Novel gene fusions in human oropharyngeal carcinoma.

Few reports have analyzed the fusion genes involved in carcinogenesis in the oropharynx, where the incidence of human papillomavirus-associated tumors is relatively low. The aim of this study was to identify novel driver fusion genes in patients with oropharyngeal cancer. The study enrolled fifty-seven patients who were diagnosed with oropharyngeal carcinoma.

Combined therapeutic effect of YHO-1701 with PD-1 blockade is dependent on natural killer cell activity in syngeneic mouse models.

The signal transducer and activator of transcription 3 (STAT3) signaling pathway is a key mediator of cancer cell proliferation, survival, and invasion. We discovered YHO-1701 as a small molecule inhibitor of STAT3 dimerization and demonstrated its potent anti-tumor activity using xenograft mouse models as monotherapy and combination therapy with molecular targeted drugs. STAT3 is also associated with cancer immune tolerance; therefore, we used the female CT26 syngeneic mouse model to examine the effect of combining YHO-1701 administration with PD-1/PD-L1 blockade.

Synchronous driver gene alterations (EGFR L858R, T790M, and ROS1) rearrangements in a patient with early-stage lung adenocarcinoma.

Concurrent EGFR mutation and ROS1 rearrangement is a rare event in early-stage non-small-cell lung cancer. In addition, a co-occurring de novo EGFR T790M mutation in such a case is extremely rare. We encountered a 72-year-old woman who developed 3 early-stage lung lesions synchronously, one each harboring EGFR L858R, ROS1 rearrangement, and EGFR L858R and de novo T790M.

Association of the KRAS genotype and clinicopathologic findings of resected non-small-cell lung cancer: A pooled analysis of 179 patients.

Background: This study assessed the clinicopathological background of early-stage KRAS-mutated non-small-cell lung cancer and analyzed the biological process of KRAS-mutated tumor using an RNA sequencing procedure.

Patients And Methods: We used a cohort of consecutive series of 179 surgically resected early-stage non-small-cell lung cancers harboring KRAS mutations and analyzed the clinicopathological features, including the KRAS genotypes, affecting the recurrence-free survival and prognosis. Consequently, we performed RNA sequencing to determine the gene expression profiles of nineteen KRAS-mutated non-small-cell cancers.

Biological Difference between L858R and Exon 19 Deletion Contributes to Recurrence-Free Survival of Resected Non-Small Cell Lung Cancer.

Introduction: The differences in biological characteristics among different genotypes of classical EGFR mutations have not been clarified. This study aimed to clarify the clinical and biological differences between L858R and 19 deletion in NSCLC.

Methods: We analyzed a cohort of 191 consecutive cases of surgically resected NSCLC harboring EGFR driver mutations (L858R or 19 deletion) in which curative resection was performed in Aichi Cancer Center Hospital, Nagoya, Japan, from January 2006 to September 2021 and in which recurrence subsequently developed.

Chemical augmentation of mitochondrial electron transport chains tunes T cell activation threshold in tumors.

Background: Cancer immunotherapy shows insufficient efficacy for low immunogenic tumors. Furthermore, tumors often downregulate antigen and major histocompatibility complex expression to escape recognition by T cells, resulting in insufficient T cell receptor (TCR) stimulation in the tumor microenvironment. Thus, augmenting TCR-mediated recognition of tumor antigens is a useful strategy to improve the efficacy of cancer immunotherapy.

Comparison between Fluorimetry (Qubit) and Spectrophotometry (NanoDrop) in the Quantification of DNA and RNA Extracted from Frozen and FFPE Tissues from Lung Cancer Patients: A Real-World Use of Genomic Tests.

Panel-based next-generation sequencing (NGS) has been carried out in daily clinical settings for the diagnosis and treatment guidance of patients with non-small cell lung cancer (NSCLC). The success of genomic tests including NGS depends in large part on preparing better-quality DNA or RNA; however, there are no established operating methods for preparing genomic DNA and RNA samples. We compared the following two quantitative methods, the QubitTM and NanoDropTM, using 585 surgical specimens, 278 biopsy specimens, and 82 cell block specimens of lung cancer that were used for genetic tests, including NGS.

