SDF-1 alone and in co-operation with HGF regulates biology of human cervical carcinoma cells

Stromal Derived Factor-1 (SDF-1)-CXCR4 axis plays a pivotal role in biology and metastasis of several tumors. The aim of this study was to see if SDF-1 alone or in combination with Hepatocyte Growth Factor (HGF) affects biology of human cervical carcinoma (HCC) cells. We found that HCC cell lines investigated in our study highly express CXCR4 on their surface. CXCR4 was also expressed on tumor cells in tissue sections derived from cervical cancer patients. At the same time normal cervical epithelium was negative for CXCR4 expression what suggests a strong correlation between CXCR4 and malignant cell phenotype. Subsequently, we studied a potential role of the SDF-1-CXCR4 axis in HCC and noticed that SDF-1 (i) chemoattracted HCC cells, (ii) enhanced their scattering, (iii) stimulated nuclear localization of beta-catenins and upregulated their target gene cyclin D1 and (iv) at the molecular level induced calcium flux and activated RAS-MAPK, PI3-AKT and JAK-STAT pathways. SDF-1-mediated functions were additionally enhanced in the presence of HGF. Thus, our data show that the SDF-1-CXCR4 axis affects biology of HCC cells. Furthermore, we postulate that this axis might become a potential target to prevent progression of cervical cancer

SDF-1 alone and in co-operation with HGF regulates biology of human cervical carcinoma cells.

Stromal Derived Factor-1 (SDF-1)-CXCR4 axis plays a pivotal role in biology and metastasis of several tumors. The aim of this study was to see if SDF-1 alone or in combination with Hepatocyte Growth Factor (HGF) affects biology of human cervical carcinoma (HCC) cells. We found that HCC cell lines investigated in our study highly express CXCR4 on their surface. CXCR4 was also expressed on tumor cells in tissue sections derived from cervical cancer patients. At the same time normal cervical epithelium was negative for CXCR4 expression what suggests a strong correlation between CXCR4 and malignant cell phenotype. Subsequently, we studied a potential role of the SDF-1-CXCR4 axis in HCC and noticed that SDF-1 (i) chemoattracted HCC cells, (ii) enhanced their scattering, (iii) stimulated nuclear localization of beta-catenins and upregulated their target gene cyclin D1 and (iv) at the molecular level induced calcium flux and activated RAS-MAPK, PI3-AKT and JAK-STAT pathways. SDF-1-mediated functions were additionally enhanced in the presence of HGF. Thus, our data show that the SDF-1-CXCR4 axis affects biology of HCC cells. Furthermore, we postulate that this axis might become a potential target to prevent progression of cervical cancer

Censoring for loss to follow-up in time-to-event analyses of composite outcomes or in the presence of competing risks

Background: In time-to-event analyses, there is limited guidance on when persons who are lost to follow-up (LTFU) should be censored. Methods: We simulated bias in risk estimates for: (1) a composite event of measured (outcome only observable in a patient encounter) and captured events (outcome observable outside a patient encounter); and a (2) measured or (3) captured event in the presence of a competing event of the other type, under three censoring strategies: (i) censor at the last study encounter; (ii) censor when LTFU definition is met; and (iii) a new, hybrid censoring strategy. We demonstrate the real-world impact of this decision by estimating: (1) time to acquired immune deficiency syndrome (AIDS) diagnosis or death, (2) time to initiation of antiretroviral therapy (ART), and (3) time to death before ART initiation among adults engaged in HIV care. Results: For (1) our hybrid censoring strategy was least biased. In our example, 5-year risk of AIDS or death was overestimated using last-encounter censoring (25%) and under-estimated using LTFU-definition censoring (21%), compared with results from our hybrid approach (24%). Last-encounter censoring was least biased for (2). When estimating 5-year risk of ART initiation, LTFU-definition censoring underestimated risk (80% vs. 85% using last-encounter censoring). LTFU-definition censoring was least biased for (3). When estimating 5-year risk of death before ART initiation, last-encounter censoring overestimated risk (5.2% vs. 4.7% using LTFU-definition censoring). Conclusions: The least biased censoring strategy for time-to-event analyses in the presence of LTFU depends on the event and estimand of interest

When to Censor?

Loss to follow-up is an endemic feature of time-to-event analyses that precludes observation of the event of interest. To our knowledge, in typical cohort studies with encounters occurring at regular or irregular intervals, there is no consensus on how to handle person-time between participants’ last study encounter and the point at which they meet a definition of loss to follow-up. We demonstrate, using simulation and an example, that when the event of interest is captured outside of a study encounter (e.g., in a registry), person-time should be censored when the study-defined criterion for loss to follow-up is met (e.g., 1 year after last encounter), rather than at the last study encounter. Conversely, when the event of interest must be measured within the context of a study encounter (e.g., a biomarker value), person-time should be censored at the last study encounter. An inappropriate censoring scheme has the potential to result in substantial bias that may not be easily corrected

MEDULLARY CARCINOMA OF THE BREAST: ROENTGENOLOGIC AND ULTRASOUND SEMIOTICS

Breast cancer (BC) is the most common female cancer type and the leading cause of female cancer mortality in Russia and in majority countries of the world. Along with the most common type of BC – ductal carcinoma, there are a lot of histological types, distinguished by structure features, which lead to a variable clinical and instrumental semiotics.These histological types of BC in the group marked out special types of BC, including medullary carcinoma. The concept of medullary cancer includes typical medullary BC, atypical medullary BC and invasive ductal BC with evidence of medullary morphology.Based on the current literature data, the authors discuss the main epidemiological, clinical and morphological diagnostic features of medullary BC. The authors pay special influence pathological picture, forming the characteristic diagnostic features of medullary cancer detected using X-ray mammography and ultrasound of the breast – the basic techniques of BC and other breast diseases detection.In 2003–2013 diagnosed 19 medullary BC cases in women aged 18–56 years, with 18 of them were recorded in patients aged 34–56 years. The authors describe in detail the features of clinical, mammographic and ultrasound semiotics of medullary BC. Article is focused on the main X-ray and ultrasound characteristics, such as mass shape and margin features, as well as its internal structure, and also the results of power Doppler. One of the main features of this article is description of ultrasound elastography pattern of medullary BC, which could be find in only a small number of scientific articles.Typical medullary BC, atypical medullary cancer and ductal carcinoma with medullary signs have different prognosis. This problem leads to necessity find reliable distinguishing features in mammograpic and ultrasound semiotics. It is seems important to reveal sites with indistinct margin. We have found the indistinct margin detection is not statistically significant for the differential diagnosis of typical forms of medullary BC from atypical forms and invasive ductal BC with evidence of medullary structure.The authors conclude that the mammographic and ultrasound semiotics of medullary BC makes accurate differential diagnosis with benign breast pathology by X-ray mammography as well as breast ultrasound impossible. There are no statistically significant differences in the results of the mammography and breast ultrasound in different histological types of medullary BC. So these diagnostic features are not reliable for the differential diagnosis. However, the application of a comprehensive usage of mammography and breast ultrasound using modern technology of ultrasound diagnosis allows to suspect BC