Hedgehog components are overexpressed in a series of liver cancer cases DOI Creative Commons

Caroline Brandi Schlaepfer Sales,

Rosane B. Dias,

Ludmila de Faro Valverde

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 22, 2024

Abstract Liver cancers, including hepatocellular carcinoma (HCC), are the sixth most common cancer and third leading cause of cancer-related death worldwide, representing a global public health problem. This study evaluated nine patients with HCC. Six cases involved hepatic explants, three segmentectomy for tumor resection. Eight out tumors were HCC, one being combined hepatocellular-cholangiocarcinoma tumor. Conventional markers differentiation (Hep Par-1, arginase, pCEA, glutamine synthetase) positive in all patients, while precursor cells (CK19, CK7, EpCAM, CD56) negative when positive, they detected small, isolated foci. Based on silico analysis HCC from The Cancer Genome Atlas database, we found that Hedgehog (HH) pathway components ( GLI1 , GLI2 GLI3 GAS1 ) have high connectivity values (module membership > 0.7) strongly correlated each other genes biologically relevant modules We further validated this finding by analyzing gene expression HH PTCH1 our samples through qPCR, as well immunohistochemical analysis. Additionally, conducted chemosensitivity using primary cultures treated panel 18 drugs affect and/or Most sensitive to sunitinib. Our results offer comprehensive view molecular landscape highlighting significance providing insight into focused treatments

Language: Английский

Cisplatin in Liver Cancer Therapy DOI Open Access

Sae Hamaya,

Kyoko Oura, Asahiro Morishita

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10858 - 10858

Published: June 29, 2023

Hepatocellular carcinoma (HCC) is the most common primary liver tumor and often diagnosed at an unresectable advanced stage. Systemic chemotherapy as well transarterial chemoembolization (TACE) hepatic arterial infusion (HAIC) are used to treat HCC. TACE HAIC have long been standard of care for patients with HCC but limited treatment intrahepatic lesions. doxorubicin or chemohormonal therapy tamoxifen also considered, neither has demonstrated survival benefits. In HCC, cisplatin administered transhepatic arterially local treatment. Subsequently, cisplatin-refractory cases due drug resistance, a shift systemic different mechanism action expected produce new antitumor effects. Cisplatin tumors other than This review summarizes resistance describes major hepatobiliary cancers which anticancer agent, focus on

Language: Английский

Citations

43
Merits and boundaries of the BCLC staging and treatment algorithm: Learning from the past to improve the future with a novel proposal DOI
Franco Trevisani, Alessandro Vitale, Masatoshi Kudo

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 80(4), P. 661 - 669

Published: Jan. 22, 2024

Language: Английский

Citations

25
Calculus bovis inhibits M2 tumor-associated macrophage polarization via Wnt/β-catenin pathway modulation to suppress liver cancer DOI
Zhen Huang, Fanying Meng,

Lin-Zhu Lu

et al.

World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 30(29), P. 3511 - 3533

Published: July 28, 2024

(CB), used in traditional Chinese medicine, exhibits anti-tumor effects various cancer models. It also constitutes an integral component of a compound formulation known as Pien Tze Huang, which is indicated for the treatment liver cancer. However, its impact on tumor microenvironment, particularly tumor-associated macrophages (TAMs), not well understood.

Language: Английский

Citations

23
Recent development of VEGFR small molecule inhibitors as anticancer agents: A patent review (2021–2023) DOI
Jing Zeng,

Qichuan Deng,

Zheng Chen

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 146, P. 107278 - 107278

Published: March 9, 2024

Language: Английский

Citations

15
Sorafenib and Piperine co-loaded PLGA nanoparticles: Development, characterization, and anti-cancer activity against hepatocellular carcinoma cell line DOI Creative Commons
Sulaiman S. Alhudaithi, Mohd Abul Kalam, Lama Binobaid

et al.

