scholarly journals Differential Expression of CADM1 in Gastrointestinal Stromal Tumors of Different Sites and with Different Gene Abnormalities

2021 ◽  
Vol 27 ◽  
Author(s):  
Jiayin Yuan ◽  
Takako Kihara ◽  
Neinei Kimura ◽  
Yuka Hashikura ◽  
Mizuka Ohkouchi ◽  
...  

Gastrointestinal stromal tumor (GIST), the most common mesenchymal tumor of the human gastrointestinal tract, differentiating toward the interstitial cell of Cajal (ICC), arises predominantly in the stomach and small intestine. Small intestinal GISTs appear to have worse prognosis than gastric GISTs. In a pilot study of a cDNA expression chip using several GISTs, we found that Cell Adhesion Molecule 1 (CADM1), which could contribute to tumor growth and infiltration, is expressed more strongly in small intestinal GISTs than gastric GISTs. In the present study, we examined CADM1 expression in GISTs of different sites and with different gene abnormalities using a large number of gastric and small intestinal GISTs. First, immunoblotting confirmed significantly higher CADM1 expression in small intestinal GISTs with exon 11 c-kit mutation than gastric GISTs with exon 11 c-kit mutation. Real-time PCR also revealed that small intestinal GISTs with exon 11 c-kit mutation showed significantly higher CADM1 mRNA than gastric GISTs with exon 11 c-kit mutation. Although most small intestinal GISTs showed high CADM1 mRNA expression regardless of gene abnormality types, different CADM1 expression was detected between gastric GISTs with c-kit mutation and those with PDGFRA mutation. Immunohistochemistry showed that many small intestinal GISTs were CADM1-positive but most gastric GISTs CADM1-negative or -indefinite. In the normal gastric and small intestinal walls, immunoreactivity of CADM1 was detected only in nerves, but neither in gastric ICCs nor small intestinal ICCs, indicating that the high CADM1expression in small intestinal GISTs might be acquired during tumorigenesis. Different CADM1 expression between gastric and small intestinal GISTs might be related to different prognoses between them. Further functional experiments are needed to elucidate the role of CADM1 on GIST biology, and there is a possibility that targeting therapy against CADM1 has a preventive effect for tumor spreading in small intestinal GISTs.

2020 ◽  
Author(s):  
Carl Heneghan ◽  
Elizabeth Spencer ◽  
Jon Brassey ◽  
Tom Jefferson

Background How SARS-CoV-2 is transmitted is of key public health importance. SARS-CoV-2 has been detected in the feces of some Covid-19 patients which suggests the possibility that the virus could additionally be transmitted via the orofecal route. Methods This review is part of an Open Evidence Review on Transmission Dynamics of Covid-19. We conduct ongoing searches using LitCovid, medRxiv, Google Scholar and Google for Covid-19; assess study quality based on five criteria and report important findings on an ongoing basis. Where necessary authors are contacted for further details or clarification on the content of their articles. Results We found 59 studies: nine reviews and 51 primary studies or reports (one cohort study also included a review) examining the potential role of orofecal transmission of SARS-CoV-2. Half (n=29) were done in China. Thirty seven studies reported positive fecal samples for SARS-CoV-2 based on RT-PCR results (n=1,034 patients). Six studies reported isolating the virus from fecal samples of nine patients, one study isolated the virus from rectal tissue and one laboratory study found that SARS-CoV-2 productively infected human small intestinal organoids. Eleven studies report on fecal samples found in sewage, and two sampled bathrooms and toilets. Conclusions Various observational and mechanistic evidence support the hypothesis that SARS-CoV-2 can infect and be shed from the human gastrointestinal tract. Policy should emphasize the importance of strict personal hygiene measures, and chlorine-based disinfection of surfaces in locations where there is presumed or known SARS-CoV-2 activity.


