WEE1 confers resistance to KRAS inhibitors in non-small cell lung cancer.

KRAS inhibitors sotorasib and adagrasib have been approved for the treatment of KRAS-mutant non-small cell lung cancer (NSCLC). However, the efficacy of single-agent treatments is limited, presumably due to multiple resistance mechanisms. To overcome these therapeutic limitations, combination strategies that potentiate the antitumor efficacy of KRAS inhibitors must be developed.

High plasma concentration of tenofovir alafenamide in people living with HIV with ABCB1 genetic variants.

Objectives: We aimed to analyze the relationships between single nucleotide polymorphisms in the ATP-binding cassette transporter B1 (ABCB1) and G2 (ABCG2) genes and plasma concentrations of tenofovir alafenamide (TAF), tenofovir (TFV), and emtricitabine (FTC).

Methods: We recruited 10 people living with HIV receiving once-daily treatment with a single tablet containing TAF (25 mg), FTC (200 mg), and bictegravir (50 mg). Peripheral blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 12, and 24 h after administration.

Efficacy and safety of nivolumab monotherapy in patients with unresectable clear cell sarcoma and alveolar soft part sarcoma (OSCAR Trial/NCCH1510).

Background: Clear cell sarcoma (CCS) and alveolar soft part sarcoma (ASPS) are rare, and standard systemic therapy is not established except for sunitinib in ASPS. It is known that CCS and ASPS have a common biological feature of melanoma and Xp11.2/TFE3 translocation renal cell carcinoma, and immune-checkpoint inhibitors (ICIs) are effective in these tumors.

Multicenter Pharmacokinetic and Pharmacodynamic Study of Pembrolizumab for Non-small-Cell Lung Cancer in Patients Aged 75 Years and Older.

Pembrolizumab is a major treatment for recurrent or advanced non-small-cell lung cancer (NSCLC). However, data on its use and pharmacokinetics (PK) in older patients are limited. This open-label, multicenter, observational study evaluated real-world data on the safety, efficacy, and PK of pembrolizumab in older patients with NSCLC.

descSPIM: an affordable and easy-to-build light-sheet microscope optimized for tissue clearing techniques.

Despite widespread adoption of tissue clearing techniques in recent years, poor access to suitable light-sheet fluorescence microscopes remains a major obstacle for biomedical end-users. Here, we present descSPIM (desktop-equipped SPIM for cleared specimens), a low-cost ($20,000-50,000), low-expertise (one-day installation by a non-expert), yet practical do-it-yourself light-sheet microscope as a solution for this bottleneck. Even the most fundamental configuration of descSPIM enables multi-color imaging of whole mouse brains and a cancer cell line-derived xenograft tumor mass for the visualization of neurocircuitry, assessment of drug distribution, and pathological examination by false-colored hematoxylin and eosin staining in a three-dimensional manner.

Rapid Response to Lenvatinib and Disease Flare After Discontinuation in a Patient With Thymic Carcinoma Harboring KIT Exon 11 Mutation: A Case Report.

Lenvatinib, a multitarget tyrosine kinase inhibitor for c-Kit and other kinases, has exhibited promising efficacy in treating advanced or metastatic thymic carcinoma (TC). Here, we present the case of a patient with metastatic TC harboring a exon 11 deletion and amplification. The patient exhibited a remarkable response to lenvatinib but experienced rapid disease progression after discontinuation of lenvatinib, referred to as a "disease flare.

Determination of intracellular tenofovir-diphosphate and emtricitabine-triphosphate concentrations in dried blood spots for pre-exposure prophylaxis adherence.

Objectives: We measured the intracellular concentrations of tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) in dried blood spots (DBS) for pre-exposure prophylaxis (PrEP) adherence using sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Methods: A total of 191 DBS were obtained from 85 participants who were receiving tenofovir disoproxil fumarate (TDF; 300 mg) and emtricitabine (FTC; 200 mg) as PrEP at the Sexual Health Clinic, National Center for Global Health and Medicine, Tokyo, Japan. DBS punch (3 mm) added to 25 μL of 50% methanol and 400 μL of internal standard solution was used for solid phase extraction.

Immunogenicity after vaccination of COVID-19 vaccines in patients with cancer: a prospective, single center, observational study.

Background: Patients with cancer, particularly those undergoing chemotherapy, are at risk from the low immunogenicity of Coronavirus Disease 19 (COVID-19) vaccines.

