Immunotherapy for recurrent hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is presented frequently in late stages that are not amenable for curative treatment.Even for patients who can undergo resection for curative treatment of HCC,up to 50%recur.For patients who were not exposed to systemic therapy prior to recurrence,recurrence frequently cannot be subjected to curative therapy or local treatments.Such patients have several options of immunotherapy(IO).This includes programmed cell death protein 1(PD-1)and cytotoxic T-lymphocyte associated protein 4 treatment,combination of PD-1 and vascular endothelial growth factor inhibitor or single agent PD-1 therapy when all other options are deemed inappropriate.There are also investigational therapies in this area that explore either PD-1 and tyrosine kinase inhibitors or a novel agent in addition to PD-1 with vascular endothelial growth factor inhibitors.This minireview explored IO options for patients with recurrent HCC who were not exposed to systemic therapy at the initial diagnosis.We also discussed potential IO options for patients with recurrent HCC who were exposed to first-line therapy with curative intent at diagnosis.

Oligospermia due to partial maturation arrest responds to low dose estrogen-testosterone combination therapy resulting in live-birth: a case report

A man having severe oligospermia, due to partial maturation arrest at spermatid stage, was given low dose estrogen-testosterone combination therapy for three months. His sperm count increased enormously, following which his wife conceived and delivered a healthy baby at term.

Immune therapies in pancreatic ductal adenocarcinoma: Where are we now?

Pancreatic ductal adenocarcinoma(PDAC)is one of the deadliest cancers,mostly due to its resistance to treatment.Of these,checkpoint inhibitors(CPI)are inefficient when used as monotherapy,except in the case of a rare subset of tumors harboring microsatellite instability(<2%).This inefficacy mainly resides in the low immunogenicity and non-inflamed phenotype of PDAC.The abundant stroma generates a hypoxic microenvironment and drives the recruitment of immunosuppressive cells through cancerassociated-fibroblast activation and transforming growth factorβsecretion.Several strategies have recently been developed to overcome this immunosuppressive microenvironment.Combination therapies involving CPI aim at increasing tumor immunogenicity and promoting the recruitment and activation of effector T cells.Ongoing studies are therefore exploring the association of CPI with vaccines,oncolytic viruses,MEK inhibitors,cytokine inhibitors,and hypoxia-and stroma-targeting agents.Adoptive T-cell transfer is also under investigation.Moreover,translational studies on tumor tissue and blood,prior to and during treatment may lead to the identification of biomarkers with predictive value for both clinical outcome and response to immunotherapy.

Long-term outcomes of combined chemotherapy in chronic refractory idiopathic thrombocytopenic purpura

Adult idiopathic thrombocytopenic purpura （ITP） is a .chronic acquired organ-specific autoimmune hemorrhagic disease characterized by the production of auto-antibodies against antigens on the membranes of platelet, resulting in enhanced Fc-mediated destruction of the platelets by macrophages in the reticuloendothelial 1-3 system. Splenectomy remains the best treatment of chronic ITP, but approximately 30% of patients do not respond or relapse after surgery;4-6 these patients are defined as patients with chronic refractory ITE There is no consensus on an appropriate sequence of treatments for patients with chronic refractory ITE79 Management of these patients remains a dilemma. We have treated 31 patients with chronic refractory ITP using low dose combination chemotherapy between 1994 and 2005, and the results are presented as follows.

A DNA Nano-train Carrying a Predefined Drug Combination for Cancer Therapy

Herein,we reported a tumor cell-targeting aptamer-nano-train to deliver paclitaxel(PTX)and combretastatin A4(CA4)at a predefined ratio to cancer cells based on DNA nanotechnology.Such a drug-carrying aptamer-nano-train(aptamer-NT-PTX/CA4)was prepared via self-assembly of two DNA hairpins,which were conjugated with PTX and CA4,respectively,induced by aptamer trigger.Our research revealed that the aptamer-NT-PTX/CA4 could specifically recognize CD71-positive cancer cells,but not CD71-negative healthy normal cells,and achieve synergistic therapeutic effect on cancer cells.The aptamer-nano-train-based strategy is simple and efficient,and provides a new platform for drug combination cancer therapy.

Traditional Chinese medicine integrated with chemotherapy for stage Ⅳ non-surgical gastric cancer: a retrospective clinical analysis

OBJECTIVE： Traditional Chinese medicine （TCM） is regarded as an important treatment for gastric cancer patients, especially for those in advanced stage. To evaluate the effects of TCM treatment on gastric cancer patients, the authors performed a retrospective study to report the result of the integrated treatment of TCM with chemotherapy for stage IV non-surgical gastric cancer. METHODS： In this study, 182 patients with stage IV and non-surgical gastric cancer were retrospectively analyzed to evaluate the effects of TCM integrated with chemotherapy. Among the 182 cases, 88 cases received integrated therapy consisting of TCM and chemotherapy, while 94 cases received chemotherapy alone. The overall survival and Karnofsky performance status （KPS） score were measured as the main outcome. RESULTS： The median overall survival of the integrated therapy group and chemotherapy group were 16.9 and 10.5 months, respectively. The 1-, 3- and 5-year survival rates of integrated therapy group vs. chemotherapy group were 70% vs. 32%, 18% vs. 4%, and 11% vs. 0%, respectively. There was a significant difference between the two groups （x2 = 42.244, P 〈 0.001 ）. After six-month treatment, KPS scores of the integrated therapy group and the chemotherapy group were 75.00 ± 14.78 and 60.64 ± 21.39, respectively （P 〈 0.001）. The Cox regression analysis showed that TCM treatment is a protective factor for patients＇ overall survival. CONCLUSION： This study demonstrated that TCM integrated with chemotherapy may prolong overal survival and improve survival rate and life quality of patients with stage IV non-surgical gastric cancer

