New Treatment Options for Hepatocellular Carcinoma Raises Questions for Optimal Sequencing of Therapies

Treatment Options ◽

Mechanisms Of Action ◽

Targeted Agents ◽

Adjuvant Setting ◽

Advanced Hcc ◽

Molecularly Targeted Agents ◽

Drug Eluting Beads ◽

Drug Eluting ◽

Overview: Management of hepatocellular carcinoma (HCC) continues to be challenging, but new treatment options are evolving. A multidisciplinary evaluation will help make the best treatment decisions for each patient. Although we continue to improve the outcomes of curative treatment with resection, liver transplant, and radiofrequency ablation (RFA), many new liver-directed regional therapies including drug-eluting beads, radioembolization, and radiation are emerging. Sorafenib remains the only approved agent for advanced HCC, and its role in the adjuvant setting following resection or RFA, with transarterial chemoembolization, or in combination with other targeted agents or chemotherapy in the advanced stage is under investigation. Many molecularly targeted agents with novel mechanisms of action are under active development.

Transarterial Radioembolization (TARE) Agents beyond 90Y-Microspheres

BioMed Research International ◽

10.1155/2018/1435302 ◽

2018 ◽

Vol 2018 ◽

pp. 1-14 ◽

Cited By ~ 7

Author(s):

C. Bouvry ◽

X. Palard ◽

J. Edeline ◽

V. Ardisson ◽

P. Loyer ◽

...

Keyword(s):

Treatment Options ◽

Hepatic Metastases ◽

Liver Malignancies ◽

Liver Tumours ◽

Alternative Technologies ◽

Transarterial Radioembolization ◽

Advanced Stages ◽

New Treatment ◽

90Y Microspheres

Liver malignancies, either primary tumours (mainly hepatocellular carcinoma and cholangiocarcinoma) or secondary hepatic metastases, are a major cause of death, with an increasing incidence. Among them, hepatocellular carcinoma (HCC) presents with a dark prognosis because of underlying liver diseases and an often late diagnosis. A curative surgical treatment can therefore only be proposed in 20 to 30% of the patients. However, new treatment options for intermediate to advanced stages, such as internal radionuclide therapy, seem particularly attractive. Transarterial radioembolization (TARE), which consists in the use of intra-arterial injection of a radiolabelled embolising agent, has led to very promising results. TARE with 90Y-loaded microspheres is now becoming an established procedure to treat liver tumours, with two commercially available products (namely, SIR-Sphere® and TheraSphere®). However, this technology remains expensive and is thus not available everywhere. The aim of this review is to describe TARE alternative technologies currently developed and investigated in clinical trials, with special emphasis on HCC.

Therapeutic Strategies in HCC: Radiation Modalities

BioMed Research International ◽

10.1155/2016/1295329 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 8

Author(s):

R. Gallicchio ◽

A. Nardelli ◽

P. Mainenti ◽

A. Nappi ◽

D. Capacchione ◽

...

Keyword(s):

Three Dimensional Conformal Radiotherapy

Treatment Options ◽

Three Dimensional ◽

Conformal Radiotherapy ◽

Normal Liver ◽

Great Promise ◽

Radical Therapy ◽

External Radiation Therapy ◽

New Treatment ◽

Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with131I Lipiodol or90Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment.

GASC1 promotes hepatocellular carcinoma progression by inhibiting the degradation of ROCK2

Cell Death and Disease ◽

10.1038/s41419-021-03550-w ◽

2021 ◽

Vol 12 (3) ◽

Author(s):

Na Shao ◽

Jiamin Cheng ◽

Hong Huang ◽

Xiaoshan Gong ◽

Yongling Lu ◽

...

