Efficacy of modified bevacizumab-XELOX therapy in Japanese patients with stage IV recurrent or non-resectable colorectal cancer

BackgroundNeoadjuvant chemotherapy (NAC) has been conducted for patients with non-resectable colorectal cancer; however, few reports of a systematic approach to NAC exist. At our hospital, bevacizumab with capecitabine and oxaliplatin (B-mab XELOX) has been used as chemotherapy for Stage IV colorectal cancer since 2014. We aimed to evaluate the efficacy and safety of NAC with a molecular-targeting agent for Stage IV colorectal cancer.MethodsA retrospective, single-institute analysis was performed including 27 patients with advanced recurrent cancer following primary tumor resection and 43 patients with non-resectable tumors and remote metastasis. At the time of resection, 17 were receiving chemotherapy. All 70 patients received at least 3 cycles of B-mab XELOX (total: 920 cycles). We determined the 1-year progression-free survival (1Y-PFS), 1-year overall survival (1Y-OS), 3Y-PFS, 3Y-OS, and number of treatment cycles. The objective response rate, clinical benefit rate, and adverse events were assessed. The number of chemotherapy cycles, survival time, and R0 surgery rate were determined for patients who underwent RO conversion surgery.ResultsThe 1Y-PFS was 28.5% [median survival time (MST): 7.4 months], 1Y-OS was 76.6% (MST not reached), 3Y-PFS was 5.5% (MST: 7.4 months), and 3Y-OS was 26.4% (MST: 25.2 months). The mean and median number of cycles of B-mab XELOX was 13.1 and 10.5, respectively. The objective response rate was 28.6%, and the clinical benefit rate was 58.6%. Grade 1 or Grade 2 adverse events occurred in 60 patients (85.7%); however, they all resolved without intervention. A single Grade 4 event (perforation of the primary tumor) occurred in 1 patient (1.4%). RO conversion surgery was performed in 7 patients (10.0%; primary + liver in 2 patients, primary + lung in 1 patient, liver in 3 patients, and primary in 1 patient). These patients received 3 to 10 cycles preoperatively (mean: 7.3; median: 6.5). R0 surgery was achieved in 5 of the 7 patients (71.4%). Postoperative survival ranged from 1 to 26 months (MST: 8 months).ConclusionsThis modified regimen was safe and effective in Japanese patients, and a high quality of life/quality-adjusted life-year was achieved. To further evaluate PFS and OS, more patients are being investigated.     

伐昔洛韦预防多发性骨髓瘤并发带状疱疹的有效性及对患者血清IFN-γ、IL-6水平的影响

目的:探讨伐昔洛韦预防多发性骨髓瘤并发带状疱疹的疗效及对患者血清IFN-γ和IL-6水平的影响。方法:将100例我院收治的多发性骨髓瘤患者随机分为观察组及对照组。两组患者均接受PAD化疗方案,观察组患者在此基础上口服盐酸伐昔洛韦片。比较两组患者治疗后的疗效、带状疱疹发生率及不良反应发生情况;比较两组患者治疗前及治疗后血清IFN-γ、IL-6及T淋巴细胞亚群(CD3＋、CD4＋、CD8＋及CD4＋/CD8＋)水平。结果:两组患者总有效率相比较无统计学差异(P＞0.05);观察组患者带状疱疹发生率(2.0%)低于对照组患者(20.0%)(P＜0.01);观察组患者恶心呕吐及乏力发生率均高于对照组患者(P＜0.05);治疗后,观察组患者血清IFN-γ水平高于对照组患者(P＜0.01),IL-6水平低于对照组患者(P＜0.01);治疗后,观察组患者血液CD3＋、CD4＋及CD4＋/CD8＋水平均高于对照组患者(P＜0.01),CD8＋水平低于对照组患者(P＜0.01)。结论:伐昔洛韦能够有效预防多发性骨髓瘤患者化疗期间带状疱疹的发生,不影响化疗的疗效,同时安全性较高,并能够调节IFN-γ、IL-6及T淋巴细胞亚群的水平。     

Triple-mutated oncolytic herpes virus for treating both fast- and slow-growing tumors

Oncolytic virus therapy has emerged as a promising treatment option against cancer. To date, oncolytic viruses have been developed for malignant tumors, but the need for this new therapeutic modality also exists for benign and slow-growing tumors. G47∆ is an oncolytic herpes simplex virus type 1 (HSV-1) with an enhanced replication capability highly selective to tumor cells due to genetically engineered, triple mutations in the γ34.5, ICP6 and α47 genes. To create a powerful, but safe oncolytic HSV-1 that replicates efficiently in tumors regardless of growth speed, we used a bacterial artificial chromosome system that allows a desired promoter to regulate the expression of the ICP6 gene in the G47∆ backbone. Restoration of the ICP6 function in a tumor-specific manner using the hTERT promoter led to a highly capable oncolytic HSV-1. T-hTERT was more efficacious in the slow-growing OS-RC-2 and DU145 tumors than the control viruses, while retaining a high efficacy in the fast-growing U87MG tumors. The safety features are also retained, as T-hTERT proved safe when inoculated into the brain of HSV-1 sensitive A/J mice. This new technology should facilitate the use of oncolytic HSV-1 for all tumors irrespective of growth speed.     

