Effect of bisphosphonates and statins on the in vitro radiosensitivity of breast cancer cell lines.

BACKGROUND: Early-stage breast cancer is usually treated with breast-conserving surgery followed by adjuvant radiation therapy. Acute skin toxicity is a common radiation-induced side effect experienced by many patients. Recently, a combination of bisphosphonates (zoledronic acid) and statins (pravastatin), or ZOPRA, was shown to radio-protect normal tissues by enhancing DNA double-strand breaks (DSB) repair mechanism. However, there are no studies assessing the effect of ZOPRA on cancerous cells. The purpose of this study is to characterize the in vitro effect of the zoledronic acid (ZO), pravastatin (PRA), and ZOPRA treatment on the molecular and cellular radiosensitivity of breast cancer cell lines. MATERIALS: Two breast cancer cell lines, MDA MB 231 and MCF-7, were tested. Cells were treated with different concentrations of pravastatin (PRA), zoledronate (ZO), as well as their ZOPRA combination, before irradiation. Anti-γH2AX and anti-pATM immunofluorescence were performed to study DNA DSB repair kinetics. MTT assay was performed to assess cell proliferation and viability, and flow cytometry was performed to analyze the effect of the drugs on the cell cycle distribution. The clonogenic assay was used to assess cell survival. RESULTS: ZO, PRA, and ZOPRA treatments were shown to increase the residual number of γH2AX foci for both cell lines. ZOPRA treatment was also shown to reduce the activity of the ATM kinase in MCF-7. ZOPRA induced a significant decrease in cell survival for both cell lines. CONCLUSIONS: Our findings show that pretreatment with ZOPRA can decrease the radioresistance of breast cancer cells at the molecular and cellular levels. The fact that ZOPRA was previously shown to radioprotect normal tissues, makes it a good candidate to become a therapeutic window-widening drug.

A Systematic Review of Pressure Injuries Associated with Urethrocutaneous Fistula.

OBJECTIVE: To review the literature about combined urologic and reconstructive management of pressure injuries (PIs) with urethral fistulas. DATA SOURCES: Authors searched the PubMed, MEDLINE, EMBASE, and Cochrane databases using the following keywords: "Perineum" or "Perineal" and "Pressure Ulcers" or '' Pressure Injury'' and "Urethral Fistula." STUDY SELECTION: The search yielded a total of 95 articles. Study selection followed the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) statement, and the study was designed according to the PICOS (Population, Intervention, Comparison, Outcomes, Study) guidelines. Congress abstracts, letters to the editor, and editorial comments were excluded. After screening, a total of 9 studies (30 patients) were included in the review. DATA EXTRACTION: Included patients received treatment for a perineal or ischial PI associated with a urinary fistula. The outcomes were recovery, complications, treatment failure, recurrence, and illness-related death. DATA SYNTHESIS: Pressure injuries were mainly ischiatic (50%) and perineal (43%). Forty-six percent of patients had spinal cord injuries, and at least 40% reported voiding dysfunction. Sixteen percent had previous ischiectomy. Flaps such as posterior thigh flap, biceps femoris flap, and inferiorly based transverse rectus abdominal muscle flap had 88% to 100% success rates when used with urinary diversion techniques. Suprapubic cystostomy, the simplest method of urinary diversion, was successful in 47% of cases when performed alone and in 100% when combined with a pedicled omental flap or a transverse rectus abdominal muscle flap. CONCLUSIONS: Prevention and wound care are essential for PI management, but when combined with a urinary fistula, surgical management is unavoidable. Urinary diversion is essential before undergoing any type of ulcer reconstruction. Urethral reconstruction showed favorable results, further strengthened when combined with a musculocutaneous flap.

Validation of the Human Papillomavirus Impact Profile in Lebanese Women With Human Papillomavirus or Associated Lesions.

OBJECTIVES: Human papillomavirus (HPV) is responsible for a multitude of lesions with high psychosocial burden. The "HPV Impact Profile" (HIP) questionnaire is one of the first and most specific tools evaluating the emotional impact of HPV. This study aimed to translate this questionnaire into Arabic and to validate it, in a sample of Lebanese female patients. MATERIALS AND METHODS: The HIP questionnaire was translated to Arabic. It was then administered to 118 Lebanese women infected with HPV or screened for HPV-associated lesions, in parallel with the Hospital Anxiety and Depression Scale questionnaire. The psychometric properties of the questionnaire were studied in our sample population. RESULTS: The internal consistency of the HIP questionnaire was weak as Cronbach α coefficients of most of the domains were low. The study of the composite matrix resulted in the improvement of the internal consistency after the elimination of some items. Moreover, the "adapted domains" were created by reverse-scoring items with positive implications.The composite reliability and the average variance extracted of all the domains were analyzed. Analysis of discriminate validity through heterotrait-monotrait ratio of correlation ratio analyses of corresponding Hospital Anxiety and Depression Scale domains was also performed along with reliability analysis. There results were satisfying for the adapted domains. CONCLUSIONS: The adapted domains of the 27 items questionnaire with reverse scoring of 8 items presented with good psychometric properties, allowing their use in clinical trials and in clinical practice.

Does Social and Religious Background Matter? A Study of the Psychosocial Impact of Human Papillomavirus on Lebanese Women.

OBJECTIVE: The human papillomavirus (HPV) has been associated with an important psychosocial impact. This impact has been poorly evaluated in developing countries, mostly because of the lack of instruments to quantify it. The HIP questionnaire aims to measure HPV-associated affective burden. Our team has previously translated this questionnaire to Arabic and used it to assess the impact of HPV on Lebanese women. MATERIALS AND METHODS: While the HIP is a specific tool to evaluate the emotional impact of HPV, the Hospital Anxiety and Depression Scale questionnaire consists of 2 scales, anxiety and depression, and assess the psychological distress in nonpsychiatric patients. The HPV impact profile and Hospital Anxiety and Depression Scale questionnaires were administered to 118 Lebanese women with an HPV-related presentation, aiming to determine which aspect of these women's lives was mostly affected. The association with different sociodemographic factors was also assessed. RESULTS: Feelings of "concerns and worries" were mostly strongly felt in our population except for women with genital warts who were more concerned with the risk of transmission and the impact on their partners. All women had predominant feelings of anxiety.Religion was a statistically significant influencing factor and employment a protective factor. Muslim women demonstrated significant adverse affects on HPV impact profile domains that included: "sexual impact," "self-image," "interaction with doctors," and "health control/life impact." CONCLUSIONS: Different women perceive the diagnosis of HPV and HPV-related lesions differently. In this study, employment was found to play a protective role, but the biggest influencers were social and religious beliefs.