STORM Super-Resolution Visualization of Self-Assembled γPFD Chaperone Ultrastructures in Methanocaldococcus jannaschii.

Gamma-prefoldin (γPFD), a unique chaperone found in the extremely thermophilic methanogen Methanocaldococcus jannaschii, self-assembles into filaments in vitro, which so far have been observed using transmission electron microscopy and cryo-electron microscopy. Utilizing three-dimensional stochastic optical reconstruction microscopy (3D-STORM), here we achieve ∼20 nm resolution by precisely locating individual fluorescent molecules, hence resolving γPFD ultrastructure both in vitro and in vivo. Through CF647 NHS ester labeling, we first demonstrate the accurate visualization of filaments and bundles with purified γPFD. Next, by implementing immunofluorescence labeling after creating a 3xFLAG-tagged γPFD strain, we successfully visualize γPFD in M. jannaschii cells. Through 3D-STORM and two-color STORM imaging with DNA, we show the widespread distribution of filamentous γPFD structures within the cell. These findings provide valuable insights into the structure and localization of γPFD, opening up possibilities for studying intriguing nanoscale components not only in archaea but also in other microorganisms.

Fabrication of Electronically Conductive Protein-Heme Nanowires for Power Harvesting.

Electronically conductive protein-based materials can enable the creation of bioelectronic components and devices from sustainable and nontoxic materials, while also being well-suited to interface with biological systems, such as living cells, for biosensor applications. However, as proteins are generally electrical insulators, the ability to render protein assemblies electroactive in a tailorable manner can usher in a plethora of useful materials. Here, an approach to fabricate electronically conductive protein nanowires is presented by aligning heme molecules in proximity along protein filaments, with these nanowires also possessing charge transfer abilities that enable energy harvesting from ambient humidity. The heme-incorporated protein nanowires demonstrate electron transfer over micrometer distances, with conductive atomic force microscopy showing individual nanowires having comparable conductance to other previously characterized heme-based bacterial nanowires. Exposure of multilayer nanowire films to humidity produces an electrical current, presumably through water molecules ionizing carboxyl groups in the filament and creating an unbalanced total charge distribution that is enhanced by the heme. Incorporation of heme and potentially other metal-center porphyrin molecules into protein nanostructures could pave the way for structurally- and electrically-defined protein-based bioelectronic devices.

Immunophenotypic classification regarding prognosis in peripheral T cell lymphoma, NOS, and nodal T follicular helper T cell lymphoma, angioimmunoblastic-type.

This study aimed to determine the clinicopathological predictive factors of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), and nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFH, AI-type). In this single-centered, retrospective study, medical records of 59 patients who were diagnosed with PTCL, NOS, or nTFH, AI-type from March 2007 to September 2022 were reviewed. The clinicopathological variables, including immunohistochemistry(IHC) subgroups, distinguishing TBX21 from the GATA3 subgroups were analyzed. Overall, 28 patients (75.7%) in the TBX21 group were PTCL, NOS. There were 9 (24.3%) patients in the GATA3 group. In univariable analyses, lymphoma subtype, age, and performance status were associated with progression-free survival (PFS), and overall survival (OS). In multivariable analyses, lymphoma subtype, and performance status were related to PFS and OS (P = 0.012, P < 0.001, P = 0.006, and P < 0.001, respectively). The GATA3 subgroup tended to have a worse prognosis in univariable analyses; however, it became more insignificant in multivariable when lymphoma subtype and performance status were adjusted (P = 0.065, P = 0.180, P = 0.972, and P = 0.265, respectively). The double-positive group showed variable prognoses of better PFS and worse OS. PD-1 and PD-L1 were associated with the EBV in situ hybridization (P = 0.027, and P = 0.005), and PD-1 was associated with CD30 expression (P = 0.043). This study demonstrated the potential of IHC classification to predict prognosis for PTCL, NOS, as well as nTFH AI-type, although further validation is necessary. Treatments targeting CD30, PD-1, and PD-L1 appear promising for lymphoma treatment.

