scholarly journals Targeting the Oncogenic FGF-FGFR Axis in Gastric Carcinogenesis

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 637 ◽  
Author(s):  
Jinglin Zhang ◽  
Patrick M. K. Tang ◽  
Yuhang Zhou ◽  
Alfred S. L. Cheng ◽  
Jun Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Therapeutic Strategy ◽  
Somatic Mutations ◽  
Synergistic Effects ◽  
Gastric Carcinogenesis ◽  
Wide Spread ◽  
Oncogenic Pathways ◽  
The World ◽  
Clinical Correlations

Gastric cancer (GC) is one of the most wide-spread malignancies in the world. The oncogenic role of signaling of fibroblast growing factors (FGFs) and their receptors (FGFRs) in gastric tumorigenesis has been gradually elucidated by recent studies. The expression pattern and clinical correlations of FGF and FGFR family members have been comprehensively delineated. Among them, FGF18 and FGFR2 demonstrate the most prominent driving role in gastric tumorigenesis with gene amplification or somatic mutations and serve as prognostic biomarkers. FGF-FGFR promotes tumor progression by crosstalking with multiple oncogenic pathways and this provides a rational therapeutic strategy by co-targeting the crosstalks to achieve synergistic effects. In this review, we comprehensively summarize the pathogenic mechanisms of FGF-FGFR signaling in gastric adenocarcinoma together with the current targeted strategies in aberrant FGF-FGFR activated GC cases.

scholarly journals Targeting the PI3K and MAPK pathways to improve response to HER2-targeted therapies in HER2-positive gastric cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
M. Janusz Mezynski ◽  
Angela M. Farrelly ◽  
Mattia Cremona ◽  
Aoife Carr ◽  
Clare Morgan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Somatic Mutations ◽  
Trastuzumab Resistance ◽  
Her2 Positive ◽  
Erbb Family ◽  
Gastric Tumour ◽  
Pi3k Signalling ◽  
Trial Setting

Abstract Background Aberrant PI3K signalling is implicated in trastuzumab resistance in HER2-positive gastric cancer (GC). The role of PI3K or MEK inhibitors in sensitising HER2-positive GCs to trastuzumab or in overcoming trastuzumab resistance is unclear. Methods Using mass spectrometry-based genotyping we analysed 105 hotspot, non-synonymous somatic mutations in PIK3CA and ERBB-family (EGFR, ERBB2, ERBB3 and ERBB4) genes in gastric tumour samples from 69 patients. A panel of gastric cell lines (N87, OE19, ESO26, SNU16, KATOIII) were profiled for anti-proliferative response to the PI3K inhibitor copanlisib and the MEK1/2 inhibitor refametinib alone and in combination with anti-HER2 therapies. Results Patients with HER2-positive GC had significantly poorer overall survival compared to HER2-negative patients (15.9 months vs. 35.7 months). Mutations in PIK3CA were only identified in HER2-negative tumours, while ERBB-family mutations were identified in HER2-positive and HER2-negative tumours. Copanlisib had anti-proliferative effects in 4/5 cell lines, with IC50s ranging from 23.4 (N87) to 93.8 nM (SNU16). All HER2-positive cell lines except SNU16 were sensitive to lapatinib (IC50s 0.04 µM–1.5 µM). OE19 cells were resistant to trastuzumab. The combination of lapatinib and copanlisib was synergistic in ESO-26 and OE-19 cells (ED50: 0.83 ± 0.19 and 0.88 ± 0.13, respectively) and additive in NCI-N87 cells (ED50:1.01 ± 0.55). The combination of copanlisib and trastuzumab significantly improved growth inhibition compared to either therapy alone in NCI-N87, ESO26 and OE19 cells (p < 0.05). Conclusions PI3K or MEK inhibition alone or in combination with anti-HER2 therapy may represent an improved treatment strategy for some patients with HER2-positive GC, and warrants further investigation in a clinical trial setting.

scholarly journals Skin and Gut Microbiome in Psoriasis: Gaining Insight Into the Pathophysiology of It and Finding Novel Therapeutic Strategies

2020 ◽  
Vol 11 ◽  
Author(s):  
Lihui Chen ◽  
Jie Li ◽  
Wu Zhu ◽  
Yehong Kuang ◽  
Tao Liu ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Therapeutic Strategies ◽  
Intestinal Microbiome ◽  
Core Microbiome ◽  
The Core ◽  
The World ◽  
Novel Therapeutic Strategies ◽  
Insight Into ◽  
Gaining Insight

Psoriasis affects the health of myriad populations around the world. The pathogenesis is multifactorial, and the exact driving factor remains unclear. This condition arises from the interaction between hyperproliferative keratinocytes and infiltrating immune cells, with poor prognosis and high recurrence. Better clinical treatments remain to be explored. There is much evidence that alterations in the skin and intestinal microbiome play an important role in the pathogenesis of psoriasis, and restoration of the microbiome is a promising preventive and therapeutic strategy for psoriasis. Herein, we have reviewed recent studies on the psoriasis-related microbiome in an attempt to confidently identify the “core” microbiome of psoriasis patients, understand the role of microbiome in the pathogenesis of psoriasis, and explore new therapeutic strategies for psoriasis through microbial intervention.

scholarly journals Helicobacter pylori Infection and Gastric Dysbiosis: Can Probiotics Administration Be Useful to Treat This Condition?

