Gastric Adenocarcinoma: An Update on Genomics, Immune System Modulations, and Targeted Therapy

Author(s):  
Jeeyun Lee ◽  
Adam J. Bass ◽  
Jaffer A. Ajani

Gastric adenocarcinoma (GAC) is a global health burden on all societies, and it was the third-leading cause of cancer-related mortality in 2012, causing 723,000 deaths worldwide. The prognosis of patients with metastatic GAC remains poor, with a median overall survival of less than 1 year in patients treated with currently available therapies. A limited number of therapeutic agents is currently available. Recent additions to the armamentarium include trastuzumab and ramucirumab, which have shown some survival advantage when added to cytotoxic(s). Genomic analyses have defined various genotypes of GACs. The novel genomic knowledge can lead to discovery of novel targets and novel therapeutic agents. In this update, we focus on the current genomic data, targeted therapies including immune system modulators, and expand on HER2/neu testing and the use of agents against this target. Several other facets of GAC and its therapy are not to be included in this review but have been discussed elsewhere.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sinead M. O’Donovan ◽  
Ali Imami ◽  
Hunter Eby ◽  
Nicholas D. Henkel ◽  
Justin Fortune Creeden ◽  
...  

AbstractThe COVID-19 pandemic caused by the novel SARS-CoV-2 is more contagious than other coronaviruses and has higher rates of mortality than influenza. Identification of effective therapeutics is a crucial tool to treat those infected with SARS-CoV-2 and limit the spread of this novel disease globally. We deployed a bioinformatics workflow to identify candidate drugs for the treatment of COVID-19. Using an “omics” repository, the Library of Integrated Network-Based Cellular Signatures (LINCS), we simultaneously probed transcriptomic signatures of putative COVID-19 drugs and publicly available SARS-CoV-2 infected cell lines to identify novel therapeutics. We identified a shortlist of 20 candidate drugs: 8 are already under trial for the treatment of COVID-19, the remaining 12 have antiviral properties and 6 have antiviral efficacy against coronaviruses specifically, in vitro. All candidate drugs are either FDA approved or are under investigation. Our candidate drug findings are discordant with (i.e., reverse) SARS-CoV-2 transcriptome signatures generated in vitro, and a subset are also identified in transcriptome signatures generated from COVID-19 patient samples, like the MEK inhibitor selumetinib. Overall, our findings provide additional support for drugs that are already being explored as therapeutic agents for the treatment of COVID-19 and identify promising novel targets that are worthy of further investigation.


2021 ◽  
Vol 27 ◽  
Author(s):  
Young Nam Kwon ◽  
Yong-Jae Kim

: The gut and brain are linked via various bidirectional pathways, communicate with and affect each other. The interaction be-tween the gut-brain axis and the gut microbiota has attracted much attention in the development of hypertension. In this review, we have discussed the gut-brain-microbiota axis and its association with gut dysbiosis in terms of regulation of blood pressure using the autonomic nervous system, immune system, metabolites, hormones, and neurotransmitters. In addition, the treat-ments using microbiota that have been tried to date are briefly summarized. By understanding the mechanism by which gut-brain-microbiota regulates blood pressure, the novel targets for hypertension treatment or a new therapeutic approach us-ing the gut-brain-microbiota could be investigated.


Author(s):  
Faridatus Soleha

This study aims to describe the feelings of the characters in the novel Juang Notes by Fiersa Bersari and researchers analyze using personality theory originated by Ludwig Klages by focusing his study on the personality structure of feelings. Feeling is a process of someone accepting or rejecting something in life. This study uses a qualitative approach by using library techniques to obtain data that will produce a description of the words or sentences in the observed study. In the analysis of this research using the hermeutics technique, in the hermeutics technique there are several stages, namely reading the research object in this study in the form of a fighting journal, the second gives a mark on the data that has been obtained from the reading results, the third provides code or coding on the data that has been found, and the fourth is to analyze data that has been obtained from the object of research in accordance with the specified research focus. Novel Notes Juang by Fiersa Besari is a novel that can be used as an inspiration for readers in living life. Based on the results of the study it was found that in the Fighting Notes novel there is a feeling that is divided into inner activities and the level of clarity, inner activities in the novel in the form of fear and guilt while viewed from the level of clarity in the form of happiness, sadness and longing.


2015 ◽  
Vol 5 (3) ◽  
pp. 185-200
Author(s):  
Robert Z. Birdwell

Critics have argued that Elizabeth Gaskell's first novel, Mary Barton (1848), is split by a conflict between the modes of realism and romance. But the conflict does not render the novel incoherent, because Gaskell surpasses both modes through a utopian narrative that breaks with the conflict of form and gives coherence to the whole novel. Gaskell not only depicts what Thomas Carlyle called the ‘Condition of England’ in her work but also develops, through three stages, the utopia that will redeem this condition. The first stage is romantic nostalgia, a backward glance at Eden from the countryside surrounding Manchester. The second stage occurs in Manchester, as Gaskell mixes romance with a realistic mode, tracing a utopian drive toward death. The third stage is the utopian break with romantic and realistic accounts of the Condition of England and with the inadequate preceding conceptions of utopia. This third stage transforms narrative modes and figures a new mode of production.