Keyword(s):

Transcriptional Repression ◽

Rho Gtpase ◽

Treatment Options ◽

Standard Of Care ◽

Malignant Cell ◽

Tumor Stage ◽

Downstream Target ◽

Demethylase Activity ◽

AbstractHepatocellular carcinoma (HCC) is a devastating malignancy without targeted therapeutic options. Our results indicated that the histone demethylase GASC1 signature is associated with later tumor stage and poorer survival in HCC patients. GASC1 depletion led to diminished HCC proliferation and tumor growth. A distinct heterogeneity in GASC1 levels was observed among HCC cell populations, predicting their inherent high or low tumor-initiating capacity. Mechanistically, GASC1 is involved in the regulation of several components of the Rho-GTPase signaling pathway including its downstream target ROCK2. GASC1 demethylase activity ensured the transcriptional repression of FBXO42, a ROCK2 protein-ubiquitin ligase, thereby inhibiting ROCK2 degradation via K63-linked poly-ubiquitination. Treatment with the GASC1 inhibitor SD70 impaired the growth of both HCC cell lines and xenografts in mice, sensitizing them to standard-of-care chemotherapy. This work identifies GASC1 as a malignant-cell-selective target in HCC, and GASC1-specific therapeutics represent promising candidates for new treatment options to control this malignancy.

Management of thoracic aortic lesions - the future is endovascular

VASA ◽

10.1024/0301-1526/a000183 ◽

2012 ◽

Vol 41 (3) ◽

pp. 163-176 ◽

Cited By ~ 6

Author(s):

Weidenhagen ◽

Bombien ◽

Meimarakis ◽

Geisler ◽

A. Koeppel

Keyword(s):

Thoracic Aorta ◽

Clinical Decision Making ◽

Treatment Options ◽

Clinical Decision ◽

Clinical Results ◽

Treatment Modalities ◽

Traumatic Rupture ◽

Descending Thoracic Aorta ◽

New Treatment ◽

Aneurysm Dissection

Open surgical repair of lesions of the descending thoracic aorta, such as aneurysm, dissection and traumatic rupture, has been the state-of-the-art treatment for many decades. However, in specialized cardiovascular centers, thoracic endovascular aortic repair and hybrid aortic procedures have been implemented as novel treatment options. The current clinical results show that these procedures can be performed with low morbidity and mortality rates. However, due to a lack of randomized trials, the level of reliability of these new treatment modalities remains a matter of discussion. Clinical decision-making is generally based on the experience of the vascular center as well as on individual factors, such as life expectancy, comorbidity, aneurysm aetiology, aortic diameter and morphology. This article will review and discuss recent publications of open surgical, hybrid thoracic aortic (in case of aortic arch involvement) and endovascular repair in complex pathologies of the descending thoracic aorta.

A Genomic Approach to Characterize the Vulnerable Patient – a Clinical Update

Journal of Interdisciplinary Medicine ◽

10.2478/jim-2019-0023 ◽

2019 ◽

Vol 4 (3) ◽

pp. 141-144

Author(s):

Evelin Szabó ◽

Zsolt Parajkó ◽

Diana Opincariu ◽

Monica Chițu ◽

Nóra Raț ◽

...

Keyword(s):

Risk Factors ◽

Myocardial Ischemia ◽

Treatment Options ◽

Ischemic Heart ◽

Pathophysiological Mechanism ◽

Ischemia And Reperfusion Injury ◽

Myocardial Ischemia And Reperfusion ◽

Vulnerable Patient ◽

Traditional Risk Factors ◽

Abstract Atherosclerosis is the elemental precondition for any cardiovascular disease and the predominant cause of ischemic heart disease that often leads to myocardial infarction. Systemic risk factors play an important role in the starting and progression of atherosclerosis. The complexity of the disease is caused by its multifactorial origin. Besides the traditional risk factors, genetic predisposition is also a strong risk factor. Many studies have intensively researched cardioprotective drugs, which can relieve myocardial ischemia and reperfusion injury, thereby reducing infarct size. A better understanding of abnormal epigenetic pathways in the myocardial pathology may result in new treatment options. Individualized therapy based on genome sequencing is important for an effective future medical treatment. Studies based on multiomics help to better understand the pathophysiological mechanism of several diseases at a molecular level. Epigenomic, transcriptomic, proteomic, and metabolomic research may be essential in detecting the pathological phenotype of myocardial ischemia and ischemic heart failure.

