Selective targeting of signet ring cell adenocarcinomas

Olgun, Abdullah

doi:10.1016/j.mehy.2019.109380

Cited by 5 publications

(6 citation statements)

References 23 publications

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“…Using next-generation sequencing, a unique profile of genes and biomarkers, including Kristen Rat Sarcoma Viral oncogene homolog wild-type (wt), PIK3CA wt, TP53, AT-rich interaction domain 1A, and CDH1, have been identified in SRCC compared with those of adenocarcinoma. 8,20 Investigations of potential therapeutics include the role of mucin proteins to selectively target SRCC 21 and clinical trials targeting a promising biomarker, Claudin18.2 (CLDN18.2). 22 Our case is the first to report colon SRCC metastasizing to the stomach and duodenum with raised coin-shaped lesions with central depression and erosion.…”

Section: Discussionmentioning

confidence: 99%

The Travels of Signet-Ring Cell Carcinoma: From Colon to Stomach and Duodenum

Tom,

Placone,

Yung

et al. 2023

ACG Case Rep J

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Colorectal cancer (CRC) metastasizing to the stomach and duodenum is rare. Even rarer is when the CRC subtype is signet-ring cell carcinoma (SRCC). Endoscopic findings of CRC metastasis to the stomach have been described as solitary and submucosal while duodenal metastasis has been observed to be exophytic. In this report, we describe a case of a middle-aged man with colon SRCC presenting with oral intolerance. He was found to have concurrent metastases to the stomach and duodenum and died 8 months after his SRCC diagnosis.

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Section: Discussionmentioning

confidence: 99%

The Travels of Signet-Ring Cell Carcinoma: From Colon to Stomach and Duodenum

Tom,

Placone,

Yung

et al. 2023

ACG Case Rep J

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“…Studies showed that the growth of the tumor can be effectively inhibited by MIF inhibitors and the inhibitory effect can be significantly enhanced by adding fluorine atoms (Dziedzic et al 2015 ). Similarly, other fluorinated compounds also exhibited stronger inhibitory effects than non-fluorinated compounds for distinct tumor cells, such as fluorinated green tea polyphenols, fluorinated largazole, fluorinated 4-thiazolidinone, fluorinated griseofulvin, fluorinated l -threonine, fluorinated aminophosphonite, and fluorinated docetaxel (Zhang et al 2019a ) (Stadlbauer et al 2018 ) (Makki et al 2019 ; Olgun 2019 ; Paguigan et al 2017 ; Sudileti et al 2019 ; Tang et al 2016 ). These results indicated that the incorporation of fluorine-substituted fragments into the inhibitor is an effective means to enhance the therapeutic effect of tumors.…”

Section: Applications Of Fluorinated Compoundsmentioning

confidence: 99%

Enzymatic synthesis of fluorinated compounds

Cheng

2021

Appl Microbiol Biotechnol

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Fluorinated compounds are widely used in the fields of molecular imaging, pharmaceuticals, and materials. Fluorinated natural products in nature are rare, and the introduction of fluorine atoms into organic compound molecules can give these compounds new functions and make them have better performance. Therefore, the synthesis of fluorides has attracted more and more attention from biologists and chemists. Even so, achieving selective fluorination is still a huge challenge under mild conditions. In this review, the research progress of enzymatic synthesis of fluorinated compounds is summarized since 2015, including cytochrome P450 enzymes, aldolases, fluoroacetyl coenzyme A thioesterases, lipases, transaminases, reductive aminases, purine nucleoside phosphorylases, polyketide synthases, fluoroacetate dehalogenases, tyrosine phenol-lyases, glycosidases, fluorinases, and multienzyme system. Of all enzyme-catalyzed synthesis methods, the direct formation of the C-F bond by fluorinase is the most effective and promising method. The structure and catalytic mechanism of fluorinase are introduced to understand fluorobiochemistry. Furthermore, the distribution, applications, and future development trends of fluorinated compounds are also outlined. Hopefully, this review will help researchers to understand the significance of enzymatic methods for the synthesis of fluorinated compounds and find or create excellent fluoride synthase in future research. Key points • Fluorinated compounds are distributed in plants and microorganisms, and are used in imaging, medicine, materials science . • Enzyme catalysis is essential for the synthesis of fluorinated compounds . • The loop structure of fluorinase is the key to forming the C-F bond . Supplementary Information The online version contains supplementary material available at 10.1007/s00253-021-11608-0.

