Artificial Intelligence-Powered Human Epidermal Growth Factor Receptor 2 and Tumor Microenvironment Analysis in Human Epidermal Growth Factor Receptor 2-Amplified Metastatic Colorectal Cancer: Exploratory Analysis of Phase II TRIUMPH Trial.

Purpose: Human epidermal growth factor receptor 2 (HER2)-targeted therapies have shown promise in treating -amplified metastatic colorectal cancer (mCRC). Identifying optimal biomarkers for treatment decisions remains challenging. This study explores the potential of artificial intelligence (AI) in predicting treatment responses to trastuzumab plus pertuzumab (TP) in patients with -amplified mCRC from the phase II TRIUMPH trial.

Repeated inhalation of GM-CSF by nonhuman primates induces bronchus-associated lymphoid tissue along the lower respiratory tract.

Background: Repeated inhalation of granulocyte-macrophage colony-stimulating factor (GM-CSF) was recently approved in Japan as a treatment for autoimmune pulmonary alveolar proteinosis. However, the detailed physiological and pathological effects of repeated inhalation in the long term, especially at increasing doses, remain unclear.

Methods: In this chronic safety study, we administered 24 cynomolgus monkeys (Macaca fascicularis) aged 2-3 years with aerosolized sargramostim (a yeast-derived recombinant human GM-CSF [rhGM-CSF]) biweekly for 26 weeks across four dosing groups (0, 5, 100, and 500 µg/kg/day).

Different efficacy of tyrosine kinase inhibitors by KIT and PGFRA mutations identified in circulating tumor DNA for the treatment of refractory gastrointestinal stromal tumors.

Background: While advanced gastrointestinal stromal tumors (GISTs) are primarily treated with tyrosine kinase inhibitors (TKIs), acquired resistance from specific mutations in KIT or PDGFRA frequently occurs. We aimed to assess the utility of circulating tumor DNA (ctDNA) as a modality of therapeutic decision-making in advanced GIST.

Methods: We conducted a pooled analysis of SCRUM-Japan studies for advanced GIST patients.

Evolution of the Cdk4/6-Cdkn2 system in invertebrates.

The cell cycle is driven by cyclin-dependent kinases (Cdks). The decision whether the cell cycle proceeds is made during G1 phase, when Cdk4/6 functions. Cyclin-dependent kinase inhibitor 2 (Cdkn2) is a specific inhibitor of Cdk4/6, and their interaction depends on D84 in Cdkn2 and R24/31 in Cdk4/6.

Novel ERBB2 Variant Potentially Associated with Resistance against Anti-HER2 Monoclonal Antibody-Based Therapy in ERBB2-Amplified Metastatic Colorectal Cancer.

Purpose: HER2-targeted therapies in ERBB2-amplified metastatic colorectal cancer (mCRC) are effective; however, a notable portion of patients do not respond to treatment, and secondary resistance occurs in most patients receiving these treatments. The purpose of this study was to investigate determinants of treatment efficacy and resistance in patients with ERBB2-amplified mCRC who received HER2-targeted therapy by analyzing multiomics data.

Experimental Design: We investigated genomic data from a nationwide large cancer genomic screening project, the SCRUM-Japan project.

A multicenter, prospective, phase II trial of second-line aflibercept plus FOLFIRI in patients with metastatic colorectal cancer refractory to an anti-EGFR antibody: HGCSG1801.

Aflibercept (AFL) plus FOLFIRI prolongs overall survival (OS) in patients with metastatic colorectal cancer (mCRC). However, there is limited evidence on the efficacy and safety of AFL plus FOLFIRI previously treated with anti-epidermal growth factor receptor (EGFR) agents. Therefore, we conducted a prospective open-label phase II trial evaluating the efficacy and safety of AFL plus FOLFIRI in Japanese patients with mCRC failing a prior oxaliplatin-based chemotherapy plus an anti-EGFR agent.

Effective modulation from the ventral medial to the dorsal medial portion of the prefrontal cortex in memory confidence-based behavioral control.

Metacognition includes the ability to refer to one's own cognitive states, such as confidence, and adaptively control behavior based on this information. This ability is thought to allow us to predictably control our behavior without external feedback, for example, even before we take action. Many studies have suggested that metacognition requires a brain-wide network of multiple brain regions.

Plasma Angiogenic Factors as Predictors of the Efficacy of Second-line Chemotherapy Combined with Angiogenesis Inhibitors in Metastatic Colorectal Cancer: Results From the GI-SCREEN CRC-Ukit Study.

