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Gastric cancer (GC) is characterized by significant intratumoral heterogeneity, and stem cells are promising therapeutic targets. Despite advancements in spatial transcriptome analyses, unexplored targets for addressing cancer stemness remain unknown. This study aimed to identify Nuclear Factor IX (NFIX) as a critical regulator of cancer stemness in GC and evaluate its clinicopathological significance and function. Spatial transcriptome analysis of GC was conducted. The correlation between NFIX expression, clinicopathological factors, and prognosis was assessed using immunostaining in 127 GC cases. Functional analyses of cancer cell lines validated these findings. Spatial transcriptome analysis stratified GC tissues based on genetic profiles, identified CSC-like cells, and further refined the classification to identify and highlight the significance of NFIX, as validated by Monocle 3 and CytoTRACE analyses. Knockdown experiments in cancer cell lines have demonstrated the involvement of NFIX in cancer cell proliferation and kinase activity. This study underscores the role of spatial transcriptome analysis in refining GC tissue classification and identifying therapeutic targets, highlighting NFIX as a pivotal factor. NFIX expression is correlated with poor prognosis and drives GC progression, suggesting its potential as a novel therapeutic target for personalized GC therapies.
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Characterization of the elemental distribution of samples with rough surfaces has been strongly desired for the analysis of various natural and artificial materials. Particularly for pristine and rare analytes with micrometer sizes embedded on specimen surfaces, non-invasive and matrix effect-free analysis is required without surface polishing treatment. To satisfy these requirements, we proposed a new method employing the sequential combination of two imaging modalities, i.e., microenergy-dispersive X-ray fluorescence (micro-XRF) and Raman micro-spectroscopy. The applicability of the developed method is tested by the quantitative analysis of cation composition in micrometer-sized carbonate grains on the surfaces of intact particles sampled directly from the asteroid Ryugu. The first step of micro-XRF imaging enabled a quick search for the sparsely scattered and micrometer-sized carbonates by the codistributions of Ca2+ and Mn2+ on the Mg2+- and Fe2+-rich phyllosilicate matrix. The following step of Raman micro-spectroscopy probed the carbonate grains and analyzed their cation composition (Ca2+, Mg2+, and Fe2+ + Mn2+) in a matrix effect-free manner via the systematic Raman shifts of the lattice modes. The carbonates were basically assigned to ferroan dolomite bearing a considerable amount of Fe2+ + Mn2+ at around 10 atom %. These results are in good accordance with the assignments reported by scanning electron microscopy-energy-dispersive X-ray spectroscopy, where the thin-sectioned and surface-polished Ryugu particles were applicable. The proposed method requires neither sectioning nor surface polishing; hence, it can be applied to the remote sensing apparatus on spacecrafts and planetary rovers. Furthermore, the non-invasive and matrix effect-free characterization will provide a reliable analytical tool for quantitative analysis of the elemental distribution on the samples with surface roughness and chemical heterogeneity at a micrometer scale, such as art paintings, traditional crafts with decorated shapes, as well as sands and rocks with complex morphologies in nature.
