A New Therapeutic Assessment Score for Advanced Hepatocellular Carcinoma Patients Receiving Hepatic Arterial Infusion Chemotherapy

MethodsWe retrospectively analyzed 90 advanced HCC patients with elevated baseline alpha-fetoprotein (AFP) and/or des-gamma-carboxy prothrombin (DCP) levels and analyzed various parameters for their possible use as predictors of response and survival. AFP and DCP responses were assessed after half a course of HAIC (2 weeks); a positive-response was defined as a reduction of ≥ 20% from baseline.ResultsMultivariate analysis identified DCP response (odds ratio 16.03, p < 0.001) as an independent predictor of treatment response. In multivariate analysis, Child-Pugh class A (hazard ratio [HR] 1.99, p = 0.018), AFP response (HR 2.17, p = 0.007), and DCP response (HR 1.90, p = 0.030) were independent prognostic predictors. We developed an Assessment for Continuous Treatment with HAIC (ACTH) score, including the above 3 factors, which ranged from 0 to 3. Patients stratified into two groups according to this score showed significantly different prognoses (≤1 vs. ≥2 points: median survival time, 15.1 vs. 8.7 months; p = 0.003).ConclusionsThe ACTH score may be useful in the therapeutic assessment of HCC patients receiving HAIC.     

A Novel Nomogram for Predicting the Overall Survival in Patients with Unresectable HCC after TACE plus Hepatic Arterial Infusion Chemotherapy

Background and aimTransarterial chemoembolization combined with hepatic arterial infusion chemotherapy (TACE-HAIC) has shown encouraging efficacy in the treatment of unresectable hepatocellular carcinoma (HCC). We aimed to develop a novel nomogram to predict overall survival (OS) of patients with unresectable HCC treated with TACE-HAIC.MethodsA total of 591 patients with unresectable HCC treated with TACE-HAIC between May 2009 and September 2020 were enrolled. These patients were randomly divided into training and validation cohorts. The independent prognostic factors were identified with Cox proportional hazards model. The model's discriminative ability and accuracy were validated using concordance index (C-index), calibration plots, the area under the time-dependent receiver operating characteristic curve (AUC) and decision curve analyses (DCAs).ResultsThe median OS was 15.6 months. A nomogram was established based on these factors, including tumor size, vein invasion, extrahepatic metastasis, tumor number, alpha fetoprotein (AFP), and albumin-bilirubin (ALBI), to predict OS for patients with unresectable HCC treated with TACE-HAIC. The C-index of the nomogram were 0.717 in the training cohort and 0.724 in validation cohort. The calibration plots demonstrated good agreement between the predicted outcomes and the actual observations. The AUC values were better than those of three conventional staging systems. The results of DCA indicated that the nomogram may have clinical usefulness. The patients in the low-risk group had a longer OS than those in intermediate-risk and high-risk groups (P<0.001).ConclusionA prognostic nomogram was developed and validated to assist clinicians in accurately predicting the OS of patients with unresectable HCC after TACE-HAIC.     

Clinical Evaluation of Targeted Arterial Infusion of Verapamil in the Interventional Chemotherapy of Primary Hepatocellular Carcinoma

This study evaluates the clinical effectiveness of targeted arterial infusion of verapamil in interventional treatment of primary hepatocellular carcinoma. For this purpose, in 273 patients with middle- or late-stage primary hepatocellular carcinoma, verapamil, IL-2, and chemotherapeutic agents were infused into the target tumor vasculature through femoral artery using Seldinger technique. The medications were infused as serial dilutions, and effectiveness was evaluated after two treatment cycles. Among these 273 patients, 76 cases showed clinical cure or significant improvement, 119 cases improved, 64 cases stabilized, while 14 cases progressed or deteriorated. In 238 patients, KPS score and body weights were stabilized. Regarding side effects, 99 patients (36.3%) developed leukopenia; 160 patients had gastrointestinal reactions (58.6%); 80 patients (29.3%) presented with elevated ALT/AST profile; and 65 cases (23.8%) had pyrexia; however, these side effects abated quickly. No elevations in BUN/Cr and/or allergic reactions were observed. Pre- and post-intervention cardiac function did not change in all the patients. No significant change was observed in ECG. Liver function was also improved after two cycles of treatment. It was concluded that verapamil management via targeted arterial infusion could effectively reverse the multidrug resistance in cancer cells in primary hepatocellular carcinoma patients and therefore enhanced the efficacy of chemotherapy.     

