Treatment Of Carcinoma Research Articles

CARMIL1 regulates liver cancer cell proliferation by activating the ERK/mTOR pathway through the TRIM27/p53 axis

Capping protein regulatory factor and myosin 1 linker 1 is termed CARMIL1. CARMIL1 is involved in several physiological processes; it forms an actin filament network and plasma membrane-bound cellular projection tissues and positively regulates the cellular components and tissues. CARMIL1 exhibits important biological functions in cancer; nonetheless, these functions have not been completely explored. We aimed to investigate the novel functions of CARMIL1 in liver cancer, particularly in cell proliferation. The cell counting kit-8, 5-ethynyl-2′-deoxyuridine, Component A experiments, and subcutaneous tumor formation model suggest that CARMIL1 is central to the proliferation of liver cancer cells both in vivo and in vitro. We extracted CARMIL1 samples from The Cancer Genome Atlas Program and analyzed its enrichment. CARMIL1 regulated the pathway activity by affecting the expression of star molecular proteins of the extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR). Moreover, it influenced the proliferation ability of liver cancer cells. Western blotting suggested that CARMIL1 downregulation could affect ERK and mTOR phosphorylation. Results of the co-immunoprecipitation demonstrated that CARMIL1 binds to tripartite motif (TRIM)27, which in turn binds to p53. Subsequently, CARMIL1 can regulate p53 stability and promote its degradation through TRIM27. Additionally, CARMIL1 inhibition enhanced the sensitivity of liver cancer cells to sorafenib. Tumor growth was significantly inhibited in the group treated with sorafenib and CARMIL1, compared with the group treated with CARMIL1 alone. Sorafenib is a first-line targeted chemotherapeutic drug for hepatocellular carcinoma treatment. It increases the long-term survival of hepatocellular carcinoma by 44%. In this study, downregulated CARMIL1 combined with sorafenib significantly reduced the tumor volume and weight of the mouse subcutaneous tumor model, indicating the potential possibility of combining CARMIL1 with sorafenib in hepatocellular carcinoma treatment. In summary, CARMIL1 promotes liver cancer cell proliferation by regulating the TRIM27/p53 axis and activating the ERK/mTOR pathway.

Dataset of weekly intra-treatment diffusion weighted imaging in head and neck cancer patients treated with MR-Linac

Radiation therapy (RT) is a crucial treatment for head and neck squamous cell carcinoma (HNSCC); however, it can have adverse effects on patients’ long-term function and quality of life. Biomarkers that can predict tumor response to RT are being explored to personalize treatment and improve outcomes. While tissue and blood biomarkers have limitations, imaging biomarkers derived from magnetic resonance imaging (MRI) offer detailed information. The integration of MRI and a linear accelerator in the MR-Linac system allows for MR-guided radiation therapy (MRgRT), offering precise visualization and treatment delivery. This data descriptor offers a valuable repository for weekly intra-treatment diffusion-weighted imaging (DWI) data obtained from head and neck cancer patients. By analyzing the sequential DWI changes and their correlation with treatment response, as well as oncological and survival outcomes, the study provides valuable insights into the clinical implications of DWI in HNSCC.

Circulating tumor cells: a valuable indicator for locally advanced nasopharyngeal carcinoma.

Advancements in nasopharyngeal carcinoma (NPC) treatment have led to a focus on personalized treatment. Circulating tumor cells (CTCs) are important for liquid biopsies and personalized treatment but are not being fully utilized. This study examined how pre- and post-treatment CTC counts, EMT subtypes, clinical characteristics, and patient prognosis are related in order to support the use of liquid biopsy in managing NPC. This retrospective study included 141 patients with locally advanced NPC. All patients underwent CanPatrol™ CTC detection pre- and post-treatment and were categorized into EMT subtypes: epithelial type, mixed type, and mesenchymal type. This study analyzed CTC enumeration, EMT subtypes, and their associations with clinical characteristics and survival outcomes. The results indicated a positive correlation between the pre-treatment detection rate of CTCs and N stage (P < 0.01), alongside a positive correlation with the TNM clinical stage (P = 0.02). Additionally, the detection rate of mesenchymal CTCs post-treatment is positively associated with the N stage (P = 0.02). The enumeration of CTCs pre- and post-treatment is negatively correlated with prognosis and has statistical significance. Additionally, an investigation into the EMT subtypes of CTCs revealed a significant association between the presence of mesenchymal CTCs pre- and post-treatment and decreased overall survival (OS) (P < 0.05). Furthermore, T stage, N stage, TNM clinical stage, and Epstein-Barr virus (EBV) DNA were also significantly correlated with OS. The study found that mesenchymal CTCs pre- and post-treatment, as well as the number of CTCs, were linked to a poor prognosis.

