Using breast cancer cell CXCR4 surface expression to predict liposome binding and cytotoxicity

The primary cause of mortality in breast cancer is tumor aggressiveness, characterized by metastases to regional lymph nodes, bone marrow, lung, and liver. C-X-C chemokine receptor type 4 (CXCR4) has been shown to mobilize breast cancer cells along chemokine gradients. Quantification of CXCR4 surface expression may predict the efficacy of anti-CXCR4 labeled liposomal therapeutics to target and kill breast cancer cells. We evaluated gene and surface receptor expression of CXCR4 on breast cancer cell lines distinguished as having low and high invasiveness, MDA-MB-175VII and HCC1500, respectively. CXCR4 surface expression did not correlate with invasiveness. MDA-MB-175VII exhibited more binding to anti-CXCR4 labeled liposomes relative to HCC1500. Increased binding correlated with greater cell death relative to IgG labeled liposomes. Quantitative cell characterization may be used to select targeted therapeutics with enhanced efficacy and minimal side effects.     

Cell-derived vesicles exposing coagulant tissue factor in saliva

On vascular damage, coagulation is initiated by extravascular tissue factor (TF). Intravascular TF, which is present on circulating cell-derived vesicles, is noncoagulant under physiologic conditions but prothrombotic under pathologic conditions. Human saliva triggers coagulation, but the mechanism and physiologic relevance are unknown. Because saliva is known to contain TF, we hypothesized that this TF may also be associated with cell-derived vesicles to facilitate coagulation when saliva directly contacts blood. The saliva-induced shortening of the clotting time of autologous plasma and whole blood from healthy subjects (n = 10) proved TF-dependent. This TF was associated with various types of cell-derived vesicles, including microparticles and exosomes. The physiologic function was shown by adding saliva to human pericardial wound blood collected from patients undergoing cardiac surgery. Addition of saliva shortened the clotting time from 300 ± 96 to 186 ± 24 seconds (P = .03). Our results show that saliva triggers coagulation, thereby reducing blood loss and the risk of pathogens entering the blood. We postulate that our reflex to lick a wound may be a mechanism to enable TF-exposing vesicles, present in saliva, to aid in the coagulation process and thus protect the organism from entering pathogens. This unique compartmentalization may be highly conserved because also animals lick their wounds.     

Patn�� en Aksyon: Addressing Cancer Disparities in Little Haiti Through Research and Social Action

Haitian women living in Miami, Florida, experience an increased risk of developing and dying from cervical cancer compared with women in other racial/ethnic minority and immigrant groups in the area. In response to this disparity, academic investigators from a local university-based cancer center and community leaders from Little Haiti, the predominately Haitian neighborhood in Miami, created Patnè en Aksyon (Partners in Action), a campus-community partnership. We describe the partnership''s effort to document the prevalence of lifetime and routine Papanicolau test use using community-based participatory research methods. Community health workers indigenous to the area recruited participants from various community venues throughout Little Haiti and administered informal, brief interviews to assess their screening practices. The results indicate that Haitian women are underscreened and underscore the importance of community involvement in study implementation.IN MIAMI, FLORIDA, HAITIAN women experience an increased risk of developing and dying from cervical cancer compared with other racial/ethnic minorities and immigrant groups in Miami.¹ The underutilization of routine Papanicolau test screening likely accounts, in large part, for this disparity ^2,3 However, previous research has not successfully examined the Papanicolau test screening behaviors of this population because of the prevalent distrust of health research in Little Haiti.⁴To overcome such barriers, academic investigators from the University of Miami and community leaders from Little Haiti created Patnè en Aksyon (Partners in Action), a campus–community partnership. This partnership was formed in late 2004 through the collective efforts of university investigators and directors of Haitian community-based organizations (CBOs) who had worked together previously to address cancer disparities in Little Haiti. The CBO directors enumerated a list of other community leaders, including pastors, traditional healers, and activists, and approached those individuals to solicit their participation. Interested persons were invited to an inaugural meeting in which we collaboratively decided upon the group''s scientific focus—to understand why Haitian women are disproportionately diagnosed with late-stage breast and cervical cancers.The partnership employs the methods of community-based participatory research (CBPR), which invites community participation throughout the research process.⁵ The design of all partnership research initiatives, including the study described here, reflects the collective input of academic and community partners.⁶ We sought to document the prevalence of lifetime and routine Papanicolau test use among ethnically Haitian women living in Little Haiti. The majority of Little Haiti residents were born in Haiti and emigrated more recently than did Haitians residing in other communities in South Florida.⁷     

Influence of continued smoking and some biological risk factors on restenosis after percutaneous transluminal coronary angioplasty

Objectives. To identify possible biological risk factors for restenosis following successful percutaneous transluminal coronary angioplasty (PTCA) in patients having single or multivessel disease. The effect of continued smoking on restenosis was also evaluated.
Design. In this prospective smoking controlled study all subjects had a routine angiographic restudy after 6 months. The biological risk factors assessed before angioplasty were adrenaline, endothelin, fibrinogen, lipoprotein (a) and tissue plasminogen activator.
Subjects. The study population consisted of 122 patients of whom 25% were current smokers.
Main outcome measures. Angiographic restenosis was defined as at least 50% diameter stenosis on the follow-up angiogram after an initially successful procedure.
Results. Restenosis was observed in 43% of patients. The restenosis rate was significantly lower among current smokers, but they were significantly younger and also had significantly less dilated stenoses. Multivariate analysis revealed the number of dilated stenoses, the mean inflation time, post-PTCA percentage diameter stenosis and left anterior descending coronary artery to be predictive of restenosis, while continued smoking was not. When only the lesion with the greatest loss in luminal diameter of each patient was considered, the multiple linear regression analysis revealed high endothelin level to be predictive of restenosis.
Conclusions. This study revealed high endothelin levels to be predictive of luminal narrowing after angioplasty. In addition, the number of dilated stenoses, the mean inflation time, post-PTCA percentage diameter stenosis and stenosis location in the left anterior descending artery were found to be predictive of restenosis. However, continued smoking after angioplasty did not emerge as a risk factor for restenosis.