Study of Toll-like Receptor 3 Gene Polymorphism as a Novel Risk Factor for HCV-related Hepatocellular Carcinoma in Egypt

Current Cancer Drug Targets ◽

10.2174/1568009620666200319102929 ◽

2020 ◽

Vol 20 (5) ◽

pp. 382-389 ◽

Cited By ~ 1

Author(s):

Shimaa EL-Sharawy ◽

Osama El- Sayed Negm ◽

Sherief Abd-Elsalam ◽

Hesham Ahmed EL-Sorogy ◽

Mona Ahmed Helmy Shehata

Keyword(s):

Risk Factor ◽

Gene Polymorphism ◽

Clinical Laboratory ◽

Treatment Options ◽

Laboratory Evaluation ◽

Toll Like Receptor ◽

Focal Lesions ◽

Tlr3 Gene ◽

Cirrhotic Patients

Background & Aims: Hepatocellular carcinoma (HCC) is a highly aggressive cancer with few treatment options. Toll-like receptor 3 (TLR3) plays a key role in innate immunity and may affect the development of cancers. This study aimed to investigate the association between TLR3 gene polymorphism and HCV-related hepatocellular carcinoma in Egypt. Methods: This work was conducted on 70 individuals; fifty HCV cirrhotic patients were included in two groups; with HCC (30 patients) and without HCC (20 patients) compared with a group of 20 apparently healthy controls. All of the studied individuals underwent clinical-laboratory evaluation. TLR3 gene single-nucleotide polymorphism (SNP) (+1234C/T) was tested by polymerase chain reaction- restriction fragment length polymorphism. Results: This study reported that the prevalence of TLR3 +1234TT genotype was significantly increased in cirrhotic patients with HCC than without HCC, while it was not detected at all among the controls. When analyzing the TLR3 SNP +1234C/T with different clinical parameters in HCC patients, there was a significant association between+1234C/T SNP; namely TT genotype and each of the hepatic focal lesions᾽ number, size and the patients᾽ higher Okuda and BCLC stages. No association could be detected between TLR3 SNP and the age, sex, Child-Pugh grades, MELD score or AFP of the studied HCC cases. Conclusion: TLR3 gene SN P +1234C/T could be a novel risk factor for the HCV-related HCC among the Egyptian population.

Proteomic Analysis of the Vitreous Body in Proliferative and Non-Proliferative Diabetic Retinopathy

Current Proteomics ◽

10.2174/1570164617666200302101442 ◽

2020 ◽

Vol 17 ◽

Cited By ~ 1

Author(s):

Van-An Duong ◽

Jeeyun Ahn ◽

Na-Young Han ◽

Jong-Moon Park ◽

Jeong-Hun Mok ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Proliferative Diabetic Retinopathy ◽

Microvascular Complications ◽

Treatment Options ◽

Vitreous Body ◽

Control Group ◽

Diabetic Patients ◽

Protein Protein Interaction ◽

Alpha Beta ◽

Background: Diabetic Retinopathy (DR), one of the major microvascular complications commonly occurring in diabetic patients, can be classified into Proliferative Diabetic Retinopathy (PDR) and Non-Proliferative Diabetic Retinopathy (NPDR). Currently available therapies are only targeted for later stages of the disease in which some pathologic changes may be irreversible. Thus, there is a need to develop new treatment options for earlier stages of DR through revealing pathological mechanisms of PDR and NPDR. Objective: The purpose of this study was to characterize proteomes of diabetic through quantitative analysis of PDR and NPDR. Methods: Vitreous body was collected from three groups: control (non-diabetes mellitus), NPDR, and PDR. Vitreous proteins were digested to peptide mixtures and analyzed using LC-MS/MS. MaxQuant was used to search against the database and statistical analyses were performed using Perseus. Gene ontology analysis, related-disease identification, and protein-protein interaction were performed using the differential expressed proteins. Results: Twenty proteins were identified as critical in PDR and NPDR. The NPDR group showed different expressions of kininogen-1, serotransferrin, ribonuclease pancreatic, osteopontin, keratin type II cytoskeletal 2 epidermal, and transthyretin. Also, prothrombin, signal transducer and activator of transcription 4, hemoglobin subunit alpha, beta, and delta were particularly up-regulated proteins for PDR group. The up-regulated proteins related to complement and coagulation cascades. Statherin was down-regulated in PDR and NPDR compared with the control group. Transthyretin was the unique protein that increased its abundance in NPDR compared with the PDR and control group. Conclusion: This study confirmed the different expressions of some proteins in PDR and NPDR. Additionally, we revealed uniquely expressed proteins of PDR and NPDR, which would be differential biomarkers: prothrombin, alpha-2-HS-glycoprotein, hemoglobin subunit alpha, beta, and transthyretin.