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INTRODUCTION: Gastric cancer (GC) remains a common health concern worldwide and is the third leading cause of death in Japan. It can be broadly classified into gastric and intestinal mucin phenotypes using immunohistochemistry. We previously reported numerous associations of kinesin family member (KIF) genes and mucin phenotypes with GC. However, no previous studies have reported on the importance of KIF18B in GC using immunostaining. Thus, in this study, we investigated the expression and functions of KIF18B, which is highly expressed in gastric mucin phenotype GC. METHODS: We performed RNA-seq of gastric and intestinal mucin type GCs, and clinicopathological studies of the KIF18B we found were performed using 96 GC cases. We also performed functional analysis using GC-derived cell lines. RESULT: RNA-seq showed the upregulation of matrisome-associated genes in gastric mucin phenotype GC and a high expression of KIF18B. KIF18B was detected in 52 of the 96 GC cases (54%) through immunohistochemistry. Low KIF18B expression was significantly associated with poor overall survival (p < 0.01). Other molecules that were significantly associated with KIF18B were MUC5AC and claudin 18; these were also significantly associated with the gastric mucin phenotype. KIF18B small interfering RNA (siRNA)-transfected GC cells showed greater growth and spheroid colony formation than the negative control siRNA-transfected cells. Furthermore, expression of snail family transcriptional repressor 1 and cadherin 2 was significantly increased and that of cadherin 1 was significantly decreased in KIF18B siRNA-transfected GC cells. CONCLUSION: These findings not only suggest that KIF18B may be a useful prognostic marker, but also provide insight into the pathogenesis of the GC phenotype.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Cinesinas/genética , Cinesinas/metabolismo , Mucinas Gástricas/genética , Mucinas Gástricas/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , RNA Interferente Pequeno , Transição Epitelial-Mesenquimal/genética , Fenótipo , Regulação Neoplásica da Expressão Gênica , Linhagem Celular TumoralRESUMO
BACKGROUND: Glutaminase 1 (GLS1), a key enzyme in glutamine metabolism in cancer cells, acts as a tumor promoter and could be a potential therapeutic target. CB-839, a GLS1-specific inhibitor, was developed recently. Herein, we aimed to elucidate the anti-tumor effects and mechanism of action of CB-839 in colorectal cancer (CRC). METHODS: Using the UCSC Xena public database, we evaluated GLS1 expression in various cancers. Immunostaining for GLS1 was performed on 154 surgically resected human CRC specimens. Subsequently, we examined the GLS1 mRNA expression levels in eight CRC cell lines and evaluated the association between GLS1 expression and CB-839 efficacy. To create a reproducible CRC model with abundant stroma and an allogeneic immune response, we co-transplanted CT26 and stem cells into BALB/c mice and treated them with CB-839. Finally, RNA sequencing of mouse tumors was performed. RESULTS: Database analysis showed higher GLS1 expression in CRC tissues than in normal colon tissues. Clinical samples from 114 of the 154 patients with CRC showed positive GLS1 expression. GLS1 expression in clinical CRC tissues correlated with vascular invasion. CB-839 treatment inhibited cancer cell proliferation depending on GLS1 expression in vitro and inhibited tumor growth and metastasis in the CRC mouse model. RNA sequencing revealed that CB-839 treatment inhibited stromal activation, tumor growth, migration, and angiogenesis. These findings were validated through in vitro and in vivo experiments and clinical specimen analysis. CONCLUSIONS: GLS1 expression in CRC plays important roles in tumor progression. CB-839 has inhibitory effects on cancer proliferation and the tumor microenvironment.
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Proliferação de Células , Neoplasias Colorretais , Glutaminase , Camundongos Endogâmicos BALB C , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Animais , Glutaminase/antagonistas & inibidores , Glutaminase/metabolismo , Glutaminase/genética , Camundongos , Proliferação de Células/efeitos dos fármacos , Feminino , Linhagem Celular Tumoral , Benzenoacetamidas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Masculino , Células Estromais/metabolismo , Células Estromais/patologia , Células Estromais/efeitos dos fármacos , Tiadiazóis/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Antineoplásicos/farmacologia , Pessoa de Meia-Idade , Modelos Animais de DoençasRESUMO
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of malignancy, with poor prognosis and rising incidence. IQ motif containing GTPase-activating protein 3 (IQGAP3) is a member of the IQGAPs family of scaffolding proteins that govern multiple cellular activities like cytoskeletal remodeling and cellular signal transduction. This study aimed to analyze the expression and biological function of IQGAP3 in PDAC. METHODS: We analyzed IQGAP3 expression in 81 PDAC samples by immunohistochemistry. RNA interference was used to inhibit IQGAP3 expression in PDAC cell lines. RESULTS: Immunohistochemical analysis of IQGAP3 showed that 54.3% of PDACs were positive for cytoplasmic expression of IQGAP3, with no expression found in non-neoplastic tissue. Furthermore, IQGAP3 expression was an independent poor prognostic factor in our immunostaining-based studies and analyses of public databases. Our cohort and the Cancer Genome Atlas database indicated that IQGAP3 is co-localized with kinesin family member C1 (KIFC1), which we previously reported as a cancer stem cell-associated protein. IQGAP3 small interfering RNA treatment decreased PDAC cell proliferation and spheroid colony formation via ERK and AKT pathways. DISCUSSION/CONCLUSION: These results suggest that IQGAP3, a transmembrane protein, is involved in survival and stemness and may be a promising new therapeutic target for PDAC.