Surgical Strategy for Hepatocellular Carcinoma Patients with Portal/Hepatic Vein Tumor Thrombosis

Background

Portal/hepatic vein tumor thrombosis (PVTT/HVTT) in hepatocellular carcinoma (HCC) is a sign of advanced stage disease and is associated with poor prognosis. This study investigated the surgical outcomes of patients with HCC and PVTT/HVTT to determine the most appropriate surgical treatment strategy for these patients.

Materials and Methods

The study population included 77 HCC patients from January 2004 to June 2009 who underwent hepatectomy in our department and were diagnosed with PVTT/HVTT based on pathological examination. The patients were divided into two groups: in group 1, PVTT/HVTT was located in the hepatic resection area and removed with the tumor en bloc (38 cases); in group 2, PVTT/HVTT was beyond the resection line and removed by suction or thrombectomy (39 cases). Concerning the factor of surgical margins, the patients were further divided into four subgroups: group 1A: patients in group 1 with surgical margins ≤1 cm (28 cases); group 1B: patients in group 1 with surgical margins >1 cm (9 cases); group 2A: patients in group 2 with surgical margins ≤1 cm (28 cases); and group 2B: patients in group 2 with surgical margins >1 cm (9 cases).

Results

Most of the characteristics of groups 1 and 2 were similar. Patients in group 2 had significantly higher median blood loss (p=0.002) and higher blood transfusion rate (p=0.002) during the operation, which were not considered prognostic factors (p=0.323 and 0.571, respectively). The median overall survival (OS) duration in group 1 was significantly longer than that in group 2 (14.3 vs. 10.4 months, p=0.047). The median OS durations in groups 1A, 1B, 2A, and 2B were 14.3, 42.7, 7.5, and 18.0 months, respectively, which were significantly different(p=0.018).

Conclusions

When PVTT/HVTT is located in the hepatic resection area and removed with the tumor en bloc, the median OS duration is longer. Based on this finding, widening the surgical margins when technically possible may increase OS.     

Hepatic Artery Infusion Chemotherapy in Hepatoma

Three patients with inoperable malignant hepatomas were treated by intra-arterial infusion of fluorouracil. In each case the treatment gave relief of symptoms: there was striking relief of pain in two cases.Preoperative angiography is essential, but the technical problems are relatively minor.The response of the tumours to chemotherapy is sufficiently encouraging to justify greater efforts for early diagnosis.     

Hepatic Resection Is Safe and Effective for Patients with Hepatocellular Carcinoma and Portal Hypertension

Background & Aims

Official guidelines do not recommend hepatic resection (HR) for patients with hepatocellular carcinoma (HCC) and portal hypertension (PHT). This study aims to investigate the safety and efficacy of HR for patients with HCC and PHT.

Methods

Mortality and survival after HR were analyzed retrospectively in a consecutive sample of 1738 HCC patients with PHT (n = 386) or without it (n = 1352). To assess the robustness of findings, we repeated the analysis using propensity score-matched analysis. We also comprehensively searched the PubMed database for studies evaluating the efficacy and safety of HR for patients with HCC and PHT.

Results

The 90-day mortality rate was 6.7% among those with PHT and 2.1% among those without it (P<.001). Patients without PHT had a survival benefit over those with PHT at 1, 3, and 5 years (96% vs 90%, 75% vs 67%, 54% vs 45%, respectively; P = .001). In contrast, PHT was not associated with worse short- or long-term survival when only propensity score-matched pairs of patients and those with early-stage HCC or those who underwent minor hepatectomy were included in the analysis (all P>.05). Moreover, the recurrence rates were similar between the two groups. Consistent with our findings, all 9 studies identified in our literature search reported HR to be safe and effective for patients with HCC and PHT.

Conclusions

HR is safe and effective in HCC patients with PHT and preserved liver function. This is especially true for patients who have early-stage HCC or who undergo minor hepatectomy.     

