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.

Immunologic Alteration After Total En-Bloc Spondylectomy with Anterior Spinal Column Reconstruction with Frozen Tumor-Containing Bone Autologous Grafts: A Case Report in a Prospective Study.

Cryotherapy could stimulate immune responses and induce abscopal effects. A novel technique was developed for treating spinal bone tumors involving the use of frozen tumor-containing autologous bone grafts for anterior spinal reconstruction following total en-bloc spondylectomy, with the aim of activating cryoimmunity. This study focused on analyzing changes in the T-cell receptor (TCR) repertoire after surgery to evaluate T-cell diversity.

Clinical outcome of patients with soft tissue sarcoma after bone metastases: Tokai musculoskeletal oncology consortium study.

Background: Soft tissue sarcomas (STSs) are a diverse group of rare malignant tumors accounting for <1% of all human tumors. Almost 50% of patients with STS develop metastatic disease, mainly within 3 years of initial diagnosis. Lung metastasis occurs in 20%-30% of STS cases, while bone metastasis is rare.

Contemporary positive signs of functional limb weakness in post-acute sequelae of SARS-CoV-2: an exploratory analysis of their utility in diagnosis and follow-up.

Background: Sequelae of the acute phase of coronavirus disease-19, termed long COVID, are characterised by numerous indicators, including neurological symptoms. Functional neurological disorder (FND) can occur with or without various structural diseases. No previous study has examined the relationship between long COVID and FND, with positive signs for FND.

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.

Comparison of histological response across patients with Ewing sarcoma treated with preoperative chemotherapy with or without preoperative radiotherapy.

Purpose: This study aimed to compare the histological response, a surrogate preoperative treatment efficacy marker, of patients treated with preoperative chemotherapy with or without preoperative radiotherapy. Moreover, local recurrence in both groups was investigated.

Methods: Surgical specimens from 210 patients with Ewing sarcoma were assessed between 2003 and 2020 to evaluate their histological response to preoperative treatment; 181 patients received preoperative chemotherapy, while 29 received both preoperative chemotherapy and radiotherapy.

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.

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 .

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.

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.

Long-term follow-up of chronic osteomyelitis after bone tumor resection.

The standard treatment for chronic osteomyelitis after trauma is affected bone resection and bone and soft tissue defect reconstruction. However, few reports exist regarding chronic osteomyelitis after bone tumor surgery. We retrospectively reviewed five cases of chronic infection after bone tumor surgery, including their treatment strategy and clinical course.

Posterior Instrumentation without Curettage Promotes Rapid Restoration of Adult Spinal Langerhans Cell Histiocytosis.

Introduction: Adult spinal Langerhans cell histiocytosis (LCH) presents a treatment challenge due to ongoing controversies. Traditional approaches such as curettage with bone grafting and internal fixation are preferred for severe cases involving mechanical instability, neurological deficits, or deformity. This study aimed to explore the efficacy of a customized approach involving simple posterior instrumentation without curettage or bone grafting in treating adult spinal LCH.

Risk Factors and Impact on Survival of Pathological Fractures in Patients With Humeral Metastasis.

Background Bone metastases often cause pathological fractures and impair patients' quality of life and survival. Although several studies have been conducted on pathological fractures in the femur and spine, limited research has been done on the upper limbs. This study aimed to reveal the risk factors and determine how pathological fractures impact survival in patients with humeral metastasis.

Selective Synergy of Recombinant Methioninase Plus Docetaxel Against Docetaxel-resistant and -sensitive Fibrosarcoma Cells Compared to Normal Fibroblasts.

Background/aim: Docetaxel combined with gemcitabine is a second-line treatment for soft-tissue sarcoma; however, its effectiveness is limited because of docetaxel resistance. The objective of the present study was to determine the potential of recombinant methioninase (rMETase) to enhance the efficacy of docetaxel on high-docetaxel-resistant human fibrosarcoma cells in vitro.

Materials And Methods: Docetaxel-resistant HT1080 (DTR-HT1080) human fibrosarcoma cells were established by culturing them in by progressively increasing concentrations of docetaxel from 0.