Prognostic analysis of transarterial chemoembolization combined with a traditional Chinese herbal medicine formula for treatment of unresectable hepatocellular carcinoma

Background Transarterial chemoembolization （TACE） is the most widely used primary treatment for unresectable hepatocellular carcinoma （HCC） due to its survival benefit, though its clinical effect is still far from satisfactory. Jiedufang （JDF） granule preparation is a commonly used Chinese herbal medicine formula for HCC. The aim of this study was to evaluate the effect of combined therapy with TACE and JDF granule preparation in treatment of unresectable HCC on survival. Methods A retrospective study of TACE was performed in 165 patients with unresectable HCC who were admitted between January 2002 and December 2007 in Changhai Hospital, Shanghai, China. Of the 165 patients, 80 patients （study group） received combined therapy consisting of TACE and a long-term maintenance treatment with oral JDF granule preparation, and the remaining 85 patients （control group） received TACE alone. The survival rates of both groups were calculated by the Kaplan-Meier method. Factors possibly affecting survival were assessed by multivariate analysis in the Cox proportional hazard model, such as maximum tumor size, number of lesions, portal vein invasion, and etc. Results The median overall survival was 9.2 months （95% CI： 6.94-11.46） in the study group versus 5.87 months （95% CI： 4.21-7.52） in the control group. In the study group,survival rates of the 1-, 2- and 3-year follow-up were 41.2%, 18.4%, and 9.6%, respectively. Significant independent prognostic factors identified by the Cox regression analysis were as follows： serum hepatitis B surface antigen （HBsAg） （P=0.014）, maximum tumor size （P=0.027）, number of lesions （P 〈0.001）, portal vein invasion （P 〈0.001）, and the therapy model （P=-0.006）. Conclusion Combination therapy of TACE and JDF granule preparation may significantly prolong survival of patients with unresectable HCC.

Combination Therapies for Advanced Biliary Tract Cancer

Biliary tract cancers(BTCs)are a group of malignant neoplasms that have recently increased in incidence and have a poor prognosis.Surgery is the only curative therapy.However,most patients are only indicated for palliative therapy because of advanced-stage disease at diagnosis and rapid progression.The current first-line treatment for advanced BTC is gemcitabine and cisplatin chemotherapy.Nonetheless,many patients develop resistance to this regimen.Over the years,few chemotherapy regimens have managed to improve the overall survival of patients.Accordingly,novel therapies such as targeted therapy have been introduced to treat this patient population.Extensive research on tumorigenesis and the genetic profiling of BTC have revealed the heterogenicity and potential target pathways,such as EGFR,VEGF,MEK/ERK,PI3K and mTOR.Moreover,mutational analysis has documented the presence of IDH1,FGFR2,HER2,PRKACA,PRKACB,BRAF,and KRAS gene aberrations.The emergence of immunotherapy in recent years has expanded the treatment landscape for this group of malignancies.Cancer vaccines,adoptive cell transfer,and immune checkpoint inhibitors have been extensively investigated in trials of BTC.Therefore,patient stratification and a combination of various therapies have become a reasonable and important clinical strategy to improve patient outcomes.This review elaborates the literature on combined treatment strategies for advanced BTC from the past few years and ongoing clinical trials to provide new inspiration for the treatment of advanced BTC.

Patient Characteristics, Safety, and Tolerability With Telaprevir Treatment for HCV in the Clinic:a Retrospective, Multicenter Study

Background and Aims: There is a paucity of information regarding similarities and differences between patients from the phase 3 studies of telaprevir and those receiving telaprevir in clinical practice. Methods: This retrospective chart review evaluated baseline characteristics and follow-up safety and tolerability data for patients with hepatitis C virus (HCV) infection treated with telaprevir and peginterferon alfa and ribavirin (PR) in clinical practice. Results: In total, 338 charts from patients at four academic and three community US treatment centers who received telaprevir and PR and had at least 12 weeks of follow-up data were included;62%were from academic centers and 38% were from community centers. Of the 338 patients, 269 completed 12 weeks of telaprevir and PR;32 discontinued due to adverse events. Mean age was 55 years;patients were predominantly white (79.3%) males (58.9%) with genotype 1a HCV infection (61.8%);35.5%were reported to have cirrhosis at baseline;and 55.3%previously received PR. Hypertension and depres-sion were the most common comorbidities. Patient charac-teristics outside the per-protocol minimum criteria used in the phase 3 studies of telaprevir were, e.g., hemoglobin, 9.2%;albumin, 5.3%;platelets, 11.5%;and neutrophil count, 5.6%. Adverse events occurred in 329/338 (97.3%) patients, with anemia, fatigue, nausea, and rash being the most common. Of 38 hospitalizations, 26 were deemed related to telaprevir and PR. Three patients died due to pneumonia, septic shock, and hepatorenal syndrome (n=1 each). Conclusions: These findings complement those reported from rigorous, randomized controlled studies with telaprevir-based treatment and provide a general assess-ment of similarities and/or differences between patients from the phase 3 studies of telaprevir and those treated with telaprevir in clinical practice.