Efficacy of Chemotherapy Combined with Targeted Arterial Infusion of Verapamil in Patients with Advanced Gastric Cancer

The present study evaluated the efficacy of chemotherapy combined with targeted arterial infusion of verapamil in patients with advanced gastric cancer. Forty patients were enrolled. Targeted arterial infusion of verapamil was done once a month, 3–5 times per patient, along with chemotherapy. After 2 bouts of combined treatment, the efficacy was evaluated. Primary gastric tumor was confirmed in 38/40 patients, and unconfirmed in 2/40 patients due to adhesion of tumors to surrounding tissue. Combined treatment was administered in 38 patients with defined tumors. Complete response to the treatment was in 5/38 (13.1 %) patients, partial response in 27/38 (71.1 %) patients, stable disease in 4/38 (10.5 %) patients, and progressive disease in 2/38 (5.26 %) patients. The effective rate (i.e., complete + partial response) comprised 84.2 %. There were 31 patients with liver metastases; 10/31 (32.3 %) patients showed complete response, 16/31 (51.6 %) patients showed partial response, 3/31 (9.7 %) patients had stable disease, and 2/31 (6.5 %) patients had progressive disease. The effective rate in these patients was 83.8 %. Thirty-seven patients were followed up, and 27/37 (73.0 %) patients were alive for 6 months or longer, 19/37 (51.3 %) for 12 months, 8 (35.1 %) for 18 months, and 8/37 (21.6 %) for 24 months. In conclusion, in patients with advanced gastric cancer, chemotherapy is more effective when combined with targeted arterial infusion of verapamil, leading to extended patients’ survival and improved quality of life.     

中国肝细胞癌患者TACE术后死亡原因分析(英文)

目的:通过探讨中国肝细胞癌患者肝动脉化疗栓塞术(TACE)术后并发症及死亡原因,来提高临床治疗效果,并积累治疗经验。方法:通过联合检索CBM及CNKI上从1994年1月到2008年9月的关于中国肝细胞癌患者行TACE术后出现并发症的相关文章,分析总结肝细胞癌患者TACE术后死亡的原因及特点。结果:中国肝细胞癌患者TACE术后并发症较为危重,致死率较高,死亡原因有84%是肝功能衰竭、上消化道出血及肝癌破裂出血,且死亡病例发生在术后1月内的占78.7%,因此大多是早期死亡。结论:中国肝细胞患者TACE术后死亡原因主要是肝功能衰竭、上消化道出血及肝癌破裂出血,且术后死亡常为早期死亡,因此TACE术后严重并发症可直接影响患者的预后情况,我们需要提高对TACE术选择时机的重视程度,规范介入治疗手段和流程,尽量避免和减少严重并发症的发生。     

肝动脉栓塞化疗术对原发性肝癌伴 有不同类型肝炎后肝硬化患者预后的影响

目的:探讨肝动脉栓塞化疗(TACE)对原发性肝癌伴有不同肝炎后肝硬化类型患者术后肝功能、凝血功能及其对远期预后的影响。方法:2007年8月至2009年8月,131例曾行TACE的伴有不同肝炎后肝硬化原发性肝癌患者,以肝炎后肝硬化类别(乙肝、丙肝)分类,乙肝后肝硬化组为组1,丙肝后肝硬化组为组2,随访观察术后一年肝功能、凝血功能、血小板等的变化以及预后。两组研究因素采用SPSS17.0进行卡方检验,随访预后采用Kaplan-Meier方法计算生存率,Log-rank法检验生存差异。以P<0.05为差异有统计学意义。结果:随访统计结果显示术后半年和一年AST、ALT、ALP、GGT、PT、PLT在两组间均无统计学差异,(P>0.05);组一半年、一年远处转移率同组二差异间无统计学意义;组一半年、一年生存率分别为70.1%,48.1%;组二半年、一年生存率分别为68.5%,58.9%,两组间同期生存率差异无统计学意义。(X2=0.039,P=0.884;X2=0.183,P=0.669)。结论:TACE治疗PHC安全可靠,对于伴有乙肝或丙肝后肝硬化患者术后肝功能、凝血功能、疗效及预后效果相当。     

Batimastat Nanoparticles Associated with Transcatheter Arterial Chemoembolization Decrease Hepatocellular Carcinoma Recurrence

