scholarly journals Role of the β-Catenin/REG Iα Axis in the Proliferation of Sessile Serrated Adenoma/Polyps Associated with Fusobacterium nucleatum

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 434
Author(s):  
Heihachiro Nishimura ◽  
Hirokazu Fukui ◽  
Xuan Wang ◽  
Nobuhiko Ebisutani ◽  
Takashi Nakanishi ◽  
...  

Although sessile serrated adenoma/polyps (SSA/Ps) may arise through a pathway different from the traditional adenoma–carcinoma sequence, details of SSA/P tumorigenesis still remain unclear. Fusobacterium nucleatum (Fn) is frequently detected in colorectal cancer (CRC) tissues and may play a pivotal role in colorectal carcinogenesis. Here, we investigated the relationship between Fn and the β-catenin/REG Iα axis in SSA/Ps and their involvement in the proliferation of these lesions. Fn was detected in SSA/Ps by fluorescence in situ hybridization using a Fn-targeted probe, and expression of β-catenin, REG Iα and Ki67 was examined using immunohistochemistry. Sixteen of 30 SSA/P lesions (53.3%) were positive for Fn. Eighteen SSA/P lesions (60%) showed β-catenin immunoreactivity in the tumor cell nuclei. A significant majority of Fn-positive lesions showed nuclear expression of β-catenin (87.5%) and higher REG Iα scores and Ki67 labeling indices relative to Fn-negative lesions. The SSA/P lesions expressing β-catenin in nuclei had significantly higher REG Iα scores and Ki67 labeling indices than those expressing β-catenin on cytomembranes. The REG Iα score was positively correlated with the Ki67 labeling index in SSA/P lesions. The treatment with Wnt agonist SKL2001 promoted nuclear β-catenin translocation and enhanced REG Ia expression in Caco2 cells. Fn may play a role in the proliferation of SSA/P lesions through promotion of β-catenin nuclear translocation and REG Iα expression.

Pathobiology ◽  
2020 ◽  
pp. 1-14
Author(s):  
José Guilherme Datorre ◽  
Ana Carolina de Carvalho ◽  
Denise Peixoto Guimarães ◽  
Rui Manuel Reis

Colorectal cancer (CRC) is one of the most frequent and deadly neoplasms worldwide. Genetic factors, lifestyle habits, and inflammation are important risk factors associated with CRC development. In recent years, growing evidence has supporting the significant role of the intestinal microbiome in CRC carcinogenesis. Disturbances in the healthy microbial balance, known as dysbiosis, are frequently observed in these patients. Pathogenic microorganisms that induce intestinal dysbiosis have become an important target to determine the role of bacterial infection in tumorigenesis. Interestingly, the presence of different bacterial strains, such as <i>Fusobacterium nucleatum</i>, has been detected in tissue and stool from patients with CRC and associated with substantial clinical and molecular features, as well as with patient therapy response. Therefore, understanding how the presence and levels of <i>F. nucleatum</i>strains in the gut affect the risk of CRC onset and progression may inform suitable candidates for interventions focused on modulation of this bacteria. Here we review new insights into the role of gut microbiota in CRC carcinogenesis and the clinical utility of using the detection of <i>F. nucleatum</i> in different settings such as screening, prognosis, and microbiota modulation as a means to prevent cancer, augment therapies, and reduce adverse effects of treatment.


2017 ◽  
Vol 30 (23) ◽  
pp. 9527-9537 ◽  
Author(s):  
In-Hong Park ◽  
Seung-Ki Min

On a subdaily time scale, the intensities of extreme precipitation are observed to increase with temperature at a rate exceeding water vapor constraints determined by the Clausius–Clapeyron (C-C) relationship. This so-called super C-C scaling has been suggested to occur as a result of 1) the statistical effect that involves the transition of precipitation types from stratiform to convective events and 2) the physical effect by which the convective process itself can overcome the thermodynamic limitation. This study examines these two mechanisms for the super C-C relationship using in situ observations in South Korea for a recent 35-yr period, focusing on the role of convective rainfall. Scaling results show that hourly extreme precipitation undergoes a transition from a C-C rate to a super C-C rate at around 20°C, supporting the statistical effect. The transition temperature observed in South Korea is, however, much higher than in European regions (12°C), which seems to be due to the climatologically lower frequency of convective events in South Korea than in Europe. Nevertheless, the threshold fraction of convective precipitation when the scaling transition starts to occur is found to very similar between two regions, around 0.2, indicating the important role of convective events in shaping the scaling. On the other hand, convective extreme precipitation alone exhibits a super C-C scaling, suggesting that the physical effect is also at work in South Korea. Also, the scaling shows a robust peaklike shape with maximum precipitation intensity near 24°C, which is closely linked with moisture limitation at high temperature, supporting the previous findings.


