had pulmonary metastases. Positive surgical margins were more common in polylobular-type tumours. Distant metastases were more likely to appear in patients with observable collateral feeding vessels and heterogeneous Gd-MRI enhancement. CONCLUSION: The present results suggest that preoperative clinical findings in SFT patients predict longer surgical times and the risk of increased intraoperative blood loss. Moreover, the risk of a positive surgical margin and postoperative distant metastases may be predicted based on preoperative MRI.


Subject(s)
Blood Loss, Surgical , Solitary Fibrous Tumors , Humans , Middle Aged , Magnetic Resonance Imaging/methods , Margins of Excision , Multicenter Studies as Topic , Prognosis , Retrospective Studies , Solitary Fibrous Tumors/diagnostic imaging , Solitary Fibrous Tumors/surgery , Solitary Fibrous Tumors/pathology
7.
Anticancer Res ; 43(7): 3273-3279, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37352003

ABSTRACT

BACKGROUND/AIM: Malignant bone tumors (MBT) and soft tissue sarcomas (STS) require wide excision. Although the number of elderly patients is increasing, wide excision may decrease limb function and quality of life (QOL) for elderly patients. However, no detailed evaluation of the functional prognosis or QOL of elderly patients with sarcoma has been reported. This study evaluated postoperative limb function and QOL in elderly patients with MBT and STS. PATIENTS AND METHODS: This retrospective study included 67 patients aged >70 years with MBT or STS who underwent surgery at a single institution. The Toronto Extremity Salvage Score (TESS), EuroQoL 5-dimension 5-level (EQ-5D-5L) questionnaire, Musculoskeletal Tumor Society (MSTS) score, and psoas muscle index (PMI) were evaluated. We also assessed factors associated with the postoperative TESS and EQ-5D-5L index. RESULTS: Detailed examination of the MSTS items perioperatively revealed significant decline in manual dexterity/walking ability and support but significant improvement in pain and emotional acceptance. The mean PMI decreased significantly from 4.7 to 4.23 perioperatively. The postoperative mean TESS and EQ-5D-5L index was 76.9 and 0.74, respectively. Patients with good performance status and clinical frailty scale scores preoperatively had better postoperative TESS and EQ-5D-5L scores. CONCLUSION: The current study strongly suggests the possibility of maintaining postoperative limb function, satisfaction, and QOL in patients with MBT and STS by choosing patients in good condition and the appropriate procedure that the patient desires. However, perioperative progression of sarcopenia should be noted.


Subject(s)
Bone Neoplasms , Sarcoma , Soft Tissue Neoplasms , Aged , Humans , Quality of Life , Retrospective Studies , Limb Salvage/methods , Extremities/pathology , Sarcoma/surgery , Sarcoma/pathology , Soft Tissue Neoplasms/surgery , Soft Tissue Neoplasms/pathology , Bone Neoplasms/surgery , Bone Neoplasms/pathology
8.
Anticancer Res ; 43(5): 2317-2321, 2023 May.
Article in English | MEDLINE | ID: mdl-37097691

ABSTRACT

BACKGROUND/AIM: The effect of multidisciplinary therapy conducted at the sarcoma center of our hospital was examined to determine whether therapy undertaken here improved the prognosis of patients with soft-tissue sarcoma. PATIENTS AND METHODS: The clinical findings and prognoses of patients treated before the establishment of the sarcoma center (72 patients from April 2016 to March 2018) and those treated after (155 patients from April 2018 to March 2021) were compared. RESULTS: The mean number of patients increased from 36.0 to 51.7 per year after the establishment of the sarcoma center. The proportion of patients with stage IV disease also increased from 8.3% to 12.9% after establishment of the sarcoma center. The 3-year survival rate of patients, considering all stages, decreased from 80.0% to 78.3% after establishment of the sarcoma center rather than showing an increase. The 3-year survival rate of patients with stage II and III disease increased from 78.6% to 84.7%, and that of stage III patients with retroperitoneal sarcoma increased from 70.0% to 86.7% after establishment of the sarcoma center. However, no statistically significant difference was observed in the survival curves. CONCLUSION: The establishment of a sarcoma center has contributed to centralizing treatment for soft-tissue sarcoma. Multidisciplinary therapy at sarcoma centers may improve the prognosis of patients with soft-tissue sarcomas.