Methods: This prospective study assessed the seroconversion rate of COVID-19 vaccines among patients with cancer and hospital staff. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific IgG (S-IgG) concentrations were evaluated before the first vaccination, and 1-3 and 4-6 months after the second vaccination.

Fucoxanthin Inhibits Development of Sigmoid Colorectal Cancer in a PDX Model With Alterations of Growth, Adhesion, and Cell Cycle Signals.

Background/aim: Fucoxanthin (Fx), a dietary marine xanthophyll, exerts potent anticancer effects in various colorectal cancer (CRC) animal models. However, therapeutic effects of Fx in human cancer tissues remain unclear. A patient-derived xenograft (PDX) mouse model transplanted with cancer tissues from patients is widely accepted as the best preclinical model for evaluating the anticancer potential of drug candidates.

Precancerous nature of intestinal metaplasia with increased chance of conversion and accelerated DNA methylation.

Objective: The presence of intestinal metaplasia (IM) is a risk factor for gastric cancer. However, it is still controversial whether IM itself is precancerous or paracancerous. Here, we aimed to explore the precancerous nature of IM by analysing epigenetic alterations.

Steady-state pharmacokinetics of plasma tenofovir alafenamide (TAF), tenofovir (TFV) and emtricitabine (FTC), and intracellular TFV-diphosphate and FTC-triphosphate in HIV-1 infected old Japanese patients treated with bictegravir/FTC/TAF.

Emtricitabine (FTC) plus tenofovir alafenamide (TAF) has demonstrated efficacy and safety for pre-exposure prophylaxis (PrEP) to prevent HIV-1 infection. We measured the plasma PK of FTC, tenofovir (TFV), and TAF in a steady-state pharmacokinetic (PK) study of bictegravir/FTC/TAF in HIV-1-infected patients. Furthermore, validated liquid chromatography-tandem mass spectrometry was used to measure intracellular TFV-diphosphate (DP) and FTC-triphosphate (TP), the active metabolites of TFV and FTC, respectively.

Development of a Detection System for Mutations in Circulating Tumour DNA Using PNA-LNA-Mediated PCR Clamping.

Although circulating tumour DNA (ctDNA)-based next-generation sequencing (NGS) is a less invasive method for assessing mutations that are essential mechanisms of endocrine therapy resistance in patients with oestrogen receptor-positive breast cancer, adequate amounts of DNA are required to assess polyclonal mutations. By combining a peptide nucleic acid and locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamping assay, we have developed a novel detection system to screen for polyclonal mutations in ctDNA. A validation assay was prospectively performed on clinical samples and compared with the NGS results.

The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan.

The journey to implement cancer genomic medicine (CGM) in oncology practice began in the 1980s, which is considered the dawn of genetic and genomic cancer research. At the time, a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells, which led to the development of molecular targeted therapies in the 2000s and beyond. Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients, the National Cancer Center (NCC) of Japan has already contributed considerably to CGM advancement for the conquest of cancer.

Trastuzumab Deruxtecan for Human Epidermal Growth Factor Receptor 2-Expressing Advanced or Recurrent Uterine Carcinosarcoma (NCCH1615): The STATICE Trial.

Purpose: To investigate the efficacy and safety of trastuzumab deruxtecan, an antibody-drug conjugate targeting human epidermal growth factor receptor 2 (HER2) with a topoisomerase I inhibitor payload, in patients with uterine carcinosarcoma (UCS) expressing HER2.

Patients And Methods: Patients with recurrent UCS with HER2 immunohistochemistry scores ≥1+ previously treated with chemotherapy were included. Patients were assigned to the HER2-high (immunohistochemistry score ≥2+; n = 22) or low (immunohistochemistry score of 1+; n = 10) groups for primary and exploratory analyses, respectively.

Impact of ramucirumab pharmacokinetics in combination with docetaxel on the efficacy and survival in patients with advanced non-small cell lung cancer.

Objectives: Ramucirumab, an anti-vascular endothelial growth factor receptor-2 antibody, has been approved for the treatment of non-small cell lung cancer (NSCLC); however, its pharmacokinetic properties in clinical practice are unknown. We aimed to measure ramucirumab concentrations and conduct a retrospective pharmacokinetic analysis using real-world data.

Materials And Methods: Patients with stage III-IV and recurrent NSCLC who received ramucirumab plus docetaxel were evaluated in this study.