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Carcinoma Ductal Pancreático , Proliferação de Células , Cinesinas , Células-Tronco Neoplásicas , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Linhagem Celular Tumoral , Feminino , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Cinesinas/genética , Cinesinas/metabolismo , Idoso , Proteínas Ativadoras de ras GTPase/genética , Proteínas Ativadoras de ras GTPase/metabolismo , Transdução de Sinais , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Imuno-Histoquímica , Proteínas Ativadoras de GTPaseRESUMO
BACKGROUND: The validity of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) in older individuals with comorbidities remains unclear. Therefore, this study evaluated the safety and efficacy of ESD and additional treatment for ESCC in older adult patients. METHODS: The clinicopathological characteristics and clinical outcomes of 398 consecutive older adult patients (≥ 65 years) with 505 lesions who underwent ESD for ESCC at the Hiroshima University Hospital between September 2007 and December 2019 were retrospectively evaluated. Additionally, the prognoses of 381 patients who were followed up for > 3 years were assessed. RESULTS: The mean patient age and procedure time were 73.1 ± 5.8 years and 77.1 ± 43.5 min, respectively. The histological en bloc resection rate was 98% (496/505). Postoperative stenosis, perforation, pneumonia, and delayed bleeding were conservatively treated in 82 (16%), 19 (4%), 15 (3%), and 5 (1%) patients, respectively. The 5-year overall and disease-specific survival rates were 78.9% and 98.0%, respectively (mean follow-up time: 71.1 ± 37.3 months). Multivariate analysis showed that age and the American Society of Anesthesiologists classification of physical status class ≥III (hazard ratio: 1.27; 95% confidence interval: 1.01-1.59, p = 0.0392) were independently associated with overall survival. A significantly lower overall survival rate was observed in the high-risk follow-up group than in the low-risk follow-up and high-risk additional treatment groups (p < 0.01). However, no significant difference in disease-specific survival was observed among the three groups. CONCLUSIONS: ESD is safe for ESCC treatment in patients aged ≥ 65 years. However, additional treatments should be considered based on the patient's general condition.
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Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Complicações Pós-Operatórias , Humanos , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Idoso , Masculino , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Feminino , Estudos Retrospectivos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Prognóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores Etários , Resultado do Tratamento , Idoso de 80 Anos ou mais , Taxa de SobrevidaRESUMO
Root-colonizing fungi, such as mycorrhizal fungi and dark septate endophyte fungi, are often found on pioneer plant species during early primary succession. However, little is known about which fungal species are responsible for the establishment of pioneer plants when these symbionts colonize simultaneously. We investigated the root-colonizing fungal communities of Pinus thunbergii that established prior to lichens, bryophytes, and short-lived herbaceous plants in a primary successional volcanic mudflow site on Kuchinoerabu Island, Japan. We collected a total of 54 current-year and 1- to 2-year-old seedlings. The colonization of root fungi was evaluated by direct observation of key structures (e.g., mantle, arbuscule, microsclerotia, and hyphae) and molecular analysis. Of the 34 current-year seedlings collected, only 12 individuals were colonized by ectomycorrhizal (ECM) fungi. By contrast, all 1- to 2-year-old seedlings were colonized by ECM fungi. Seedlings colonized by pine-specific ECM fungi, specifically Rhizopogon roseolus and Suillus granulatus, showed higher nitrogen and phosphorus contents in their needles compared to non-ECM seedlings. Arbuscular mycorrhizal fungi and dark septate endophyte fungi were found in only two and three individuals, respectively. The high density of mycophagous deer on Kuchinoerabu-jima may contribute to the favored dispersal of ECM fungi over other root-colonizing fungi. In conclusion, the seedling establishment of P. thunbergii at the volcanic mudflow may be largely supported by ECM fungi, with negligible effects of arbuscular mycorrhizal fungi and dark septate endophytes.