Metahumaniora ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 100
Author(s):  
Muhamad Adji

AbstrakPenelitian ini bertujuan untuk memperoleh gambaran tentang sikap kebangsaananak muda Indonesia pada tiga novel populer yaitu Ali Topan Anak Jalanan karya TeguhEsha, Lupus: Makhluk Manis dalam Bis karya Hilman Hariwijaya, dan Balada Si Roy karya GolaGong. Alasan pemilihan objek penelitian di atas adalah karena ketiga novel tersebut memilikitingkat popularitas yang tinggi pada tiap zamannya sehingga membuat tokoh utamanyamenjadi representasi anak muda Indonesia pada zamannya masing-masing. Pertanyaanpertanyaanyang memandu tulisan ini adalah 1) Bagaimana keindonesiaan digambarkanpada ketiga novel tersebut dan 2) Bagaimana sikap kebangsaan direpresentasikan tokohanak muda pada ketiga novel tersebut. Dari hasil kajian didapatkan simpulan bahwasikap kebangsaan yang ditampilkan pada ketiga novel tersebut memiliki tingkatan yangberbeda-beda. Novel Ali Topan Anak Jalanan menunjukkan sikap kebangsaan dengan lebihkritis. Hegemoni orde Baru pada masa itu belum berhasil karena novel populer masihmenampilkan tokoh anak muda yang kritis dan cenderung memberontak terhadap nilainilaiideologi Orde Baru. Periode ’80-an menampilkan novel populer dengan tokoh anakmuda yang memiliki sikap kebangsaan yang terbelah. Pertama, anak muda yang dapatmenerima realitas yang dikontruksi Orde Baru, dengan menjalani sistem tersebut danmemposisikan dirinya sebagai bagian dari sistem tersebut. Hal itu direpresentasikan olehtokoh Lupus dalam novel Lupus: Makhluk Manis dalam Bis. Kedua, anak muda yang tidakdapat menerima realitas yang dikonstruksi Orde Baru, dengan cara keluar dari bagiansistem tersebut. Hal itu direpresentasikan oleh tokoh Roy dalam Balada Si Roy.Kata kunci: kebangsaan, anak muda, novel populer, Orde BaruAbstractThis study aims to obtain a picture of Indonesian nationalism in the three popularnovels that were Ali Topan Anak Jalanan by Teguh Esha, Lupus: Makhluk Manis dalam Bisby Hilman Hariwijaya, dan Balada Si Roy by Gola Gong. The reason for choosing the object ofresearch above is that all three novels are recognized to have high levels of popularity in eachera so that made the main characters became a representation of Indonesian youth at that time.The questions that guide the writing are 1) How Indonesianness described in the third novel?2) How does nationalism represented by youth in these three novels. From the study results isobtained the conclusion that nationalism is displayed on the third novel has a level different.Ali Topan Anak Jalanan show a nationalism more critically. The New Order’s hegemony atthat time has not been successful because the novel still showing a critical youth and tends torevolt against the ideological values of the New Order. The ‘80s period featured a popular novelwith a youth character who had a split nationalism. First, the youth who can accept the realitythat the New Order has constructed, with the system and position itself as part of the system.It was represented by the Lupus’s character in the Lupus: Makhluk Manis dalam Bis. Second,the youth who can not accept the facts constructed by the New Order, by going out from thatpart of the system. It was represented by Roy’s character in the Balada Si Roy.Keywords: nationalism, youth, popular novel, New Order


Author(s):  
Anatoly S. Kuprin ◽  
Galina I. Danilina

The purpose of this study is the analysis of limit situation in the narrative of war. The material of the study is the novel of Daniil Granin “My Lieutenant” and related texts. In the first part of the paper, the authors explore existing approaches to the term “limit situation” and similar concepts into scientific and philosophical traditions; limits of its applicability in literary studies and its relation to the categories of “narrative instances” and “event”. Proposed a literary-theoretical definition of the limit situation, which can be used in the analysis of fiction texts. Existing approaches to the examination of the situation of war are analyzed: philosophical-existential, psychoanalytic, sociological, literary. In the second part of the paper, the authors propose their method for analyzing limit situations in texts about war, which basis on existing approaches and preserves the text-centric principle of studying the structure of the story. Two interrelated areas of research have been identified: the study of war as a continuous limit situation in the intertextual aspect (the discourse of war); the study of limit situations (death, suffering, guilt, accident) in the narrative of war as part of a specific text. In the third part of the scientific work,the analysis of war as a continuous limit situation results in the study of the concept of “limit” (border) in a fiction text. The role of “limit” (border) concept in the texts about the war is studied, the possible types of limits in the discourse of war are examined. Limit situations in the narrative of war are analyzed on the basis of the novel “My Lieutenant” by Daniil Granin. A review of journalistic and scientific works about the novel revealed both the continuity and the differences between the novel and the “lieutenant” prose of the 20th century. An analysis of the limit situations in the novel revealed their key position in the narrative. These situations are independent of the fiction time, of the fluctuation of the point of view’; the function of the abstract author is to build the narrative as a “directive” immersion of the hero and narrator in these situations.