Glycyrrhetinic Acid as a Hepatocyte Targeting Ligand-Functionalized Platinum(IV) Complexes for Hepatocellular Carcinoma Therapy and Overcoming Multidrug Resistance.

Promising targeted therapy options to overcome drug resistance and side effects caused by platinum(II) drugs for treatment in hepatocellular carcinoma are urgently needed. Herein, six novel multifunctional platinum(IV) complexes through linking platinum(II) agents and glycyrrhetinic acid (GA) were designed and synthesized. Among them, complex 20 showed superior antitumor activity against tested cancer cells including cisplatin resistance cells than cisplatin and simultaneously displayed good liver-targeting ability. Moreover, complex 20 can significantly cause DNA damage and mitochondrial dysfunction, promote reactive oxygen species generation, activate endoplasmic reticulum stress, and eventually induce apoptosis. Additionally, complex 20 can effectively inhibit cell migration and invasion and trigger autophagy and ferroptosis in HepG-2 cells. More importantly, complex 20 demonstrated stronger tumor inhibition ability than cisplatin or the combo of cisplatin/GA with almost no systemic toxicity in HepG-2 or A549 xenograft models. Collectively, complex 20 could be developed as a potential anti-HCC agent for cancer treatment.

Surveillance for metachronous cancers after endoscopic resection of esophageal squamous cell carcinoma.

The literature pertaining to surveillance following treatment for esophageal squamous cell carcinoma (SCC) was reviewed and summarized, encompassing the current status and future perspectives. Analysis of the standardized mortality and incidence ratios for these cancers indicates an elevated risk of cancer in the oral cavity, pharynx, larynx, and lungs among patients with esophageal SCC compared to the general population. To enhance the efficacy of surveillance for these metachronous cancers, risk stratification is needed. Various factors, including multiple Lugol-voiding lesions, multiple foci of dilated vascular areas, young age, and high mean corpuscular volume, have been identified as predictors of metachronous SCCs. Current practice involves stratifying the risk of metachronous esophageal and head/neck SCCs based on the presence of multiple Lugol-voiding lesions. Endoscopic surveillance, scheduled 6-12 months post-endoscopic resection, has demonstrated effectiveness, with over 90% of metachronous esophageal SCCs treatable through minimally invasive modalities. Narrow-band imaging emerges as the preferred surveillance method for esophageal and head/neck SCC based on comparative studies of various imaging techniques. Innovative approaches, such as artificial intelligence-assisted detection systems and radiofrequency ablation of high-risk background mucosa, may improve outcomes in patients following endoscopic resection.

Prognostic role of circulating cytokines and inflammation indexes for avelumab maintenance in metastatic urothelial carcinoma

BackgroundAvelumab maintenance after first-line platinum-based chemotherapy represents a cornerstone for the treatment of metastatic urothelial carcinoma (mUC). However, identifying prognostic biomarkers is paramount for optimizing patients’ benefits while minimizing toxicity. Cytokines represent circulating mediators of the complex interaction between cancer, the immune system, and inflammation. Inflammation, a hallmark of cancer, can be expressed by circulating factors. In different tumor subtypes, peripheral blood biomarkers, such as circulating cytokines, and systemic inflammatory indexes, have been addressed as potential prognostic factors for immune checkpoint inhibitors. However, their role in mUC still needs to be determined.MethodsBetween February 2021 and April 2023, we prospectively collected plasma cytokines and inflammation indexes in 28 patients with mUC before starting avelumab as first-line maintenance. The primary endpoint was the relationship between baseline cytokines and inflammatory indexes with the clinical benefit (CB), defined as the number of Responders. Secondary endpoints included the correlation of baseline cytokines and inflammatory indexes with progression-free survival (PFS), overall survival (OS), and the number and grade of immune-related adverse events.ResultsHigh pre-treatment levels of interferon (IFN)-γ and interleukin (IL)-2, and low levels of IL-6, IL-8, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and systemic-inflammation index (SII) were associated with clinical benefit and longer survival. In the multivariate analysis, low IL-8, NLR, and SII levels maintained a positive prognostic value for OS.ConclusionOur data suggest that, in mUC patients receiving avelumab, pre-treatment levels of plasma cytokines and inflammatory indexes may serve as potential prognostic biomarkers for response and efficacy. In particular, patients with signs of pre-therapeutic inflammation showed a significantly lower response and survival to avelumab. On the contrary, low systemic inflammation and high levels of cytokines characterized responders and longer survivors.