Hepatocellular carcinoma (HCC) is a malignant tumor characterized by easy metastasis and frequent recurrence. Transarterial chemoembolization (TACE) remains the routine treatment for patients with HCC who are not eligible for surgical resection or percutaneous tumor ablation; however, 5-year survival rates following interventional therapy are only 17–38.8 %, with liver recurrence due to incomplete embolization and tumor angiogenesis being a significant reason for treatment failure. Ischemia and hypoxia induced by TACE is correlated with an increased expression of angiogenic factor and stimulates an increase in angiogenesis, including endothelial cells (ECs) proliferation. Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic endopeptidases involved in tumor angiogenesis. In addition, MMPs stimulate tumor cell growth, migration and invasion, and metastasis. Hypoxia enhanced EC migration in a MMP-2-dependent manner while MMP inhibitors (MMPIs) significantly decreased the number of migrating cells in hypoxic cultures. We hypothesize batimastat (synthetic MMPI) nanoparticles associated with TACE could decrease HCC recurrence and metastasis. At first, batimastat nanoparticles were made from batimastat and poly(lactic-co-glycolic acid). Then, nanoparticles were mixed with lipiodol and chemotherapeutic drugs solution. The mixture was infused super-selectively into supplied artery of HCC through catheter. The disseminated area of batimastat might be same with TACE-induced hypoxia area. In the hypoxia area, batimastat inhibited the activity of MMPs, weakened the angiogenesis of tumor vascular system and migration of HCC cells. HCC cells could not escape from hypoxia area and tumor angiogenesis inhibited could not supply sufficient nutrients and O₂ to residual HCC cells. With the help of batimastat, the killing effect of chemotherapeutic drugs might be enhanced. The rate of complete necrosis of HCC lesion might be increased and local recurrence and metastasis of HCC might be reduced. The hypothesis might increase the clinical efficacy of TACE and improve the prognosis of HCC patients.     

Immunological Studies in Ugandan Patients with Hepatocellular Carcinoma

Immunological studies were performed on Ugandan patients with hepatocellular carcinoma to test the hypothesis that the high rate of persistence of hepatitis-associated antigen in these patients is the result of defects in host immune response. The responses to 1-chloro-2,4-dinitrobenzene sensitization and to a battery of recall skin test antigens were normal, as was the humoral antibody response to tularaemia antigen. Neither hypogammaglobulinaemia nor specific immunoglobulin deficiencies were found. Thus it appears unlikely that generalized defects in host immune responses can account for the high incidence of persistent hepatitis B virus infection found in Ugandan patients with hepatocellular carcinoma.     

肝癌破裂出血行肝动脉栓塞治疗的护理

目的:探讨肝癌自发性破裂出血行急诊肝动脉栓塞治疗手术前后的护理方法。方法:回顾性分析17例原发性肝癌自发性破裂出血患者的急救及护理措施的临床资料。结果:17例患者入院后均有失血性休克表现,经肝动脉栓塞治疗后,治愈出院14例,死亡1例,放弃治疗2例,治疗总有效率为82.4%,死亡率为5.9%。结论:急诊肝动脉栓塞治疗肝癌破裂出血简单、有效,手术前后的护理非常重要,术前应密切注意患者病情变化,做好术前准备,术后常规止血、止吐,加强支持护理,及时观察手术并发症及疗效,积极预防和治疗各种并发症,是降低患者死亡率的关键。     

A Prognostic Score for Patients with Intermediate-Stage Hepatocellular Carcinoma Treated with Transarterial Chemoembolization

Background

Intermediate-stage hepatocellular carcinoma (HCC), defined according to the Barcelona Clinic Liver Cancer (BCLC) staging system, is a heterogeneous condition with variable clinical benefits from transarterial chemoembolization (TACE). This study aimed to develop a simple validated prognostic score based on the predictive factors for survival in patients with intermediate-stage HCC treated with TACE.

Methods

Three-hundred and fifty patients with intermediate-stage HCC undergoing initial TACE at Chiba University Hospital (training cohort; n = 187) and two affiliated hospitals (validation cohort; n = 163) were included. Following variables were entered into univariate and multivariate Cox regression models to develop a points-based clinical scoring system: gender, age, etiology, pretreatment, Child–Pugh score, aspartate aminotransferase, creatinine, C-reactive protein, alfa-fetoprotein, size of the largest lesion, and number and location of lesions.

Results

The number of lesions and the Child–Pugh score were identified as independent prognostic factors in the training cohort. The development of a 0–7-point prognostic score, named the Chiba HCC in intermediate-stage prognostic (CHIP) score, was based on the sum of three subscale scores (Child–Pugh score = 0, 1, 2, or 3, respectively, number of lesions = 0, 2, or 3, respectively, HCV-RNA positivity = 0 or 1, respectively). The generated scores were then differentiated into five groups (0–2 points, 3 points, 4 points, 5 points, and 6–7 points) by the median survival time (65.2, 29.2, 24.3, 13.1, and 8.4 months, respectively; p < 0.0001). These results were confirmed in the external validation cohort (p < 0.0001).

Conclusions

The CHIP score is easy-to-use and may assist in finding an appropriate treatment strategy for intermediate-stage HCC.     

