A ruptured hepatocellular carcinoma (HCC) is often fatal. In addition to surgery and transarterial embolization, radiofrequency ablation (RFA) might be another option for treating a ruptured HCC. Unfortunately, conventional RFA has a limited ablation zone; as such, it is rarely used to treat ruptured tumors. This case was a 60-year-old man who had a large, ruptured HCC in which hydrochloric acid (HCl)-enhanced RFA successfully controlled the bleeding and made the tumor completely necrotic. Considering the effectiveness of HCl-enhanced RFA in achieving hemostasis and tumor ablation, it might be a new option for treating large, ruptured HCCs.
1 September 2014 in Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Denticleless E3 ubiquitin protein ligase homolog (DTL), the substrate receptor of the CRL4A complex, plays a central role in genome stability. Even though the oncogenic function of DTL has been investigated in several cancers, its specific role in hepatocellular carcinoma (HCC) still needs further elucidation. Data from a clinical cohort (n = 209), RNA-sequencing, and public database (TCGA and GEO) were analyzed, indicating that DTL is closely related to patient prognosis and could serve as a promising prognostic indicator in HCC. Functionally, DTL promoted the proliferation, metastasis, and sorafenib resistance of HCC in vitro. In the orthotopic tumor transplantation and tail vein injection model, DTL promoted the growth and metastasis of HCC in vivo. Mechanically, we revealed for the first time that DTL was transcriptionally activated by hypoxia-inducible factor 1α (HIF-1α) under hypoxia and functioned as a downstream effector molecule of HIF-1α. DTL promotes the ubiquitination of SAFB-like transcription modulator (SLTM) and subsequently relieves the transcriptional repression of Notch1. These results suggested that DTL may be a potential biomarker and therapeutic target for HCC.
Transarterial chemoembolization (TACE) is an effective locoregional treatment for unresectable hepatocellular carcinoma (HCC). Arterial administration can enhance local drug concentrations while reducing systemic toxicity. The potential synergistic effects of combining locoregional treatments with systemic therapy in advanced HCC warrant further investigation. This phase 2 study (NCT04796025) aimed to evaluate the efficacy and safety of TACE combined with intra-arterial infusion of sintilimab and bevacizumab in patients with advanced HCC. Eligible patients received TACE on demand plus intra-arterial infusion of sintilimab and bevacizumab for four cycles. Maintenance therapy included intravenous administration of sintilimab and bevacizumab until disease progression or unacceptable side effects. The primary outcome was the objective response rate (ORR) based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). A total of 34 patients (median age, 53 years [IQR 45-59]; 33 men) were enrolled. With a median follow-up of 10.3 months (IQR 5.8-15.6), our results showed a favorable ORR of 70.6 %. The median PFS was calculated as 6.0 months (95 % CI 4.8 - not reached), and the median OS was 12.2 months (95 % CI 9.3 - not reached). Common treatment-related adverse events (any grade) included elevated alanine transaminase (17.6 %), abdominal pain (14.7 %), elevated aspartate aminotransferase (11.8 %), and hypertension (11.8 %). Grade 3 adverse events included hypertension (2.9 %) and gastrointestinal hemorrhage (8.8 %). No serious treatment-related adverse events were observed. TACE combined with sintilimab and bevacizumab has demonstrated a favorable ORR and promising efficacy in advanced HCC, with manageable side effects.