Clinicopathologic Characteristics Associated with Prognosis in Ocular Extranodal Marginal Zone B Cell Lymphoma.

Background and Objectives: Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) type is the most common subtype of the ocular adnexal lymphoma. Despite its excellent prognosis, some patients experience partial remission or progressive disease. We aimed to evaluate clinicopathologic differences in the treatment responder group by comparing complete remission (CR) and non-complete remission (non-CR). Materials and Methods: This study retrospectively reviewed 48 patients who were diagnosed with ocular adnexal MALT lymphoma at Ulsan University Hospital between March 2002 and August 2018. Patients who were followed up for less than 6 months were excluded. Histologic and clinical features were analyzed. The patients were divided into two groups: CR and non-CR. Results: Among the 48 patients, 33 achieved CR and 15 achieved non-CR during the median follow-up period of 40.00 months (range, 7-109 months). In univariable analysis, more patients tend to undergo treatment in the CR group, and post-radiotherapy (post-RT) SUVmax, PET and serum lactate dehydrogenase (LDH) levels were higher in the non-CR group (p = 0.043, p = 0.016, and p = 0.042, respectively). In a multivariable analysis, only application of treatment, including radiotherapy or chemotherapy with immunotherapy, was related to CR (odd ratio 7.301, 95% confidence interval 1.273-41.862, p = 0.026). In subgroup analysis according to the site of involvement, none of the variables were significant except for the post-RT SUVmax of PET and level of serum LDH in the non-conjunctiva group (p = 0.026, and p = 0.037, respectively). Seven (14.6%) patients had a recurrence, and those with a recurring site other than the primary site had a higher Ki-67 labeling index, although it was not statistically significant (9.56% vs. 18.00%, p = 0.095). Conclusions: Although belonging to the early stages, the non-CR rate was high in patients with high serum LDH levels, and recurred patients had higher Ki-67. Thus, considering active treatment is recommended in this group of patients.

Non-steroidal anti-inflammatory drug-induced enteropathy as a major risk factor for small bowel bleeding: a retrospective study.

BACKGROUND: Small bowel (SB) bleeding accounts for 5% of all gastrointestinal (GI) bleeding cases and 80% of obscure GI bleeding cases. Although angioectasia is the common etiology of SB bleeding, nonsteroidal anti-inflammatory drug (NSAID)-induced SB lesions are also reported as a major cause in studies from Eastern countries. Herein, we assessed the frequency of occurrence of NSAID-induced SB lesions in Korean patients with obscure GI bleeding. METHODS: We retrospectively analyzed medical records of all consecutive patients aged ≥18 years who underwent capsule endoscopy from March 2018 to February 2019 at Ulsan University Hospital and Kosin University Gospel Hospital. RESULTS: Of the 83 subjects (all Korean; mean age ± standard deviation: 59 ± 18 years; age range: 18-84 years; men: n = 52; women: n = 31), 55 (66.2%) had stool with clear blood and 28 (33.8%) had normal stool with iron deficiency anemia. The detection rate of SB bleeding and lesions using capsule endoscopy was 72.3% (60 of 83 patients). A significantly higher frequency (40 of 51) of ulcerative/erosive lesions than other causes was observed in patients with inactive bleeding but visible SB lesions. As a result, NSAID-induced enteropathy accounted for 30.1% of 83 patients with obscure GI bleeding (25 of the all 60 SB bleeding cases). CONCLUSIONS: Contrary to what is reported for patients in Western countries, this study in Korean patients showed an improved diagnostic yield of capsule endoscopy for obscure GI bleeding and that NSAID-induced enteropathy was the most common etiology of SB bleeding. Aggressive small intestine examination is required for patients with unexplained GI bleeding.

Whole-Cell Photoenzymatic Cascades to Synthesize Long-Chain Aliphatic Amines and Esters from Renewable Fatty Acids.