肝动脉化疗栓塞联合索拉菲尼治疗中晚期肝细胞癌的临床疗效评估

目的:探讨中晚期肝细胞癌(HCC)采用肝动脉化疗栓塞联合索拉菲尼治疗的临床疗效。方法:按照随机数字表法将2012年3月-2014年3月我院收治的中晚期HCC患者分为两组,对照组行肝动脉化疗栓塞术治疗,观察组在对照组基础上联合索拉菲尼治疗。比较两组的疗效,毒副反应及远期生存率。结果:观察组患者治疗后6个月的临床疗效优于对照组,差异有统计学意义(Z=-2.316,P=0.021),观察组有效率52.50%,高于对照组的28.21%,差异有统计学意义(x2=4.837,P=0.028)。治疗后观察组手足皮肤反应和口腔黏膜炎症的发生率为22.50%、25.00%,分别高于对照组的5.13%、5.13%,差异有统计学意义(P0.05)。观察组6、12个月的生存率为95.00%、85.00%,分别高于对照组的79.49%、64.10%,差异有统计学意义(P0.05)。结论:肝动脉化疗栓塞联合索拉菲尼治疗HCC具有疗效好、明显延长患者生存时间的特点,临床有重要的参考价值。     

Metronomic Chemotherapy: Possible Clinical Application in Advanced Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a hypervascular highly angiogenic tumor usually associated with liver cirrhosis. Vascular endothelial growth factor plays a critical role in vascular development in HCC. In contrast to the treatment of early-stage HCC, the treatment options for advanced HCC are limited and prognosis is often poor, which contributes to this tumor type being the third leading cause of cancer-related deaths worldwide. Metronomic chemotherapy, which was originally designed to inhibit angiogenesis, involves low-dose chemotherapeutic agents administered in a frequent regular schedule with no prolonged breaks and minimizes severe toxicities. We reviewed the potential effects and impact of metronomic chemotherapy in preclinical studies with HCC models and in patients with advanced HCC, especially when combined with a molecular targeted agent. Metronomic chemotherapy involves multiple mechanisms that include antiangiogenesis and antivasculogenesis, immune stimulation by reducing regulatory T cells and inducing dendritic cell maturation, and possibly some direct tumor cell targeting effects, including the cancer stem cell subpopulation. The total number of preclinical studies with HCC models shows impressive results using metronomic chemotherapy-based protocols, especially in conjunction with molecular targeted agents. Four clinical trials and two case reports evaluating metronomic chemotherapy for HCC indicate it to be a safe and potentially useful treatment for HCC. Several preclinical and clinical HCC studies suggest that metronomic chemotherapy may become an alternative type of chemotherapy for advanced unresectable HCC and postsurgical adjuvant treatment of HCC.     

Negative Impact of Skeletal Muscle Loss after Systemic Chemotherapy in Patients with Unresectable Colorectal Cancer

Background

Skeletal muscle depletion (sarcopenia) is closely associated with limited physical ability and high mortality. This study evaluated the prognostic significance of skeletal muscle status before and after chemotherapy in patients with unresectable colorectal cancer (CRC).

Methods

We conducted a retrospective analysis of 215 consecutive patients with unresectable CRC who underwent systemic chemotherapy. Skeletal muscle cross-sectional area was measured by computed tomography. We evaluated the prognostic value of skeletal muscle mass before chemotherapy and the rate of skeletal muscle change in cross-sectional area after chemotherapy.

Results

One-hundred-eighty-two patients met our inclusion criteria. There were no significant differences in progression-free survival (PFS) or overall survival (OS) associated with skeletal muscle mass before chemotherapy. However, 22 patients with skeletal muscle loss (>5%) after chemotherapy showed significantly shorter PFS and OS compared with those without skeletal muscle loss (PFS, log-rank p = 0.029; OS, log-rank p = 0.009). Multivariate Cox regression analysis revealed that skeletal muscle loss after chemotherapy (hazard ratio, 2.079; 95% confidence interval, 1.194–3.619; p = 0.010) was independently associated with OS.

Conclusions

Skeletal muscle loss after chemotherapy was an independent, negative prognostic factor in unresectable CRC.     

Long-Term Outcomes of Percutaneous Cryoablation for Patients with Hepatocellular Carcinoma within Milan Criteria

Background

Accumulating evidences have suggested that percutaneous cryoablation could be a valuable alternative ablation therapy for HCC but there has been no large cohort-based analysis on its long-term outcomes.