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Giovanni Bruno ◽  
Giulia Rocco ◽  
Piera Zaccari ◽  
Barbara Porowska ◽  
Maria Teresa Mascellino ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Lymphoid Tissue ◽  
Therapy Resistance ◽  
Mechanisms Of Action ◽  
Pathogenic Agent ◽  
The World ◽  
Gastric Microbiota ◽  
Common Infections

Helicobacter pylori (Hp) is responsible for one of the most common infections in the world. The prevalence exceeds 50% of the population in developing countries, and approximately one-third of the adults are colonized in North Europe and North America. It is considered a major pathogenic agent of chronic gastritis, peptic ulcer, atrophic gastritis, gastric cancer, and mucosa-associated lymphoid tissue lymphoma (MALT). Hp colonization modifies the composition of gastric microbiota that could drive the development of gastric disorders. Currently, an emerging problem in Hp treatment is represented by the increasing rate of antimicrobial therapy resistance. In this context, the search for adjuvant agents can be very useful to overcome this issue and probiotics administration can represent a valid option. The aim of this review is to describe the gastric microbiota changes during Hp colonization, the mechanisms of action, and a possible role of probiotics in the treatment of this infection.

scholarly journals The Role of PPARγinHelicobacter pyloriInfection and Gastric Carcinogenesis

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Jong-Min Lee ◽  
Sung Soo Kim ◽  
Young-Seok Cho
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Current Knowledge ◽  
Mucosal Injury ◽  
Gastric Carcinogenesis ◽  
Etiologic Factor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
H Pylori

Peroxisome proliferator-activated receptorγ(PPARγ) is a nuclear receptor that is important in many physiological and pathological processes, such as lipid metabolism, insulin sensitivity, inflammation, cell proliferation, and carcinogenesis. Several studies have shown that PPARγplays an important role in gastric mucosal injury due toHelicobacter pylori(H. pylori). AsH. pyloriinfection is the main etiologic factor in chronic gastritis and gastric cancer, understanding of the potential roles of PPARγinH. pyloriinfection may lead to the development of a therapeutic target. In this paper, the authors discuss the current knowledge on the role of PPARγinH. pyloriinfection and its related gastric carcinogenesis.

Resurrecting Old Arguments: Responding to Four Essays

2005 ◽  
Vol 3 (2) ◽  
pp. 209-231 ◽  
Author(s):  
N. Wright
Keyword(s):  
Cognitive Processes ◽  
Early Church ◽  
Post Mortem ◽  
Wide Spread ◽  
Two Stage ◽  
Son Of God ◽  
Second Stage ◽  
Bodily Resurrection ◽  
The World

AbstractThe author is grateful for the attention given to his book The Resurrection of the Son of God by the four reviewers. David Bryan is right to highlight the Enoch literature as a more fertile source of resurrection ideas than the book allowed for; but he has overstated his objection. Granted that the stream of thought represented by resurrection is more diverse even than RSG allowed, the book's argument did not hinge on the wide spread of resurrection belief at the time but on the meaning of 'resurrection', i.e. a two-stage post-mortem existence, the second stage being a new embodiment. Bryan's suggested elevation of Enoch, Elijah and others as precursors of the exaltation of Jesus fails in that these figures neither die nor are resurrected. James Crossley's counter-proposal—resurrection stories grew from 'visions' which gave rise to the idea of an empty tomb as an attempt to 'vindicate' the 'ideas and beliefs of Jesus'—fails on several counts, not least because it ignores Jesus' kingdom-proclamation which was not the promulgation of ideas and beliefs but the announcement that Israel's God was going to do something that would claim his sovereignty over the world. Michael Goulder revives the highly contentious hypothesis that the early Church was polarized between the Jerusalem apostles, who believed in a non-bodily resurrection, and Pauline Christians for whom the resurrection was bodily. The claim that Mark 16.1-8 is full of contradictions and impossibilities is rejected. Larry Hurtado warns against downplaying the role of experience both in the Christian life and in describing the devotion and liturgy of the early Church. While cautioning against the use of the word 'metaphor' to mean 'less than fully real', I acknowledge the force of the argument, and suggest the cognitive processes I propose and the devotional life sketched by Hurtado are complementary.

scholarly journals The Free Improvisation Game: Performing John Zorn’s Cobra

2013 ◽  
Author(s):  
Dylan Van der Schyff
Keyword(s):  
Music Education ◽  
Wide Spread ◽  
Relevant Research ◽  
Music Psychology ◽  
Free Improvisation ◽  
Person Perspective ◽  
The World ◽  
And Performance ◽  
Musical Communication