Factors Impacting Provider Treatment Decision-Making in Early Glottic Cancer.

Transoral laser microsurgery (TLMS) and radiotherapy (XRT) are mainstays of treatment for early glottic carcinoma (EGC). Here, we investigated case-dependent provider treatment preferences and identify factors which impact decision-making in EGC. This cross-sectional survey of laryngologists, head-and-neck surgeons, and radiation oncologists presented five diagrammatic cases of progressively advanced EGC (T1/2, N0). Respondents indicated preference for TLMS or XRT and ranked factors which influenced their recommendation for each case. Analysis utilized descriptive statistics, Fischer's exact tests, and Kruskal-Wallis tests for nonparametric data. A total of 141 complete responses (69.5% laryngologists) were received. Most respondents practiced in academic settings (93.5%) and within multidisciplinary teams (94.0%). Anterior commissure involvement was the most important a priori tumor factor for case-independent treatment recommendation (Likert Scale: 4.22/5), followed by Laterality (Likert Scale: 4.02/5). Across all specialties, TLMS was recommended for unilateral T1a lesions. Laryngologists continued recommending TLMS in T2 lesions (41.0%) more than head-and-neck surgeons (5.0%) and radiation oncologists (0.0%). Across all cases, survival and voice outcomes were the most important clinical factors impacting treatment decisions. Radiation oncologists weighed voice more heavily than laryngologists in more complex presentations of EGC (rank: 1.6 vs. 2.7, Kruskall-Wallis: p < 0.05). In more complex clinical presentations of EGC, preference for TLMS compared to XRT differed across specialists, despite similar rankings of factors driving these treatment recommendations. This may be driven by differing experiences and viewpoints on case-dependent voice outcomes following TLMS versus XRT, suggesting a need for increased understanding of how tumor location and depth impact voice outcomes. V Laryngoscope, 2024.

Dynamics of the neutrophil‑to‑lymphocyte ratio during lenvatinib treatment for unresectable hepatocellular carcinoma

Dynamics of the neutrophil‑to‑lymphocyte ratio during lenvatinib treatment for unresectable hepatocellular carcinoma

Case Report: Urothelial urethral carcinoma in HIV patient underwent total urethrectomy and perineal urethrostomy

Introduction HIV affects over 38 million people worldwide, affecting the immune system and leading to symptoms like fever, lymphadenopathy, and sore throat. High viral loads can lead to opportunistic infections and tumors. The life expectancy of HIV patients has increased due to high-efficiency combination anti-retroviral therapy. Urothelial carcinoma, a malignant development, damages the urinary canal lining. The connection between HIV and urinary cancers is unclear, the aims of this study to report a case of urethral urothelial Carcinoma in HIV patient who underwent total urethrectomy and perineal urethrostomy. Case presentation A 34-year-old male patient with a papilliferous lump on the glans penis for over six months was admitted to the hospital. Preoperative screening revealed HIV and a urethral mass was found. A partial urethrectomy was performed, revealing high grade papillary urothelial Carcinoma. Five months after surgery, the patient developed a recurrent lump, requiring a total urethrectomy, TUR (transurethral resection) of the mass in the prostatic urethra, and perineal urethrostomy. Conclusion Primary carcinoma of the urethra in HIV patient is an extremely rare case. To date, there is no consensus on the primary urethral carcinoma therapy. The treatment of primary urethral carcinoma is tailored specifically to the patient based on the location, histology, and stage of the carcinoma.

Efficacy and survival of nivolumab treatment for recurrent/unresectable esophageal squamous-cell carcinoma: real-world clinical data from a large multi-institutional cohort.