Methods

A series of 866 patients with Child-Pugh class A-B cirrhosis and HCC within Milan criteria who underwent percutaneous cryoablation was long-term followed. The safety, efficacy, 5-year survival, and prognostic factors of percutaneous cryoablation in the treatment of HCC were analyzed.

Results

A total of 1197 HCC lesions were ablated with 1401 cryoablation sessions. Complete response (CR) was achieved in 1163 (97.2%) lesions and 832 (96.1%) patients with 34 (2.8%) major complications, but no treatment-related mortality. After a median of 30.9 months follow-up, 502 (60.3%) patients who achieved CR developed different types of recurrence. The cumulative local tumor recurrence rate was 24.2% at 5-years. Multiple tumor lesions, tumor size > 3 cm, and repeated ablation of same lesion were independent risk factors associated with local recurrence. The 5-year overall survival (OS) rates were 59.5%. Age < 36 years, HCC family history, baseline hepatitis B virus DNA >10⁶ copies/ml, and three HCC lesions were independently and significantly negative predictors to the post-cryoablation OS.

Conclusions

Percutaneous cryoablation is an effective therapy for patients with HCC within Milan criteria, with comparable efficacy, safety and long-term survival to the reported outcomes of radiofrequency ablation.     

Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma

BackgroundPrognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC.ConclusionsThe ITA.LI.CA prognostic system includes both a tumor staging—stratifying patients with HCC into six main stages (0, A, B1, B2, B3, and C)—and a prognostic score—integrating ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations.     

沙利度胺对原发性肝癌介入后血管内皮生长因子及生存质量的影响

目的:探讨沙利度胺对原发性肝癌(HCC)介入后血管内皮生长因子(VEGF)及生存质量的影响。方法:将2014年1月至2016年1月期间我院收治的拟行肝动脉栓塞化疗(TACE)的HCC患者60例按照随机数字表法分为A、B两组,各30例。A组患者采用TACE+沙利度胺治疗,每晚200 mg,口服一个月;B组患者单行TACE治疗。分别于治疗前、治疗后3周检测两组患者的VEGF水平,于治疗前、治疗后1个月应用生存质量评分量表(QOL)评价患者生存质量,并比较两组患者治疗前后的体重及治疗过程中的不良反应。结果:治疗前两组患者血清VEGF水平差异无统计学意义(P0.05)。治疗后两组患者VEGF水平均较治疗前升高,其中A组患者治疗后VEGF水平显著低于B组患者(P0.01)。治疗前两组患者QOL分数和体重比较差异无统计学意义(P0.05)。而治疗后两组患者的QOL分数较治疗前均有所降低,但A组患者的QOL分数显著高于B组患者(P0.05),而两组患者治疗后的体重无统计学差异(P0.05)。A组30例患者中有1例(3.33%)患者因严重嗜睡、2例(6.67%)患者因严重口腔干燥而终止口服沙利度胺,其余27例患者均能耐受。结论:沙利度胺联合TACE方法治疗HCC可降低VEGF水平和改善癌症患者的生存质量,值得在临床上推广使用。     

Giant Lysosomes as a Chemotherapy Resistance Mechanism in Hepatocellular Carcinoma Cells

Despite continuous improvements in therapeutic protocols, cancer-related mortality is still one of the main problems facing public health. The main cause of treatment failure is multi-drug resistance (MDR: simultaneous insensitivity to different anti-cancer agents), the underlying molecular and biological mechanisms of which include the activity of ATP binding cassette (ABC) proteins and drug compartmentalisation in cell organelles. We investigated the expression of the main ABC proteins and the role of cytoplasmic vacuoles in the MDR of six hepatocellular carcinoma (HCC) cell lines, and confirmed the accumulation of the yellow anti-cancer drug sunitinib in giant (four lines) and small cytoplasmic vacuoles of lysosomal origin (two lines). ABC expression analyses showed that the main ABC protein harboured by all of the cell lines was PGP, whose expression was not limited to the cell membrane but was also found on lysosomes. MTT assays showed that the cell lines with giant lysosomes were more resistant to sorafenib treatment than those with small lysosomes (p<0.01), and that verapamil incubation can revert this resistance, especially if it is administered after drug pre-incubation. The findings of this study demonstrate the involvement of PGP-positive lysosomes in drug sequestration and MDR in HCC cell lines. The possibility of modulating this mechanism using PGP inhibitors could lead to the development of new targeted strategies to enhance HCC treatment.