Pertuzumab Retreatment for Human Epidermal Growth Factor Receptor 2-Positive Locally Advanced/Metastatic Breast Cancer (PRECIOUS Study): Final Overall Survival Analysis.

In the primary analysis of the open-label phase III PRECIOUS study, pertuzumab retreatment combined with trastuzumab plus chemotherapy of physician's choice (PTC) significantly improved investigator-assessed progression-free survival (PFS) compared with trastuzumab plus physician's choice chemotherapy (TC) in patients with human epidermal growth factor receptor 2 (HER2)-positive locally advanced/metastatic breast cancer (LA/mBC). Here, we report final overall survival (OS) at the median follow-up of 25.8 months.

Transanal Minimally Invasive Surgery for a Gastrointestinal Stromal Tumor of the Lower Rectum: A Case Report.

Rectal gastrointestinal stromal tumors (GISTs) are prevalent in the lower rectum, and the existing literature suggests that transanal interventions are advantageous for anorectal preservation. Herein, we present a case of rectal GIST resection using transanal minimally invasive surgery. A 75-year-old woman reported vaginal discomfort and was subsequently diagnosed with GIST via transanal tumor biopsy.

Pharmacokinetic and Exposure-Response Modeling Support Body Surface Area-Based Dosing of Farletuzumab Ecteribulin in Japanese Patients with Solid Tumors.

The first-in-human, Phase 1 Study 101 showed antitumor activity and a tolerable safety profile of farletuzumab ecteribulin in Japanese patients with platinum-resistant ovarian and non-small cell lung cancer. A pharmacometric assessment evaluated farletuzumab ecteribulin pharmacokinetics and exposure-response (E-R) relationships for efficacy and safety to support dose optimization. Patients received 0.

Eosinophil is a predictor of severe immune-related adverse events induced by ipilimumab plus nivolumab therapy in patients with renal cell carcinoma: a retrospective multicenter cohort study.

Introduction: Immune-related adverse events (irAEs) induced by immune checkpoint inhibitors are difficult to predict and can lead to severe events. Although it is important to develop strategies for the early detection of severe irAEs, there is a lack of evidence on irAEs associated with ipilimumab plus nivolumab therapy for metastatic renal cell carcinoma (RCC). Therefore, this study aimed to investigate the association between eosinophil and severe irAEs in patients receiving ipilimumab plus nivolumab therapy for RCC.

WT1-mRNA dendritic cell vaccination of patients with glioblastoma multiforme, malignant pleural mesothelioma, metastatic breast cancer, and other solid tumors: type 1 T-lymphocyte responses are associated with clinical outcome.

Cell therapies, including tumor antigen-loaded dendritic cells used as therapeutic cancer vaccines, offer treatment options for patients with malignancies. We evaluated the feasibility, safety, immunogenicity, and clinical activity of adjuvant vaccination with Wilms' tumor protein (WT1) mRNA-electroporated autologous dendritic cells (WT1-mRNA/DC) in a single-arm phase I/II clinical study of patients with advanced solid tumors receiving standard therapy. Disease status and immune reactivity were evaluated after 8 weeks and 6 months.

Enhancing the efficacy of near-infrared photoimmunotherapy through intratumoural delivery of CD44-targeting antibody-photoabsorber conjugates.

Background: Photoimmunotherapy (PIT) is a potent modality for cancer treatment. The conventional PIT regimen involves the systemic delivery of an antibody-photoabsorber conjugate, followed by a 24-h waiting period to ensure adequate localisation on the target cells. Subsequent exposure to near-infrared (NIR) light selectively damages the target cells.

Receptor discordance after nipple-sparing mastectomy.

Background: Recent studies have shown that receptor status of breast cancer change between primary tumor and recurrence, which may influence treatment strategy and prognosis, but there are few reports on receptor discordance between primary tumors and local recurrence (LR) after nipple-sparing mastectomy (NSM).

Patients And Methods: We collected 74 patients who had LR after NSM for newly diagnosed stages 0 to 3 breast cancer between 2008 and 2016 at 14 institutions. We classified into 4 subtypes based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2).

Indications for chemoradiotherapy in older patients with locally advanced head and neck cancer in Japan: a questionnaire survey in the JCOG head and neck cancer study group.