Positive Correlation Between the Number of Circulating Tumor Cells in the Pulmonary Vein and Tumor Spread Through Air Spaces in Resected Non-small Cell Lung Cancer.

Background/aim: Circulating tumor cells (CTCs) is one of the promising markers that predict dissemination and metastases. This study aimed to identify the relationship between CTCs in pulmonary vein (PuV) and spread through air space (STAS) in non-small cell lung cancers.

Materials And Methods: We applied a cytology-based microfluidic platform for rare cell isolation.

Survival benefit of immune checkpoint inhibitor monotherapy in patients with non-small cell lung cancer recurrence after completely pulmonary resection.

Background: Selected patients in non-small cell lung cancer (NSCLC) responded to the treatment of immune checkpoint inhibitors (ICIs) have the survival benefit for advanced stages or metastatic status.

Methods: We investigated whether a response to ICI monotherapy since 2016 influences the survival of NSCLC patients with recurrence after completely pulmonary resection between 2009 and 2017. Disease control rate (DCR) was calculated as complete plus partial response plus stable disease during more than 6 months.

Fetal Megalencephaly with Cortical Dysplasia at 18 Gestational Weeks Related to Paternal UPD Mosaicism with Mutation.

The phosphatase and tensin homolog () gene is a tumor-suppressor gene located on 10q22-23. Since the introduction of molecular genetics in prenatal diagnostics, various birth defects associated with gene mutations have been diagnosed. However, no reports on fetal cases related to mutation have been found, so far.

Impact of reproductive factors on breast cancer incidence: Pooled analysis of nine cohort studies in Japan.

Prior studies reported the association of reproductive factors with breast cancer (BC), but the evidence is inconsistent. We conducted a pooled analysis of nine cohort studies in Japan to evaluate the impact of six reproductive factors (age at menarche/age at first birth/number of births/age at menopause/use of female hormones/breastfeeding) on BC incidence. We conducted analyses according to menopausal status at the baseline or at the diagnosis.

Subsegmental resection preserves regional pulmonary function: A focus on thoracoscopy.

Background: The aim of this study was to evaluate regional postoperative preserved pulmonary function (PPPF) and three-dimensional (3D) volumetric changes according to the number of resected subsegments and investigate the factors that most affected pre-/post PPPF.

Methods: Patients who underwent thoracoscopic lobectomy (n = 73), and segmentectomy (n = 87) were eligible for inclusion in the study. They were classified according to the number of resected subsegments which ranged from 1 to 10.

Across-Site Differences in the Mechanism of Alcohol-Induced Digestive Tract Carcinogenesis: An Evaluation by Mediation Analysis.

A genetic variant on ( rs671, Glu504Lys) contributes to carcinogenesis after alcohol consumption. Somewhat conversely, the Lys allele also confers a protective effect against alcohol-induced carcinogenesis by decreasing alcohol consumption due to acetaldehyde-related adverse effects. Here, we applied a mediation analysis to five case-control studies for head and neck, esophageal, stomach, small intestine, and colorectal cancers, with 4,099 cases and 6,065 controls, and explored the potentially heterogeneous impact of alcohol drinking on digestive tract carcinogenesis by decomposing the total effect of the Lys allele on digestive tract cancer risk into the two opposing effects of the carcinogenic effect (direct effect) and the protective effect (indirect effect mediated by drinking behavior).

Smoking and Pancreatic Cancer Incidence: A Pooled Analysis of 10 Population-Based Cohort Studies in Japan.

Background: Detailed prospective evaluation of cigarette smoking associated with pancreatic cancer risk in large Asian populations is limited. The aim of this study was to examine this association in a Japanese population, with a particular focus on evaluating sex differences.

Methods: We performed a pooled analysis of 10 population-based cohort studies.

Recent Improvement in the Long-term Survival of Breast Cancer Patients by Age and Stage in Japan.

Background: Recent improvements in 5-year survival of breast cancer have been reported in Japan and other countries. Though the number of long-term breast cancer survivors has been increasing, recent improvements in 10-year survival have not been reported. Moreover, the degree of improvement according to age and disease stage remains unclear.

Gender-specific association of early age-related macular degeneration with systemic and genetic factors in a Japanese population.