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Cervos , Micorrizas , Pinus , Humanos , Animais , Pinus/microbiologia , Plântula/microbiologia , Japão , Raízes de Plantas/microbiologiaRESUMO
PURPOSE: The transmembrane serine protease 4 (TMPRSS4) gene is upregulated in various human cancers. However, its biological functions in pancreatic ductal adenocarcinoma remain unclear. We examined the expression of TMPRSS4 in pancreatic ductal adenocarcinoma tissues and its correlation with clinicopathological parameters in patients with pancreatic ductal adenocarcinoma who underwent surgery. METHODS: The TMPRSS4 expression was immunohistochemically examined in 81 PDAC patients with pancreatic ductal adenocarcinoma. We analyzed the association between the TMPRSS4 expression and clinicopathological factors, the recurrence-free survival (RFS), and the overall survival (OS) and examined the effect of TMPRSS4 expression on cell migration and sensitivity to 5-fluorouracil. RESULTS: The expression rate of TMPRSS4 in the samples was 62.9% (51/81). The TMPRSS4 expression was not correlated with any clinicopathological feature. The five-year overall and recurrence-free survival rates were significantly lower in the TMPRSS4-positive group than in the TMPRSS4-negative group. On a multivariate analysis, TMPRSS4 positivity, poorly differentiated histology, and non-adjuvant chemotherapy predicted a poor OS, while TMPRSS4 positivity and poorly differentiated histology predicted a poor RFS. TMPRSS4-silenced pancreatic ductal adenocarcinoma cells showed higher sensitivity to 5- fluorouracil than did the control siRNA-transfected cells. CONCLUSIONS: TMPRSS4 can be considered a prognostic factor and therapeutic target for pancreatic ductal adenocarcinoma.
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BACKGROUND: Maximum phonation time (MPT) is used to assess speech and other oral rehabilitation-related issues. Various factors contribute to MPT decline in older individuals. Although the impact of physical frailty on MPT has been suggested, this has not been conclusively determined. OBJECTIVE: To examine the relationship between MPT and physical frailty in community-dwelling individuals aged ≥60 years who were independently mobile. MPT-associated factors were investigated. METHODS: This cross-sectional study analysed the clinical data of 122 patients (age [interquartile range]: 80.0 [74.0-83.0] years) without dementia who visited a neurology department between 1 February 2021 and 31 January 2023. Investigated factors included age, sex, weight, height, body mass index, smoking history, grip strength, functional independence measure, vital capacity, oral diadochokinesis, MPT and the Japanese Cardiovascular Health Study score. Physical frailty was assessed based on the total score from five items (weight loss, weakness, exhaustion, slowness and low physical activity). The relationship between MPT and physical frailty was examined using Spearman's rank correlation coefficient and hierarchical multiple regression analysis. RESULTS: The MPT was negatively correlated with age (r = -0.347, p < .01) and physical frailty (r = -0.681, p < .01) and positively correlated with vital capacity (r = 0.474, p < .01) and height (r = 0.248, p < .01). The hierarchical multiple regression analysis, conducted with MPT as the dependent variable, demonstrated that physical frailty (ß = -.59, 95% confidence interval: -0.74 to 0.43, p < .001) had a strong influence on MPT. CONCLUSION: In older individuals, MPT is associated with physical frailty. When assessing MPT in clinical settings, it is advisable to perform a concurrent assessment of physical frailty.