2004 ◽  
Vol 61 (21) ◽  
pp. 2544-2558 ◽  
Author(s):  
Kathleen K. Crahan ◽  
Dean A. Hegg ◽  
David S. Covert ◽  
Haflidi Jonsson ◽  
Jeffrey S. Reid ◽  
...  

Abstract Although the importance of the aerosol contribution to the global radiative budget has been recognized, the forcings of aerosols in general, and specifically the role of the organic component in these forcings, still contain large uncertainties. In an attempt to better understand the relationship between the background forcings of aerosols and their chemical speciation, marine air samples were collected off the windward coast of Oahu, Hawaii, during the Rough Evaporation Duct project (RED) using filters mounted on both the Twin Otter aircraft and the Floating Instrument Platform (FLIP) research platform. Laboratory analysis revealed a total of 17 species, including 4 carboxylic acids and 2 carbohydrates that accounted for 74% ± 20% of the mass gain observed on the shipboard filters, suggesting a possible significant unresolved organic component. The results were correlated with in situ measurements of particle light scattering (σsp) at 550 nm and with aerosol hygroscopicities. Principal component analysis revealed a small but ubiquitous pollution component affecting the σsp and aerosol hygroscopicity of the remote marine air. The Princeton Organic-Electrolyte Model (POEM) was used to predict the growth factor of the aerosols based upon the chemical composition. This output, coupled with measured aerosol size distributions, was used to attempt to reproduce the observed σsp. It was found that while the POEM model was able to reproduce the expected trends when the organic component of the aerosol was varied, due to large uncertainties especially in the aerosol sizing measurements, the σsp predicted by the POEM model was consistently higher than observed.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Deenaz Zaidi ◽  
Jeffrey K. Turner ◽  
Michelle A. Durst ◽  
Graham F. Wagner

The polypeptide hormone stanniocalcin-1 (STC-1) is widely expressed in mammals and signals both locally and systemically. In many tissues STC-1 ligand is sequestered by target cell organelles (mitochondria, nuclei, and cholesterol lipid droplets) to exert diverse biological effects. Most notably, STC-1 serves as an uncoupler of oxidative phosphorylation in liver, muscle, and kidney mitochondria. The present paper describes the identification of STC-1 receptors in mouse pancreatic β cells and the discovery that the ligand co-localizes with insulin in pancreatic β cells. In situ hybridization (ISH) analysis subsequently revealed that pancreatic β cells were the source of the ligand. Intriguingly however, all ISH signal was localized over putative islet cell nuclei as opposed to the cell cytoplasm. Real-time qPCR and agarose gel electrophoresis revealed that the STC-1 amplicon generated from islet cell total RNA was the same size as that from kidney. However, relative levels of STC-1 gene expression were >100-fold lower in islets than those in kidney tissue. Collectively, these findings are indicative of a local STC-1 signalling pathway in pancreatic β cells. The role of STC-1 in this context remains to be established, but it could very well entail the regulation of β cell mitochondria membrane potential which is an integral aspect of regulated insulin release. Interestingly, STC-1 immunoreactivity was not evident in embryonic pancreatic islets, suggesting that ligand synthesis may only commence postnatally.


2011 ◽  
Vol 301 (1) ◽  
pp. R97-R104 ◽  
Author(s):  
Iban Seiliez ◽  
Nathalie Sabin ◽  
Jean-Charles Gabillard

In mammals, much evidence has demonstrated the important role of myostatin (MSTN) in regulating muscle mass and identified the transcription factor forkhead box O (FoxO) 1 as a key regulator of its gene expression during atrophy. However, in trout, food deprivation leads to muscle atrophy without an increase of the expression of mstn genes in the muscle. We therefore studied the relationship between FoxO1 activity and the expression of both mstn genes ( mstn1a and mstn1b) in primary culture of trout myotubes. To this aim, two complementary studies were undertaken. In the former, FoxO1 protein activity was modified with insulin-like growth factor-I (IGF-I) treatment, and the consequences on the expression of both mstn genes were monitored. In the second experiment, the expression of both studied genes was modified with growth hormone (GH) treatment, and the activation of FoxO1 protein was investigated. We found that IGF-I induced the phosphorylation of FoxO1 and FoxO4. Moreover, under IGF-I stimulation, FoxO1 was no longer localized in the nucleus, indicating that this growth factor inhibited FoxO1 activity. However, IGF-I treatment had no effect on mstn1a and mstn1b expression, suggesting that FoxO1 would not regulate the expression of mstn genes in trout myotubes. Furthermore, the treatment of myotubes with GH decreased the expression of both mstn genes but has no effect on the phosphorylation of FoxO1, FoxO3, and FoxO4 nor on the nuclear translocation of FoxO1. Altogether, our results showed that mstn1a and mstn1b expressions were not associated with FoxO activity, indicating that FoxO1 is likely not a key regulator of mstn genes in trout myotubes.


