Background: Ageing induces functional and structural alterations in organs, and age-dependent parameters have been identified in various medical data sources. However, there is currently no specific clinical test to quantitatively evaluate age-related changes in bronchi. This study aimed to identify age-dependent bronchial features using explainable artificial intelligence for bronchoscopy images.
View Article and Find Full Text PDFCancer cells sometimes transdifferentiate into different histological type(s) and tumors with multiple histological types can share a common ancestor cell. However, diagnosis of the origin of multiple tumor lesions with different histological features remains a clinical challenge. A 45-year-old woman with a history of cervical squamous cell carcinoma (CeSq) presented with abdominal pain and vomiting.
View Article and Find Full Text PDFRationale: Pulmonary pleomorphic carcinoma is a rare tumor with a poor prognosis and has no standard chemotherapy. We herein report a case of small intestinal metastasis of pulmonary pleomorphic carcinoma that resulted in intestinal bleeding and was successfully treated with pembrolizumab monotherapy.
Patient Concerns: A 54-year-old man with a history of pulmonary pleomorphic carcinoma resection was referred to our hospital due to a 1-month history of a fever and general fatigue.
Rearrangements of specific tyrosine kinases are associated with an elevated risk of venous thrombosis in lung adenocarcinoma, although their effects on arterial thrombosis have not been fully elucidated. Here, we report two cases of ROS proto-oncogene 1 ()-rearranged lung adenocarcinoma with cerebral infarction during the peri-diagnostic period. Two cases took contrasting clinical courses: one patient could not receive targeted therapy because of a significant decline in performance status, whereas in the other patient, the performance status was maintained and targeted therapy drastically reduced the tumour size.
View Article and Find Full Text PDFRationale: Malignant peritoneal mesothelioma is a rare tumor with a poor prognosis and has no recommended therapy after first-line pemetrexed and platinum-based chemotherapy. Moreover, effects of immune checkpoint inhibitors on peritoneal mesothelioma remains to be elucidated. We herein report the case of a 75-year-old man with peritoneal mesothelioma treated with cisplatin plus pemetrexed and subsequent nivolumab.
View Article and Find Full Text PDFA 75-year-old woman presented with difficulty in swallowing. Esophagogastroduodenoscopy(EGD)revealed a Borrmann type 3 advanced gastric cardia carcinoma. Computed tomography(CT)revealed three lymph node metastases, and thus, the preoperative diagnosis was cT4aN2M0, cStage ⅢB.
View Article and Find Full Text PDFBackground: Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), is effective against EGFR-mutated non-small cell lung carcinoma resistant to first- or second-generation EGFR-TKIs in patients in whom an EGFR T790M mutation has been detected. Detection of the T790M mutation using circulating tumor DNA (ctDNA) is less invasive than a tissue re-biopsy, including a transbronchial lung biopsy; however, the prognostic implications of the T790M mutation in ctDNA have not been fully elucidated.
Methods: We retrospectively reviewed the clinical features of non-small cell lung carcinoma patients in whom an EGFR T790M mutation had been detected at our hospital and assessed the clinical outcomes of osimertinib for these patients in terms of detection sites.
Although there has been significant progress in immune-checkpoint inhibitor (ICI) treatment, it remains controversial whether they should be used in the treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). We herein report the case of an NSCLC patient with uncommon complex EGFR mutations (G719S and L861Q) who was refractory to afatinib treatment but who showed a good response to pembrolizumab treatment. A 65-year-old female ex-smoker was diagnosed with right upper lobe NSCLC (clinical stage IVB; cT2bN3M1c).
View Article and Find Full Text PDFLung spindle cell carcinoma is a rare lung tumour with a poor prognosis, and its standard therapy has not been established. Furthermore, little work has been conducted on the genetic characteristics of lung spindle cell carcinomas. Here, we report an 82-year-old woman who was referred to our hospital due to a fever and dyspnoea.
View Article and Find Full Text PDFSystemic lupus erythematosus (SLE) is a multisystem disorder, which occurs mostly in young women. However, late-onset SLE does exist and sometimes presents with an atypical, diversified course. We describe an 85-year-old woman who was admitted to our hospital for lower extremity edema and hand grip weakness.
View Article and Find Full Text PDFThe eradication of tumor cells requires communication to and signaling by cells of the immune system. Natural killer (NK) cells are essential tumor-killing effector cells of the innate immune system; however, little is known about whether or how other immune cells recognize tumor cells to assist NK cells. Here, we show that the innate immune receptor Dectin-1 expressed on dendritic cells and macrophages is critical to NK-mediated killing of tumor cells that express N-glycan structures at high levels.