Introduction: Chemoradiation therapy (CRT) with concurrent high-dose cisplatin (CDDP) is one of the standard treatment options for locally advanced head and neck cancer. Since the indications specific to the older population have not been reported, we conducted a multicenter survey on the indications.

Methods: In April and May 2023, a questionnaire survey was emailed to all institutions belonging to the JCOG-HNCSG, consisting of 37 institutions.

A network analysis of postpartum depression and mother-to-infant bonding shows common and unique symptom-level connections across three postpartum periods.

Postpartum depression and mother-to-infant bonding difficulties (MIBD), two issues crucial to maternal and infant mental health, often coexist and affect each other. Our study aims to dissect their complex relationship through a graphical LASSO network analysis of individual symptoms in 5594 Japanese postpartum women, whose geographical distribution was nationally representative. We identified 'fear', 'enjoyment', 'overwhelm', and 'insomnia' as common bridge symptoms linking postpartum depression and MIBD across three distinct postpartum periods.

Immune evasion through mitochondrial transfer in the tumour microenvironment.

Cancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T cell attack. For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumour immune responses. However, detailed mechanisms of such processes remain unclear.

Evaluation of Treatment Outcomes Using dNLR and GNRI in Combination Therapy With Atezolizumab and Bevacizumab for Hepatocellular Carcinoma.

Aim: This study aims to investigate the clinical utility of the derived neutrophil-to-lymphocyte ratio (dNLR) and the Geriatric Nutritional Risk Index (GNRI) in predicting treatment outcomes for patients with unresectable hepatocellular carcinoma (HCC) undergoing combination therapy with atezolizumab and bevacizumab (Atez/Bev).

Methods: A retrospective analysis was conducted on 310 patients. The dNLR, NLR, and GNRI were calculated, and their impact on progression-free survival (PFS) and overall survival (OS) was assessed.

Granulomatous inflammatory responses are elicited in the liver of PD-1 knockout mice by genome mutagenesis.

Introduction: Programmed death-1 (PD-1) is a negative regulator of immune responses. Upon deletion of PD-1 in mice, symptoms of autoimmunity developed only after they got old. In a model experiment in cancer immunotherapy, PD-1 was shown to prevent cytotoxic T lymphocytes from attacking cancer cells that expressed neoantigens derived from genome mutations.

Metabolism and effects of acetoaceto--toluidine in the urinary bladder of humanized-liver mice.

Occupational exposure to aromatic amines is a major risk factor for urinary bladder cancer. Our previous studies showed that acetoaceto--toluidine, which is produced using -toluidine as a raw material, promotes urinary bladder carcinogenesis in rats. We also found high concentrations of -toluidine, a human bladder carcinogen, in the urine of acetoaceto--toluidine-treated rats, indicating that urinary -toluidine derived from acetoaceto--toluidine may play an important role in bladder carcinogenesis.

Longitudinal associations between informal caring, social network, and psychological distress among adolescents and young adults: modelling within-person effects.

Background: Informal caring is associated with mental health deterioration among young people and impacts their help-seeking ability. Social network can provide social support and mitigate the impact of informal care. However, young carers may avoid identification and withdraw from social networks.

Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

Expression rate of LAT1 in high-grade parotid gland carcinoma and potential of BNCT as a treatment option for recurrent parotid gland carcinoma.

Purpose: Boron neutron capture therapy (BNCT) perform as a treatment option for locally advanced or recurrent unresectable head and neck cancers since June 2020 in Japan. The effect of BNCT on parotid carcinoma, which presents a variety of histologic types, remains unclear. The object of this study was to investigate the antitumor efficacy of BNCT against parotid gland carcinoma by focusing on LAT1, which is involved in the uptake of L-BPA, the boron compound used in BNCT.

Pharmacokinetic characterization and exposure-response relationship of crovalimab in the COMMODORE 1, 2 and 3 and COMPOSER trials of patients with paroxysmal nocturnal haemoglobinuria.

Aims: Crovalimab is a novel C5 inhibitor administered first intravenously and then subcutaneously in patients with paroxysmal nocturnal haemoglobinuria (PNH) naive to complement inhibition or switching from eculizumab or ravulizumab. Crovalimab showed efficacy and safety comparable to eculizumab in the pivotal COMMODORE 2 and supporting studies.

