Clinical and prognostic characteristics of metastatic colorectal cancer with minor mutations.

Metastatic colorectal cancer (mCRC) presents notable therapeutic challenges. Rat sarcoma virus () mutations, including those in exon 2, are critical for treatment decisions; however, the role of minor mutations ( exons 3 and 4, and ) remains underexplored. Because these mutations are increasingly identified in routine practice due to advances in mutation testing that now routinely includes exons 3 and 4, and , clarifying their clinical relevance has become important for ensuring appropriate treatment selection.

[Current Status and Issue of Emesis and Vomiting Caused by Trastuzumab Deruxtecan].

Emesis and vomiting are the most common adverse events related to trastuzumab deruxtecan(T-DXd). T-DXd is listed as a moderate emetogenic chemotherapy(MEC)agent in the latest guidelines for the appropriate use of antiemetic drugs in Japan; however, the National Comprehensive Cancer Network Guidelines regard it as a highly emetogenic chemotherapy (HEC)agent. We investigated the risk factors for chemotherapy-induced nausea and vomiting(CINV)associated with T-DXd by analyzing data from 40 patients with advanced breast cancer(median age, 56 years)were receiving T-DXd administration between June 2020 and July 2023.

Evaluation of MAGE-A4 expression in breast cancer and its impact on prognosis.

Melanoma-associated antigen (MAGE)-A4, a cancer testis antigen, presents a promising target for chimeric antigen receptor T cell therapy in refractory solid tumors, including breast cancer (BC). However, the lack of highly specific Abs against MAGE-A4 is a major challenge for the development of MAGE-A4-targeted immunotherapies. This study aimed to validate the specificity of a novel MAGE-A4 Ab (E701U) and examine MAGE-A4 expression in clinical BC samples.

Long-Term Survival Outcomes and Risk Factors for Axillary and Locoregional Recurrence in Japanese Patients with Sentinel Node-Positive Breast Cancer Treated in Accordance with the ACOSOG Z0011 Strategy.

Introduction: In 2018, we reported the results of a study to assess the feasibility of applying the ACOSOG Z0011 criteria to Japanese patients with early-stage breast cancer (median follow-up, 3 years). Their results over the longer term can now be presented. Risk factors for axillary and locoregional recurrence in Z0011-eligible patients are unknown.

Histological Assessment of Synovial Sarcoma Before and After TCR-T Cell Therapy and Cryoablation: A Case Report.

Background/aim: Cancer/testis antigens (CTAs) are well-known molecular targets with expression restricted to testicular germ cells and malignant tumors. T-cell receptor (TCR)-engineered T-cell (TCR-T) therapy against CTAs in patients with sarcoma has shown substantial progress, but resistance to TCR-T therapy remains a critical problem. In this report, we present a case of synovial sarcoma treated with TCR-T therapy targeting the New York-esophageal squamous cell carcinoma (NY-ESO)-1 protein.

Safety and Efficacy of NY-ESO-1 Antigen-Specific T-Cell Receptor Gene-Transduced T Lymphocytes in Patients with Synovial Sarcoma: A Phase I/II Clinical Trial.

Purpose: To determine, for patients with advanced or recurrent synovial sarcoma (SS) not suitable for surgical resection and resistant to anthracycline, the safety and efficacy of the infusion of autologous T lymphocytes expressing NY-ESO-1 antigen-specific T-cell receptor (TCR) gene and siRNA to inhibit the expression of endogenous TCR (product code: TBI-1301).

Patients And Methods: Eligible Japanese patients (HLA-A*02:01 or *02:06, NY-ESO-1-positive tumor expression) received cyclophosphamide 750 mg/m2 on days -3 and -2 (induction period) followed by a single dose of 5×109 (±30%) TBI-1301 cells as a divided infusion on days 0 and 1 (treatment period). Primary endpoints were safety-related (phase I) and efficacy-related [objective response rate (ORR) by RECIST v1.

αβ-T cell receptor transduction gives superior mitochondrial function to γδ-T cells with promising persistence.

Adoptive cell therapy using allogeneic γδ-T cells is a promising option for off-the-shelf T cell products with a low risk of graft-versus-host disease (GVHD). Long-term persistence may boost the clinical development of γδ-T cell products. In this study, we found that genetically modified Vγ9Vδ2 T cells expressing a tumor antigen-specific αβ-TCR and CD8 coreceptor (GMC) showed target-specific killing and excellent persistence.

Ganglioside GD2 Expression Is Associated With Unfavorable Prognosis in Early Triple-negative Breast Cancer.

Background/aim: Gangliosides (acidic glycosphingolipids) have crucial regulatory roles in normal physiological processes, as well as in pathological conditions, including tumor onset and progression. GD2 is highly expressed in triple-negative breast cancer (TNBC), particularly in cancer stem cells. However, little is known on the clinical impact of GD2 expression on the prognosis of TNBC.

Detection of high-risk patients resistant to CDK4/6 inhibitors with hormone receptor-positive HER2-negative advanced and metastatic breast cancer in Japan (KBCSG-TR-1316).

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) improve the prognosis of hormone receptor-positive HER2-negative advanced/metastatic breast cancer (HR+/HER2- mBC). However, some cancers show resistance to CDK4/6i and have a poor prognosis. The non-luminal disease score (NOLUS) was developed to predict non-luminal disease using immunohistochemical analysis.