Modelling seasonal and weather dependency of cardiac arrests using the covariate order method

A data set concerning cardiac arrests treated by the Emergency Medical Service in Trondheim during a nine year period is analysed. The relationship between the occurrence of cardiac arrest and covariates related to weather and season is examined. The covariate order method is used in the analysis of the data. It is explained how this method can be extended to recurrent event data, and the practical usefulness and flexibility of the method is demonstrated in these analyses. In the analyses a significant relationship between outdoor air temperature, or factors closely related to outdoor air temperature, and the occurrence of cardiac arrest is found. The incidence of cardiac arrest decreases with increasing temperature. Further a significant effect of snowfall is also found, with increased intensity of cardiac arrest on days with snowfall. A more borderline significant effect of precipitation is also identified.     

The 894 G > T variant of endothelial nitric oxide synthase (eNOS) increases the risk of recurrent venous thrombosis through interaction with elevated homocysteine levels.

BACKGROUND: Venous thrombosis is a multicausal disease involving both genetic as well as acquired risk factors. Hyperhomocysteinemia is associated with a 2-fold increased risk of recurrent venous thrombosis (RVT). Recently, the 894 G > T variant of endothelial nitric oxide synthase (eNOS) was postulated to be associated with hyperhomocysteinemia. OBJECTIVES: We hypothesized an interrelation of hyperhomocysteinemia, the eNOS 894 G > T variant and RVT risk. METHODS: The eNOS 894 G > T variant was studied in 170 cases with a history of RVT and 433 controls from the general population. RESULTS: The eNOS 894 TT genotype may increase RVT risk [odds ratio (OR) 1.3 (0.7-2.6)], but no association of the eNOS 894 G > T variant with elevated homocysteine was found in controls. Interestingly, in RVT cases the coexistence of both the 894 TT genotype and elevated tHcy levels (> 90th percentile) was more frequently present than in controls, which led to a substantially increased risk of recurrent venous thrombosis [fasting tHcy OR 5.3 (1.1-24.1), postload tHcy OR 6.5 (1.6-29.5)]. CONCLUSION: The results of the present study demonstrate that the eNOS 894 G > T variation interacts with elevated tHcy levels, leading to an increased risk of recurrent thrombotic events. This interaction points in the direction of S-nitrosation as a mechanism by which homocysteine exerts its detrimental effects on the hemostatic system.     

Implications of uterine NK cells and regulatory T cells in the endometrium of infertile women

A range of studies have shown that the complex process of implantation and an establishment of a pregnancy also involves immune factors. Disturbances in these underlying immune mechanisms might lead to implantation and pregnancy failure and may be involved in the pathogenesis of unexplained infertility. Several studies have reported that imbalances in uterine NK (uNK) cell abundance are associated with infertility; however, controversies exist. An increased amount of CD56⁺ uNK cells along with a decrease in CD16⁺ uNK cells have been associated with normal fertility in some studies. Very few studies of FoxP3⁺ regulatory T cells (Tregs) in the pre-implantation endometrium have been performed. Results are sparse and controversial, studies reporting both increased and decreased numbers of Tregs, respectively, in women suffering from infertility. In conclusion, studies imply that uNK cells, Tregs and HLA-G carry pivotal roles regarding the establishment of a healthy pregnancy, and that abnormal immune mechanisms involving these parameters may be associated with infertility. However, more research in early phases of the reproductive cycle, such as investigating the conditions in the endometrium before implantation, is needed to further clarify the underlying mechanisms.     

Semen analysis in laboratory practice: an overview of routine tests

Semen analysis is a basic step in the investigation of several disturbances affecting the male genital tract. Analysis of seminal parameters provides important clinical information on the spermatogenesis and functional competence of spermatozoa, as well as on the secretory pattern of the accessory genital glands. Semen analysis is particularly useful in the evaluation of couples requiring fertility investigation (to detect genital infections and pathologies) and in verifying the influence of environmental factors, drugs, lifestyle, chemical products, and professional activities on several diseases affecting male reproductive health. Measure of semen quality is of substantial interest for diagnoses in clinical urology, andrology, and gynecology. Currently, basic requirements for semen analysis are standardized by World Health Organization (WHO) guidelines that describe several procedures for an objective evaluation of the semen quality with diagnostic purposes. These guidelines include: parameters for the physical and biochemical evaluation of semen; parameters for the analysis of sperm characteristics; and other seminal parameters that can be easily adopted in any laboratory. This report summarizes current concepts on semen analysis and the significance of the seminal parameters for reaching a diagnosis based on the procedures recommended by WHO guidelines.