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Idoso Fragilizado , Fragilidade , Avaliação Geriátrica , Vida Independente , Fonação , Humanos , Masculino , Feminino , Idoso , Estudos Transversais , Idoso de 80 Anos ou mais , Fonação/fisiologia , Fragilidade/fisiopatologia , Pessoa de Meia-Idade , Instituições de Assistência AmbulatorialRESUMO
PURPOSE: The prognosis of patients with pT3 upper tract urothelial carcinoma (UTUC) varies. The current study aimed to further classify patients with pT3 UTUC into different survival outcome groups based on tumor location and site of invasion. METHODS: This retrospective study included 323 patients with pT3 UTUC who underwent nephroureterectomy at 11 hospitals in Japan. Histological and clinical data were obtained via a chart review. Univariate and multivariate Cox proportional hazards analyses showed the effect of different variables on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: The median age of the patients was 72 years. Patients with pT3 UTUCs were divided into two groups: those with renal parenchymal invasion only (pT3a, n = 95) and those with peripelvic or periureteral fat invasion (pT3b, n = 228). pT3b UTUC was significantly associated with hydronephrosis, low preoperative estimated glomerular filtration rate (eGFR), histological nodal metastasis, nuclear grade 3, lymphovascular invasion (LVI), carcinoma in situ, and positive surgical margin. Based on the univariate analyses, patients with pT3b UTUC had a significantly lower 5-year RFS (42.4% vs. 70.1%, p < 0.0001), 5-year CSS (54.3% vs. 80.0%, p = 0.0002), and 5-year OS (47.8% vs. 76.8%, p < 0.0001) than those with pT3a UTUC. According to the multivariate analyses, nodal metastasis, LVI, adjuvant chemotherapy, preoperative eGFR, nuclear grade (RFS only), surgical margin (RFS only), and Charlson comorbidity index (OS only), but not pT3b stage, were associated with survival. CONCLUSION: Compared with pT3a UTUC, pT3b UTUC was significantly associated with worse histological features, consequently resulting in unsatisfactory survival outcomes.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Humanos , Idoso , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/cirurgia , Estudos Retrospectivos , Prognóstico , Nefroureterectomia/métodos , Neoplasias Urológicas/patologiaRESUMO
INTRODUCTION: Gastric cancer (GC) is a leading cause of cancer-related death worldwide. This study focused on minichromosome maintenance 4 (MCM4), a DNA helicase component that functions in DNA replication. Using spheroid colony formation, having a colony rich in cancer stem cells, this study aimed to investigate the clinicopathological importance of MCM4. METHODS: We examined MCM4 expression using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) analysis in 10 and 113 GC cases, respectively. MCM4 function in GC was also investigated by RNA interference in GC cell lines. RESULTS: In qRT-PCR and IHC analysis, high MCM4 expression was found in 60% and 83% of GC cases, respectively. MCM4-positive GC cases were significantly associated with higher T grade and tumor stage. Additionally, high MCM4 expression was significantly associated with poor prognosis and was an independent prognostic factor in multivariate analysis. MCM4 was significantly coexpressed with CD133, matrix metalloproteinase 7 (MMP7), epidermal growth factor (EGFR), and mesenchymal-epithelial transition factor (cMET). In GC cell lines, MCM4 knockdown affected cell growth and protein kinase B (Akt), extracellular signal-regulated kinase (ERK), and EGFR pathways. CONCLUSION: These results indicate that MCM4 expression could be a key regulator in GC progression and is pivotal in treating GC.
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DNA Helicases , Neoplasias Gástricas , Humanos , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , DNA Helicases/metabolismo , Receptores ErbB , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Células-Tronco NeoplásicasRESUMO
INTRODUCTION: Esophageal cancer is the sixth leading cause of cancer-related death worldwide. However, molecular targeted therapy and novel therapeutic targets are needed for esophageal squamous cell cancer (ESCC). In a previous study, we reported that protocadherin (PCDH) B9 plays an important role in several cancers. Therefore, in this study, we examined the clinical significance of PCDHB9 expression in ESCC. METHODS: PCDHB9 expression was examined using immunohistochemistry in 128 cases and using quantitative reverse transcription-polymerase chain reaction in 16 cases of ESCC. PCDHB9 function in ESCC cells was examined using RNA interference. RESULTS: High PCDHB9 expression was identified in 5 of 16 (31.3%). In total, 51 (40%) ESCC cases showed strong PCDHB9 expression, whereas nonneoplastic mucosa rarely showed its expression. High PCDHB9 expression was significantly associated with T classification, N grade, and stage in ESCC. In ESCC cell lines, PCDHB9 knockdown affected cell growth, migration, and adhesion. Further, the expression of integrin (ITG) A3, ITGA4, ITGA5, ITGB1, ITGB6, vimentin, snail family transcriptional repressor 1, and cadherin 2 (NCAD) was significantly reduced and cadherin 1 was significantly increased in PCDHB9 knockdown ESCC cells. CONCLUSION: These results suggest that PCDHB9 plays a tumor-promoting role and is a potential biomarker and therapeutic target in ESCC.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Neoplasias Esofágicas/metabolismo , Protocaderinas , Carcinoma de Células Escamosas/metabolismo , Interferência de RNA , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Proliferação de CélulasRESUMO
