Imaging-guided interventions modulating portal venous flow: Evidence and controversies

Cannella, Roberto; Tselikas, Lambros; Douane, Frédéric; Cauchy, François; Rautou, Pierre‐Emmanuel; Durán, Rafael; Ronot, Maxime

doi:10.1016/j.jhepr.2022.100484

Cited by 2 publications

(1 citation statement)

References 160 publications

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“…Current CRC liquid biopsies rely on peripheral blood (14). However, physiologically, the portal venous carries approximately 75% of the total liver blood flow, connecting the colorectum and liver (15). Tumor cells metastasize and spread to the liver through portal venous blood (16,17).…”

Section: Introductionmentioning

confidence: 99%

5-hydroxymethylcytosine features of portal venous blood predict metachronous liver metastases of colorectal cancer and reveal phosphodiesterase 4 as a therapeutic target

Lin

Xu²,

Gao

et al. 2023

Preprint

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Metachronous liver metastases (MLM) are characterized by high incidence and high mortality in clinical colorectal cancer treatment. Currently traditional clinical methods cannot effectively predict and prevent the occurrence of metachronous liver metastasis in colorectal cancer. Based on 5hmC-Seal analysis of blood and tissue samples, this study found that portal venous blood was more relevant to tumor gDNA than peripheral blood. We performed a novel epigenetic liquid biopsy strategy using the 10 5hmC epigenetic alterations, to accurately distinguish MLM patients from patients without metastases. Among these epigenetic alterations, phosphodiesterase 4 (PDE4D) was highly increased in MLM patients and correlated with poor survival. Moreover, our studies demonstrated that PDE4D was a key metastasis-driven target for drug development. Interfering with the function of PDE4D significantly repressed liver metastases. Similarly, roflumilast, a PDE4 inhibitor approved for Chronic obstructive pulmonary disease (COPD) also inhibits liver metastases. Roflumilast treatment significantly inhibited the protein levels of HIF-1α, CCN2, p-AKT and p-ERK, thus suppressing metastases. To develop a more efficient PDE4D inhibitor and reduce the occurrence of adverse events, we also designed several new compounds based on 2-arylbenzofurans and discovered lead L11 with potent affinity for PDE4D and significant suppression of liver metastases. Interestingly, we further found that compound L11 was better tolerated in terms of emetic activity on beagle dogs than roflumilast. Summarily, our study provides a promising strategy for predicting metachronous liver metastasis and discovers roflumilast as a potential repurposed drug for inhibiting liver metastasis, which have the potential to benefit patients with CRC in the future.

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Section: Introductionmentioning

confidence: 99%

5-hydroxymethylcytosine features of portal venous blood predict metachronous liver metastases of colorectal cancer and reveal phosphodiesterase 4 as a therapeutic target

Lin

Xu²,

Gao

et al. 2023

Preprint

View full text Add to dashboard Cite

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Порталдық Гипертензия (Әдеби Шолу)

Tanabayeva¹,

АЛМАБАЕВ²,

Akhmad³

et al. 2023

Vestnik

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Портальная гипертензия является следствием повышенного давления воротной вены. Наиболее частой причиной портальной гипертензии является цирроз печени. В этих условиях увеличивается внутрипеченочное сопротивление, что приводит к повышению портального давления. В результате повышенного давления в воротной вене может возникнуть ряд осложнений, в том числе развитие варикозного расширения вен пищевода, желудка, асцит, печеночная энцефалопатия, а также появляется риск развития вторичных осложнений по отношению к дисфункции кровообращения, таких как гепаторенальный синдром, портопульмональный синдром и гепатопульмональный синдром. Увеличивая портальный кровоток, внутренностная вазодилатация еще больше усугубляет гипертензию, устанавливаются новые патогенные пути, которые могут привести к новым терапевтическим стратегиям. В этом обзоре описана классификация портальной гипертензии и ее осложнения. Рассматриваются вопросы диагностики и лечения различных клинических последствий. Portal hypertension is an important complication of liver diseases. The most common cause of portal hypertension is cirrhosis of the liver. Under these conditions, intrahepatic resistance increases, which leads to an increase in portal pressure. As a result of increased pressure in the portal vein, a number of complications may occur, including the development of varicose veins of the esophagus and stomach, ascites, hepatic encephalopathy, as well as complications secondary to circulatory dysfunction, such as hepatorenal syndrome, portopulmonary syndrome and hepatopulmonary syndrome. By increasing portal blood flow, internal vasodilation further aggravates portal hypertension. New pathogenic pathways are being established that may lead to new therapeutic strategies.This review describes the classification and complications of portal hypertension, as well as some aspects of the diagnosis and treatment of these various important clinical consequences. Портальды гипертензия бауыр ауруларының маңызды асқынуы болып табылады. Портальды гипертензияның ең көп таралған себебі- бауыр циррозы. Мұндай жағдайларда бауырішілік кедергі артады, бұл қақпа венасындағы қысымының жоғарылауына әкеледі. Қақпа венасындағы жоғары қысымның нәтижесінде бірқатар асқынулар пайда болуы мүмкін, соның ішінде өңеш пен асқазанның варикозды кеңеюі, асцит, бауыр энцефалопатиясы, сондай-ақ қан айналым дисфункциясынан кейінгі асқынулар, мысалы, гепаторенальды синдром, портопульмональды синдром және гепатопульмональды синдром. Қақпа венасындағы қан ағымын жоғарылату, ішкі вазодиляция портальды гипертензияны одан әрі күшейтеді. Осыған орай жаңа терапиялық стратегияға әкелуі мүмкін жаңа патогендік жолдар орнатылуда. Бұл шолуда портальды гипертензияның жіктелуі мен асқынулары, сондай-ақ әртүрлі маңызды клиникалық салдарды диагностикалау мен емдеудің кейбір сәттері сипатталған.

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Imaging-guided interventions modulating portal venous flow: Evidence and controversies

Cited by 2 publications

References 160 publications

5-hydroxymethylcytosine features of portal venous blood predict metachronous liver metastases of colorectal cancer and reveal phosphodiesterase 4 as a therapeutic target

5-hydroxymethylcytosine features of portal venous blood predict metachronous liver metastases of colorectal cancer and reveal phosphodiesterase 4 as a therapeutic target

Порталдық Гипертензия (Әдеби Шолу)

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