The use of improvisation is wide spread in musical practice around the world. Nevertheless, Western academic circles tend to ignore this ubiquitous activity and have maintained a focus on composition and interpretation. This is beginning to change, however, and the role of improvisation in performance and music education is receiving an increasing amount of attention. This paper contributes to this project by examining the practice of ‘free improvisation’ in a large ensemble context. A rehearsal and performance of John Zorn’s Cobra––a ‘game’ piece for improvisers––is analyzed from a first-person perspective; relevant research in music psychology is considered; and suggestions are made with regard to how we may better understand the nature of musical communication in improvised contexts. Pedagogical applications are also considered.

scholarly journals Interdisciplinary insights into the link between gut microbiome and gastric carcinogenesis—what is currently known?

2021 ◽  
Author(s):  
Karolina Kaźmierczak-Siedlecka ◽  
Agnieszka Daca ◽  
Giandomenico Roviello ◽  
Martina Catalano ◽  
Karol Połom
Keyword(s):  
Gastric Cancer ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Gastric Carcinogenesis ◽  
Point Of View ◽  
Molecular Techniques ◽  
Nitroso Compounds ◽  
Gastric Microbiota ◽  
Development Of Gastric Cancer

AbstractCurrently, gastric cancer is one of the leading death-related cancer globally. The etiopathogenesis of gastric cancer is multifactorial and includes among others dysbiotic alterations of gastric microbiota. Molecular techniques revealed that stomach is not a sterile organ and it is resides with ecosystem of microbes. Due to the fact that the role of Helicobacter pylori infection in development of gastric cancer is established and well-studied, this paper is mainly focused on the role of other bacterial as well as viral and fungal gut microbiota imbalance in gastric carcinogenesis. Notably, not only the composition of gastric microbiota may play an important role in development of gastric cancer, but also its activity. Microbial metabolites, such as short-chain fatty acids, polyamines, N-nitroso compounds, and lactate, may significantly affect gastric carcinogenesis. Therefore, this paper discussed aforementioned aspects with the interdisciplinary insights (regarding also immunological point of view) into the association between gut microbiome and gastric carcinogenesis based on up-to-date studies.

scholarly journals The role of perioperative radiotherapy in gastric cancer

2012 ◽  
Vol 6 (2) ◽  
pp. 23 ◽  
Author(s):  
Thales Paulo Batista ◽  
Lucas Marque De Mendonça ◽  
Ana Luiza Fassizoli-Fonte
Keyword(s):  
Gastric Cancer ◽  
Therapeutic Strategy ◽  
Multimodal Therapy ◽  
Early Stage ◽  
Locally Advanced ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Locally Advanced Tumors ◽  
Related Mortality

Gastric cancer is one of the most common neoplasms and a main cause of cancer-related mortality worldwide. Surgery remains the mainstay for cure and is considered for all patients with potentially curable disease. However, despite the fact that surgery alone usually leads to favorable outcomes in early stage disease, late diagnosis usually means a poor prognosis. In these settings, multimodal therapy has become the established treatment for locally advanced tumors, while the high risk of locoregional relapse has favored the inclusion of radiotherapy in the comprehensive therapeutic strategy. We provide a critical, non-systematic review of gastric cancer and discuss the role of perioperative radiation therapy in its treatment.

scholarly journals Types of Gastric Carcinomas

2018 ◽  
Vol 19 (12) ◽  
pp. 4109 ◽  
Author(s):  
Helge Waldum ◽  
Reidar Fossmark
Keyword(s):  
Gastric Cancer ◽  
Stem Cell ◽  
Gastric Carcinogenesis ◽  
Cell Of Origin ◽  
Gastric Carcinomas ◽  
Ecl Cell ◽  
Cells Of Origin ◽  
Increased Risk

Gastric cancer has reduced prevalence, but poor prognoses. To improve treatment, better knowledge of carcinogenesis and cells of origin should be sought. Stomach cancers are typically localized to one of the three mucosae; cardial, oxyntic and antral. Moreover, not only the stem cell, but the ECL cell may proliferate and give rise to tumours. According to Laurén, the classification of gastric carcinomas seems to reflect biological important differences and possible different cell of origin since the two subtypes, intestinal and diffuse, do not transform into the other and show different epidemiology. The stem cell probably gives rise to the intestinal type, whereas the ECL cell may be important in the diffuse type. Elevation of gastrin may be the carcinogenic factor for Helicobacter pylori as well as the recently described increased risk of gastric cancer due to proton pump inhibitor treatment. Therefore, it is essential to determine the role of the gastrin target cell, the ECL cell, in gastric carcinogenesis. Clinical trials with gastrin antagonists could improve prognoses in those with gastrin receptor positive tumours. However, further studies on gastric carcinomas applying relative available methods and with the highest sensitivity are warranted to improve our knowledge of gastric carcinogenesis.

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