Real-world clinical outcomes of and prognostic factors for nivolumab treatment for esophageal squamous-cell carcinoma (ESCC) remain unclear. This study aimed to evaluate real-world outcomes of nivolumab monotherapy in association with relevant clinical parameters in recurrent/unresectable advanced ESCC patients. This population-based multicenter cohort study included a total of 282 patients from 15 institutions with recurrent/unresectable advanced ESCC who received nivolumab as a second-line or later therapy between 2014 and 2022. Data, including the best overall response, progression-free survival (PFS), and overall survival (OS), were retrospectively collected from these patients. Objective response and disease control rates were 17.0% and 47.9%, respectively. The clinical response to nivolumab treatment significantly correlated with development of overall immune-related adverse events (P < .0001), including rash (P < .0001), hypothyroidism (P = .03), and interstitial pneumonia (P = .004). Organ-specific best response rates were 20.6% in lymph nodes, 17.4% in lungs, 15.4% in pleural dissemination, and 13.6% in primary lesions. In terms of patient survival, the median OS and PFS was 10.9 and 2.4months, respectively. Univariate analysis of OS revealed that performance status (PS; P < .0001), number of metastatic organs (P = .019), C-reactive protein-to-albuminratio (CAR; P < .0001), neutrophil-lymphocyte ratio (P = .001), and PMI (P = .024) were significant. Multivariate analysis further identified CAR [hazard ratio (HR) = 1.61, 95% confidence interval (CI) 1.15-2.25, P = .0053)] in addition to PS (HR = 1.65, 95% CI 1.23-2.22, P = .0008) as independent prognostic parameters. CAR and PS before nivolumab treatment are useful in predicting long-term survival in recurrent/unresectable advanced ESCC patients with second-line or later nivolumab treatment. UMIN000040462.

Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK

The efficient clinical treatment of oral squamous cell carcinoma (OSCC) is still a challenge that demands the development of effective new drugs. Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors, however, not much is known about the influence of phenformin on OSCC cells. We found that phenformin suppresses OSCC cell proliferation, and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro. RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4 (DNA damage inducible transcript 4) and NIBAN1 (niban apoptosis regulator 1). We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy. Further, the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4 (activation transcription factor 4), which was induced by phenformin treatment in OSCC cells. Mechanistically, these results revealed that phenformin triggers endoplasmic reticulum (ER) stress to activate PERK (protein kinase R-like ER kinase), which phosphorylates the transitional initial factor eIF2, and the increased phosphorylation of eIF2 leads to the increased translation of ATF4. In summary, we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth. Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

Assessment of efficacy and safety of irreversible electroporation versus TACE for treatment of difficult location hepatocellular carcinoma

IntroductionRadiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted as the established treatment options for patients diagnosed with early-stage hepatocellular carcinoma (HCC) who are deemed unfit for surgical procedures. However, the effective implementation of these techniques is hindered by various challenges, primarily associated with the precise targeting of tumors within the liver. The utilization of thermal ablative methods is not recommended for hepatocellular carcinoma (HCC) that is located near intestinal loops, bile ducts, or in eccentric positions. The unmet need for non-thermal methods in the treatment of hepatocellular carcinoma (HCC) was addressed following the introduction of irreversible electroporation (IRE) as an innovative approach.Aim of the workTo assess the efficacy, safety, and outcomes of IRE in the treatment of difficult-located HCC compared to transarterial chemoembolization (TACE).MethodsThis is a prospective study that included 24 patients with HCC who presented to the National Hepatology and Tropical Medicine Research Institute (NHTMRI) during the period from January 2017 to January 2020. Ten patients underwent IRE, while 14 patients underwent TACE.ResultsSixteen patients (66.7%) were males; eight patients were females (33.3%). Their median age was 60.5 years (48–70 years). Seventeen patients (70.8%) were Child–Pugh class A, while seven patients (29.2%) were Child–Pugh class B. All the study population had a single focal lesion; the mean size of the focal lesions was 2.94 ± 0.59 cm. The most frequent difficult locations of HCC were segment V focal lesions adjacent to both the common bile duct and portal vein in eight patients (33.3%) followed by lesions adjacent to the inferior vena cava in five patients (20%) followed by the subcapsular lesions in three patients (12.5%) and lesions adjacent to the right kidney in two patients (8.3%). Complete response (CR) was higher in the IRE group (80%) compared to the TACE group (50%). Clinical decompensation occurred in six patients in the IRE group (60%) and eight patients in the TACE group (57.1%) (P value 1). Recurrence occurred in five patients (50%) treated with IRE and in seven patients (50%) treated with TACE (P value 1). Within the IRE group, two patients (20%) remained alive; on the other hand, within the TACE group six patients (42.9%) remained alive by the end of the study (P value 0.388).ConclusionOur data suggest that IRE is an effective procedure in the treatment of difficult-located HCC in terms of complete response, fewer sessions, and fewer side effects as compared to TACE.