Saudi Pharmaceutical Journal, Journal Year: 2024, Volume and Issue: 32(5), P. 102064 - 102064

Published: April 7, 2024

Hepatocellular carcinoma (HCC) exhibits high mortality rates in the advanced stage (>90 %). Sorafenib (SORA) is a targeted therapy approved for treatment of HCC; however, reported response rate to such therapeutic suboptimal (<3%). Piperine (PIP) an alkaloid demonstrated exert direct tumoricidal activity HCC and improve pharmacokinetic profiles anticancer drugs including SORA. In this study, we developed strategy efficacy outcomes using PIP as add-on support first-line SORA biodegradable Poly (D, L-Lactide-co-glycolide, PLGA) nanoparticles (NPs). (both exhibit low aqueous solubility) were co-loaded into PLGA NPs (PNPs) stabilized with various concentrations polyvinyl alcohol (PVA). The PIP-loaded PNPs (SP-PNPs) characterized Fourier Transform Infrared (FTIR) Spectroscopy, X-ray Powder Diffraction (XRD), Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), Release these from SP-PNPs was investigated vitro at both physiological acidic pH, kinetic models employed assess mechanism drug release. against cells (HepG2) also evaluated. FTIR XRD analyses revealed that encapsulated amorphous state, no observed chemical interactions among or excipients. Assessment release pH 5 7.4 showed loaded 0.5 % PVA released sustained manner, unlike pure drugs, which exhibited relatively fast spherical, had average size 224 nm, encapsulation efficiency (SORA ∼ 82 %, 79 %), well superior cytotoxicity compared monotherapy vitro. These results suggest combining may be effective set comprehensive vivo study evaluate safety novel formulation murine model.

Language: Английский

Citations

10
The Resistance to EGFR-TKIs in Non-Small Cell Lung Cancer: From Molecular Mechanisms to Clinical Application of New Therapeutic Strategies DOI Creative Commons
Carmelo Laface,

Felicia Maria Maselli,

Anna Santoro

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(6), P. 1604 - 1604

Published: May 27, 2023

Almost 17% of Western patients affected by non-small cell lung cancer (NSCLC) have an activating epidermal growth factor receptor (EGFR) gene mutation. Del19 and L858R are the most-common ones; they positive predictive factors for EGFR tyrosine kinase inhibitors (TKIs). Currently, osimertinib, a third-generation TKI, is standard first-line therapy advanced NSCLC with common mutations. This drug also administered as second-line treatment those T790M mutation previously treated first- (erlotinib, gefitinib) or second- (afatinib) generation TKIs. However, despite high clinical efficacy, prognosis remains severe due to intrinsic acquired resistance EGRF-TKIs. Various mechanisms been reported including activation other signalling pathways, development secondary mutations, alteration downstream phenotypic transformation. further data needed achieve goal overcoming EGFR-TKIs, hence necessity discovering novel genetic targets developing new-generation drugs. review aimed deepen knowledge molecular EGFR-TKIs new therapeutic strategies overcome TKIs' resistance.

Language: Английский

Citations

22
The current status and future of targeted-immune combination for hepatocellular carcinoma DOI Creative Commons

Liyuan Hao,

Shenghao Li,

Fanghang Ye

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 5, 2024

Hepatocellular carcinoma (HCC) is one of the most common cancers and third leading cause death worldwide. surgery, transarterial chemoembolization (TACE), systemic therapy, local ablation radiotherapy, targeted drug therapy with agents such as sorafenib. However, tumor microenvironment liver cancer has a strong immunosuppressive effect. Therefore, new treatments for are still necessary. Immune checkpoint molecules, programmed death-1 (PD-1), death-ligand 1 (PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), along high levels cytokines, induce cell inhibition key mechanisms immune escape in HCC. Recently, immunotherapy based on inhibitors (ICIs) monotherapy or combination tyrosine kinase inhibitors, anti-angiogenesis drugs, chemotherapy agents, topical therapies offered great promise treatment cancer. In this review, we discuss latest advances ICIs combined drugs (targeted-immune combination) other targeted-immune regimens patients advanced HCC (aHCC) unresectable (uHCC), provide an outlook future prospects. The literature reviewed spans last five years includes studies identified using keywords "hepatocellular carcinoma," "immune inhibitors," "targeted therapy," "combination "immunotherapy".