Long-chain aliphatic amines such as (S,Z)-heptadec-9-en-7-amine and 9-aminoheptadecane were synthesized from ricinoleic acid and oleic acid, respectively, by whole-cell cascade reactions using the combination of an alcohol dehydrogenase (ADH) from Micrococcus luteus, an engineered amine transaminase from Vibrio fluvialis (Vf-ATA), and a photoactivated decarboxylase from Chlorella variabilis NC64A (Cv-FAP) in a one-pot process. In addition, long chain aliphatic esters such as 10-(heptanoyloxy)dec-8-ene and octylnonanoate were prepared from ricinoleic acid and oleic acid, respectively, by using the combination of the ADH, a Baeyer-Villiger monooxygenase variant from Pseudomonas putida KT2440, and the Cv-FAP. The target compounds were produced at rates of up to 37 U g-1 dry cells with conversions up to 90 %. Therefore, this study contributes to the preparation of industrially relevant long-chain aliphatic chiral amines and esters from renewable fatty acid resources.

Expression of programmed cell death 1 and programmed cell death ligand 1 in extranodal NK/T-cell lymphoma, nasal type.

Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) are new therapeutic targets in cancer immunotherapy. The aim of this study was to investigate the clinicopathological characteristics of PD-1 and PD-L1 expression in extranodal natural killer/T­cell lymphoma, nasal type (ENKTL). We performed PD-1 and PD-L1 immunostaining in 79 ENKTL biopsy samples and retrospectively analyzed medical records of all 79 patients from four tertiary referral hospitals. The expression of PD-1 and PD-L1 by tumor cells and/or infiltrating immune cells was evaluated. The expression rates of PD-L1 in tumor cells and infiltrating immune cells were 79.7 and 78.5 %, respectively, whereas PD-1 in tumor cells and infiltrating immune cells were 1.3 and 11.4 %. The PD-L1 positivity in tumor cells and infiltrating immune cells was significantly associated with low international prognostic index (IPI) (P = 0.044 and 0.037, respectively). Patients with normal range of serum lactate dehydrogenase demonstrated a significantly higher PD-L1 positivity in tumor cells (P = 0.020). PD-L1-positive patients had a trend toward better overall survival compared with that in patients with PD-L1-negative in tumor cells and infiltrating immune cells (P = 0.498 and 0.435, respectively). The expression rate of PD-L1 was up to 79.7 % in ENKTL, while PD-1 expression rate was very low. This is the first report describing the clinicopathological features and survival outcome according to expression of PD-1 and PD-L1 in ENKTL.

Ovarian microcystic stromal tumor: A novel extracolonic tumor in familial adenomatous polyposis.

Ovarian microcystic stromal tumor (MCST) is a very rare neoplasm; hence, its nomenclature was recently designated as "Distinctive morphologic and immunohistochemical features" in 2009. Its exact origin, etiological genetic alterations, and background are not yet clearly known. Familial adenomatous polyposis (FAP) is an autosomal dominant disease that leads to development of colorectal polyps via germ-line mutations of the APC gene on chromosome 5q21∼22. In this study, we report a 40-year-old female patient who had ovarian MCST and FAP. On sequencing the APC gene in ovarian MSCT, we detected a novel somatic mutation of the APC gene in exon 11, with a heterozygous deletion at nucleotide position c.1540delG (p.Ala514 Profs*9). Mutations of ß-catenin (CTNNB1) and FOXL2 were not detected. Although one case demonstrating involvement of Wnt/ß-catenin in ovarian MCST associated with FAP has been presented previously, no detailed information was provided. Thus, this is the ovarian MCST with a somatic mutation of APC in a patient with FAP.

Insulin-like growth factor-1 receptor is associated with better prognosis in classical Hodgkin's lymphoma: Correlation with MET expression.

