Targeting of circulating hepatocellular carcinoma cells to prevent postoperative recurrence and metastasis

Currently,the main treatment for hepatocellular carcinoma(HCC)involves the surgical removal of tumors or liver transplantation.However,these treatments are often not completely curative,as they are associated with a risk for postoperative recurrence and metastasis.Circulating tumor cells(CTCs)are increasingly recognized as the main source for recurrence and metastasis after radical hepatectomies are performed.Many studies have demonstrated the association between the presence of either pre-or postoperative CTCs and an increased risk for HCC recurrence.To improve the therapeutic outcome of HCC,a personalized,comprehensive and multidisciplinary approach should be considered,involving the application of appropriate diagnostic and therapeutic measures targeting HCC CTCs in different stages throughout the course of treatment.This article proposes some HCC CTC-based strategies for the treatment of HCC,including the monitoring of HCC CTCs before,during and after radical hepatectomy,therapeutic targeting of HCC CTCs,prevention of the generation and colonization of CTCs,as well as the use of CTC indexes for the selection of indications,prediction of prognoses,and planning of individualized therapeutic regimens.Innovation and technological development of therapies targeting CTCs,as well as their translation into clinical practice,will help to effectively reduce postoperative recurrence and metastasis,and significantly prolong the survival of HCC patients.

Clinical analysis of the risk factors for recurrence of HCC and its relationship with HBV

AIM: To comprehend the risk factors of recurrence of hepatocellular carcinoma (HCC) and its relationship with the infection patterns of hepatitis B virus (HBV). METHODS: All materials of 270 cases of postoperative HCC were statistically analyzed by SPSS software. Recurrence and metastasis were classified into early (≤2 years) and late phase (＞2 years). Risk factors for recurrence and metastasis after surgery in each group were analyzed.RESULTS: Out of 270 cases of HCC, 162 cases were followed up in which recurrence and metastasis occurred in 136 cases. There were a lot of risk factors related to recurrence and metastasis of HCC; risk factors contributing to early phase recurrence were serum AFP level, vascular invasion, incisal margin and operative transfusion, gross tumor classification and number of intrahepatic node to late phase recurrence. The HBV infective rate of recurrent HCC was 94.1%, in which 'HBsAg, HBeAb, HBcAb' positive pattern reached 45.6%. The proportion of HBV infection in solitary large hepatocellular carcinoma (SLHCC) evidently decreased compared to nodular hepatocellular carcinoma (NHCC) (P＜0.05).CONCLUSION: The early and late recurrence and metastasis after hepatectomy of HCC were associated with different risk factors. The early recurrence may be mediated by vascular invasion and remnant lesion, the late recurrence by tumor's clinical pathology propert, as multicentric carcinogenesis or intrahepatic carcinoma denovo. HBV replication takes a great role in this process. From this study, we found that SLHCC has more satisfactory neoplasm biological behavior than NHCC.

Clinical significance and characteristics of recurrent laryngeal nerve lymph node metastasis of thoracic esophageal cancer

Objective To investigate the clinical significance and characteristics of recurrent laryngeal nerve lymph node metastasis of thoracic esophageal cancer. Methods One hundred and twenty-four patients who had undergone thoracic esophageal resection with recurrent laryngealnerve lymph node dissection in our hospital from March 2007 to February 2010. All clinical data were retrospectively analysed. Results Recurrent laryngeal

Tumor Local Microenvironment Is a Key Factor Affecting the Efficacy of PD-1 Inhibitor in Advanced Cervical Cancer: A Case Report and Literature Review

Introduction: Conventional radiotherapy or chemotherapy is ineffective in the treatment of recurrent and metastatic cervical cancer. In recent years, immunotherapy has shown promise in the treatment of various solid tumours, including cervical cancer. The overall response rate of the PD-1/PD-L1 inhibitor in cervical cancer is 14% - 27%, and when combined with radiotherapy or conventional chemotherapy, the overall response rate can be further improved. Case presentation: We report here a case of a 49-year-old female patient presenting with two metastatic lesions of cervical cancer after postoperative radiotherapy, the first was located in the para-aortic region and the second in the presacral region. The enlarged para-aortic lymph nodes had not previously received radiotherapy, while the enlarged presacral lymph nodes had previously received postoperative radiotherapy. Treatment results showed that the recurrent presacral mass did not respond to the PD-1 inhibitor (camrelizumab) alone, whereas the metastatic para-aortic lymph nodes responded favourably to camrelizumab combined with low-intensity radiotherapy. Conclusion: PD1/PD-L1 inhibitors combined with radiotherapy should make it possible to overcome the bottleneck of conventional radiotherapy, improve patient prognosis or achieve better local control rates with lower radiotherapy doses.