Subject(s)
Sarcoma , Soft Tissue Neoplasms , Humans , Retrospective Studies , Prognosis , Soft Tissue Neoplasms/drug therapy , Sarcoma/therapy
9.
Anticancer Res ; 43(4): 1767-1773, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36974815

ABSTRACT

BACKGROUND/AIM: Reports on the effects of timing of the surgery on the patient survival rate or the results of palliative laminectomy are limited. The aim of the study was to investigate the postoperative ambulatory status of neurologically impaired metastatic spinal cord compression (MSCC) patients who underwent laminectomy and evaluate predictors of postoperative ambulation recovery after laminectomy for MSCC. PATIENTS AND METHODS: We included 175 patients who underwent decompressive surgery for MSCC. Changes in the Frankel grade (FG) were evaluated perioperatively. Among all patients, 113 were unable to walk preoperatively and were divided into two groups: 70 and 43 patients in the ambulation-regained and ambulation-not regained postoperatively groups, respectively. The percentage of patients eligible for postoperative chemotherapy and overall survival rate in each group were investigated. Furthermore, predictors of postoperative ambulation recovery after laminectomy for MSCC were examined. RESULTS: The most common primary tumor sites were the lung, prostate, and breast. FG improved with surgery in 80 cases, remained unchanged in 94 cases, and worsened in one case. In the ambulation-regained group, 70% were eligible for postoperative chemotherapy, while only 26% of the not-regained group were eligible for postoperative chemotherapy. The postoperative survival rate of the ambulation-regained group was significantly better than that of the not-regained group. Univariate predictors for not regaining the ability to walk were Karnofsky Performance Status ≤40 prior to surgery, FG B prior to surgery, and time to surgery since the inability to walk >48 h. CONCLUSION: Decompressive surgery benefits motor function postoperatively. Both good neurological status prior to surgery and prompt surgery for non-ambulatory MSCC are important predictors of improved functional outcome.


Subject(s)
Spinal Cord Compression , Spinal Neoplasms , Male , Humans , Spinal Cord Compression/etiology , Spinal Cord Compression/surgery , Retrospective Studies , Walking , Karnofsky Performance Status , Spinal Neoplasms/surgery , Spinal Neoplasms/secondary , Treatment Outcome
10.
Cureus ; 15(2): e34618, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36891014

ABSTRACT

We encountered an uncommon case of a non-seminomatous germ cell tumor with solitary bone metastasis at the initial presentation. A 30-year-old male patient with testicular cancer underwent an orchidectomy and was diagnosed with non-seminoma. Positron emission tomography-computed tomography detected an isolated metastatic lesion in the right sacral wing, which disappeared after a series of chemotherapy. En-bloc surgical resection was performed as curative local treatment, and the patient was able to perform his activities of daily living with no apparent recurrence. Therefore, this surgical method is considered safe and beneficial for the treatment of sacral wing lesions.

11.
Asia Pac J Clin Oncol ; 19(5): e320-e325, 2023 Oct.
Article in English | MEDLINE | ID: mdl-36658668

ABSTRACT

AIM: To investigate the relationship between surgical techniques used in our hospital to treat metastatic bone tumors of the proximal femur and activity level and prognosis of patients and whether the location of the tumor is considered when selecting surgical techniques. METHODS: We retrospectively reviewed 82 patients with metastatic bone tumors of the proximal femur who underwent intramedullary nail fixation (IMN), bipolar hip arthroplasty (BHP) or modular megaprosthesis (MMP) in our hospital from 2007 to 2020. We measured the distance from the center of femoral head to the proximal (x) and distal (y) end of the of tumor, using preoperative computed tomography images to determine the location of metastasis. We also measured revised Katagiri score at the time of fracture, postoperative ISOLS/MSTS (functional outcome) scores, and overall survival. RESULTS: The value of x was significantly different among the three groups. The value of y showed a significant difference between the IMN and BHP groups and the BHP and MMP groups. The functional outcome score was significantly lower in the IMN group. The survival rate of the patient tended to be higher in the BHP and MMP groups than in the IMN group 1 year postoperatively. CONCLUSION: IMN was favored when the distance from the center of femoral head to the proximal end of the tumor was ≥15 mm. In the case of prosthetic replacement, BHP was chosen if the distance from the center of femoral head to the distal end of the tumor was ≤70 mm. BHP and MMP were preferred over IMN functionally.