The purpose of this study was to examine the prognostic significance of insulin-like growth factor-1 receptor (IGF-1R) expression alone and in relation to the expression of the MET- receptor and the MET-homologous receptor RON, in classical Hodgkin's lymphoma (cHL). Tumour samples from patients with cHL (n = 202; median age 37.5 years) were analysed retrospectively for IGF-R1, MET or RON expression by immunohistochemistry using tissue microarrays. The median follow-up time was 3.7 years (range, 0.1-20 years). Twenty-nine patients (14.3%) expressed IGF-1R protein in Hodgkin/Reed-Sternberg (HRS) cells, which was associated with a better overall survival (OS) (P = 0.036). IGF-1R expression was closely associated with MET receptor expression and low level of lactate dehydrogenase. In patients with cHL receiving doxorubicin, bleomycin, vinblastine and dacarbazine, those expressing IGF-1R showed a trend towards better OS and event-free survival than IGF-1R-negative patients (P = 0.129 and P = 0.115 respectively), but statistical significance was not reached. This study suggests that IGF-1R expression could be associated with better clinical outcome in cHL but is significantly associated with the expression of MET receptor.

The absolute lymphocyte to monocyte ratio is associated with poor prognosis in classical Hodgkin lymphoma patients younger than 60 years of age.

Recent studies suggest that absolute lymphocyte count, absolute monocyte count and their ratio [lymphocyte/monocyte ratio (LMR)] at diagnosis may predict survival in classical Hodgkin lymphoma (cHL). Here, we investigated the prognostic significance of LMR in cHL patients in relation to age of patients. Subjects included 351 cHL patients (age range from 4 to 84 years, median age 34 years, sex ratio 1.58) who had been followed-up for a median period of 59 months (range, 0.1-245 months). The estimated 5-year overall survival (OS) rate was 86.8%. Subgroup analysis was performed according to patients' age; non-elderly group (<60 years of age) versus elderly group (≥60 years of age). There was no significant difference in the level of absolute lymphocyte count, absolute monocyte count or LMR between the age groups. Using receiver operating characteristic curve analysis, the optimal cut-off value of LMR for the entire cohort was determined at 2.8, whereas the optimal cut-off for the elderly group was 2.2. In the non-elderly group (<60 years old), patients with LMR <2.8 had significantly lower OS or lymphoma-specific survival compared with those with LMR ≥2.8 (p < 0.001, both). In contrast, neither the LMR value of 2.8 or 2.2 predicted survival in the elderly group. In multivariate analysis, LMR remained a significant prognostic factor for OS (p = 0.049). The results of our analysis suggest that low LMR is associated with poor OS in patients of <60 years old.

TCL1 expression predicts overall survival in patients with mantle cell lymphoma.

OBJECTIVES: Mantle cell lymphoma (MCL) has a heterogeneous clinical course. Although most cases show a poor prognosis, a minority has an indolent course. It is difficult to identify indolent MCL cases prospectively. T-cell leukemia/lymphoma protein 1 (TCL1) is expressed by several B-cell lymphomas, including MCL. This study examined the expression of TCL1 and its prognostic relevance for MCL. METHODS: Clinical data for 162 patients with MCL were collected. Of these, 144 cases with available tissues for tissue microarray construction and immunostaining were included in the analysis. TCL1 staining was quantified using the Nuclear Quant application with Pannoramic™ Viewer v. 1.14. High TCL1 expression was defined as moderate to strong nuclear and/or cytoplasmic staining in 40% or more of the cells. RESULTS: High TCL1 expression was observed in 39 of 144 samples (27.1%). Patients with low TCL1 expression were more likely to present with blastoid/pleomorphic morphology (P = 0.010). Low TCL1 expression was associated with significantly shorter overall survival (OS, P = 0.006). Multivariate analysis identified low TCL1 expression (P = 0.003), high-risk MIPI (P = 0.027), and anemia (P = 0.018) as adverse prognostic factors. CONCLUSIONS: Our study suggests that TCL1 expression profile may have a role in the prediction of overall outcome in patient with MCL and call for prospective studies.

