Eradication of Extensive Lymph-Node, Bone and Pleural Metastases of a Breast-Cancer Patient Treated With Radiation, Immunotherapy and Oral Recombinant Methioninase.

Background/aim: Metastatic breast cancer is a recalcitrant disease with a poor prognosis. Novel targets and therapies are necessary to improve the survival rate of patients with metastatic breast cancer. Previous pre-clinical and clinical studies, have demonstrated the effectiveness of oral recombinant methioninase (o-rMETase) against breast cancer.

Limited predictive value of pretreatment P-glycoprotein immunostaining for chemotherapy efficacy and survival in long-follow-up osteosarcoma patients.

The clinical utility of P-glycoprotein (P-gp) in osteosarcoma remains controversial. This retrospective cohort study aimed to investigate the association between P-gp expression and clinicopathological factors, chemotherapy (CTx) response, and prognosis in osteosarcoma. Twenty-three osteosarcoma patients treated at our institution between 2007 and 2013 were included.

National survey of Hutchinson-Gilford progeria syndrome and progeroid laminopathy in Japan.

Background And Aim: Hutchinson-Gilford Progeria Syndrome (HGPS) and progeroid laminopathies (PL) are rare genetic disorders characterized by accelerated aging and early onset cardiovascular complications. Despite recent advances in the genetic diagnosis of HGPS and PL and the advent of lonafarnib treatment, the epidemiology and clinical characteristics of these disorders in Asia remain unclear. This study aimed to assess the prevalence, clinical features, and diagnostic trends of the HGPS and PL in Japan.

The Combination of the Autophagy Inhibitor Chloroquine and Recombinant Methioninase Has Selective Synergistic Efficacy on Human Colon Cancer Cells But Not on Normal Human Fibroblasts.

Background/aim: Metastatic colon cancer is a recalcitrant disease with a 5-year survival rate of 15.7-26.0%, and more effective treatments are necessary.

Primary Osseous Leiomyosarcoma of Talus Mimicking Idiopathic Transient Osteoporosis: A Case Report and Literature Review.

Primary leiomyosarcoma of the bone (LMSB) is an exceptionally rare malignant bone tumor. We report a case of a 60-year-old woman with LMSB of the talus initially misdiagnosed as idiopathic transient osteoporosis of the talus based on clinical and initial MRI findings, which showed extensive bone marrow edema without soft tissue invasion. Despite initial improvement with off-loading treatment, the patient's symptoms recurred, and subsequent imaging revealed progression and soft tissue involvement.

Prognostic factors and the impact of neoadjuvant chemotherapy on the development of metastasis in patients with undifferentiated pleomorphic sarcoma of soft tissue.

Background: Although undifferentiated pleomorphic sarcoma (UPS), previously termed as malignant fibrous histiocytoma (MFH), is one of the most common soft tissue sarcomas, the number of studies focusing on UPS remains limited. This retrospective study aimed to identify prognostic factors and assess the clinical impact of chemotherapy on the development of metastasis in patients with UPS.

Methods: This study included 147 patients with UPS who underwent tumor resection.

A perspective on patient-derived orthotopic xenograft (PDOX) mouse models for identification of novel and individualized treatment for sarcoma.

Sarcomas, including osteosarcoma and soft tissue sarcoma, are heterogeneous and rare diseases with limited treatment options and a high metastatic potential. Despite advancements in immunotherapy and targeted therapies, many sarcoma patients have limited durable responses to these treatments. Therefore, individualized precision medicine and novel drug discovery are greatly needed.

Selective Synergy of Ivermectin Combined With Recombinant Methioninase Against Colon-Cancer Cells in Contrast to Normal Fibroblasts.

Background/aim: Recent studies have shown that ivermectin, developed as an anti-parasitic drug, has efficacy against several cancer types. Methionine restriction, including the use of recombinant methioninase (rMETase), has been developed to target methionine addiction, a fundamental hallmark of cancer, termed the Hoffman effect. Metastatic colorectal cancer (CRC) is a recalcitrant disease that requires novel and disruptive treatment approaches.

Current and emerging systemic treatment options for malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma.