Immunotherapy and potential predictive biomarkers in the treatment of neuroendocrine neoplasia

Future Oncology ◽

10.2217/fon-2020-0703 ◽

2020 ◽

Author(s):

Guanghui Xu ◽

Yuhao Wang ◽

Hushan Zhang ◽

Xueke She ◽

Jianjun Yang

Keyword(s):

Current Knowledge ◽

Checkpoint Inhibitors ◽

Treatment Options ◽

Predictive Biomarkers ◽

The Body ◽

Low Grade ◽

Ablative Therapies ◽

Cancer Types ◽

New Treatment ◽

Well Differentiated

Neuroendocrine neoplasias (NENs) are a heterogeneous group of rare tumors scattered throughout the body. Surgery, locoregional or ablative therapies as well as maintenance treatments are applied in well-differentiated, low-grade NENs, whereas cytotoxic chemotherapy is usually applied in high-grade neuroendocrine carcinomas. However, treatment options for patients with advanced or metastatic NENs are limited. Immunotherapy has provided new treatment approaches for many cancer types, including neuroendocrine tumors, but predictive biomarkers of immune checkpoint inhibitors (ICIs) in the treatment of NENs have not been fully reported. By reviewing the literature and international congress abstracts, we summarize the current knowledge of ICIs, potential predicative biomarkers in the treatment of NENs, implications and efficacy of ICIs as well as biomarkers for NENs of gastroenteropancreatic system, lung NENs and Merkel cell carcinoma in clinical practice.

Inhibition of Proinflammatory Cytokines in Cutibacterium acnes-Induced Inflammation in HaCaT Cells by Using Buddleja davidii Aqueous Extract

International Journal of Inflammation ◽

10.1155/2020/8063289 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Anh Thu Nguyen ◽

Ki-young Kim

Keyword(s):

Proinflammatory Cytokines ◽

Proinflammatory Cytokine ◽

Treatment Options ◽

Mapk Signaling ◽

Cytokine Expression ◽

Proinflammatory Cytokine Expression ◽

Cutibacterium Acnes ◽

Anti Inflammatory ◽

New Treatment ◽

Hacat Keratinocyte

Acne is an inflammatory skin disorder; although some anti-inflammatory medicines for treating acne are available in a market, they have considerable side effects; therefore, new treatment options are needed. In the present study, among the 16 aqueous extracts of plants collected from Jeju Island in Korea which are used to test anti-inflammatory activity, B. davidii showed the strong decline of the proinflammatory cytokine expression against the inflammatory process caused by C. acnes in Human HaCaT keratinocyte cells. B. davidii downregulated the expression of 57% of COX-2, 41% of iNOS, and proinflammatory cytokines 29% of TNF-α, 32% of IL-1β, 21% of IL-6, and 35% of IL-8. Furthermore, B. davidii inhibited NF-κB and MAPK signaling cascades in keratinocytes that activated by toll-like receptor 2 (TLR-2) in response to C. acnes. Given those results, B. davidii is a potential agent to reduce the proinflammatory cytokine expression against C. acnes-induced inflammation and might provide an alternative to the current medications.