Tumor suppressor p53 plays a key role in induction of both tristetraprolin and let-7 in human cancer cells.

Tristetraprolin (TTP) and let-7 microRNA exhibit suppressive effects on cell growth through down-regulation of oncogenes. Both TTP and let-7 are often repressed in human cancers, thereby promoting oncogenesis by derepressing their target genes. However, the precise mechanism of this repression is unknown. We here demonstrate that p53 stimulated by the DNA-damaging agent doxorubicin (DOX) induced the expression of TTP in cancer cells. TTP in turn increased let-7 levels through down-regulation of Lin28a. Correspondingly, cancer cells with mutations or inhibition of p53 failed to induce the expression of both TTP and let-7 on treatment with DOX. Down-regulation of TTP by small interfering RNAs attenuated the inhibitory effect of DOX on let-7 expression and cell growth. Therefore, TTP provides an important link between p53 activation induced by DNA damage and let-7 biogenesis. These novel findings provide a mechanism for the widespread decrease in TTP and let-7 and chemoresistance observed in human cancers.

Frequent detection of BRAF(V600E) mutations in histiocytic and dendritic cell neoplasms.

AIMS: In this study, we examined BRAF mutation in a wide range of histiocytic and dendritic cell neoplasms and compared its detection rate in each disease group. METHODS AND RESULTS: A total of 129 cases of histiocytic, dendritic cell and other related lesions were reviewed from the archives of 10 hospitals in Korea. The cases consisted of histiocytic sarcoma, follicular dendritic cell (FDC) sarcoma, interdigitating cell sarcoma, Langerhans cell histiocytosis (LCH), Langerhans cell sarcoma, blastic plasmacytoid dendritic cell neoplasm, acute monocytic leukaemia M5, giant cell tumour, xanthogranuloma, inflammatory myofibroblastic tumour and Rosai-Dorfman disease. BRAF mutation analysis was performed by Sanger sequencing and PNAcqPCR. All the detected mutations of BRAF were V600E. Histiocytic sarcoma exhibited the highest rate of BRAF(V600E) (62.5%, five of eight), followed by Langerhans cell tumours (25%, seven of 28), FDC sarcoma (18.5%, five of 27) and giant cell tumour (6.7%, two of 30). The other tumours did not harbour BRAF mutations. In histiocytic sarcoma, FDC sarcoma and LCH, there were no significant differences in clinical features between tumours containing BRAF(V600E) and those with BRAF(wt) . CONCLUSIONS: BRAF(V600E) was not limited to LCH and was detected more frequently in histiocytic sarcoma. Our findings suggest that the BRAF pathway may contribute to the pathogenesis or malignant transformation of histiocytic and dendritic cell neoplasms.

Ectopic over-expression of tristetraprolin in human cancer cells promotes biogenesis of let-7 by down-regulation of Lin28.

Tristetraprolin (TTP) is a AU-rich element (ARE) binding protein and exhibits suppressive effects on cell growth through down-regulation of ARE-containing oncogenes. The let-7 microRNA has emerged as a significant factor in tumor suppression. Both TTP and let-7 are often repressed in human cancers, thereby promoting oncogenesis by derepressing their target genes. In this work, an unexpected link between TTP and let-7 has been found in human cancer cells. TTP promotes an increase in expression of mature let-7, which leads to the inhibition of let-7 target gene CDC34 expression and suppresses cell growth. This event is associated with TTP-mediated inhibition of Lin28, which has emerged as a negative modulator of let-7. Lin28 mRNA contains ARE within its 3'-UTR and TTP enhances the decay of Lin28 mRNA through binding to its 3'-UTR. This suggests that the TTP-mediated down-regulation of Lin28 plays a key role in let-7 miRNA biogenesis in cancer cells.

FLI-1 is expressed in a wide variety of hematolymphoid neoplasms: a special concern in the differential diagnosis.