View Article and Find Full Text PDFCold Spring Harb Symp Quant Biol
March 2015
The interferon-regulatory factor (IRF) family, originally identified as transcriptional regulators of the type I interferon system, consists of nine members in mammals. A large number of studies have revealed the versatile and critical functions performed by this transcription factor family in immunity and other biological processes. Most notably, the advances in the study of signal transducing innate immune receptors have placed many IRF members as central mediators in the regulation of innate immune responses.
View Article and Find Full Text PDFTransforming growth factor (TGF)-β plays crucial roles in embryonic development and adult tissue homeostasis by eliciting various cellular responses in target cells. TGF-β signaling is principally mediated through receptor-activated Smad proteins, which regulate expression of target genes in cooperation with other DNA-binding transcription factors (Smad cofactors). In this study, we found that the basic helix-loop-helix transcription factor Olig1 is a Smad cofactor involved in TGF-β-induced cell motility.
View Article and Find Full Text PDFHelix-loop-helix (HLH) family transcription factors regulate numerous developmental and homeostatic processes. Dominant-negative HLH (dnHLH) proteins lack DNA-binding ability and capture basic HLH (bHLH) transcription factors to inhibit cellular differentiation and enhance cell proliferation and motility, thus participating in patho-physiological processes. We report the first structure of a free-standing human dnHLH protein, HHM (Human homologue of murine maternal Id-like molecule).
View Article and Find Full Text PDFAlthough the concept of cancer stem cells or cancer-initiating cells had created a new paradigm for the treatment of malignant tumors, it remains unclear how cancer-initiating cells can be eradicated. We have previously reported that the transforming growth factor-β (TGF-β)-Sox4-Sox2 pathway is essential for glioma-initiating cells to retain their stemness, and inhibition of TGF-β signaling may lead to differentiation of glioma-initiating cells (Ikushima, H., Todo, T.
View Article and Find Full Text PDFTransforming growth factor-β (TGF-β) signaling is controlled by a variety of regulators, of which Smad7, c-Ski, and SnoN play a pivotal role in its negative regulation. Arkadia is a RING-type E3 ubiquitin ligase that targets these negative regulators for degradation to enhance TGF-β signaling. In the present study we identified a candidate human tumor suppressor gene product RB1CC1/FIP200 as a novel positive regulator of TGF-β signaling that functions as a substrate-selective cofactor of Arkadia.
View Article and Find Full Text PDFTransforming growth factor (TGF)-β signaling has been implicated as an important regulator of almost all major cell behaviors, including proliferation, differentiation, cell death, and motility. Which cell responses are induced or suppressed in response to TGF-β depends on the cell type and the context in which TGF-β signaling is received. TGF-β ligands, their receptors, and intracellular Smad effectors lie in the center of TGF-β signaling.
View Article and Find Full Text PDFTransforming growth factor (TGF)-β signaling is involved in almost all major cell behaviors under physiological and pathological conditions, and its regulatory system has therefore been vigorously investigated. The fundamental elements in TGF-β signaling are TGF-β ligands, their receptors, and intracellular Smad effectors. The TGF-β ligand induces the receptors directly to phosphorylate and activate Smad proteins, which then form transcriptional complexes to control target genes.
View Article and Find Full Text PDFThe distortion of growth factor signalling is the most important prerequisite in tumour progression. Transforming growth factor-beta (TGFbeta) signalling regulates tumour progression by a tumour cell-autonomous mechanism or through tumour-stroma interaction, and has either a tumour-suppressing or tumour-promoting function depending on cellular context. Such inherent complexity of TGFbeta signalling results in arduous, but promising, assignments for developing therapeutic strategies against malignant tumours.
View Article and Find Full Text PDFTransforming growth factor (TGF)-beta signaling has interesting characteristics in the context of cancer. Although perturbations of TGF-beta signaling are strongly implicated in cancer progression, TGF-beta signaling has both tumor-suppressive and tumor-promoting effects. For example, TGF-beta inhibits cancer cell proliferation in some cellular contexts, but promotes it in others.
View Article and Find Full Text PDFDespite aggressive surgery, radiotherapy, and chemotherapy, treatment of malignant glioma remains formidable. Although the concept of cancer stem cells reveals a new framework of cancer therapeutic strategies against malignant glioma, it remains unclear how glioma stem cells could be eradicated. Here, we demonstrate that autocrine TGF-beta signaling plays an essential role in retention of stemness of glioma-initiating cells (GICs) and describe the underlying mechanism for it.
View Article and Find Full Text PDFActa Crystallogr Sect F Struct Biol Cryst Commun
January 2009
GCIP/HHM is a human nuclear protein that is implicated in regulation of cell proliferation. Its primary structure contains helix-loop-helix and leucine-zipper motifs but lacks a DNA-binding basic region. Native and selenomethionine-derivatized (SeMet) crystals of full-length GCIP/HHM were obtained using the hanging-drop vapour-diffusion method.
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