Publications by authors named "Kieko Hara"

Background: Thymic squamous cell carcinoma and type B3 thymoma are primary neoplasms of the anterior mediastinum that are sometimes difficult to differentiate from one another histologically. However, only a few immunohistochemical markers are available for the differential diagnosis. The purpose of this study was to discover a novel marker for differentiating between thymic squamous cell carcinoma and type B3 thymoma.

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Objectives: Programmed death ligand 1 and 2 (PD-L1 and PD-L2) bind programmed death 1 (PD-1). PD-L1 is an established predictive biomarker of response to immunotherapies targeting PD-1 and PD-L1 in lung adenocarcinoma (LUAD). However, the clinical relevance of PD-L2 expression in patients with LUAD remains unclear; we aimed to examine this aspect using LUAD specimens.

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Background: The role of radiotherapy in metastatic renal cell carcinoma is controversial. We prospectively tested the feasibility and efficacy of radiotherapy to defer systemic therapy for patients with oligometastatic renal cell carcinoma.

Methods: This single-arm, phase 2, feasibility trial was done at one centre in the USA (The MD Anderson Cancer Center, Houston, TX, USA).

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Objectives: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker of response to immunotherapies targeting programmed death-1/PD-L1 in advanced-stage lung adenocarcinoma. The aim of this study was to investigate the associations between PD-L1 expression and clinicopathological features, prognosis, and driver oncogene alterations in patients with lung adenocarcinoma.

Materials And Methods: We evaluated PD-L1 expression in 1,005 surgically resected lung adenocarcinoma specimens, by immunohistochemistry using the 22C3 antibody.

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Article Synopsis
  • The study uses single-cell RNA sequencing to analyze 186,916 cells from early-stage lung adenocarcinoma (LUAD) and normal lung tissues, revealing how cell lineages and states evolve spatially from normal to cancerous regions.
  • Findings show significant intratumor heterogeneity in LUAD and variations in immune cell populations, with an increase in T regulatory cells near tumors and a decrease in cytotoxic CD8 T cells and other immune cell types in those areas.
  • Researchers present a spatial atlas of LUAD evolution that identifies potential therapeutic targets for early intervention, highlighting the need for further investigation of the peripheral lung's geospatial ecosystem.
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The novel coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Severely symptomatic COVID-19 is associated with lung inflammation, pneumonia, and respiratory failure, thereby raising concerns of elevated risk of COVID-19-associated mortality among lung cancer patients. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for SARS-CoV-2 entry into lung cells.

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Aims: In the evolving era of precision medicine, increasing emphasis is placed on detecting molecular alterations driving the development of specific cancers and targeting them with matched therapies that can yield the best outcomes for patients. Lung adenocarcinomas with uncommon actionable alterations, including MET exon 14 skipping (METex14), ERBB2 and BRAF mutations, are rare and poorly characterised cancers.

Methods And Results: To more clearly understand the histopathological features of lung adenocarcinoma with uncommon actionable alterations, we compared the histological features of 678 cases with mitogenic driver alterations from 996 surgically resected lung adenocarcinomas.

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Invasive mucinous adenocarcinoma (IMA) of the lung is a unique variant of lung adenocarcinoma. Aberrant mucin expression is associated with cancer development and metastasis. However, the clinicopathological significance of mucin expression in IMA is not fully understood.

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Early pathogenesis of lung adenocarcinoma (LUAD) remains largely unknown. We found that, relative to wild-type littermates, the innate immunomodulator (lipocalin-2) was increased in normal airways from mice with knockout of the airway lineage gene () and that are prone to developing inflammation and LUAD. Yet, the role of LCN2 in lung inflammation and LUAD is poorly understood.

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The extensive clinical applications of next-generation sequence analyzers have made uncommon and compound EGFR mutations more prevalent than previously described. However, clinicopathological impacts of compound EGFR mutations in lung adenocarcinoma remain unclear. We earlier examined the presence of compound EGFR mutations primarily in the cis allele by EGFR exon sequencing and droplet digital polymerase chain reaction in 462 completely resected EGFR-mutated adenocarcinomas of the lung and identified 64 tumors with compound mutations.

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We have previously shown that galectin-4 expression is an independent predictor for lymph node metastasis and serves as an adverse prognostic indicator in patients with acinar adenocarcinoma of the lung. In contrast, thyroid transcription factor-1 (TTF-1) expression in non-small cell lung carcinoma has been shown to be associated with a favorable prognosis. In the present study, 208 cases of acinar adenocarcinoma of the lung and 36 cases with distant metastatic lesions of lung adenocarcinoma were immunohistochemically examined for expression of galectin-4 and TTF-1 to elucidate their correlation with clinicopathological factors.

