In vitro synergistic cytoreductive effects of zoledronic acid and radiation on breast cancer cells

INTRODUCTION: Bisphosphonates are mostly used in the treatment of bone metastases. They have been shown to act synergistically with other chemotherapeutic agents. It is not known, however, whether similar synergistic effects exist with radiation on breast cancer cells. METHODS: Human MCF-7 breast cancer cells were treated with up to 100 μM zoledronic acid, were irradiated with up to 800 cGy or were exposed to combinations of both treatments to determine the antiproliferative effects of zoledronic acid and radiation. RESULTS: Zoledronic acid and radiation caused a dose-dependent and time-dependent decrease in cell viability (approximate 50% growth inhibition values were 48 μM and 20 μM for 24 hours and 72 hours, respectively, for zoledronic acid and 500 cGy for radiation). A synergistic cytotoxic effect of the combination of zoledronic acid and radiation was confirmed by isobologram analysis. CONCLUSION: These data constitute the first in vitro evidence for synergistic effects between zoledronic acid and radiation. This combination therapy might thus be expected to be more effective than either treatment alone in patients with metastatic breast carcinoma

Bisphosphonates as antimyeloma drugs

In patients with symptomatic multiple myeloma (MM), bisphosphonate (BP) treatment has been widely used to prevent bone loss and preserve skeletal health because of its proven effects on inhibiting osteoclast-mediated bone resorption. In addition to their effects on osteoclasts, it is becoming increasingly evident that BPs may have additional effects on the bone microenvironment and cells other than osteoclasts that may potentially inhibit the development and progression of MM. This review focuses on the pathophysiology of MM with an emphasis on the events that drive MM progression within the bone and the mechanisms by which BPs may inhibit specific processes. The underlying molecular mechanisms that drive the modulation of cellular fate and function and consequent physiological outcomes are described. Direct effects on myeloma cell growth and survival and the interactions between myeloma cells and the bone microenvironment are discussed. Clinical evidence of the antimyeloma effects of BPs is emerging and is also reviewed

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Determining the localization of premolar zenith positions according to the gingival line

Background: The gingival zenith (GZ) positions according to a reference line in the premolar (PM) area remain concern, especially for the clinicians in placing the gingival contours during surgery.Objectives: The objectives of this study are to determine the maxillary PM GZ positions according to GZ line (GZL).Materials and Methods: A sample population of 63 patients with healthy gingival tissue was studied. The GZ was determined at the most apical point of the gingival marginal scallop. A horizontal‑zenith line (ZL) was drawn connecting the GZ from the ipsilateral canine (C) and central incisor teeth. Reference lines were drawn, and bilateral measurements were taken in the respective stone casts in the PM area.Results: No statistically significant differences were found between bilateral first premolars (FPM) and second premolars (SPM). When considering ipsilateral FPM and SPM, statistically significant differences were found between them. For all PM teeth, the mean distance value of GZ to GZL was approximately 1.32 mm.Conclusions: The present study results showed that GZs of FPM and SPM teeth for both left and right sight was coronally located according to ZL.Key words: Gingival aesthetics, gingival localization, maxillary premolar

Identification of polymorphisms on the MDR1 gene among Turkish population and their effects on multidrug resistance in acute leukemia patients

Multidrug-resistance (MDR) phenotype is a serious limitation to the effective chemotherapeutic treatment of many cancer types, including leukemia. One of the most important proteins, the over-expression of which is responsible for the multidrug-resistance phenotype in many cancer types, is P-glycoprotein. This protein is the product of the MDR1 gene. In previous studies, single-nucleotide polymorphisms (SNPs) C3435T, G2677T, and T-129C in the MDR1 gene were shown to be correlated with lower P-glycoprotein expression in normal tissues. It was suggested that this might have an advantage in cancer chemotherapy by resulting in a low drug-resistance phenotype. The frequencies of these SNPs were studied in 45 acute leukemia patients (25 of which were primary refractory and 20 of which were drug-sensitive) and 17 healthy individuals, forming a Turkish population of 62 individuals. In the first part of the study, these polymorphisms were compared with other populations. Marked differences were apparent between African and Turkish populations for the C3435T polymorphism. On the other hand, similarities were found between other Caucasian/Asian and Turkish populations (P < 0.001). However, for the G2677T polymorphism, the Turkish population is different than Japanese and German populations (P < 0.001). For the T-129C polymorphism, all individuals in the studied population were homozygous for the T/T genotype. In the second part of this study, drug-resistant and drug-sensitive acute leukemia patients were compared for these SNPs. These polymorphisms did not seem to have a significant effect on P-glycoprotein-mediated drug resistance in the patients studied