Undifferentiated pleomorphic sarcoma (UPS)/malignant fibrous histiocytoma (MFH) is the second most common soft-tissue sarcoma. The standard treatment options for UPS/MFH include tumor excision with appropriate surgical margins, radiation therapy, and chemotherapy. Preferable clinical outcomes can be expected in patients with resectable disease, whereas the clinical outcomes in patients with metastatic disease are unsatisfactory despite multidisciplinary treatment.

Perspective on an Innovative Curative Strategy for Peritoneal Metastasis Involving Peritonectomy, Hyperthermic Intraperitoneal Chemotherapy, and Adjuvant Chemotherapy Identified as Effective in the Histoculture Drug Response Assay (HDRA).

Background/aim: Peritoneal carcinomatosis is the end stage for patients with gastrointestinal cancer, with survival ranging between 2 and 9 months. Pancreatic acinar cell carcinoma (PACC) is rare and can result in peritoneal metastases. The efficacy of chemotherapy for patients with PACC is unknown, and a systemic treatment strategy has not been established.

Recombinant Methioninase and Cisplatinum Act Synergistically to Inhibit Lewis Lung Carcinoma Cells But Not Normal Fibroblasts.

Background/aim: Cisplatinum (CDDP) is used as first-line therapy in lung cancer. To further improve the therapeutic efficacy of CDDP, we focused on methionine addiction of cancer, known as the Hoffman effect. The present study aimed to determine the synergistic efficacy of the combination of CDDP and recombinant methioninase (rMETase) to target methionine addiction of lung cancer.

HT1080 Human Fibrosarcoma Cells Selected for Super-eribulin Resistance Become More Malignant and Are Arrested Synergistically by Methionine Restriction in Combination With Eribulin in Nude Mice.

Background/aim: Eribulin is a microtubule inhibitor used in the treatment of various malignancies, including soft-tissue sarcoma. However, the development of eribulin resistance is a recalcitrant clinical problem. The present study demonstrates that super eribulin-resistant HT1080 human fibrosarcoma cells become highly malignant but can be eradicated synergistically by the combination of eribulin and methionine restriction in nude mice.

Highly Synergistic Eradication of 143B Osteosarcoma Cells by the Combination of Recombinant Methioninase, Chloroquine, and Rapamycin Targeting Methionine Addiction, Autophagy, and mTOR, Respectively.

Background/aim: Drug-resistant osteosarcoma is a highly aggressive malignancy with limited therapeutic options. Recombinant methioninase (rMETase) targets the methionine addiction of cancer and acts synergistically with many cancer-chemotherapy agents. The present study investigated the synergistic efficacy of the combination of rMETase, chloroquine (CQ) which targets autophagy, and rapamycin (RAPA) which targets mTOR, on human 143B osteosarcoma cells .

Comparative surgical invasiveness of internal fixation for pathological fractures in metastatic bone disease versus traumatic fractures: a quantitative analysis of operative time and blood loss.

Objective: The primary aim of this study was to compare the surgical invasiveness of internal fixation for pathological fractures caused by metastatic bone tumors with that for traumatic fractures. The secondary aim was to identify factors contributing to the complexity of surgeries for metastatic bone disease and provide insights for improving surgical strategies by analyzing operative time and blood loss.

Methods: Patients undergoing internal fixation for femoral fractures at 10 institutions between January 2021 and December 2023 were included.

HT1080 Fibrosarcoma With Acquired Trabectedin Resistance: Increased Malignancy But Sustained Sensitivity to Methionine Restriction.

Background/aim: Trabectedin is a DNA-binding agent that has shown moderate efficacy for soft-tissue sarcomas. We have previously shown that methionine restriction enhances trabectedin efficacy on both parental and trabectedin-resistant HT1080 (TR-HT1080) cells The aim of the present study was to determine whether fibrosarcoma cells that acquire trabectedin resistance become more malignant but maintain sensitivity to methionine restriction Materials and Methods: TR-HT1080 was established by culturing HT1080 cells in stepwise increasing concentrations of trabectedin. An wound-healing invasion assay was used to compare malignancy of HT1080 and TR-HT1080.

Dynamic Fluorescence Imaging of Orally-administered Tumor-targeting A1-R Expressing Green Fluorescent Protein Trafficking Through the Gastrointestinal System to Target Fibrosarcomas in Nude Mice.