ßIII-Tubulin, encoded by the TUBB3 gene, is a microtubule protein. We previously reported that TUBB3 is overexpressed in renal cell carcinoma. We investigated the clinicopathological significance of TUBB3 in upper tract urothelial carcinoma (UTUC) by immunohistochemistry. In normal tissue, TUBB3 expression was weak or absent. In contrast, TUBB3 overexpression was observed in urothelial carcinoma (UC) tissues in 51 (49%) of 103 UTUC cases. TUBB3 overexpression was associated with nodular/flat morphology, high-grade disease, high T stage, and a poor prognosis. Similar results were obtained in The Cancer Genome Atlas bladder cancer cohort. TUBB3 expression was also associated with high Ki-67 labeling index, CD44v9, HER2, EGFR, and p53 expression in UTUC. Among representative cancer-related molecules, TUBB3 was an independent predictor of progression-free survival and high-grade UC. Finally, using urine cytology samples, we analyzed TUBB3 expression by immunocytochemistry. TUBB3 expression was more frequently found in UC cells than in nonneoplastic cells. The diagnostic accuracy of urine cytology was improved when combined with TUBB3 immunostaining. The findings suggest the importance of TUBB3 in tumor progression and its potential application as a biomarker for high-grade disease and the prognosis of UC. Moreover, combination with TUBB3 immunostaining might improve the diagnostic accuracy of urine cytology.
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Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Tubulina (Proteína) , Citodiagnóstico , Neoplasias Renais/diagnósticoRESUMO
The primary succession of ectomycorrhizal (ECM) fungi has been well described for Pinus and Salix, but the succession for other pioneer hosts is almost unknown. Here, we investigated ECM fungal communities of Alnus sieboldiana at different host growth stages in a primary successional volcanic site on Izu-Oshima Island, Japan. ECM root tips were collected from 120 host individuals, encompassing seedling, sapling, and mature tree stages. The taxonomic identity of the ECM fungi was determined based on rDNA internal transcribed spacer region sequences. Nine molecular taxonomic units were detected from a total of 807 root tips. The initial ECM fungal community on the pioneer seedlings was composed of only three species, where an undescribed Alpova species (Alpova sp.) was exclusively frequent. With host growth, other ECM fungal species were added to the communities, while the initial colonizers remained even at mature tree stages. Thus, the ECM fungal composition significantly changed along host growth stages and showed the nested community structure. Although most of the ECM fungi confirmed in this study had a broad Holarctic geographical distribution, the Alpova sp. had no previous records in other regions. These results suggest that a locally evolved Alpova sp. plays an essential role in the initial seedling establishment of A. sieboldiana at early successional volcanic sites.
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Alnus , Basidiomycota , Micorrizas , Alnus/genética , Alnus/microbiologia , Japão , Basidiomycota/genética , DNA Ribossômico/genética , Árvores/microbiologia , Plântula/microbiologia , FungosRESUMO
ABSTRACT: Matsuda, T, Takahashi, H, Nakamura, M, Ogata, H, Kanno, M, Ishikawa, A, and Sakamaki-Sunaga, M. Influence of the menstrual cycle on muscle glycogen repletion after exhaustive exercise in eumenorrheic women. J Strength Cond Res 37(4): e273-e279, 2023-The purpose of this study was to investigate the effect of the menstrual cycle on muscle glycogen repletion postexercise. Eleven women with regular menstrual cycles (age: 20.2 ± 1.3 years, height: 161.1 ± 4.8 cm, and body mass: 55.5 ± 5.7 kg) were assessed in 3 phases of the cycle: the early follicular phase (E-FP), late follicular phase (L-FP), and luteal phase (LP). Each test day began with glycogen-depleting exercise, followed by 5 hours of recovery. Muscle glycogen concentrations, using 13 C-magnetic resonance spectroscopy, and estradiol, progesterone, blood glucose, blood lactate, free fatty acid (FFA), and insulin concentrations were measured at t = 0, 120, and 300 minutes postexercise. During the 5-hour recovery period, subjects consumed 1.2g·(kg body mass) -1 ·h -1 of carbohydrates every 30 minutes. The muscle glycogen concentrations increased at t = 120 and t = 300 minutes postexercise ( p < 0.01) but were not significantly different between the menstrual cycle phases ( p = 0.30). Blood lactate concentrations were significantly higher in the L-FP and LP than in the E-FP ( p < 0.05). Nonetheless, the blood glucose, FFA, insulin concentrations, and the exercise time until exhaustion in the E-FP, L-FP, and LP were similar (blood glucose, p = 0.17; FFA, p = 0.50; insulin, p = 0.31; exercise time, p = 0.67). In conclusion, the menstrual cycle did not influence muscle glycogen repletion after exercise.
