IMPORTANCE Minimal residual disease (MRD) refers to the presence of disease in cases deemed to be in complete remission by conventional pathologic analysis. Assessing the association of MRD status following induction therapy in patients with acute lymphoblastic leukemia (ALL) with relapse and mortality may improve the efficiency of clinical trials and accelerate drug development.OBJECTIVE To quantify the relationships between event-free survival (EFS) and overall survival (OS) with MRD status in pediatric and adult ALL using publications of clinical trials and other databases.DATA SOURCES Clinical studies in ALL identified via searches of PubMed, MEDLINE, and clinicaltrials.gov.STUDY SELECTION Our search and study screening process adhered to the PRISMA Guidelines. Studies that addressed EFS or OS by MRD status in patients with ALL were included; reviews, abstracts, and studies with fewer than 30 patients or insufficient MRD description were excluded. CONCLUSIONS AND RELEVANCE The value of having achieved MRD negativity is substantial in both pediatric and adult patients with ALL. These results are consistent across therapies, methods of and times of MRD assessment, cutoff levels, and disease subtypes. Minimal residual disease status warrants consideration as an early measure of disease response for evaluating new therapies, improving the efficiency of clinical trials, accelerating drug development, and for regulatory approval. A caveat is that an accelerated approval of a particular new drug using an intermediate end point, such as MRD, would require confirmation using traditional efficacy end points.

A covalent conjugate (NR-LU-10͞SA) was prepared between streptavidin (SA) and NR-LU-10, a mAb that binds an antigen expressed on the surface of most human carcinomas. NR-LU-10͞SA was injected into nude mice bearing human tumor xenografts. Injection of biotinylated galactosyl-human serum albumin reduced the circulating levels of conjugate by 95%. Subsequent administration of 90 Y-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-biotin achieved peak uptake at the tumor within 2 hr while >80% of the radioactivity was eliminated in the urine. A single dose of 600 -800 Ci of 90 Y-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-biotin produced cures in 10͞10 mice with established (>200 mm 3 ) s.c. human small cell lung or colon cancer xenografts and 8͞10 cures in mice with human breast cancer xenografts without significant toxicity.

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Current evidence about the association between pioglitazone and bladder cancer risk remains conflict. We aimed to assess the risk of bladder cancer associated with the use of pioglitazone and identify modifiers that affect the results. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to 25 August 2016 for randomized controlled trials (RCTs) and observational studies that evaluated the association between pioglitazone and bladder cancer risk. Conventional and cumulative meta‐analyses were used to calculate the odds ratio (OR) with 95% confidence interval (CI). A restricted spline regression analysis was used to examine the dose–response relationship with a generalized least‐squares trend test. We included two RCTs involving 9114 patients and 20 observational studies (n = 4,846,088 individuals). An increased risk of bladder cancer in patients treated with pioglitazone versus placebo was noted from RCTs (OR, 1.84; 95%CI, 0.99 to 3.42). In observational studies, the increased risk of bladder cancer was slight but significant among ever‐users of pioglitazone versus never‐users (OR, 1.13; 95%CI, 1.03 to 1.25), which appeared to be both time‐ (P = 0.003) and dose‐dependent (P = 0.05). In addition, we observed the association differed by region of studies (Europe, United States, or Asia) or source of funding (sponsored by industry or not). Current evidence suggests that pioglitazone may increase the risk of bladder cancer, possibly in a dose‐ and time‐dependent manner. Patients with long‐term and high‐dose exposure to pioglitazone should be monitored regularly for signs of bladder cancer.

As a co-receptor for vascular endothelial growth factor (VEGF), Neuropilin-1 (NRP-1) plays an important role in angiogenesis and malignant progression of many human cancers. However, the role of NRP-1 in hepatocellular carcinoma (HCC) is not well understood. The study aimed to detected the expression of Neuropilin-1 in HCC and investigate the association between its expression and the clinicopathological characteristics and prognosis of HCC. Quantitative real-time PCR (qRT-PCR), Western blot, Immunofluorescence and immunohistochemistry (IHC) analyses were performed to characterize the expression of NRP-1 in HCC cell lines and tissues. The association of NRP-1 expression with the clinicopathological characteristics and the prognosis was subsequently assessed. qRT-PCR and Western blot assays revealed that the expression of NRP-1 in HCC was significantly increased relative to that of normal live cells and tissues (P < 0.05,and <0.001, respectively). In addition, high expression of NRP-1 was significantly associated with intrahepatic metastasis (P = 0.036), Edmondson grade (P = 0.007), TNM classification (P = 0.0031), and portal vein invasion (P = 0.004). Furthermore, the HCC patients with high NRP-1 expression had shorter overall survival (OS), and recurrence-free survival (RFS), whereas, patients with low NRP-1 expression had better OS and RFS (P = 0.0035, and 0.0048, respectively). These data indicate that NRP-1 expression may play an important role in the progression of HCC, and that high NRP-1 expression suggests unfavorable clinicopathological characteristics and survival in HCC patients.

MicroRNA-132 (miR-132), an angiogenic growth factor inducible microRNA in the endothelium, facilitates pathological angiogenesis. Previous study showed that miR-132 was downregulated in human osteosarcoma. However, its functional attributes associated with tumor progression of osteosarcoma have not been fully elucidated. The aim of this study was to investigate the clinical significance of miR-132 expression in human osteosarcoma. miR-132 expression was detected by quantitative reverse transcription polymerase chain reaction using 166 pairs of osteosarcoma and noncancerous bone tissues. Then, the association of miR-132 expression with clinicopathological factors or survival of osteosarcoma patients was also evaluated. miR-132 expression was significantly lower in osteosarcoma tissues than that in corresponding noncancerous bone tissues (P < 0.001). In addition, miR-132 expression was decreased in the osteosarcoma specimens with advanced clinical stage (P = 0.009), positive distant metastasis (P = 0.006), and poor response to chemotherapy (P = 0.009). Moreover, both the univariate and multivariate analyses showed that osteosarcoma patients with low miR-132 expression had poorer overall and disease-free survival (both P < 0.001), and low miR-132 expression was an independent prognostic factor for both overall (P = 0.001) and disease-free survival (P = 0.006). These findings offer the convinced evidence for the first time that miR-132 may participate in tumor progression of osteosarcoma and loss of miR-132 expression may be a predictor for unfavorable outcome of osteosarcoma patients.

Current evidence indicates that use of diuretics might be associated with increased risk of KC, while ACE inhibitors or ARBs might be associated with decreased risk in high-risk individuals. β-blockers or CCBs might be positively associated with BCC risk. Further postmarketing surveillance studies and investigations to clarify the possible underlying mechanisms are warranted.