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The prognostic value of BRAF and TERT promoter mutation in papillary thyroid carcinoma (PTC) is controversial. We examined alterations in BRAF and TERT promoter by PCR-direct sequencing in PTC of 144 Japanese patients. Alternative lengthening of telomeres was examined as another mechanism of telomere maintenance by immunohistochemical staining for ATRX and DAXX.

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Background: Targeted therapies based on the molecular and histological features of cancer types are becoming standard practice. The most effective regimen in lung cancers is different between squamous cell carcinoma (SCC) and adenocarcinoma (AD). Therefore a precise diagnosis is crucial, but this has been difficult, particularly for poorly differentiated SCC (PDSCC) and AD without a lepidic growth component (non-lepidic AD).

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Lymphangioleiomyomatosis (LAM), a rare progressive disease that almost exclusively affects women, is characterized by pulmonary cysts and neoplastic proliferation of smooth muscle-like cells (LAM cells). Airflow obstruction is a physiologic consequence that is commonly observed in LAM and has been attributed to narrowing of peripheral airways. However, histopathologic examinations of the entire airway have been precluded by the limited availability of such specimens.

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Adipophilin, a lipid droplet-associated protein that regulates lipid droplet structure and formation, is expressed in a wide variety of tumors. The aims of this study were to evaluate the frequency and distribution pattern of adipophilin expression in gastric epithelial neoplasia and to correlate these variables with clinicopathological features and the mucin phenotype. We retrospectively examined 159 cases of gastric epithelial neoplasia, which were classified according to the Vienna classification system as 52 noninvasive low-grade adenoma (category 3), 65 noninvasive high-grade neoplasia (category 4), and 42 invasive neoplasia (category 5).

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A case of prenatally diagnosed, giant cord hemangioma is reported, which was accompanied by the elevation of maternal serum alpha-fetoprotein (MS-AFP) and human chorionic gonadotropin (MS-hCG) levels. A 30-year-old woman without a previous history of gravida or para, presented with intermittent abdominal pain at 26 weeks of gestation. Doppler studies showed the fetus developing heart failure as the tumor grew larger.

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Appendiceal mucinous tumors (AMTs) are classified as low-grade appendiceal mucinous neoplasms (LAMNs) or mucinous adenocarcinomas (MACs), although their carcinogenesis is not well understood. As somatic activating mutations of GNAS are considered to be characteristic of LAMNs while TP53 mutations have been shown to be specific to MACs, MACs are unlikely to result from transformation of LAMNs. However, emerging evidence also shows the presence of GNAS mutations in MACs.

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Article Synopsis
  • The study investigates the NAB2-STAT6 fusion gene's role in the malignant behavior of solitary fibrous tumors (SFT), analyzing variations in 40 SFT cases alongside secondary genetic alterations in TP53, PDGFRB, and TERT.
  • The results show that the majority of cases have nuclear STAT6 staining, and certain genotypes correlate with tumor location and aggressiveness, including findings that p53-positive staining predicts poorer disease-free survival rates.
  • Additionally, the presence of TP53 and TERT promoter mutations, particularly together, is linked to tumor dedifferentiation, emphasizing their significance in the tumor's malignancy development.
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Solitary fibrous tumors (SFTs), initially observed in the pleura, were later found to develop in almost any extrapleural site. Dedifferentiation within SFTs was characterized only recently. We report a case of dedifferentiated SFT arising within the pelvis of a 70-year-old Japanese woman.

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Solitary fibrous tumors (SFTs), initially observed in the pleura, were later found to develop in almost any extrapleural site. Dedifferentiation within SFTs, a rare phenomenon, was characterized only recently, although it was previously described in soft tissue and bone tumors. We report a case of dedifferentiated SFT arising in the right pleura of a 69-year-old man.

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Metastasis is still a major issue in cancer, and the discovery of biomarkers predicting metastatic capacity is essential for the development of better therapeutic strategies for treating lung adenocarcinoma. By using a proteomic approach, we aimed to identify novel predictors for lymph node metastasis in lung adenocarcinoma. Two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis showed 6 spots differentially expressed between lymph node metastasis-positive and lymph node metastasis-negative groups in a discovery set.

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