Friend Leukemia Virus Integration 1 (FLI-1) is a member of E26 transformation-specific family of transcription factors that participates in hematopoietic and vascular endothelial cell development. Immunohistochemical detection of FLI-1 has been widely used to diagnose vascular tumors or, more evidently, Ewing's sarcoma. However, the expression pattern of FLI-1 in hematolymphoid neoplasms remains unclear. Therefore, in this study, we aimed to investigate the expression of FLI-1 in these tumors, focusing on high-grade lesions, which presents a diagnostic challenge by mimicking Ewing's sarcoma. We evaluated the expression FLI-1 in various types of lymphoid and plasmacytic tumors, including 27 plasmablastic lymphomas, 229 diffuse large B-cell lymphomas, 22 precursor T- or B-lymphoblastic lymphomas, 24 angioimmunoblastic-type nodal T-follicular helper cell lymphomas, 52 peripheral T-cell lymphomas, NOS, 18 Burkitt lymphomas, 18 non-gastric lymphomas of mucosa-associated lymphoid tissue, 38 chronic lymphocytic leukemia/small lymphocytic lymphomas, 15 mantle cell lymphomas, 23 gastric MALT lymphomas, 50 plasma cell myelomas, and 38 follicular lymphomas. We calculated the H-scores of FLI-1 immunostaining, ranging from 0 to 200, and used the scores to analyze the clinicopathological significance of FLI-1 statistically. FLI-1 was expressed to varying degrees in all types of hematological tumors. FLI-1 expression was detected in 84.1% of patients (466/554). FLI-1 was highly expressed in precursor T- or B-lymphoblastic lymphomas. Follicular lymphomas exhibited low FLI-1 expression. In plasmablastic lymphoma, 85.2% of the patients were focally positive for FLI-1. FLI-1 expression did not correlate with clinicopathological variables, such as demographic data or disease stage, in patients with plasmablastic lymphoma and diffuse large B-cell lymphoma. However, FLI-1 overexpression was associated with poorer overall survival in patients with plasmablastic lymphoma. This study demonstrates that FLI-1 is expressed in various hematolymphoid neoplasms. FLI-1 expression can lead to diagnostic confusion, especially in small blue round cell tumors, such as lymphoblastic lymphoma, plasmablastic lymphoma, and plasma cell myeloma, when distinguishing tumors positive for CD99 and CD56 without CD3, CD20, or CD45. Our findings also suggested the possibility of FLI-1 as a potential prognostic biomarker for plasmablastic lymphoma.

A stepwise approach to fine needle aspiration cytology of lymph nodes.

The cytological diagnosis of lymph node lesions is extremely challenging because of the diverse diseases that cause lymph node enlargement, including both benign and malignant or metastatic lymphoid lesions. Furthermore, the cytological findings of different lesions often resemble one another. A stepwise diagnostic approach is essential for a comprehensive diagnosis that combines: clinical findings, including age, sex, site, multiplicity, and ultrasonography findings; low-power reactive, metastatic, and lymphoma patterns; high-power population patterns, including two populations of continuous range, small monotonous pattern and large monotonous pattern; and disease-specific diagnostic clues including granulomas and lymphoglandular granules. It is also important to remember the histological features of each diagnostic category that are common in lymph node cytology and to compare them with cytological findings. It is also essential to identify a few categories of diagnostic pitfalls that often resemble lymphomas and easily lead to misdiagnosis, particularly in malignant small round cell tumors, poorly differentiated squamous cell carcinomas, and nasopharyngeal undifferentiated carcinoma. Herein, we review a stepwise approach for fine needle aspiration cytology of lymphoid diseases and suggest a diagnostic algorithm that uses this approach and the Sydney classification system.

A Case of Late-Onset Neuromyelitis Optica Spectrum Disorder Associated With Cryptogenic Organizing Pneumonia.