Methods: We characterized crovalimab pharmacokinetics and the relationship between exposure pharmacokinetic parameters and pharmacodynamic biomarkers, efficacy and safety endpoints using pooled data (healthy volunteers [n = 9], naive [n = 210] and switched [n = 211] patients).

Effect of Proteinuria Before Lenvatinib Administration on Treatment Response After Atezolizumab Bevacizumab Combination Therapy.

Aim: We investigated the impact of proteinuria on the therapeutic effect before lenvatinib administration as second-line treatment after atezolizumab-bevacizumab.

Methods: We examined 64 patients who were administered lenvatinib as second-line treatment after discontinuation of atezolizumab and bevacizumab. Proteinuria assessed before lenvatinib administration was considered severe if the qualitative value test (QV) was 3+ or the urine protein/creatinine ratio (UPCR) was ≥ 2.

MicroRNA-3145 as a potential therapeutic target for hepatitis B virus: inhibition of viral replication via downregulation of HBS and HBX.

Current treatments for hepatitis B virus (HBV), such as interferons and nucleic acid analogs, have limitations due to side effects like depression and the development of drug-resistant mutants, highlighting the need for new therapeutic approaches. In this study, we identified microRNA-3145 (miR-3145) as a host-derived miRNA with antiviral activity that is upregulated in primary hepatocytes during HBV infection. The expression of its precursor, pri-miR-3145, increased in response to the the virus infection, and miR-3145 downregulated the hepatitis B virus S (HBS) antigen and hepatitis B virus X (HBX), thereby inhibiting viral replication.

Increased Non-Relapse Mortality in Older People With Allogeneic Hematopoietic Stem Cell Transplantation Using Fludarabine and Myeloablative Dose of Busulfan-Based Regimen.

Fludarabine and myeloablative busulfan (FluBu4) in allogeneic hematopoietic stem cell transplantation (HSCT) for older people have not been adequately examined. This retrospective study analyzed data from a large-scale, nationwide database in Japan. Adult patients (> 15 years old, y/o) who received their first HSCT with FluBu4 for hematological malignancies were included.

PI5P4K inhibitors: promising opportunities and challenges.

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4K), also known as type II PIPKs or PIPKIIs, convert the lipid second messenger PI5P to PI(4,5)P. The PI5P4K family consists of three isozymes in mammals-PI5P4Kα, β, and γ-which notably utilize both GTP and ATP as phosphodonors. Unlike the other two isozymes, which can utilize both ATP and GTP, PI5P4Kβ exhibits a marked preference for GTP over ATP, acting as an intracellular GTP sensor that alters its kinase activity in response to physiological changes in GTP concentration.

[A CASE OF TESTICULAR TUMOR UNDER CONSIDERATION FOR PARTIAL ORCHIECTOMY THROUGH RAPID INTRAOPERATIVE DIAGNOSIS].

A 35-year-old man visited a local doctor for continuing analysis of his infertility. Semen analysis revealed azoospermia while an ultrasonography detected a right testicular tumor with a diameter of 10 mm. A blood test was negative for tumor markers.

A single-arm, phase II study of sotorasib plus carboplatin/pemetrexed in advanced non-squamous non-small cell lung cancer patients with KRAS G12C mutation (WJOG14821L, SCARLET).

Background: The efficacy and safety of sotorasib plus platinum-doublet chemotherapy in KRAS G12C-mutated non-squamous non-small cell lung cancer (non-Sq NSCLC) were previously reported with limited follow-up period.

Method: SCARLET was a single-arm phase II study of chemotherapy-naïve patients with KRAS G12C-mutated non-Sq NSCLC. Participants received sotorasib 960 mg daily plus four cycles of carboplatin (area under the curve, 5)/pemetrexed 500 mg/m, followed by sotorasib/pemetrexed until disease progression.

Low survival due to higher risk of relapse and non-relapse mortality after allogeneic HSCT in ATL compared with AML and ALL.

Background: Patients with adult T-cell leukemia/lymphoma (ATL) are considered to have worse outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) than patients with other hematological malignancies, owing to high risk of relapse and immunocompromised status. However, no studies have compared transplant outcomes between patients with ATL and those with other hematological malignancies using a large-scale database.

Objectives: To compare transplant outcomes between patients with ATL and those with other leukemias and to identify factors contributing to worse transplant outcomes in ATL patients.