2001 ◽  
Vol 120 (5) ◽  
pp. A534-A534
Author(s):  
A ZHAO ◽  
D MULLOY ◽  
J URBANJR ◽  
W GAUSE ◽  
T SHEADONOHUE

2016 ◽  
Vol 82 (6) ◽  
pp. 518-521 ◽  
Author(s):  
Mohd Raashid Sheikh ◽  
Houssam Osman ◽  
Susannah Cheek ◽  
Shenee Hunter ◽  
Dhiresh Rohan Jeyarajah

Treatment of gall bladder cancer (GBC) has traditionally been viewed with pessimism and lymph node positivity has been associated with worse prognosis. The aim of this study is to analyze the role of radical cholecystectomy in T2 tumors. All patients who underwent surgery for GBC between September 2005 and June 2014 were identified retrospectively. Data collected included clinical presentation, operative findings, and histopathological data. Twenty-five patients had incidental GBC diagnosis after cholecystectomy. Ten patients were T2 on initial cholecystectomy pathology and all underwent radical resection. Two patients were N1 on initial cholecystectomy pathology. Four were upstaged to N1 and two patients were upstaged to T3 after further surgery. Overall, 60 per cent patients with T2 disease had node positivity and 60 per cent were upstaged by further surgery. Eleven patients were diagnosed on imaging. Four of these patients were unresectable and six were either stage T3 or higher or node positive. Sixty per cent of T2 GBC was node positive and 60 per cent were upstaged with radical cholecystectomy. This finding supports the call for radical resection in patients with incidental diagnosis of T2 tumor on cholecystectomy. This study also emphasizes the role of radical surgery in accurate T staging.


2021 ◽  
Vol 22 (14) ◽  
pp. 7494
Author(s):  
Przemyslaw Wielgat ◽  
Katarzyna Niemirowicz-Laskowska ◽  
Agnieszka Z. Wilczewska ◽  
Halina Car

The cell surface is covered by a dense and complex network of glycans attached to the membrane proteins and lipids. In gliomas, the aberrant sialylation, as the final stage of glycosylation, is an important regulatory mechanism of malignant cell behavior and correlates with worse prognosis. Better understanding of the role of sialylation in cellular and molecular processes opens a new way in the development of therapeutic tools for human brain tumors. According to the recent clinical observation, the cellular heterogeneity, activity of brain cancer stem cells (BCSCs), immune evasion, and function of the blood–brain barrier (BBB) are attractive targets for new therapeutic strategies. In this review, we summarize the importance of sialic acid-modified nanoparticles in brain tumor progression.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yanpeng Ding ◽  
Nuomin Liu ◽  
Mengge Chen ◽  
Yulian Xu ◽  
Sha Fang ◽  
...  

Abstract Background BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA patients can benefit from ICT. MT1L is a pseudogene, and a previous study suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been determined. Methods Data were collected from TCGA, and logistic regression, Kaplan-Meier plotter, and multivariate Cox analysis were performed to demonstrate the correlation between the pseudogene MT1L and the prognosis of BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. Additionally, GSEA was performed to elucidate the potential biological function. Results The expression of MT1L was decreased in BLCA. Additionally, MT1L was positively correlated with immune cells, such as Tregs (ρ = 0.708) and MDSCs (ρ = 0.664). We also confirmed that MT1L is related to typical markers of immune cells, such as PD-1 and CTLA-4. In addition, a high MT1L expression level was associated with the advanced T and N and high grade in BLCA. Increased expression of MT1L was significantly associated with shorter OS times of BLCA patients (p < 0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor in BLCA. Conclusion Collectively, our findings demonstrated that the pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and is an independent prognostic biomarker in BLCA.