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Glicemia , Glicogênio , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Ciclo Menstrual/fisiologia , Músculos , Ácido Láctico , InsulinaRESUMO
Laparoscopic proximal gastrectomy(LPG)for upper gastric cancer is still inadequate. We verified the validity of LPG by comparing the surgical outcomes of 15 cases who underwent LPG(PG group)and 14 cases who underwent laparoscopic total gastrectomy(TG group)in 29 cases who underwent laparoscopic surgery for upper gastric cancer at our hospital between January 2014 and December 2022. As a patient background, the PG group was significantly older(p=0.03)than the TG group and tended to have more high-risk cases(p=0.12). As a tumor factor, cancer progression tended to be earlier in the PG group(p=0.05). As a surgical(short-term)outcomes, although the range of lymph nodes dissection was narrow (p<0.01)and the amount of blood loss was significantly lower(p=0.01)in the PG group, there was no difference in operation time or postoperative complications between the 2 groups. Furthermore, there was no difference in the rate of weight loss, the rate of change in nutritional indicators in the medium-term(1 year after surgery), or the long-term prognosis.
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Laparoscopia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Resultado do Tratamento , Estudos Retrospectivos , Gastrectomia , Complicações Pós-OperatóriasRESUMO
We report a case of rectal cancer that was resected 1 year and 3 months after SEMS implantation. An 89-year-old man was previously diagnosed with sigmoid colon cancer at another hospital but did not undergo surgery. Three years and 7 months after the diagnosis, SEMS was implanted at another hospital. Four years and 10 months after the diagnosis, the patient was diagnosed with intestinal obstruction at our hospital. Since the SEMS was open on colonoscopy, the patient was also suspected of having flaccid constipation. The primary tumor was resected, and a colostomy was constructed in the descending colon. Bridge to surgery for obstructive colorectal cancer was performed within a few weeks after SEMS implantation. At our hospital, resection was performed after a long time. No complications, such as obstruction or perforation, were observed. In addition, although there were concerns regarding increased vascular invasion due to compression and drainage of the cancerous tissue, in our case, the vascular invasion was mild, and no distant metastasis or invasion of other organs was observed. SEMS can be used for long-term implantation and does not necessarily cause cancer progression.
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Neoplasias Colorretais , Obstrução Intestinal , Neoplasias Retais , Masculino , Humanos , Idoso de 80 Anos ou mais , Neoplasias Colorretais/cirurgia , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Neoplasias Retais/complicações , Neoplasias Retais/cirurgia , Colonoscopia/efeitos adversos , Constipação Intestinal/etiologia , Constipação Intestinal/cirurgia , Resultado do Tratamento , Stents/efeitos adversos , Estudos RetrospectivosRESUMO
Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. The spheroid colony formation assay is a useful method to identify cancer stem cells (CSCs). Using the DLD-1 and WiDr CRC cell lines, we performed microarray analyses of spheroid body-forming and parental cells and demonstrated that aldolase, fructose-bisphosphate C (ALDOC) was overexpressed in the spheroid body-forming cells of both lines. Cells transfected with small interfering RNA against ALDOC demonstrated lower proliferation, migration, and invasion compared with negative control cells. Both the number and size of spheres produced by the CRC cells were significantly reduced by ALDOC knockdown. Additionally, inhibition of ALDOC reduced lactate production. Immunohistochemistry was used to analyze ALDOC protein expression in tissues from 135 CRC patients and revealed that 66 (49%) cases were positive for ALDOC. The ALDOC-positive cases were associated with higher T and M grades and, as determined by Kaplan-Meier analysis, a poorer prognosis. Univariate and multivariate analyses indicated that ALDOC expression was an independent prognostic factor for CRC patients. Furthermore, ALDOC expression was associated with CD44 expression. These results suggest that ALDOC contributes to CRC progression and plays an important role in CSCs derived from CRC.