Subject(s)
Bone Neoplasms , Femur , Humans , Retrospective Studies , Femur/surgery , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/surgery , Bone Neoplasms/secondary , Prognosis , Treatment Outcome
12.
Cancer Diagn Progn ; 2(6): 681-685, 2022.
Article in English | MEDLINE | ID: mdl-36340450

ABSTRACT

BACKGROUND/AIM: Chondrosarcoma (CS) is a rare primary malignant bone tumor, which is the second most common tumor after osteosarcoma. Since chemotherapy and radiotherapy have poor efficacy for CS, amputation or surgical wide resection is the main strategy for localized high-grade CS, making CS therapy difficult. As studies on high-grade CS are limited owing to its rare nature, there are many unknown prognostic factors for survival. PATIENTS AND METHODS: This retrospective cohort study included 44 patients with high-grade CS who underwent surgery at a single institution. Overall survival (OS), distant failure-free survival (DFFS), and local failure-free survival (LFFS) were evaluated using the Kaplan-Meier method. Furthermore, we evaluated prognostic factors for survival in patients with high-grade CS using univariate and multivariate analyses. RESULTS: The 5-year OS, LFFS, and DFFS rates of high-grade CS were 75.9%, 90.8%, and 66.5%, respectively. Univariate analysis revealed that tumor size, tumor grade, and surgical margin were significant prognostic factors for OS and DFFS, and distant metastasis was significantly associated with OS. Furthermore, the multivariate analysis indicated that the presence of local recurrence and distant metastasis was significantly associated with OS. CONCLUSION: Local recurrence and distant metastasis were significant prognostic factors for high-grade CS.

13.
Anticancer Res ; 42(4): 2139-2144, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35347038

ABSTRACT

BACKGROUND/AIM: The effectiveness of clavicula pro humero (CPH) reconstruction for pediatric proximal humerus sarcoma has been reported in a small number of cases. We aimed to investigate the effectiveness of biological CPH reconstruction for malignant bone tumors of the proximal humerus in children and adults. PATIENTS AND METHODS: This was a retrospective cohort study that included eight patients who underwent CPH reconstruction due to a malignant bone tumor around the proximal humerus. Postoperative parameters, including complications, postoperative upper limb function, and the period until bone fusion, were investigated. RESULTS: Three patients had non-union and fracture of the clavicular segment. Among them, one patient underwent revision surgery for internal fixation and bone grafting. Five patients achieved bone fusion, and the overall mean Musculoskeletal Tumor Society score was 70%, which is comparable to previous reports. CONCLUSION: CPH reconstruction is an effective technique for malignant bone tumors of the proximal humerus in all ages.


Subject(s)
Bone Neoplasms , Plastic Surgery Procedures , Adult , Bone Neoplasms/pathology , Bone Neoplasms/surgery , Child , Clavicle/pathology , Humans , Humerus/pathology , Humerus/surgery , Plastic Surgery Procedures/methods , Retrospective Studies
14.
Anticancer Res ; 41(12): 6013-6021, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34848455

ABSTRACT

BACKGROUND/AIM: The thioredoxin-1 (Trx-1) inhibitor, PX-12, is active against several cancer types. This study aimed to evaluate its effects on local osteosarcoma (OS) progression and to describe PX-12-related signal transduction pathways. MATERIALS AND METHODS: Publicly available expression cohort data were analyzed to determine the relationship between the expression levels of TXN, which codes for the Trx protein, and survival in patients with OS. Murine LM8 OS cells were stimulated with PX-12. Apoptosis-related protein levels, cell viability, caspase activity, and wound healing were evaluated. PX-12 efficacy in suppressing tumor progression was evaluated in C3H mice injected with LM8 cells. RESULTS: High TXN expression was a negative prognostic factor for metastasis and overall survival in OS patients. PX-12 induced apoptosis in OS cells via the oxidative stress-MAPK-caspase 3 pathway and suppressed OS cell migration. PX-12 suppressed local OS progression. CONCLUSION: PX-12 is a potential therapeutic agent for use in suppressing local OS progression.


Subject(s)
Antineoplastic Agents/pharmacology , Disulfides/pharmacology , Imidazoles/pharmacology , Thioredoxins/antagonists & inhibitors , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Disease Models, Animal , Disease Progression , Dose-Response Relationship, Drug , Humans , Mice , Oxidative Stress/drug effects , Xenograft Model Antitumor Assays
15.
Anticancer Res ; 41(12): 6273-6278, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34848483

ABSTRACT

BACKGROUND/AIM: There are no reports evaluating sleep disturbance and skeletal muscle loss in response to the treatment of soft tissue sarcoma (STS) with chemotherapy. This study investigated the effects of combined doxorubicin (DXR) and ifosfamide (IFM) on sleep and skeletal muscle. PATIENTS AND METHODS: This retrospective cohort study included 14 patients with high-grade STS. Participants underwent five 7-day hospitalizations during which they received chemotherapy for 5 consecutive days. Sleep analysis and muscle-volume evaluation were investigated using a wearable device during hospitalization and by bioelectrical impedance analysis at each chemotherapy course. RESULTS: Chemotherapy significantly impeded sleep, increased wake-time after sleep onset, and aggravated movement index during hospitalization. In long-term body composition assessment, chemotherapy induced muscle-mass loss and fat-mass gain. CONCLUSION: Combination of DXR and IFM for STS induces skeletal muscle loss and sleep disruption.