2021 ◽  
Vol 15 (1) ◽  
pp. 367-376
Author(s):  
Julián F. Beltran ◽  
SM Viafara-Garcia ◽  
Alberto P. Labrador ◽  
Johan Basterrechea

Chronic periodontal disease and oral bacteria dysbiosis can lead to the accumulation of genetic mutations that eventually stimulate Oral Squamous Cell Cancer (OSCC). The annual incidence of OSCC is increasing significantly, and almost half of the cases are diagnosed in an advanced stage. Worldwide there are more than 380,000 new cases diagnosed every year, and a topic of extensive research in the last few years is the alteration of oral bacteria, their compositional changes and microbiome. This review aims to establish the relationship between bacterial dysbiosis and OSCC. Several bacteria implicated in periodontal disease, including Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, and some Streptococcus species, promote angiogenesis, cell proliferation, and alteration in the host defense process; these same bacteria have been present in different stages of OSCC. Our review showed that genes involved in bacterial chemotaxis, the lipopolysaccharide (LPS) of the cell wall membrane of gram negatives bacteria, were significantly increased in patients with OSCC. Additionally, some bacterial diversity, particularly with Firmicutes, and Actinobacteria species, has been identified in pre-cancerous stage samples. This review suggests the importance of an early diagnosis and more comprehensive periodontal therapy for patients by the dental care professional.


1990 ◽  
Vol 41 (5) ◽  
pp. 581 ◽  
Author(s):  
RL Oliver

Apparent and inherent optical properties were determined for a range of water types in the Murray- Darling basin by using a combination of field and laboratory techniques. The absorption coefficient was calculated directly from in situ irradiance measurements of photosynthetically active radiation, whereas the scattering coefficient was determined from the irradiance measurements in conjunction with published nomograms relating the apparent and inherent optical properties. The validity of the nomograms for use in these waters was confirmed by comparing values of the average cosine calculated directly from in situ measurements with those estimated from the nomograms. These were closely correlated except for sites with chlorophyll concentrations greater than 200 mg m-3. The scattering coefficients estimated from the nomograms were approximately numerically equal to the turbidity in nephelometric turbidity units, but the variability of the relationship made it unsuitable for checking the validity of the nomograms. The relative role of dissolved and particulate components in the absorption and scattering of irradiance was examined by using spectrophotometry and linear regression of inherent optical properties on concentrations of the components. Estimates of specific absorption and scattering coefficients for algae, non-chlorophyllous suspended particles, and dissolved yellow colour were comparable to similar coefficients reported in the literature. The relative importance of these components to absorption and scattering varied considerably between sites and demonstrated the need for information on inherent optical properties in understanding the factors causing changes in optical water quality.


2020 ◽  
Vol 106 (6) ◽  
pp. NP67-NP72
Author(s):  
Ileana Carnevali ◽  
Eleonora Di Lauro ◽  
Valeria Pensotti ◽  
Nora Sahnane ◽  
Eleonora Leoni ◽  
...  

Introduction: The relationship between endocervical cancer and cancer susceptibility syndromes is not yet fully understood. We present 2 cases of endocervical cancer: 1 arising in a patient carrier with a pathogenic BRCA1 variant and the second detected in a Lynch syndrome family carrying the MSH2 germline pathogenic variant. Case description: Somatic analyses including loss of heterozygosity and fluorescent in situ hybridization demonstrated that the second hit in patient 1 is BRCA1-related. Mismatch repair somatic analyses in the second family demonstrated that the endocervical cancers of patient 2 and of her sister are MSH2-related. These data confirm the relationship between the pathogenesis of endocervical cancer and the presence of germline BRCA1 and MSH2 mutations. Conclusions: Our study confirms that gynecologic cancers including rare entities such as non–human papillomavirus–related endocervical cancer (NHPVA) are sentinels for inherited cancer syndromes. Endocervical cancer NHPVAs might be considered for cancer genetic counseling in order to improve cancer prevention. For this reason, the role of pathologists is particularly important for the correct identification of the cervical tumor site.


1998 ◽  
Vol 53 (5-6) ◽  
pp. 352-358 ◽  
Author(s):  
Yutaka Takeuchi ◽  
Hiroshi Ohashi ◽  
Paul J. Birckbichler ◽  
Takashi Ikejim

Abstract Tissue type (type 2) transglutaminase (TGase, EC 2.3.2.13) has been implicated in various cellular processes including cell death. In order to better understand the role of this enzyme in cell death, human melanocytic A375-S2 cells were treated with sphingosine, a cell-signaling mediator. During the rapid onset of cytotoxicity caused by this lipidic agent, tissue TGase was translocated from the cytoplasm to the cell nuclei. This observation was further remarked in relevance to its previously undescribed activity for DNA degradation. The DNA hydrolytic activity associated with tissue TGase was dependent on Mg2+ in contrast to the Ca2+ requirement for the classical cross-linking acrivity of TGase, and was inhibited by Zn2+. Based on the results shown here, we propose a novel aspect of tissue TGase in cell death.


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