Chimeric antigen receptor T-cell therapy targeting a MAGE A4 peptide and HLA-A*02:01 complex for unresectable advanced or recurrent solid cancer: protocol for a multi-institutional phase 1 clinical trial.

Introduction: Adoptive cell transfer of genetically engineered T cells is a promising treatment for malignancies; however, there are few ideal cancer antigens expressed on the cell surface, and the development of chimeric antigen receptor T cells (CAR-T cells) for solid tumour treatment has been slow. CAR-T cells, which recognise major histocompatibility complex and peptide complexes presented on the cell surface, can be used to target not only cell surface antigens but also intracellular antigens. We have developed a CAR-T-cell product that recognises the complex of HLA-A*02:01 and an epitope of the MAGE-A4 antigen equipped with a novel signalling domain of human GITR (investigational product code: MU-MA402C) based on preclinical studies.

Atezolizumab-Induced Sarcoidosis-Like Reaction in a Patient with Metastatic Breast Cancer.

Tumor-related sarcoidosis-like reactions (SLR) have been reported with the use of immune checkpoint inhibitors (ICIs). We report a case of 50-year-old woman who observed an enlarged lymph node in the right hilar region and the appearance of a subcutaneous mass in the extremities during chemotherapy with atezolizumab plus nab-paclitaxel for metastatic triple-negative breast cancer (TNBC). Skin biopsy revealed the formation of epithelioid granulation species with the Langhans giant cell.

CD204-positive macrophages accumulate in breast cancer tumors with high levels of infiltrating lymphocytes and programmed death ligand-1 expression.

Although immunotherapy has been demonstrated to be promising in triple-negative (TN) breast cancer (BC), most BC cases are classified as non-TN. To enrich the responders for immunotherapy regardless of their subtypes, classification based on tumor-infiltrating lymphocyte (TIL) levels and programmed death ligand-1 (PD-L1) status may be useful. However, this classification has not been fully applied to BC.

Risk factors for cisplatin-induced acute kidney injury: A pilot study on the usefulness of genetic variants for predicting nephrotoxicity in clinical practice.

Several studies have reported risk factors for predicting cisplatin-induced acute kidney injury (AKI), including old age, female sex, smoking, hypoalbuminemia, hypokalemia, hypomagnesemia, a high body surface area, advanced cancer and the total dose of cisplatin administered. Recently, some studies have focused on the associations between genetic alterations in the genes coding for renal drug transporters, such as organic cation transporter 2 (OCT2), and the nephrotoxicity of cisplatin. However, genetic variants have not been fully elucidated for clinical use.

MAGE-A4, NY-ESO-1 and SAGE mRNA expression rates and co-expression relationships in solid tumours.

Background: Cancer testis (CT) antigens are promising targets for cancer immunotherapies such as cancer vaccines and genetically modified adoptive T cell therapy. In this study, we evaluated the expression of three CT antigens, melanoma-associated antigen A4 (MAGE-A4), New York oesophageal squamous cell carcinoma 1 (NY-ESO-1) and sarcoma antigen gene (SAGE).

Methods: MAGE-A4, NY-ESO-1 and/or SAGE antigen expression in tumour samples was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR).

The Japanese Breast Cancer Society Clinical Practice Guidelines for systemic treatment of breast cancer, 2018 edition.

Purpose: We present the English version of The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer, 2018 edition.

Methods: The JBCS formed a task force to update the JBCS Clinical Practice Guidelines, 2015 edition, according to Minds Handbook for Clinical Practice Guideline Development 2014. First, we set multiple outcomes for each clinical question (CQ).

First-in-human phase I clinical trial of the NY-ESO-1 protein cancer vaccine with NOD2 and TLR9 stimulants in patients with NY-ESO-1-expressing refractory solid tumors.

Cholesteryl pullulan (CHP) is a novel antigen delivery system. CHP and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen complexes (CHP-NY-ESO-1) present multiple epitope peptides to the MHC class I and II pathways. Adjuvants are essential for cancer vaccines.

First Case of Cytokine Release Syndrome after Nivolumab for Gastric Cancer.

Introduction: Cytokine release syndrome (CRS) is a potentially life-threatening systemic disease that has been observed after treatment with antibodies and adoptive T cell therapies. In this case, we observed nivolumab-induced CRS in a patient with gastric cancer.

Case Presentation: A 43-year-old male with advanced gastric cancer was treated with nivolumab as a third-line chemotherapy.

Pertuzumab, trastuzumab and eribulin mesylate therapy for previously treated advanced HER2-positive breast cancer: a feasibility study with analysis of biomarkers.

The standard treatment for advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer is the triple combination of pertuzumab, trastuzumab and docetaxel, but some patients cannot tolerate taxane. To explore a non-taxane triple therapy, we conducted a feasibility study of pertuzumab, trastuzumab and eribulin mesylate (PTE) therapy for previously treated advanced HER2-positive breast cancer with analyses of quality of life and biomarkers. Ten patients were enrolled, two of whom had a history of docetaxel allergy.

A Case of Hyperammonemia Associated with High Dihydropyrimidine Dehydrogenase Activity.

Over the past decades, 5-Fluorouracil (5-FU) has been widely used to treat several types of carcinoma, including esophageal squamous cell carcinoma. In addition to its common side effects, including diarrhea, mucositis, neutropenia, and anemia, 5-FU treatment has also been reported to cause hyperammonemia. However, the exact mechanism responsible for 5-FU-induced hyperammonemia remains unknown.