Subject(s)
Antibiotics, Antineoplastic/adverse effects , Antineoplastic Agents, Alkylating/adverse effects , Doxorubicin/adverse effects , Ifosfamide/adverse effects , Muscular Atrophy/chemically induced , Sarcoma/drug therapy , Sleep Wake Disorders/chemically induced , Adolescent , Adult , Aged , Antibiotics, Antineoplastic/pharmacology , Antibiotics, Antineoplastic/therapeutic use , Antineoplastic Agents, Alkylating/pharmacology , Antineoplastic Agents, Alkylating/therapeutic use , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Female , Humans , Ifosfamide/pharmacology , Ifosfamide/therapeutic use , Male , Middle Aged , Young Adult
16.
Anticancer Res ; 41(10): 4947-4955, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34593442

ABSTRACT

BACKGROUND/AIM: Auranofin (AUR), a thioredoxin reductase (TXNRD) inhibitor, shows anticancer activity against several cancers. This study investigated the effects of AUR on the local progression and pulmonary metastasis of osteosarcoma (OS). MATERIALS AND METHODS: Publicly available expression cohorts were analysed to study the relationship between TXNRD-2 expression and the survival of patients with OS. The murine OS cell line LM8 was stimulated with AUR. Cell viability, apoptosis-related protein levels, caspase activity, and wound healing were analysed. Tumor progression and pulmonary metastasis were investigated in C3H mice implanted with LM8 cells. RESULTS: High-level expression of TXNRD-2 represented a negative prognostic factor for metastasis and overall survival in patients with OS. AUR induced apoptosis of OS cells via the oxidative stress-MAPK-Caspase 3 pathway, and suppressed the migration of OS cells. AUR inhibited the pulmonary metastasis of OS, but not local progression. CONCLUSION: AUR represents a potential therapeutic drug for suppressing pulmonary metastasis of OS.


Subject(s)
Auranofin/pharmacology , Bone Neoplasms/drug therapy , Lung Neoplasms/drug therapy , Osteosarcoma/drug therapy , Thioredoxin-Disulfide Reductase/antagonists & inhibitors , Animals , Antirheumatic Agents/pharmacology , Apoptosis , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Cell Movement , Cell Proliferation , Female , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/secondary , Mice , Mice, Inbred C3H , Osteosarcoma/metabolism , Osteosarcoma/pathology , Prognosis , Survival Rate , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
17.
Anticancer Res ; 41(8): 4027-4032, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34281869

ABSTRACT

BACKGROUND/AIM: We aimed to investigate the effectiveness of postoperative radiotherapy (RT) on local recurrence-free survival (LRFS) in high-grade infiltrative soft tissue sarcomas (STSs) and determine its prognostic factors. PATIENTS AND METHODS: This was a retrospective cohort study and included 132 patients with high-grade STSs. Patients were divided into two groups: Group RT (n=48) who underwent postoperative RT and Group No-RT (n=84) who underwent only surgery. We analysed 5-year LRFS and its prognostic factors between these groups. Furthermore, 5-year LRFS in infiltrative and non-infiltrative STSs were evaluated. RESULTS: Five-year LRFS was not significantly different in Group RT (83.6%) and Group No-RT (79.6%) (p=0.698). Overall, significant prognostic factors influencing LRFS were age at diagnosis (p=0.02) and tumour growth pattern (p=0.04). Postoperative RT was less effective in the infiltrative than in non-infiltrative pattern of STSs. CONCLUSION: Postoperative RT does not influence local recurrence outcomes in infiltrative STSs.


Subject(s)
Soft Tissue Neoplasms/radiotherapy , Adolescent , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Postoperative Period , Retrospective Studies , Soft Tissue Neoplasms/mortality , Soft Tissue Neoplasms/pathology , Young Adult
18.
Oncol Rep ; 46(1)2021 Jul.
Article in English | MEDLINE | ID: mdl-34036394