Introduction: Systemic diseases can be found in neuromyelitis optica spectrum disorder (NMOSD) as a co-existing disease with paraneoplastic syndrome, sarcoidosis, or connective tissue disease. Cryptogenic organizing pneumonia (COP) in NMOSD with no evidence of these systemic disorders has rarely been reported. Case presentation: We present a 75-year-old patient who showed multifocal longitudinally extensive transverse myelitis and bilateral lung lesions that was seropositive for aquaporin-4 (AQP4) antibody. The patient initially presented with chronic cough, myalgia, and severe bilateral truncal neuropathic pain, and initial chest computed tomography demonstrated multifocal consolidations with reversed halo sign involving both lobes. Since this patient was over 50 years of age, our differential diagnoses included lung cancer and sarcoidosis. Through extensive studies including lung biopsy, an idiopathic type of diffuse interstitial lung disease-cryptogenic organizing pneumonia (COP)-was finally diagnosed. The patient was treated with high-dose methylprednisolone and it was tapered with oral steroids; mycophenolate mofetil was later added to the regimen. After treatment, the severe neuropathic pain and multifocal lung consolidation resolved. Conclusion: Herein, we presented a case of late-onset NMO with nonneoplastic, nonsarcoidosis, diffuse interstitial lung lesions, which is the finding of COP.

Rotation aiding technique for endobronchial ultrasound-guided transbronchial needle aspiration biopsy of intrathoracic lymph nodes: A complementary approach to the conventional jabbing method.

BACKGROUND: This study aimed to compare the lymph node core tissue lengths obtained via mediastinal or hilar lymphadenopathy using the complementary "rotation aiding" and conventional Jab technique. METHODS: We prospectively measured the lymph node core tissue length in patients who sequentially underwent the Jab and rotation aiding (RA) techniques between October 2012 and December 2014. Wilcoxon signed-rank test was used to compare the core tissue length and grade of diagnostic cells obtained by each technique. McNemar's test was used to compare the proportion of adequate cellularity (≥grade 2) between the aspiration techniques. RESULTS: The core tissue length of 61 lymph nodes from 43 patients (mean age: 63 years, range: 16-86 years) was analyzed. Pathological findings were consistent with malignant lesions in 25 (41%) patients and benign lesions in 36 (59%). The most common diagnosis in benign lymph nodes was reactive, followed by tuberculosis and sarcoidosis. We obtained longer core tissue with RA technique than with the Jab technique (83.2 ± 12.7 vs. 60.1 ± 10.1 mm; p = 0.02). There was a significant increase in cellularity grade and proportion of ≥grade 2 cells with the RA technique than with the Jab technique (2.39 ± 1.08 vs. 1.84 ± 1.14; p < 0.001, 78.7% vs. 52.5%; p = 0.002), regardless of the pathological diagnosis. CONCLUSIONS: RA technique facilitated more lymph node samples in terms of core tissue length and cellularity than the Jab technique.

Tristetraprolin regulates phagocytosis through interaction with CD47 in head and neck cancer.

CD47 is expressed in all human cancer cells, including head and neck cancer, and initiates a signaling cascade to inhibit macrophage phagocytosis. However, the mechanism underlying CD47 overexpression has not been elucidated in radioresistant head and neck cancer. The present study demonstrated that decreased Tristetraprolin (TTP) expression induced a sustained overexpression of CD47 using reverse transcription-quantitative PCR and western blotting, and that CD47 overexpression prevented phagocytosis using a phagocytosis assay in a radioresistant HN31R cell line. Subsequently, using TTP transfection, RNA interference, duel-luciferase assay and EMSA, it was revealed that TTP transfection enhanced phagocytosis through degradation of CD47 mRNA by directly binding to CD47 AREs within the CD47 3'UTR. Based on our previous study, methylation-specific PCR and western blotting revealed that DNMT1 was overexpressed in radioresistant HN31R cell line and TTP expression was decreased epigenetically by DMNT1 associated DNA methylation. Overall, these findings provided novel insight into the role of TTP as a biomarker of CD47-positive head and neck cancer patients.