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Neoplasias Colorretais/etiologia , Frutose-Bifosfatase/genética , Frutose-Bifosfato Aldolase/genética , Esferoides Celulares/patologia , Linhagem Celular Tumoral , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Frutose-Bifosfatase/metabolismo , Frutose-Bifosfato Aldolase/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Esferoides Celulares/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Exercise capacity in idiopathic pulmonary fibrosis (IPF) is limited by exercise-induced hypoxaemia. This study aimed to examine the effect of high-flow nasal cannula oxygen therapy (HFNC) on exercise tolerance in patients with IPF. METHODS: We conducted a single-centre, open-label, randomized crossover trial to compare HFNC and Venturi mask (VM) therapy in terms of exercise tolerance. Patients underwent constant-load symptom-limited exercise testing at 80% peak work rate with HFNC or a VM in a randomized order. The settings were 60 L/min and a 50% fraction of inspired oxygen (FiO2 ) for HFNC and 12 L/min and 50% FiO2 for VM. The primary outcome was endurance time, and the secondary outcomes were heart rate (HR), percutaneous oxygen saturation (SpO2 ), dyspnoea and leg fatigue, as determined by the modified Borg Scale at the isotime and endpoint, and the level of comfort while using the devices. RESULTS: Twenty-four participants (75.0% men; age, median [interquartile range]: 77.5 [68.8-83.0] years) were enrolled. Compared with VM, HFNC significantly improved the endurance time (647.5 s [454.0-1014.8] vs. 577.5 s [338.0-861.5]), minimum SpO2 (96.0% [95.0-98.0] vs. 94.0% [92.8-96.0]) and leg fatigue at the isotime (3.0 [1.6-4.0] vs. 5.0 [3.0-6.3]) and endpoint (4.0 [2.8-5.0] vs. 5.0 [3.8-6.3]). Differences in maximum HR, dyspnoea at the isotime and endpoint and comfort were non-significant between HFNC and VM therapy. CONCLUSION: HFNC increased exercise tolerance in patients with stable IPF experiencing exercise-induced hypoxaemia.
Assuntos
Fibrose Pulmonar Idiopática , Insuficiência Respiratória , Idoso , Cânula , Estudos Cross-Over , Tolerância ao Exercício/fisiologia , Feminino , Humanos , Fibrose Pulmonar Idiopática/terapia , Masculino , Oxigênio , Oxigenoterapia , Insuficiência Respiratória/terapiaRESUMO
OBJECTIVES: Although the treatment strategy for advanced urothelial carcinoma (aUC) has drastically changed since pembrolizumab was introduced in 2017, studies revealing current survival rates in aUC are lacking. This study aimed to assess (1) the improvement in survival among real-world patients with aUC after the introduction of pembrolizumab and (2) the direct survival-prolonging effect of pembrolizumab. METHODS: This multicenter retrospective study included 531 patients with aUC undergoing salvage chemotherapy, including 200 patients treated in the pre-pembrolizumab era (2003-2011; earlier era) and 331 patients treated in a recent 5-year period (2016-2020; recent era). Using propensity score matching (PSM), cancer-specific survival (CSS) and overall survival (OS) were compared between the earlier and recent eras, in addition to between the recent era, both with and without pembrolizumab use, and the earlier era. RESULTS: After PSM, the recent era cohort had significantly longer CSS (21 months) and OS (19 months) than the earlier era cohort (CSS and OS: 12 months). In secondary analyses using PSM, patients treated with pembrolizumab had significantly longer CSS (25 months) and OS (24 months) than those in the earlier era cohort (CSS and OS: 11 months), whereas patients who did not receive pembrolizumab in the recent era had similar outcomes (CSS and OS: 14 months) as the earlier era cohort (CSS and OS: 12 months). CONCLUSIONS: Patients with aUC treated in the recent era exhibited significantly longer survival than those treated before the introduction of pembrolizumab. The improved survival was primarily attributable to the use of pembrolizumab.