ABSTRACT

Osteosarcoma (OS) is the most common malignant bone tumor, and its sensitivity to preoperative chemotherapy is a significant prognostic factor. The present study aimed to identify potential genomic markers for the prediction of chemosensitivity in patients with OS using a genomic approach. A total of 50 pediatric and adolescent patients diagnosed with high­grade OS were selected. Each pre­therapeutic biopsy sample was subjected to comparative genomic hybridization array analysis and targeted exome sequencing. Although no recurrent gene mutation was observed in chemoresistant tumors, copy number analysis detected recurrent gain of chromosome 12q14.1, which was significantly more frequent (5/21; 24%) in the poor responder cohort than in the good responder cohort (0/29; 0%; P<0.01). Subsequent expression analysis revealed that CDK4 was the only gene in the 12q14.1 gained region with an expression level that was positively associated with copy number gains. In order to elucidate the effect of CDK4 on drug sensitivity, CDK4­overexpressing OS cell lines were treated with cisplatin (CDDP); significant attenuation of CDDP sensitivity, demonstrated by increased cell viability and decreased expression of cleaved caspase­9, was induced by enforced expression of CDK4. In addition, treatment with CDK4/6 inhibitor palbociclib in CDK4­overexpressing U2OS cells facilitated apoptosis and a significant decrease in cell viability in a dose­dependent manner. In conclusion, the results of the present study showed that higher expression and amplification of CDK4 in tumors is a predictive biomarker for resistance to conventional chemotherapy in patients with OS and that palbociclib is a promising drug for this therapeutically challenging cohort.


Subject(s)
Biomarkers, Tumor/genetics , Bone Neoplasms/genetics , Cyclin-Dependent Kinase 4/genetics , Drug Resistance, Neoplasm , Osteosarcoma/genetics , Piperazines/pharmacology , Pyridines/pharmacology , Up-Regulation , Adolescent , Bone Neoplasms/drug therapy , Cell Line, Tumor , Cell Proliferation , Cell Survival , Child , Child, Preschool , Cisplatin/pharmacology , Comparative Genomic Hybridization , Drug Resistance, Neoplasm/drug effects , Gene Dosage , Gene Expression Profiling , Humans , Osteosarcoma/drug therapy , Up-Regulation/drug effects , Exome Sequencing
19.
Anticancer Res ; 41(2): 1041-1046, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33517313

ABSTRACT

BACKGROUND/AIM: This study aimed to investigate the effectiveness of knee rotationplasty (KRP) as salvage surgery for uncontrolled infection and implant failure of total knee arthroplasty (TKA) for sarcoma around the knee in adolescents and young adults (AYA). PATIENTS AND METHODS: This retrospective cohort study included 33 patients who underwent KRP and were grouped based on the treatment received: initial surgery for sarcoma around the knee (n=18) or as salvage surgery (n=15). Musculoskeletal Tumor Society (MSTS) score, range of motion (ROM) and postoperative results were analyzed. RESULTS: All 15 patients who underwent salvage KRP had TKA as an initial surgery. Although there were five infections in salvage KRP, which originated from the initial TKA, all cases were controllable, no implant failure occurred. MSTS score and ROM were deemed acceptable in both groups. CONCLUSION: Salvage KRP is an effective option for uncontrolled complications of initial TKA for sarcoma around the knee.


Subject(s)
Limb Salvage/methods , Prosthesis-Related Infections/surgery , Reoperation/methods , Sarcoma/surgery , Adolescent , Adult , Arthroplasty, Replacement, Knee/adverse effects , Female , Humans , Knee/physiopathology , Male , Prosthesis Design , Prosthesis Failure , Range of Motion, Articular , Retrospective Studies , Rotation , Sarcoma/physiopathology , Treatment Outcome , Young Adult
20.
Case Rep Dermatol Med ; 2020: 4898965, 2020.
Article in English | MEDLINE | ID: mdl-32774941

ABSTRACT

Undifferentiated pleomorphic sarcoma (UPS) is a high-grade, aggressive, soft tissue sarcoma that is often fatal. Although there are reports describing associations of sarcoma and skin lesions such as burns, radiation, and trauma, to our knowledge, UPS development in a keloid scar has not been reported. Herein, we present the case of a 76-year-old woman who had undergone surgery for endometrial cancer, 5 years before. She presented with a protruding lesion that was continuous to a keloid scar on the abdominal wall. The tumor appeared clinically malignant as it was protruding and doubled in size within three weeks, reaching approximately 6 × 6 × 2 cm. Since the tumor was diagnosed as UPS after pathological evaluation by needle biopsy, wide resection was performed. Intraoperatively, the tumor was apparently continuous to the keloid, protruding and pedunculated outside the body, and had not invaded the abdominal cavity. Histopathological examination of the resected tumor showed evidence of UPS and no suspicion of metastasis of endometrial cancer. No recurrence, metastases, or other complications were noted 6 months after surgery. The current case study reminds us that keloids may cause high-grade sarcoma such as UPS, and careful follow-up is required.

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