The Tsuruoka Metabolomics Cohort Study included subjects aged 35-74 years from participants in annual health check-up programs in Tsuruoka, Japan. The gender-specific associations of early age-related macular degeneration (AMD) with systemic and genetic factors was assessed cross-sectionally. Of these, 3,988 subjects had fundus photographs of sufficient quality, and early AMD was present in 12.

Estimation of cancer incidences in Aichi prefecture: use of a model area with good quality registry data.

In Japan, local government is responsible for organization of population-based cancer registries and the quality of the registration remains modest, mainly due to dependence on voluntary-based operations without legal obligations. Aichi Prefecture cancer registry covers a large population, estimated at 7 million, and its quality has yet to reach the level required internationally. The derived cancer incidences for Aichi Prefecture therefore tend to be underestimated.

Severe hepatitis caused by Epstein-Barr virus without infection of hepatocytes.

Although hepatitis is a common feature of primary Epstein-Barr virus (EBV) infection, severe liver injury is rare and its pathogenesis is unclear. A previously healthy girl developed severe hepatitis with prolonged jaundice. Serologic examination showed that she had primary infection with EBV.

A small deletion in the 3'-untranslated region of the cyclin D1/PRAD1/bcl-1 oncogene in a patient with chronic lymphocytic leukemia.

The cyclin DI/PRAD1 oncogene, a key regulator of the G1 phase of the cell cycle, has been incriminated in the pathogenesis of human neoplasia. Cyclin D1 was also demonstrated to be identical to the long-sought bcl-1 oncogene in B-cell malignancies with the t(11;14)(q13;q32) translocation. We report here a small deletion in the 3'-untranslated portion of the cyclin D1 gene in leukemia cells of a patient diagnosed with B-chronic lymphocytic leukemia (CLL), associated with overexpression of the corresponding cyclin D1 mRNA.

Reduction of glutathione S-transferase P-form mRNA expression in remodeling nodules in rat liver revealed by in situ hybridization.

Glutathione S-transferase P-form (GST-P) mRNA levels and distribution were sequentially analyzed by in situ hybridization histochemistry (ISH) in rat livers during and after induction of preneoplastic foci and nodules in the Solt-Farber model. Dot blot analysis showed GST-P transcripts in the liver to be elevated coincidental with the development of GST-P-positive lesions. GST-P ISH indicated that the majority of early foci and some of the resultant lesions showed uniformly high levels of GST-P mRNA.

Development of aberrant crypt foci involves a fission mechanism as revealed by isolation of aberrant crypts.

Morphological analysis of isolated colonic crypts in rats, postnatally, indicated that the crypts reproduce themselves by a fission mechanism, the division beginning at the crypt base and proceeding upwards until there are two separate crypts. Occasionally, before the separation is complete, a second fission process starts on one or both sides of a bifurcating crypt and a triple-branched or quadruple-branched crypt results. Analysis of isolated aberrant crypt foci (ACF) in rats treated with 1,2-dimethylhydrazine revealed that the development of ACF consisting of multiple crypts is also due to a fission mechanism.

Role of a signal transduction pathway which controls disassembly of microfilament bundles and suppression of high-molecular-weight tropomyosin expression in oncogenic transformation of NRK cells.

Role of disassembly of microfilament bundles and suppression of high-molecular-weight tropomyosin (TM) expression in growth factor- and various oncogene-induced transformation was studied by using NRK cells and its transformation-deficient mutants. In NRK cells which show a transformed phenotype by treatment with EGF and TGF-beta, cellular stress fibers became dissociated by EGF or EGF and TGF-beta combination, whereas TGF-beta alone caused thicker appearance of stress fibers. Accompanying these changes, the expression of TM isoforms 1 and 2 was suppressed by treatment with EGF or EGF and TGF-beta, but elevated by TGF-beta with similar time courses.

Structure and expression during development of Drosophila melanogaster gene for DNA polymerase alpha.

The Drosophila melanogaster gene and cDNA which span the entire open reading frame for DNA polymerase alpha, were cloned, and their nucleotide sequences were determined. The gene consists of 6 exons separated by 5 short introns. The major transcription initiation site was localized 85 bp upstream from the initiation codon.