2021 ◽  
Vol 9 (3) ◽  
pp. 509
Author(s):  
Amanda Carroll-Portillo ◽  
Henry C. Lin

Conventional phage therapy using bacteriophages (phages) for specific targeting of pathogenic bacteria is not always useful as a therapeutic for gastrointestinal (GI) dysfunction. Complex dysbiotic GI disorders such as small intestinal bowel overgrowth (SIBO), ulcerative colitis (UC), or Crohn’s disease (CD) are even more difficult to treat as these conditions have shifts in multiple populations of bacteria within the microbiome. Such community-level structural changes in the gut microbiota may require an alternative to conventional phage therapy such as fecal virome transfer or a phage cocktail capable of targeting multiple bacterial species. Additionally, manipulation of the GI microenvironment may enhance beneficial bacteria–phage interactions during treatment. Mucin, produced along the entire length of the GI tract to protect the underlying mucosa, is a prominent contributor to the GI microenvironment and may facilitate bacteria–phage interactions in multiple ways, potentially serving as an adjunct during phage therapy. In this review, we will describe what is known about the role of mucin within the GI tract and how its facilitation of bacteria–phage interactions should be considered in any effort directed at optimizing effectiveness of a phage therapy for gastrointestinal dysbiosis.


Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1617
Author(s):  
Pierluigi Scalia ◽  
Antonio Giordano ◽  
Caroline Martini ◽  
Stephen J. Williams

Insulin receptor (IR) and IR-related signaling defects have been shown to trigger insulin-resistance in insulin-dependent cells and ultimately to give rise to type 2 diabetes in mammalian organisms. IR expression is ubiquitous in mammalian tissues, and its over-expression is also a common finding in cancerous cells. This latter finding has been shown to associate with both a relative and absolute increase in IR isoform-A (IR-A) expression, missing 12 aa in its EC subunit corresponding to exon 11. Since IR-A is a high-affinity transducer of Insulin-like Growth Factor-II (IGF-II) signals, a growth factor is often secreted by cancer cells; such event offers a direct molecular link between IR-A/IR-B increased ratio in insulin resistance states (obesity and type 2 diabetes) and the malignant advantage provided by IGF-II to solid tumors. Nonetheless, recent findings on the biological role of isoforms for cellular signaling components suggest that the preferential expression of IR isoform-A may be part of a wider contextual isoform-expression switch in downstream regulatory factors, potentially enhancing IR-dependent oncogenic effects. The present review focuses on the role of isoform- and paralog-dependent variability in the IR and downstream cellular components playing a potential role in the modulation of the IR-A signaling related to the changes induced by insulin-resistance-linked conditions as well as to their relationship with the benign versus malignant transition in underlying solid tumors.


2013 ◽  
pp. 23-25
Author(s):  
P. Faggioli ◽  
S. Finazzi ◽  
E. Vicenzi ◽  
L. Giani ◽  
M. Rondena ◽  
...  

BACKGROUND Scleroderma, when complicated with pulmonary hypertension (PHT), presents a worse prognosis; recently treatment with new drugs seems to offer good perspectives, especially in early diagnosis and treatment. The standard approach for diagnosing PHT consists in measurement of the pulmonary artery pressure (PAP) by means of echodoppler. AIM OF INVESTIGATION Aim of this work is evaluating the significance of the NT-proBNP parameter, matched to echodoppler, in diagnosing scleroderma PHT. MATERIALS AND METHODS Sixty (60) patients, who came to observation for progressive systemic sclerosis underwent echodoppler in order to measure the PAP (normal values up to 30 mmHg). NT-proBNP was determined on serum sample using ECLIA method by Modular E170 (Roche Diagnostics); manufacturer reference values for age and gender were used. Forty-three (43) patients underwent a further NT-proBNP sampling 5 days later in order to assess parameter stability. RESULTS PHT and non- PHT patients showed statistically different (p < 0,001) medians (126 vs 69 pg/ml). No pathologic values of NT-proBNP were measured in the group with PAP < 30 mmHg, while 27% of cases who had PAP between 30 and 40 showed pathologic concentrations. The positivity ratio increases to 57% in patients showing PAP > 40 mmHg. No relevant correlation (r = 0,2) was found between PAP and NT-proBNP. Mean average between the two sampling groups was 31%. CONCLUSIONS In scleroderma patients, combination of NT-proBNP and PAP seems to improve the diagnosis of pulmonary hypertension, especially in presence of borderline pulmonary pressure values. We therefore propose the biochemical observation of NT-proBNP when PAP is > 30 mmHg and in monitoring the evolution of the pathology.


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