Background/aim: A1-R (A1-R) expresses green fluorescent protein (GFP) and has the ability to selectively target and inhibit all major cancer types in murine models without persistently infecting healthy tissue. A1-R is being developed for tumor targeting by oral administration. The aim of the present study was to demonstrate real-time imaging of orally-administered A1-R in a fibrosarcoma nude-mouse model and to visualize its trafficking through the gastrointestinal system to the tumor and normal organs.

Predictive variables for intraoperative blood loss and surgical time in resection of malignant soft tissue tumors without reconstruction.

Background: Procedural techniques such as dissection and separation of blood vessels or nerves from the tumor for preserving limbs and functions involves high surgical difficulty. We hypothesized the relation of vessel and/or nerve preservation to surgical time and blood loss, accurately reflecting surgical difficulty. In this study, we elucidated the variables affecting surgical time and intraoperative bleeding in patients with malignant soft tissue tumors who did not undergo any reconstruction after tumor resection.

Clinicopathological background of local recurrence in high grade sarcoma of the extremity with preoperative chemotherapy: a supplementary analysis of JCOG0304.

Background: The mainstay of treatment for soft-tissue sarcomas is complete resection with negative surgical margins. However, treatment strategies for local control including the frequency of adjuvant radiotherapy (RT) and surgical margin differ greatly between Japan and other countries, and the optimal strategy of local control remains controversial.

Methods: A total of 70 patients with high-grade sarcoma who underwent surgery of the 72 patients enrolled in JCOG0304, were included.

Recombinant Methioninase (rMETase) Synergistically Sensitizes Ivermectin-resistant MCF-7 Breast Cancer Cells 9.9 Fold to Low-dose Ivermectin.

Background/aim: Ivermectin is a widely-used anti-parasitic agent and has shown early promise as an anticancer agent. Recombinant methioninase (rMETase) is a methionine-depleting enzyme targeting the methionine addiction of cancer and has broad efficacy against all tested cancer types. However, the combination efficacy of ivermectin and rMETase on breast cancer cells remains unexplored.

Complete Response (CR) in a Previously-progressing Chronic Lymphocytic Leukemia (CLL) Patient Treated With Methionine Restriction in Combination With First-line Chemotherapy.

Background/aim: Chronic lymphocytic leukemia (CLL) is currently incurable. CLL is characterized by disordered DNA methylation. The aim of the present study was to target methylation with methionine restriction in a patient with progressive CLL.

Synergistic Eradication of Fibrosarcoma With Acquired Ifosfamide Resistance Using Methionine Restriction Combined With Ifosfamide in Nude-mouse Models.

Background/aim: Ifosfamide is used clinically with doxorubicin as first-line chemotherapy for soft-tissue sarcoma. However, ifosfamide efficacy for soft-tissue sarcoma is limited due to frequent occurence of ifosfamide resistance and thus more effective therapy is needed. The present study aimed to determine the synergy of recombinant methioninase (rMETase) plus ifosfamide against HT1080 human fibrosarcoma cells in vitro.

The Combination of Tumor-targeting A1-R Plus the Autophagy-inhibitor Chloroquine Synergistically Eradicates HT1080 Fibrosarcoma Cells and .

Background/aim: Salmonella typhimurium A1-R (A1-R) targets and inhibits a wide range of cancer types without continuously infecting healthy tissue. Chloroquine, an antimalarial drug, induces apoptosis and inhibits autophagy in cancer cells. The aim of the present study was to determine the synergy of A1-R plus chloroquine on HT1080 human fibrosarcoma cells in vitro and in a nude-mouse model.

Ivermectin Combined With Recombinant Methioninase (rMETase) Synergistically Eradicates MiaPaCa-2 Pancreatic Cancer Cells.

Background/aim: Ivermectin was initially utilized as a veterinary medication, demonstrating efficacy against various parasites. Pancreatic cancer is currently one of the most recalcitrant diseases. The aim of the present study was to demonstrate the synergy of the combination of recombinant methioninase (rMETase) and ivermectin to eradicate human pancreatic cancer cells in vitro.