Therapeutic sponge prevents postoperative breast cancer recurrence by sustainably dissociating into CD44-targeted nanoplatform

Locoregional recurrence and distant metastasis of breast cancer still pose a significant risk for patients’survival.To address the clinical challenge,functional absorbable sponges(HA-SH/PP-Dox/Lap/COL I(HCNPs))were constructed by biomimetic extracellular matrix of collagen I/hyaluronic acid complex conjugated with doxorubicin/lapatinib(Dox/Lap)-loaded nanoparticles.The HCNPs sponge exhibited excellent clotting ability and blood absorption rate.Worthily,Dox/Lap-loaded nanoparticles were synchronously endowed with a large number of oligo hyaluronic acid segments after degradation,which thus enhanced the ability of targeting into CD44-overexpressed tumor cells.The implantable HCNPs sponge in resected cavity of postoperative 4T1 models inhibited the spread of scattered tumor cells by absorbing the inevitable bleeding.More importantly,CD44 targeted nanoparticle with suitable Dox/Lap proportion continuously released from sponge to kill tumor cells of surrounding HCNPs and those remaining at surgical margin,thus prevented local recurrence as well as distant metastasis.Therefore,the functional HCNPs sponge might provide a safer and more effective strategy for postoperative treatment of cancer.

HLA-A*02-B*46 Haplotype: an Adverse Prognostic Factor in Han Patients with Nasopharyngeal Carcinoma

Epidemiological studies have shown that human leukocyte antigen（HLA） allelic polymorphisms are closely correlated to susceptibility to nasopharyngeal carcinoma（NPC）, and in a previous study, we showed that HLA-B＊46 and HLA-A＊02-B＊46 haplotypes were strongly associated with NPC susceptibility. In this retrospective study, we investigated the phenotype of the HLA-A and HLA-B alleles and haplotypes and correlated these data to the clinical and pathological parameters of NPC to understand the role of HLA alleles and haplotypes in NPC prognosis. The cohort comprised 117 NPC patients from a Han population in Xinjiang. The local recurrence-free survival（LRFS）, distant metastasis-free survival（DMFS）, disease-free survival（DFS）, and overall survival（OS） were analyzed. The 5-year DMFS of the HLA-A＊02-B＊46 haplotype carriers and non-carriers was 66.4% and 90.3%, respectively. In addition, age was found to be a prognostic factor for LRFS, DFS, and OS（P=0.032, 0.040, and 0.013, respectively）. We found that the HLA-A＊02-B＊46 haplotype might be a prognostic marker in addition to the traditional TNM staging in patients with NPC.

Study on Preventive and Therapeutic Effect of Radix Salviae Miltiorrhizae on Recurrence and Metastasis of Liver Cancer

Objective: To study the inhibitory effect of Radix Salviae Miltiorrhizae (RSM) on adhesive and invasive ability of SMMC 7721 liver cancer cells, and on the metastasis and recurrence on post hepatectomy liver cancer in nude mice. Methods: Effect of RSM on SMMC 7721 cell membrane intercellular adhesive molecule 1 (ICAM 1) expression was observed by immunofluorescence flow cytometry; effect on invasive ability and of SMMC 7721 cell and the detachment of which attached to fibronectin (FN) by cell migration experiment; effect on adhesion of SMMC 7721 cell with FN by MTT method and effect on adhesion between 7721 7721, 7721 lymphocyte and 7721 endothelial cell by cell adhesion experiment. LCI D20 human liver cancer metastasis model, after hepatectomy, was used to observe the effect of RSM on recurrence and metastasis of liver carcinoma in nude mice. Results: ICAM 1 expression in SMMC 7721 cells incubated with RSM was significantly lower than that in cells did not treated with RSM. RSM could inhibit the invasive ability of SMMC 7721 cell and made the cells already attached to FN exfoliated. It could also inhibit the adhesion of 7721 7721, 7721 lymphocyte and 7721 endothelial cell. And RSM showed preventive and therapeutic effect on intrahepatic and remote metastasis/recurrence of early and late human post hepatectomy liver cancer in nude mice. Conclusion: RSM could inhibit the invasion and adhesion of SMMC 7721 cell and could also prevent and inhibit metastasis and recurrence of human liver cancer after hepatectomy in nude mice.

Three advantages of using traditional Chinese medicine to prevent and treat tumor

Traditional Chinese medicine （TCM）, an important component of complementary and alternative medicine, has evolved over thousands of years with its own unique system of theories, diagnostics and therapies. TCM has been increasingly used in the last decades and become well known for its significant role in preventing and treating cancer. We believe that TCM possesses advantages over Western medicine in specific aspects at a certain stage of cancer treatment. Here we summarize the advantages of TCM from three aspects： preventing tumorigenesis; attenuating toxicity and enhancing the treatment effect; and reducing tumor recurrence and metastasis.