Plasma Metabolic Profiles-Based Prediction of Induction Chemotherapy Efficacy in Nasopharyngeal Carcinoma: Results of a Bidirectional Clinical Trial.

The efficacy of induction chemotherapy (IC) as a primary treatment for advanced nasopharyngeal carcinoma (NPC) remains a topic of debate, with a lack of dependable biomarkers for predicting its efficacy. This study seeks to establish a predictive classifier utilizing plasma metabolomics profiling. A total of 166 NPC patients enrolled in the clinical trial NCT05682703 and undergoing IC were included in the study. Plasma lipoprotein profiles were obtained using 1H-NMR before and after IC treatment. An AI-assisted radiomics method was developed to effectively evaluate the efficacy. Metabolic biomarkers were identified through a machine learning approach based on a discovery cohort and subsequently validated in a validation cohort that mimicked the most unfavorable scenario in real-world. Our research findings indicate that the effectiveness of IC varies among individual patients, with a correlation observed between efficacy and changes in metabolite profiles. Utilizing machine learning techniques, it was determined that the XGB model exhibited notable efficacy, attaining an Area Under the Curve (AUC) value of 0.792 (95% CI, 0.668-0.913). In the validation cohort, the model exhibited strong stability and generalizability with an AUC of 0.786 (95%CI, 0.533-0.922). In this study, we found that dysregulation of plasma lipoprotein may result in resistance to IC in NPC patients. The prediction model constructed based on the plasma metabolites' profile as good predictive capabilities and potential for real-world generalization. This discovery has implications for the development of treatment strategies and may offer insight into potential targets for enhancing the effectiveness of IC.

The Application of "Table Tennis Racquet" Random Skin Flap in the Treatment of Facial Skin Carcinoma.

The repair of facial skin and soft tissue defects remains a clinical challenge. The author introduced a novel "table tennis racquet" random skin flap for wound repair after facial skin cancer excision and discussed its survival mechanisms. A lateral mandibular neck skin flap shaped like a table tennis racquet with no well-known blood vessels at the narrow pedicle was designed in 31 cases to repair tissue defects. Among them, there were 8 cases of skin carcinoma in the frontotemporal area and 23 cases of skin carcinoma in the cheek. The flap area was 8.0 × 7.0 cm at maximum and 3.0 × 2.5 cm at minimum, with a pedicle width of 1.0-2.0 cm and a pedicle length of 2.0-6.0 cm. All 31 "table tennis racquet" random skin flaps survived, although there were 3 cases with delayed healing of distal flap bruising. All of them had an ideal local shape after repair with a concealed donor area and inconspicuous scars. This flap has a "table tennis racquet" shape with a pedicle without well-known blood vessels and has a length-to-width ratio that exceeds that of conventional random flaps, making it unconventional. Because of its long and narrow pedicle, it not only has a large rotation and coverage area but also can be designed away from the defect area, avoiding the defect of no donor tissue being localized near the defect. Overall, this approach is an ideal option for repairing tissue defects after enlarged excision of facial skin carcinoma.

Sorafenib plus TACE with or without camrelizumab for the treatment of intermediate and advanced hepatocellular carcinoma.