Author(s):  
Michael P. DeJonge

If, as Chapter 12 argues, much of Bonhoeffer’s resistance thinking remains stable even as he undertakes the novel conspiratorial resistance, what is new in his resistance thinking in the third phase? What receives new theological elaboration is the resistance activity of the individual, which in the first two phases was overshadowed by the resistance role played by the church. Indeed, as this chapter shows, Bonhoeffer’s conspiratorial activity is associated with what he calls free responsible action (type 6), and this is the action of the individual, not the church, in the exercise of vocation. As such, the conspiratorial activity is most closely related to the previously developed type 1 resistance, which includes individual vocational action in response to state injustice. But the conspiratorial activity differs from type 1 resistance as individual vocational action in the extreme situation.


2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Padmalochan Hembram

Abstract Background Coronavirus disease 19 is a viral infection caused by a novel coronavirus, SARS-CoV-2. It was first notified in Wuhan, China, is now spread into numerous part of the world. Thus, the world needs urgent support and encouragement to develop a vaccine or antiviral treatments to combat the atrocious outbreak. Main body of the abstract The origin of this virus is yet unknown; however, rapid transmission from human-to-human “Anthroponosis” has widely confirmed. The world is witnessing a continuous hike in SARS-CoV-2 infection. In light of the outbreak of coronavirus disease 19, we have aimed to highlight the basic and vital information about the novel coronavirus. We provide an overview of SARS-CoV-2 transmission, timeline and its pathophysiological properties which would be an aid for the development of therapeutic molecules and antiviral drugs. Immune system plays a crucial role in virus infection in order to control but may have dark side when becomes uncontrollable. The host and SARS-CoV-2 interaction describe how the virus exploits host machinery and how overactive host immune response can cause disease severity also addressed in this review. Short conclusion Safe and effective vaccines may be the game-changing tools, but in the near future wearing mask, washing hands at regular intervals, avoiding crowed, maintaining physical distancing and hygienic surrounding, must be good practices to reduce and break the transmission chain. Still, research is ongoing not only on how vaccines protect against disease, but also against infection and transmission.


Pathobiology ◽  
2021 ◽  
pp. 1-17
Author(s):  
Ana Margarida Barbosa ◽  
Alexandra Gomes-Gonçalves ◽  
António G. Castro ◽  
Egídio Torrado

The immune system plays a critical role in preventing cancer development and progression. However, the complex network of cells and soluble factor that form the tumor microenvironment (TME) can dictate the differentiation of tumor-infiltrating leukocytes and shift the antitumor immune response into promoting tumor growth. With the advent of cancer immunotherapy, there has been a reinvigorated interest in defining how the TME shapes the antitumor immune response. This interest brought to light the microbiome as a novel player in shaping cancer immunosurveillance. Indeed, accumulating evidence now suggests that the microbiome may confer susceptibility or resistance to certain cancers and may influence response to therapeutics, particularly immune checkpoint inhibitors. As we move forward into the age of precision medicine, it is vital that we define the factors that influence the interplay between the triad immune system-microbiota-cancer. This knowledge will contribute to improve the therapeutic response to current approaches and will unravel novel targets for immunotherapy.


2017 ◽  
Vol 45 (3) ◽  
pp. 581-609 ◽  
Author(s):  
Sarah J. OWENS ◽  
Justine M. THACKER ◽  
Susan A. GRAHAM

AbstractSpeech disfluencies can guide the ways in which listeners interpret spoken language. Here, we examined whether three-year-olds, five-year-olds, and adults use filled pauses to anticipate that a speaker is likely to refer to a novel object. Across three experiments, participants were presented with pairs of novel and familiar objects and heard a speaker refer to one of the objects using a fluent (“Look at the ball/lep!”) or disfluent (“Look at thee uh ball/lep!”) expression. The salience of the speaker's unfamiliarity with the novel referents, and the way in which the speaker referred to the novel referents (i.e., a noun vs. a description) varied across experiments. Three- and five-year-olds successfully identified familiar and novel targets, but only adults’ looking patterns reflected increased looks to novel objects in the presence of a disfluency. Together, these findings demonstrate that adults, but not young children, use filled pauses to anticipate reference to novel objects.


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