Cervical cancer remains the fourth most common cause of cancer worldwide and the third leading cause of cancer deaths for women in developing countries. Traditional screening tools, such as human papillomavirus and Pap tests, cannot provide results in real-time and cannot localize suspicious regions. Colposcopy-directed biopsies are invasive in nature and only a few sites of the cervix may be chosen for investigation. A non-invasive, label-free and real-time imaging method with a resolution approaching that of histopathology is desirable for early detection of the disease.Methods: Ultrahigh-resolution optical coherence microscopy (OCM) is an emerging imaging technique used to obtain 3-dimensional (3-D) “optical biopsies” of biological samples with cellular resolution. In this study, 497 3-D OCM datasets from 159 specimens were collected from 92 patients.Results: Distinctive patterns for normal cervix, squamocolumnar junction, ectropion, low-grade and high-grade squamous intraepithelial lesions (LSIL and HSIL) and invasive cervical lesions were clearly observed from OCM images, which matched well with corresponding histological slides. OCM images demonstrated a sensitivity of 80% (95% confidence interval, CI, 72%-86%) and a specificity of 89% (95% CI, 84%-93%) for detecting high-risk lesions (HSIL and invasive lesions) when blindly tested by three investigators. A substantial inter-observer agreement was observed (κ=0.627), which showed high diagnostic consistency among three investigators.Conclusion: These results laid the foundation for future non-invasive optical evaluation of cervical tissue in vivo, which could lead to a less invasive and more effective screening and “see-and-treat” strategy for the management of cervical cancer.

Aim: To evaluate the diagnostic value of serum cancer antigen (CA)125, CA19-9 and CA15-3 concentrations in endometriosis. Methods: Case-control studies evaluating CA125, CA19-9 and CA15-3 and endometriosis, published between January 2000 and November 2014 were retrieved from PubMed Õ and Google Scholar. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated. Subgroup analyses were carried out by ethnicity and disease stage (early, stage I/II; advanced, stage III/IV). Results: The analysis included 12 case-control studies (963 cases, 855 controls). CA125 was associated with endometriosis in the overall population (SMD 0.82, 95% CI 0.72, 0.92), Caucasian subgroup (SMD 1.08, 95% CI 0.96, 1.19), and early (SMD 1.20, 95% CI 0.93, 1.48) or advanced disease (SMD 1.29, 95% CI 1.04, 1.55). CA19-9 was associated with endometriosis in the overall population (SMD 0.48, 95% CI 0.24, 0.72), Caucasian subgroup (SMD 0.31, 95% CI 0.07, 0.55), Asian subgroup (SMD 9.65, 95% CI 7.88, 11.42) and advanced disease (SMD 0.60, 95% CI 0.34, 0.87). CA15-3 was significantly associated with advanced disease (SMD 0.47, 95% CI 0.09, 0.84). Conclusions: Serum CA125 and CA19-9 may represent useful biomarkers for the noninvasive diagnosis of endometriosis.

Ultrahigh-resolution optical coherence microscopy (OCM) has recently demonstrated its potential for accurate diagnosis of human cervical diseases. One major challenge for clinical adoption, however, is the steep learning curve clinicians need to overcome to interpret OCM images. Developing an intelligent technique for computer-aided diagnosis (CADx) to accurately interpret OCM images will facilitate clinical adoption of the technology and improve patient care. Methods: 497 high-resolution three-dimensional (3-D) OCM volumes (600 cross-sectional images each) were collected from 159 ex vivo specimens of 92 female patients. OCM image features were extracted using a convolutional neural network (CNN) model, concatenated with patient information [e.g., age and human papillomavirus (HPV) results], and classified using a sup

Breakpoint cluster region (BCR)-Abelson murine leukemia (ABL)1 + acute B-lymphoblastic leukemia (B-ALL) is a disease associated with a dismal prognosis and a high incidence of central nervous system (CNS) metastasis. However, BCR-ABL1 + B-ALL with CNS infiltration has not been previously characterized, at least to the best of our knowledge. In the present study, a murine model of BCR-ABL1 + B-ALL with CNS metastasis was established using retroviral transduction. The vast majority of BCR-ABL1 + leukemic cells were found to be immature B cells with a variable proportion of pro-B and pre-B populations. The present results indicated that the BCR-ABL1 + B-leukemic cells expressed high levels integrin subunit alpha 6 (Itga6) and L-selectin adhesion molecules, and have an intrinsic ability to disseminate and accumulate in CNS tissues, predominantly in meninges. On the whole, these results provide an approach for addressing the mechanisms of BCR-ABL1 + B-ALL with CNS metastasis and may guide the development of novel therapeutic strategies.

Acquired tamoxifen-resistance is an important cause of death in patients with hormone-dependent breast tumors. Therefore, understanding the molecular mechanisms underlying the development of tamoxifen-resistance is critical for successful endocrine therapy. This study aimed to define the role of WW domain-containing oxidoreductase (WWOX) in acquired tamoxifen-resistance. Our results show that low WWOX expression was significantly related to tamoxifen-resistance. Moreover, WWOX-knockdown increased resistance to tamoxifen, while WWOX overexpression decreased the resistance. Furthermore, WWOX silencing decreased Yes-associated protein (YAP) phosphorylation and increased YAP nuclear translocation. Finally, YAP silencing decreased tamoxifen-resistance in WWOX-knockdown cells. Our findings demonstrate that WWOX downregulation can lead to the development of tamoxifen-resistance by inactivating Hippo signaling. Thus, WWOX might be a valuable target and prognostic marker for tamoxifen-resistance. Impact statement Understanding the molecular pathways leading to the development of tamoxifen-resistance is an important research focus as acquired tamoxifen-resistance is the main cause of death in patients with benign primary prognosis. Although WW domain-containing oxidoreductase (WWOX) has been related to breast tumorigenesis, its role in acquired tamoxifen-resistance has not yet been demonstrated. Our findings show that WWOX might be a valuable therapeutic target and prognostic marker for tamoxifen-resistance.