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“…In this framework, a particular role is played by 4-fluoro-threonine (hereafter 4F-Thr), the only naturally occurring fluorinated amino acid. Quite recently, 4F-Thr has been proposed as an effective bioisostere for diagnostic and therapeutic use toward adenocarcinomas, one of the most malignant and aggressive cancers …”

Section: Introductionmentioning

confidence: 99%

“…The key role of fluorine in medicinal chemistry 1,2 is witnessed by its presence in a large number of drugs and its increasing importance in biological studies by the extensive use of 18 Flabeled molecules in positron emission tomography. 2,3 Indeed, the incorporation of fluorine in key positions of a molecular system can affect its conformational stability (see, e.g., the "gauche effect"), 1a,c,2,4 membrane permeability, metabolic stability, and binding affinity, 1a,c,2 thus representing a very useful and versatile tool for drug design.…”

Section: ■ Introductionmentioning

confidence: 99%

“…17 and therapeutic use toward adenocarcinomas, one of the most malignant and aggressive cancers. 18 While 4F-Thr was found in Streptomyces cattleya, 19 its relevance to metabolic pathways is still unknown, although the antimicrobial activity of 4F-Thr has been demonstrated. 20 Instead, the metabolic pathways leading to 4F-Thr have been fully elucidated, 21 with the key enzymatic role in fluorine incorporation being played by fluorinase, 22 which activates the fluoride ion for the conversion of S-adenosyl-L-methionine (SAM) into 5′-deoxy-5′-fluoroadenosine.…”

Section: ■ Introductionmentioning

confidence: 99%

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4-Fluoro-Threonine: From Diastereoselective Synthesis to pH-Dependent Conformational Equilibrium in Aqueous Solution

et al. 2021

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4-Fluoro-threonine, the only fluoro amino acid of natural origin discovered so far, is an interesting target for both synthetic and theoretical investigations. In this work, we lay the foundation for spectroscopic characterization of 4-fluoro-threonine. First, we report a diastereoselective synthetic route, which is suitable to produce synthetic material for experimental characterization. The addition of the commercially available ethyl isocyanoacetate to benzyloxyacetaldehyde led to the corresponding benzyloxy-oxazoline, which was hydrolyzed and transformed into ethyl (4S*,5S*)-5-hydroxymethyl-2-oxo-4-oxazolidinecarboxylate in a few steps. Fluorination with diethylamino sulfur trifluoride (DAST) afforded ethyl (4S*,5S*)-5-fluoromethyl-2-oxo-4-oxazolidinecarboxylate, which was deprotected to give the desired diastereomerically pure 4-fluoro-threonine, in 8–10% overall yield. With the synthetic material in our hands, acid–base titrations have been carried out to determine acid dissociation constants and the isoelectric point, which is the testing ground for the theoretical analysis. We have used machine learning coupled with quantum chemistry at the state-of-the-art to analyze the conformational space of 4-fluoro-threonine, with the aim of gaining insights from the comparison of computational and experimental results. Indeed, we have demonstrated that our approach, which couples a last-generation double-hybrid density functional including empirical dispersion contributions with a model combining explicit first-shell molecules and a polarizable continuum for describing solvent effects, provides results and trends in remarkable agreement with experiments. Finally, the conformational analysis applied to fluoro amino acids represents an interesting study for the effect of fluorine on the stability and population of conformers.

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Selective targeting of signet ring cell adenocarcinomas

Cited by 5 publications

References 23 publications

The Travels of Signet-Ring Cell Carcinoma: From Colon to Stomach and Duodenum

The Travels of Signet-Ring Cell Carcinoma: From Colon to Stomach and Duodenum

Enzymatic synthesis of fluorinated compounds

4-Fluoro-Threonine: From Diastereoselective Synthesis to pH-Dependent Conformational Equilibrium in Aqueous Solution

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