Language: Английский

Citations

7
Autotaxin–Lysophosphatidate Axis: Promoter of Cancer Development and Possible Therapeutic Implications DOI Open Access
Carmelo Laface, Angela Dalia Ricci,

Simona Vallarelli

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7737 - 7737

Published: July 15, 2024

Autotaxin (ATX) is a member of the ectonucleotide pyrophosphate/phosphodiesterase (ENPP) family; it encoded by ENPP2 gene. ATX secreted glycoprotein and catalyzes hydrolysis lysophosphatidylcholine to lysophosphatidic acid (LPA). LPA responsible for transduction various signal pathways through interaction with at least six G protein-coupled receptors, Receptors 1 6 (LPAR1-6). The ATX-LPA axis involved in physiological pathological processes, such as angiogenesis, embryonic development, inflammation, fibrosis, obesity. However, significant research also reported its connection carcinogenesis, immune escape, metastasis, tumor microenvironment, cancer stem cells, therapeutic resistance. Moreover, several studies suggested relevant biomarkers and/or targets. In this review literature, we aimed deepen knowledge about role promoter progression invasion, Finally, explored potential application prognostic/predictive biomarker target treatment.

Language: Английский

Citations

6
Immunotherapy and the Combination with Targeted Therapies for Advanced Hepatocellular Carcinoma DOI Open Access
Carmelo Laface, Girolamo Ranieri,

Felicia Maria Maselli

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(3), P. 654 - 654

Published: Jan. 20, 2023

One of the most important abilities a tumor is to establish state immunosuppression inside microenvironment. This made possible through numerous mechanisms immune escape that have been identified in experimental studies during last decades. In addition, hepatic microenvironment commonly oriented towards tolerance because liver receives blood from arteries and portal veins containing variety endogenous antigens. Therefore, establishes an autoimmune tolerance, preventing reaction liver. On this basis, cells may system, avoiding being recognized destroyed by cells. Moreover, since etiology Hepatocellular Carcinoma (HCC) often related cirrhosis, hepatitis B or C, develops context chronic inflammation. Thus, HCC characterized cell infiltration. Given these data poor prognosis advanced HCC, different immunotherapeutic strategies developed evaluated for patients. review, we describe all clinical applications immunotherapy drugs already approved ongoing trials.

Language: Английский

Citations

14
TACE Combined with Lenvatinib and Camrelizumab for Unresectable Multiple Nodular and Large Hepatocellular Carcinoma (>5 cm) DOI Creative Commons

Zhanwang Xiang,

Guohong Li, Luwen Mu

et al.

Technology in Cancer Research & Treatment, Journal Year: 2023, Volume and Issue: 22

Published: Jan. 1, 2023

Background The incidence and mortality of hepatocellular carcinoma (HCC) had increased globally over the past decades. Previous studies found that transarterial chemoembolization (TACE) combined with lenvatinib also shown efficacy in unresectable HCC. We aimed to evaluate safety TACE camrelizumab treat multiple nodular large HCC (>5 cm). Materials methods Between November 2018 June 2021, we retrospectively recruited 82 patients (BCLC stage B or C a single diameter >5 Of who not previously been treated, 33 received + (group A, TLC), 49 treated B, TLB) as initial treatment. Related results were recorded assessed. Results median follow-up periods groups A 14.5 ± 7.9 months (range, 3-36) 12.5 8.2 3-32), respectively (P = 0.799). progression-free survival (PFS) was 9.4 5.9 < 0.01), respectively, overall (OS) significantly longer group (16.4 vs 11.0 months, P 0.01). In local response rate (LRR) disease control (DCR) 51.5% 81.8%, which higher than corresponding 46.9% 77.6% observed 0.233; 0.429). Patients BCLC better PFS OS 0.05). an independent factor affected OS. There no massive bleeding treatment-related deaths. Conclusions (single cm), target therapy immunotherapy is safe effective.

Language: Английский

Citations

14