To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with sorafenib and camrelizumab or with sorafenib alone in patients with intermediate or advanced hepatocellular carcinoma (HCC). We retrospectively analyzed 78 patients with intermediate or advanced HCC who were treated at our centers between January 2018 and December 2021. 26 of them received sorafenib and camrelizumab plus TACE (the TACE + Sor + C group), while 52 received TACE and sorafenib (the TACE + Sor group). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated. Univariate and multivariate analyses were used to determine the factors affecting survival. The mOS (22 vs. 10 months, P < 0.001) and mPFS (11 vs. 6 months, P = 0.008) of the TACE + Sor + C group were significantly higher than those of the TACE + Sor group. Multivariate analysis showed that compared with TACE + Sor + C, TACE + Sor increased the risk of all-cause mortality and tumor progression. For grade I and II adverse events (AEs), the incidence of skin capillary hyperplasia and hypothyroidism in the TACE + Sor + C group was significantly higher than that in the TACE + Sor group. For serious AEs (grade III or IV), there was no significant difference in any adverse reaction between the two groups (P > 0.05). Patients with intermediate or advanced HCC appeared to benefit more in terms of survival from TACE + Sor + C than from TACE + Sor, and the AEs were tolerable. 1.Subgroup analysis demonstrated TACE+ Sorafenib+ Camrelizumab could benefit HCC patients regardless of whether they had PVTT, BCLC B or C, or CHILD A or B；2.We reported the immunotherapy related adverse events (irAEs) occurred with a significant higher incidence in triple treatment, but all the adverse events are tolerable.

Potential treatment of squamous cell carcinoma by targeting heparin-binding protein 17/fibroblast growth factor-binding protein 1 with vitamin D3 or eldecalcitol.

Heparin-binding protein 17 (HBp17), first purified in 1991 from the conditioned medium of the human A431 squamous cell carcinoma (SCC) cell line, was later renamed fibroblast growth factor-binding protein 1 (FGFBP-1). HBp17/FGFBP-1 is specifically expressed and secreted by epithelial cells, and it reversibly binds to fibroblast growth factor (FGF)-1 and FGF-2, as well as FGFs-7, -10, and -22, indicating a crucial involvement in the transportation and function of these FGFs. Our laboratory has investigated and reported several studies to elucidate the function of HBp17/FGFBP-1 in SCC cells and its potential as a molecular therapeutic target. HBp17/FGFBP-1 transgene exoression in A431-4 cells, a clonal subline of A431 that lacks tumorigenicity and does not express HBp17/FGFBP-1, demonstrated a significantly enhanced proliferation in vitro compared with A431-4 cells, and it acquired tumorigenicity in the subcutis of nude mice. Knockout (KO) of the HBp17/FGFBP-1 by genome editing significantly suppressed tumor growth, cell motility, and tumorigenicity compared with control cells. A comprehensive analysis of expressed molecules in both cell types revealed that molecules that promote epithelial cell differentiation were highly expressed in HBp17/FGFBP-1 KO cells. Additionally, we reported that 1α,25(OH)2D3 or eldecalcitol (ED-71), which is an analog of 1α,25(OH)2D3, suppresses HBp17/FGFBP-1 expression and tumor growth in vitro and in vivo by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway. Here, we discuss the prospects of molecular targeted therapy targeting HBp17/FGFBP-1 with 1α,25(OH)2D3 or ED71 in SCC and oral SCC.

Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma

BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma (HCC), and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than monotherapy. However, the mechanisms underlying this innovative treatment modality have not been elucidated. AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX in patients with unresectable HCC. METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy, immunotherapy, and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen. RESULTS The objective response rate was 60.4% (32/53), complete response was 24.5% (13/53), partial response was 35.9% (19/53), and stable disease was 39.6% (21/53). The median duration of response and median progression-free survival were 9.1 and 13.9 months, respectively. The surgical conversion rate was 34.0% (18/53), and 1-year overall survival was 83.0% without critical complicating diseases or adverse events (AEs). CONCLUSION The regimen of HAIC of FOLFOX, targeted therapy, and immunotherapy was curative for patients with unresectable HCC, with no serious AEs and a high rate of surgical conversion.

Targeting therapy for hepatocellular carcinoma by delivering microRNAs as exosomal cargo

Exosomes, the smallest extracellular vesicles, have gained significant attention as key mediators in intercellular communication, influencing both physiological and pathological processes, particularly in cancer progression. A recent review article by Wang et al was published in a timely manner to stimulate future research and facilitate practical developments for targeted treatment of hepatocellular carcinoma using exosomes, with a focus on the origin from which exosomes derive. If information about the mechanisms for delivering exosomes to specific cells is incorporated, the concept of targeted therapy for hepatocellular carcinoma using exosomes could be more comprehensively understood.