Background: The significance of angiogenic factors as predictors of second-line (2L) chemotherapy efficacy when combined with angiogenesis inhibitors for metastatic colorectal cancer (mCRC) remains unestablished.

Patients And Methods: In this multicenter prospective observational study, 17 angiogenic factors were analyzed in plasma samples collected at pretreatment and progression stages using a Luminex multiplex assay. Patients who received chemotherapy plus bevacizumab (BEV group), FOLFIRI plus ramucirumab (RAM group), or FOLFIRI plus aflibercept (AFL group) as the 2L treatment were included.

Anti-epidermal growth factor receptor treatment for patients with Neo wild-type metastatic colorectal cancer: a case report of two cases.

The Neo phenomenon is defined as the conversion of tumor status from mutant-type (MT) to wild-type (WT) after systemic chemotherapy in metastatic colorectal cancer (mCRC). Cetuximab, an anti-epidermal growth factor receptor (EGFR) antibody, is effective in patients with WT mCRC but ineffective in those with MT mCRC; however, its outcome in patients with Neo WT mCRC is unclear. Herein, we report two cases of Neo WT mCRC that responded clinically to anti-EGFR treatment.

Rats adaptively seek information to accommodate a lack of information.

Metacognition is the ability to adaptively control one's behavior by referring to one's own cognitive processes. It is thought to contribute to learning in situations where there is insufficient information available from the environment. Information-seeking behavior is a type of metacognition in which one confirms the necessary information only when one does not have the necessary and sufficient information to accomplish a task.

The BEETS (JACCRO CC-18) trial: an observational and translational study of -mutated metastatic colorectal cancer.

For V600E-mutated metastatic colorectal cancer (mCRC), the BEACON phase 3 trial showed survival benefit of triplet therapy with cetuximab (anti-EGFR antibody), encorafenib (BRAF inhibitor) and binimetinib (MEK inhibitor) as well as doublet therapy with cetuximab and encorafenib over irinotecan-based chemotherapy plus anti-EGFR antibody. Both regimens are standards of care in Japan, but definite biomarkers for predicting efficacy and selecting treatment remain lacking. The mechanisms underlying resistance to these regimens also warrant urgent exploration to further evolve treatment.

Clinical outcomes of intensive versus less intensive first-line chemotherapy for metastatic colorectal cancer.

Physicians determine the treatment regimen for metastatic colorectal cancer on a case-by-case bases, according to the individual disease characteristics. We retrospectively compared the baseline characteristics and efficacies of first-line treatment among patients with metastatic colorectal cancer who received intensive therapy involving fluoropyrimidine plus oxaliplatin and/or irinotecan, potentially with molecularly targeted agents as well, versus less intensive fluoropyrimidine and/or bevacizumab therapy. Data were collected from a medical claims database.

Dihydroisocoumarins of Hydrangea macrophylla var. thunbergia inhibit binding of the SARS-CoV-2 spike protein to ACE2.

Binding of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the cognate angiotensin-converting enzyme 2 (ACE2) receptor is the initial step in the viral infection process. In this study, we screened an in-house extract library to identify food materials with inhibitory activity against this binding using enzyme-linked immunosorbent assays and attempted to ascertain their active constituents. Hydrangea macrophylla var.

Golden berry leaf extract containing withanolides suppresses TNF-α and IL-17 induced IL-6 expression in HeLa Cells.

Inflammation, characterized by the overexpression of IL-6 in various tissues, has been reported as a symptom of coronavirus disease 2019. In this study, we established an experimental system for overexpression of IL-6 in HeLa cells stimulated by TNF-α and IL-17, along with identification of anti-inflammatory materials and components from local agricultural, forestry, and fishery resources. We constructed a library of extracts from natural sources, of which 111 samples were evaluated for their anti-inflammatory activities.

Assessment for the timing of comprehensive genomic profiling tests in patients with advanced solid cancers.

Comprehensive genomic profiling (CGP) tests have been covered by public insurance in Japan for patients with advanced solid tumors who have completed or are completing standard treatments or do not have them. Therefore, genotype-matched drug candidates are often unapproved or off-label, and improving clinical trial access is critical, involving the appropriate timing of CGP tests. To address this issue, we analyzed the previous treatment data for 441 patients from an observational study on CGP tests discussed by the expert panel at Hokkaido University Hospital between August 2019 and May 2021.