Constructing immune and prognostic features associated with ADCP in hepatocellular carcinoma and pan-cancer based on scRNA-seq and bulk RNA-seq

AimDespite the significant therapeutic outcomes achieved in systemic treatments for liver hepatocellular carcinoma (LIHC), it is an objective reality that only a low proportion of patients exhibit an improved objective response rate (ORR) to current immunotherapies. Antibody-dependent cellular phagocytosis (ADCP) immunotherapy is considered the new engine for precision immunotherapy. Based on this, we aim to develop an ADCP-based LIHC risk stratification system and screen for relevant targets.MethodUtilizing a combination of single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data, we screened for ADCP modulating factors in LIHC and identified differentially expressed genes along with their involved functional pathways. A risk scoring model was established by identifying ADCP-related genes with prognostic value through LASSO Cox regression analysis. The risk scoring model was then subjected to evaluations of immune infiltration and immunotherapy relevance, with pan-cancer analysis and in vitro experimental studies conducted on key targets.ResultsBuilding on the research by Kamber RA et al., we identified GYPA, CLDN18, and IRX5 as potential key target genes regulating ADCP in LIHC. These genes demonstrated significant correlations with immune infiltration cells, such as M1-type macrophages, and the effectiveness of immunotherapy in LIHC, as well as a close association with clinical pathological staging and patient prognosis. Pan-cancer analysis revealed that CLDN18 was prognostically and immunologically relevant across multiple types of cancer. Validation through tissue and cell samples confirmed that GYPA and CLDN18 were upregulated in liver cancer tissues and cells. Furthermore, in vitro knockdown of CLDN18 inhibited the malignancy capabilities of liver cancer cells.ConclusionWe have identified an ADCP signature in LIHC comprising three genes. Analysis based on a risk scoring model derived from these three genes, coupled with subsequent experimental validation, confirmed the pivotal role of M1-type macrophages in ADCP within LIHC, establishing CLDN18 as a critical ADCP regulatory target in LIHC.

Laparoscopic-assisted microwave ablation in treatment of small hepatocellular carcinoma: safety and efficacy in comparison with laparoscopic hepatectomy

Laparoscopic-assisted microwave ablation (LAMWA), as one of the locoregional therapies, has been employed to treat hepatocellular carcinoma (HCC). This study aims to compare the efficacy and safety of LAMWA and laparoscopic hepatectomy in the treatment of small HCC.This study included 140 patients who met the inclusion criteria. Among them, 68 patients received LAMWA and 72 patients underwent laparoscopic hepatectomy. The perioperative condition, liver function recovery, the alpha fetoprotein (AFP) level, morbidities, hospitalization time, overall survival (OS), disease-free survival (DFS) and recurrence rate between the two groups were compared. The rate of complete elimination of tumor tissue was 100% and the AFP level was returned to normal within 3 months after surgery in both groups (P > 0.05). The mean alanine transaminase (ALT) and aspartate transaminase (AST) peak in the LAMWA group was lower than that in the laparoscopic hepatectomy group (259.51 ± 188.75 VS 388.9 ± 173.65, P = 0.000) and (267.34 ± 190.65 VS 393.1 ± 185.67, P = 0.000), respectively. The mean operation time in the LAMWA group was shorter than that in the laparoscopic hepatectomy group (89 ± 31 min VS 259 ± 48 min, P = 0.000). The blood loss in the LAMWA group was less than that in the laparoscopic hepatectomy group (58.4 ± 64.0 ml VS 213.0 ± 108.2 ml, P = 0.000). Compared with the laparoscopic hepatectomy group, patients in the LAMWA group had lower mean hospital stay (4.8 ± 1.2d VS 11.5 ± 2.9d, P = 0.000). The morbidities of the LAMWA group and the hepatectomy group were 14.7%(10/68) and 34.7%(25/72), respectively (P = 0.006). The one-, three-, and five-year OS rates were 88.2%, 69.9%, 45.6% for the LAMWA group and 86.1%, 72.9%, 51.4% for the laparoscopic hepatectomy group (P = 0.693). The corresponding DFS rates for the two groups were 76.3%, 48.1%, 27.9% and 73.2%, 56.7%, 32.0% (P = 0.958). Laparoscopic-assisted microwave ablation is a safe and effective therapeutic option for selected small HCC.